Medicine and Health Sciences Commons^™

Dexmedetomidine On Supraventricular Tachycardia In Critical Illness: A Time-Dependent Propensity Score Matching Study, Qiaonan Zhong, Marin H Kollef, Patrick G Lyons, Andrew P Michelson

2020-Current year OA Pubs

BACKGROUND: Supraventricular tachycardia affects many critically ill patients. Dexmedetomidine, a commonly used sedative, has sympatholytic and vagotonic effects that may alter atrioventricular nodal conduction and contribute to SVT. We aim to determine the association between dexmedetomidine exposure and clinically significant supraventricular tachycardia in a heterogeneous cohort of mechanically ventilated, critically ill adults. METHODS: This retrospective cohort study included critically ill patients from 11 hospitals admitted between July 2018 and October 2022, who were intubated within 48 h of admission. The primary exposure was intravenous dexmedetomidine. The primary outcome was occurrence of clinically significant supraventricular tachycardia, defined as heart rate > 100 …

Avian Influenza Preparedness In Ghana: A Cross-Sectional Assessment Of Knowledge, Attitudes, And Practices Among Residents Of Nsawam-Adoagyiri Municipality, Eastern Region, Christopher Yaw Dumevi, George Boateng Kyei, Et Al.

2020-Current year OA Pubs

BACKGROUND: Avian influenza (AI) represents a persistent threat to public health, food security, and livelihoods in Ghana, where outbreaks of H5N1 and H9N2 have occurred. This cross-sectional study evaluated the knowledge, attitudes, and practices (KAP) related to avian influenza among residents of the Nsawam-Adoagyiri Municipality; an area characterized by intensive poultry production with the aim of delineating deficits in community-level preparedness and guiding evidence-based public health interventions. METHODS: A community-based cross-sectional study was conducted from May to July 2025 using a four-stage sampling technique. We surveyed 321 adults via structured questionnaires, evaluating socio-demographics and KAP related to AI. Scale reliability …

Cell Type-Specific Enhancers Regulate Il-22 Expression In Innate And Adaptive Type 3 Lymphoid Cells, Ankita Saini, Leone S Hopkins, Vanida A Serna, Matthew V D Mccullen, Nicholas G Selner, Bishan Bhattarai, José L Fachi, Rebecca A Glynn, Katharina E Hayer, Craig H Bassing, Marco Colonna, Eugene M Oltz

2020-Current year OA Pubs

IL-22, a signature cytokine for type 3 lymphoid cells, including T helper 17/22 (Th17/22) and type 3 innate lymphoid cells (ILC3), mediates epithelial homeostasis and protective pathogen responses in barrier tissues. Upon dysregulation, IL-22 can drive chronic inflammatory diseases, yet little is known about transcriptional elements modulating its expression. Here, we identify two enhancers, E22-1 and E22-2, with distinct capacities for regulating Il22 expression in type 3 lymphoid cells. Both enhancers are necessary for protection from Citrobacter rodentium infection and for the onset of IL-22-mediated psoriasis. E22-2 is specifically required for IL-22 expression in ILC3s, while E22-1 functions in both …

Mechanism-Informed Transition From Pediatric To Adult Care In Sickle Cell Disease: A Case Study, Jane S Hankins, Tarun Aurora, Rachel Matsumoto, Sara Malone, Ana A Baumann

2020-Current year OA Pubs

BACKGROUND: Healthcare transition (HCT) refers to the shift from a child-centered to an adult-centered model of care, a process that, when well-functioning, can reduce disengagement and improve satisfaction with care. The Six Core Elements (6CE) framework structures HCT services; however, its implementation process remains understudied, limiting its broader applicability. Learning how to effectively implement the 6CE strategies can enhance their application in real clinical contexts. This case study describes the successful implementation of a 6CE-informed transition program for adolescents and young adults with sickle cell disease (SCD), a genetic condition associated with reduced life expectancy. We also propose a mechanism-informed …

Commonality And Co-Occurrence Of Discrete Strategies Within Implementation Strategy Bundles: Findings From The Living Database Of Hiv Implementation Science Systematic Review, 2014-2021, Sita Lujintanon, Ingrid Eshun-Wilson, Noelle Le Tourneau, Laura K Beres, Sheree Schwartz, Stefan Baral, Ryan Thompson, Ashley Underwood, Branson Fox, Elvin H Geng, Christopher G Kemp

2020-Current year OA Pubs

BACKGROUND: HIV services and innovations are delivered through implementation strategy bundles that are often complex, comprising numerous discrete strategies. Systematically characterizing the use patterns of discrete strategies may inform strategy prioritization and selection to optimize service delivery. We used the Living Database of HIV Implementation Science (LIVE) to describe the commonality and co-occurrence of discrete strategies within multi-component strategy bundles in published HIV implementation studies from low- and middle-income countries.

METHODS: The LIVE systematic review identified studies from PubMed, Embase, and CINAHL, and included HIV implementation studies that reported ≥ 1 HIV care cascade outcome, were conducted in low- and …

Longitudinal Profiles Of Executive Function In Autistic And Non-Autistic Children At High Likelihood Of Autism, Tanya St John, Neva M Corrigan, Ariel Rokem, Annette M Estes, Heather C Hazlett, Juhi Pandey, Robert T Schultz, Natasha Marrus, Lonnie Zwaigenbaum, Chimei M Lee, Stephen R Dager, Joseph Piven, Ibis Network

2020-Current year OA Pubs

BACKGROUND: Executive functioning (EF) difficulties are common in autistic children and may aggregate in families. Longitudinal studies examining EF development in autistic children and their siblings are limited. In the current study, we characterized EF development from later infancy through school-age in autistic and non-autistic high likelihood (HL; with an older autistic sibling) and low likelihood (LL; without older autistic sibling) children. METHODS: Participants were 83 autistic and 235 non-autistic HL children, and 132 LL children from the Infant Brain Imaging Study. EF was assessed at ages 12 and 24 months using the A-not-B task and ages 5–14 years (school-age) …

Cost-Effectiveness And Implementation Strategies For Hypertension Management Using Non-Physician Healthcare Workers In Low- And Middle-Income Countries: A Systematic Review, Gabriel Lamkur Shedul, Olutobi Adekunle Sanuade, Emmanuel Iroboudu Okpetu, Molly Beestrum, Dike Bevis Ojji, Lisa R Hirschhorn, Mark D Huffman, Dustin D French

2020-Current year OA Pubs

BACKGROUND: This review assessed the cost-effectiveness and implementation strategies of hypertension management by non-physician healthcare workers (NPHCWs) in low- and middle-income countries (LMICs).

METHODS: A systematic search (inception-May 2024) included adults ≥18 years managed by NPHCWs LMICs, following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Economic evaluations were assessed using Drummond's checklist and ROBINS-I.

RESULTS: Seven studies (2002-2022) conducted across eight countries enrolled 96-10,000 participants and included randomized, modeling, observational, and quasi-experimental designs. NPHCWs included pharmacists, community and village health workers, and nurses. Patients' mean age ranged 58-71 years, with 57-82% female. Outcomes assessed included cost per …

Cortical-Limbic Circuit Dynamics Of Approach-Avoidance Conflict In Humans, Brooke R Staveland, Julia Oberschulte, Barbara Berger, Tamas Minarik, Olivia Kim-Mcmanus, Jon T Willie, Peter Brunner, Mohammad Dastjerdi, Jack J Lin, Elizabeth L Johnson, Michelle Paff, Ming Hsu, Robert T Knight

2020-Current year OA Pubs

Choosing to approach or avoid is common in everyday life and excessive avoidance is a cardinal feature of anxiety disorders. We use intracranial EEG to define a prefrontal-limbic circuit supporting approach and avoidance. Presurgical epilepsy patients (n = 20) performed an approach-avoidance conflict decision-making task inspired by the arcade game Pac-Man, where patients trade off rewards against losses from ghost attack. During approach, theta power increases across a limbic circuit including the hippocampus, amygdala, orbitofrontal cortex and anterior cingulate cortex, which drops during avoidance. Theta connectivity between this circuit and lateral prefrontal cortex increases during approach and falls during avoidance. …

Spatial Transcriptomic Landscape Of Invasion Patterns In Human Papillomavirus-Associated Endocervical Adenocarcinoma, Margaret L Axelrod, Ruiwen Zhou, Lulu Sun

2020-Current year OA Pubs

Human papillomavirus (HPV)-associated endocervical adenocarcinoma is the second-most common cancer of the uterine cervix. HPV-associated endocervical adenocarcinoma can be classified into histologic Silva patterns of invasion, which are associated with clinical outcome. However, the mechanisms underlying these patterns of invasion are incompletely understood. We used whole transcriptome spatial transcriptomics to examine gene expression differences separately in the tumor epithelium and the surrounding stromal immune microenvironment (SIME). Seven cases were evaluated, focusing on cases with two distinct patterns of invasion within the same tumor, to control for inter-patient heterogeneity. The most strongly upregulated pathways in both higher-risk tumor epithelium and SIME …

Megakaryocyte And Platelet Thrombospondin-1 Regulates Matrix Remodeling By Stabilizing Basement Membrane Col6a1 In Lung Injury, Hernán F Peñaloza, Atish Gheware, Ananya Gupta, Donovan Watza, Anupam Kumari, Zeyu Xiong, Pooja Bhojraj, Jae-Sung Kim, Bo-Ram Jin, Kyunghee Choi, Matthew R Rosengart, Jaehyung Cho, Janet S Lee, Et Al.

2020-Current year OA Pubs

An early event after lung injury is extracellular matrix (ECM) remodeling and the formation of a provisional matrix. While megakaryocytes and platelets (Mgk/plt) play important roles in hemostasis, their impact on the matrix in lung injury is not fully understood. Using lung intravital microscopy, 3D large area scanning with multiphoton confocal hybrid imaging, and label-free quantitative proteomics, the matricellular protein thrombospondin-1 (TSP1) arising from Mgk/plt protects the lung from alveolar injury. Mgk/plt cell-specific Thbs1 knockout (cKO) mice show increased alveolar barrier disruption with exaggerated neutrophil-mediated injury. The cKO mice exhibit striking extracellular matrix re-organization with reduction in basement membrane matrix …

Leveraging Patient Data To Detect Systematic Shifts In Daptomycin Susceptibility Testing Associated With Reduced Prescribing, Mark A Zaydman, Laurel Glaser, Daniel S Herman, Mason Kressloff, Vahid Azimi, Christine R Lockowitz, Rebekah E Dumm

2020-Current year OA Pubs

UNLABELLED: Systemic shifts in antimicrobial resistance rates can be due to epidemiologic shifts in microbial susceptibility patterns or artifactual shifts introduced by technical biases in antimicrobial susceptibility testing (AST)-both ultimately leading to changes in antimicrobial prescribing. To reduce technical variability, quality control (QC) criteria for AST are published by manufacturers and standards organizations. However, traditional QC metrics, in isolation, are fallible. In this study, we describe a systematic shift in daptomycin AST results between 2022 and 2025 in isolates tested in two independent health systems. Comprehensive analysis of clinical isolate AST results and retrospective mining of QC data from this …

Get Social Media And Risk-Reduction Training (Get Smart) To Improve Infant Safe Sleep Practices Through A Mobile Text Message-Delivered Video Safe Sleep Intervention For New Parents: Study Protocol For A Type 3 Hybrid Implementation-Effectiveness Cluster Randomized Trial In 20 Us Birth Hospitals, Rachel Y Moon, Sunah S Hwang, Fern R Hauck, Ann L Kellams, Paul R Shafer, Bryanne N Colvin, Hannah Karpman, Rebecca F Carlin, Michael J Corwin, Eve Colson, Margaret G Parker

2020-Current year OA Pubs

BACKGROUND: Annually, more than 3500 US infants die suddenly and unexpectedly. Many sudden unexpected infant deaths (SUID) are preventable with greater adherence to safe infant sleep guidelines. There are racial and socioeconomic disparities, both in adherence to these guidelines and in SUID rates. In the original Social Media and Risk-Reduction Training for Infant Care Practices (SMART) study in which 1600 mothers were randomized to receive short educational videos, focused on safe sleep vs. control, those receiving the safe sleep intervention had ~ 10% point higher rates of following safe sleep practices, with elimination of racial and socioeconomic disparities in safe …

Molecular Insights Into The Regulation Of Gnptαβ By Lyset, Xi Yang, Balraj Doray, Danielle Henn, Varsha Venkatarangan, Benjamin C Jennings, Zhongzheng Dong, Jiaxuan Liang, Weichao Zhang, Bokai Zhang, Linchen Yu, Liang Chen, Stuart Kornfeld, Ming Li

2020-Current year OA Pubs

In vertebrates, newly synthesized lysosomal enzymes traffic to lysosomes through the mannose-6-phosphate (M6P) pathway. The Golgi membrane protein LYSET was recently discovered to regulate lysosome biogenesis by controlling the level of GlcNAc-1-phosphotransferase (GNPT). However, its working mechanism remained unclear. In this study, we demonstrate that LYSET is a two-transmembrane protein essential for GNPT stability, cleavage by Site-1 Protease (S1P), and enzymatic activity. We reconcile conflicting models by showing that LYSET enhances GNPT cleavage and prevents its mislocalization to lysosomes for degradation. We further establish that LYSET achieves this by interacting with GOLPH3 and retromer complexes to anchor the LYSET-GNPT complex …

Adaptations To An Implementation Study For Integrating Hypertension Management Into Hiv Care In Lagos, Nigeria: Application Of The Frame, Chioma Hope Nwankwo, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Implementation strategies are dynamic and multi-faceted, and may require adaptations to fit implementation contexts, especially in lower-and-middle income countries. We report the adaptations for an ongoing late-stage implementation science trial (R01HL147811) that integrates hypertension management into HIV care in Lagos, Nigeria - a country with a high dual-disease burden - through the Task Strengthening Strategy for Hypertension (TASSH) intervention and Practice Facilitation implementation strategy.

METHODS: FRAME (Framework for Reporting Adaptations and Modifications-Enhanced) modules were used to record adaptations to the intervention (i.e., TASSH) respectively, enhance participant recruitment and retention rates, and increase frequency of trainings. Data collection sources included …

Recommendations For The Diagnosis And Management Of Cln3 Disease (Batten Disease) Using The Delphi Consensus Methodology, Jonathan W Mink, Jonathan D Cooper, Et Al.

2020-Current year OA Pubs

BACKGROUND: CLN3 disease, also called Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), or Batten disease, is an ultra‑rare, neurodegenerative lysosomal storage disorder generally affecting individuals during the first decade of life. There can be a delay in diagnosis or misdiagnosis due to a lack of awareness, and when the most common presenting symptom of visual loss is attributed to more common conditions affecting vision. METHODS: We used a previously published Expert Mapping Tool (EMT) to identify multidisciplinary professionals with diagnostic or clinical management expertise, as well as patient advocates with experience of CLN3 disease. A systematic literature review of published evidence using …

A Practice-Based Implementation Strategy Bundle For Integrating Behavioral Health In Primary Care: A Matrixed Multiple Case Study, Gretchen Buchanan, Kelley Mccall, Lorella Palazzo, Michelle Bagwell, Shivani Patel, Shravya Allena, Byron J Powell

2020-Current year OA Pubs

BACKGROUND: Integrated behavioral health (IBH) is an evidence-based approach to addressing mental health in primary care settings. It typically involves augmenting a primary care team with a behavioral health professional (e.g., psychologist, licensed clinical social worker) who sees patients for brief, focused concerns; can function as a bridge to specialty care; and provides medical providers with support and education about patient behavioral health concerns. IBH has slowly begun to disseminate across the United States, but practices encounter significant implementation barriers. How IBH is implemented has not been systematically studied outside of trials, yet this study could provide a rich foundation …

Hematopoietic Cell Transplantation For Wiskott-Aldrich Syndrome: A Pidtc Report, Jessie L Alexander, Jeffrey J Bednarski, Et Al.

2020-Current year OA Pubs

Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to affect overall survival (OS). However, the influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium from 1990 to 2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and …

Differential Contributions Of Clpx And Clpp To Pulmonary Virulence In Classical And Hypervirulent Klebsiella Pneumoniae, Nathan M Lin, Emily C Marino, Jordan M Schlotmann, David A Rosen

2020-Current year OA Pubs

No abstract provided.

Ultrasound-Guided Skeletal Muscle Biopsy Technique Permits Measurement Of Structural, Functional, Cellular And Biochemical Properties, Addison Barber, Amber Willbanks, Guadalupe Meza, Jeremie L A Ferey, Gretchen A Meyer, Sudarshan Dayanidhi, W David Arnold, Richard L Lieber, Ishan Roy

2020-Current year OA Pubs

Human muscle biopsies are often required to study or diagnose diseases. However, traditional approaches are challenging due to limited sample size, quality, or participant discomfort. Fine-gauge needle biopsies (≥ 14-gauge), present an alternative but may yield insufficient tissue for comprehensive analysis. Ultrasound guidance, coupled with vacuum-assisted, single needle-insertion multiple sampling addresses these challenges. In 19 healthy participants (mean age: 30.1 ± 10 years, 42% male), 2-3 samples were collected from a single needle insertion into the vastus lateralis (VL) and tibialis anterior (TA). Summed VL and TA sample masses averaged 148 ± 38 mg and 166 ± 64 mg, with …

Patient And Healthcare Professionals' Perceptions Of Educational Tools To Reduce Urine Culture Contamination In Outpatient Clinics: A Qualitative Study., Ashley Collazo, Trenton M Haltom, Johanan Luna Rodriguez, Kiara Olmeda, Azalia Mancera, Fabrizia Faustinella, Michael K Paasche-Orlow, Zach Landis-Lewis, Roger Zoorob, Barbara W Trautner, Larissa Grigoryan

2020-Current year OA Pubs

OBJECTIVE: Iteratively develop educational tools (instructional video and flyer) to improve midstream clean catch (MSCC) urine sample collection using patient and healthcare professionals' input.

DESIGN: Multi-method qualitative study.

SETTING: Outpatient clinics in Houston, Texas, United States.

PARTICIPANTS: Adult patients recruited from public and private clinics (

METHODS: Twelve patient interviews and three focus groups with HCPs (May 2024-November 2024). Interviews discussed patient experiences using the educational tools to guide urine specimen collection. Focus groups elicited HCPs' perspectives on the comprehensibility and utility of the tools in their respective clinics. We identified themes using directed content analysis.

RESULTS: We garnered insight …

Crossing The Finish Line Towards A Disease-Modifying Treatment For Angelman Syndrome, Matthew C Judson, Jason J Yi, Et Al.

2020-Current year OA Pubs

Recent progress in the development of genetic therapies promises that impactful treatments for single-gene neurodevelopmental disorders are imminent. But can derailed neurodevelopmental processes be mended after broken genes are replaced or otherwise restored? The results of ongoing clinical trials for Angelman syndrome will soon yield answers to this pressing question, yet the trials face significant obstacles. Here we identify insights needed to aid the quest for a disease-modifying Angelman syndrome therapy, which could serve as a roadmap for the expeditious development of genetic therapies for other single-gene neurodevelopmental disorders.

Blood And Body Fluid Exposure And Reporting Behaviors Among Healthcare Workers: A Decade-Long Comparative Study At A Tertiary Medical Center, Ziad Kaddour, Rami Abdul-Halim, Zeina Al-Khalil, Lea Al Zoghby, Raafat Alameddine, Reem Mansour, Jack El Sawda, Zeina A Kanafani

2020-Current year OA Pubs

BACKGROUND: Occupational exposure to blood and body fluids (BBFE) remains a significant risk for healthcare workers (HCWs), yet underreporting persists despite the implementation of institutional policies. This study aimed to compare BBFE prevalence, reporting practices, and HCWs' knowledge, perceptions, attitudes, and behaviors, and identify predictors of BBFE and failure to report incidents over a ten-year period at a tertiary medical center.

METHODS: Two cross-sectional surveys were conducted at the American University of Beirut Medical Center (AUBMC) in 2013-2014 and 2023-2024. In 2013-2014, all participants completed paper-based questionnaires, whereas in 2023-2024, medical students, residents, and nurses completed online surveys, and housekeeping/laundry …

A New Chromosome-Level Genome Assembly For Western Painted Turtle Chrysemys Picta Bellii, A Model For Extreme Physiological Adaptations, Junhao Chen, John R Bermingham Jr, Patrick Minx, Milinn Kremitzky, Zhenguo Lin, Daniel E Warren

2020-Current year OA Pubs

The western painted turtle, Chrysemys picta bellii, has the greatest tolerance to anoxia of any tetrapod studied to date. These turtles reside in the northern United States and southern Canada, and survive months of anoxia while submerged in ice-locked ponds and bogs. Reference genomes provide an important resource for elucidating the molecular bases for such unique physiological traits. The initial reference genome for this species, published in 2013, is highly fragmented, thereby limiting downstream analyses and biological interpretation. We created a new and improved assembly by combining PacBio HiFi, 10 × Genomics Chromium, Hi-C sequence data and Bionano optical mapping …

Development Of A Sustainable Blended Food Aid Product Using Local Ingredients For Nutritionally Vulnerable Populations In Haiti, Sherlie Jean Louis Dulience, Rachel Zimmerman, Michelle Dorce, Ilana Seff, Andrea Spray Bulungu, Patricia Kohl, Carolyn Lesorogol, Bazelais Dulience, Lora Iannotti

2020-Current year OA Pubs

OBJECTIVES: This study aimed to: (1) identify optimal blended food recipe options using local flours; (2) assess behaviors, attitudes, and practices around the use of blended foods among nutritionally vulnerable groups in Haiti; and (3) evaluate the nutrient composition of prototype blended food product relative to nutrient requirements for vulnerable populations.

METHODS: Blended food recipes made from local flours were identified through matrix scoring and stakeholder consensus. Focus groups (n = 7) assessed behaviors and attitudes toward blended foods. Prototype recipes were selected based on matrix scoring, program participant feedback, and feasibility of bringing to scale. Nutrient composition of the …

Translation Of Expanded Cgg Repeats In Lrp12 Associated Oculopharyngodistal Myopathy, Chengcheng Li, Jil A Daw, Sara K Pittman, Connor J Maltby, Hidetoshi Sakurai, Peter K Todd, Conrad C Weihl

2020-Current year OA Pubs

Oculopharyngodistal myopathy (OPDM) is characterized by ptosis, ophthalmoparesis, dysphagia, and distal weakness. Myopathological features include rimmed vacuoles and intranuclear inclusions. OPDM is associated with a pathogenic CGG repeat expansions in the 5'UTR of LRP12, NOTCH2NLC, GIPC1, RILPL1 and ABCD3. Translation of the repeat in the glycine reading frame has been demonstrated for expansions in FMR1, NOTCH2NLC and GIPC1. To assess for a similar phenomenon with LRP12, we expressed normal or expanded CGG repeats in the context of the 5'UTR of LRP12, upstream of a green fluorescent protein (GFP) in the three repeat reading frames. Repeat dependent translation occurs exclusively in …

Integrating Interferon Gamma Receptor Pathways, Antigenicity, And Immune Contexture As Predictors Of Immunotherapeutic Strategies For Mucosal Melanomas, Matilde Monti, Jinglun Li, Obi Griffith, Malachi Griffith, William Vermi, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mucosal melanomas (MM) arise from mucosal melanocytes at various anatomical sites. These tumors are rare, highly aggressive, and often associated with poor outcomes. Current treatments, including immune checkpoint inhibitors, show limited efficacy in advanced disease. Compared with cutaneous melanomas, there is a lack of data on the immunogenicity and interferon (IFN)-γ sensitivity of MM. In this study, we examined these features in sino-nasal melanomas (SN-MM) cell lines and clinical samples using microscopy and functional genomics.

METHODS: The immune contexture of SN-MM was analyzed by immunohistochemistry on 48 tumor biopsies. RNA sequencing and mass spectrometry-based proteomic approaches were used to …

Single-Center Experience Of Voclosporin Use For Pediatric Lupus Nephritis: A Case Series, Ran Hazan, Nazlican Tang Civilibal, Kevin Baszis, Tarin M Bigley

2020-Current year OA Pubs

No abstract provided.

Brd4-Mediated Er Membrane Contact Creates Functionally Distinct Mitochondrial Subtypes, Brandon Chen, Rachel M Guerra, David J Pagliarini, Et Al.

2020-Current year OA Pubs

Inter-organellar communication is critical for cellular metabolism. One of the most abundant inter-organellar interactions occurs at the endoplasmic reticulum and mitochondria contact sites (ERMCSs). However, an understanding of the mechanisms governing ERMCS regulation and their roles in cellular metabolism is limited by a lack of tools that permit temporal induction and reversal. Through screening approaches, we identified fedratinib, an FDA-approved drug that dramatically increases ERMCS abundance by inhibiting the epigenetic modifier BRD4. Fedratinib rapidly and reversibly modulates mitochondrial and ER morphology, induces a distinct ER-mitochondria envelopment structure, and alters metabolic homeostasis. Moreover, ERMCS modulation depends on mitochondrial electron transport chain …

A Neural Circuit Framework For Economic Choice: From Building Blocks Of Valuation To Compositionality In Multitasking, Aldo Battista, Camillo Padoa-Schioppa, Xiao-Jing Wang

2020-Current year OA Pubs

Value-guided decisions are a cornerstone of cognition, yet the underlying circuit-level mechanisms remain elusive. We used reinforcement learning to train recurrent neural network models endowed with Dale's law on a battery of economic choice tasks, which revealed a two-stage computational framework. First, value estimation occurs at the input level, where learned weights store subjective preferences and approximate the non-linear multiplication of reward magnitude and probability to yield expected values. This feedforward mechanism enables generalization to novel choice options. Second, option values are compared within the recurrent network, where specific connectivity patterns mediate robust winner-take-all decisions, with both excitatory and inhibitory …

Longitudinal Profiling Of Tumor And Immune Compartments Uncovers Patterns Of Dysregulation And Associations With Response In Multiple Myeloma, Denis J Ohlstrom, Reyka G Jayasinghe, Yizhe Song, Ravi Vij, Li Ding, Et Al.

2020-Current year OA Pubs

UNLABELLED: Multiple myeloma is a malignancy of clonally expanded plasma cells shaped by complex interactions with the immune microenvironment (IME). To investigate immune correlates of treatment response and disease progression, we conducted multi-omics profiling including CD138neg single-cell RNA sequencing of 243 bone marrow samples from 102 patients (631,226 cells) and CD138pos bulk RNA and whole-genome sequencing from 209 samples. In longitudinal analyses, interferon-γ signaling associated with markers of impaired T-cell memory after autologous stem cell transplant, whereas naïve B-cell abundance and immunoglobulin diversity correlated with improved progression-free survival (HR = 0.48; P = 2.3e-4). At disease progression, multiple myeloma cells …