Medicine and Health Sciences Commons^™

Stakeholder Perspectives On Humanistic Implementation Of Computer Perception In Health Care: Qualitative Study, Kristin M Kostick-Quenet, Meghan E Hurley, Syed Ayaz, John D Herrington, Casey J Zampella, Julia Parish-Morris, Birkan Tunç, Gabriel Lázaro-Muñoz, Jennifer Blumenthal-Barby, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Background: Computer perception (CP) technologies-including digital phenotyping, affective computing, and related passive sensing approaches-offer unprecedented opportunities to personalize health care, especially mental health care, yet they also provoke concerns about privacy, bias, and the erosion of empathic, relationship-centered practice. At present, it remains elusive what stakeholders who design, deploy, and experience these tools in real-world settings perceive as the risks and benefits of CP technologies.

Objective: This study aims to explore key stakeholder perspectives on the potential benefits, risks, and concerns associated with integrating CP technologies into patient care. A better understanding of these concerns is crucial for responding to …

A Prognostic Matrix Gene Expression Signature Defines Functional Glioblastoma Phenotypes And Niches, Monika Vishnoi, Zeynep Dereli, Zheng Yin, Elisabeth K Kong, Meric Kinali, Kisan Thapa, Ozgun Babur, Kyuson Yun, Nourhan Abdelfattah, Xubin Li, Behnaz Bozorgui, Mary C Farach-Carson, Robert C Rostomily, Anil Korkut

Faculty, Staff and Student Publications

Interactions among tumor, immune, and vascular niches play major roles in glioblastoma (GBM) malignancy and treatment responses. The composition and heterogeneity of extracellular core matrix proteins (CMPs) that mediate such interactions are not well understood. Here, we present an analysis of the clinical relevance of CMP expression in GBM at bulk, single-cell, and spatial anatomical resolution. We show that CMP enrichment is associated with worse patient survival, specific driver oncogenic alterations, mesenchymal state, pro-tumor immune infiltration, and immune checkpoint expression. Matrisome expression is enriched in vascular and leading edge/infiltrative niches that are known to harbor glioma stem cells. Finally, we …

Vacmap: An Accurate Long-Read Aligner For Unraveling Complex Genomic Rearrangements, Hongyu Ding, Fritz J Sedlazeck, Christos Proukakis, Caoimhe Morley, Marco Toffoli, Anthony Hv Schapira, Zhirui Liao, Lianrong Pu, Shanfeng Zhu

Faculty, Staff and Students Publications

Sequence alignment is essential for genomic research and clinical diagnostics, yet detecting complex rearrangements such as inversions, duplications, and gene conversions remains challenging due to allele complexity and limitations of current methods. We introduce VACmap, a non-linear mapping approach to enhance the detection and representation of all genetic variations. VACmap improves duplication detection from 20% to 90% in the Challenging Medically-Relevant Genes (CMRG) benchmark and improves characterization of complex inversions in repetitive regions and gene conversion events. It improves resolving clinically significant loci, including the LPA gene (with repetitive KIV-2 units linked to coronary heart disease), GBA1 and STRC genes …

Environmental Enteric Dysfunction In Well-Nourished And Undernourished Women In Bangladesh, Mustafa Mahfuz, Md Shabab Hossain, Ar-Rafi Khan, Mehjabin Tishan Mahfuz, Rumana Sharmin, A H M Rezwan, Musarrat Tasnim, S M Tafsir Hasan, S M Khodeza Nahar Begum, M Masudur Rahman, Michael J Barratt, Jeffrey I Gordon, Tahmeed Ahmed

2020-Current year OA Pubs

INTRODUCTION: Environmental Enteric Dysfunction (EED) is a subacute inflammation of the small intestinal (SI) mucosa associated with undernutrition and perturbation of the SI microbiota. Its diagnosis relies on histopathological assessment of small intestinal biopsies, with a lack of validated biomarkers contributing to underdiagnosis. This study assessed the prevalence and histological features of EED in undernourished Bangladeshi women living in an urban slum in Dhaka, compared to well-nourished women from slum and non-slum areas, and examined the factors associated with histologically confirmed EED.

METHODS: This analysis included non-pregnant, non-lactating Bangladeshi women aged 18-45 years classified by location of residence and nutritional …

Performance Of A Rapid, Highly Multiplexed Nucleic Acid Detection Assay For Identification Of Viral And Bacterial Pathogens From Upper Respiratory Tract Specimens, Coreen L Johnson, James J Dunn

Faculty, Staff and Students Publications

Background: Accurate and timely identification of upper respiratory tract pathogens can improve patient management by decreasing unnecessary additional testing, reducing the cost of care, and informing antimicrobial stewardship. We evaluated the FDA-cleared Diasorin LIAISON PLEX® Respiratory Flex (RSP Flex), a highly multiplexed, rapid nucleic acid detection assay that can identify 14 viral and 5 bacterial respiratory pathogens.

Methods: In total, 215 residual patient upper respiratory tract specimens were tested using the RSP Flex assay and results compared to standard-of-care (SOC) molecular testing.

Results: Positive percentage agreement (PPA) was 100% for the following targets: adenovirus, human coronavirus, Bordetella pertussis, Bordetella parapertussis, …

Omg! A Proteomic Determinant Of Neurodegenerative Resiliency, Michael R Duggan, Muhammad Ali, Menghan Liu, Ying Xu, Daniel Western, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Biofluid proteomics can enhance our understanding of the neurodegenerative mechanisms underlying Alzheimer's disease and related dementias (ADRDs). Oligodendrocyte myelin glycoprotein (OMG) is a brain-specific protein implicated in myelination, but its potential mechanistic, biomarker, and therapeutic roles in ADRDs requires further elucidation.

METHODS: After detecting an inverse association between its abundance in peripheral circulation and cortical amyloid deposition in two community-based cohorts, the current study characterized OMG's role in ADRDs with high-throughput proteomics from sixteen independent cohorts. Data included a variety of cross-sectional and longitudinal community-based and clinical cohorts from North America, Europe, and Asia, and incorporated complementary biofluids, biospecimens, …

Clinical Performance Of A Novel Point-Of-Care High-Sensitivity Cardiac Troponin I Assay, Alan H B Wu, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays performed in the central laboratory have long turnaround times. This study evaluates the clinical performance of a novel bedside point-of-care (POC) hs-cTnI assay (i-STAT® hs-TnI) to aid in the diagnosis of myocardial infarction (MI).

METHODS: A prospective multisite cohort study involving emergency department (ED) patients with symptoms suggestive of acute coronary syndrome was conducted at 28 sites across the United States. Serial whole blood samples were collected at 0-1 h and >1-3 h from ED presentation. Primary outcome was MI or non-MI. Sensitivity, specificity, and negative predictive value (NPV) for MI were calculated with …

Accurate Chromatin Marks Peak Calling With Omnipeak, Oleg Shpynov, Maxim N Artyomov

2020-Current year OA Pubs

Chromatin immunoprecipitation sequencing (ChIP-seq) is a widely used technique for identifying transcription-factor binding and histone modifications across the genome. Peaks in ChIP-seq data vary in length depending on the biological context, from narrow transcription factor binding sites to broad histone modification domains. However, commonly used peak-calling tools are tailored to the specific types of data and struggle to consistently handle various peak lengths, datasets of varying quality, and missing control tracks-common issues in comparative or meta-analyses. These limitations are addressed with Omnipeak, a universal unsupervised peak-calling algorithm based on a constrained three-state hidden Markov model. Omnipeak accurately models global genomic …

Β2 And Β3a Regulatory Subunits Can Coassemble In The Same Bk Channels, Yu Zhou, Vivian Gonzalez-Perez, Xiao-Ming Xia, Gopal S Kallure, Sandipan Chowdhury, Christopher J Lingle

2020-Current year OA Pubs

Ca2+- and voltage-activated BK-type K+ channels are influenced profoundly by associated regulatory subunits, including β subunits (Kcnmb1-4; β1-β4). Although overlap in expression of different BK β subunits occurs in native tissues, whether they can coassemble in the same channel complex is not known. We coexpress β2 and β3a subunits together with BK α and, through a combination of macroscopic and single-channel recordings, along with quantitative pull-down of tagged subunits, test whether coassembly can occur. We evaluate two models: (1) random mixing in which β2 and β3a subunits coassemble in the same channels, and (2) segregation in which β2 and β3a …

Towards A Unified Gating Scheme For The Cnbd Ion Channel Family, Jenna L Lin, Baron Chanda

2020-Current year OA Pubs

Cyclic nucleotide-binding domain (CNBD) channels are critical components of numerous bioelectrical processes, including cardiac pacemaking, neuronal signaling, phototransduction in the eye, and stomatal regulation in plants. While members of this channel family share a conserved overall structure, they exhibit striking differences in voltage sensitivity. Hyperpolarization-activated cyclic nucleotide-gated channels are activated by membrane hyperpolarization, whereas ether-à-go-go channels open upon depolarization. Mutagenesis and chimeragenesis studies have revealed that some mutants display bipolar gating behavior-remaining closed at intermediate membrane potentials but capable of opening in response to both hyperpolarization and depolarization. Remarkably, in certain cases, just a few mutations are sufficient to reverse …

Micrornas In Prostate Cancer Liquid Biopsies: Early Detection, Prognosis, And Treatment Monitoring, Seyyed Mohammad Yaghoubi, Erfan Zare, Sina Jafari Dargahlou, Maryam Jafari, Mahdiye Azimi, Maedeh Khoshnazar, Solmaz Shirjang, Behzad Mansoori

Student Papers, Posters & Projects

Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged as stable, non-invasive biomarkers obtainable via liquid biopsies (blood, urine, semen) that could transform PCa management. These small regulatory RNAs reflect underlying tumor biology and are detectable at early disease stages, enabling improved early detection when used alongside or in place of PSA. Distinct miRNA expression patterns correlate with tumor aggressiveness. For example, miR-141 and miR-375 are …

Celltra: Aligning Cell Names With Gene Expression Via A Pathway-Informed Transformer, Zhao Li, Zaiyi Zheng, Rongbin Li, Wenbo Chen, Yuntao Yang, Meer A Ali, Jundong Li, W Jim Zheng

Faculty, Staff and Student Publications

Motivation: Single-cell RNA sequencing (scRNA-Seq) technology enables detailed exploration of gene expression at the individual cell level, crucial for annotating cell types and understanding cellular diversity. Traditional methods for cell type annotation often rely on marker genes and manual labeling, posing challenges due to low data quality and incomplete reference datasets.

Results: We developed CeLLTra, a novel contrastive learning framework that leverages a Transformer-based model integrating biological pathway information to group genes into super tokens, effectively capturing comprehensive gene expression from scRNA-Seq data. By combining this pathway-informed Transformer with a pretrained domain-specific language model, CeLLTra accurately aligns cell-type annotations with …

Anti-Csf-1r Therapy With Combined Immuno-Chemotherapy Coordinate An Adaptive Immune Response To Eliminate Macrophage Enriched Triple Negative Breast Cancers, Diego A Pedroza, Xueying Yuan, Fengshuo Liu, Hilda L Chan, Christina Zhang, William Bowie, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Weiguo Wu, Paul Porter, Poonam Sarkar, Na Zhao, Constanze V Oehler, Ondrej Peller, M Waleed Gaber, Qian Zhu, Charles M Perou, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women diagnosed with metastatic triple negative breast cancer (mTNBC) have limited treatment options, are more prone to develop resistance and are associated with high mortality. A cold tumor immune microenvironment (TIME) characterized by low T cells and high tumor associated macrophages (TAMs) in mTNBC is associated with the failure of standard-of-care chemotherapy and immune checkpoint blockade (ICB) treatment. We demonstrate that the combination of immunomodulatory low-dose Cyclophosphamide (CTX) coupled with anti-CSF-1R antibody targeted therapy (SNDX-ms6352) and anti-PD-1 (ICB), was highly effective against aggressive metastatic Trp53 null TNBC transplantable syngeneic models that present with high macrophage infiltration. Mechanistically, CSF-1R inhibition along …

Deep-Learning Serial Ct Prediction Of Survival In Immunotherapy-Treated Non-Small Cell Lung Cancer., Chiharu Sako, Brenda F Kurland, Taly G Schmidt, Jing He, Marius De Groot, Arpan A Patel, Dwight H Owen, Arya Amini, Brendan D Curti, Ronan J Kelly, Ray D Page, Aurelie Swalduz, Jean-Paul Beregi, Jan Chrusciel, Stephane Sanchez, Jakob Weiss, An Liu, Olivier Gevaert, Alma Hart, George R Simon, Ravi B Parikh, Jasper Van Der Aart, Petr Jordan

Oncology Articles

IMPORTANCE: Reliable early response biomarkers for overall survival (OS) are lacking for patients receiving immune checkpoint inhibitor (ICI) therapy for advanced non-small cell lung cancer (NSCLC). Existing imaging-based measures, such as Response Evaluation Criteria in Solid Tumors (RECIST) and tumor volume change (TVC), have limited predictive value for long-term outcomes, and advanced imaging-based biomarkers may enhance decision-making in clinical practice and clinical trials.

OBJECTIVE: To develop and validate a fully automated deep-learning imaging-based biomarker using pretherapy and 12-week follow-up computed tomography (CT) scans.

DESIGN, SETTING, AND PARTICIPANTS: This prognostic study used retrospectively collected HER data from routine clinical practice (RCP) …

Career Plans Among Graduating Us Emergency Medicine Residents, Dave W. Lu, Bo Gu, D. Mark Courtney, Bryan G. Kane, Michelle D. Lall, Michael Gottlieb, Yvette Calderon, Christopher Bennett

Department of Emergency Medicine Faculty Papers

IMPORTANCE: The emergency medicine (EM) workforce is undergoing complex change, including a potential projected physician surplus, the volatile and evolving interests of medical students, and the continued high rates of burnout. Understanding the career intentions of graduating residents is critical to inform workforce planning.

OBJECTIVE: To examine the career plans, anticipated career durations, and key factors associated with the career decisions of graduating US EM residents.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study, which sampled graduating residents from all Accreditation Council for Graduate Medical Education-accredited categorical EM programs, was conducted after the 2023 American Board of Emergency Medicine In-Training …

Career Plans Among Graduating Us Emergency Medicine Residents, Dave W. Lu, Bo Gu, D. Mark Courtney, Bryan G. Kane, Michelle D. Lall, Michael Gottlieb, Yvette Calderon, Christopher Bennett

Department of Emergency Medicine Faculty Papers

IMPORTANCE: The emergency medicine (EM) workforce is undergoing complex change, including a potential projected physician surplus, the volatile and evolving interests of medical students, and the continued high rates of burnout. Understanding the career intentions of graduating residents is critical to inform workforce planning.

OBJECTIVE: To examine the career plans, anticipated career durations, and key factors associated with the career decisions of graduating US EM residents.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study, which sampled graduating residents from all Accreditation Council for Graduate Medical Education-accredited categorical EM programs, was conducted after the 2023 American Board of Emergency Medicine In-Training …

Cost-Effectiveness Of Home-Based Self-Sampling Vs Clinician Sampling For Anal Precancer Screening, Haluk Damgacioglu, Timothy L Mcauliffe, Timothy J Ridolfi, Elizabeth Chiao, Maria E Fernandez, Vanessa Schick, Jennifer S Smith, Bridgett Brzezinski, Jenna Nitkowski, Ashish A Deshmukh, Alan G Nyitray

Faculty, Staff and Student Publications

Importance: Anal cancer screening is recommended for high-risk populations, particularly sexual and gender minority (SGM) individuals. However, the cost-effectiveness of home-based self-sampling in increasing anal cancer screening uptake has not yet been evaluated in the US.

Objective: To evaluate the cost-effectiveness of home-based anal self-sampling compared with clinic-based screening among SGM individuals.

Design, setting, and participants: This economic evaluation used data from a 2-group randomized clinical trial conducted in Milwaukee, Wisconsin, from January 2020 to August 2022, enrolling SGM individuals aged 25 years or older. Participants were randomized to home-based self-sampling or clinic-based screening. Costs for home-based screening were obtained …

Cholesterol Efflux Protein, Abca1, Supports Anticancer Functions Of Myeloid Immune Cells, Shruti V Bendre, Yu Wang, Basel Hajyousif, Rajendra K C, Shounak G Bhogale, Dhanya Pradeep, Natalia Krawczynska, Claire P Schane, Erin Weisser, Avni Singh, Simon Han, Hannah Kim, Lara Kockaya, Anasuya Das Gupta, Adam T Nelczyk, Hashni Epa Vidana Gamage, Yifan Fei, Desirée Rodríguez-Casiano, Xingyu Guo, Haoyun Li, Ryan J Deaton, Fei Mo, Maria Sverdlov, Peter H Gann, Saurabh Sinha, Sahil Sahni, Kun Wang, Kevin Van Bortle, Emad Tajkorshid, Wendy A Woodward, Wonhwa Cho, Erik R Nelson

Faculty, Staff and Student Publications

Breast and other solid tumors respond poorly to immune therapy. Myeloid cells (MCs) such as macrophages contribute to resistance. Established clinical evidence links cholesterol to cancer outcomes, with MC function being regulated by cholesterol metabolism. We screened MC-expressed regulators of cholesterol homeostasis linked to survival and identified the cholesterol efflux protein ABCA1. ABCA1 activity increases anticancer functions of macrophages: enhancing tumor infiltration, decreasing angiogenic potential, reducing efferocytosis, and improving support of CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, through both PI3K-dependent and PI3K-independent mechanisms. Highlighting the clinical relevance of our findings are correlations between ABCA1 in macrophages …

Nf2 Loss Malignantly Transforms Human Pancreatic Acinar Cells And Enhances Cell Fitness Under Environmental Stress, Yi Xu, Michael H Nipper, Angel A Dominguez, Chenhui He, Francis E Sharkey, Sajid Khan, Han Xu, Daohong Zhou, Lei Zheng, Yu Luan, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) occurs as a complex, multifaceted event driven by the interplay of tumor-permissive genetic mutations, the nature of the cellular origin, and microenvironmental stress. In this study, using primary human pancreatic acinar 3D organoids, we performed a CRISPR-KO screen targeting 199 potential tumor suppressors curated from clinical PDAC samples. Our data revealed significant enrichment of a list of candidate genes, with neurofibromatosis type 2 associated gene (NF2) emerging as the top target. Functional validation confirmed that loss of NF2 promoted the transition of PDAC to an invasive state, potentially through extracellular matrix modulation. NF2 inactivation …

Racial, Ethnic, And Socioeconomic Survival Disparities In Early-Onset Metastatic Colorectal Cancer, Jennifer S Wang, Benny Johnson, Caitlin C Murphy

Faculty, Staff and Student Publications

Importance: Rates of metastatic colorectal cancer (mCRC) are rising among young adults. Disparities by race and ethnicity and neighborhood-level socioeconomic status (SES) among this population are understudied.

Objective: To examine the association of race and ethnicity and neighborhood-level SES with mortality among a community-based sample of young adults with mCRC.

Design, setting, and participants: This cohort study used a large electronic health record-derived database of young adults with cancer treated at 280 community-based US clinics between 2013 and 2021. Eligible patients were young adults aged 18 to 49 years diagnosed with de novo or recurrent mCRC. Patients were followed up …

Reported Safety Practices Of Publicly Advertised Psychedelic Retreats, Amy L Mcguire, Logan Neitzke-Spruill, Jill O Robinson, Caroline S Beit, Nikita Singh, David S Mathai, Lynnette A Averill

Center for Medical Ethics and Health Policy Staff Publications

Importance: The availability of psychedelic retreats has grown to meet the demand for access to these substances. Despite centuries of use among Indigenous communities, psychedelics can pose serious risks for some users.

Objective: To determine safety precautions that retreat organizations that offer psychedelic substances currently use.

Design, setting, and participants: This qualitative study included structured interviews conducted by phone or email with representatives from 49 organizations publicly advertising psychedelic retreat offerings from July to October 2023. Organizations were eligible if they marketed their services in English, offered at least 1 psychedelic substance, and made contact information available online. Organizations were …

Prospective Audit And Feedback By Antibiotic Stewardship Teams To Reduce Antibiotic Overuse At Hospital Discharge: A Stepped-Wedge Cluster-Randomized Clinical Trial, Daniel J Livorsi, Michael Joshua Hendrix, Erin Rachmiel, Jahnavi Bongu, Alice Bewley, Kevin Hsueh, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Antibiotics prescribed at hospital discharge are frequently unnecessary or suboptimal. Strategies to improve prescribing are not well defined.

OBJECTIVE: To evaluate whether a discharge-focused prospective audit and feedback process decreases antibiotic overuse at hospital discharge.

DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster-randomized clinical trial was conducted across participating units at 10 hospitals with antibiotic stewardship (AS) teams and supporting staff from December 5, 2022, to November 17, 2023. After a 24-week baseline period, 1 hospital crossed into the intervention arm every 2 weeks.

INTERVENTION: The intervention consisted of disseminating institutional guidelines for oral antibiotic step-down to frontline prescribers and …

Cumulative Lifespan Stress, Inflammation, And Racial Disparities In Mortality Between Black And White Adults, Isaiah D Spears, Aaron J Gorelik, Sara A Norton, Michael J Boudreaux, Megan W Wolk, Jayne Siudzinski, Sarah E Paul, Mary A Cox, Cynthia E Rogers, Thomas F Oltmanns, Patrick L Hill, Ryan Bogdan

2020-Current year OA Pubs

IMPORTANCE: In the US, Black individuals experience higher mortality risk than White individuals. Greater stress exposure and its biological sequelae are theorized to drive this heightened risk.

OBJECTIVE: To evaluate whether greater cumulative lifespan stress exposure and elevated inflammation are associated with increased mortality risk among Black compared with White US individuals.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study (St Louis Personality and Aging Network) recruited participants from 2007 to 2011 from the St Louis, Missouri, metropolitan area. Participants were required to have a mailing address to permit longitudinal follow-up and sixth grade reading level to facilitate understanding of …

White Matter Hyperintensity Burden And Decline In Driving Performance Among Older Adults, Madhur Parihar, Yasheng Chen, Byron Xu, Semere Bekena, Ramkrishna K Singh, Yiqi Zhu, Jean-Francois Trani, Jin-Moo Lee, David B Carr, Chia-Ling Phuah, Ganesh M Babulal, Driving Real-World In-Vehicle Evaluation System (Drives) Project

2020-Current year OA Pubs

IMPORTANCE: White matter hyperintensity (WMH) burden is associated with cognitive decline, but its association with driving performance among older adults and the associations of modifiable risk factors remain unclear.

OBJECTIVE: To evaluate the association of total and regional WMH burden with longitudinal naturalistic driving performance in cognitively normal older adults and evaluate moderating associations of cognitive decline and antihypertensive therapy.

DESIGN, SETTING, AND PARTICIPANTS: This prospective longitudinal cohort study enrolled community-dwelling older adults (≥65 years) in the Driving Real-World In-Vehicle Evaluation System Project. Baseline 3-T brain magnetic resonance imaging (MRI) scans and data from continuous in-vehicle driving monitoring were collected …

Impaired Complement Regulation Drives Chronic Lung Allograft Dysfunction After Lung Transplantation, Hrishikesh S. Kulkarni, Laneshia K. Tague, Fuyi Liao, Zhiyi Liu, Lorena Garnica, Nishanth R. Shankar, Xiaobo Wu, Dequan Zhou, Yan Tao, Victoria E. Davis, Cory T. Bernardt, Derek E. Byers, Chad A. Witt, Daniel Kreisel, John P. Atkinson, Andrew E. Gelman, Et Al.

2020-Current year OA Pubs

A greater understanding of chronic lung allograft dysfunction (CLAD) pathobiology, the primary cause of death after lung transplantation (LTx), is needed to improve outcomes. The complement system links innate to adaptive immune responses and is activated early after lung transplantation to form C3 convertase, a critical enzyme that cleaves the central complement component C3. We hypothesized that LTx recipients with a genetic predisposition to enhanced complement activation have worse CLAD-free survival mediated through increased adaptive alloimmunity. We interrogated a known functional C3 polymorphism (C3 R102G) that increases complement activation through impaired C3 convertase inactivation in 2 independent LTx recipient cohorts. …

Amyloid Β-Cholesterol Interplay: Removal Of Cholesterol From The Membranes To Catalyze Aggregation And Amyloid Pathology, Rishiram Baral, Ruan Van Deventer, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

The interplay between the cholesterol metabolism and assembly of Aβ42 (the 42-residue form of the amyloid-β peptide) peptides in pathological aggregates is considered one of the major molecular mechanisms in the development of Alzheimer's disease (AD). Numerous in vitro studies led to the finding that high cholesterol levels in membranes accelerate the production of Aβ aggregates. The molecular mechanisms explaining how cholesterol localized inside the membrane bilayer catalyzes the assembly of Aβ aggregates above the membrane remain unknown. We addressed this problem by combining different AFM modalities, including imaging and force spectroscopy, with fluorescence spectroscopy. Our combined studies revealed that …

Differential Sensitivity Of Leukocyte Populations To Staphylococcus Aureus Biofilm, Nichole D. Brandquist, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of prosthetic joint infection (PJI) typified by biofilm formation. Anti-inflammatory granulocytic myeloid-derived suppressor cells (G-MDSCs) represent the main leukocyte population in a mouse model of S. aureus PJI, followed by neutrophils (PMNs), and macrophages (Mφs), which is also seen during human PJI. Defining how each leukocyte population responds to S. aureus biofilm vs planktonic bacteria could have important implications for how S. aureus evades immune detection to facilitate biofilm persistence. This study compared the kinetics of leukocyte death and relationship to mitochondrial ROS (mtROS) production following exposure to planktonic S. aureus or biofilm. Mφs …

Somatosensory Realignment Following Single And Dual Force-Field Adaptation, Dylan Zangakis, Aaron Wong, Amanda S. Therrien

Moss-Magee Rehabilitation Papers

Evidence that adaptive motor learning coincides with a realignment of somatosensory perception has led to hypotheses that a shared mechanism underlies both processes. This implies that these two phenomena should exhibit similar properties. However, studies of somatosensory realignment with visuomotor adaptation have shown mixed support, possibly due to a confounding coactivation of sensory prediction errors and multisensory integration. Although the former is thought to drive adaptation, both processes may contribute to somatosensory realignment. Here, we examined somatosensory realignment following force-field adaptation, which is not confounded by multisensory integration. Across two experiments, we tested whether somatosensory realignment mimics three canonical properties …

Factors Affecting Detection And Quantification Of Schistosoma Haematobium Eggs In Pooled Urine Samples, Abraham Degarege, Bruno Levecke, Christopher R. Bilder, David Brett-Major, Abebe Animut, Yohannes Negash, M. Jana Broadhurst, Tzeyu L. Michaud, Berhanu Erko

Journal Articles: Epidemiology

BACKGROUND: Building on our previous work showing that pooled urine testing can rapidly detect Schistosoma haematobium infections but has limited sensitivity in low-intensity settings or with large pool sizes, this study evaluated how urine volume, pool size, infection intensity, and diagnostic method affect the detection and quantification of S. haematobium eggs in pooled samples.

METHODS: Between July 2022 and April 2023, 2,134 urine samples from school-age children living in three regional states of Ethiopia were individually examined by deploying urine filtration microscopy (UFM). Subsequently, 5, 10, 20 and 40 individual samples were strategically pooled and examined by deploying UFM and …

Strengthening Rural Health Care: A Scoping Review Of Nurse Recruitment And Retention Strategies, Kelley Arredondo, Laura Witte, Alexander Paterson-Roberts, Alexandra Caloudas, Matthew Vincenti, Bradley V Watts, Bronwyn Sutherland, Hilary Touchett

Library Staff Publications

Background: Despite nursing being the largest US health profession, only 16% of registered nurses (RNs) practice in rural areas, where health care access is limited. This significantly impacts rural residents, including over 2.7 million rural veterans receiving care at the Veterans Health Administration, leading to compromised health outcomes. Nurses are vital in primary care, improving coordination and management of chronic conditions.

Objectives: Identify recruitment and retention programs for rural nurses (licensed vocational nurses/licensed practical nurses and RNs), including strategy characteristics and location.

Research design: We conducted a scoping review of published and gray literature. Eligible studies targeted US rural nurse …