Medical Specialties Commons^™

Limosilactobacillus Reuteri Promotes Melatonin Release From Human Intestinal Organoids Via 5′Ectonucleotidase Activity, Heather A Danhof, Ludwig Ermann Lundberg, Stefan Roos, Robert A Britton

Faculty, Staff and Students Publications

Strains of Limosilactobacillus reuteri have been used to prevent or treat various conditions; however, the mechanisms by which they exert beneficial effects are not completely understood. Infant colic is one example in which L. reuteri DSM 17938 reduces clinical symptoms. While the etiology of colic is unknown, abnormal melatonin levels in infants have been suggested as a possible contributor. L. reuteri DSM 17938 has been shown to produce adenosine from AMP via production of the extracellular enzyme 5′ectonucleotidase (5′NT). Adenosine is a potent signaling molecule that impacts several important aspects of host physiology, including the release of melatonin from the …

Steroid Receptor Coactivator 3-Deficient Regulatory T Cells Eradicate Multiple Solid Tumors In Syngeneic Mouse Models, Yuri Park, Adam M Dean, Yan Xia, Jianming Xu, Clifford C Dacso, David M Lonard, Sang Jun Han

Faculty, Staff and Students Publications

Steroid receptor coactivator 3 (SRC-3) is highly expressed in regulatory T cells (Tregs) and is important for their immunosuppressive activity. Recently, we demonstrated that disrupting SRC-3 expression in Tregs eliminates triple-negative breast cancer (TNBC) and prostate cancer in syngeneic animal models by generating an anti-tumor immune microenvironment without inducing immune-related adverse events (irAEs). Further analysis of these mice revealed that SRC-3 knockout (KO) Tregs infiltrated breast tumors and facilitated the infiltration of CD8

When Probiotics Guidelines Differ: A Practical Guide For Clinicians And Researchers, Howard Bauchner, Daniel J Merenstein

Faculty, Staff and Students Publications

Many professional organizations publish clinical practice guidelines for the use of probiotics in gastrointestinal disorders. Generally, no two guidelines align perfectly, and some differ markedly. These discrepancies occur because clinical practice guidelines are not purely mechanical outputs of data synthesis. They are shaped by structured interpretation, value judgments, and predefined thresholds for uncertainty. These elements become particularly visible when effect sizes are small, heterogeneity is high, and outcomes vary in clinical relevance-as is the case with probiotic research. This article examines why discordance among probiotic guidelines is predictable and provides practical guidance for clinicians who must decide among conflicting recommendations …

Mtorc2-Nav1.2 Signaling Drives Early Hyperexcitability In Alzheimer’S Disease Mouse Model

Faculty, Staff and Students Publications

Hyperexcitability is a biomarker of early-stage Alzheimer’s Disease (AD) and hastens cognitive decline later in its course. Mechanistic target of rapamycin (mTOR) signaling contributes to the slope of this trajectory, as evidenced by early increased brain expression and the rescue of hyperexcitability by genetic deletion of mTOR complex 2 (mTORC2); however, a molecular mechanism directly linking mTOR signaling to membrane hyperexcitability in early-stage AD remains elusive. Here, we show that hyperactive mTOR signaling stimulates the voltage-gated Na+ channel 1.2 (Nav1.2), a previously identified downstream phosphorylation target of mTORC2 and a key regulator of membrane electrogenesis. Augmented Nav1.2 channel function induced …

In-Hospital Mortality Patterns And Readmissions In Patients With Chronic Obstructive Pulmonary Disease: An Analysis Of The Role Of Pulmonary Hypertension, Saad Afzal Khan, Trishna Parikh, Adishwar Rao, Akriti Agrawal, Aarohi Parikh, Sarah Shin, Maulin Patel, Kha Dinh, Bela Patel, Bindu Akkanti

Faculty, Staff and Student Publications

Chronic obstructive pulmonary disease (COPD) may be complicated by pulmonary hypertension (PH). We aimed to understand the impact of PH on in-hospital mortality and quantify the 30-day readmission rate among patients with COPD. For this cross-sectional study, we used the Nationwide Readmissions Database from 2017-2020 to identify adults ≥18 years with COPD. Patients were stratified according to PH diagnosis. Baseline characteristics between groups were compared using the Pearson chi-square test and two-sample t-test. Predictors of in-hospital mortality were determined using multivariate logistic regression analysis adjusted for demographics and confounders. The 30-day readmission rate and prevalence of PH subgroups by baseline …

Comparative Performance Of Predictive Nomograms For Pathological Upstaging In Clinical T1 Renal Masses: An Independent External Validation, Michael Vainrib, Amos Neheman, Omri Schwarztuch Gildor

Faculty, Staff and Students Publications

Background: Preoperative identification of pathological upstaging (≥ pT3a) in clinical T1 (cT1) renal masses is critical for surgical planning. We externally validated three established predictive models, Barra, Nocera, and Mei, to assess their discrimination, calibration, and clinical utility in a contemporary cohort.

Patients and methods: We retrospectively reviewed patients undergoing surgery for cT1 renal masses at our institution. The primary endpoint was pathological upstaging to pT3a. Model performance was evaluated using the Area Under the Curve (AUC) for discrimination and the Brier Score for overall accuracy. Calibration was assessed using parametric and nonparametric Loess-smoothed curves. Clinical utility was quantified using …

Glial Dysfunction And Memory Impairments In A Model Of Pediatric Obstructive Sleep Apnea, Thea Zlatkov, Akdes Serin Harmanci, Christopher J Yates, Kenneth Nobleza, Roshan Ailani, Adam C Adler, Farrah Kheradmand, Hyun Kyoung Lee, Benjamin Deneen, Hyun-Hwan Jeong, Arvind Chandrakantan

Faculty, Staff and Students Publications

Pediatric obstructive sleep apnea (POSA) is a common childhood disease that often causes aberrant brain development and cognitive deficits. The pathophysiological underpinnings of cognitive impairments in POSA remain unclear. Here, we examined cellular and molecular aspects of pathology in a mouse model of POSA that features learning and memory deficits. We performed single-nucleus RNA-sequencing (snRNA-seq) of the hippocampus to examine gene expression changes in an unbiased and cell type-specific manner. This dataset revealed a striking perturbation of transcriptomes across all brain cell types, particularly within glia and neural stem cells. We validated reduced expression of several differentially expressed genes at …

Natural History Of Pi-Rads 3 Lesions On Serial Prostate Mpmri, Ron Marom, Yuval Rand, Meitar Atias, Sophie Barnes, Ibrahim Fahoum, Gal Keren-Paz, Mario Sofer, Ofer Yossepowitch, Snir Dekalo, Avi Beri, Roy Mano

Faculty, Staff and Students Publications

Objective: PI-RADS 3 lesions on prostate multiparametric MRI (mpMRI) are indeterminate findings with debated management. We evaluated their radiologic evolution on follow-up mpMRI and correlated imaging changes with biopsy outcomes.

Methods: We retrospectively identified 166 men with at least one PI-RADS 3 lesion on initial mpMRI and at least one follow-up mpMRI without intervening treatment. Lesions were classified at follow-up as regressed (downgraded to PI-RADS ≤ 2), stable (remained PI-RADS 3), or progressed (upgraded to PI-RADS 4-5). Lesions were stratified by zonal location. MRI-targeted biopsy results were reviewed when available (n = 64).

Results: On follow-up, 52% of lesions regressed, …

Hyaluronic Acid Rectal Wall Infiltration And Reversal In Patients With Prostate Cancer Undergoing Radiation Therapy-A Case Series, Michael K Rooney, Stephen R Lee, Stephen E Mcrae, Ketan Y Shah, Mohamed E Abdelsalam, Ethan Y Lin, Comron Hassanzadeh, Seungtaek Choi, Quynh-Nhu Nguyen, Steven J Frank, Mohamed Shelan, Lauren L Mayo, Sean Mcguire, Steven Yevich, Osama Mohamad

Faculty, Staff and Students Publications

No abstract provided.

Progressive Remodeling Of Global Protein Interaction Networks In A Mouse Model Of Tauopathy, Noah Lampl, Morgan C Stephens, Zihan Wang, Joseph T Nigro, Alejandro Rondon Ortiz, Ryan Hekman, Anna Lourdes F Cruz, Rebecca Roberts, Lulu Jiang, Juan Botas, Andrew Emili, Benjamin Wolozin

Faculty, Staff and Students Publications

Neurodegenerative disease is marked not just by loss of proteins or cells, but by dynamic rewiring of macromolecular interaction networks that precede and drive pathology. Here, we present a temporally resolved, systems-scale map of multi-protein complex remodeling in a tauopathy model, integrating co-fractionation mass spectrometry, quantitative phosphoproteomics, and machine learning to decode phosphorylation-dependent shifts in protein interactomes across disease progression. This interactomic atlas serves as a resource to investigate functional assemblies, including MAPT-Dpysl2 and Cyfip1-actin, as well as ptk2b-Kars/Dars and ptk2b-Msn-Farsb-complexes, that modulate early disease phenotypes in vivo. Notably, it captures the composition, dynamics, and regulatory state of protein complexes …

Progressive Remodeling Of Global Protein Interaction Networks In A Mouse Model Of Tauopathy, Noah Lampl, Morgan C Stephens, Zihan Wang, Joseph T Nigro, Alejandro Rondon Ortiz, Ryan Hekman, Anna Lourdes F Cruz, Rebecca Roberts, Lulu Jiang, Juan Botas, Andrew Emili, Benjamin Wolozin

Faculty, Staff and Students Publications

Neurodegenerative disease is marked not just by loss of proteins or cells, but by dynamic rewiring of macromolecular interaction networks that precede and drive pathology. Here, we present a temporally resolved, systems-scale map of multi-protein complex remodeling in a tauopathy model, integrating co-fractionation mass spectrometry, quantitative phosphoproteomics, and machine learning to decode phosphorylation-dependent shifts in protein interactomes across disease progression. This interactomic atlas serves as a resource to investigate functional assemblies, including MAPT-Dpysl2 and Cyfip1-actin, as well as ptk2b-Kars/Dars and ptk2b-Msn-Farsb-complexes, that modulate early disease phenotypes in vivo. Notably, it captures the composition, dynamics, and regulatory state of protein complexes …

Frequency-Dependent Cerebellar Circuits Independently Gate Social Vocalizations And Movement, Tao Lin, Benjamin R Arenkiel, Roy V Sillitoe

Faculty, Staff and Students Publications

Communication depends on precise coordination between motor execution and cognition. Here we reveal that the cerebellum exerts real-time control over social vocalizations in adult mice. Optogenetic activation of excitatory cerebellar output in the superior cerebellar peduncle suppressed ultrasonic vocalizations with frequency-dependent potency while inducing distinct motor phenotypes. Systematic functional mapping across cerebellar regions and cell types revealed that vocal suppression can occur in the absence of overt motor impairment, suggesting selective control of vocal output beyond gross movement disruption. We identified the periaqueductal gray (PAG), a conserved midbrain vocal control center, as a key downstream mediator of this effect. Deep …

Aberrant One-Carbon Metabolism And Ancestral Genetics Underlie Edematous Severe Acute Malnutrition, Aarti Jajoo, Jared Redmond, Aparna Haldipur, Solome Zewdu, Emilyn Banfield, Shanker Swaminathan, Sharon Howell, Orgen Brown, Roa Sadat, Nancy J Hall, Kwesi Marshall, Katharina V Schulze, Thaddaeus May, Marvin E Reid, Carolyn Taylor-Bryan, Mark J Manary, Indi Trehan, Mamana Mbiyavanga, Wisdom A Akurugu, Colin A Mckenzie, Dhriti Sengupta, Elizabeth G Atkinson, Ananyo Choudhury, Neil A Hanchard

Faculty, Staff and Students Publications

Edematous severe childhood malnutrition is distinct from the non-edematous form of malnutrition and remains a major cause of under-five mortality. Its etiology remains unclear, although aberrant one-carbon metabolism has emerged as a potential contributor. Here, we assess genetic variants at loci known to influence one-carbon metabolism, and determine their association with edematous malnutrition in Jamaica and Malawi. Six loci show evidence of association, including four related to homocysteine and folate metabolism - AHCYL1, PRICKLE2, GABBR2, and PLD2, with SNPs at the latter three also having direct effects on homocysteine-related metabolites in Mendelian Randomization. Collectively, one-carbon metabolism-related variants were significantly associated …

Corrigendum To “Characterizing The Metabolites Of The Tyrosine-Kinase Inhibitor Pexidartinib In Mouse Feces, Urine, Plasma, And Liver” [J. Pharm. Biomed. Anal. 265 (2025) 117034], Jian Wang, Lei Guo, Ashish Dogra, Zhaoyong Hu, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

No abstract provided.

Single-Nuclei Transcriptomics Reveals Cellular Senescence In Pediatric Anthracycline-Induced Cardiomyopathy, Hanna J Tadros, Yi Zhao, Lalita Wadhwa, Iki Adachi, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Chemotherapy drugs that fight childhood cancer can age heart cells prematurely. We found this "cellular aging" throughout the hearts of children with treatment-related heart failure.

Transcriptomic Data And Biomedical Literature Synergize In Finding Pharmacologic Gene Regulators, Athanasios Papastathopoulos-Katsaros, Yi Zhong, Yidan Li, Tianyun Wang, Kelsey Hennick, Druha Karunakaran, Hanna Berk-Rauch, Zhandong Liu, Aravinda Chakravarti, Tomasz Nowakowski, Evan E Eichler, Huda Zoghbi

Faculty, Staff and Students Publications

Autism affects male individuals four times more often than female individuals, yet the basis of this sex bias remains unclear. One hypothesis is that this sex bias is due to genetic variants in X chromosome genes where haploinsufficiency causes neurodevelopmental disorders (NDDs). In heterozygous XX female probands, a complete loss-of-function variant in one of these genes often causes syndromic NDD, but the same variant is too deleterious for survival in hemizygous XY males. A mild hypomorphic variant, however, may be tolerated in a female carrier but may produce milder neurological phenotypes in a male proband. We tested this by investigating …

Expanding The Clinical And Molecular Spectrum Of Tubb2b Through Distinct Variants Identified Across Multiple Families, Haowei Du, Lauren E Westerfield, Chloe Munderloh, Divya Kalra, Yifan Wu, Yi Chen, Marie-Claude Gingras, Shalini N Jhangiani, Sarenur Yilmaz, Maha S Zaki, Daniel G Calame, Davut Pehlivan, Richard A Gibbs, Richard A Lewis, James R Lupski, Jennifer E Posey

Faculty, Staff and Students Publications

TUBB2B encodes a β-tubulin isotype essential for neuronal proliferation, migration, and organization during brain development. Pathogenic heterozygous variants in TUBB2B are associated with neurodevelopmental disorders including polymicrogyria and corpus callosum abnormalities. However, the phenotypic spectrum remains heterogeneous, most likely reflecting variant-specific effects on microtubule formation and stability. Homozygous TUBB2B variants are exceedingly rare, with one family reported to date. We describe five individuals in four families with rare TUBB2B variants. Four variants are described, including a previously reported de novo missense variant, c.292G>A (GenBank: NM_178012.5) (p.Gly98Arg), with potential phenotypic expansion including panhypopituitarism; a previously reported de novo missense variant, …

Expanding The Clinical And Molecular Spectrum Of Tubb2b Through Distinct Variants Identified Across Multiple Families, Haowei Du, Lauren E Westerfield, Chloe Munderloh, Divya Kalra, Yifan Wu, Yi Chen, Marie-Claude Gingras, Shalini N Jhangiani, Sarenur Yilmaz, Maha S Zaki, Daniel G Calame, Davut Pehlivan, Richard A Gibbs, Richard A Lewis, James R Lupski, Jennifer E Posey

Faculty, Staff and Students Publications

TUBB2B encodes a β-tubulin isotype essential for neuronal proliferation, migration, and organization during brain development. Pathogenic heterozygous variants in TUBB2B are associated with neurodevelopmental disorders including polymicrogyria and corpus callosum abnormalities. However, the phenotypic spectrum remains heterogeneous, most likely reflecting variant-specific effects on microtubule formation and stability. Homozygous TUBB2B variants are exceedingly rare, with one family reported to date. We describe five individuals in four families with rare TUBB2B variants. Four variants are described, including a previously reported de novo missense variant, c.292G>A (GenBank: NM_178012.5) (p.Gly98Arg), with potential phenotypic expansion including panhypopituitarism; a previously reported de novo missense variant, …

Diopt: The Drsc Integrative Ortholog Prediction Tool, 2026 Update, Austin Veal, Shinya Yamamoto, Stephanie E Mohr, Norbert Perrimon

Faculty, Staff and Students Publications

Mapping orthologous proteins is a critical step for cross-species literature mining, data integration, experimental design, and more, making the ability to quickly predict orthologs across species a key tool for functional genomic studies. The DRSC Integrative Ortholog Prediction Tool (DIOPT) was initially developed in 2011 to provide a centralized portal for identifying inferred orthologs among major model organisms. By integrating results from multiple ortholog prediction algorithms, DIOPT allows users to compare predictions across methods and prioritize high-confidence ortholog relationships. Over the years, we regularly updated the underlying genome annotations and refreshed predictions from each integrated algorithm. In addition, both the …

Social Responsiveness As A Mediator In Adapted Cognitive Behavioral Therapy For Autistic Youth With Maladaptive And Interfering Anxiety, Karen S Wood, Philip C Kendall

Faculty, Staff and Students Publications

Numerous adaptations to interventions have been included in cognitive behavioral therapy (CBT) for autistic youth. This study examines the degree to which CBT adapted to the social needs of autistic youth confers significant benefit by promoting social responsiveness. A secondary analysis was conducted on a multisite randomized clinical trial (Wood et al. in JAMA Psychiatry 77:474-483, 2020) comparing adapted CBT with standard-of-practice CBT and treatment-as-usual (TA). Autistic youth (N = 167; aged 7-13) with maladaptive and interfering anxiety participated. The adapted CBT (BIACA) uses a modular format, with an emphasis on supplementing common CBT practice elements (reframing and graded exposure) …

A Rare Recurring Gain-Of-Function Variant In Bmpr2 Causes Neurodevelopmental Phenotypes In Humans And Flies, Zhi Tan, Ariel Brautbar, Maria Descartes, Erica T Gray, Alejandro Iglesias, Scott D Mclean, Morgan Nutter, Olivia Daugherty, Amber Begtrup, Ingrid M Wentzensen, Yufeng Shen, Damian W Young, Martin M Matzuk, Oguz Kanca, Michael F Wangler, Hugo J Bellen, Wendy K Chung, Shinya Yamamoto

Faculty, Staff and Students Publications

Bone morphogenetic protein receptor type 2 (BMPR2) encodes an evolutionarily conserved serine/threonine kinase that phosphorylates type-1 BMP receptors to mediate intercellular communication upon ligand binding. Loss-of-function variants in BMPR2 are known to cause pulmonary arterial hypertension and other cardiovascular disorders. Here, we report a rare recurrent missense variant in BMPR2 (c.1126G>A [GenBank: NM_001204] [p.Glu376Lys]) identified in six individuals, who all present with neurodevelopmental phenotypes including autism spectrum disorder and global developmental delay. Trio analysis demonstrates de novo occurrence of this variant in at least five of the individuals. Using the fruit fly Drosophila melanogaster, we show that this variant …

A Spatial Atlas Of Muscle-Invasive Bladder Cancer Reveals Lineage-Specific Vulnerabilities And Immune Architecture, Sajith Nair, Emanuele Crupi, Elshad Hasanov, Ying Mei, Xueshuai Han, Yang Liu, Yunhe Liu, Guangsheng Pei, Fuduan Peng, Jianlong Liao, Enyu Dai, Tian Chu, Kyung Serk Cho, Jiahui Jiang, Xinmiao Yan, Yibo Dai, Jun Wang, Baifeng Zhang, Giannicola Genovese, Nagireddy Putluri, Livia Eberlin, Liuqing Yang, Chunru Lin, Lawrence N Kwong, Diana Shamsutdinova, Khalida M Wani, Bogdan A Czerniak, Wendong Yu, Jianping Zhao, Charles C Guo, Donna Hansel, Curtis Pettaway, Louis Pisters, Kelly Bree, Neema Navai, Byron H Lee, Ashish M Kamat, Padmanee Sharma, Paul Corn, Cindy Y Jiang, Amishi Y Shah, Omar Alhalabi, Pavlos Msaouel, Arlene O Siefker-Radtke, Christopher J Logothetis, Matthew T Campbell, Alexander J Lazar, Jianjun Gao, Linghua Wang

Faculty, Staff and Students Publications

Muscle-invasive bladder cancer (MIBC) is clinically heterogeneous, and current molecular subtyping does not capture the spatial organization of tumor states and microenvironmental context. In this study, we construct a spatial atlas of MIBC by integrating spatial transcriptomics from 22 tumors with matched bulk RNA and whole-exome sequencing data. We identify a continuous, spatially organized luminal-to-basal axis within individual tumors that is associated with greater chromosomal instability and transcriptional plasticity. Luminal tumor cores are enriched for FGFR3 and NECTIN4, whereas basal-like states localize toward invasive margins and are associated with elevated EGFR signaling, epithelial-mesenchymal transition, genomic instability, immune infiltration, and greater …

Adjunctive Embolization Of Target Vessel Dissections To Improve Suitability For Fenestrated-Branched Endovascular Aortic Repair, Steven Maximus, Naveed Saqib, Erin Greenleaf, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Students Publications

Suitability of renal-mesenteric target arteries is an essential criterion for fenestrated-branched endovascular aortic repair (FB-EVAR). We describe a staged adjunctive technique of target vessel false lumen (FL) embolization to improve suitability for FB-EVAR in patients with chronic postdissection thoracoabdominal aortic aneurysms (PD-TAAA) and dissection extension into the superior mesenteric artery (SMA). Three patients with SMA dissection and ectasia (diameter > 12-14 mm) underwent staged FL embolization with pre-emptive stent placement to optimize SMA incorporation. Using bilateral transfemoral access with intravascular ultrasound guidance, the proximal SMA true lumen was stented with an 8 L × 39 mm VBX balloon-expandable stent graft (W. …

Increasing Co2 Levels Fertilize C4 Grass Production, William J Bond, Corli Coetsee, Nita C M Pallett, Adam F A Pellegrini, Sarah L Raubenheimer, Brad S Ripley, Maria Val Martin, Colin P Osborne

Faculty, Staff and Students Publications

Rising atmospheric CO2 concentrations are impacting the global terrestrial biosphere through indirect climate effects and direct effects on plant performance1–3. In tropical forests, long-term monitoring indicates a substantial CO2-driven carbon sink4. C4-grass-dominated tropical and subtropical savannas contribute approximately 30% of terrestrial net primary production5, and yet equivalent long-term analyses of CO2 responses are lacking. Here we show a clear and consistent result across a meta-analysis of 70 CO2-addition experiments and 32 years of in situ field observations from southern Africa: CO2 fertilization of wild C4 grasses is widespread in dry conditions. In …

Nlgn3 Autism Variants Have Distinct Functional Impact On Synapses And Sleep Behavior In Drosophila, Sharayu V Jangam, Shabab B Hannan, Oguz Kanca, Paul C Marcogliese, Shinya Yamamoto, Michael F Wangler

Faculty, Staff and Students Publications

Neuroligin-3 (NLGN3) was first identified as a X-linked risk gene associated with autism spectrum disorder (ASD). Most reported variants are identified in males who inherited their variants from an unaffected mother, but de novo variants have also been identified in both affected heterozygous females and hemizygous males. The p.R451C variant was the initial variant associating NLGN3 with ASD and has been heavily investigated, yet little is known about the functional consequences of other NLGN3 variants. To determine the functional consequences of other NLGN3 variants in vivo, we generated transgenic Drosophila models corresponding to a de novo variant (p.R175W) identified in …

Tertiary Lymphoid Structures In Lupus Nephritis Are Associated With Aging And Chronic Kidney Injury, Naoya Toriu, Yuichiro Kitai, Keita P Mori, Takahisa Yoshikawa, Shinya Yamamoto, Naoki Sawa, Yoshifumi Ubara, Motoko Yanagita

Faculty, Staff and Students Publications

No abstract provided.

Engagement And Weight Change In An Online Weight Management Program In Clinical Settings: An Implementation Project, Caroline M Apovian, Ashley C Mccarthy, Alexander J Blood, Lipika Samal, Naomi D L Fisher, E John Orav, Matthew Wien, Jorge Plutzky, Jason P Block, David W Bates, Ronen Rozenblum, Michela Tucci, Marian Mcpartlin, Michael Oates, Katherine D Mcmanus, Benjamin M Scirica

Faculty, Staff and Students Publications

Background: There is an urgent need for scalable strategies for treatment of overweight and obesity that can be implemented in clinical settings.

Objective: To implement and evaluate an online weight management program in a large, diverse population of patients.

Design: Clinical implementation project in primary care and specialty clinics.

Participants: Eligible patients were ≥ 20 years old, spoke English or Spanish, and had a body mass index (BMI) of ≥ 30 kg/m2 or a BMI of 25-29.9 kg/m2 plus ≥ 1 cardiovascular risk factor or obesity-related condition.

Intervention: Enrolled patients were encouraged to register for a 12-month digital health program …

Spell: A Scalable Nlp Method Using Regular Expressions And Large Language Models For Clinical Information Extraction, Kathryn J Gray, Vesela P Kovacheva

Faculty, Staff and Students Publications

Background and objectives: Electronic health records (EHRs) contain valuable information for research and decision-making, but much resides in unstructured notes that are challenging to analyze at scale. We developed SPELL (Snippet-Primed rEgex LLM Pipeline), a scalable natural language processing workflow that combines regular-expression-based snippet retrieval with locally hosted large language model (LLM) inference to extract structured variables from large collections of clinical narratives.

Methods: SPELL uses task-specific regular expressions to retrieve short context windows ("snippets") from unstructured texts and applies task-prompted LLM inference on snippets rather than full documents. All processing occurs within institutional computing environments. Accuracy was evaluated on …

Considering Access And Methodological Rigor In Framing Results Of The Bergen 4 Day Treatment Program For Obsessive-Compulsive Disorder

Faculty, Staff and Students Publications

No abstract provided.

A Genetic Risk Variant Associated With The Risk Of Primary Biliary Cholangitis Is Inherited From Neanderthals, Heather J Cordell, George F Mells, Richard N Sandford, David E Jones, Gideon Hirschfield, Katherine A Siminovitch, M Eric Gershwin, Brian D Juran, Elizabeth J Atkinson, Angela Cheung, Mariza De Andrade, Aris Baras, Konstantinos N Lazaridis, Rosanna Asselta, Pietro Invernizzi, Manuela Sironi, Sriram Sankararaman, Canadian‐Us Pbc Consortium, Uk‐Pbc Consortium, Italian Pbc Genetics Study Group

Faculty, Staff and Students Publications

Background: Primary Biliary Cholangitis (PBC) is an autoimmune cholangiopathy with polygenic architecture and unknown aetiology. Evidence links Neanderthal-derived genetic variants to autoimmune conditions; however, their contribution to PBC susceptibility remains unexplored.

Objective: We investigate whether archaic alleles influence PBC risk.

Design: Genotype data from four PBC cohorts were analysed: CANUK (4615 cases, 9233 controls), OLD IT (444 cases, 901 controls), NEW IT (255 cases, 579 controls) and MAYO (891 cases, 621 controls). Association testing with 235 592 Neanderthal Informative Markers (NIMs) was performed, adjusting for population stratification. Heritability was estimated using RHE-mc and temporal haplotype dynamics were assessed using ancient …