Implications of the choice of method to identify major depressive disorder in large research cohorts.

Background: Clinical heterogeneity and variations in methods to identify major depressive disorder (MDD) across studies compromise replicability of research findings. This study evaluated potential implications of different MDD case definitions in a large biobank cohort.

Methods: Among Mayo Clinic Biobank participants, MDD was identified using two methods: self-report MDD in a participant questionnaire (PQ-MDD) and MDD ICD codes in the electronic health record (EHR-MDD).

Multilevel Intervention and Human Papillomavirus Vaccination Disparities: A Secondary Analysis of a Cluster Randomized Trial.

Importance: Uptake of human papillomavirus (HPV) vaccination varies by characteristics, exposing some children to higher HPV cancer risks than others.

Objective: To examine whether the effectiveness of a multilevel intervention on HPV vaccination differed by race and ethnicity, rurality, and Area Deprivation Index (ADI) in children ages 11 to 12 years.

Design, Setting, And Participants: A stepped-wedge cluster randomized trial was conducted from April 2018 to August 2022 among children at 6 Mayo Clinic primary care practices in Minnesota to improve HPV vaccination.

Significance of common genetic variants associated with non-ischaemic cardiomyopathy in the general population.

Aims: Common genetic variants have been linked to an increased risk of non-ischaemic cardiomyopathy (NICM). The primary objective of this study was to evaluate the significance of these variants in a general population.

Methods And Results: Thirteen NICM risk alleles, previously validated by meta-analyses of case-control genetic association studies, were used to determine genetic risk (GR) in a large, unselected cohort (n = 1897) of Olmsted County residents aged >45 years.

Impact of Interventions to Improve Human Papillomavirus Vaccine Uptake on Other Vaccines Due: A Secondary Analysis of a Randomized Trial.

Objective: We sought to determine if our recent trial of human papillomavirus (HPV) vaccine uptake improved influenza, meningococcal ACWY, and tetanus-diphtheria-acellular pertussis (Tdap) vaccine uptake.

Methods: We conducted a secondary analysis of our 4-year factorial stepped-wedge cluster-randomized trial of 6 primary care practices affiliated with the Mayo Clinic. We restricted our analysis to those adolescents 11- to 12-years-old due for at least 1 of 3 vaccines in addition to HPV.

A cross-sectional analysis of factors associated with cervical cancer screening in a large midwest primary care setting.

Background: Lower cervical cancer screening (CCS) rates have been reported among non-White populations, older women, rural populations, and populations with low socioeconomic status (SES). We evaluate associations between CCS status and individual, healthcare, and SES variables in a large primary care setting in southeast Minnesota.

Methods: We identified participants assigned female sex at birth, aged 21-65 years, without hysterectomy, and eligible for CCS via cross-sectional analysis of the electronic health record.

Deciphering distinct genetic risk factors for FTLD-TDP pathological subtypes via whole-genome sequencing.

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 patients and 3,153 controls compiled from 26 institutions/brain banks in North America, Europe and Australia, and meta-analysis with the Dementia-seq cohort. We confirm UNC13A as the strongest overall FTLD-TDP risk factor and identify TNIP1 as a novel FTLD-TDP risk factor.

Antidepressant Non-refill as a Proxy Measure for Medication Acceptability in Electronic Health Records.

Background: Pharmacogenomic studies on antidepressant treatment outcomes could be conducted using previously collected data from electronic health record (EHR)-linked biobanks. However, absence of EHR based outcome measures is an unmet need in designing such studies We aimed to define EHR-derived antidepressant outcome measures and explore their utility in showing associations between treatment outcomes and Cytochrome P450 (CYP) metabolizer phenotypes in a proof-of-concept study.

Methods: Using data from the EHR-linked cohort, Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment (RIGHT 10K) Study, we collected prescription data and patient health questionnaire 9 (PHQ-9) scores to compute 3 proxy measures for antidepressant response, efficacy, and acceptability: change in PHQ-9 scores, longest treatment interval with a single antidepressant, and antidepressant non-refill.

Follow-up Colorectal Cancer Screening After Negative-Result and Positive-Result Multitarget Stool DNA Tests: A Population-Based Study in Southeast Minnesota.

Objective: To provide contemporary data on subsequent screening after negative-result multitarget stool DNA (mt-sDNA) tests and follow-up colonoscopy after positive-result mt-sDNA tests.

Patients And Methods: Negative-result mt-sDNA tests (for patients aged 50-72 years) and positive-result mt-sDNA tests (for patients aged 50-75 years) were identified among average risk patients from a 9-county region in Southeast Minnesota from January 1, 2016 to December 31, 2022. Competing risks models of time to subsequent colorectal cancer (CRC) screening were modeled separately for the negative mt-sDNA and positive mt-sDNA cohorts.

Exploration of Genetic Liability to Insomnia and Substance Use Disorders in Patients With Bipolar Disorder.

Background: Insomnia and substance use disorders (SUD) are common comorbidities of bipolar disorder (BD). Genome-wide association studies (GWAS) have uncovered shared genetic contributions to insomnia and BD as well as SUDs and BD. Electronic health record (EHR) derived phenotypes (phecodes) and questionnaire data were used to examine the relationship between insomnia genetic liability and SUDs in BD.

Evaluation of parent reminder-recall letters to promote human papillomavirus vaccination.

Objective: Human papillomavirus (HPV) vaccine uptake remains suboptimal. Our stepped-wedge cluster randomized trial found that reminder-recall letters sent to parents of age-eligible children significantly increased vaccine uptake compared to usual care. Subsequently, we conducted a process evaluation to assess the mechanisms of the letter's effectiveness.

Deciphering Distinct Genetic Risk Factors for FTLD-TDP Pathological Subtypes via Whole-Genome Sequencing.

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 cases and 3,153 controls, and meta-analysis with the Dementia-seq cohort, compiled from 26 institutions/brain banks in the United States, Europe and Australia. We confirm as the strongest overall FTLD-TDP risk factor and identify as a novel FTLD-TDP risk factor.

Characterising plasmacytoid and myeloid AXL+ SIGLEC-6+ dendritic cell functions and their interactions with HIV.

AXL+ Siglec-6+ dendritic cells (ASDC) are novel myeloid DCs which can be subdivided into CD11c+ and CD123+ expressing subsets. We showed for the first time that these two ASDC subsets are present in inflamed human anogenital tissues where HIV transmission occurs. Their presence in inflamed tissues was supported by single cell RNA analysis of public databases of such tissues including psoriasis diseased skin and colorectal cancer.

Primary human papillomavirus testing by clinician- versus self-collection: Awareness and acceptance among cervical cancer screening-eligible women.

Objectives: Primary human papillomavirus (HPV) testing by clinician-collection is endorsed by U.S. guideline organizations for cervical cancer screening, but uptake remains low and insights into patients' understanding are limited.

Primary Human Papillomavirus Test Uptake and Cervical Cancer Screening Trends in the Midwest, United States.

Introduction/objectives: Despite U.S. Preventive Services Task Force and American Cancer Society endorsement of primary HPV screening, limited published data shows low uptake.

Pharmacogenomic overlap between antidepressant treatment response in major depression & antidepressant associated treatment emergent mania in bipolar disorder.

There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD.

Multilevel Implementation Strategies for Adolescent Human Papillomavirus Vaccine Uptake: A Cluster Randomized Clinical Trial.

Importance: Despite availability of a safe and effective vaccine, an estimated 36 500 new cancers in the US result from human papillomavirus (HPV) annually. HPV vaccine uptake falls short of national public health goals and lags other adolescent vaccines.

Objective: To evaluate the individual and combined impact of 2 evidence-based interventions on HPV vaccination rates among 11- and 12-year-old children.

Age-Dependent Sex Differences in the Prevalence of Selective Serotonin Reuptake Inhibitor Treatment: A Retrospective Cohort Analysis.

Antidepressants are among the most prescribed medications in the United States. The aim of this study was to explore the prevalence of antidepressant prescriptions and investigate sex differences and age-sex interactions in adults enrolled in the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment (RIGHT) study. We conducted a retrospective analysis of the RIGHT study.

Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of and Cardiac Fibrosis.

Background: Dilated cardiomyopathy (DCM) is a major cause of heart failure and carries a high mortality rate. Myocardial recovery in DCM-related heart failure patients is highly variable, with some patients having little or no response to standard drug therapy. A genome-wide association study may agnostically identify biomarkers and provide novel insight into the biology of myocardial recovery in DCM.

Cancer incidence in the Somali population of Olmsted County: A Rochester epidemiology project study.

Background: Somali immigrants and refugees constitute one of the largest African ethnic groups immigrating to the United States over the past three decades with the majority resettling in the state of Minnesota. Previous studies have documented significant cancer screening disparities between the Somali population and the general population. However, little is known about cancer incidence among Somali groups living in the United States.

Myocardial Fibrosis and Cardiomyopathy Risk: A Genetic Link in the MESA.

Background: Common genetic variants are associated with risk for hypertrophic cardiomyopathy and dilated cardiomyopathy and with left ventricular (LV) traits. Whether these variants are associated with myocardial fibrosis, an important pathophysiological mediator of cardiomyopathy, is unknown.

Methods: Multi-Ethnic Study of Atherosclerosis participants with T1-mapping cardiac magnetic resonance imaging in-whom extracellular volume was assessed, and genotyping information was available were included (N=1255).

Phenotypic distinctions in depression and anxiety: a comparative analysis of comorbid and isolated cases.

Background: Anxiety and depression are frequently comorbid yet phenotypically distinct. This study identifies differences in the clinically observable phenome across a wide variety of physical and mental disorders comparing patients with diagnoses of depression without anxiety, anxiety without depression, or both depression and anxiety.

Methods: Using electronic health records for 14 994 participants with depression and/or anxiety in the Mayo Clinic Biobank, a phenotype-based phenome-wide association study (PheWAS) was performed to test for differences between these groups across a broad range of clinical diagnoses observed in the electronic health record.

Temporal Relationships Between Saharan Dust Proxies, Climate, and Meningitis in Senegal.

The Harmattan, a dry, northeasterly trade wind, transports large quantities of Saharan dust over the Sahelian region during the dry season (December-March). Studies have shown that bacterial meningitis outbreaks in Sahelian regions show hyper-endemic to endemic levels during high-dust months. We examine the (a) seasonality and intraseasonal variability of dust, climate, and meningitis and the (b) quantitative relationships between various dust proxies with meningitis lags of 0-10 weeks in Senegal from 2012 to 2017.

Verification of operational numerical weather prediction model forecasts of precipitation using satellite rainfall estimates over Africa.

Rainfall is an important variable to be able to monitor and forecast across Africa, due to its impact on agriculture, food security, climate-related diseases and public health. Numerical weather models (NWMs) are an important component of this work, due to their complete spatial coverage, high resolution and ability to forecast into the future. In this study, the spatio-temporal skill of short-term forecasts of rainfall across Africa from 2016 through 2018 is evaluated.