Digital Commons Network^™

Vps13b Is Localized At The Interface Between Golgi Cisternae And Is A Functional Partner Of Fam177a1, Berrak Ugur, Florian Schueder, Jimann Shin, Michael G Hanna, Yumei Wu, Marianna Leonzino, Maohan Su, Anthony R Mcadow, Catherine Wilson, John Postlethwait, Lilianna Solnica-Krezel, Joerg Bewersdorf, Pietro De Camilli

2020-Current year OA Pubs

Mutations in VPS13B, a member of a protein family implicated in bulk lipid transport between adjacent membranes, cause Cohen syndrome. VPS13B is known to be concentrated in the Golgi complex, but its precise location within this organelle and thus the site(s) where it achieves lipid transport remains unclear. Here, we show that VPS13B is localized at the interface between proximal and distal Golgi subcompartments and that Golgi complex reformation after Brefeldin A (BFA)-induced disruption is delayed in VPS13B KO cells. This delay is phenocopied by the loss of FAM177A1, a Golgi complex protein of unknown function reported to be a …

Heterozygous Btnl8 Variants In Individuals With Multisystem Inflammatory Syndrome In Children (Mis-C), Evangelos Bellos, Erica G Schmitt, Et Al.

2020-Current year OA Pubs

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5-5.3, P < 10-6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2.

Functional Role Of Myosin-Binding Protein H In Thick Filaments Of Developing Vertebrate Fast-Twitch Skeletal Muscle, Andrew F Mead, Marilyn J Cipolla, Aaron N Johnson, Christina A Gurnett, Et Al.

2020-Current year OA Pubs

Myosin-binding protein H (MyBP-H) is a component of the vertebrate skeletal muscle sarcomere with sequence and domain homology to myosin-binding protein C (MyBP-C). Whereas skeletal muscle isoforms of MyBP-C (fMyBP-C, sMyBP-C) modulate muscle contractility via interactions with actin thin filaments and myosin motors within the muscle sarcomere "C-zone," MyBP-H has no known function. This is in part due to MyBP-H having limited expression in adult fast-twitch muscle and no known involvement in muscle disease. Quantitative proteomics reported here reveal that MyBP-H is highly expressed in prenatal rat fast-twitch muscles and larval zebrafish, suggesting a conserved role in muscle development and …

Redesigning The Hospital Environment To Improve Restfulness, Caellagh D Catley, Kayla Paynter, Kendall Jackson, Ashley Huggins, Jenny Ji, Sai Anusha Sanka, Michelle Simkins, Thomas M Maddox, Patrick G Lyons

2020-Current year OA Pubs

IMPORTANCE: Hospital wards are often not conducive to patient sleep, negatively affecting patient health and experience.

OBJECTIVES: To assess determinants of in-hospital restfulness and to design and test rest-promoting interventions on the wards in partnership with clinicians, staff, and patients.

DESIGN, SETTING, AND PARTICIPANTS: This rapid-sequential mixed-methods quality improvement study was performed at a large urban academic hospital in St Louis, Missouri, from May 1, 2021, to December 31, 2022, with follow-up through hospitalization. Mixed-methods activities involved purposively selected hospitalized adults on the wards, nurses, hospitalists, and hospital staff. Interventions included all adult hospitalizations on the study wards.

INTERVENTIONS: Sequential …

Secure Messaging Use And Wrong-Patient Ordering Errors Among Inpatient Clinicians, Sunny S Lou, Daphne Lew, Linlin Xia, Laura Baratta, Elise Eiden, Thomas Kannampallil

2020-Current year OA Pubs

IMPORTANCE: Use of secure messaging for clinician-to-clinician communication has increased exponentially over the past decade, but its association with clinician work is poorly understood.

OBJECTIVE: To investigate the association between secure messaging use and wrong-patient ordering errors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included inpatient attending physicians, trainee physicians, and advanced practice practitioners (APPs) from 14 academic and community hospitals. Secure messaging volume was assessed over a 3-month period (February 1 to April 30, 2023).

EXPOSURE: Secure messaging volume per clinician-day, measured as the count of secure messages sent and received by a clinician on a given clinician-day.

MAIN …

Medical And Surgical Episodes Among Hospital Participants In The Bundled Payments For Care Improvement-Advanced Program, Keenan J Robbins, Jie Zheng, R J Waken, E John Orav, Arnold M Epstein, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: Hospital participation in the Bundled Payments for Care Improvement-Advanced (BPCI-A) initiative has been associated with modest savings and stable clinical outcomes overall, but it is unknown whether the program performs differently for medical and surgical or procedural (henceforth, surgical) episodes.

OBJECTIVE: To assess the association of BPCI-A participation with Medicare spending and clinical outcomes for medical and surgical episodes.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective difference-in-differences cohort study utilized 100% Medicare fee-for-service inpatient claims for episodes initiated between January 1, 2017, and September 30, 2019, and included 90 days of follow-up. The setting was hospitals participating in BPCI-A and …

Allostatic Load, Educational Attainment, And Risk Of Cancer Mortality Among Us Men, Cynthia Li, Sydney P Howard, Charles R Rogers, Sydney Andrzejak, Keon L Gilbert, Keith J Watts, Malcolm S Bevel, Myles D Moody, Marvin E Langston, Judah V Doty, Adetunji T Toriola, Darwin Conwell, Justin X Moore

2020-Current year OA Pubs

IMPORTANCE: Health disparities among racial and ethnic minoritized populations, particularly for cancer mortality rates, remain a major public health concern. Men from underrepresented backgrounds (Black and Hispanic men, specifically) face the pervasive effects of discrimination in their daily lives, which also contribute to the complex associations among allostatic load (a marker of chronic stress), educational opportunities, and elevated risks of cancer mortality.

OBJECTIVE: To elucidate the associations among educational attainment, allostatic load, and cancer mortality risk among men.

DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective cohort analysis of data from the National Health and Nutrition Examination Survey, a nationally …

Neuroanatomical Variability And Substance Use Initiation In Late Childhood And Early Adolescence, Alex P Miller, David A A Baranger, Sarah E Paul, Hugh Garavan, Scott Mackey, Susan F Tapert, Kimberly H Leblanc, Arpana Agrawal, Ryan Bogdan

2020-Current year OA Pubs

IMPORTANCE: The extent to which neuroanatomical variability associated with early substance involvement, which is associated with subsequent risk for substance use disorder development, reflects preexisting risk and/or consequences of substance exposure remains poorly understood.

OBJECTIVE: To examine neuroanatomical features associated with early substance use initiation and to what extent associations may reflect preexisting vulnerability.

DESIGN, SETTING, AND PARTICIPANTS: Cohort study using data from baseline through 3-year follow-up assessments of the ongoing longitudinal Adolescent Brain Cognitive Development Study. Children aged 9 to 11 years at baseline were recruited from 22 sites across the US between June 1, 2016, and October 15, …

Major Depressive Disorder And Driving Behavior Among Older Adults, Ganesh M Babulal, Ling Chen, Jean-Francois Trani, David C Brown, David B Carr, Beau M Ances, Eric J Lenze, Drives Project

2020-Current year OA Pubs

IMPORTANCE: Depression and antidepressant use are independently associated with crash risk among older drivers. However, it is unclear what factors impact daily driving that increase safety risk for drivers with depression.

OBJECTIVE: To examine differences in naturalistic driving behavior and safety between older adults with and without major depressive disorder (MDD).

DESIGN, SETTING, AND PARTICIPANTS: A prospective longitudinal cohort study was conducted among older adults (≥65 years) from the Driving Real-World In-Vehicle Evaluation System Project collected from July 1, 2021, to December 30, 2023. The sample included 85 participants with MDD and 310 participants without. Neurological, clinical, mood, and neuropsychological …

Alcohol Use Disorder Polygenic Score Compared With Family History And Adh1b, Dongbing Lai, Michael Zhang, Marco Abreu, Tae-Hwi Schwantes-An, Grace Chan, Danielle M Dick, Chella Kamarajan, Weipeng Kuang, John I Nurnberger, Martin H Plawecki, John Rice, Marc Schuckit, Bernice Porjesz, Yunlong Liu, Tatiana Foroud

2020-Current year OA Pubs

IMPORTANCE: Identification of individuals at high risk of alcohol use disorder (AUD) and subsequent application of prevention and intervention programs has been reported to decrease the incidence of AUD. The polygenic score (PGS), which measures an individual's genetic liability to a disease, can potentially be used to evaluate AUD risk.

OBJECTIVE: To assess the estimability and generalizability of the PGS, compared with family history and ADH1B, in evaluating the risk of AUD among populations of European ancestry.

DESIGN, SETTING, AND PARTICIPANTS: This genetic association study was conducted between October 1, 2023, and May 21, 2024. A 2-stage design was used. …

Leveraging Group Model Building To Operationalize Implementation Strategies Across Implementation Phases: An Exemplar Related To Child Maltreatment Intervention Selection, Gracelyn Cruden, Byron J Powell, Leah Frerichs, Paul Lanier, C Hendricks Brown, Lisa Saldana, Kristen Hassmiller Lich

2020-Current year OA Pubs

BACKGROUND: Implementation strategies can help support the adoption and implementation of health interventions that are appropriate for a local context and acceptable to decision makers and community members. Implementation strategies should be designed to handle the complexity of the multi-level, dynamic contexts in which interventions are implemented. Systems science theories and methods explicitly attend to complexity and can be valuable for specifying implementation strategies. Group Model Building (GMB) combines research partner engagement strategies with systems science to support researchers' and partners' learning about complex problems and to identify solutions through consensus. This paper specifies how GMB can operationalize implementation strategies …

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society Expert Consensus Statement On Catheter And Surgical Ablation Of Atrial Fibrillation, Stylianos Tzeis, Ralph J Damiano, Et Al.

2020-Current year OA Pubs

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a …

Cannabidiol Prescribing In The United States: An Analysis Of Real-World Data, Binx Yezhe Lin, Chloe Lessard, Yifan Li, Lisa Gong, Ruth Ling, Pallawi Jyotsana, Jacob Steinle, Jacob T Borodovsky, Fábio A Nascimento, Kevin Y Xu

2020-Current year OA Pubs

BACKGROUND: Off-label prescribing of Epidiolex® (pharmaceutical cannabidiol) comes with both potential benefits and risks for patients. The aims of this study were to: (1) identify the percentage of people prescribed Epidiolex® who do not have diagnostic indications for Epidiolex® (Lennox Gastaut Syndrome [LGS], Dravet Syndrome [DS], and Tuberous Sclerosis Complex [TSC]) and (2) examine potential co-prescribing of medications that may interact with Epidiolex®.

METHOD: Using TriNetX analytics, a web-based database of de-identified electronic health records spanning >110 million people in the United States, we analyzed 4214 people receiving Epidiolex® in 2022. We computed the number of people prescribed Epidiolex® who …

Healthcare Disparities, Screening, And Molecular Testing In The Changing Landscape Of Non-Small Cell Lung Cancer In The United States: A Review, Razelle Kurzrock, Aadel A Chaudhuri, David Feller-Kopman, Narjust Florez, Jed Gorden, Ignacio I Wistuba

2020-Current year OA Pubs

Inequitable access to care continues to hinder improvements in diagnosis and treatment of lung cancer. This review describes healthcare disparities in the changing landscape of non-small cell lung cancer (NSCLC) in the United States, focusing on racial, ethnic, sex-based, and socioeconomic trends. Furthermore, strategies to address disparities, overcome challenges, and improve patient outcomes are proposed. Barriers exist across lung cancer screening, diagnosis, and treatment regimens, varying by sex, age, race and ethnicity, geography, and socioeconomic status. Incidence and mortality rates of lung cancer are higher among Black men than White men, and incidences in young women are substantially greater than …

Patient With Post-Operative Recurrent Pancreatic Cancer Treated With Cone Beam Computed Tomography-Guided Stereotactic Adaptive Radiotherapy: A Case Report, Farnoush Forghani, Alden D'Souza, Eric Laugeman, Allen Mo, Pamela P. Samson, Hyun Kim

2020-Current year OA Pubs

CT-guided adaptive radiotherapy (ART) for the treatment of pancreatic adenocarcinoma is rapidly increasing and has been shown to provide advanced treatment tools comparable to magnetic resonance imaging (MRI)-guided adaptive therapy. Here, we provide the first case report of a local pancreatic recurrence treatment after definitive resection using cone beam computed tomography (CBCT)-guided ART (CT-guided ART) enabled by HyperSight imaging (Varian Medical Systems, Inc., Palo Alto, CA, USA) for daily delineation of organs-at-risk (OARs) and target to improve the quality of online ART. A 61-year-old female was diagnosed with pancreatic adenocarcinoma, and her CT demonstrated a 1.9 cm lesion abutting the …

Predictors Of No-Shows After An Endoscopic Mucosal Resection In Veterans: A Retrospective Analysis, Mahmoud Y. Madi, Yassine Kilani, Hayden Rotramel, Michelle Baliss, Jill Elwing, Gregory Sayuk, Ahmad Bazarbashi

2020-Current year OA Pubs

Introduction Endoscopic mucosal resection (EMR) is a common intervention for large colorectal polyps, but its long-term success depends heavily on post-procedure surveillance to detect recurrence. Despite the critical importance of follow-up appointments, some patients fail to attend these crucial visits. This study aims to identify demographic, clinical, and socioeconomic factors that predict missed follow-up appointments after EMR. By understanding which patients are at the highest risk for non-compliance, we can develop targeted strategies to improve follow-up adherence and optimize long-term outcomes in this population. Methods We conducted a single-center retrospective study at the Saint Louis Veterans Affairs Healthcare System of …

Nivolumab Plus Relatlimab And Nivolumab Plus Ipilimumab For Patients With Advanced Renal Cell Carcinoma: Results From The Open-Label, Randomised, Phase Ii Fraction-Rcc Trial, T K Choueiri, R K Pachynski, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology study in patients with aRCC (FRACTION-RCC) was designed to assess new immuno-oncology (IO) combinations in patients with advanced renal cell carcinoma (aRCC). We present results in IO-naive patients treated with nivolumab (NIVO) + relatlimab (RELA) or NIVO + ipilimumab (IPI) in track 1.

METHODS: The open-label, randomised, phase II FRACTION-RCC trial enrolled patients with aRCC from 32 hospitals and cancer centres across six countries. Patients were enrolled in track 1 (IO-naive) or track 2 (IO-experienced). IO-naive patients were stratified by previous tyrosine kinase inhibitor therapy and randomised to NIVO (240 …

Delivery Of Hand Care To Patients With High Anxiety Burden, Caellagh D Catley, Sarah C Romans, Abby L Cheng, Ryan P Calfee

2020-Current year OA Pubs

PURPOSE: To determine whether patients presenting with Patient-Reported Outcome Measurement Information System (PROMIS) anxiety scores at >95th percentile of the US population undergo elective hand surgery at rates different from patients with less anxiety. Secondarily, we aimed to assess surgeon notation of these patients' emotional states and incidences of postoperative complications.

METHODS: This single-center retrospective cohort study analyzed data from new adult patients presenting for hand care between January 2019 and December 2020. Patients with initial PROMIS anxiety scores ≥70 were identified as the high anxiety burden (HAB) group. For each patient with HAB presenting with carpal tunnel syndrome, trigger …

Pain Interference Prior To And 1 Year After Surgery For Adult Traumatic Brachial Plexus Injury, Christopher J Dy, David M Brogan, Bryan J Loeffler, Steve K Lee, Harvey Chim, Mihir J Desai, Sami H Tuffaha, Yusha Liu, Planet Study Group

2020-Current year OA Pubs

PURPOSE: Pain after brachial plexus injury (BPI) can be severely debilitating and is poorly understood. We hypothesized that pain interference (PI) ("the extent to which pain hinders engagement in life") would be predicted by depression, anxiety, severity of pain symptoms, and poorer preoperative muscle function.

METHODS: Among patients in a prospective multicenter BPI cohort study, 37 completed Patient-Reported Outcomes Measurement Information System (PROMIS) PI questionnaires before and 1 year after surgery. At both times, participants completed anxiety and depression questionnaires and BPI-specific measures of pain symptoms, physical limitations, and emotional recovery. Surgeon-graded muscle testing, injury severity, age at the time …

Effect Of Screw Length In Volar Plating For Intra-Articular Distal Radius Fractures: A Biomechanical Study, Thomas S Hong, Daniel J Lee, Babak Jahani, Kaitlyn S Broz, Donald A Aboytes, Simon Tang, Stephen Demartini, David M Brogan

2020-Current year OA Pubs

PURPOSE: The purpose of this study was to compare the effect of varying screw lengths on load to failure and retention of the dorsal ulnar corner fragment after fixation of comminuted intra-articular distal radius fractures in a cadaveric model.

METHODS: Twenty-four fresh frozen cadaveric forearms were subjected to a standardized distal radius osteotomy to mimic an intra-articular fracture pattern. Dual X-ray absorptiometry scans were performed to ensure minimal variability in bone density. All fractures were fixed with a volar locking plate and distal locking screws. Three different lengths of distal locking screws were used in each group of eight specimens …

Molecular Imaging Of Macrophage Composition And Dynamics In Masld, Bin Q Yang, Mandy M Chan, Gyu Seong Heo, Lanlan Lou, Hannah Luehmann, Christopher Park, Alexandria Li, Divangana Lahad, Deborah Sultan, Peter Voller, Kathleen Byrnes, Christina Fu, Yongjian Liu, Joel D Schilling

2020-Current year OA Pubs

BACKGROUND & AIMS: Metabolic-dysfunction associated steatohepatitis (MASH) is associated with obesity and diabetes, and is linked to liver fibrosis and cardiovascular disease. Identification of patients who have MASH is challenging and the development of non-invasive strategies to diagnose and follow this condition is an important unmet need. Recent studies in mouse and humans have identified that significant changes occur in liver macrophage composition during MASH progression; namely, resident Kupffer cells decrease in number while recruited monocyte-derived macrophages increase.

METHODS: We developed peptide radiotracers targeted to C-C motif chemokine receptor 2 (CCR2) and CD163 to conduct positron emission tomography (PET) imaging …

Stereotactic Body Radiation Therapy For Palliative Reirradiation Of Acrometastasis In The Hand From Breast Cancer, Thomas R Mazur, H Michael Gach, Joshua P Schiff, Laura L Ochoa, Michael J Naughton, Imran Zoberi

2020-Current year OA Pubs

No abstract provided.

Molecular Imaging In Experimental Pulmonary Fibrosis Reveals That Nintedanib Unexpectedly Modulates Ccr2 Immune Cell Infiltration, Hasan Farooq, Hannah P Luehmann, Jeffrey R Koenitzer, Gyu Seong Heo, Deborah H Sultan, Devesha H Kulkarni, Sean P Gunsten, Rekha M Sashti, Tao Huang, Amanda R Keller, Kory J Lavine, Jeffrey J Atkinson, Laura M Wingler, Yongjian Liu, Steven L Brody

2020-Current year OA Pubs

BACKGROUND: Pulmonary fibrosis is a challenging clinical problem with lung pathology featuring immune cell infiltrates, fibroblast expansion, and matrix deposition. Molecular analysis of diseased lungs and preclinical models have uncovered C-C chemokine receptor type 2 (CCR2)+ monocyte egress from the bone marrow into the lung, where they acquire profibrotic activities. Current drug treatment is focused on fibroblast activity. Alternatively, therapeutic targeting and monitoring CCR2+ cells may be an effective patient management strategy.

METHODS: Inhibition of CCR2+ cells and, as a benchmark, the clinical antifibrotic agent, nintedanib, were used in mouse lung fibrosis models. Lungs were evaluated directly for CCR2+ cell …

Vitamin D In Patients With Low Tumor-Burden Indolent Non-Hodgkin Lymphoma Treated With Rituximab Therapy (Ilyad): A Randomized, Phase 3 Clinical Trial, Jonathan W Friedberg, Brad S Kahl, Et Al.

2020-Current year OA Pubs

BACKGROUND: There is a significant association between low vitamin D levels at diagnosis of indolent B-cell lymphomas and inferior overall survival (OS). To determine whether supplemental vitamin D improves event-free survival (EFS) in these patients, we conducted a comparative double-blind study of vitamin D

METHODS: In this phase 3, randomized, double-blind, placebo-controlled trial, patients with low tumor burden follicular, marginal zone or small lymphocytic lymphoma, age 18 or older, with stage two or greater disease and no prior systemic treatment were enrolled at 7 academic cancer centers. Patients were stratified by histology and FLIPI (Follicular Lymphoma International Prognostic Index) score …

Complex Emotion Processing And Early Life Adversity In The Healthy Brain Network Sample, Emily J Furtado, M Catalina Camacho, Jenna H Chin, Deanna M Barch

2020-Current year OA Pubs

OBJECTIVE: Early life adversity (ELA) has shown to have negative impacts on mental health. One possible mechanism is through alterations in neural emotion processing. We sought to characterize how multiple indices of ELA were related to naturalistic neural socio-emotional processing.

METHOD: In 521 5-15-year-old participants from the Healthy Brain Network Biobank, we identified scenes that elicited activation of the Default Mode Network (DMN), Ventral Attention Network (VAN), Cingulo-Opercular Network (CON) and amygdala, all of which are networks shown to be associated with ELA. We used linear regression to examine associations between activation and ELA: negative parenting, social status, financial insecurity, …

Disentangling The Unique Contributions Of Age, Pubertal Stage, And Pubertal Hormones To Brain Structure In Childhood And Adolescence, Mark Curtis, John C Flournoy, Sridhar Kandala, Ashley F P Sanders, Michael P Harms, Adam Omary, Leah H Somerville, Deanna M Barch

2020-Current year OA Pubs

Puberty and associated changes in pubertal hormones influence structural brain development. Hormones such as dehydroepiandrosterone (DHEA) and progesterone remain understudied, and it remains unclear how these aspects of puberty contribute uniquely to structural brain development. We used the Human Connectome Project in Development cross-sectional sample of 1304 youth (aged 5-21 years) to investigate unique contributions of sex, age, pubertal stage, DHEA, testosterone, estradiol, and progesterone to cortical thickness, surface area, and subcortical volume development within functionally-relevant networks. Sex and age explain the most unique variance in all three aspects of structural development. Pubertal stage and pubertal hormones uniquely contribute more …

Quantifying Brain Development In The Healthy Brain And Child Development (Hbcd) Study: The Magnetic Resonance Imaging And Spectroscopy Protocol, Douglas C Dean 3rd, Chad M Sylvester, Michael P Harms, Christopher D Smyser, Et Al.

2020-Current year OA Pubs

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life. Overcoming these challenges requires an innovative and harmonized approach, combining age-appropriate acquisition protocols together with specialized pediatric neuroimaging strategies. The HBCD MRI Working Group aimed to establish a core acquisition …

The Sodium-Proton Exchangers Snhe And Nhe1 Control Plasma Membrane Hyperpolarization In Mouse Sperm, Analia G Novero, Celia M Santi, Et Al.

2020-Current year OA Pubs

Sperm capacitation is a complex process that takes place in the female reproductive tract and empowers mammalian sperm with the competence to fertilize an egg. It consists of an intricate cascade of events that can be mimicked in vitro through incubation in a medium containing essential components, such as bicarbonate, albumin, Ca

Minority Stress Mediates Associations Of Sexual Minority State Policies And Tobacco Use Among Us Sexual Minority Young Adults, Katelyn F Romm, Erin A Vogel, Christina Dyar, Laurie A Drabble, Patricia A Cavazos-Rehg, Carla J Berg

2020-Current year OA Pubs

INTRODUCTION: State policies surrounding sexual minority (SM) rights are associated with tobacco use among SM individuals. Research is scant regarding the role of distinct SM policy categories on SM young adults' (SMYAs) tobacco use and mechanisms explaining these associations.

METHODS: We analyzed 2023 survey data from 1100 SMYAs (ages 18-34; 14.2 % gender minority; 66.1 % bisexual+, 29.1 % monosexual; 53.2 % racial/ethnic minority) with representation across 45 US states and DC. Regression-based models examined: 1) direct associations of residing in states with negative and limited (vs. comprehensive) SM state policies with respect to 7 policy categories (relationship/parent recognition, nondiscrimination, …

Tyk2 Regulates Tau Levels, Phosphorylation And Aggregation In A Tauopathy Mouse Model, Jiyoen Kim, Bakhos Tadros, Yan Hong Liang, Youngdoo Kim, Cristian Lasagna-Reeves, Jun Young Sonn, Dah-Eun Chloe Chung, Bradley Hyman, David M Holtzman, Huda Yahya Zoghbi

2020-Current year OA Pubs

Alzheimer's disease is one of at least 26 diseases characterized by tau-positive accumulation in neurons, glia or both. However, it is still unclear what modifications cause soluble tau to transform into insoluble aggregates. We previously performed genetic screens that identified tyrosine kinase 2 (TYK2) as a candidate regulator of tau levels. Here we verified this finding and found that TYK2 phosphorylates tau at tyrosine 29 (Tyr29) leading to its stabilization and promoting its aggregation in human cells. We discovered that TYK2-mediated Tyr29 phosphorylation interferes with autophagic clearance of tau. We also show that TYK2-mediated phosphorylation of Tyr29 facilitates pathological tau …