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AIDeepLearningAidsinExaminationofProstateTumorArchitectural DifferencesbetweenAfricanAmericansandCaucasians EllaHarshyne,AnkitaSrivastava,RajanikanthVadigepalli DepartmentofPathologyandGenomicMedicineStepUp!toCancerResearchProgram SidneyKimmelComprehensiveCancerCenter

Introduction
ProstateCancerisaleadingdeathamongmen AfricanAmericanmenarediagnosedmorefrequentlyandhavehgher mortaityratescomparedtoCaucasianmen
- 176xhigherlkelhoodofdiagnosis
-214xhighermortaltyrate
-Understudiedarchtecturaldifferencesinthetumortssuesmaybea contributingfactortotheracia dispartesobservedinprostatecancer outcomes butremainunderexploredinresearch
TheuseofAIalowsforaquickanddetaledanayss,comparedtohumans, ofmorphologicalfeaturesfromhistoogyimages Woudtakeahuman30min–1hourcomparedtoAIonlytakng5-15minper core
Hypothesis

-Therewillbemorphologicaldifferencesintheprostatetumortissues


Results ofAfricanAmericanversusCaucasiansandbetweentumorgrades withinthoseracesprostatetumors:3+3,3+4,4+3 -Attheglandular,luminal,andnuclearlevelbetweenracesdisparitiesinprostatetumorlikeaggressiveness,treatment responseandsurvivalrates Thesedifferencesmaycontributetotheexplanationofknown
MaterialsandMethods

-We usedanAIbasedimageanalysstoo caledVisiopharmtoanalyze tumormorphologyinH&EstainedTumorMicroArray(TMA)prostate cancersamples RegionofInterests(ROIs)
-
-ManuallyannotatedonanH&EstainedTMAimageandeachannotated areamarkedadifferenttumorsection Apps -Orderallowedfordatalinkage
-Glanddetectionapp:GlandDETECT Modified -HighlightsglandsinbluetocreatenewROIs
-Providesinformationusefultoevaluatingstructuraldifferences -Providesinformationlikeglandcount,glandarea,largerandsmaller diameters,majorandminors,andperimeter -Lumenidentficationapp:Lumen ID NewModified - Isranineachseparateglandcreatedinthepreviousstep -Provides nformationlikelumencount,lumenperimeter,minorand major,andareainwhichweusetolookatratiosandlookfor abnormalities
-Nucleidetectionapp:NucleiDetection parameter
-Informationlikenucleicount,largestandsmallestdiameter,perimeter, nuceieccentricity cellsoldarityisextracted RStudio - packagesfordatacleaningandcreatingvisuals
--dplyr:filterng&groupingdata ggplot2:creatingplots purrr:loopingoverlistsofdata readr:reading csvfiles stringr:cleaningandextractingstrings




Discussion

-SignificantdifferencesinRacewereobservedinglandareatotalnumberofglands




lumen andnuclei andnucleieccentricity Blackpatientsexhibitedlargerglands hgher nucle counts,andmoreirregulartyinnucleishape Thesestructuraldifferenceswerestill presentinseparateracesevenwhentheGeasonscoreswerethesame Gleason3+3
-AfrcanAmericanmenshowlessarchitectura disruptionbutearlysignsofnuclear atypia,whieWhitemenshowmoretumorcel density
Gleason3+4
-AfrcanAmercanmenstumorbeginlosngstructure,earierthanwhitemen,andshow greaternuclear rregularitywhchcanreflectearlyprogressiontowardsaggressive behavor
Gleason4+3

Conclusions


Acknowledgements I

-BothshowaggressivefeaturesbutAfricanAmericanmenshowmoreseverestructural breakdownandvariabiitywhichcanbeasignofmoreaggressvetumorbehavor

@ResearchAtJeff


GabrielleMcFarlane,,GabrielaDaszewska-Smith,ElenaBlano-Suarez
Background

Intheearlystagesofbraindevelopment immaturesynapsesfeaturecalciumpermeable AMPA glutamate receptors AMPA receptors play a crucial role in neuronal plasticity, learning, and memory As synapses stabilize and mature, the calcium-permeable AMPA receptors are replaced with calciumimpermeableGluA2AMPAreceptors
Chordin-like1(Chrdl1),aproteinsecretedbyastrocytes,hasbeenfoundto haveanegativeeffectonneuronalplasticitybyregulatingsynapticmaturation oftheAMPAreceptors
Chrdl1expressionisconcentratedincertainareasofthemousebrain,and whenischemicstrokes orstrokesresultingincelldamageanddeath occurin thoseareasthenChrdl1isupregulated,potentiallyhinderingcellrecovery
• IthasbeenpreviouslyfoundthatwhenChrdl1isknockedoutinmicepriorto birth,theyrecoverfromcelldamageandmotorcontrolfasterthanwildtype mice
Researchquestion

CanknockingoutChordin-like1expressioninadultmice leadtofasterischemicstrokerecovery?




Figure1.(A)BargraphcomparisonoftimespentinthecenterofopenfieldtestingareabetweenCre (-)andCkomice,beforeand1dayafterstrokesurgery Eachbarrepresentsthemean±SEMofthe specifiedgroupatagiventimepoint.(B)Bargraphcomparisonofthetotaldistancetraveledwithin theopenfieldtestingareabetweenCre(-)andCkomice,beforeand1dayafterstrokesurgery. Statisticaldifferencesbetweengroupsortimepoints,whereapplicable,areindicatedbyasterisks(*p< 0.05,**p<0.01).(C)Bargraphcomparisonoftimespentintheperipheryoftheopenfieldtesting areabetweenCre(-)andCkomice,beforeand1dayafterstrokesurgery.(D)Bargraphcomparisonof themeanspeedwhilstintheopenfieldtestingareabetweenCre(-)andCkomice,beforeand1day afterstro@keRessue





















Figure 2. (A-B) Representative MRI images showcasing the lesioned brain area ofChrdl1 Ckoand Cre(-)mice at1daypost-stroke and 7days post-stroke. (C) Bar graph comparison of stroke volume between Cre (-) andCkomice,1dayand7dayspoststroke.Statisticaldifferencesbetween groups or time points, where applicable, are indicated by asterisks (*p< 0.05, **p<0.01). (D) Line graph comparison of stroke area percentage betweenCre(-)andCkomice,1dayand7dayspoststroke.


ComparedtoCre(-)mice,Chrdl1Ckomicerecovermotorfunctionata slowerrate.ThiscouldsuggestthattheChrdl1proteinisimportantfor motorfunctionandrecovery.
Sincethesynapsesarealreadymaturatedinadults,theAMPAreceptors couldalreadyhavelessplasticitycomparedtoyoungerages,which wouldhaveadverseeffectsonneuronalcellrecovery.
ApossiblefuturedirectioncouldbetoseeifandhowtheAMPA receptorsareaffectedinadultsonceChrdl1hasbeenknockedout.
Partofamuchlargerstudy,soconsequently,moredatacouldshowa moredefinitivepicture.

IamgratefultohavebeenabletoparticipateintheStepUp!ToCancer Researchprogramoverthissummer!Throughthisprogram Ihave beenabletohearaboutmanydifferentstories,trajectories,andcareer paths,whichhaveallhelpedtoimpactmydecisionsaboutmyfuture Beforeenteringthisprogram IhadarockyvisionofwhatIwantedmy futuretolooklike,whatstepsIhadtotaketogetthere,andhowI wouldmanagemyselfasIpursuedevenhighereducationandentered theworkingfield Now Ihavemoreexperiences connections and knowledgetodrawbackasIcontinuetothinkaboutwhatmyown careerpathmaylooklike
Acknowledgment

IwouldliketoacknowledgetheworkandeffortsofDr.AnaMariaLopez,Dr.ElenaBlanco-Suarez,andGabriela Daszewska-Smithfortheirhelpinthecollection,analysis,and presentationofthisdata.Iwouldalsoliketothanktherestof theStepUp!ToCancerResearchcohortfortheircontinued support.


fisticaldifferencesbetweengroupsortimepoints,whereapplicable,are indicatedbyasterisks(*p<0.05,**p<0.01).


Background
Mindfulness-BasedStressReduction(MBSR)hasbeenshownto reducestress,anxiety,anddepressioninindividualsdiagnosed withbreastcancer.Researchhasshownthatmindfulnesscanhelp withemotionalwell-being,supportcopingandcognitivefunction, decreaseinflammation,andsupportsurvivorship.
-Mindfulnessinvolvesintentionallyfocusingonthepresent momentwithopennessandacceptance,usingtechniqueslike meditation,breathingexercises,andmindfulawarenessof thoughts,emotions,anddailyexperiences.
-Dr.Lopez’steamhasjustcompletedamindfulnessinterventionfor personswithbreastcancerwhoareundergoingchemotherapy.
-Iamexploringwhethermindfulnessinterventionscanprovide meaningfulbenefitsforindividualswithmetastaticbreastcancer.
Methods







Ofimportantnote:
-"Anothertask"–Mindfulnessfeltlikeanaddedburdenduringan alreadyoverwhelmingtime.
-"Goodteacherisamust"–Askilled,compassionateinstructorwas seenasessentialforengagement.
-"Mindisallovertheplace"–Difficultyfocusingwascommon, highlightingbothachallengeandapotentialbenefitofmindfulness.
-“Helpsmecalmandlessstressful”–Participantsnotedthat mindfulnesspracticeshelpedreducestressandpromoteasenseof calm.

Mindfulnessisflexible:Participantspracticeditindifferent ways,oftenwithoutusingtheterm“mindfulness.”Clear, relatableframingisimportant.
-Stronginterestacrosstheboard:Eventhosenewto mindfulnessshowedopennesstolearningandparticipating.
-Barriersexist:Fatigue,techaccess,andgroupdiscomfort suggestaneedforflexible,low-effortformats(e.g.,Zoom, phone).
-Groupvs.Individual:Somevaluedgroupsupport;others preferred1-on-1.Choicematters.
-Timingiskey:Earlyintroduction—atdiagnosisortreatment changes—mayincreaseimpact.

-Mindfulnesshelpedparticipantsmanagestress,buildresilience, andregainasenseofcontrolduringtreatment.
-Eventhoseunfamiliarwithmindfulnesswereopenandcurious onceintroduced.
-Listeningtopatients’storieswasapowerfulreminderoftheneed forpatient-centered,flexiblecare.
-Asapre-medstudent,thisexperiencedeepenedmy understandingoftheemotionalandpsychologicalneedsof patients,andtheimportanceofcompassionate,holistic approachesinmedicine.
FutureDirection
-Expandthemindfulnessprogramtoincludepatientswith metastaticbreastcancer,apopulationthatoftenexperiences heightenedpsychologicaldistress.
-Integratedigitaltools(e.g.,mobileappsoronlineplatforms) toincreaseaccessibility,engagement,andadherencetothe program.
-Broadenthestudytoincludediversepatientpopulationsand exploredifferentdeliverymodalities(e.g.,one-on-one, group,virtual).
-Investigatepotentialbiologicalcorrelatestobetter understandthemechanismsthroughwhichmindfulness mayimpacthealthoutcomes.
Acknowledgement
IwouldliketothankDr LopezandLe'Annfortheirmentorshipand leadershipthroughoutthisproject IamalsogratefultoJuliaforher invaluablecontributionstothedevelopmentandimplementationof thestudy SpecialthankstotheAmericanCancerSocietyfor supportingthisresearch



Background
Breastcanceristhemostcommonlydiagnosedcancerinwomen,where 20%-30%ofpatientsexperiencebreastcancerbrainmetastasis.
SLC7A11isaproteinthatservesasanaminoacidtransporterinvolvedin glutamateandcystineexchange;promotingcancercellsurvivalthrough oxidativestress
ProteomicanalysisofSLC7A11overexpressingcellsshowedincreasedin extracellularmatrix(ECM)proteins






Figure3.FAKinhibitionshrinks
preformedBCBMtumorsexvivo


Figure4. SLC7A11 overexpressing cellshas increasedFAK activityandtotal levels
TheoverexpressionofSLC7A11increasestheactivation,or phosphorylation,ofFAKinbreastcancerbrainmetastaticcelllines. TargetingFAKwithsmallmoleculeinhibitorsshrinksBCBMtumorsex vivo
ThesefindingssuggestapotentialroleforSLC7A11inregulatingFAK signalinginBCBM.Ongoingworkwillclarifywhethertargetingthis pathwaycouldbeaneffectivestrategytoinhibitbrainmetastaticgrowth.


Objectives
DoesSLC7A11regulateECMsignalingandFAKphosphorylation inBCBMcells?
●ProjectAims
○DetermineifSLC7A11regulatesactincytoskeletonandFAKsignaling inBCBMcells
○EvaluateiftargetingFAKblocksBCBMgrowthexvivo

Immunofluorescence-usedtovisualizeproteinlocalizationand expressionincells WesternBlot-performedtodetectandquantifyproteinlevels Exvivoassay-braintissuesliceswereusedtoassesstheeffectsofFAK inhibitionontumorgrowth


Figure1.BCBMcellsandSLC7A11overexpressing

Figure2.SLC7A11knockdownBCBMcellshas
TotestiftargetingFAKreducesSLC7A11-mediatedgrowthinBCBM cellsinvivo
TotestiftargetingFAKinBCBMinducescelldeath
TounderstandthemechanismbywhichSLC7A11regulatesFAKand ECMsignaling
Acknowledgements





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I have great faith in a seed. Convince me that you have a seed there, and I am prepared to expect wonders.
Henry David Thoreau