Medicine and Health Sciences Commons^™

Association Of Shock Index And Variants With Mortality In Acute Pulmonary Embolism, Cameron P Upchurch, Kristen Sanfilippo, Daphne Lew, Maanasi Samant, Rachel Mcdonald

2020-Current year OA Pubs

INTRODUCTION: Pulmonary embolism (PE) is common with potential for morbidity and mortality. Several PE risk-stratification tools exist; however, more granular and patient-specific indicators of potential decompensation or short-term mortality that can be easily obtained are needed for the bedside clinician to further sub-stratify risk and inform management decisions. We sought to determine the association of early emergency department (ED) measurement of the shock index (SI) and SI variants (modified SI, SI to peripheral oxygen saturation ratio, age-adjusted SI, respiratory-adjusted SI, and double product) and mortality among patients with acute PE.

METHODS: This was an observational case-control study of adult patients …

Ribosomal Protein Control Of Hematopoietic Stem Cell Transformation Through Regulation Of Metabolism, Bryan Harris, Stephen Sykes, Et Al.

2020-Current year OA Pubs

We report here that expression of the ribosomal protein RPL22 is frequently reduced in human myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), and reduced RPL22 expression is associated with worse outcomes. Mice null for Rpl22 display characteristics of an MDS-like syndrome and develop leukemia at an accelerated rate. Rpl22-deficient mice also display enhanced hematopoietic stem cell (HSC) self-renewal and obstructed differentiation potential, which arises not from reduced protein synthesis but from altered metabolism, including increased fatty acid oxidation (FAO) and a striking induction of the stemness factor Lin28b in the resulting leukemia. Lin28b promotes a substantial increase in lipid …

Simultaneous Initiation Of Finerenone And Empagliflozin Across The Spectrum Of Kidney Risk In The Confidence Trial, Muthiah Vaduganathan, Jennifer B Green, Hiddo J L Heerspink, Sung Gyun Kim, Johannes F E Mann, Janet B Mcgill, Amy Mottl, Masaomi Nangaku, Julio Rosenstock, Peter Rossing, Li Li, Na Li, Katja Rohwedder, Charlie Scott, Rajiv Agarwal

2020-Current year OA Pubs

BACKGROUND: The CONFIDENCE (COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with CKD and type 2 diabetes using a UACR Endpoint) trial investigated the safety and efficacy of simultaneously initiating finerenone and empagliflozin for patients with chronic kidney disease (CKD) and type 2 diabetes. This prespecified analysis aimed to determine if the predicted risk of kidney disease progression, based on KDIGO risk categories, influenced the benefits and safety of this combination therapy.

METHODS: The double-blind, double-dummy trial randomized 818 adults with CKD and type 2 diabetes [urine albumin-creatinine ratio (UACR) ≥100 to < 5000 mg/g] to receive once-daily finerenone plus empagliflozin, finerenone alone or empagliflozin alone, all in addition to a renin-angiotensin system inhibitor. The relative change in UACR from baseline to day 180 (primary endpoint) and a >30% reduction in UACR (secondary endpoint) across KDIGO …

Investigating The Relationship Between Breast Cancer Risk Factors And An Ai-Generated Mammographic Texture Feature In The Nurses' Health Study Ii, Xueyao Wu, Shu Jiang, Aaron Ge, Constance Turman, Graham Colditz, Rulla M Tamimi, Peter Kraft

2020-Current year OA Pubs

The mammogram risk score (MRS), an AI-driven mammographic texture feature, strongly predicts breast cancer risk independently of breast density, though underlying mechanisms remain unclear. Using data from the Nurses' Health Study II (292 cases, 561 controls), we validated MRS's association with breast cancer and evaluated its relationships with established breast cancer risk factors through observational analyses, polygenic score analyses, and Mendelian randomization. MRS was significantly associated with breast cancer risk before (OR=1.92 per SD increase; 95% CI:1.57 to 2.35; 10-year AUC=0.69) and after adjustment for predicted BI-RADS density (OR=1.85; 95% CI:1.49 to 2.30). Early life body size and adult body …

Acl Injuries In Major League Soccer: A 10-Year Analysis Of Injury Rate And Return To Play, And Performance Metrics By Player Position, Brian Forsythe, Catherine Hand, Camden Bohn, Francis Hand, Vahram Gamsarian, Daanish Khazi-Syed, Joshua Chang, Vikranth Mirle, Eric Giza, Robert Brophy, Danyal Nawabi, Bert Mandelbaum

2020-Current year OA Pubs

BACKGROUND: Anterior cruciate ligament (ACL) injuries are among the most debilitating injuries in professional soccer, often leading to extended recovery times and performance impacts. While much is known about ACL injury outcomes in European leagues, data specific to the Major League Soccer (MLS) remains limited.

PURPOSE/HYPOTHESIS: This study aimed to assess the return to play (RTP) times, RTP rates, and performance outcomes after ACL reconstruction in MLS athletes. It was hypothesized that RTP times would improve over the study period and that player performance would stabilize by the third post-injury season, consistent with findings from other professional soccer leagues.

STUDY …

Enteric Nervous System Degeneration In Human And Murine Cln3 Disease, Is Ameliorated By Gene Therapy In Mice, Ewa A Ziółkowska, Letitia L Williams, Matthew J Jansen, Sophie H Wang, Elizabeth M Eultgen, Jaiprakash Sharma, Marco Sardiello, Rebecca P Bradley, Ineka T Whiteman, Mark S Sands, Robert O Heuckeroth, Jonathan D Cooper

2020-Current year OA Pubs

Severe gastrointestinal (GI) symptoms occur in people with CLN3 disease, a neurodegenerative disorder. If left untreated these GI symptoms compromise life quality and may contribute to death. We hypothesized GI symptoms in CLN3 disease are at least partially due to neurodegeneration in the enteric nervous system (ENS), the master regulator of bowel function. We examined the integrity of the ENS in human CLN3 autopsy small bowel and colon, and in CLN3 deficient (Cln3Δex7/8) mice. We performed detailed immunohistological analyses of enteric neurons and glia and assessed bowel transit times at multiple disease stages. We then tested the therapeutic potential of …

Implementation Of Single-Pill Combination Medication For Hypertension Treatment By Nonphysician Health Care Workers At Primary Healthcare Facilities In Nigeria: An Explanatory Mixed Methods Study, Emmanuel I Okpetu, Chisom Obiezu-Umeh, Boni M Ale, Abigail S Baldridge, Rosemary C B Okoli, Grace J Shedul, Gabriel L Shedul, Nanna R Ripiye, Ikechukwu A Orji, Lisa R Hirschhorn, Dike B Ojji, Mark D Huffman, Hypertension Treatment In Nigeria Program Investigators

2020-Current year OA Pubs

BACKGROUND: Single-pill combination (SPC) therapy improves hypertension control; however, its implementation in primary care settings remains limited. In Nigeria, there is insufficient evidence on factors influencing SPC uptake, particularly from the perspective of healthcare workers (HCWs). This study examined the implementation of SPC medications for hypertension treatment by nonphysician HCWs at primary healthcare facilities (PHCs) in Nigeria.

METHODS: An explanatory sequential mixed methods study was conducted, building on a cluster randomized controlled trial embedded within the Hypertension Treatment in Nigeria Program. The trial compared SPC medications with free-equivalent combination therapies across 60 PHCs (January-June 2021). A subsequent qualitative component (September-December …

Current Controversies On Adequate Circulating Vitamin D Levels In Ckd, Adriana S Dusso, Daniela J Porta, Carlos Bernal-Mizrachi

2020-Current year OA Pubs

Management of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) has evolved dramatically over the past five decades, driven by discoveries that have fundamentally reshaped our understanding of the vitamin D endocrine system and its role in disease progression. This review synthesizes the key pathophysiological insights and clinical evidence underlying three critical paradigm shifts. The first shift moved beyond simple calcitriol replacement with the development of selective vitamin D receptor activators (VDRAs) designed to minimize hypercalcemia while maximizing PTH suppression. Crucially, these analogs revealed unexpected survival benefits, suggesting protective VDR actions extending beyond mineral metabolism. The second shift recognized the …

A Protein Complex In The Extreme Distal Tip Of Vertebrate Motile Cilia Controls Their Organization, Length, And Function, Juyeon Hong, Jiehong Pan, Amjad Horani, Steven L Brody, Et Al.

2020-Current year OA Pubs

The beating of cilia on multi-ciliated cells (MCCs) is essential for normal development and homeostasis in animals. But while the structure and function of basal bodies and axonemes have received significant attention recently, the distal tips of MCC cilia remain relatively poorly defined. Here, we characterize the molecular organization of the distal tip of vertebrate MCC cilia, characterizing two distinct domains occupied by distinct protein constituents. Using frog, mouse, and human MCCs, we find that two largely uncharacterized proteins, Ccdc78 and Ccdc33, occupy a previously undefined region at the extreme distal tip, and these are required for the normal organization …

Imlunestrant, An Oral Selective Estrogen Receptor Degrader, In Combination With Her2 Directed Therapy, With Or Without Abemaciclib, In Er-Positive, Her2-Positive Advanced Breast Cancer: Results From The Phase 1a/1b Ember Study, Manali Bhave, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

BACKGROUND: Hormone receptor-positive (HR+), human epithelial growth factor receptor 2 (HER2) overexpressed breast cancer (BC) represents the more aggressive subtype of HR + BC, typically associated with poor clinical outcomes. Despite significant advancements in the treatment of estrogen receptor-positive (ER+)/HER2 + BC, resistance to endocrine therapy (ET) poses a continued challenge. Imlunestrant is a next-generation, oral, brain-penetrant, pure antagonistic ER degrader designed to deliver continuous ER target inhibition. It has shown favorable clinical benefit, safety, and pharmacokinetics (PK) when used as monotherapy or with targeted therapy in patients with ER+/HER2- advanced BC (ABC). Here, we present the safety and efficacy …

The Common Cold Is Associated With Protection From Sars-Cov-2 Infections, Camille M Moore, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

BACKGROUND: Adults and children often respond differently to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with adults facing a higher risk of symptomatic and severe illness. We hypothesize that children's protection from symptomatic SARS-CoV-2 may be due to more frequent respiratory viral infections, which prime their airway antiviral defenses.

METHODS: Using case-cohort and case-control analyses in the Human Epidemiology and Response to SARS-CoV-2 cohort, we evaluated whether infection with common respiratory viruses protects against SARS-CoV-2 infections and investigated airway molecular mechanisms by which this protection is achieved. We tested 10 493 longitudinal nasal swabs from 1156 participants for 21 …

Baseline Exposure-Response Assessment Of Metals From Dried Blood Spots And Personal Household Air Pollution Concentrations Among Pregnant Women In Rwanda: Household Air Pollution Intervention Network Trial, Adolphe Ndikubwimana, Lisa De Las Fuentes, Victor G Dávila-Román, Et Al.

2020-Current year OA Pubs

BACKGROUND: Exposure to metals from the combustion of biomass via inhalation may result in negative health outcomes affecting a variety of organs and systems. Pregnant women cooking with biomass fuels may be exposed to metals, such as lead (Pb) and cadmium (Cd), and have unique risks for adverse health effects with potential impacts on the growing fetus. We assessed the associations between household air pollution and metals detected in dried blood spots from pregnant women at baseline in Rwanda.

METHODS: We analyzed data from 781 pregnant women aged 18-35 years who resided in rural households using biomass fuel and who …

Comparison Of Cervical Spine Injury Clinical Prediction Rules For Children After Blunt Trauma, Lois K. Lee, Fahd A. Ahmad, Lorin R. Brown, Monica Harding, Lawrence Cook, Kathleen Adelgais, Rebecca K. Burger, Alexander Rogers, Leah Tzimenatos, Lauren C. Riney, Daniel Rubalcava, Caleb E. Ward, Kenneth Yen, Julie C. Leonard

2020-Current year OA Pubs

No abstract provided.

Genomic Characterization Of Colorectal Tumors: Insights Into Significantly Mutated Genes, Pathways, And Survival Outcomes, Tabitha A Harrison, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: Identifying significantly mutated genes in tumors aids in understanding disease etiology and survival and may aid in the discovery of new drug targets. We aimed to detect and characterize mutated genes from a large, well-characterized group of colorectal cancers.

METHODS: In tumor and paired normal samples from 6,111 colorectal patients, we sequenced 199 genes identified from whole exome sequencing of over 1,100 tumors. Analyses focused on non-silent mutations. We classified significantly mutated genes after stratification by hypermutation status, and estimated associations of mutated genes/pathways with disease-specific (DS)-survival using Cox regression, adjusting for age, sex, mutation burden, hypermutation status, and …

Applied Methods For Matching Implementation Strategies To Determinants: A Scoping Review Of Scientific And Grey Literature, And Qualitative Exploration Of Practice Experiences, Christiaan Vis, Leti Van Bodegom-Vos, Bethany Hipple-Walters, Byron J Powell, Erwin Ista, Femke Van Nassau

2020-Current year OA Pubs

BACKGROUND: Tailored implementation addresses the inherent dynamic complexity and heterogeneous nature of implementation practice. In general, tailored implementation involves setting implementation objectives, identifying determinants, matching strategies to those determinants, and developing an evaluation plan. How matching a specific implementation strategy to a determinant is done remains largely unknown. This study aimed to provide an overview of methods for matching strategies that have been applied in research and practice.

METHODS: A scoping review of scientific and grey literature was conducted. A Rapid Assessment Procedure approach guided the design and analysis. Five online scientific bibliographic databases and various Dutch websites were searched …

Pooled Randomised Quartet Trials Assessing Effectiveness Of A Single Pill For Hypertension, Simone Marschner, Mark D Huffman, Desi Quintans, Jody Ciolino, Abigail Baldridge, Danielle Lazar, Emily R Atkins, Graham S Hillis, Mark R Nelson, Markus Schlaich, Anthony Rodgers, Clara K Chow

2020-Current year OA Pubs

BACKGROUND: Hypertension is a major cause of premature death worldwide, controlled by only one in five adults. Two trials (Australia and USA) found a single quadpill containing a quarter dosage of four classes of medication effective in reducing blood pressure (BP) among participants with hypertension. By pooling these trials, we can estimate the overall benefit of the quadpill and its heterogeneity across subgroups and two important barriers for BP control: clinician medication inertia and participant medication adherence.

METHODS: In a prespecified pooled individual participant data analysis of two QUARTET randomised, multicentre, double-blinded trials in people with hypertension using ≤1medication, quadpill …

Presence Of Eosinophils May Represent An Earlier Stage In Achalasia Pathogenesis, Andrea Costantini, Chandra Prakash Gyawali, Francesca Forattini, Valentina Angerilli, Matteo Ghisa, Luca Provenzano, Giovanni Capovilla, Loredana Nicoletti, Michele Valmasoni, Matteo Fassan, Edoardo Vincenzo Savarino, Renato Salvador

2020-Current year OA Pubs

BACKGROUND: Intraepithelial eosinophils have been described in patients with esophageal motor disorders. Conversely, motor disorders and even achalasia have been reported in patients with eosinophilic esophagitis (EoE).

OBJECTIVES: This prospective study aimed to further investigate the association between eosinophilia and achalasia.

DESIGN: This is a prospective study.

METHODS: A series of 30 consecutive treatment-naïve achalasia patients (mean age: 45.5 years, 53% female) undergoing laparoscopic myotomy were prospectively enrolled. Preoperative demographic and clinical data, radiological findings, and high-resolution manometry (HRM) features were collected. Patients underwent upper endoscopy with biopsy sampling before surgery, and two samples of distal esophageal muscle were obtained …

Limited Agreement On Acl Tear Location Between Arthroscopy And Mri: A Prospective Evaluation, Richard Silverman, Derrick M Knapik, Matthew V Smith, Jonathan C Baker, Kelby Napier, Matthew J Matava, Robert H Brophy

2020-Current year OA Pubs

BACKGROUND: Renewed interest in anterior cruciate ligament (ACL) preservation has led to increased focus on tear location within the knee joint in treatment decisions, with primary ACL repair reserved for proximal tears. Retrospective studies have reported varying tear locations in adults when assessed on magnetic resonance imaging (MRI), with few studies comparing tear location on MRI versus intraoperative findings.

PURPOSE: To prospectively determine the distribution of ACL tear location assessed on MRI versus intraoperative evaluation to test the hypothesis that < 15% of ACL tears are proximal type avulsions.

STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 2.

METHODS: A total of 174 patients with clinically confirmed full-thickness ACL …

Her2-Low And Her2-Ultralow Metastatic Breast Cancer And Trastuzumab Deruxtecan: Common Clinical Questions And Answers, Nusayba A Bagegni, Karthik V Giridhar, Daphne Stewart

2020-Current year OA Pubs

Approximately 80% of invasive breast cancers are classified as human epidermal growth factor receptor 2 (HER2)-negative; however, many of these tumors have detectable levels of HER2 surface expression. Trastuzumab deruxtecan (T-DXd) is a HER2-directed antibody-drug conjugate with a membrane-permeable payload that is cytotoxic to both HER2-expressing tumor cells and neighboring cells via the bystander antitumor effect. T-DXd has shown significant antitumor activity in clinical trials for patients with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+) breast cancer. In addition, the results of the DESTINY-Breast04 trial demonstrated the clinical benefit of T-DXd in patients with HER2-low (IHC 1+ …

Investigating The Polygenic Relationship Between Heavy Cannabis Use And Schizophrenia In The All Of Us Research Program, Isabelle Austin-Zimmerman, Hayley H A Thorpe, John J Meredith, Jibran Y Khokhar, Tian Ge, Marta Di Forti, Arpana Agrawal, Emma C Johnson, Sandra Sanchez-Roige

2020-Current year OA Pubs

BACKGROUND: Decades of research have identified a strong association between heavy cannabis use and schizophrenia (SCZ), with evidence of correlated genetic factors. However, many studies on the genetic relationship between cannabis use and psychosis have lacked data on both phenotypes within the same individuals, creating challenges due to unmeasured confounding. We aimed to address this by using multimodal data from the All of Us Research Program, which contains genetic data as well as information on SCZ diagnosis and cannabis use.

METHODS: We tested the association between cannabis use disorder (CUD) and SCZ polygenic scores (PGSs) with SCZ and heavy cannabis …

Resident-Led Peer Support Groups In Emergency Medicine: A Pilot Framework For Peer Leader Training, Kyra D Reed, Alexandria P Weston, Alexandra E Serpe, Destiny D Folk, Jacob M Destrampe, Heather P Kelker, Aloysius J Humbert, Katie E Pettit, Julie L Welch

2020-Current year OA Pubs

Peer support has demonstrated efficacy in alleviating symptoms of anxiety and depression, while fostering empathy and mitigating burnout among healthcare professionals. Given the considerable demands of residency training, there is a strong rationale for resident-led peer support interventions. However, structured programs to train residents for such leadership roles remain limited. Our objective was to implement a peer support leader training program for residents, evaluate its perceived effectiveness, and identify common themes discussed in sessions. Between June 2021 and June 2023, we performed a longitudinal, prospective cohort survey study of Emergency Medicine (EM) and EM/Pediatrics (EM/P) residents participating in a novel …

Wdfy4-Dependent Cross-Presentation Proceeds Via A Vacuolar Antigen-Processing Route, J Luke Postoak, Alyssa Koch, Sicong Shan, Ray A Ohara, Suin Jo, Jing Chen, Pritesh Desai, Feiya Ou, Magdalena Kraft, Michael S Diamond, Sunkyung Kim, Theresa L Murphy, Kenneth M Murphy

2020-Current year OA Pubs

The intracellular processing route used by type I conventional dendritic cells (cDC1) for cross-presentation of viral- or tumor-associated antigens remains controversial. One model proposes that captured antigens exit from damaged phagolysosomes and enter the cytosol, where they are processed for presentation by MHC class I molecules (MHC-I). This model relies on proteasomal degradation and TAP-dependent peptide transport into the endoplasmic reticulum (ER) for loading by the peptide loading complex (PLC). An alternative model proposes a vesicular route in which captured antigens are retained and processed within an endocytic compartment. A compelling argument favoring the cytosolic model is the dramatic loss …

Intracellular Acinetobacter Baumannii Acts As A Transient Reservoir In Lung Infection Via A "Persist And Resist" Strategy, Manon Janet-Maitre, Gisela Di Venanzio, Clay D Jackson-Litteken, Nichollas E Scott, Mario F Feldman

2020-Current year OA Pubs

Although considered primarily extracellular,

Holter Monitor Qt Dispersion And Qtc-Dispersion In Pediatric Long Qt Syndrome And Development Of A Diagnostic And Arrhythmia Risk Prediction Model, Hadeel Allam, Na Le Dang, Edita Karasalihovic, Nathan Miller, Lisa Roelle, William B Orr, Dustin Nash, Anthony G Pompa, Jennifer N A Silva

2020-Current year OA Pubs

BACKGROUND: Holter monitors can provide temporal QT analysis, allowing for calculation of QT dispersion and corrected QT dispersion over time. We describe the results of the QT dispersion and corrected QT dispersion over a 24-hour period in pediatric patients with long QT syndrome (LQTS), compared with a normal cohort, and develop 2 new machine learning models for diagnosis and arrhythmia risk prediction in LQTS.

METHODS: A single-center retrospective case-control study was conducted comparing patients with congenital LQTS and normal controls who underwent a clinically indicated Holter between January 2022 and May 2024. After identifying patients with cardiac events, 2 neural …

Baseline Ecg And Cardiovascular Outcomes In People With Hiv: Insights From Reprieve, Aya Awwad, Shashwatee Bagchi, Et Al.

2020-Current year OA Pubs

BACKGROUND: With antiretroviral therapy, people with HIV (PWH) have an increased burden of cardiovascular disease. The REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) trial demonstrated that pitavastatin reduces major adverse cardiovascular events (MACEs) among PWH at low to moderate traditional atherosclerotic risk. Electrocardiographic abnormalities are common in PWH, but little is known about their association with MACEs. We sought to examine whether baseline electrocardiographic abnormalities are associated with increased MACE risk among a global primary cardiovascular disease prevention cohort of PWH in REPRIEVE.

METHODS: In this observational analysis, entry electrocardiographic abnormalities were adjudicated and classified as major or …

The Inferred Functional Connectome Underlying Circadian Synchronization In The Mouse Suprachiasmatic Nucleus, K L Nikhil, Bharat Singhal, Daniel Granados-Fuentes, Jr-Shin Li, István Z Kiss, Erik D Herzog

2020-Current year OA Pubs

Circadian rhythms in mammals arise from the spatiotemporal synchronization of ~20,000 neuronal clocks in the suprachiasmatic nucleus (SCN). Although anatomical, molecular, and genetic approaches have revealed diverse SCN cell types, how network-level wiring enables their synchronization remains unclear. To overcome the challenges of inferring functional connectivity from fixed tissue, we developed Mutual Information & Transfer Entropy (MITE), an information-theoretic framework to infer directed cell-cell connections with high fidelity from long-term live-cell imaging. Recording and analyzing 3,290 h of clock gene expression from 8,261 SCN neurons across 17 mice, we uncovered a highly conserved, sparse SCN network organized into two asymmetrically …

Intracranial Injection Of Genetically Modified, Mosquito Non-Transmissible Zika Virus: Safety In Primates And Ramifications For Brain Tumor Therapy, Alec J Hirsch, Amanda De Andrade Costa, Emilie Russler-Germain, Ashwani Kesarwani, Yuping Li, Michael S Diamond, Milan G Chheda, Et Al.

2020-Current year OA Pubs

Glioblastomas (GBMs) are incurable brain tumors. Zika virus (ZIKV) has specificity in killing GBM stem cells, which drive treatment resistance. In mouse models of GBM, ZIKV also generates an anti-tumor inflammatory response and prolongs survival. To support clinical development and address safety concerns for intra-tumoral treatment, we assessed the effects of injection of an immune-sensitized ZIKV (Δ10 3'-UTR ZIKV), which cannot be transmitted by mosquitos, into non-tumor-bearing rhesus macaque brains. After injection, the primates showed no clinical signs of illness. Histologically, as expected, ZIKV infection elicited mild inflammation, which resolved within 2 weeks. No infectious virus was detected in the …

Exploiting Large Language Models For Diagnosing Autism Associated Language Disorders And Identifying Distinct Features, Chuanbo Hu, Wenqi Li, Mindi Ruan, Xiangxu Yu, Shalaka Deshpande, Lynn K Paul, Shuo Wang, Xin Li

2020-Current year OA Pubs

Diagnosing language disorders associated with autism is a complex challenge, often hampered by the subjective nature and variability of traditional assessment methods. In this study, we explored large language models (LLMs) to overcome the speed and precision obstacles by enhancing sensitivity and profiling linguistic features for autism diagnosis. This research utilizes natural language understanding capabilities of LLMs to simplify and improve the diagnostic process, focusing on identifying autism-related language patterns. We showed that the proposed method demonstrated improvements over the baseline models, with over a 10% increase in both sensitivity and positive predictive value in a zero-shot learning configuration. Combining …

A Proteogenomic Gene Signature Defines Prognostic Subgroups Highlighting Pi3k/Akt/Mtor Signaling Pathway As A Therapeutic Vulnerability In Myeloid Malignancies, Fan He, Shuyang Lin, Bei Gao, Varun Ramesh, Alexander B Kim, Tim Kong, Daniel A C Fisher, Christopher T Letson, Molly Brakhane, Mary Fulbright, Yanbo Yu, Marco Sardiello, Jorge Di Paola, Stephen M Sykes, Stephen T Oh

2020-Current year OA Pubs

INTRODUCTION: Myeloid malignancies, including acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN), exhibit overlapping pathophysiology. Chronic MPNs can transform into secondary AML (sAML), which is associated with poor prognosis and limited treatment options. However, the process and prognostic significance of leukemic transformation remain incompletely understood.

METHOD: Through a two-sample bidirectional Mendelian randomization (MR) analysis, we showed that genetic liability to MPN significantly predicts the risk of developing AML, establishing MPN as the precursor to leukemia. To identify mediators of this risk, we integrated population-level plasma proteomics data, identifying 55 proteins associated with MPN. Upon integrative analysis with the BEAT-AML cohort, …

Enhancing Exercise Engagement And Gait In Parkinson Disease: Participation Factors, Novel Approaches, And The Role Of Rhythmic Auditory Cueing, Allison Haussler

WUSM Theses and Dissertations – All Programs

Parkinson disease (PD) is the second most common neurodegenerative disease, characterized by gait and balance impairments that reduce independence and diminish quality of life. Exercise and other rehabilitation strategies, such as rhythmic auditory cueing, are well-researched methods to address motor impairments. However, despite the strong body of research supporting these approaches, many individuals with PD remain sedentary and do not meet current exercise recommendations. This highlights a critical gap between evidence and real-world behavior.

While prior research identified general motivators and barriers to exercise in people with PD, emerging exercise modalities and the growing diversity of community-based programs emphasize the …