Clinical Research Insider Summit No. 11 - English

SUMMIT INTERNATIONAL

CLINICAL RESEARCH INSIDER 2023

STAFF DIRECTORY

Marco Cid Fabian

Villanueva

Marco A. Cid

Diana Foster

Jeremy Mitchell

Cristobal Thompson

Laura Velasquez

Miriam Márquez

Yesika S. Muñoz

Ailyn Cerda Pavel Moreno Cesar

Jose L. Medina-Franco

Fernanda Saldivar-Gonzalez

Valdes Calleja

Perez

Ivette Venegas Karen Espinoza Victoria Arnauda

Delon Human

Karl-Olov Fagerström

Luis Fernando Tejado

Marco Antonio Loza

Guillermo Pepe

Maria Fernanda Arboleda

Carmen de la Rocha

Claudia Mejia Morales

Wendy Lopez Romero

Juan Jose Rivera Valdes

Saul Flores Unzueta

Ana Villaseñor-Todd

Mario A. Flores Valdez

Blanca Peredo

Mauro Orozco Moreno

Origenes Romero

Rick Ruiz-Dana

/ Georgina Garcia, Hakim Mohamed & Vicente Alciturri

56

Pag.

CLIR SUMMIT 2023 SCIENTIFIC POSTER

Comparison of the antiobesogenic effect of 10-gingerol vs a mix of ginger phenols in adipocytes of the 3T3-L1 cell line

Juan Jose Rivera Valdes et al.

24

SCIENCE TODAY

Smoke Free Sweden

Delon Human & Karl-Olov Fagerström

Challenges in clinical research; Antagonisms and challenges overcome Dr. Ana Villaseñor-Todd

Clinical study to evaluate the nonspecific protection conferred by Bacillus Calmette-Guerin bacteria

Mario Alberto Flores Valdes

70

NEO-GEEK Pag.

Pag. 70

Pag. 72 Pag. 47

ChatGPT: hero, villain, anti-hero, or sidekick?

Mauro Orozco Moreno

First 3D Bioprinter made from LEGO pieces capable of printing human skin created Brain chips; Neuralink obtains FDA approval to begin human clinical trials

Clinical Research Insider Editorial

73

Pag.

BETWEEN ART AND SCIENCE

Darwinist Hitler Orígenes Romero Porras

Pag.

68

PEOPLE IN SCIENCE

Evolutionary Anthropology, the work of Svante Pääbo

Blanca M. Peredo Vazquez

Pag.

75

CARTOON INSIDER

Rick Ruiz-Dana

Validation Services

For The Pharmaceutical Industry

CENEBA BIOPROCESS lab is an leader in the filter validation techniques and services.

Our ongoing success is based on a dedication to technical excellence and exceptional cu stomer service. Our future will continue to be built on our investment in research and development, and to provide innovative new products that exceed the expectations of our customers in solving the challenges they face.

Depending on the process requirements the following validation options are available:

• filter compatibility assessment

• bacterial challenge testing

• extractables and leachables analysis

• adsorption studies

• product wetted integrity test st udies.

During validation, our philosophy is to mimic the process as closely as feasible.

Scientific convergences; united voices for the construction of our future

“Move fast and break things. The idea is that if you never break anything, you’re probably not moving fast enough”

- Mark Zuckerberg

Clinical research is a complex and rigorous process that requires a sharp mind and infinite patience to achieve meaningful results. It combines science and art, reason and intuition, precision and creativity. The human being makes clinical research a dance between mind and body, between theory and practice, between knowledge and experience.

All this deserves to be exhibit, therefore, in our eagerness to go further in the field of clinical research, together with Drox Health Science we celebrated our 4th International Research Congress called Clinicial Research Insider Summit 2023; a dialogic, interactive and transformative space, where the tensions of reason and the most current knowledge about the clinical world were put on the table to guide us to the experimentation of knowledge in community.

In our 11th edition of your journal Clinical Research Insider we share a little of what we experience with the presence and enthusiastic participation of key agents of the academy, clinical and pharmaceutical industry of Mexico and the world. We thank each of them for joining us in undertaking a deep exploration of the mysteries of the human body and giving us the opportunity to discover new paths to health and wellness.

At its core, clinical research is an act of love for humanity, a sign of commitment and dedication to improving people’s quality of life. Today, we are committed to continue creating communication ties through our media to share the latest advances in technology, research and clinical development, in order to be a vehicle for the growth of the industry and thereby make Mexico an international landmark.

Because we are in the era of speed where information does not know rest, because the world evolves and what yesterday were taboos today are passable paths to modernity, in Clinical Research Insider we mark the points of reference, memory and progress in clinical research.

Distinguished guests, researchers, and experts in the field of clinical research, I am honored to welcome you to the Clinical Research Insider Summit 2023, our fourth international clinical research congress. This event is an opportunity to come together and share our knowledge, experiences and perspectives around a topic that is of vital importance to humanity: health.

Clinical research is an essential tool for better understanding diseases and discovering new ways to prevent and treat them. In a world where globalization and technological advances have allowed diseases to spread rapidly across borders and affect people of all ages and socioeconomic conditions, clinical research becomes a fundamental cornerstone to address these challenges.

This congress is not only an opportunity to present the latest research and advances

in the field of health, but also to discuss how we can make this research accessible to all people, especially those living in developing countries. Inequality in access to healthcare is a reality that continues to exist in our world and is something we must address effectively.

In this sense, the impact of this congress is not only limited to the presentation of research, but can also have a lasting impact on the most vulnerable communities on our planet. By sharing our ideas and knowledge, we can work together to develop innovative and affordable solutions to improve the health and well-being of people around the world.

I hope everyone can make the most of this unique opportunity to learn, share and collaborate. Together we can make a meaningful difference in the lives of millions of people and move towards a fairer and healthier world for all.

Thanks a lot!

THE LANDSCAPE OF

DIVERSITY, EQUITY, AND INCLUSION: TRANSFORMING CLINICAL TRIALS

Diana L. Foster, PhD

CEO and Chief Diversity Officer of the Association of Diversity. She is renowned for developing the influential Diversity Site Assessment Tool (DSAT). With six industry books and leading research studies on clinical site diversity, Dr. Foster is a highly soughtafter expert and recognized thought leader in diversity and clinical site best practices.

Jeremy Mitchell, MBA

Our Director of Business Development is a 25-year sales professional driven by a passion for diversity and making a positive impact. He actively contributes to Minorities in Clinical Research, advocating for diversity and inclusivity in healthcare. Jeremy firmly believes in the power of diversity to foster innovation, creativity, and excellence and remains dedicated to championing this cause in all aspects of his life.

Contact Information:

JJeremy Mitchell, Director of Business Development, AOD

Email: jmitchell@associationofdiversity.org

Phone: 989-780-4244

Introduction

The imperative of diversity in clinical trials has been acknowledged not only by the United States Food and Drug Administration (FDA) as a legal requirement but also by various countries worldwide recognizing its crucial role in advancing scientific knowledge and ensuring comprehensive representation. In this regard, Marco Cid, the forward-thinking CEO of DROX CRO, has taken proactive measures to support this philosophy, exemplifying a commitment to equitable access. Notably, DROX has recently emerged as a Supporting Partner of the Association of Diversity in Clinical Trials (AOD), with Mr. Cid assuming a position on the AOD Advisory Board to further its mission.

Mission Statement

The primary mission of the AOD is to establish industry standards and best practices that enhance the representation of diverse participants in clinical trials. This objective will be accomplished through the development, integration, and meticulous monitoring of robust and consistent diversity methodologies across the research industry.

Upcoming Collaborative Effort

A seminal event bringing together multiple stakeholders will take place at the Drug Information Association conference in Boston,

Massachusetts from June 25th to 27th. During this occasion, the importance of diversity in clinical trials will be emphasized through discussions and messaging within the clinical trials industry. The AOD will have a dedicated booth where constituents can engage with experts and exchange ideas. At this event, Dr. Jerome Adams, former US Surgeon General and Chairman of the Board, will address the partner meeting and will be available for a brief meet-and-greet in booth XXL.

Leadership and Impact

Dr. Diana Foster, President and Chief Diversity Officer of the AOD, expressed confidence in the transformative impact that Marco Cid and his team will have on this global issue, particularly in Mexico, by actively addressing diversity participation. It is acknowledged that each country faces distinct challenges in improving representation and defining the problem. The progressive stance of the CID Group underscores their dedication to increasing access for underrepresented populations.

Promoting Global Dialogue

As an illustrative example of the commitment to advancing diversity in clinical trials, the upcoming 2024 CLIR Summit in Mexico City in March will feature a dedicated breakout session focused on developing strategies and executing plans for inclusive trial design. Mr. Cid strongly encourages his Mexican counterparts involved in clinical research to join this influential gathering of industry partners. For more information on participation, interested individuals can contact Mr. Jeremy Mitchell, the Director of Business Development at the AOD, whose contact details are provided below.

THE IMPORTANCE OF RESEARCH IN MEXICO: CHALLENGES

AND OPPORTUNITIES

FOR THE PRIVATE SECTOR

Cristobal Thompson

Executive Coach focused on behavioral change and strategy; Executive Director of the Mexican Association of Pharmaceutical Research Industries (AMIIF).

Currently, clinical research is a topic that has gained great relevance and occupies a special place on the national agenda and in health forums. Mexico has a great opportunity in this area due to the level of researchers and institutions it has.

AMIIF is an Association in which national and international companies from more than 11 countries participate, the same ones that act actively in the national market. Global clinical research represents more than 60% of research. For this reason, the national market represents a challenge and an opportunity to develop work that benefits the world’s population.

At present, Mexico has modified several important aspects of its health and sanitary regulations, which has allowed it to create opportunities and be more attractive to foreign investment.

Research processes currently implemented were designed a few years ago. That has allowed us to be on the right track and close the gap that existed in this field. We must seize the opportunity in all areas and with all the actors involved to make this circumstance a reality for the country in matters of research and growth.

The pharmaceutical industry invests 140 billion dollars globally. An important fact: eight out of every 10 dollars come from clinical research. However, the region receives only 6% of global investment; in other words, we receive the least,

and we have to change that. One of the strategies is to continue with the efforts and go out and promote it.

Likewise, the pharmaceutical industry is investing in new therapeutic areas, mainly in noncommunicable diseases (which are becoming increasingly important due to epidemiological changes), but also working to develop drugs for transmissible diseases, such as the new outbreaks we are seeing.

Regarding the different phases of research, we need to increase research development in its early phases, especially phases III and IV, which are more frequent. This is a strength of the country, which we should promote even more.

We’re convinced that we can move forward, achieving the consolidation of process improvements and, with the active collaboration of the main stakeholders: COFEPRIS, SAT, IMSS, CONBIOETICA, and all the national institutes and hospitals that today carry out clinical research.

People are beginning to realize the importance of clinical research for Mexico and the great opportunity we have to position ourselves globally and capitalize on everything that is being done. It is also important to highlight the investments that are being made in tropical diseases. The industry has returned to creating very important investment funds and working with other players.

Diagnosis of diseases through Artificial Intelligence

What is the importance of artificial intelligence in clinical research?

One of the biggest challenges we have seen in research is not only the clinical process itself but also the strategy for patient identification, recruitment, and enrollment processes, as well as patient drop-out during clinical trials. This is where we have proven that Artificial Intelligence generates high value. Today, with Arkangel AI, se-veral partners use our technology to create their own AI models for the recruitment process, aiming to create an algorithm to identify which potential patients are optimal for enrollment in clinical research. Similarly, AI models have been developed to predict the drop-out of patients, allowing better decisions to be made during the clinical study so that the process is more efficient and the results are optimized.

How can technology help human beings in the field of health?

Since the pandemic, the relationship between health and technology has grown rapidly and, in some areas, exponentially. Adoption and implementation of technology based on Artificial Intelligence allow for more scalable and efficient processes, in addition to generating cost-effective disease prevention and early detection. Similarly, technology serves to optimize administrative processes that accelerate decision-making and access to healthcare, all to save lives.

Artificial Intelligence is basically about turning raw data into knowledge that can be processed to make decisions more efficiently; by capturing all those numbers, trends, and graphs, we turn them into something that can be used to make decisions about diagnosis, treatment, access, clinical research, and even administrative processes.

Laura Velasquez Herrera President and co-founder of Arkangel AI

The Future of Clinical Research: Realities, Solutions, and Expectations

Undoubtedly, the future of clinical research came to all of us earlier than expected due to the pandemic we have been experiencing globally since 2020. There was talk about the digital age and remote visits, but as of March 2020 life changed, without warning or preparation on our part.

Patients could not go to research sites from one day to the next, which forced us to adapt to the new circumstances, look for plan B to help research protocols survive, and avoid as many deviations as possible to have valid data, while still taking care of patient safety.

What is the future of clinical research? The first logical answer would be to say that its advancement through technology, which is a fundamental part, but we have to understand that technology does not define us. On the contrary, this should be one more tool in our kit to be able to give a solution to the enormous continuous and

“live” challenges that are presented day by day in a clinical research site, to the CRA responsible for monitoring the study, to the data analysts, to the local and international authorities, as well as to those responsible for pharmacovigilance and to the patients themselves.

Is there a perfect formula? No, it all depends on how we adapt, and how we individualize each study depending on the complexity, indication, number of patients, number of visits, and enrollment times. With all this data we must establish risks, as well as preventive and corrective plans applied as quickly as possible, with the key being MonitorSite-Patient communication.

It is essential to define what we can be flexible about and what we must correct at the same time, what we cannot be flexible about and when we must pursue compliance.

Miriam Marquez

Director of Centralized Monitoring at PPD, part of Thermo Fisher Scientific.

Fernanda I. SaldivarGonzalez Jose L. MedinaFranco*

Contact: medinajl@unam.mx

Computational technologies for drug discovery

Drug development is a complex process because there are still many unknowns in human diseases. For decades and particularly in recent years, computational models and, in particular, artificial intelligence (AI) models have been integrated into basic research and decision-making during the drug design process in combination with experience-based human intelligence and intuition. This manuscript discusses recent examples of AI applications in drug design and development. The concepts and computational approaches used are discussed, and the possibilities and limitations of drug design using AI are analyzed.

Artificial intelligence is being incorporated into our daily lives. For example, voice assistants and image recognition work with AI. The algorithms process and transform images, words, or phrases from a natural language into a format readable by computer programs. During this process, algorithms identify rules to relate data and extract

patterns and information to make predictions that make it easier to make decisions and/or solve problems. Scientific publications that include AI terms such as “machine learning” (ML), referring to machine learning or machine learning , or “deep learning” (DL), referring to deep learning, are increasingly frequent.

Since the 50’s, AI has been used in various areas of Chemistry. However, technological advances and the parallel development of theories and models have accelerated its application. Adopting AI in the drug development process faces challenges such as low success rates, where more and more money is invested in obtaining new drugs and only few molecules reach clinical phases. In general, the average time required for discovery, preclinical and clinical studies, approval and marketing of a drug is approximately sixteen years and costs a median of 985 million dollars. Implementing AI can reduce the development time of a new drug to just two or three years.

DIFACQUIM research group, Department of Pharmacy, Faculty of Chemistry, National Autonomous University of Mexico

Recently, the term “augmented intelligence” was integrated into the model of association between human intelligence and AI with the aim of improving cognitive performance, learning, decision making and the generation of new experiences. Under the concept of augmented intelligence, it is not intended that machines replace scientists, but that scientists understand AI methodologies, allowing them to move into the field of systems biology and take advantage of their own experience, along with the capabilities offered by AI models.

The goal of QSAR (quantitative structure-activity relationships) is to find a mathematical model that approximates the intrinsic associations

between chemical structures and biological activity. Currently, AI algorithms are seeing numerous applications within the different stages of the drug discovery and development process. For example, in the early stages, AI methods have had a substantial impact on predicting the threedimensional (3D) structure of proteins. They have also helped suggest a large number of drug-like compounds to effectively test their biological/ biochemical activity in high-throughput screening (HTS) studies.

The role of AI in the prediction of properties related to absorption, distribution, metabolism, elimination and toxicity (ADME-Tox) is an important part of decision making, as it facilitates

the selection of compounds for synthesis and biological evaluation. In this area, AI models are used to plan and optimize compound syntheses, to estimate the synthetic accessibility of compounds present in chemical libraries that may have thousands or millions of compounds, and to automate the synthesis process. AI methods are also employed at preclinical stages to identify tissue-specific biomarkers and at clinical stages for patient selection in clinical trials, to identify new uses of existing medicines, and in pharmacovigilance, to understand and prevent adverse drug effects.

Methods and applications of AI in drug design

The science of the XXI century is having great transformations due to the increasing access of

information available in databases, many of them public. To make sense of the information contained in the data requires new ways of thinking and learning and new work methodologies. Examples of the use of AI methods in drug research are discussed below.

3D structure prediction of therapeutic molecular targets

The design of drug candidates based on the 3D structure of the therapeutic target has been a successful strategy. The hypothesis of structurebased design is that compounds with affinity for functional sites of these structures can induce or result in a clinical effect. Notable examples of this strategy are the development of antivirals such as relenza and drugs used to treat AIDS. X-ray

crystallography, nuclear magnetic resonance and electron microscopy make key contributions to elucidating the 3D structure of molecular targets. 3D structures can also be employed in computer-aided design, employing molecular coupling, fragment-based design, and de novo design. Although the 3D coordinates of almost 200,000 structures are available in the Protein Data Bank to date, it is laborious and expensive to experimentally elucidate the structures of all therapeutic targets. Here, AI has advances to predict the folding of proteins from the knowledge of their sequence.

De novodesign of new compounds

Generative models, de novo or “from scratch”, are used to design new chemical compounds. Examples of DL architectures used in de novo design are: Variational Autoencoders (VAEs), Generative Adversarial Networks (GANs), and Recurrent Neural Network (RNN). In addition, hybrid approaches can be designed. Generative design has made considerable progress, however, more evidence of its efficiency is required. Current challenges of generative approaches include the chemical synthesis of compounds and the various solutions for a given property.

Systematic evaluation of molecular targets

Understanding the mechanism by which a compound exerts therapeutic effect is essential for drug design and optimization. Identifying biological targets for bioactive compounds is considered a bottleneck to the informed design of “chemical probes” and lead drugs. Fortunately, high-throughput experimentation has generated a wealth of chemical and biological data that makes it possible to produce models to link biological targets with bioactive compounds. These data have shown that compounds are rarely selective for a single given biological target. The interaction of a compound involving several related or unrelated macromolecules is known as polypharmacology that is exploited in the design of multi-target drugs and in drug repositioning.

Prediction of ADME-Tox properties

The number of organic molecules that could potentially be synthesized in a drug discovery program is approximately 1063. To limit the number of molecules to be considered in the real world, there are AI applications to predict the ADME-Tox properties of a molecule before its synthesis. Properties such as aqueous solubility, intestinal permeability and plasma protein binding are important parameters to consider in achieving systemic exposure of an oral drug. Similarly, knowing how quickly a drug is metabolized and eliminated, and what the mechanism of action is, determines the success of a drug, since these properties have an impact on the bioavailability and safety of a drug. Toxicity is also a critical parameter to evaluate not only in the pharmaceutical industry but also in cosmetics and agrochemicals. The number of possible causes for a compound to fail and have adverse effects is large and, as such, the number of properties to check in a laboratory is expensive and time-consuming. In this context, AI models help improve predictions of drug efficacy and safety.

Chemical synthesis

AI techniques are also used to analyze chemical synthesis information available in the literature

and databases. For example, different reactions can be compared and processed to produce a given compound. This information can lead to: a) retrosynthetic analyses that divide the problem into subproblems, and generate stepby-step synthesis suggestions, b) in the recommendation of reaction conditions that will lead to a successful direct reaction and c) in the prediction of products from a set of materials and initial conditions that is used to validate the proposed synthetic steps. It is worth mentioning that, for a synthetic planning tool to help increase chemical knowledge and accelerate the synthesis process, it must be easy to use and be intuitive in its handling and interpretation of results. In addition, the suggested routes should result in materials that can be purchased in the market.

Personalized medicine

In classical drug design and development, it is assumed that the clinical response of patients is approximately the same. However, the response to a clinical treatment may vary from patient to patient. All of these factors are difficult to consider systematically from the outset in a drug design program and therefore further hin-

der the successful therapeutic use of drugs. In this context, the adoption of AI and other innovative technologies, and the use of the great information available in multiple sources, allows specific, more precise treatments and changing the health system towards a future where medicine is personalized, predictive, preventive and participatory. In the future, the inclusion of more diverse data including understudied populations, the implementation of strategies to minimize exclusion and bias, and new AI technologies are expected to have a significant impact on treatments and patient outcomes.

Drug discovery and development combine computational, experimental and clinical methods. There is currently no single solution that guarantees successful drug discovery and it is important to remain receptive to new technologies. The socalled “augmented intelligence” has applications in the process of drug discovery and development, in decision-making, and also in the development of more effective therapies from already approved drugs. The variability in the response among patients to the same therapeutic treatment imposes another challenge.

Additional challenges include lack of data transparency and collaboration; the lack of interdisciplinary trained personnel and efficient human communication between research groups. However, AI methods provide the opportunity to diversify applications in drug design, provide better predictive models, streamline research and help propose effective treatments in a personalized way. Proper validation of AI results will allow feedback and improvement of existing models and lay the groundwork for new paradigms.

The proper integration of basic and more sophisticated bioinformatics, computing, nano-

References

technology and pharmacogenomics strategies is expected to lead to the next stage of advances in successful drug discovery and therapeutic use.

Acknowledgements

To the program of Research Projects in Artificial Intelligence in the Innovation Space UNAM –HUAWEI, project no. 7, and to the DGAPA, UNAM, Program of Support for Research and Technological Innovation Projects (PAPIIT), project No. IN201321. F.I. S-G. thanks CONACyT, Mexico, for PhD Scholarship No. 848061.

Bajorath, J. (2022). Deep machine learning for computer-aided drug design. Frontiers in Drug Discovery 2 , 829043.

Bender, A., Schneider, N., Segler, M., Patrick Walters, W., Engkvist, O., & Rodrigues, T. (2022). Evaluation guidelines for machine learning tools in the chemical sciences. Nature Reviews Chemistry 6 , 428–442.

Gasteiger, J. (2020). Chemistry in Times of Artificial Intelligence. Chemphyschem: A European Journal of Chemical Physics and Physical Chemistry 21 , 2233–2242.

Jiménez-Luna, J., Grisoni, F., Weskamp, N., & Schneider, G. (2021). Artificial intelligence in drug discovery: recent advances and future perspectives. Expert Opinion on Drug Discovery 16 , 949–959.

López-López, E., Bajorath, J., & Medina-Franco, J. L. (2021). Informatics for Chemistry, Biology, and Biomedical Sciences. Journal of Chemical Information and Modeling 61, 26–35.

Medina-Franco, J.L., Martinez-Mayorga, K., Fernández-de Gortari E., Kirchmair, J., & Bajorath, J. (2021). Rationality over fashion and hype in drug design [version 1; peer review: 2 approved]. F1000Research 10(Chem Inf Sci), 397.

Saldívar-González, F. I., Aldas-Bulos, V. D., Medina-Franco, J. L., & Plisson, F. (2022). Natural product drug discovery in the artificial intelligence era. Chemical Science 13 , 1526–1546.

Saldívar-González, F. I., & Medina-Franco, J. L. (2022). Approaches for enhancing the analysis of chemical space for drug discovery. Expert Opinion on Drug Discovery 17, 789-798.

Schneider, G. (2018). Automating drug discovery. Nature Reviews. Drug Discovery 17 , 97–113.

Schneider, G., & Clark, D. E. (2019). Automated DE Novo drug design: Are we nearly there yet? Angewandte Chemie 58 , 10792–10803.

SMOKE FREE SWEDEN 2023

A ROADMAP TO A SMOKE FREE SOCIETY

Smoking cigarettes or other combustible tobacco products is the biggest cause of noncommunicable deaths in the world. According to the World Health Organization (WHO), eight million deaths were attributable to tobacco in 2017(1). Yet there remain more than one billion smokers in the world today, despite the health risks of smoking being widely known. The bulk of tobacco-related illness and death is ultimately caused by the inhalation of toxic smoke from combustible cigarettes into the lungs(2). Nicotine, while addictive, has not been proven to be the direct cause of diseases or health damage, such as lung cancer, stroke, and chronic obstructive pulmonary disease (COPD)(3).

For several decades now, reducing the risk associated with tobacco consumption has been a central issue for different health authorities worldwide, such as in countries like the United Kingdom, Germany, and New Zealand, which have a strategy of focusing on the use or consumption of reduced risk options by the smoking population, such as heated tobacco, snus and electronic nicotine delivery systems or vapes.

Recently Sweden, a country with a population of just over ten million will, based on current trends, soon become the first nation to give up cigarette smoking. Both the European Network for Smoking and Tobacco Prevention (ENSP) and the World Health Organization (WHO) consider countries to be officially smoke free when less than 5% of the adult population smokes tobacco.

The European Union (EU) has tasked all its Member States with becoming ‘smoke free’ by 2040. Barring a dramatic shift in progress, most will miss this target by some distance. Sweden, however, will achieve this historic milestone as

Source: Figures post 2012,

Health

Useoftobaccoandnicotineproducts(self-reported)byage,genderandyearPre

The Public

Agency of Swede,

2012 extracted from Karl Fagerstrom, The case of snus.

soon as this year - 2023. That is an incredible 17 years ahead of the EU target date and before every other nation in the bloc is even within sight of the achievement.

To obtain such a result, Sweden has proactively implemented what the WHO Framework Convention on Tobacco Control (FCTC), Article 1 (d) suggests: “tobacco control” means a range of supply, demand and harm reduction strategies that aim to improve the health of a population by eliminating or reducing their consumption of tobacco products and exposure to tobacco smoke. By employing strict tobacco control measures, the consumption of combustible tobacco products was made less attractive for adult smokers, while facilitating the use of less harmful noncombustible forms of tobacco and nicotine. Because of this, Sweden has always had lower smoking rates than the rest of Europe. Key to Sweden’s tobacco control success was embracing harm reduction strategies, thereby creating a realistic and replicable roadmap to a smoke-free world.

During the last five decades, the Swedes have progressively and systematically made smokeless and less harmful alternatives to cigarette smoking

accessible, affordable, and acceptable to their population. In supporting these smoke free options such as snus and, in recent years, oral nicotine pouches and electronic systems for nicotine administration (otherwise called vape

products), their pragmatic, enlightened approach has delivered public health gains. In fact, a study by the Swedish Institutet för Tobaksstudier, or Institute for Tobacco Studies, using data from the WHO’s 2012 Global Report on Mortality Attributable to Tobacco, concluded that if other EU countries practiced the same tobacco

*2022 – data for age group 16+ (data available only for 2021 and 2022); snus and nicotine pouches include categories of ‘tobacco snus’ and ‘nicotine snus’. Nicotine snus means nicotine pouches without tobacco. Source: The Public Health Agency of Sweden, Use of tobaccoandnicotineproducts(self-reported)byage , gender and year, 2022.

Source: Global Burden of Disease Database, 2019.

consumption patterns as Sweden, no fewer than 355,000 lives per year could have been saved.

Results:

Over the past 15 years, Sweden has slashed its smoking rates from 15% in 2008 to 5.6% today(4).

The EU’s average smoking rate is currently 23%almost five times higher than Sweden’s. In many EU countries, one in three people still smokes(5).

Sweden’s incidence of cancer is 41% lower than the rest of its European counterparts, corresponding to a 38% lower level of total cancer deaths(6).

24 of the other 27 EU Member States have a tobacco-related mortality rate twice as high or more than Sweden relative to population size(7).

Sweden has a 39.6% lower rate of death of all tobacco-related diseases compared to the EU average. Sweden is one of the three countries with the lowest number of deaths attributed to lung cancer(8).

With a smoking level of only 3% in those aged 1629 years, Sweden boasts the lowest level of youth smoking in Europe(9).

The International Multi-Stakeholder Study Group on Smoke Free Sweden will be engaging widely to elicit more views and insights to better understand Sweden’s success. Nonetheless, Sweden’s experience tells us that the following steps are key to driving considerable reductions in smoking prevalence:

1. Fundamental differentiation between combustible and non-combustible forms of tobacco and nicotine: recognition of the evidence that smoke free alternatives are genuinely less harmful and pose fewer risks than smoking, combined with support and encouragement for smokers, who cannot or will not quit, to switch.

2. Risk differentiation between various forms of tobacco and nicotine products: the Swedish Government has recently requested the recognition and mapping of the “relative risk” of all tobacco and nicotine product categories. This could facilitate the provision of more accurate risk communication to consumers, allowing smokers to better understand the relative risk and more carefully choose the smoke free product that is most effective for them. The gold standard remains, of course, that consumers quit all forms of tobacco and nicotine altogether.

Source: European Commission, Special Eurobarometer 506, 2021.

3. Access to smoke free alternatives to cigarettes: tobacco control measures alone are not sufficient. Access to smoke free alternatives is critically important. In Sweden, snus, oral nicotine pouches, e-cigarettes and heated tobacco are all available, and can be bought both on and offline.

4. Educating the public on the smoke free alternatives: no product is risk-free but being able to achieve a risk reduction of 95% or higher will translate into significant benefits for smokers who quit. Smokers need access to evidence-based information about better alternatives to smoking, especially in view of a spate of misinformation about their safety. For example, a recent survey conducted in the United Kingdom found that two thirds of smokers believed e-cigarettes to be just as harmful as cigarettes, despite evidence showing they are at least 95% less harmful.

5. Consumer acceptance: smoke free alternatives must also be genuinely acceptable to smokers as a better alternative to cigarettes. For this to be the case, products need to be satisfying and capable of being smokers’ first preference –which means ensuring a range of flavours and

nicotine concentrations for consumers to buy. In a nutshell, there is a need for clear differentiation between the treatment of cigarettes and alternative products that make it easier for smokers to switch.

6. Affordability: policy settings should support the adoption of reduced harm, smoke free alternatives by making them more affordable than the most harmful combustible cigarettes. This means low or no excise on smoke free alternatives, which in turn eliminates financial barriers to switching away from cigarettes.

Taken together, these learnings will help countries struggling to beat smoking. It is our view that if the policies and approach of Sweden are replicated, countries around the world will be able to become smoke free, just as Sweden has done. Governments around the world have implemented tobacco control measures, yet they have struggled to further reduce stubbornly high smoking rates. In order to make further progress and to achieve a smoke free society, other policies must be considered.

Source: WHO International Agency for Research on Cancer, Estimated age-standardized incidence rates (World) (2022)

References

World Health Organization (2019), WHO global report on trends in tobacco smoking 2000-2025. third edition.

Abrams, D., Glasser, A., Pearson, J. Villanti, A., Collins, L., and Niaura, R. (2018). Harm Minimization and Tobacco Control: Reframing Societal Views of Nicotine Use to Rapidly Save Lives, Annual Review of Public Health. From: https://doi.org/10.1146/annurevpublhealth040617-013849

Benowitz, N. L., Hukkanen, J., & Jacob, P., 3rd (2009). Nicotine chemistry, metabolism, kinetics and biomarkers. Handbook of experimental pharmacology, (192), 29–60. From: https://doi.org/10.1007/978-3-540-69248-5_2

The Swedish Public Health Agency, Use of tobacco and nicotine products (self-reported) by age, gender and year, 2022.

Special Eurobarometer 506: Attitudes of Europeans towards tobacco and electronic cigarettes (v1.00). (2021). European Commission, Directorate-General for Communication. From: http://data.europa.eu/88u/dataset/S2240_506_ENG

Ramström, L. (2020). Institute for Tobacco Studies. Death rates per 100,000 attributable to tobacco – Sweden and the rest of the EU in 2019. Compiled from The Global Burden of Disease Study. DOI - 10.13140/RG.2.2.29008.12806

Snus Commission (2017) Snus saves lives: A study of snus and tobacco-related mortality in the EU.

Eurostat (2019) Cancer Statistics - Specific Cancers.

Global Burden of Disease Database, (2019)

Karl-Olov Fagerström, PhD

Swedish psychologist at the University of Uppsala, ex-Editor in Chief for Journal for Behaviour Therapy; specialist in the fight against smoking. Co-author, The Swedish Experience: A Roadmap for a smoke-free society.

Dr. Delon Human

President and CEO of Health Diplomats, a specialized health, nutrition and wellness consulting group operating worldwide. He has acted as adviser to three WHO Directors-General and to the UN SecretaryGeneral on global public health strategies.

Hakim Mohamed

Co-Founder & CEO Triwest Research Associates USA

This is my third year attending the Clinical Research Insider Summit, and every year it gets better and better. I am so happy to be one of the speakers; it is an honor to be part of this event because I think it is very beneficial for anyone who would like to be part of the process involved in clinical trials. It is a very educational Congress, thank you very much!

Vicente Alciturri

I am so happy to have participated again in this event and in the conference, which I believe is very important to continue promoting clinical research in Mexico; this will be a meeting forum for many years to come so that all of us involved in research continue to grow as a community. We will continue to collaborate!

Thank you!

International Director at Semicrol Spain

It has been a privilege to have participated in this event, in three days of continuous work with Workshops, Panels, and a lot of interaction between all the participants of an interdisciplinary event, with a level that forces us to continue working in favor of health through research. Congratulations to Marco Cid for this initiative and to Drox Health Science for what they have put as a very fertile ground to continue building.

Thanks a lot!

Georgina Garcia

President of the Medical Cluster in Jalisco. Mexico

For those of us have worked in the generation of evidence and clinical trials for a long time, we know how complex it can be to reach a conclusion and publish it. But none of this is new. The first clinical study as we know it today was conducted by Dr. James Lind in England in 1747. Your objective was to learn about the importance of citrus fruits in the prevention of scurvy. The result was key for understanding the cause of the disease as well as its treatment. This fact opened up the possibility of continuing to make long-distance sea voyages. Thanks to him, International Clinical Trials Day is celebrated every May 20.

But unfortunately, it doesn’t always have a happy ending, as it would in a fairy tale. To put it in context, out of more than 10,000 molecules that are candidates to become a drug that goes on sale to the public, only one will make it. The complete

Luis Fernando Tejado Gallegos PhD

Generation Lead LATAM; Clinical Trials Medical Manager at AstraZeneca, Mexico.

development process of a new molecule can take anywhere from 10 to 15 years, counting from the early research phase through to application in human clinical trials (phases I to III).

This is not the only unoptimistic figure. It’s mentioned that up to 90% of the processes do not reach a successful conclusion. It is worth mentioning here that this is due to various factors and different stages of research development. So we can divide the cases of failure between those caused by the product under development itself and what happens during the human clinical trial phases.

The literature mentions that among the main causes of failure of the product under development to reach term and subsequent commercialization is the lack of clinical efficacy (40-50%) as the main

The ideal clinical study: dream possible or fairy tale?

Evidence

“Science, my lad, is made up of mistakes, but they are mistakes which it is useful to make, because they lead little by little to the truth”

-Julio Verne

factor, which is generated due to failures in the early stages of the search for the ideal product for the desired disease.

In the second place, it mentions the toxicity it produces (30%) because it is often not easy to extrapolate what happens in vitro or animal studies with what happens in a more complex organism such as ours. In third place, we have the properties of the drug (10-15%) related to mechanisms such as solubility and bioavailability. And lastly, poor strategic planning (10%) on the part of the sponsor.

Speaking of the failures during clinical studies, in chronological order, we will talk about the difficulty of enrolling healthy subjects in phase I studies; there is not much data reported, but the percentage of inclusion vs. expected is so low (in China it is mentioned in a review of studies that the average success rate was only 27.8%). The success

of enrollment can determine the quality of the clinical trial; low recruitment can lead to the study being canceled or not progressing to the clinical trial, in addition to the impact on the resources and money invested.

These problems are also present in phases II and III, where other types of reasons are observed, among which are the budget for the project (financial), those related to the study itself (delays in starting, lack of interest of the subjects, etc.), the design itself (unclear or relevant objectives) and those related to the work team, which can be as simple or as complex depending on the type of study, such as lack of education and/ or training, rotation, work overload, etc. Finally, some of the biggest conflicts are those related to the subjects, the most important part of the study, due to the interest or benefit for them to participate in the research study.

As illustrated in the graphic above, there are many areas and parties involved, from design and basic research to the implementation of the clinical study in its phases with humans. Each of those involved has specific responsibilities in getting that research product to the final stage and seeing it on pharmacy shelves for the benefit of patients.

Finally, I don’t believe that there has ever been an ideal clinical trial since each one is made for and by human beings, which immediately gives it the status of imperfection. There are still many things to continue working on in the different stages of the development of a new molecule. We must learn from our mistakes and have increasingly skilled and interrelated teams for the conduct of clinical studys.

References

Duxin S. et al. 2022. Why 90% of Clinical drug development fails and how to improve it. Acta Pharmaceutica Sinica B. 12 (7) : 3049-3062 Hongmin L. et al. 2022. A retrospective study: screening failure analysis of 1,058 healthy volunteers in phase I clinical trials. Annals of Palliative Medicine. 11 (7): 2464-2477

Briel M. et al . 2022. Exploring reasons for recruitment failure in clinical trials: a qualitative study with Clinical trial stakeholders in Switzerlad, Germany and Canada. BMC Open Access. 22 : 844

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Marco Antonio Loza Mejia, PhD Professor and researcher, Department of Chemical Sciences, Universidad La Salle, Mexico.

Research and Development of Molecules from the Perspective of Universities

Research of new molecules with therapeutic activity is an activity that requires highly trained personnel in various fields of chemical-biological sciences, health sciences, and administration. In addition, a significant investment of time and economic resources is required.

Depending on the type of molecule (macrobiomolecule such as a monoclonal antibody or a chemically synthesized small molecule) and therapeutic application (oncological, anti-infectious, cardiovascular), the figures can range from 850

to 2 billion dollars, with development times ranging from 7 to 16 years. These figures force us to analyze why we have reached these levels of investment of time and money and what opportunities exist to optimize this process.

Once again, depending on the therapeutic application and the type of molecule, the percentages of investment allocated to the preclinical and clinical sides vary. Although, in the last twenty years, costs have increased in the clinical phase due to greater demands and regulatory oversight

to guarantee the safety and efficacy of the treatments being evaluated, the fact is that there has also been an increase in time and costs in the preclinical phase.

This is where Universities can support and catalyze the development of new molecules. It is estimated that 60% of new therapeutic ideas, either the proposal of new mechanisms of action or the generation of new chemical structures, do not come directly from large pharmaceutical companies, but from what we call “The Academy” (that is to say, universities), and spin-offs that arise from the postgraduate programs of higher education institutions.

Since academic institutions do not aim to launch new pharmaceutical products, many of these inventions end up being licensed to large pharmaceutical companies, which are responsible

for 76% of the drugs that reach higher clinical stages. In this scenario, the pharmaceutical industry and academic institutions can be allies to achieve the objectives pursued by each sector. In Mexico, although there are clear examples of industry-academia linkages, these are more of an exception than the norm. But it is not because our country lacks strength and inventiveness: since 2013, according to the Scopus database, more than 271 thousand papers and 1,825 patents have been published by Mexican institutions, of which 43 thousand papers and just over 300 patents have as keywords or in their title the term drug.

On the other hand, the academic sector can be an excellent ally as a consultant for the resolution of industry problems, providing expert insight that allows innovative and effective responses to the difficulties that may arise in both the preclinical and clinical areas.

Guillermo Pepe

Business economist from Di Tella University in Buenos Aires. He has been at the helm of Mamotest, the healthtech winner of the Zayed Sustainability Prize (United Arab Emirates, 2022) and the Global Humanitarian Award given by the American College of Radiology (United States, 2019), for more than a decade. In addition, Mamotest is a Tech Partner of the World Economic Forum and has been recognized by the United Nations as one of the five most disruptive global startups in healthcare. The Norrsken Foundation named it one of 100 companies that can save one billion lives.

Defeating breast cancer with the Power of Data

Breast cancer has the highest incidence in the world, although it is also cancer with the potential to become the least lethal, as it has a 98% sur-vival rate if detected and treated at an early stage. All in all, it is responsible for the death of almost 700,000 women each year and although this disease does not “discriminate” against any woman based on her origin or socioeconomic profile, 70 percent of them live in developing countries. So what is the big difference between a woman who manages to beat breast cancer and one who does not? The answer is directly related to her degree of access to a health system that guarantees her first-rate care and, of course, that all this happens on time.

Unfortunately, it is not only about the (titanic) task of raising awareness and educating women about the vital importance of having their annual mammography. What we have learned at Mamotestafter more than a decade of development, innovation and expansion in Latin America, going deep into the field and accessing real-world data like no other healthcare company, including laboratories - is that we are facing a problem with several causes and also that it is necessary to act on multiple fronts to drastically reduce deaths caused by breast cancer, and that none of this can be achieved without data.

DataForGood: data that saves lives

The history of Mamotest began in 2013, intending to democratize access to health for all women in Latin America. Thus, long before the accelerated and forced explosion of telemedicine due to the Covid-19

pandemic, we had already created a company with a technological footprint and proven social impact, owner of the first remote mastography network in the region and globally recognized by some of the most prestigious organizations in the world such as the United Nations, American College of Radiology, Harvard University, MIT, World Economic Forum, Inter-American Development Bank and Norrsken Foundation, among others.

Along the way, we became aware of the invisible but relentless power of cultural and psychological barriers: fear of pain, shame, or embarrassment as factors that we could not underestimate in understanding why there is still so much work to be done in encouraging women to have an annual check-up.

But we also discovered an insight that is equally overlooked by the actors in the healthcare system, from medical professionals and local hospitals to large international laboratories. The fact is that, from Mexico to Argentina, throughout the region, we find a fragmented healthcare system that is not designed to accompany the patient, so the woman must try to navigate it alone, without information, and without the possibility of making the best decision for her diagnosis.

In other words, defeating breast cancer and providing a quick and accurate diagnosis was just the tip of the iceberg: according to our data, around 30% of patients did not access treatment in time to be cured, as a combination of lack of professional guidance, psychological assistance and emotional support throughout the process led them to give up and drop out.

Through our latest technological development, Bolder, which combines the latest advances in Artificial Intelligence with a 100% human approach, we reach more than half a million women (regardless of their resources) and 3,500 healthcare professionals with 100% traceability, providing and generating data that already saves lives: during 2022, the first year of Bolder’s operation, 87% of our patients diagnosed with breast cancer accessed treatment on time.

Artificial Intelligence, the next frontier

By accompanying them throughout the process from all aspects (medical, psychological, emotional, economic), we are generating new knowledge,

based on real world data, which will be available to leaders in different areas (local and national governments, global policymakers, health centers and professionals, the pharmaceutical industry, the scientific community, etc.) to reduce time, costs and effort in breaking down barriers to treatment, developing better drugs, passing laws, influencing public policy and promoting awareness campaigns, among other key courses of action to combat the disease on all fronts.

In the medium/long term, Bolder’s next frontier will have everything to do with using the full potential of Artificial Intelligence, not only for breast cancer diagnosis but also to accompany each patient throughout her treatment. There are certain basic functionalities that we intend to include, such as, for example, that her doctor notifies her through Bolder

that she should have a breast ultrasound and then the platform collects and presents to the user the available appointments for such a study in the nearest days, taking into account different health centers near her home, so that she can complete the request “in just one click”.

In a second and more ambitious stage, at Mamotest we are working so that Bolder can become a platform for predicting the outcome of treatments, that is, combining all the information available on each patient (including medical, clinical, psychological, and even socioeconomic conditions) and predicting the ideal treatment for each case. Science fiction? No, only science or, better said, ethical science: what we at Mamotest call “data for good”.

In Search of Exponential Impact

The best technology on the planet can be developed, but it is useless if there is no culture of care and prevention. This is a challenge that society as a whole must take on. Therefore, our mission is to generate a movement of companies, governments and allies who want to be agents of change and contribute to create a health system that keeps us healthy.

Health is and should be a public matter, with policies, rights, and guarantees that reach all people, no matter where they live or their level of resources.

Since our inception, Mamotest has been working with national, provincial, and local governments in search of greater scale and penetration. However, there are countries and regions where the absence of a strong, efficient, and/or committed government often leads us to diversify our strategies.

In recent years, we have developed a new business model that allows us to think of an exponential growth of our impact by empowering us in the corporate environment. This involves generating alliances with private companies that, especially after the Covid-19 pandemic, understand that looking after the health of their employees (especially in terms of prevention) is both a responsibility and an opportunity.

The main differential of our partnership system is that we aim to move from a dynamic of one-shot action (as it would have been in the past, for example, a specific campaign for “Pink October”) to a continuous and long-term collaboration. Under this premise, we invite companies to address the issue of breast cancer with an eye toward the inside of their organization.

In other words, we focus on generating a culture of care among its employees, providing women at risk with all our tools and services so that they can have their annual mammography and, in the event of a positive diagnosis, receive the necessary support from us to get through the treatment process in the best possible way.

The companies that trust Mamotest receive all the guidance, logistics, and infrastructure necessary to implement these alliances, which, on the other hand, have already shown very positive results in terms of the positioning of their employer brand, improving engagement rates, and sense of belonging. This is further proof that, if we manage to create -everyone in his or her role in society- a health system that keeps us healthy, this is what is generated: a virtuous circle with multiple benefits and exponential impact for all parties.

Courtesy: Mamotest

Dr. Mafer Arboleda

Associate Director of Research at Santé Cannabis, a leading clinic specializing in the prescription of medical cannabis in Quebec, Canada. Anesthesiologist specialized in chronic pain and palliative care by UNAM and INCMNSZ. Medical surgeon from the Pontificia Universidad Javeriana, Bogotá. Clinical fellowship and postdoctoral studies in Supportive Care in Cancer and Medical Cannabis at McGill University, Montreal, Canada.

#DrMaferArboleda #MaferCannabisMD

Speaker at International Clinical Research Insider Summit 2024

How much do you know about the therapeutic use of cannabis?

Dr. Mafer Arboleda seeks to inform and demystify cannabis so that its benefits can be used by those who need them in a responsible and safe way. In our special edition, Dr. Arboleda shares with us a series of essential facts for the correct use of medical cannabis.

Who cannot use cannabis for medical purposes?

Today we know that this is not for everyone and that cannabis has indications but also contraindications; some patients should not be consuming cannabis for any reason. For example, a person who had an arrhythmia, i.e., the heart beats irregularly, if given THC, I promise you that this patient ends up in an emergency room. The same thing happens with a person suffering from schizophrenia, bipolar disorder, or uncontrolled psychotic episodes when receiving THC.

Whenever we talk about a responsible and safe prescription of cannabis-based medicines there must be a trinomial: 1) we need a patient who is a candidate for this therapy with a complete clinical history; 2) a physician properly trained in prescribing cannabinoid-based medicines; currently there are courses and workshops offered from different universities around the world. And 3) we need a product that complies with quality standards and sanitary support, which is the biggest problem we have today in most countries.

¿Who is vulnerable to the development of psychotic episodes due to cannabis use?

Psychotic episodes are part of intoxication and problematic cannabis use. Research shows that cannabis may be linked to mental health problems, especially disorders involving psychosis. Cannabis use in adolescents and young adults increases the risk of developing psychotic episodes, anxiety, or suicidal ideation. These effects account for 25-30% of emergency department visits related to cannabis use, and up to 50% of patients with psychotic episodes associated with cannabis use may develop schizophrenia.

In summary:

1. Those who started using them at an early age during adolescence.

2. Those with a genetic predisposition to psychosis.

3. Those who have had childhood trauma.

4. Those suffering from other psychiatric

disorders.

6 facts every cannabis user should know

1. We all have cannabinoids in our bodies that we produce naturally from our organisms.

2. Cannabis use for adult use can lead to cannabis use disorder or problematic cannabis use, especially when we are talking about excessive use, that is, several times a week or consuming high concentrations of THC.

3. THC use in children under 18 years affects their neurocognitive development and may increase the risk of developing psychological disorders.

4. THC and CBD are useful tools to control the symptoms produced by some diseases such

as chronic pain, refractory epilepsy, multiple sclerosis, nausea and vomiting secondary to chemotherapy, anorexia in HIV and cancer (lack of appetite), Parkinson’s disease, social anxiety disorder, post-traumatic stress disorder, among others.

5. THC consumption can produce side effects such as tachycardia, hypotension (lowering of blood pressure levels), anxiety, and headache, and at much higher concentrations of THC, one can experience a feeling of euphoria, paranoia, and even psychotic episodes.

6. Currently, especially in the United States, products containing Delta 8 THC are marketed, which may endanger public health and, in addition, are marketed for therapeutic purposes that have not yet been evaluated or supported by clinical studies. Among its adverse effects, vomiting, hallucinations, difficulty in standing up and even loss of consciousness have been reported.

Brain chips; Neuralink obtains FDA approval to begin human clinical trials

Elon Musk has taken a new step in his career by presenting his new project called Neuralink, a technology that seeks to implement electronic devices in the human brain to establish two-way communication between the mind and technological devices. The device is the size of a coin and measures about 8 millimeters in diameter.

This chip would have the ability to read and write information directly in the brain, which could allow users to control computers, mobile devices, and even vehicles just by thinking about them. Its goal is to help people with paralysis, neurological disorders, spinal cord injuries, and brain conditions. According to Elon Musk, Neuralink’s technology could be used in the future to treat diseases such as epilepsy, depression, and Parkinson’s by allowing doctors to more accurately and efficiently access the human brain.

For the time being, the first applications in humans will be made to improve vision and for people with

little or no ability to manage their muscles, and they even promise to connect the Neuralink device to the spinal cord for people with a broken neck. In addition, the device could be used to improve the cognitive capacity of humans to enable them to process complex information faster. So far, they have only conducted tests on animal brains; they shared their success through a video showing a monkey playing a mind-controlled video game.

The Neuralink project has been enthusiastically received by the scientific and technological community, although some experts have raised concerns about the security and privacy of the technology. However, Musk has assured that the technology will be completely secure and that users will have full control over the data collected. Patient recruitment is expected to begin in the coming months.

Clinical Research Insider Editorial

Carmen

de la Rocha

PhD

Clinical research in academia vs. industry-sponsored;

opportunities from both sides

Research is an activity aimed at obtaining and applying knowledge to solve problems using the scientific method.

Pharmaceutical and medical device companies fund most clinical trials; their efforts are directed to a greater extent at the initial authorization of their products. On the other hand, the research conducted in academia is usually non-commercial and its main objective is the generation of knowledge to answer questions associated with the usual practice of products that are already available in the market.

In academia, the researcher is the one who conceives the idea, develops the protocol, obtains funding, and analyzes the results. Both areas are important in the generation of knowledge, they have their strengths and limitations, and it is very important that both parties share the results obtained in their research, since the medical community requires to know them to apply them in their medical practice.

Globally, it is estimated that about 17% of clinical studies are not published in any source or format. On the other hand, 32% of the trials generated

Director of Research and Development at Drox Health Science. PhD in Biotechnology, Master in Biochemical Engineering. Member of the National System of Researchers level I.

by the industry are only published in registries, but not in medical articles. In Mexico, as of March 15, 2023, 528 active clinical studies (recruiting patients) were found on the Clinical Trials page, of which 72% are industry-sponsored. In relation to intellectual property, the vast majority of Mexican patent holders registered in Mexico correspond to public research institutions. That is, in Mexico, scientific and technological production is very balanced between both areas in terms of quantity.

Part of the challenges of academic research is the generation of new products that can reach the market. This difficulty is largely associated with the fact that researchers carry out other tasks such as teaching, and therefore cannot focus their activity exclusively on research. Also, their experience in commercial, intellectual property and regulatory issues is not as strong, while in the industry they

References

have specialized areas that facilitate these tasks. In addition, the availability of material, economic and infrastructure resources is limited.

On the other hand, academic research is independent, therefore impartial and devoid of conflict of interest. Because of this, it presents results with clinical relevance in scenarios not covered by industry-sponsored research.

It is essential to build solid relationships between academia and industry for the strengthening of clinical research, as well as to promote the publication of results in both areas, share regulatory, intellectual property and commercial knowledge within academia and strengthen regulatory requirements within universities, so that the results of studies generated within academia can be extrapolated across borders and regulations.

U.S. National Library of Medicine at the National Institutes of Health - Clinicaltrials.gov. Accessed March 15, 2023. Retrieved from: https://clinicaltrials.gov/ Blümle, A., Wollmann, K., Bischoff, K. et al. (2021) Investigator initiated trials versus industry sponsored trials - translation of randomized controlled trials into clinical practice (IMPACT). BMC Med Res Methodol 21 , 182. Retrieved from: https://doi.org/10.1186/ s12874-021-01359-x

Instituto Mexicano de la Propiedad Intelectual. Consultation date: March 15, 2023. Retrieved from: https://www.gob.mx/impi/ documentos/ López, A. (2021). Reflexiones sobre el lX Premio FEI al Investigador Innovador del año 2021. Dificultades del desarrollo de nuevos fármacos en la investigación académica. Real Acad. Farm. Vol. 87. nº 4. PP. 367-370. Retrieved from: https://analesranf.com/wp-content/ uploads/2021/87_04/8704_00.pdf

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Claudia Mejia Morales PhD

Research and Development Analyst at Drox Health Science.

Natural products for the development of new drugs

An extensive review of therapeutic agents approved worldwide after 39 years has identified that about 32% of the small molecules approved during that period correspond to natural products (Newman & Cragg, 2020). Additionally, more than 60% of synthetic drugs are derived from natural products, of which the natural active compound constitutes 75% of cancer drugs. (Sharifi-Rad, et al., 2019).

Vincristine, an alkaloid of natural origin, isolated from the plant Catharanthus roseus L., included in the list of essential medicines of the World Health Organization, has been of great importance to treat different types of cancer, such as acute lymphoblastic leukemia, diffuse large B-cell lymphoma, among others. In 2019, there was an acute shortage of vincristine sulfate globally, leaving the oncology community in an ongoing struggle to find an immediate solution for the treatment of pediatric patients. (Palmer, 2019).

This naturally occurring drug has complex chemical structures that are often difficult to replicate through synthetic chemistry. Other drugs that come from natural products are: Qutenza®, a patch used for neuropathic pain and whose active ingredient is capsaicin isolated from the pepper plant, Capsicum annuum L., also, the drug Taxol® with antitumor activity whose active ingredient paclitaxel was isolated from the bark of conifers such as Taxus baccata L., or the case of metformin used for the treatment of type II diabetes worldwide, which has emerged inspired by the active ingredient galegina, from the plant Galega officinalis L.

Despite the importance that natural products deserve for obtaining new drugs, the structural complexity of the molecules, their separation and elucidation, in addition to the impact that species can suffer, has led to natural products being the inspiration for many of the synthetic or semisynthetic drugs, such as, anticancer drug Yondelis®, approved for the treatment of soft tissue sarcoma and recurrent ovarian cancer, and whose synthetic active ingredient, trabectedin, was initially obtained from a marine organism (Ecteinascidia turbinata), and after deciphering its biosynthetic route it was possible to find new chemical precursors for its formation. Nature continues and will continue to be a great source of inspiration for the generation of new medicines.

References

Newman, D. J., & Cragg, G. M. (2020). Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. Journal of natural products, 83(3), 770-803.

Palmer, E. (2019). Pfizer scrambles to fill void after Teva stops making chemo drug often given to children. FiercePharma. Published October 15, 2019.

Sharifi-Rad, J., Ozleyen, A., Boyunegmez Tumer, T., Oluwaseun Adetunji, C., El Omari, N., Balahbib, A., ... & C. Cho, W. (2019). Natural products and synthetic analogs as a source of antitumor drugs. Biomolecules, 9(11), 679.

Courtesy: Rally! Foundation

Wendy Lopez Romero PhD

Research and Development Analyst at Drox Health Science. PhD in Innovation in Medical and Pharmaceutical Biotechnology. Master in Molecular Biology.

Device validation and diagnostic tests

Validation is a process that determines the suitability of a test that has been properly developed, optimized and standardized for a specific purpose. One of the main reasons why the validation of a diagnostic device or test is sought is to assert that such an instrument will allow us to discriminate between patients suffering from a disease, syndrome or pathological process in particular from those who do not (healthy subjects). Then, the result of the device or test, together with the signs and symptoms for which the patient is entering, are the data that will help the doctor establish a diagnosis as accurate as possible to indicate the therapy that he believes is appropriate.

The validation process comprises a series of steps where more than one particular question will have to be answered, which will help establish the performance characteristics and technical specifications with which it will operate. As a first step, it is necessary to define the design and conditions under which the device or diagnostic test works, that is, what analyte does it identify?, what type of biological sample does it require (blood, saliva, urine, etc.)?, does the sample require a pretreatment, or how it will have to be prepared / diluted?, how many samples can I read simultaneously?, does it require a calibration curve or not?, What is the Gold Standard to use as a reference?

Subsequently, it will be necessary to define the target population, that is, the condition, syndrome or pathological process that the device or test can diagnose, in addition to the number of necessary individuals that will have to be tested through a sample calculation, establishing target values of sensitivity and specificity, with respect to the values operated by the gold standard, that is, If the Gold Standard has an 80% sensitivity, it would be desirable for the device or diagnostic test to have a sensitivity ≥ 80%, in order to operate as well or better than the reference test.

Some of the important aspects to consider for the study population that will have to be included are: 1) include patients with and without the disease; 2) those sick patients who are admitted must be patients to whom in common practice the test would be applied, that is, if they are considered for the diagnosis of tuberculosis, to be applied in subjects of whom tuberculosis is suspected and not of some other disease; and 3) that patients have a similar level of disease, to avoid spectrum bias. This will allow us to answer the following question: does the test discriminate between patients and healthy people where it is reasonable for the disease to exist? and Are patients with certain values in the test result more likely to make a diagnosis than others with other values?

Once the necessary patients have been included according to the sample size and established design, which can suggestively be: cross-sectional (from a single group made up of subjects to whom the test would be applied in usual practice), case-controls (defined by the gold standard) or cohorts (defined by the device or diagnostic test), we proceed to the evaluation of all participants in the test, which should be blinded (without knowing what the result of the GS was or if it is sick/healthy) to avoid over/underestimation bias.

Finally, we proceed to the statistical analysis of the results, for this conventionally a ROC curve (ReceiverOperating-Characteristic) is constructed, a statistical tool that is used to evaluate the discriminative capacity of a dichotomous diagnostic test (presence/ absence) and a cut-off point (threshold) is established from the observed results, which will help us define the final result of the test. Finally, the calculation of the performance characteristics is made: sensitivity, specificity, predictive values, probability rates, etc., by means of contingency tables (2x2 tables).

Although the statistical methods mentioned are not the only ones by which the validation of a device or diagnostic test can be reached, they are the most used for dichotomous and scale tests.

As an additional step, it is advisable to determine reproducibility, for this it will be necessary to follow a prospective study with cohort design in undiagnosed subjects, in order to evaluate the predictive diagnostic capacity of the device or test. This prospective nature and the fact of applying the test before making the diagnosis, allows the control of the main biases, being able to ensure both the independent and blind evaluation of the test to be validated and the diagnostic test with which it is compared.

As additional points of reproducibility, it is advisable to do tests with different operators and in different laboratories, to make sure of the measure of precision with which the device or test operates, regardless of who handles it or where it is used, as long as the methodology of use is followed.

References

Hajian-Tilaki, K. (2013). Receiver operating characteristic (ROC) curve analysis for medical diagnostic test evaluation. Caspian journal of internal medicine, 4(2), 627.

Donis, J. H. (2012).Evaluation of the validity and reliability of a diagnostic test. Avances en biomedicina, 1(2), 73-81.

Medina, M. C. (2011). Generalities of diagnostic tests, and their usefulness in medical decision making. Revista Colombiana de Psiquiatría, 40(4), 787-797.

Márquez-Fernández, A. J., Ramos-Ligonio, A., & López-Monteon, A. (2015). What do you know about the validation of diagnostic tests?. Revista Mexicana de Ciencias Farmacéuticas, 46(3), 86-90.

Cerda, J., & Cifuentes, L. (2012). Use of ROC curves in clinical research: Theoretical and practical aspects. Revista chilena de infectología, 29(2), 138-141.

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Saul Flores Unzueta PhD

Pharmacovigilance Units; adverse event reporting in Vigiflow, E2B and e-Reporting

Pharmacovigilance in Mexico is an activity aimed at the detection, identification, quantification, evaluation, and prevention of possible risks derived from use of medicines. Its scope includes the monitoring of adverse drug reactions/events, medication errors, failures in efficiency, counterfeit drugs, as well as drug abuse, misuse, and interactions.

This surveillance, in Mexico, is integrated into different levels, starting from the National Center for Pharmacovigilance, to state and institutional centers, the pharmaceutical industry, hospitals and health professionals inside and outside the facilities. All are governed by the World Health Organization (WHO). The WHO has established different efficient Pharmacovigilance mechanisms, one of them being

VigiFlow, which is a program that functions as the basis for Pharmacovigilance in each country. This program allows the collection, process, and analyze the data provided by the Adverse Drug Reactions (ADR) and Events Supposedly Attributable to Vaccination or Immunization (ESAVI) reports. In addition, it has the feature of being able to share this information with the WHO-UMC global databases or other national centers.

It has very useful features, such as using software with medical terminologies, like MeDRA and WHODrug, as well as causality analysis, like WHOUMC causality, Naranjo, and WHO AEFI systems. Undoubtedly, technological progress has favored Pharmacovigilance; it is important to be at the

Doctor of Science in Biotechnology. CEO of Lahoja Association for Research and Pharmacovigilance.

forefront of these changes. However, the scope of Pharmacovigilance in our country, and probably in the rest of the world, is more focused on Adverse Drug Events (ADE), than really adequate prevention and early detection of all the scopes that Pharmacovigilance has.

Thus, as health personnel, institutions, and even patients, it is our responsibility to carry out Effective

Pharmacovigilance, that is, give timely follow-up on the appropriate storage and distribution of medications, always review clinical interactions, interactions with food and between the drugs to be used, prepare an adequate prescription, follow schedules and the established dosage, as well as continuous monitoring of the patient in terms of efficacy and safety, and finally report adverse events.

Pharmaceutical Industry Health research establishments Distributors and marketers

Health professionals patients/consumers

VigiFlow

New VigiFlow CEFV, CICFV, CIFV, UFV

Courtesy: Saul Flores Unzueta, PhD

Dr. Ana Villaseñor-Todd

Challenges in clinical research; Antagonisms and challenges overcome

Slowing down science means being able to learn again, reacquainting oneself with things, reweaving the bonds of interdependence. It means thinking and imagining and, in the process, creating. It means, therefore, creating among ourselves and with others the kind of relationship that works for people who need each other to learn—with others, from others, thanks to others—what a life worth living demands, and knowledge worth cultivating. (Stengers, 2018, p. loc 1, 366).

In Mexico, we began the month of May with the decree that marks the end of the covid-19 health emergency, which began on March 23, 2020, three years ago. Four days after the World Health Organization (WHO) announced the end of the international emergency. The coronavirus pandemic

has left around 334,000 deaths and more than seven million infections in Mexico since its inception, according to figures from the National Council of Science and Technology (Conacyt).

At the beginning of the pandemic, when everyone paused their activities, including my research project in the clinical field and in the laboratory, a decade spent studying minimal hepatic encephalopathy was threatened. At that time, I witnessed the death of thousands of health professionals and I, in charge of the research project, had to review the safety conditions of each of the researchers and the study population before thinking about continuing with the committed goals.

Scientist, doctor by profession and Mexican businesswoman noted for her studies in minimal hepatic encephalopathy, oxidative stress, quality of life and social cognition. Certified by the Pan American Health Organization (PAHO) as a facilitator of MhGap; CEO VICOMMA Group.

“A crisis can be a real blessing to any person, to any nation. For all crises bring progress. Creativity is born from anguish, just like the day is born form the dark night. It’s in crisis that inventiveness is born, as well as discoveries made and big strategies. He who overcomes crisis, overcomes himself, without getting overcome.”

- Albert Einstein

Thanks to the wonders of Zoom, with the purpose of safeguarding the safety of the members of the research team, we linked in an emergent way with the president of the Mexican Psychiatric Association, at that time Dr. Bernardo Ng. We both invited Dr. Marlon Saavedra and Dr. Sandra Patricia Caicedo to the team and with the firm intention of making decisions in a reasoned way, we got to work.

We could not remain inherent while the world practically collapsed. We began our reflection

with a brainstorming among which stood out the film starring Jim Carrey, Stanley Ipkiss, the famous character of The Mask, who dictated in his most famous script: It is (The Mask) a bond of strength ... It’s supposed to make you feel powerful. This cinematic dialogue adapts perfectly to the prominence of masks during the covid-19 pandemic, becoming a synonym for authority, a valuable possession.

The psychological symbolism of the mask is explained by the use of facial expressions to construct ideas about feelings and desires, so the distortion caused by the mask encourages an individual response that works in two modes: one controlled and one implicit. Afterwards, our talk was immersed in the history of the famous “plague doctor” masks, described by Charles de Lorme.

Martin Kirschner (1879-1942) described its necessity in a chapter of his operating theory: “Measures to Combat Infections.” It was first used in the surgical field in Germany and the United States in the 1920s. The use of protective equipment against respiratory infections within the clinical setting was not questioned regarding its usefulness. This allowed this measure to be transferred to the general population with a beneficial impact, so even masks made with homemade materials are considered a better alternative to the absence of protection.

At the beginning of the pandemic, the general recommendation regarding the use of masks was to rationalize them to the medical field since it was considered that the evidence did not provide conclusive information to indicate it broadly. However, the concern of us and the entire scientific community generated a debate that led to the dissemination of multiple publications that support its usefulness. After weighing the scientific data, the World Health Organization (WHO) updated the guideline for widespread use. The systematic review and meta-

analysis that Lancet published in June 2020 was the final endorsement in favor of the indication. Unfortunately, not all countries (including Mexico) had considered making this measure mandatory for their citizens.

Given the circumstances, we chose to conduct an observational, descriptive, and cross-sectional study. The objective was to make a comparison between the countries that had adopted a stricter policy against the use of masks as a protective measure against the COVID-19 disease versus those that had not, comparing the proportion of infected and deceased by the SARS-CoV-2 virus.

We collected the information of the figures of cases and deaths from covid-19 registered on the official page of the coronavirus resource center of Johns Hopkins University. The type of policy against the use of masks was obtained from the official website of the #MASK4ALL movement,

and a flattening variable of the curve was added, with data obtained from the official website of the ENDCORONAVIRUS.org movement. The date for collecting the data was August 30, 2020. In our work we found a significant relationship between the mask policy and the number of infections, which supports the previous findings. The analysis carried out so far was useful.

The recommendation of the widespread use of masks was a valid measure with sufficient scientific support to reduce the number or speed of infections by the SARS-CoV-2 virus, and even gave us available scientific evidence supporting its impact on mortality/lethality, so it was necessary to consider it when establishing containment measures for critical episodes similar to that of the recent pandemic. Later, Eureka! Despite the pandemic and the fact that we are facing a modification in the technique of quantifying the products of oxidative stress, we included Dr. Lazaro,

an enthusiastic medical student who would bring valuable curricular tools at the end of the rotation. Because unexpectedly we had put together a manuscript of sufficient scientific value to support decision makers, who also had not increased the costs of the project.

By telling a little about this fantastic adventure in my sphere as a clinical researcher, I intend to present an example of how knowledge mobilization and capacity building in parallel sites can flexibly produce research to improve health services.

In the survey of damages, no one talks about the orphans of the pandemic. The COVID-19 pandemic has left more than 765 million diagnoses and 6.9 million deaths globally, according to the official count, although the WHO itself raised the figure to 20 million lives lost in relation to the disease.

The economic contraction that the covid-19 pandemic has caused (in Mexico of around 8.5% of GDP during 2020 according to INEGI data released in 2021) translates into a reorientation of the public budget and a reduction in international and private financing, particularly in areas not directly dedicated to the prevention, diagnosis, and treatment of the disease. Science in Mexico is one of many orphans that must be treated in an emergent way.

In general, we experienced a slowdown in all administrative and management processes, including access to analytical services (materials characterization and others), since many laboratory technicians were not working, or because they worked with as few people as possible.

We had difficulties in accessing and maintaining equipment (supply chains for laboratory reagents

were severely affected worldwide), as well as in procuring materials or components of laboratory equipment (because specialized technicians from abroad servicing certain equipment were not allowed to travel to Mexico). Even for cases in the area of clinical research, access to hospital or field samples was also delayed, affecting the timely delivery of research advances or results. The same applies in the case of experiments with living organisms, since the regulations to avoid contagion had limited this type of work.

Scientists in developing countries must remain focused and aware of cutting-edge science, regardless of how fast or slow they are conducting their own research. Promoting responsible and planned progress in the field of clinical research

is necessary. The current situation of health crisis and its ravages can be an opportunity to promote a demand from the community. It is also an opportunity to advance in terms of standardization and regulation, as well as to promote better practices in research, teaching, administration, and institutional management, in such a way that resilience can be cemented in the country’s scientific and educational activity. This implies that research and evaluation must take a more practical and participatory form to support continuous learning.

References

Saavedra-Delgado, Marlon E., Villaseñor-Todd, Ana, Caicedo-Agudelo, Sandra P., Lazaro-Presenda, David A., & Ng-Solis, Bernardo. (2021). Impact on COVID-19 morbidity and mortality according to mask use regulations. Gaceta médica de México, 157(3), 288-295. Epub Sep 13, 2021. Retrieved from: https://doi.org/10.24875/gmm.20000801

Delgado Ramos, G., Zanella, R., Cota Araiza, L., & Lopez Torres, R. (2021). Impact of the COVID-19 pandemic on research and teaching in nanosciences and nanotechnology in Mexico. Mundo Nano. Revista Interdisciplinaria En Nanociencias Y Nanotecnología, 14(27), 1e-19e. Retrieved from: https://doi.org/10.22201/ceiich.24485691e.2021.27.69685

Thomaz, S., & Mormul, R.. (2014). Misinterpretation of ‘slow science’ and ‘academic productivism’ may obstruct science in developing countries. Brazilian Journal of Biology, 74(3), S001–S002. Retrieved from: https://doi.org/10.1590/1519-6984.03013

Jorm, C., Iedema, R., Piper, D., Goodwin, N., & Searles, A. (2021). “Slow science” for 21st century healthcare: reinventing health service research that serves fast-paced, high-complexity care organisations. Journal of health organization and management, ahead-ofprint(ahead-of-print), 701–716. Retrieved from: https://doi.org/10.1108/JHOM-06-2020-0218

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Mission

Get civil society to join the contribution of a social cause, confront the challenge of demonstrating, with transparency and factual evidence, the social impact that has its contribution, as well as the positive meaning of its social investment. With the sole objective of reducing the effects caused by cancer, improving the life of children and young people who suffer from it.

Vision

Coordinate a lodging house for your temporary stay “a place away from home”, in Jalisco. For children and young people suffering from some type of CANCER or other complex disease.

During the stay you will accompany your father or mother or (some other relative), advising them so that they can go for studies or treatments to doctors. With our support, they will not have to worry about the expenses they involves getting a roof under which to rest, a bed to sleep in, a place where to eat. Thus, they will be able to focus their thoughts and energies on healing.

Sponsor a child with cancer:

BANCOMER

Vamos Guerreros AC

Bank account number: 0117334990

Standardized Bank Code: 01230001173349909

Mario Alberto Flores Valdez, PhD

Senior Researcher C at CIATEJ, A.C. in Medical and Pharmaceutical Biotechnology. Doctor of Science with a specialty in Biochemistry from the UNAM. Research Member of the international network VALIDATE “Vaccine development for complex intracellular neglected pathogens.”

Clinical study to evaluate the non-specific protection conferred by Bacillus CalmetteGuerin bacteria

Tuberculosis (TB) continues to be the bacterial disease that affects the most people worldwide, with about 10 million new cases each year, as well as the unfortunate death of 1.5 million people annually. Due to the ravages that TB continues to wreak worldwide, there are several efforts to replace or to boost the only vaccine available today against this disease: the attenuated bacteria (does not cause disease in immunocompetent people)

Mycobacterium bovis Bacillus Calmette-Guerin, better known as BCG.

BCG vaccine protects against the most deadly forms of TB during early infancy and childhood, such as disseminated and cerebral manifestations. However, BCG does not appear to be able to maintain good protection against the pulmonary form, which usually occurs in 8 out of 10 patients and results in transmission to others in the environment of those affected by TB. In addition to the protective effect,

even if limited against the pulmonary form of BCG against TB, attention has recently been drawn to the fact that this vaccine promotes, in a non-specific manner, a response that reduces complications of various diseases, especially of the respiratory type (so much so that there are several clinical studies to evaluate whether it helps to protect against COVID-19).

In particular, studies have found that the BCG vaccine:

1. In adults, decreased peak yellow fever vaccine viremia and improved resistance to malaria infection.

2. In addition, the BCG vaccine increases the antibody response to concomitantly or subsequently administered vaccines such as hepatitis B, H. influenzae type B, pneumococcal, tetanus toxoid, and influenza vaccines.

Due to these properties, the results of a randomized, placebo-controlled clinical trial were recently reported to verify the ability of BCG, in 3 different schedules, to promote an ex vivo immune response against various pathogens, both Mycobacterium tuberculosis and different from this one, including Escherichia coli, Staphylococcus aureus and Candida albicans (1). The schemes evaluated were: 1) to apply one regular dose (0.75 mg/mL of Danish BCG, applying 0.1 mL per person) to adults not previously vaccinated with BCG; 2) to apply a high dose (1.5 mg/mL of Danish BCG, applying 0.1 mL per person) to adults not previously vaccinated with BCG, and 3) revaccination with regular dose to persons who had already been vaccinated during childhood with BCG.

The latter scheme was proposed because of a recent report showing that the revaccination of adolescents with BCG promoted a reduction in Quantiferon® conversion from negative to positive, which was taken as evidence of protection against TB (2).

References

In this work it is mentioned that revaccination with BCG or the administration of high doses of BCG does not contribute to improve the capacity to induce cytokines in the face of non-specific stimulation beyond that induced by a standard dose of BCG, ex vivo. These results even represent an advance in the sense that, at least in the case of vaccinating adults for the first time with BCG, with standard or regular doses, protection against other diseases could be maintained without the need to increase the amount of vaccine applied.

Of course, there is a long way to go in defining whether these effects vary in the case of BCG vaccination of infants or toddlers, whether the strain used for vaccination would have any effect on the induction of nonspecific protection, and whether different populations have different capacities to respond to such nonspecific challenges.

Debisarun, P., Kilic, G., L. de Bree, C., Pennings, L., van Ingen, J., Benn, C., Aaby, P., Dijkstra, H., Lemmers, H., Domínguez-Andrés, J., van Crevel, R., G. Netea, M. (2023) The impact of BCG dose and revaccination on trained immunity. Clinical Immunology. Volume 246, Retrieved from: https://doi.org/10.1016/j.clim.2022.109208.

Nemes, E., Geldenhuys, H., Rozot, V., Rutkowski, K., Ratangee, F., Bilek, N., Mabwe, S., Makhethe, L., Erasmus, M., Toefy, A., Mulenga, H., Hanekom, W., Self, S., Bekker, L., Ryall, R., Gurunathan, S., Diaz-Granados, C., Andersen, P., Kromann, I., Evans, T.,... Mark Hatherill. (2018) Prevention of M. tuberculosis infection with H4:IC31 vaccine or revaccination with BCG. The New England Journal of Medicine; 379:138-149. Retrieved from: http://doi.org/10.1056/NEJMoa1714021

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Engineer in Biological Systems

Blanca Margarita Peredo Vazquez

Evolutionary Anthropology, the work of Svante Pääbo

On October 03, 2022, Professor Thomas Perlmann announced that the Nobel Prize in Physiology or Medicine was awarded to Svante Pääbo for his discoveries on the genomes of extinct hominids and human evolution.

Who is Svante Pääbo?

Svante Pääbo was born on April 20, 1955, in Stockholm, Sweden. He is the son of a relationship between chemist Karin Pääbo and biochemist Sune Karl Bergström, winner of the 1982 Nobel Prize in Physiology or Medicine. He did his postdoctoral studies under the tutelage of Allan Wilson, who in turn was a pioneer in the field of evolutionary biology at the University of Zurich, Switzerland.

By 1990 he became a professor at the University of Munich in Germany, and in 1999 he founded the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

What makes your research so interesting?

Pääbo was a pioneer in developing methodologies for the study of DNA in Neanderthals, a path that would take him several decades of his life; however, his efforts have been reflected in several important publications and discoveries, laying the foundations for a completely new scientific discipline, now called Paleogenomics.

Thanks to the standardization of methods, Pääbo

Clinical Trial Assistant at Drox Health Science

accomplished something seemingly impossible: sequencing the genome of the Neanderthal, through a 40,000-year-old bone. His study surprised many because when compared with the DNA of contemporary humans and chimpanzees, it was shown that this sequence was unique, giving rise to the discovery of a new ancestor, the Denisova. By 2010, Pääbo and his team published a paper showing the first comparative analysis of the genome of Homo sapiens and a Neanderthal, changing the course of history by demonstrating that the common ancestor between them existed 800,000 years ago.

References

Comparative analyzes have also shown that Neanderthal DNA is more similar to the DNA of contemporary humans of European or Asian origin relative to people of African origin.

This means that Denisova Neanderthals and Homo sapiens coexisted and interbred. Thanks to these discoveries we understand that gene sequences from our archaic ancestors influence the physiology of present-day humans, providing a new avenue for understanding human evolution and migration.

Nobel Prize in Physiology or Medicine 2022. NobelPrize.org. Nobel Prize in Disclosure AB (2023). May 6, 2023. Retrieved from: <https:// www.nobelprize.org/prizes/medicine/2022/summary/>

Krings, M., Stone, A., Schmitz, R. W., Krainitzki, H., Stoneking, M., & Pääbo, S. (1997). Neandertal DNA Sequences and the Origin of Modern Humans. Cell, 90(1), 19-30. Retrieved from: https://doi.org/10.1016/s0092-8674(00)80310-4

Pääbo, S. P., Kelson, J. K., & Reich, D. R. (2012). A high-coverage genome sequence from an archaic Denisovan individual. Science, 338(6104). Retrieved from: https://doi.org/10.1126/ciencia.1224344

Courtesy: Jens Schlueter/Getty Images

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Mauro Orozco Moreno

ChatGPT: hero, villain, anti-hero, or sidekick?

Artificial intelligence (AI) has revolutionized many areas of our society, including the writing of journalism, literature, and scientific texts. With significant advances in natural language processing, AI algorithms can generate coherent and compelling content, mimicking the style and structure of human writers. However, as this technology continues to evolve, there are also significant questions and risks associated with its use in these key areas.

Indeed, the entire paragraph above was written by ChatGPT when I asked him to talk about the risks of AI in journalism, literature, or scientific texts. At the risk that now you, the reader, may not trust when I am talking to you or when you are our protagonist of

the day, I ask you, are these dangers really real? Is it so difficult to differentiate the text that was created by an AI from one created by a human?

I would divide these questions into two aspects: veracity in the case of journalism or scientific texts and creativity and the author’s voice in such a case as literature or opinion texts. It’s possible that in the case of journalism or scientific texts we do need to pay special attention, let’s start there.

One of the main risks of AI in copywriting is the lack of truthfulness and accuracy. While algorithms can generate content that appears authentic, they lack human discernment and can spread misleading or false information without being aware of it. The two sentences above were also written by the ChatGPT. We will be playing with this throughout the text to test our questions.

I will tell you something personal, but I used it as an example. My family is originally from a neighborhood in Guadalajara known as the Atemajac Factory. In 1921 they founded the Club Deportivo Occidente, as a team of the textile factory workers. Anyone who likes soccer and its history will know (or can research) that even though it was never a professional team, it is historic for the sport in the city. When I asked ChatGPT about the history of the club, he gave me a mixture of real data, such as the date of foundation, but false information about the players, telling me that its historical figure was a Spanish soccer player named Paco Gento, who, upon investigation, turned out to have played his entire career in Real Madrid.

Communicator and Historian from the University of Guadalajara. Dedicated to journalism and content creation about technology, geek culture and video games on the internet.

This poses challenges for journalism and science communication, as the reliability of information is fundamental in these fields. Spreading fake news or incorrect scientific studies can have detrimental consequences for society and even undermine trust in the media and science. Again, the above two sentences were written by ChatGPT. I don’t know if we are getting the hang of the exercise. So why and what should we rely on ChatGPT for? Is it right to use it? This is where the human comes in. The criteria of one’s needs will dictate whether you are looking for a proofreader, maybe a tool that gives ideas, or just a kind of search engine.

Another risk is the loss of human uniqueness and creativity. While AI algorithms are capable of mimicking the style of well-known writers, they lack the originality and unique perspective that only a human author can bring. Yes, again this paragraph starter is courtesy of

ChatGPT. The issue of creativity in texts in which more emotions and very personal voices are at stake is a bit simpler, although some notes should be made.

In short, while AI offers promising advances in journalism, literature, and scientific writing, it also carries significant risks. Thank you, ChatGPT, for that conclusion in the above statement.

If you think about it, ChatGPT is nothing more than a tool that has the same notion of ethics or morals as our cars or a cell phone. We are the ones who are obliged to use it ethically. But beyond that, Were you able to identify my voice, and what was ChatGPT’s voice? Whether this chat will be a hero, villain, antihero, or our faithful companion will be answered with our moral compass, with the most efficient formation of critical thinking, and with having more contact with reading.

First 3D Bioprinter made from LEGO pieces capable of printing human skin created

Scientists at Cardiff University in the United Kingdom have created the first 3D bioprinter built from LEGO pieces capable of printing human tissue.

Although the printing of biological material is an established achievement in the world of clinical research, this is the first time that biological printing has been combined with a high degree of engineering and the use of materials as rudimentary as LEGO pieces. According to the scientists in charge of the research, the 3D bioprinter was designed to serve as a machine scientifically capable of producing delicate biological material from robust, simply constructed, and, above all, inexpensive components, all without compromising performance.

The most altruistic part of the project is that the scientists shared their research with open source, that is to say, they intentionally published every element of the construction, including the specific LEGO parts used, as well as their capabilities, with the ultimate goal that “it can be easily replicated in any lab, anywhere in the world,” Dr. Coulman mentions.

The Bioprinter was conceived to recreate the threedimensional architecture of the skin. So far the model has successfully printed hydrogel droplets containing cells. Future research is expected to aid in the creation of viable skin models to test treatments for skin diseases including cancer, or to create grafts to replace this damaged organ.

Clinical Research Insider Editorial

Reference

Courtesy of the researchers: Dr. Christopher Thomas, Dr. Oliver Castell and Dr. Sion Coulman.

Moukachar, A., Harvey, K., Roke, E., Sloan, K., Pool, C., Moola, S., Alshukri, A., Jarvis, D., Crews-Rees, P., McDermott, G., Evans, L., Li, J., Thomas, C., Coulman & S., Castell, O., (2023) Development and Evaluation of a Low-Cost LEGO 3D Bioprinter: From BuildingBlocks to Building Blocks of Life. Adv. Mater. Technol. 8, 2100868. Retrieved from: https://doi.org/10.1002/admt.202100868

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Origenes

Romero Porras

Darwinist Hitler

Christian Anton Mayer was his real name. His prose is simple but the concatenation of ideas makes it unreadable at times. That is why a couple of parallel readings of the text are useful, to unravel it.

Mayer, later known as Carl Amery, was a German writer dedicated to science fiction and was also a very ecologically oriented political activist, being a founding member of the Green party and a member of the 47’ group, to which novelists such as the Nobel Prize in Literature winner Günter Grass belonged. His biography is elementary to understanding the concerns that motivated the writing of Auschwitz, the beginning of the 21st century? Hitler as a precursor.

In 2002, just after the publication of that text, Javier Valenzuela wrote in El Pais that humanity can think “there is not enough for everyone to live well”. And that’s Amery’s fear. On the other hand, Valenzuela points to the emergence of right-wing movements:

See the electoral strength of formations such as the French National Front and the growing assimilation by right-wing parties, such as the Spanish PP, of the discourse of fear and rejection of immigrants, the reinforcement of external borders and internal police controls, the intrusion into private life thanks to new

technological instruments, the selection of the youngest and most submissive in the world of work.

According to Ramon Campderrich Bravo (2005), there are three elementary concepts in Amery’s book: elitism, social Darwinism, and Eurocentrism. And that is, only for the sake of an alleged political superiority, the Nazi proposal of racial extermination was justified, taken from a misinterpretation of Darwin’s theory of natural selection, and ensured the survival of mankind.

Amery is not trying to warn of a resurgence of Nazism in the 21st, he points out that to face today’s problems, there is a latent possibility that the idea that a nation can survive at the expense of a weaker one may arise again. Thus, the genocide and suffering of non-Western societies have been allowed in exchange for economic profit for the powers through cost reduction and the economic benefit of arms sales, just as the Jewish genocide was allowed to ensure the survival of the Aryan Germans.

These are problems that the West generated in the past for Africa thanks to the implicit idea that African suffering is permissible because they are inhuman, that is, they were considered non-human for cen-

Degree in History from the University of Guadalajara. Former Paralympic athlete (2006-2017). Interested in the relationship between art and history. Literary analyst.

turies. Classism and colonialism appear as two phenomena of social Darwinism born in the Western world to ensure the prevailing social order.

Amery proposes the idea that Nazism has been the most consistent radical attempt at social order. A science fiction writer and environmentalist, the author feared a dystopian ending in which, in order to save an elite of humanity from a global disaster, millions of people would be condemned to death.

Ramon Campderrich understands in the text a division into two sections of humanity: the elites, whether local, national, or international, and the masses. The elite decides by nature the destiny of humanity. However, Campderrich himself falls into natural law when he says that “this order of things is a necessary order.”

On the other hand, with the 2020 pandemic, Alberto Mataran approached Amery’s propositions from a present that the German had prophesied:

This social majority is in permanent dispute with elites who, instead of cooperation, prefer exclusion,

who use lies to undermine democracy, and who, to avoid strengthening public services, local economies, and social networks, promote destruction and the law of the strongest [...]. If we want to prevent History from repeating itself in a tragic way, it is essential that no one takes a step back in this dispute and that we increase our efforts so that the inertia of inequality and scarcity do not mark our future.

This is Carl Amery’s effort. The author tries, through a diffuse timeline and the analysis of Adolf Hitler’s devised - not written - book, Mein Kampf: My Struggle, to establish a continuity not of Hitlerian ideas but of cultural conditions and thinking.

Even today it is possible that a group of people in power thinks of continuing with the exploitation of natural resources to, in the end, betray the workers by leaving them to their fate in the inhospitable conditions of a cataclysm. Amery invites us to reflect before it happens.

Deuterium, Bobert, help me with the gifts for our booth.

Sure, anything to be part of #Summit2023!

I'm bored by these things…

Look, there's Dr. Deuterium!

The doctor with more than 10 million subscribers?

I want a selfie!

Doctor?

See you later. I'm off with my fans to sign autographs and cover myself with bills.

I can't believe a rat has more fans than us. And that being so lazy, he has time to maintain a YouTube channel.

Story and Drawings: Rick Ruiz-Dana