Medicine and Health Sciences Commons^™

Lymphoid Gene Expression Supports Neuroprotective Microglia Function, Pinar Ayata, Maud Gratuze, Jason D Ulrich, David M Holtzman, Et Al.

2020-Current year OA Pubs

Microglia, the innate immune cells of the brain, play a defining role in the progression of Alzheimer's disease (AD)

Short-Lived Relief: The Racial Geography Of Rebounding Eviction Rates In Postmoratorium St. Louis, Anne Brown, Samuel H. Kye, Yi Wang

2020-Current year OA Pubs

No abstract provided.

Eus-Guided Fine-Needle Biopsy Sampling Of Solid Pancreatic Masses With And Without Rapid Onsite Evaluation For Commercial Next-Generation Genomic Profiling, Mohamad Dbouk, Brenton G Davis, Matthew Peller, Erika Sloan, Thomas Hollander, Juan Pablo Reyes-Genere, Ahmad Bazarbashi, Mohammad K Ismail, Gabriel Lang, Vladimir Kushnir, Dayna Early, Samuel Ballentine, Sun-Chuan Dai, Abdul Kouanda, Koushik K Das

2020-Current year OA Pubs

BACKGROUND AND AIMS: Although EUS-guided fine-needle biopsy sampling (EUS-FNB) of solid pancreatic lesions with or without the use of rapid onsite evaluation (ROSE) provides a high diagnostic yield, the utility of ROSE for commercial genomic analysis is unclear.

METHODS: A multicenter retrospective review was conducted of consecutive patients where genomic analysis was requested from EUS-FNB of solid pancreatic lesions, performed with 22-gauge fine-needle biopsy (FNB) needles. Data were collected at 2 academic centers, one that routinely uses ROSE to assess adequacy for all EUS-FNB cases (University of California San Francisco, n = 44) and one that does not use ROSE …

Introducing The Outpace Framework For Health Care Quality Improvement, Michele Bolles, Heather M. Alger, Mitchell S. V. Elkind, Howard Haft, Sabra C. Lewsey, Mariell Jessup, Karen E. Joynt Maddox, Chiadi E. Ndumele, Clyde W. Yancy, Christine Rutan, Michelle Congdon, Katherine Overton, Lynn Serdynski, Kathie Thomas, Gregg C. Fonarow

2020-Current year OA Pubs

Equitable, timely, and evidence-based care remains a central goal across health care ecosystems, yet significant quality gaps, care variability, and health disparities persist. Professional societies, including the American Heart Association, have long developed clinical practice guidelines to provide standardized, evidence-based recommendations across the cardiovascular care continuum. These guidelines are operationalized into quality measures to monitor care, identify gaps, and guide improvement. Professional societies, agencies, and health systems have applied implementation science strategies, such as education, data sharing, and evaluation, to improve care quality and achieve quality measures defined in the clinical practice guidelines. American Heart Association's Get With The Guidelines …

Obesity Promotes Conserved Inflammatory And Metabolic Transcriptional Programs In Colon Tumors: Evidence From Mouse Models And The Colocare Study Patient Cohort, Elaine M Glenny, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: The global prevalence of obesity, an established risk and progression factor for colon cancer, is high and rising. Unfortunately, the mechanisms underlying the obesity-colon cancer association are incompletely understood, and new molecular targets enabling more effective intervention strategies to break the obesity-colon cancer link are urgently needed.

OBJECTIVES: This study integrated RNA sequencing data from mouse and human colon tumor samples, as well as human adipose samples, to rigorously establish obesity-associated transcriptomic signatures conserved between the 2 species.

METHODS: We employed a mouse colon cancer model with colonoscopy-guided orthotopic transplantation of syngeneic Apc

RESULTS: Diet-induced obesity reduced survival in …

Streptavidin-Drug Conjugates Streamline Optimization Of Antibody-Based Hematopoietic Stem Cell Transplant Conditioning, Aditya R Yelamali, Ezhilarasi Chendamarai, Julie K Ritchey, Michael P Rettig, John F Dipersio, Stephen P Persaud

2020-Current year OA Pubs

Hematopoietic stem cell transplantation (HSCT) conditioning using antibody-drug conjugates (ADC) is a promising approach to preparing patients for transplant, potentially avoiding the severe toxicities of conventional chemotherapy- and irradiation-based conditioning regimens. The toxic payload determines the efficacy and potential toxicities of an ADC, but comparison of different payloads in conjugates designed for HSCT conditioning has not been reported. Such comparisons would be greatly facilitated by methods enabling efficient screening of many combinations of antibody and payload. Herein, we used Click chemistry to conjugate four different small molecule payloads to a streptavidin backbone, yielding streptavidin-drug conjugates that can be combined with …

Mechanical Explanation For The Hemodynamic Efficacy Of Right Atrial Appendage Autografts Used In Neo-Semilunar Valve Leaflet Reconstruction, Andrew Behrmann, Kate Appleman, Katarina Lettner, Balaji Cherupala, Jessica Cayton, Shamik Bhattacharya, Pirooz Eghtesady

2020-Current year OA Pubs

BACKGROUND: Pediatric pulmonic and aortic valve insufficiency has recently been treated with novel procedures that use autologous right atrial appendage tissue. Whether atrial tissue's tensile strength correlates with pressures it can withstand to function as a neo-semilunar valve has not been studied. We therefore studied these properties using an ex vivo porcine heart model.

METHODS: Aortic cusps, pulmonic cusps, and right and left atrial appendage tissues were excised from 10 porcine hearts. Native leaflets and atrial appendage samples underwent circumferential and radial stretching by a uniaxial tensile machine. Right atrial appendage tissue from 14 additional porcine hearts was used to …

Proteogenomics In Cerebrospinal Fluid And Plasma Reveals New Biological Fingerprint Of Cerebral Small Vessel Disease, Ilana Caro, Daniel Western, Chengran Yang, Jigyasha Timsina, Laura Ibanez, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific treatment, of which molecular mechanisms remain poorly understood. To identify potential biomarkers and therapeutic targets, we applied Mendelian randomization to examine over 2,500 proteins measured in plasma and, uniquely, cerebrospinal fluid, in relation to magnetic resonance imaging (MRI) markers of cSVD in more than 40,000 individuals. Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid. We highlight associations that are consistent across platforms and ancestries, and supported by complementary observational analyses, and we explore differences …

Clinical Characteristics And Real-World Outcomes In Patients With Mucopolysaccharidosis Ii Over 18 Years: Final Report Of The Hunter Outcome Survey, Joseph Muenzer, Jaco Botha, Hernan Amartino, Roberto Giugliani, Paul Harmatz, Christoph Kampmann, Bianca Link, Shuan-Pei Lin, David Molter, Julian Raiman, Maurizio Scarpa, Anna Tylki-Szymańska, Siddharth Jain, David A H Whiteman, Barbara K Burton

2020-Current year OA Pubs

BACKGROUND: Mucopolysaccharidosis II (MPS II) is a rare, progressive, X-linked lysosomal storage disease. Enzyme replacement therapy (ERT) with intravenous (IV) idursulfase has been approved for the treatment of patients with MPS II since 2005. The Hunter Outcome Survey (HOS; NCT03292887) was established as a condition of approval to monitor the long-term safety and effectiveness of idursulfase. Here, we report the final results from HOS.

METHODS: HOS was a multicenter, long-term, observational registry that enrolled patients with a biochemically and/or genetically confirmed diagnosis of MPS II who were untreated or treated with idursulfase and/or bone marrow transplant. Patients were enrolled prospectively …

Risk Factors For Early Right Ventricular-To-Pulmonary Artery Conduit Failure In Congenital Heart Disease, Fawaz Naeem, Travus J White, J William Gaynor, Xuemei Zhang, Steve Ampah, Andrew C Glatz, Laura Mercer-Rosa, Meryl S Cohen

2020-Current year OA Pubs

OBJECTIVES: Right ventricle-to-pulmonary artery conduits are a mainstay of treatment for patients with congenital heart defects. We investigated the association of underlying genetic abnormalities with conduit failure and hypothesized that 22q11.2 deletion syndrome was associated with shorter time to failure.

METHODS: We conducted a single-center retrospective cohort study at the Children's Hospital of Philadelphia. Patients who underwent right ventricle-to-pulmonary artery conduit placement as part of a biventricular repair at 0 to 24 months of age between January 2010 and June 2020 were included. The primary exposure of interest was diagnosis of 22q11.2 deletion syndrome, and the outcome was time to …

Improved Accuracy For Myocardial Blood Flow Mapping With Deep Learning-Enabled Cmr Arterial Spin Labeling (Deepmasl): Validation By Microsphere In Vivo, Ran Li, Caleb Berberet, Qi Huang, Pamela K Woodard, Jie Zheng

2020-Current year OA Pubs

BACKGROUND: Current myocardial arterial spin labeling (ASL) methods are sensitive to noise (background and physiology), which limits the accuracy of myocardial blood flow (MBF) measurement. In this study, we demonstrated a new deep learning-enabled myocardial ASL approach (DeepMASL) and evaluated its accuracy to quantify MBF in a canine model of coronary arterial disease in vivo. The reference method was invasive microsphere measurements.

METHODS: Eighteen mongrel dogs were divided into two groups: healthy (n = 9) and coronary stenosis (n = 9). The latter was induced in an open-chest model with 3 types of stenosis: 50% (n= 3), 70% (n = …

Semi-Annual And Annual Mass Drug Administration Of Diethylcarbamazine And Albendazole Are Equally Effective Regimens For Eliminating Lymphatic Filariasis In Papua New Guinea, Michael C. Payne, Nelly Sanuku, Brooke E. Mancuso, Yao-Chieh Cheng, Gary J. Weil, Peter U. Fischer, Moses Laman, Leanne J. Robinson, Daniel J. Tisch, Christopher L King

2020-Current year OA Pubs

Annual mass drug administration (MDA) is currently recommended for the local elimination of lymphatic filariasis (LF). Modeling studies of LF transmission suggest that conducting MDA twice a year could accelerate LF elimination. To test this idea, we compared the effects of 3 rounds of yearly MDA and 5 rounds of semiannual MDA using diethylcarbamazine with albendazole on LF infection measures in Papua New Guinea (PNG) across 2 treatment areas with high LF prevalence. From 2013 to 2018, we conducted 4 annual community surveys at 4 sentinel sites in each treatment area. We sampled 2,854 people at the start and 2,746, …

Molecular Response To The Non-Lytic Peptide Bac7 (1-35) Triggers Disruption Of Klebsiella Pneumoniae Biofilm, Robert L Beckman I V, Berta Martinez, Flor Z. Santiago, Gabriela N. Echeverria, Bruno V. Pinheiro, Marcelo D. T. Torres, Logan Suits, Shantal Garcia, Paeton L. Wantuch, Cesar De La Fuente-Nunez, Prahathees Eswara, David A. Rosen, Renee M. Fleeman

2020-Current year OA Pubs

Klebsiella pneumoniae is becoming increasingly difficult to treat as multidrug-resistant (MDR) strains become more prevalent. The formation of biofilm heightens this threat by embedding bacterial cells in a polysaccharide-rich matrix that limits antibiotic penetration. Here we dissect the anti-biofilm bovine host-defense cathelicidin peptide fragment bac7 (1-35), exploring its anti-biofilm mechanism, evaluating its ability to curb colonization of the vital organs by hypervirulent K. pneumoniae, and testing its breadth of activity against diverse clinical isolates. Transcriptomic profiling revealed that bac7 (1-35) simultaneously compromises the bacterial membrane and inhibits ribosomal function, a dual assault that precipitates rapid biofilm collapse and blocks bacterial …

The Impact Of Sleep In High-Risk Infants, Ann-Cathrine Neukamm, Mirja Quante, Christian F Poets, Renée A Shellhaas, “Neonatal Sleep Talks (Nest)” Group

2020-Current year OA Pubs

Most of an infant's day is devoted to sleep - and normal sleep is vital to normal brain development. Sleep disruptions may impair overall health, well-being, and neurodevelopment. Disruptors of sleep and circadian health, such as noise, light, respiratory support, and clinical interventions, are highly prevalent in hospital and nursing care facilities. These factors particularly affect infants who already have an increased risk of sleep disorders and their consequences due to an underlying disease. Preterm infants and infants with disorders such as neonatal abstinence syndrome, craniofacial malformations, congenital heart disease, hypoxic-ischemic encephalopathy, Chiari-malformation/myelomeningocele, congenital musculoskeletal disease, and Down syndrome are …

Does Health Insurance Coverage Improve Cardiometabolic Risk Factor Levels? Quasi-Experimental Evidence From India, Kavita Singh, Anubha Agarwal, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Chronic conditions cause notable health and economic burdens. While health insurance enables access to healthcare, its effects on chronic care outcomes remain under-explored.

OBJECTIVE: To examine the association between health insurance coverage and cardiometabolic risk factors among people with chronic conditions in India.

METHODS: Data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) and Solan studies, including 2,926 adults with chronic conditions were analyzed using propensity score weighting to evaluate the associations between health insurance and cardiometabolic risk factors (HbA1c, low-density lipoprotein cholesterol [LDLc], and blood pressure [BP]) and self-reported health status (measured using European Quality …

Cholinergic Dysfunction In Occupational Manganese Exposure, T Noah Hutson, Susan Searles Nielsen, Natalie Senini, John O'Donnell, Hubert P Flores, Tamara Hershey, Joel S Perlmutter, Anil Kumar Soda, Stephen M Moerlein, Zhude Tu, Michael Kasper, Lianne Sheppard, Brad A Racette, Susan R Criswell

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVE: Excessive exposure to manganese (Mn) produces a clinical syndrome of parkinsonism and cognitive impairment. However, our understanding of the mechanisms of Mn neurotoxicity remains limited. This study aimed to evaluate the relationships between Mn exposure, cholinergic function, and cognitive impairment in exposed workers.

METHODS: We assessed brain cholinergic function using vesicular acetylcholine transporter (VAChT) radiotracer (-)-(1-(8-(2-[(18)F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-piperidin-4-yl)(4-fluorophenyl)methanone (VAT) with positron emission tomography (PET) in 21 Mn-exposed workers. We estimated occupational Mn exposure from work histories and the MRI pallidal index. A cognitive control battery consisting of the Verbal Fluency (VF), Letter Number Sequencing (LNS), Two-Back Letter Task (2B), …

Rhinovirus C15 Infection Induces Airway Epithelial Cell Remodeling And Robust Inflammatory Responses: Potential Implications For Airway Obstruction In Children, Yiran Li, Shilpi Singh, Hannah L Briggs, Jordan E Kreger, Alex L Sliwicki, Emily L Eberhardt, Shiuhyang Kuo, Jessica A Czapla, J Kelley Bentley, Heidi R Flori, Amjad Horani, Steven L Brody, Marc B Hershenson

2020-Current year OA Pubs

Despite recognition of rhinovirus-C (RV-C) as a cause of severe respiratory exacerbations, little is known about the pathogenesis of RV-C infections. We infected mucociliary-differentiated primary tracheobronchial epithelial cells with RV-C15 or RV-A16. Initial RNASeq data showed that, compared to RV-A16, RV-C15 decreased expression of genes related to ciliary function while increasing expression of genes associated with mucus secretion and inflammation. Using different airway epithelial cell isolates, we confirmed greater reduction in DNAI2 and FOXJ1 (regulates production of motile cilia) and increased FOXA3 (regulates mucin -related gene expression) after RV-C15 infection compared to RV-A16. Similarly, nasal swab samples from children with …

Early And Mid-Term Outcomes Of Mitral Annular Calcification And Transcatheter Mitral Therapy: A Systematic Review, Yosuke Sakurai, Ashton Mcdonald, Tsuyoshi Kaneko

2020-Current year OA Pubs

BACKGROUND: Mitral annular calcification (MAC) poses technical and clinical challenges in patients undergoing mitral valve intervention. Patients with severe MAC were excluded from major previous randomized controlled trials evaluating mitral therapies. Consequently, outcomes following mitral transcatheter edge-to-edge repair (M-TEER) in this population remain controversial.

METHODS: MEDLINE and EMBASE were searched through June 2025 to identify studies reporting outcomes after M-TEER in patients with MAC. This systematic review assessed the difference in MAC grading and M-TEER eligibility across studies. The definition of procedural success was documented to highlight inconsistencies. The primary endpoint was all-cause mortality during follow-up. Secondary endpoints included procedural …

Peptide Vaccines For Pediatric High-Grade Glioma And Diffuse Midline Glioma: Current Progress And Future Perspectives, Aron K Mebrahtu, Vatsal Jain, Eliese M Moelker, Alexandra M Hoyt-Miggelbrink, Katayoun Ayasoufi, Eric M Thompson

2020-Current year OA Pubs

High-grade gliomas (HGGs) and diffuse midline gliomas (DMGs) in pediatric patients carry a poor prognosis, necessitating the rapid development of novel therapies. Peptide vaccines represent a safe, repeatable, and rational immunotherapeutic modality aimed at inducing potent, tumor-specific T-cell responses. In this review, we define the scope of current progress by arguing that immunogenicity in children with HGG/DMG hinges on three factors: appropriate antigen class (neoantigen vs. TAA), the use of potent immunoadjuvants, and successful navigation of immune suppression. To address the gap between biological promise and clinical reality, we analyze clinical trials targeting shared tumor-associated antigens (e.g., CMV pp65, Survivin) …

Implementing And Evaluating Visual Key Information Pages Compared To Text-Based Key Information: Protocol For A Stepped-Wedge Cluster Randomized Trial, Krista E Cooksey, Eliana C Goldstein, Clara N Lee, Jessica Mozersky, Kimberly A Kaphingst, Jingxia Liu, Shuang Wu, Molly Volkmar, Victor Catalan-Gallegos, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Informed consent is a key aspect of conducting research studies, yet many participants do not understand critical study details after reviewing long, complex consent documents. The 2018 Common Rule aimed to address this challenge by requiring a key information section, a "concise and focused" presentation of important and relevant study information. In our ongoing work, we developed a template and toolkit to improve the presentation of key information by incorporating health literacy best practices, including color and visual icons. The goal of this study is to assess the impact of the visual key information (KI) pages at both the …

Development Of Intestinal Tissue-Resident T Cells In Early-Life Mice Before And After Weaning, Catherine Montenegro, Siyuan Ding, Federico Perdomo-Celis, Manuel A Franco

2020-Current year OA Pubs

Intestinal tissue-resident T cells have been poorly characterized during early-life. Here, we phenotypically characterized tissue-resident (intravascular staining negative) CD4

Participatory Implementation Science To Enhance Knowledge And Build The Capacity To Increase The Uptake And Sustainability Of Hpv Vaccination Among Girls In Nigeria, Peter Kalulu, Olufunto A Olusanya, Nkiruka Obodoechina, Maria A Afadapa, Temitope Ojo, Priscilla A Kabutey, Caven N Ngoe, Ashley Bardon, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Human papillomavirus (HPV) vaccination can prevent cancer in low- and middle-income countries (LMICs), but its uptake remains low, especially in Nigeria. Understanding participatory approaches can help identify local strategies to increase, build capacity for, and sustain vaccine uptake. This study evaluated the effectiveness of an innovation bootcamp in enhancing the knowledge and skills of youth implementers about HPV and cervical cancer as a strategy to increase vaccine uptake among Nigerian girls aged 9-14 years. An innovation bootcamp is an intensive training program that engages end users to build capacity and skills.

METHODS: This was a five-week hybrid bootcamp guided …

Structure Of An Lgr Dimer, An Evolutionary Predecessor Of Glycoprotein Hormone Receptors, Zhen Gong, Shuobing Chen, Ziao Fu, Brian Kloss, Chi Wang, Jonathan Kim, Oliver B Clarke, Qing R Fan, Wayne A Hendrickson

2020-Current year OA Pubs

Glycoprotein hormones (GpHs) produced in the human pituitary act through receptors (GpHRs) in the gonads to support reproduction and in the thyroid for metabolism. GpHs are heterodimeric cystine-knot proteins; their receptors bind cognate hormones at an extracellular domain and signal through a transmembrane domain to heterotrimeric G proteins. GpHs and GpHRs have co-evolved from invertebrate counterparts. Structures of the human receptors as isolated for cryogenic electron microscopy (cryo-EM) are all monomeric despite compelling evidence for their functioning as dimers. Here we characterize the homologous receptor from Caenorhabditis elegans. Its biochemical properties are notably similar to those of the thyroid stimulating …

Variation In State Policies On Sideline Medical Coverage Of High School Athletic Events, Marcus Allen, Aravind Athiviraham, Darlington Nwaudo, Lutul D Farrow, Aossm Bold Study Group, Matthew Matava

2020-Current year OA Pubs

BACKGROUND: Certified athletic trainers (ATs) are the primary source of sideline coverage for high school athletic events, providing an essential role in student-athlete health. However, there is a paucity of literature evaluating the existence of state requirements regarding the presence of ATs and mandatory sideline medical coverage of high school athletic events.

HYPOTHESIS: It was hypothesized that there is significant variation among state policies on sideline medical coverage and AT requirements for high school athletic events.

STUDY DESIGN: Cross-sectional study.

METHODS: A 17-question survey was emailed to the executive directors (or analogous position) of the state high school athletic associations …

So What? Elevating The Impact Of Implementation Science, Ross C Brownson, Juliet Iwelunmor, Thomas A Odeny, Enola K Proctor, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: Given the substantial public funding of health-related research, tangible benefits of this support must be demonstrated. Implementation science provides actionable methods to enhance population health, reduce health inequities, and guide effective public health and clinical practices and policies. We must elevate the notion of impact (the "so-what gap") and the role of implementation science, particularly in university settings.

MAIN TEXT: We distinguish between scientific output and impacts. Impacts in implementation science are commonly defined as improvements in health outcomes, quality of life, quality of services, or policy change. In contrast, traditional academic outputs, such as citation counts and grant …

Successful Implementation Of Stroke Risk Screening For Sickle Cell Anemia In The Displace Study: Results Of A Cluster Randomized Trial, Alyssa M Schlenz, Monica L Hulbert, Et Al.

2020-Current year OA Pubs

BACKGROUND: Stroke risk screening using transcranial Doppler (TCD) is a critical evidence-based tool for children with sickle cell anemia (SCA) that has been poorly implemented in the United States. The Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) study was designed to improve rates of stroke risk screening for SCA using interventions informed by an extensive multi-level barriers and facilitators assessment. This report describes the final outcomes of a large, randomized implementation trial comparing two intervention arms: 1) an application designed to track TCD implementation, ProviderMinder™, versus 2) ProviderMinder™ plus a single coordinator intervention. All sites …

Strengthening Implementation Science Research To Improve Adolescent And Young Adult Hiv-Prevention And Care In Sub-Saharan Africa: Patc3h-In, Geri R Donenberg, Ucheoma Nwaozuru, Sylvia Adebajo, Joseph D Tucker, Juliet Iwelunmor, Lisa M Kuhns, Brenda Gati Mirembe, Lisa Hightow-Weidman, Brian Zanoni, Tapiwa A Tembo, Maria Felix Lupogo, Franklin Yates

2020-Current year OA Pubs

BACKGROUND: Despite significant progress in HIV prevention and treatment, uptake of evidence-based interventions among adolescents and young adults (AYA), particularly in low- and middle-income countries (LMICs), remains low. Implementation research can optimize strategies to enhance reach, uptake, and equitable access to these innovations. The Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource-Constrained Settings Implementation Science Network (PATC

METHODS: The PATC

RESULTS: The PATC

CONCLUSIONS: The PATC

CLINICAL TRIAL NUMBER: Not Applicable.

Oligomerisation Of Ku From Mycobacterium Tuberculosis Promotes Dna Synapsis, Sayma Zahid, Ankita Chadda, Eric Galburt, Et Al.

2020-Current year OA Pubs

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is estimated to infect nearly one-quarter of the global population. A key factor in its resilience and persistence is its robust DNA repair capacity. Non-homologous end joining (NHEJ) is the primary pathway for repairing DNA double-strand breaks (DSBs) in many organisms, including Mtb, where it is mediated by the Ku protein and the multifunctional LigD enzyme. In this study, we demonstrate that Ku is essential for mycobacterial survival under DNA-damaging conditions. Using cryogenic electron microscopy (cryo-EM), we solved high-resolution structures of both the apo and DNA-bound forms of the Ku-Mtb homodimer. …

The Pitfalls Of Multiple-Choice Questions In Generative Ai And Medical Education, Shrutika Singh, Anton Alyakin, Daniel Alexander Alber, Jaden Stryker, Ai Phuong S Tong, Karl Sangwon, Nicolas Goff, Mathew De La Paz, Miguel Hernandez-Rovira, Ki Yun Park, Eric Claude Leuthardt, Eric Karl Oermann

2020-Current year OA Pubs

The performance of Large Language Models (LLMs) on multiple-choice question (MCQ) benchmarks is frequently cited as proof of their medical capabilities. We hypothesized that LLM performance on medical MCQs may in part be illusory and driven by factors beyond medical content knowledge and reasoning capabilities. To assess this, we created a novel benchmark of free-response questions with paired MCQs (FreeMedQA). Using this benchmark, we evaluated three state-of-the-art LLMs (GPT-4o, GPT-3.5, and LLama-3-70B-instruct) and found an average absolute deterioration of 39.43% in performance on free-response questions relative to multiple-choice (p = 1.3 * 10

Clinical And Implementation Outcomes Of An Antimicrobial Stewardship Intervention For Rapid Blood Culture Diagnostics, Monica Abdelnour, Christine R Lockowitz, Evan E Facer, Andrew Atkinson, Sara Malone, Virginia R Mckay, Rebekah E Dumm, Alexander S Plattner, Matthew M Sattler, Jason G Newland

2020-Current year OA Pubs

OBJECTIVE: To evaluate the clinical and implementation outcomes of an antimicrobial stewardship program (ASP) intervention to improve antibiotic therapy for a rapid diagnostic test (RDT) for bloodstream infections (BSIs).

DESIGN: Retrospective pre and postintervention study.

SETTING: Single pediatric tertiary center from August 2022 to May 2024.

PARTICIPANTS: Patients presenting with a positive blood culture accompanied by the Verigene (VG) Gram-positive Blood Culture Nucleic Acid (BC-GP) assay. Implementation outcomes surveys were completed by infectious diseases (ID) clinicians and non-ID clinicians.

METHODS: We implemented a 24 hours a day, 7 days a week (24/7) ASP intervention to improve response to BC-GP assay …