Digital Commons Network^™

Targeted Genomic Sequencing Of Tsc1 And Tsc2 Reveals Causal Variants In Individuals For Whom Previous Genetic Testing For Tuberous Sclerosis Complex Was Normal, Hannah D West, Mark Nellist, Rutger W W Brouwer, Mirjam C G N Van Den Hout-Van Vroonhoven, Luiz Gustavo Dufner De Almeida, Femke Hendriks, Peter Elfferich, Meera Raja, Peter Giles, Rosa M Alfano, Angela Peron, Yves Sznajer, Liesbeth De Waele, Anna Jansen, Marije Koopmans, Anneke Kievit, Laura S Farach, Hope Northrup, Julian R Sampson, Laura E Thomas, Wilfred F J Van Ijcken

Faculty, Staff and Student Publications

Tuberous sclerosis complex (TSC) is caused by inactivating variants in TSC1 and TSC2. Somatic mosaicism, as well as the size and complexity of the TSC1 and TSC2 loci, makes variant identification challenging. Indeed, in some individuals with a clinical diagnosis of TSC, diagnostic testing fails to identify an inactivating variant. To improve TSC1 and TSC2 variant detection, we screened the TSC1 and TSC2 genomic regions using targeted HaloPlex custom capture and next-generation sequencing (NGS) in genomic DNA isolated from peripheral blood of individuals with definite, possible or suspected TSC in whom no disease-associated variant had been identified by previous …

Chimeric Rnas Reveal Putative Neoantigen Peptides For Developing Tumor Vaccines For Breast Cancer, Brandon Mistretta, Sakuni Rankothgedera, Micah Castillo, Mitchell Rao, Kimberly Holloway, Anjana Bhardwaj, Maha El Noafal, Constance Albarracin, Randa El-Zein, Hengameh Rezaei, Xiaoping Su, Rehan Akbani, Xiaoshan M Shao, Brian J Czerniecki, Rachel Karchin, Isabelle Bedrosian, Preethi H Gunaratne

Faculty, Staff and Student Publications

INTRODUCTION: We present here a strategy to identify immunogenic neoantigen candidates from unique amino acid sequences at the junctions of fusion proteins which can serve as targets in the development of tumor vaccines for the treatment of breastcancer.

METHOD: We mined the sequence reads of breast tumor tissue that are usually discarded as discordant paired-end reads and discovered cancer specific fusion transcripts using tissue from cancer free controls as reference. Binding affinity predictions of novel peptide sequences crossing the fusion junction were analyzed by the MHC Class I binding predictor, MHCnuggets. CD8+ T cell responses against the 15 peptides were …

Changes In Distribution Of Severe Neurologic Involvement In Us Pediatric Inpatients With Covid-19 Or Multisystem Inflammatory Syndrome In Children In 2021 Vs 2020, Kerri L Larovere, Amanda R Kolmar, Et Al.

2020-Current year OA Pubs

IMPORTANCE: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications.

OBJECTIVE: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021.

DESIGN, SETTING, AND PARTICIPANTS: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having …

Inhibition Of Mirna Associated With A Disease-Specific Signature And Secreted Via Extracellular Vesicles Of Systemic Lupus Erythematosus Patients Suppresses Target Organ Inflammation In A Humanized Mouse Model, Nicholas A Young, Emily Schwarz, Braden M Zeno, Shane Bruckner, Rosana A Mesa, Kyle Jablonski, Lai-Chu Wu, Elisha D O Roberson, Wael N Jarjour

2020-Current year OA Pubs

INTRODUCTION: Distinct, disease-associated intracellular miRNA (miR) expression profiles have been observed in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematous (SLE) patients. Additionally, we have identified novel estrogenic responses in PBMCs from SLE patients and demonstrated that estrogen upregulates toll-like receptor (TLR)7 and TLR8 expression. TLR7 and TLR8 bind viral-derived single-stranded RNA to stimulate innate inflammatory responses, but recent studies have shown that miR-21, mir-29a, and miR-29b can also bind and activate these receptors when packaged and secreted in extracellular vesicles (EVs). The objective of this study was to evaluate the association of EV-encapsulated small RNA species in SLE …

Hepatocellular Carcinoma With Hepatic Vein And Inferior Vena Cava Invasion, Akash Shukla, Abhinav Jain

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) invades intrahepatic vessels causing tumor thrombosis. Infrequently, there is involvement of the hepatic vein (HV) and inferior vena cava (IVC). In this review, we summarize the epidemiology, classification, clinical features, and management of HCC with HV and IVC invasion. While the involvement of HV and IVC usually portends an overall poor survival, selected patients may be candidates for aggressive treatment and thus improving outcomes.

Examining Decisional Needs And Contextual Factors Influencing Fertility Status Assessment Among Young Female Survivors Of Childhood Cancer: A Sequential Mixed Methods Study Protocol, Brooke Cherven, Nataliya V. Ivankova, Jessica B. Spencer, Anne M. Fitzpatrick, Karen C. Burns, Jenna Demedis, Holly R Hoefgen, Ann C. Mertens, James L. Klosky

2020-Current year OA Pubs

INTRODUCTION: Female cancer survivors who received gonadotoxic cancer treatment are at risk for profound diminished ovarian reserve and/or primary ovarian insufficiency with resulting infertility, which can be associated with distress and decreased quality of life.. Despite prioritizing future parenthood, many survivors are unsure of the impact of their treatment on their future fertility, and little is known about the perceived reproductive health needs and factors associated with receipt of a fertility status assessment (FSA). There is a lack of developmentally appropriate reproductive health decisional support interventions available for emerging adult cancer survivors. This study will explore the perceived reproductive health …

A Novel Biosignature Identifies Patients With Dcis With High Risk Of Local Recurrence After Breast Conserving Surgery And Radiation Therapy, Frank A Vicini, G Bruce Mann, Chirag Shah, Sheila Weinmann, Michael C Leo, Pat Whitworth, Rachel Rabinovitch, Mylin A Torres, Julie A Margenthaler, David Dabbs, Jess Savala, Steven C Shivers, Karuna Mittal, Fredrik Wärnberg, Troy Bremer

2020-Current year OA Pubs

PURPOSE: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT.

METHODS AND MATERIALS: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were …

The Neurotoxin Dsp-4 Dysregulates The Locus Coeruleus-Norepinephrine System And Recapitulates Molecular And Behavioral Aspects Of Prodromal Neurodegenerative Disease, Alexa F. Iannitelli, Michael A. Kelberman, Daniel J. Lustberg, Anu Korukonda, Katharine E. Mccann, Bernard Mulvey, Arielle Segal, L Cameron Liles, Steven A. Sloan, Joseph D. Dougherty, David Weinshenker

2020-Current year OA Pubs

The noradrenergic locus coeruleus (LC) is among the earliest sites of tau and α-synuclein pathology in Alzheimer's disease (AD) and Parkinson's disease (PD), respectively. The onset of these pathologies coincides with loss of noradrenergic fibers in LC target regions and the emergence of prodromal symptoms including sleep disturbances and anxiety. Paradoxically, these prodromal symptoms are indicative of a noradrenergic hyperactivity phenotype, rather than the predicted loss of norepinephrine (NE) transmission following LC damage, suggesting the engagement of complex compensatory mechanisms. Because current therapeutic efforts are targeting early disease, interest in the LC has grown, and it is critical to identify …

Population-Based Mini-Mental State Examination Norms In Adults Of Mexican Heritage In The Cameron County Hispanic Cohort, Avram S Bukhbinder, Miriam Hinojosa, Kristofer Harris, Xiaojin Li, Christine M Farrell, Madison Shyer, Nathan Goodwin, Sahar Anjum, Omar Hasan, Susan Cooper, Lois Sciba, Amanda Falk Vargas, David H Hunter, Guadalupe J Ortiz, Karen Chung, Licong Cui, Guo-Qiang Zhang, Susan P Fisher-Hoch, Joseph B Mccormick, Paul E Schulz

Faculty, Staff and Student Publications

Background:

Accurately identifying cognitive changes in Mexican American (MA) adults using the Mini-Mental State Examination (MMSE) requires knowledge of population-based norms for the MMSE, a scale which has widespread use in research settings.

Objective:

To describe the distribution of MMSE scores in a large cohort of MA adults, assess the impact of MMSE requirements on their clinical trial eligibility, and explore which factors are most strongly associated with their MMSE scores.

Methods:

Visits between 2004–2021 in the Cameron County Hispanic Cohort were analyzed. Eligible participants were ≥18 years old and of Mexican descent. MMSE distributions before and after stratification by …

Risk Of Depression In A Suburban Primary Care Setting Before And During The Covid-19 Pandemic, Carman H Whiting, Pouran Yousefi, Jude K A Des Bordes, Nahid J Rianon

Faculty, Staff and Student Publications

INTRODUCTION: Major depression is a common disorder affecting millions of adults each year. Many population-based surveys showed an increase in the number people with symptoms of depression at the onset of the COVID-19 pandemic. Our aim was to determine and compare the prevalence of depression risk in a primary care setting before and during the COVID-19 pandemic.

METHODS: We conducted a cross-sectional study based on retrospective review of medical records from a large suburban primary care clinic. Records of adults 18 years and older, seen between January 1, 2019 and December 31, 2020 and who had also been screened for …

Similar Overall Expression, But Different Profiles, Of Autistic Traits, Sensory Processing, And Mental Health Between Young Adult Males And Females, Garrett Cardon

Faculty Publications

Recent trends suggest that autism is more common in females than traditionally held. Additionally, some argue that females express autistic traits differently than males. Dimensional views of autism could shed light on these issues, especially with regards to understudied behavioral areas, such as sensory processing. We examined autistic traits, sensory processing, anxiety, and related behaviors in a large sample of neurotypical young adult males and females (n = 1122; 556 female; ages 19–26). Participants completed an online survey containing questionnaires related to the above. Between groups statistical analyses, as well as within groups correlations and mediation analyses containing these constructs …

Similar Overall Expression, But Different Profiles, Of Autistic Traits, Sensory Processing, And Mental Health Between Young Adult Males And Females, Garrett Cardon, Miranda Mcquarrie, Savanah Calton, Terisa P. Gabrielsen

Faculty Publications

Recent trends suggest that autism is more common in females than traditionally held. Additionally, some argue that females express autistic traits differently than males. Dimensional views of autism could shed light on these issues, especially with regards to understudied behavioral areas, such as sensory processing. We examined autistic traits, sensory processing, anxiety, and related behaviors in a large sample of neurotypical young adult males and females (n = 1122; 556 female; ages 19–26). Participants completed an online survey containing questionnaires related to the above. Between groups statistical analyses, as well as within groups correlations and mediation analyses containing these constructs …

Lesbian, Anorexic, Disabled, And Big: Other Ways Of Being A Female Physical Education Teacher, Gustavo González-Calvo, Valeria Varea

Research outputs 2022 to 2026

Research has shown that Physical Education (PE) is a white, male, and able body-dominated profession, particularly in Spain. When some female pre-service PE teachers, who had a difficult relationship with their bodies and sports abilities, enrol in such a degree, some of these problematic relations come to light. Participants for this study were four female pre-service teachers who self-identified as lesbian, anorexic, visually impaired, and big respectively. Data were collected through participant-produced texts, graphical representations, and interviews. The authors then reconstructed the participants’ stories which are presented in the form of narratives. The conceptual tool of embodying norm-criticality helped us …

Attitudes, Beliefs, And Perceptions On Cannabis Among Older Adults Aged 65 And Older: A Cross-Sectional Survey., Alex M Kleidon, Andrew M Peterson, Ilene Warner-Maron, Allen Glicksman

PCOM Scholarly Works

OBJECTIVE: With the rise of medical and recreational cannabis use among older adults, concerns about the potential risks and benefits of cannabis use are increasing. This pilot study aimed to determine the attitudes, beliefs, and perceptions of older adults toward cannabis as a medicinal product, to establish a foundation for future research on how healthcare providers communicate with this population regarding cannabis.

METHODS: A cross-sectional survey was conducted on adults aged 65 and older living in Philadelphia. The survey included questions related to participants' demographics, knowledge, attitudes, beliefs, and perceptions of cannabis. Participants were recruited via flyer distributions, publications in …

Supplementary Feeding And Infection Control In Pregnant Adolescents-A Secondary Analysis Of A Randomized Trial Among Malnourished Women In Sierra Leone, Aminata S Koroma, Mariama Ellie, Kadiatu Bangura, Per O Iversen, David T Hendrixson, Kevin Stephenson, Mark J Manary

2020-Current year OA Pubs

Undernutrition during pregnancy in adolescence confers a high risk of maternal morbidity and adverse birth outcomes, particularly in low-resource settings. In a secondary analysis, we hypothesized that younger undernourished pregnant adolescents (<18 years) would benefit more than undernourished pregnant adults (>20 years) from the intervention of supplementary food and anti-infective treatments. The original trial in Sierra Leone enrolled 236 younger adolescents (<18 years), 454 older adolescents (aged 18-19 years), and 741 adults (≥20 years), all with a mid-upper arm circumference ≤23 cm. Younger adolescents had lower final fundal height as well as smaller newborns (-0.3 kg; 95% confidence interval [CI], -0.3, -0.2; p < 0.001) and shorter newborns (-1.1 cm; 95% CI, -1.5, -0.7; p < 0.001) than adults. The intervention's effect varied significantly between maternal age groups: adults benefited more than younger adolescents with respect to newborn birth weight (difference in difference, 166 g; 95% CI, 26, 306; interaction p = 0.02), birth length (difference in difference, 7.4 mm; 95% CI, 0.1, 14.8; interaction p = 0.047), and risk for low birth weight (<2.5 kg) (interaction p = 0.019). The differences in response persisted despite adjustments for maternal anthropometry, the number of prior pregnancies, and human immunodeficiency virus status. Older adolescents similarly benefited more than younger adolescents, though differences did not reach statistical significance. In conclusion, newborns born to younger adolescent mothers had worse outcomes than those born to adult mothers, and adults and their newborns benefited more from the intervention than younger adolescents.

Validity And Diagnostic Performance Of Computing Fractional Flow Reserve From 2-Dimensional Coronary Angiography Images, Vahid Mohammadi, Massoud Ghasemi, Reza Rahmani, Maryam Mehrpooya, Hamidreza Babakhani, Akbar Shafiee, Mohammad Sadeghian

The Texas Heart Institute Journal

BACKGROUND: Measurement of fractional flow reserve (FFR) is the gold standard for determining the physiologic significance of coronary artery stenosis, but newer software programs can calculate the FFR from 2-dimensional angiography images.

METHODS: A retrospective analysis was conducted using the records of patients with intermediate coronary stenoses who had undergone adenosine FFR (aFFR). To calculate the computed FFR, a software program used simulated coronary blood flow using computational geometry constructed using at least 2 patient-specific angiographic images. Two cardiologists reviewed the angiograms and determined the computational FFR independently. Intraobserver variability was measured using κ analysis and the intraclass correlation coefficient. …

Renewed Calls For Abortion-Related Research In The Post-Roe Era, Sophie L Schott, April Adams, Ryan J Dougherty, Taylor Montgomery, Folasade C Lapite, Faith E Fletcher

Center for Medical Ethics and Health Policy Staff Publications

Nearly 50 years after Roe versus Wade, the United States Supreme Court's decision in Dobbs versus Jackson Women's Health Organization unraveled the constitutional right to abortion, allowing individual states to severely restrict or ban the procedure. In response, leading medical, public health, and community organizations have renewed calls for research to elucidate and address the burgeoning social and medical consequences of new abortion restrictions. Abortion research not only includes studies that establish the safety, quality, and efficacy of evidence-based abortion care protocols, but also encompasses studies on the availability of abortion care, the consequences of being denied an abortion, and …

Cognition And Education Benefits Of Increased Hemoglobin And Blood Oxygenation In Children With Sickle Cell Disease, Joanna P. Macewan, Allison A. King, Andy Nguyen, Anuj Mubayi, Irene Agodoa, Kim Smith-Whitley

2020-Current year OA Pubs

BACKGROUND: Among individuals with sickle cell disease (SCD), decreased hemoglobin is associated with lower oxygen saturation (SpO2) and increased risk of stroke, both of which are associated with lower intelligence quotient (IQ) scores. Thus, increasing hemoglobin and SpO2 in individuals with SCD may increase IQ and educational attainment.

METHODS: A cohort simulation model was built to determine academic performance and educational attainment based on cognitive function (measured by IQ) of a pediatric SCD cohort randomly assigned to treatment and control groups. The model contained two key stages: childhood (<10 years) and adolescence (≥10 years). In stage 1, increased hemoglobin and increased SpO2 (assigned to the treatment group) were determinants of higher IQ, prevention of IQ deterioration over time. Increased hemoglobin was also a determinant of decreased stroke risk. In stage 2, improvement in adolescent IQ as a result of treatment was a determinant of academic performance.

RESULTS: In a simulated cohort of 2000 children and adolescents with …

The Oral Selective Estrogen Receptor Degrader Gdc-0810 (Arn-810) In Postmenopausal Women With Hormone Receptor-Positive Her2-Negative (Hr + /Her2 -) Advanced/Metastatic Breast Cancer, Aditya Bardia, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: GDC-0810 (ARN-810) is a novel, non-steroidal, orally bioavailable, selective estrogen receptor degrader (SERD) that potentially inhibits ligand-dependent and ligand-independent estrogen receptor (ER)-mediated signaling.

METHODS: A phase Ia/Ib/IIa dose escalation, combination treatment with palbociclib or a luteinizing hormone-releasing hormone, and expansion study determined the safety, pharmacokinetics, and recommended phase 2 dose (RP2D) of GDC-0810 in postmenopausal women with ER + (HER2 -) locally advanced or metastatic breast cancer (MBC). Baseline plasma ctDNA samples were analyzed to determine the ESR1 mutation status.

RESULTS: Patients (N = 152) received GDC-0810 100-800 mg once daily (QD) or 300-400 mg twice daily, in dose …

The Plasma Virome In Longitudinal Samples From Pregnant Patients, Molly J Stout, Anoop K Brar, Brandi N Herter, Ananda Rankin, Kristine M Wylie

2020-Current year OA Pubs

INTRODUCTION: Nucleic acid from viruses is common in peripheral blood, even in asymptomatic individuals. How physiologic changes of pregnancy impact host-virus dynamics for acute, chronic, and latent viral infections is not well described. Previously we found higher viral diversity in the vagina during pregnancy associated with preterm birth (PTB) and Black race. We hypothesized that higher diversity and viral copy numbers in the plasma would show similar trends.

METHODS: To test this hypothesis, we evaluated longitudinally collected plasma samples from 23 pregnant patients (11 term and 12 preterm) using metagenomic sequencing with ViroCap enrichment to enhance virus detection. Sequence data …

Apolipoprotein E Genetic Variation, Atherogenic Index And Cardiovascular Disease Risk Assessment In An African Population: An Analysis Of Hiv And Malaria Patients In Ghana, Nicholas Ekow Thomford, Akwasi Anyanful, Richmond Owusu Ateko, Dee Blackhurst, Robert Peter Biney, Dennis Boadi, Samuel Badu Nyarko, Martins Ekor, George Boateng Kyei

2020-Current year OA Pubs

BACKGROUND: Apolipoprotein E is involved in lipid transport and clearance of lipoprotein through low-density lipoprotein receptors (LDLR). ApoE variation has been linked to cardiovascular disease (CVD) risk. There are 3 isoforms of ApoE which originate from two non-synonymous single nucleotide polymorphisms denoted as ε2, ε3 and ε4. The ε2 isoform is implicated in higher levels of atherogenic lipoprotein with the ε4 isoform causing LDLR downregulation. This leads to variable effects and differential CVD risk. Malaria and HIV are life-threatening diseases affecting several countries globally especially in sub-Saharan Africa. Parasite and viral activities have been implicated in lipid dysregulation leading to …

Leveraging Health Infrastructure To Optimize Hpv Vaccination For Adolescents In Zambia: Protocol For An Implementation Study, Sam Miti, Thembekile Shato, Comfort Asante, Ana Baumann, Gershom Chongwe, Patricia M. Bobo, Michelle I. Silver, Jean M. Hunleth

2020-Current year OA Pubs

BACKGROUND: Cervical cancer is the leading cause of cancer death in Zambia, where HIV prevalence is also high (11.3%). HIV heightens the risk of developing and dying from cervical cancer. The human papillomavirus (HPV) vaccine can prevent 90% of cervical cancers, and in Zambia is recommended for adolescent girls ages 14-15 years, including those with HIV. Currently they mainly deliver HPV vaccination via school-based campaigns, which may exclude the most vulnerable adolescents-those out-of-school or who irregularly attend. Adolescents living with HIV (ALHIV) are more likely to have these vulnerabilities. Further, school-based campaigns are not tailored to the WHO-recommended HPV vaccination …

Sex-Related Differences In Premature Cardiovascular Disease In Familial Hypercholesterolemia, Anandita Agarwala, Elena Deych, Laney K Jones, Amy C Sturm, Karen Aspry, Zahid Ahmad, Christie M Ballantyne, Anne C Goldberg

2020-Current year OA Pubs

BACKGROUND: Familial hypercholesterolemia (FH) is associated with an increased prevalence of premature atherosclerotic cardiovascular disease (ASCVD), however, little is known about sex-specific differences in premature ASCVD and its risk factors.

OBJECTIVE: The present study seeks to assess the burden and risk factors for premature ASCVD among men and women with FH.

METHODS: In this study we retrospectively examined sex-specific differences in ASCVD prevalence, risk factor burdens, and lipid treatment outcomes in 782 individuals with clinically or genetically confirmed FH treated in 5 U.S. lipid and genetics clinics. A generalized linear model using Binomial distribution with random study site effect and …

Pregnancy-Induced Differential Expression Of Sars-Cov-2 And Influenza A Viral Entry Factors In The Lower Respiratory Tract, Tusar Giri, Santosh Panda, Arvind Palanisamy

2020-Current year OA Pubs

Despite differences in the clinical presentation of coronavirus disease-19 and pandemic influenza in pregnancy, fundamental mechanistic insights are currently lacking because of the difficulty in recruiting critically ill pregnant subjects for research studies. Therefore, to better understand host-pathogen interaction during pregnancy, we performed a series of foundational experiments in pregnant rats at term gestation to assess the expression of host entry factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) and genes associated with innate immune response in the lower respiratory tract. We report that pregnancy is characterized by a decrease in host factors mediating …

Neuroinflammation And Amyloid Deposition In The Progression Of Mixed Alzheimer And Vascular Dementia, Chunwei Ying, Peter Kang, Michael M Binkley, Andria L Ford, Yasheng Chen, Jason Hassenstab, Qing Wang, Jeremy Strain, John C Morris, Jin-Moo Lee, Tammie L S Benzinger, Hongyu An

2020-Current year OA Pubs

BACKGROUND: Alzheimer's disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) pathologies coexist in patients with cognitive impairment. Abnormal amyloid beta (Aβ) deposition is the hallmark pathologic biomarker for AD. Neuroinflammation may be a pathophysiological mechanism in both AD and VCID. In this study, we aimed to understand the role of neuroinflammation and Aβ deposition in white matter hyperintensities (WMH) progression and cognitive decline over a decade in patients with mixed AD and VCID pathologies.

METHODS: Twenty-four elderly participants (median [interquartile range] age 78 [64.8, 83] years old, 14 female) were recruited from the Knight Alzheimer Disease Research …

Milder Loss Of Insulin-Containing Islets In Individuals With Type 1 Diabetes And Type 2 Diabetes-Associated Tcf7l2 Genetic Variants, Maria J Redondo, Sarah J Richardson, Daniel Perry, Charles G Minard, Alice L J Carr, Todd Brusko, Irina Kusmartseva, Alberto Pugliese, Mark A Atkinson

Faculty, Staff and Students Publications

AIMS/HYPOTHESIS: TCF7L2 variants are the strongest genetic risk factor for type 2 diabetes. In individuals with type 1 diabetes, these variants are associated with a higher C-peptide AUC, a lower glucose AUC during an OGTT, single autoantibody positivity near diagnosis, particularly in individuals older than 12 years of age, and a lower frequency of type 1 diabetes-associated HLA genotypes. Based on initial observations from clinical cohorts, we tested the hypothesis that type 2 diabetes-predisposing TCF7L2 genetic variants are associated with a higher percentage of residual insulin-containing cells (ICI%) in pancreases of donors with type 1 diabetes, by examining genomic data …

A Systematic Review And Meta-Analysis Of Long Term Physical And Mental Sequelae Of Covid-19 Pandemic: Call For Research Priority And Action, Na Zeng, Yi-Miao Zhao, Wei Yan, Chao Li, Qing-Dong Lu, Lin Liu, Shu-Yu Ni, Huan Mei, Kai Yuan, Le Shi, Peng Li, Teng-Teng Fan, Jun-Liang Yuan, Michael V Vitiello, Thomas Kosten, Alexandra L Kondratiuk, Hong-Qiang Sun, Xiang-Dong Tang, Mei-Yan Liu, Ajit Lalvani, Jie Shi, Yan-Ping Bao, Lin Lu

Faculty, Staff and Students Publications

The long-term physical and mental sequelae of COVID-19 are a growing public health concern, yet there is considerable uncertainty about their prevalence, persistence and predictors. We conducted a comprehensive, up-to-date meta-analysis of survivors' health consequences and sequelae for COVID-19. PubMed, Embase and the Cochrane Library were searched through Sep 30th, 2021. Observational studies that reported the prevalence of sequelae of COVID-19 were included. Two reviewers independently undertook the data extraction and quality assessment. Of the 36,625 records identified, a total of 151 studies were included involving 1,285,407 participants from thirty-two countries. At least one sequelae symptom occurred in 50.1% (95% …

Risk Stratification For Hepatocellular Cancer Among Patients With Cirrhosis Using A Hepatic Fat Polygenic Risk Score, Aaron P Thrift, Fasiha Kanwal, Yanhong Liu, Saira Khaderi, Amit G Singal, Jorge A Marrero, Nicole Loo, Sumeet K Asrani, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Spiridon Tsavachidis, Xiangjun Gu, Christopher I Amos, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND: Polygenic risk scores (PRS) hold the promise to refine prognostication in hepatocellular cancer (HCC). The few available HCC PRS include germline risk variants identified among individuals of mostly European ancestry, but data are lacking on the transportability of these PRS in multiethnic U.S patients with cirrhosis from multiple etiologies.

METHODS: We used data from 1644 patients with cirrhosis enrolled in two prospective cohort studies in the U.S. Patients were followed until HCC diagnosis, death, liver transplantation, or last study visit through June 30, 2021. The high-risk variants in PNPLA3-MBOAT7-TM6SF2-GCKR were combined in a PRS and we evaluated its association …

Impact Of The Covid Pandemic On Mental Health And Training Opportunities Of Public Health Residents From 4 European Countries: A Cross-Sectional Study, Giovanna Failla, Marta Caminiti, José Chen-Xu, Giuseppina Lo Moro, Nausicaa Berselli, Madalena Cabral Ferreira, Filipa Malcata, David Peyre-Costa, Roberto Croci, Giorgia Soldà, Angelo Capodici, Caterina Morcavallo, Francesco Traglia, Fabrizio Cedrone, Ilaria Storti, Alfonso Alonso Jaquete, Martina Antinozzi, Anca Vasiliu

Faculty, Staff and Students Publications

OBJECTIVES: There is little evidence on the impact of the COVID-19 pandemic on Public Health Residents' (PHR) mental health (MH). This study aims at assessing prevalence and risk factors for depression, anxiety and stress in European PHR during the COVID-19 pandemic.

METHODS: Between March and April 2021, an online survey was administered to PHR from France, Italy, Portugal and Spain. The survey assessed COVID-19 related changes in working conditions, training opportunities and evaluated MH outcomes using the Depression Anxiety Stress Scales-21. Multivariable logistic regressions were applied to identify risk factors.

RESULTS: Among the 443 respondents, many showed symptoms of depression …

Optical Coherence Tomography For Dynamic Investigation Of Mammalian Reproductive Processes, Kohei Umezu, Irina V Larina

Faculty, Staff and Students Publications

The biological events associated with mammalian reproductive processes are highly dynamic and tightly regulated by molecular, genetic, and biomechanical factors. Implementation of live imaging in reproductive research is vital for the advancement of our understanding of normal reproductive physiology and for improving the management of reproductive disorders. Optical coherence tomography (OCT) is emerging as a promising tool for dynamic volumetric imaging of various reproductive processes in mice and other animal models. In this review, we summarize recent studies employing OCT-based approaches toward the investigation of reproductive processes in both, males and females. We describe how OCT can be applied to …