Featured Publications
Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions
Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, Aslan M, Quaden R, Harrington KM, Nuñez YZ, Overstreet C, Radhakrishnan K, Sanacora G, McIntosh AM, Shi J, Shringarpure SS, Concato J, Polimanti R, Gelernter J. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience 2021, 24: 954-963. PMID: 34045744, PMCID: PMC8404304, DOI: 10.1038/s41593-021-00860-2.Peer-Reviewed Original ResearchConceptsTranscriptome-wide association studyMillion Veteran ProgramTranscriptome-wide association study (TWAS) analysisGenomic risk lociComplex psychiatric traitsGenetic architectureRisk lociGene expressionAssociation studiesLikely pathogenicityPsychiatric traitsVeteran ProgramNew therapeutic directionEuropean ancestryNew insightsAncestryUK BiobankAfrican ancestrySubstantial replicationExpressionLarge independent cohortsGWASTherapeutic directionsGenesLociA Comparison of Two Statewide Datasets to Understand Population Prevalence of Substance Use in Pregnancy: Findings and Considerations for Policy & Research
Sieger M, Morin J, Budris L, Sienna M, Ostfeld-Johns S, Hart L, Morosky C. A Comparison of Two Statewide Datasets to Understand Population Prevalence of Substance Use in Pregnancy: Findings and Considerations for Policy & Research. Maternal And Child Health Journal 2024, 28: 1121-1131. PMID: 38539033, PMCID: PMC11060901, DOI: 10.1007/s10995-024-03914-6.Peer-Reviewed Original ResearchConceptsSubstance use disordersSubstance useBlack mothersPregnancy-related deathsFederal Child Abuse PreventionMental health conditionsPublic health aimSelf-reported drug useMaternal self-reportDrug usePrevalence of substance useChild protective services involvementProtective services involvementMothers self-reportedChild abuse preventionSelf-reported dataStatistically similar ratesPrenatal substance exposureSelf-report ratingsHealth aimRate of whitesHispanic mothersHealth conditionsHospital personnelSelf-reportThe impact of cannabis on non-medical opioid use among individuals receiving pharmacotherapies for opioid use disorder: a systematic review and meta-analysis of longitudinal studies
Costa G, Nunes J, Heringer D, Anand A, De Aquino J. The impact of cannabis on non-medical opioid use among individuals receiving pharmacotherapies for opioid use disorder: a systematic review and meta-analysis of longitudinal studies. The American Journal Of Drug And Alcohol Abuse 2024, 50: 12-26. PMID: 38225727, DOI: 10.1080/00952990.2023.2287406.Peer-Reviewed Original ResearchConceptsNon-medical opioid useOpioid use disorderOpioid useCannabis useOpioid use disorder pharmacotherapyUse disorderImpact of cannabis useAverage follow-up timeFollow-up timeMeta-analysisEvidence of moderate heterogeneityImpact of cannabisPooled odds ratioOpioids non-medicallyRandom-effects modelMeta-analysis of longitudinal studiesCannabis abstinenceTreatment modalitiesOdds ratioModerate heterogeneityPharmacotherapyCannabisOpioidComprehensive searchPublication biasCommon Pathways of Epileptogenesis in Patients With Epilepsy Post–Brain Injury
Misra S, Khan E, Lam T, Mazumder R, Gururangan K, Hickman L, Goswami V, Funaro M, Eldem E, Sansing L, Sico J, Quinn T, Liebeskind D, Montaner J, Kwan P, Mishra N. Common Pathways of Epileptogenesis in Patients With Epilepsy Post–Brain Injury. Neurology 2023, 101: e2243-e2256. PMID: 37550071, PMCID: PMC10727219, DOI: 10.1212/wnl.0000000000207749.Peer-Reviewed Original ResearchConceptsStandardized mean differencePoststroke epilepsyBrain injuryGenetic susceptibilityDisparate time pointsRisk of epileptogenesisLate-onset seizuresDevelopment of epilepsyBlood glucose levelsTraumatic brain injuryMean biomarker levelsIndividual genetic susceptibilityWeb of ScienceReported biomarkersPrimary outcomeEpileptogenic processBiofluid biomarkersBias assessmentBiomarker levelsCommon biological pathwaysEnrichment analysisGlucose levelsHigh riskPrognostic studiesEpilepsyIndividualising intensive systolic blood pressure reduction in hypertension using computational trial phenomaps and machine learning: a post-hoc analysis of randomised clinical trials
Oikonomou EK, Spatz ES, Suchard MA, Khera R. Individualising intensive systolic blood pressure reduction in hypertension using computational trial phenomaps and machine learning: a post-hoc analysis of randomised clinical trials. The Lancet Digital Health 2022, 4: e796-e805. PMID: 36307193, PMCID: PMC9768739, DOI: 10.1016/s2589-7500(22)00170-4.Peer-Reviewed Original ResearchConceptsSystolic blood pressure controlBlood pressure controlIntensive systolic blood pressure controlType 2 diabetesPressure controlCardiovascular benefitsClinical trialsMajor adverse cardiovascular eventsFirst major adverse cardiovascular eventLarge randomised clinical trialsACCORD-BP trialAdverse cardiovascular eventsRandomised clinical trialsSystolic blood pressureCox regression analysisTreatment effectsHazard ratio estimatesACCORD-BPBP trialCardiovascular eventsBlood pressurePrimary outcomeStandard treatmentBaseline variablesIndex patientsTrends in Racial and Ethnic Disparities in Barriers to Timely Medical Care Among Adults in the US, 1999 to 2018
Caraballo C, Ndumele CD, Roy B, Lu Y, Riley C, Herrin J, Krumholz HM. Trends in Racial and Ethnic Disparities in Barriers to Timely Medical Care Among Adults in the US, 1999 to 2018. JAMA Health Forum 2022, 3: e223856. PMID: 36306118, PMCID: PMC9617175, DOI: 10.1001/jamahealthforum.2022.3856.Peer-Reviewed Original ResearchConceptsTimely medical careSerial cross-sectional studyNational Health Interview SurveyCross-sectional studyHealth Interview SurveyMedical careLack of transportationEthnic disparitiesHispanics/LatinosWhite individualsEthnicity groupsInterview SurveyCost of careSelf-reported raceStudy cohortClinic hoursMAIN OUTCOMEMedical officesCarePrevalenceLatino individualsBlack individualsSignificant differencesSignificant increasePopulation groupsHuman WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation
Cai WL, Chen JF, Chen H, Wingrove E, Kurley SJ, Chan LH, Zhang M, Arnal-Estape A, Zhao M, Balabaki A, Li W, Yu X, Krop ED, Dou Y, Liu Y, Jin J, Westbrook TF, Nguyen DX, Yan Q. Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation. ELife 2022, 11: e78163. PMID: 36043466, PMCID: PMC9584608, DOI: 10.7554/elife.78163.Peer-Reviewed Original ResearchConceptsBreast cancer cellsMetastatic breast cancerBreast cancerRibosomal gene expressionCancer cellsKnockdown of WDR5Vivo genetic screenReversible epigenetic mechanismsGenetic screenTranslation regulationTriple-negative breast cancerEpigenetic regulatorsEpigenetic mechanismsBreast cancer growthCancer-related deathTranslation efficiencyWDR5Novel therapeutic strategiesTranslation rateGene expressionCell growthAdvanced diseaseEffective therapyMetastatic capabilityPotent suppressionElectronic Alerts to Improve Heart Failure Therapy in Outpatient Practice A Cluster Randomized Trial
Ghazi L, Yamamoto Y, Riello RJ, Coronel-Moreno C, Martin M, O'Connor KD, Simonov M, Huang J, Olufade T, McDermott J, Dhar R, Inzucchi SE, Velazquez EJ, Wilson FP, Desai NR, Ahmad T. Electronic Alerts to Improve Heart Failure Therapy in Outpatient Practice A Cluster Randomized Trial. Journal Of The American College Of Cardiology 2022, 79: 2203-2213. PMID: 35385798, DOI: 10.1016/j.jacc.2022.03.338.Peer-Reviewed Original ResearchConceptsGuideline-directed medical therapyUsual careEjection fractionHeart failureMedical therapyPrimary outcomeCluster-randomized comparative effectiveness trialSodium-glucose cotransporter 2 inhibitorsElectronic health record alertsAldosterone system inhibitorsReduced ejection fractionUsual care armCotransporter 2 inhibitorsMineralocorticoid receptor antagonistsVentricular ejection fractionComparative effectiveness trialNumber of patientsKnowledge of guidelinesLow-cost interventionCare armDays postrandomizationEligible patientsGDMT useFailure therapyPatient characteristicsLongitudinal Trajectories of Multiple Nicotine Product Use Among Youths in the Population Assessment of Tobacco and Health Study
Simon P, Jiang Y, Buta E, Sartor CE, Krishnan-Sarin S, Gueorguieva R. Longitudinal Trajectories of Multiple Nicotine Product Use Among Youths in the Population Assessment of Tobacco and Health Study. JAMA Network Open 2022, 5: e223549. PMID: 35319763, PMCID: PMC8943628, DOI: 10.1001/jamanetworkopen.2022.3549.Peer-Reviewed Original ResearchConceptsNicotine product useCigar useTobacco usersTobacco useHealth StudyCigarette useProduct useWave 1Significant public health concernLongitudinal trajectoriesPublic health concernNon-Hispanic whitesTobacco product useLogistic regression modelsTobacco use behaviorsComplex survey designMultinomial logistic regression modelsDays of useSocioecological factorsMAIN OUTCOMESmokeless tobaccoLower oddsNicotine productsLatent class growth analysisSociodemographic factorsSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactionsPerspectives About Emergency Department Care Encounters Among Adults With Opioid Use Disorder
Hawk K, McCormack R, Edelman EJ, Coupet E, Toledo N, Gauthier P, Rotrosen J, Chawarski M, Martel S, Owens P, Pantalon MV, O’Connor P, Whiteside LK, Cowan E, Richardson LD, Lyons MS, Rothman R, Marsch L, Fiellin DA, D’Onofrio G. Perspectives About Emergency Department Care Encounters Among Adults With Opioid Use Disorder. JAMA Network Open 2022, 5: e2144955. PMID: 35076700, PMCID: PMC8790663, DOI: 10.1001/jamanetworkopen.2021.44955.Peer-Reviewed Original ResearchConceptsUntreated opioid use disorderOpioid use disorderEmergency departmentED visitsOUD treatmentUse disordersPublic safety-net hospitalRural critical access hospitalsEmergency department careSafety-net hospitalUrban academic centerLife-saving treatmentCritical access hospitalsImplementation science frameworkPatient factorsTreatment initiationED careUS patientsStaff trainingDemand treatmentPatient readinessNet hospitalPatient's perspectivePromoting ActionImproved careSex Differences across Retrospective Transitions in Posttraumatic Stress and Substance Use Disorders
Peltier MR, Roberts W, Verplaetse TL, Zakiniaeiz Y, Burke C, Moore KE, McKee SA. Sex Differences across Retrospective Transitions in Posttraumatic Stress and Substance Use Disorders. Journal Of Dual Diagnosis 2021, 18: 11-20. PMID: 34965199, PMCID: PMC9086923, DOI: 10.1080/15504263.2021.2016027.Peer-Reviewed Original ResearchConceptsDrug use disordersOngoing posttraumatic stress disorderSubstance use disordersSUD/PTSDPosttraumatic stress disorderNew PTSD diagnosisImpact of sexUse disordersDiagnosis of SUDPast-year substance use disorderPTSD diagnosisConcurrent substance use disordersDiagnosis of PTSDPoor treatment outcomesNational Epidemiologic SurveyBidirectional relationshipSex-specific analysesPotential sex-specific differencesTreatment outcomesm6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity
Qin Y, Li B, Arumugam S, Lu Q, Mankash SM, Li J, Sun B, Li J, Flavell RA, Li HB, Ouyang X. m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity. Cell Reports 2021, 37: 109968. PMID: 34758326, PMCID: PMC8667589, DOI: 10.1016/j.celrep.2021.109968.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseProgression of NAFLDLineage-restricted deletionFatty liver diseaseMultiple mRNA transcriptsMyeloid cell activationDiet-induced developmentMethyladenosine (m<sup>6</sup>A) RNA modificationMRNA metabolismProtein methyltransferaseLiver diseaseRNA modificationsCellular stressMetabolic reprogrammingDDIT4 mRNACell activationObesityDifferential expressionMammalian targetMRNA transcriptsSignificant downregulationCytokine stimulationPathway activityMetabolic phenotypeMRNA levelsAn open-access volume electron microscopy atlas of whole cells and tissues
Xu CS, Pang S, Shtengel G, Müller A, Ritter AT, Hoffman HK, Takemura SY, Lu Z, Pasolli HA, Iyer N, Chung J, Bennett D, Weigel AV, Freeman M, van Engelenburg SB, Walther TC, Farese RV, Lippincott-Schwartz J, Mellman I, Solimena M, Hess HF. An open-access volume electron microscopy atlas of whole cells and tissues. Nature 2021, 599: 147-151. PMID: 34616045, PMCID: PMC9004664, DOI: 10.1038/s41586-021-03992-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCells, CulturedDatasets as TopicDrosophila melanogasterFemaleGolgi ApparatusHumansInformation DisseminationInterphaseIslets of LangerhansMaleMiceMicroscopy, Electron, ScanningMicrotubulesNeurogliaNeuronsOpen Access PublishingOrganellesOvarian NeoplasmsRibosomesSynaptic VesiclesT-Lymphocytes, CytotoxicConceptsDrosophila neural tissueWhole cellsThin-section electron microscopyVolume electron microscopyCellular architectureMouse pancreatic isletsCancer cellsEM tomographyCellular structureCellsCellular samplesNeural tissuePancreatic isletsEnhanced signal detectionAtlasBeam-scanning electron microscopyTissueElectron microscopyOpen access dataBiologyImmune cellsSubsequent analysisSEM scanningMicroscopyMPEP Lowers Binge Drinking in Male and Female C57BL/6 Mice: Relationship with mGlu5/Homer2/Erk2 Signaling
Huang G, Thompson SL, Taylor JR. MPEP Lowers Binge Drinking in Male and Female C57BL/6 Mice: Relationship with mGlu5/Homer2/Erk2 Signaling. Alcohol Clinical And Experimental Research 2021, 45: 732-742. PMID: 33587295, PMCID: PMC8076072, DOI: 10.1111/acer.14576.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinge DrinkingDose-Response Relationship, DrugDrug Evaluation, PreclinicalExcitatory Amino Acid AntagonistsFemaleHomer Scaffolding ProteinsMaleMAP Kinase Signaling SystemMice, Inbred C57BLMitogen-Activated Protein Kinase 1Nucleus AccumbensPyridinesReceptor, Metabotropic Glutamate 5Septal NucleiSex CharacteristicsConceptsEffects of MPEPFemale C57BL/6 miceAlcohol intakeAlcohol consumptionNegative allosteric modulatorsLocomotor activityC57BL/6 miceFemale miceMale miceHomer2 expressionBinge drinkingMetabotropic glutamate receptor 5MGlu5 negative allosteric modulatorsSex differencesBinge alcohol consumptionGlutamate receptor 5Dose-response effectExcessive alcohol useERK2 expressionDose-response relationshipPotential sex differencesERK2 signalingBed nucleusNucleus accumbensStria terminalisAssessment of Acute Kidney Injury and Longitudinal Kidney Function After Hospital Discharge Among Patients With and Without COVID-19
Nugent J, Aklilu A, Yamamoto Y, Simonov M, Li F, Biswas A, Ghazi L, Greenberg J, Mansour S, Moledina D, Wilson FP. Assessment of Acute Kidney Injury and Longitudinal Kidney Function After Hospital Discharge Among Patients With and Without COVID-19. JAMA Network Open 2021, 4: e211095. PMID: 33688965, PMCID: PMC7948062, DOI: 10.1001/jamanetworkopen.2021.1095.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAgedAged, 80 and overBlack or African AmericanCohort StudiesComorbidityCOVID-19CreatinineFemaleFollow-Up StudiesGlomerular Filtration RateHispanic or LatinoHumansHypertensionKidney Function TestsLongitudinal StudiesMaleMiddle AgedPatient DischargeProportional Hazards ModelsRenal Insufficiency, ChronicRetrospective StudiesSARS-CoV-2United StatesConceptsCOVID-19-associated acute kidney injuryAcute kidney injuryHospital acute kidney injurySubgroup of patientsKidney functionKidney injuryCohort studyHospital dischargeAKI recoveryKidney diseaseCOVID-19Peak creatinine levelsRetrospective cohort studyChronic kidney diseaseDays of dischargeHalf of patientsGlomerular filtration rateCoronavirus disease 2019AKI severityBaseline comorbiditiesEGFR decreaseDialysis requirementEGFR slopeKidney recoveryCreatinine levelsThe Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study
Moledina DG, Simonov M, Yamamoto Y, Alausa J, Arora T, Biswas A, Cantley LG, Ghazi L, Greenberg JH, Hinchcliff M, Huang C, Mansour SG, Martin M, Peixoto A, Schulz W, Subair L, Testani JM, Ugwuowo U, Young P, Wilson FP. The Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study. American Journal Of Kidney Diseases 2021, 77: 490-499.e1. PMID: 33422598, PMCID: PMC7791318, DOI: 10.1053/j.ajkd.2020.12.007.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAgedC-Reactive ProteinCohort StudiesCOVID-19CreatinineDiureticsFemaleHospital MortalityHumansIntensive Care UnitsLength of StayMaleMiddle AgedProportional Hazards ModelsRenal DialysisRenal Insufficiency, ChronicRespiration, ArtificialRisk FactorsSARS-CoV-2Severity of Illness IndexUnited StatesVasoconstrictor AgentsConceptsAcute kidney injurySARS-CoV-2Cohort studyRisk factorsCOVID-19Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testingTime-updated Cox proportional hazards modelsDialysis-requiring acute kidney injuryYale New Haven Health SystemHigher inflammatory marker levelsMore acute kidney injuryCox proportional hazards modelMulticenter cohort studyHigh rateInflammatory marker levelsTraditional risk factorsProportional hazards modelCoronavirus disease 2019KDIGO criteriaNephrotoxin exposureKidney injuryInjury independentUnivariable analysisNasopharyngeal samplesMarker levelsBarriers and Facilitators to Clinician Readiness to Provide Emergency Department–Initiated Buprenorphine
Hawk KF, D’Onofrio G, Chawarski MC, O’Connor P, Cowan E, Lyons MS, Richardson L, Rothman RE, Whiteside LK, Owens PH, Martel SH, Coupet E, Pantalon M, Curry L, Fiellin DA, Edelman EJ. Barriers and Facilitators to Clinician Readiness to Provide Emergency Department–Initiated Buprenorphine. JAMA Network Open 2020, 3: e204561. PMID: 32391893, PMCID: PMC7215257, DOI: 10.1001/jamanetworkopen.2020.4561.Peer-Reviewed Original ResearchConceptsOpioid use disorderEmergency departmentAdvanced practice cliniciansED cliniciansClinicians' readinessOngoing treatmentTreatment of OUDEmergency Department-Initiated BuprenorphineUntreated opioid use disorderDrug Addiction Treatment ActDecrease opioid useVisual analog scaleHealth Services frameworkAcademic emergency departmentMixed-methods formative evaluationQuality of careSubset of participantsBuprenorphine initiationClinician typeOpioid useED patientsAnalog scaleOngoing careDepartmental protocolPractice cliniciansIL‐1β Drives Production of FGF‐23 at the Onset of Chronic Kidney Disease in Mice
McKnight Q, Jenkins S, Li X, Nelson T, Marlier A, Cantley LG, Finberg KE, Fretz JA. IL‐1β Drives Production of FGF‐23 at the Onset of Chronic Kidney Disease in Mice. Journal Of Bone And Mineral Research 2020, 35: 1352-1362. PMID: 32154933, PMCID: PMC7363582, DOI: 10.1002/jbmr.4003.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseOnset of CKDEarly chronic kidney diseaseFGF-23 expressionFGF-23Renal dysfunctionParathyroid hormoneIL-1βCongenital chronic kidney diseaseFGF-23 levelsSerum parathyroid hormoneGlomerular capillary tuftCongenital modelSerum phosphateIron bioavailabilitySystemic elevationVitamin DInflammatory cytokinesKidney diseaseEarly biomarkersIron statusMouse modelPhosphate imbalanceInitial upregulationCapillary tuftReproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program
Levey DF, Gelernter J, Polimanti R, Zhou H, Cheng Z, Aslan M, Quaden R, Concato J, Radhakrishnan K, Bryois J, Sullivan PF, Stein M. Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program. American Journal Of Psychiatry 2020, 177: 223-232. PMID: 31906708, PMCID: PMC7869502, DOI: 10.1176/appi.ajp.2019.19030256.Peer-Reviewed Original ResearchConceptsNovel genome-wide significant associationsGene expressionGenome-wide significant signalsGenome-wide significant associationMillion Veteran ProgramWide association studyGenetic risk lociSignificant genetic correlationsGenetic risk mechanismsGenetic architectureGlobal regulatorChromosome 3Risk lociChromosome 6Chromosome 7Association studiesLargest GWASLarge biobanksGlobal regulationGenetic correlationsContinuous traitsVeteran ProgramGWASsLociPrevious GWASs
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