Medicine and Health Sciences Commons^™

Developing Ehealth Interventions To Improve Diabetes Management In Emerging Adulthood: Qualitative Formative Study, April Idalski Carcone, Deepika Baskar, Aishah Mahmood, Karen Macdonell, Susan Eggly, Samiran Ghosh, Colleen Buggs-Saxton, Steven J Ondersma, Deborah A Ellis

Faculty, Staff and Student Publications

Background: Emerging adulthood is a high-risk period during which many with type 1 diabetes demonstrate suboptimal diabetes management and glycemic control. There is a need for effective, scalable interventions designed specifically for this population. Technology-based approaches are readily accessible to this age group. Furthermore, interventions consistent with self-determination theory-which posits that the fulfillment of psychological needs for autonomy, self-efficacy, and relatedness promotes intrinsic motivation for change-may resonate well with emerging adults' developmental needs for establishing independence and autonomy, and growing their social network.

Objective: This study aimed to enhance the potential relevance, sustainability, and efficacy of 3 self-determination theory-informed mobile …

Human Plasma Proteomic Profile Of Clonal Hematopoiesis, Zhi Yu, Amélie Vromman, Ngoc Quynh H Nguyen, Art Schuermans, Linke Li, Thiago Rentz, Tetsushi Nakao, Shamsudheen K Vellarikkal, Md Mesbah Uddin, Abhishek Niroula, Gabriel Griffin, Michael C Honigberg, Amy E Lin, Christopher J Gibson, Daniel H Katz, Usman A Tahir, Shi Fang, Jacqueline S Dron, Michael Pan, Sara Haidermota, Shriienidhie Ganesh, Tajmara Antoine, Joshua Weinstock, Thomas R Austin, Ramachandran S Vasan, Gina M Peloso, Whitney Hornsby, Peter Ganz, Joann E Manson, Bernhard Haring, Charles Kooperberg, Alexander P Reiner, Joshua C Bis, Bruce M Psaty, Yuan-I Min, Adolfo Correa, Leslie A Lange, Wendy S Post, Jerome I Rotter, Stephen S Rich, James G Wilson, Benjamin L Ebert, Bing Yu, Christie M Ballantyne, Josef Coresh, Vijay G Sankaran, Alexander G Bick, Siddhartha Jaiswal, Robert E Gerszten, Nhlbi Trans-Omics For Precision Medicine, Peter Libby, Rajat M Gupta, Pradeep Natarajan

Faculty, Staff and Student Publications

Plasma proteomic profiles associated with subclinical somatic mutations in blood cells may offer insights into downstream clinical consequences. Here we explore these patterns in clonal hematopoiesis of indeterminate potential (CHIP), which is linked to several cancer and non-cancer outcomes, including coronary artery disease (CAD). Among 61,833 participants (3881 with CHIP) from TOPMed and UK Biobank (UKB) with blood-based DNA sequencing and proteomic measurements (1,148 proteins by SomaScan in TOPMed and 2917 proteins by Olink in UKB), we identify 32 and 345 proteins from TOPMed and UKB, respectively, associated with CHIP and most prevalent driver genes (DNMT3A, TET2, and ASXL1). These …

Met Overexpression Is Associated With Superior Immunotherapy Benefit In Advanced Non-Small Cell Lung Cancer, Hui Li, Lingzhi Hong, Pedro Rocha, Rafael Bach, Luisa M Solis Soto, Waree Rinsurongkawong, Bingnan Zhang, Haniel A Araujo, Yasir Y Elamin, Mehmet Altan, Claudio A Arrechedera, Jianling Zhou, Khaja B Khan, Wei Lu, Elliana Young, Carl M Gay, Tina Cascone, Lauren A Byers, Ferdinandos Skoulidis, George Blumenschein, Frank V Fossella, Anne Tsao, Marcelo V Negrao, Natalie Vokes, Jia Wu, Hai T Tran, Ignacio I Wistuba, J Jack Lee, Don L Gibbons, Ara A Vaporciyan, John V Heymach, Xiuning Le, Jianjun Zhang

Faculty, Staff and Student Publications

Background/objectives: MET overexpression is common in non-small cell lung cancer (NSCLC). The correlation between MET overexpression and immune checkpoint inhibitor (ICI) efficacy in NSCLC is underexplored.

Methods: In this retrospective observational cohort study, we curated a dataset of 279 stage IV NSCLC patients who received ICI treatment and had MET expression assessed by CLIA-certified immunohistochemistry (IHC) assay. MET expression was graded on a scale from 0 to 3+, with overexpression defined as 2+ or 3+. Clinicopathological features associated with MET expression were assessed using logistic regression. Overall survival (OS) and progression-free survival (PFS) were evaluated via Kaplan-Meier analysis and the …

Improving Diagnostic Accuracy In Preoperative Glioma Classification: Performance Of Knowledge-Enhanced Large Language Models Compared With Radiologists, Shuang Li, Xin Fang, Yuqi Jin, Yujiao Deng, Wei Hu, Bing Wu, Xiaobo Zhou, Guotai Wang, Kang Li, Qiang Yue

Faculty, Staff and Student Publications

Accurate preoperative MRI classification of gliomas is essential but challenging due to complex radiological features and inter-observer variability. This study evaluated three large language models (LLMs) for VASARI-based glioma classification compared to radiologist interpretations. We retrospectively analyzed 150 histopathologically confirmed gliomas (43 circumscribed astrocytic, 53 high-grade diffuse, 54 low-grade diffuse gliomas) using standardized MRI protocols. Three radiologists extracted VASARI features, while three LLMs (GPT-4, Claude3.5-Sonnet, Claude3.0-Opus) analyzed these features using standard input-output or knowledge-enhanced prompting incorporating diagnostic guidelines. Knowledge-enhanced prompting consistently outperformed standard prompting, improving diagnostic consistency (intra-model agreement: Sonnet κ = 0.91, Opus κ = 0.92, GPT-4 κ = …

Brain Power Comparison Between Microgravity And Head-Down Tilt Bed Rest: An Electroencephalography Approach, María Sevilla-García, Adrián Quivira-Lopesino, Pablo Cuesta, Sandra Pusil, Ricardo Bruña, Patrique Fiedler, Fernando Maestu, Ana Maria Cebolla, Guy Cheron, Katharina Brauns, Alexander C Stahn, Michael E Funke

Faculty, Staff and Student Publications

This study examines neurophysiological changes in microgravity by comparing EEG data from two ground analog 60-day head-down tilt bed rest (HDBR) experiments (ESA/DLR “Cocktail” and “RSL”) and the NEUROSPAT experiment in space. The primary objective was to determine whether HDBR could effectively model spaceflight’s impact on the human brain’s EEG signal. In the HDBR dataset, increases in relative delta (2–4 Hz) (p <  0.01) and theta (4–8 Hz) (p <  0.001) power bands were observed during a two-month HDBR experiment, predominantly in the left temporal and parieto-occipital regions. Conversely, the NEUROSPAT dataset showed a significant increase in beta (12–30 Hz) (p <  0.05) power in the left somatosensory cortex during in-flight conditions, suggesting a potential adaptation to disrupted proprioceptive input and motor control in microgravity. The contrasting findings between the two datasets indicate that while HDBR can simulate some aspects of microgravity, it may not serve as a model for all central nervous system changes, especially those related to proprioception and motor functions. This highlights the need for further research, including larger sample sizes, consistent EEG recording conditions, and integration of additional physiological and cognitive markers to fully understand the effects of prolonged microgravity.

Accelerating Digital Mental Health: The Society Of Digital Psychiatry's Three-Pronged Road Map For Education, Digital Navigators, And Ai, John Torous, Kathryn Taylor Ledley, Carla Gorban, Gillian Strudwick, Julian Schwarz, Soumya Choudhary, Margaret Emerson, Michelle Patriquin, Allison Dempsey, Jason Bantjes, Laura Ospina-Pinillos, Jennie Hornick, Shruti Kochhar

Faculty, Staff and Student Publications

Digital mental health tools such as apps, virtual reality, and artificial intelligence (AI) hold great promise but continue to face barriers to widespread clinical adoption. The Society of Digital Psychiatry, in partnership with JMIR Mental Health, presents a 3-pronged road map to accelerate their safe, effective, and equitable implementation. First, education: integrate digital psychiatry into core training and professional development through a global webinar series, annual symposium, newsletter, and an updated open-access curriculum addressing AI and the evolving digital navigator role. Second, AI standards: develop transparent, actionable benchmarks and consensus guidance through initiatives like MindBench.ai to assess reasoning, safety, and …

Microrna Profiling Identifies Diagnostic And Prognostic Markers In Pediatric Sarcoma., Terrie Flatt, Leonid M. Yermakov, Shreeram Akilesh, Eleanor Y. Chen, Elizabeth Gonzalez, Alejandro Parrales, Marta Zapata-Tarres, Rocio Cardenas-Cardos, Liliana Velasco-Hidalgo, Celso Corcuera-Delgado, Rodolfo Rodriguez-Jurado, Lillia García-Rodríguez, Midhat S. Farooqi, Atif Ali Ahmed

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: MicroRNAs (miRNAs) function as post-transcriptional gene expression regulators and influence the development and progression of several cancers, yet their roles in pediatric sarcomas remain poorly defined.

METHODS: RNA extracted from formalin-fixed paraffin-embedded tumor tissue scrolls of 108 pediatric tumors, including 32 osteosarcoma (OS), 26 Ewing's sarcoma (EWS), and 50 rhabdomyosarcoma (RMS) cases, were analyzed for microRNA expression using the NanoString multiplex nCounter platform that yielded information on 827 human miRNAs. The expression of candidate miRNAs was validated with in situ hybridization (miRNA-ISH) and QuPath quantification on tissue microarray slides comprising an independent set of 48 OS, 17 EWS, and …

A Phase 1/2 Study Of Ds-1594 Menin Inhibitor In Relapsed/Refractory Acute Leukemias, Jayastu Senapati, Marina Konopleva, Ghayas C Issa, Elias Jabbour, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Naveen Pemmaraju, Nicholas J Short, Musa Yilmaz, Indraneel Deshmukh, Joie Alvarez, Sanam Loghavi, Guilin Tang, Hussein A Abbas, Michael Andreeff, Kapil Bhalla, Narasimha M Midde, Nabil Said, Amy Noyalis, Derek E Mires, Jing Ning, Lianchun Xiao, Farhad Ravandi, Guillermo Garcia-Manero, Hagop M Kantarjian, Naval G Daver

Faculty, Staff and Student Publications

Several menin inhibitors are in development targeting menin dependent leukemias, however available preclinical results show variable level of activity. We report the phase 1 portion (to establish a recommended phase 2 dose [RP2D]) and pharmacokinetic analysis of a phase 1/2 first-in-human clinical trial of DS-1594b menin inhibitor. Eligible patients included adults (≥ 18 years of age) with relapsed/refractory (R/R) acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) including but not restricted to those with KMT2A-rearrangement (r) or NPM1 mutation. Seventeen patients at a median of age 56 years (range, 19-82 years) were treated, 15 (88%) had R/R AML, and …

The 23rd International Medical, Pharmaceutical, Cosmeceutical And Health Science Symposium (Impachs), Sultan Qaboos University

Sultan Qaboos University Medical Journal

No abstract provided.

Soluble Immune Factor Profiles In Blood And Csf Associated With Lrrk2 Mutations And Parkinson's Disease, Roshni Jaffery, Yuhang Zhao, Sarfraz Ahmed, Jackson G Schumacher, Jae Ahn, Leilei Shi, Yujia Wang, Yukun Tan, Jiayin Zhang, Ken Chen, Hussein Tawbi, Jian Wang, Michael A Schwarzschild, Weiyi Peng, Xiqun Chen

Faculty, Staff and Student Publications

Mutations in LRRK2, a leading genetic cause of Parkinson's disease (PD), are linked to immune dysregulation, but the immune profiles in the periphery and central nervous system (CNS) remain incompletely defined. This study utilized a large cohort of serum samples (n = 651) and matched CSF samples (n = 129) from LRRK2 mutation carriers and non-carriers, with and without PD, to assess immune regulators using Luminex immunoassay. After correction for multiple comparisons, LRRK2 mutations were associated with significantly elevated serum levels of SDF-1 alpha and TNF-RII, while CSF markers such as BAFF, CD40L, and IL-27 were nominally reduced. Regardless of …

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 …

Addressing The Burden Of Prematurity And Its Prevention In Developing Countries: Is It Time To Act Now?, Mahaveer Singh Lakra, Amar Taksande, Revat J. Meshram, Ashwini Lakra, Amit Kumar, Deepak Gandhi, Roshan Prasad, Mayur Wanjari

Chulalongkorn Medical Journal

Around 3.5 million preterm births occur in India annually, accounting for about 25% of all preterm births worldwide. Prematurity poses a significant burden world-wide but leaves a special impact on the families and health systems of low-socioeconomic countries where easy and universal access to adequate health services is compromised. Premature birth imposes a significant risk of neonatal death among all under-fives due to organ immaturity, sepsis, and respiratory distress syndrome. Efforts to address prematurity on a global scale involve a multifaceted approach, including improving access to quality prenatal care, enhancing neonatal care services, and implementing public health interventions to reduce …

An Art Of Port Wine Birthmark - A Case Report On Type Ii Sturge Weber Syndrome, Dr Sushmitha S, Dr Aravind Warrier S, Dr Dhivya Bharathi

Chulalongkorn Medical Journal

Sturge Weber Syndrome is a Phakomatoses group of neurocutaneous disorders. They manifest in the dermal, neural, ocular, and oral regions due to a mutation in the GNAQ gene. These lesions often are unilateral following the course of the trigeminal nerve.Here we present a case of 54-year-old woman with a history of glaucoma with a unilateral reddish-purple discoloration of the palate and a port-wine stain limited to the left side of her face. The clinical course of Sturge-Weber syndrome is quite complex and necessitates a multidisciplinary approach. In type 2 cases of Sturge-Weber syndrome, patients present with facial angiomas and glaucoma, …

Rare Case Of Recurrent Cystic Mediastinal Mass: Giant Pericardial Cyst, Melina Tanadi, Anggraini Dwi Sensusiati Phd

Chulalongkorn Medical Journal

Pericardial cyst is unusual benign congenital malformations, with incidence of 1 person per 100.000. Although considered congenital lesion by incomplete fusion of embryogenesis, there are less frequent causes such as surgery, post trauma, and inflammatory process. Pericardial cyst can mimick malignant mediastinal tumor, cardiac chamber enlargement, bronchogenic cyst from Chest X-ray. Most of pericardial cyst are asymptomatic until they got bigger, such as dypsnea, sudden death, cardiac tamponade, rupture of the cyst. Radiology Imaging play important roles for rule out diagnostic therefore to prevent the complications. Computed tomography is modality of choice for pericardial cyst. We report a case of …

Bony Affair – A Rare Case Of Osseous Metaplasia In A Native Non Functioning Kidney, Arthi M Dr, Leena Dennis Joseph Dr, Velmurugan P Dr, Meryl Saji Kottarathil Dr

Chulalongkorn Medical Journal

Renal osseous metaplasia is a rare condition in a native kidney with end stage renal disease showing mature bone with marrow elements in a background of chronic pyelonephritis. Although the pathogenesis is unknow, chronic ischemia and inflammation seems to be a trigger factor for the same. Osseous metaplasia has been reported in renal allograft specimen, but in this case report we present a histologically rare finding of osseous metaplasia in a native kidney.

Key words - Osseous metaplasia, native kidney, marrow elements

Clinical Characteristics And Risk Factors Associated With Acute Kidney Injury Among Hospitalized Primary Covid-19 Infected Patients, Monchai Siribamrungwong, Kamontip Chaikomon

Chulalongkorn Medical Journal

Background: Coronavirus disease 19 (COVID-19) mainly affects to respiratory system from mild to severe symptoms. Additionally, acute kidney injury (AKI) is an important complication causing substantially high morbidity and mortality. During the pandemic of COVID-19, Public health care in Thailand experienced many cases and complications.

Objectives: This study demonstrated an incidence, clinical characteristic, independent risk factors of AKI and mortality in hospitalized COVID-19 patients with AKI and non-AKI patients.

Methods: A retrospective, observational study was performed in Lesdsin Hospital from August 2021 to August 2022. A total of 576 hospitalized patients with diagnosis of COVID-19 infection were analyzed. AKI was …

Functional Outcome Of The Patients Treated Surgically For Traumatic Brain Injury (Tbi) Fast Tract (Gcs 9-12), Narongpong Lowprukmanee

Chulalongkorn Medical Journal

Background: Traumatic brain injury (TBI) is a major cause of disability, morbidity, and mortality worldwide Objectives: This study aimed to determine the effect of the fast-track protocol on clinical outcome of traumatic brain injury (TBI) patients. Hospitals should consider implementing similar protocols to enhance care for TBI patients and decreasing preventable death and preventable disability.

Methods: This study evaluates the functional outcomes in surgical groups of traumatic brain injury (TBI) fast track, with Glasgow Coma Scale (GCS) scores between 9 and 12. Data were retrospectively collected from 52 TBI patients treated surgically at Sawanpracharak Hospital between September 1, 2016, …

Factors Influencing Turnover Intention Among Registered Nurses In Thailand: A Preliminary Study, Vachira Posai, Associate Professor Chanokporn Jitpanya, Rn, Ms, Ph.D., Assistant Professor Wisarut Srisinthorn, Md, Associate Professor Paramee Thongsuksaid, Md

Chulalongkorn Medical Journal

Background: The global nursing shortage impacts healthcare systems. Understanding factors influencing nurses' turnover intentions is essential for developing effective retention strategies.

Objective: To identify predictors of turnover intention among nurses, focusing on variables such as age, number of children, years of nursing experience, monthly personal income, burnout, emotional labor, job stress (assessed through effort, reward, and overcommitment), nurse-practice environment, work-family conflict, and work engagement.

Methods: A secondary data analysis was conducted using data from a multicenter, longitudinal study involving 1,005 nurses from two public hospitals in Thailand. Data collection instruments included a demographic questionnaire, the Burnout Assessment Tool, the Emotional …

Knowledge, Attitude And Practice Of Butchers Regarding Crimean Congo Hemorrhagic Fever In An Endemic Area Of Iran, Mohammad Amin Gorouhi, Abbas Aghaei Afshar, Najmeh Mansoori, Parya Jangipour Afshar, Leila Shirani-Bidabadi, Ismaeil Alizadeh, Nariman Shahhosseini

Chulalongkorn Medical Journal

Background: In endemic countries, Crimean-Congo hemorrhagic fever (CCHF) is an important zoonotic disease with significant public health implications. Previous studies in Iran suggests that CCHF poses a significant health risk to slaughterhouse workers and butchers. The main objecive of this study was to investigate the knowledge, attitude, and practice of butchers regarding CCHF at their workplace in an endemic area in southeastern Iran.

Methods: A descriptive cross-sectional study was conducted from January to March 2022 in Zarand city. In total, 60 butchers were included in the city. Statistical analysis was performed using SPSS version 22.

Results: The average scores of …

Impact Of The Rs1050757 C>T Variant In The 3'Utr Of The G6pd Gene On Mrna Structure And Mirna Binding In G6pd Deficiency: A Nanopore Minion Sequencing Study, Lawrence Billy Vasco Djama, Vorthon Sawaswong Ph.D., Prangwalai Chanchaem, Punchalee Mungkalasut Ph.D., Thanaporn Pimpakan, Poonlarp Cheepsunthorn Ph.D., Sunchai Payungporn Ph.D., Chalisa L. Cheepsunthorn Ph.D.

Chulalongkorn Medical Journal

Background: Glucose 6-phosphate dehydrogenase (G6PD) deficiency is a genetic disorder caused by impaired enzyme function or instability due to mutations in the G6PD gene, resulting in reduced enzyme activity. This study aimed to investigate mutations in the regulatory regions of the G6PD gene using Nanopore MinION sequencing to explore the potential impact of non-coding variants on G6PD activity.

Methods: Blood samples from 19 males (13 adults, 6 neonates) with G6PD deficiency or intermediate enzyme activity but unidentified coding sequence mutations were analysed. Genomic DNA was amplified using degenerate oligonucleotide-primed PCR (DOP-PCR) and sequenced with the Oxford Nanopore MinION platform. Bioinformatic …

Quality Improvement Project: Impact Of Simulation Training On The Self-Efficacy Of Registered Nurses During A Code Stroke, Kakeya James

Doctor of Nursing Practice Projects

Self-efficacy levels affect decision-making skills and overall confidence in handling critical situations. However, knowledge gaps often hinder the maintenance of high self-efficacy. (Farčić, et al., 2020). The project site provides limited training opportunities that may not adequately prepare registered nurses with the confidence and skills needed to respond to stroke emergencies, potentially causing delays in patient care and adverse health outcomes. As a result, the quality improvement project aims to examine how simulation-based training impacts registered nurses’ self-efficacy in managing stroke emergencies. The project employed a quasi-experimental pretest/posttest design and was guided by the Plan-Do-Study-Act (PDSA) cycle, the Jeffries Simulation …

High Prevalence And Atypical Genotype Distribution Of Oral Human Papillomavirus In An East African Hiv Cohort: A Cross-Sectional Study, Ian G. Munabi, Adriane Kamulegeya, Dunstan Kalanzi, David P. Kateete, Fred Collins Semitala, Catherine-Lutalo Mwesigwa, Samuel Kalungi, Jennifer E. Cameron, Kimon Divaris, William Buwembo

School of Medicine Faculty Publications

BACKGROUND: Globally, Human Papillomavirus type 16 (HPV-16) is the predominant genotype associated with oropharyngeal cancers. However, little is known about the prevalence and type distribution of Oral Human Papillomavirus (OHPV) in people living with HIV (PLWHIV) in the East African region. The objective of this study was to document the prevalence and circulating genotypes of OHPV infection in a large cohort of PLWHIV attending an urban HIV clinic in Eastern Africa METHODS: This was a cross-sectional study among 1,715 participants of the Makerere University Joint AIDS Program clinic, located in Kampala, Uganda, in East Africa. A salivary sample was collected …

Exploring Recruitment Strategies For Place-Based Research In Rural Areas Of Australia: A Comparative Case Study Analysis, Tracy L. Schumacher, Anna K. Jansson, Lucy Kocanda, Jennifer May Phd, Rn, Anp-Bc, Leanne J. Brown, Clare E. Collins

Publications

BACKGROUND: Recruitment of participants into research studies is commonly challenging and becomes more difficult when targeting underrepresented population groups. Recruiting individuals living in rural locations, must use appropriate strategies if the sample size is to be achieved. The aim of this case study was to explore factors associated with research capacity, and to determine their impact on recruitment strategies, including timeframe and participant recruitment outcomes.

METHODS: This case study investigated the recruitment outcomes of four rurally based research projects performed between 2016-2024. Participants were enrolled either directly by the researchers (face-to-face method [f2f]), or through General Practitioners as trusted local …

Dietary Fiber Modulates Gut Microbiota And Lipid Metabolism Ameliorating Alzheimer's Pathology In 5xfad Mice, Yuhai Zhao, Christopher M. Taylor, Walter J. Lukiw, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

The gut-brain axis plays a critical role in maintaining neuronal integrity and influencing the progression of Alzheimer's disease (AD). Here, we investigated how commonly consumed dietary fibers modulate gut microbiota, lipid metabolism, and AD pathology in 5xFAD mice. Male mice were fed either fiber-free (FF) or fiber-plus (FP; 1% cellulose, 2% pectin, 2% inulin) diets for five months, followed by integrated analyses of gut microbiota (16 S rRNA sequencing), fecal lipid metabolites (LC-MS/MS), and neuropathological and behavioral outcomes. FP diets markedly altered microbial composition, characterized by increases in Muribaculaceae, Ileibacterium, and Lachnospiraceae NK4A136 group and reductions in Faecalibaculum and Coriobacteriaceae …

Multimodal Cardiac Imaging Of Immune-Mediated Complications Post Heart Transplantation: A Contemporary Review, Bruno Bezerra Lima, Tam T Doan, Atilla Feher, James C Wilkinson, Marvin W Kronenberg, Chloe Carr, Malek Nayfeh, Tania Ruiz, Luke L Laws, Melissa Lou Silva, John A Wells, Leandro Slipczuk, Emily T Lippincott, John J Carr, Kaushik Amancherla, Cameron Henry, David Parra, Kelly Schlendorf, Quinn S Wells, Sean G Hughes, Jonathan Soslow

Faculty, Staff and Students Publications

Heart transplantation significantly enhances survival and quality of life for patients with end-stage heart failure. Despite advances in surgical and postoperative care, immune-mediated complications, acute graft rejection and cardiac allograft vasculopathy (CAV), remain major barriers to long-term success. Acute rejection predominantly affects early posttransplant survival, whereas CAV becomes a leading cause of mortality in later years. The gold standards for diagnosis, endomyocardial biopsy for rejection and coronary angiography for CAV, are invasive and imperfect. Noninvasive multimodality imaging is increasingly used to complement or, in selected scenarios, defer invasive testing. Echocardiography with strain detects early myocardial dysfunction when ejection fraction is …

Waiting Room And Hallway Care For Older Adults: A Qualitative Study With Emergency Nurses And Technicians, Sarah J Nessen, Ari B Friedman, Annika R Bhananker, K Jane Muir, Anita N Chary

Faculty, Staff and Students Publications

Background: Emergency Department (ED) crowding places older ED patients at risk for adverse outcomes. Crowding often necessitates ED waiting room and hallway care, but there has been limited research on approaches to care for older adults in these settings. Frontline clinician insights can inform best practices for older adults in the context of the ongoing ED crowding crisis. Our objective was to describe the experiences of emergency nurses and technicians in providing waiting room and hallway care for older adults.

Methods: This qualitative study used individual, semi-structured interviews with a purposive sample of 20 ED nurses and technicians at a …

Investigating The Neuronal Role Of The Proteasomal Atpase Subunit Gene Psmc5 In Neurodevelopmental Proteasomopathies, Sébastien Küry, Janelle E Stanton, Geeske M Van Woerden, Amélie Bosc-Rosati, Tzung-Chien Hsieh, Lise Bray, Marielle Oloudé, Cory Rosenfelt, Marie Pier Scott-Boyer, Victoria Most, Tianyun Wang, Jonas J Papendorf, Charlotte De Konink, Wallid Deb, Virginie Vignard, Maja Studencka-Turski, Thomas Besnard, Anna M Hajdukowicz, Franziska G Thiel, Sophie Wolfgramm, Laëtitia Florenceau, Silvestre Cuinat, Sylvain Marsac, Yann Verrès, Audrey Dangoumau, Léa Poirier, Ingrid M Wentzensen, Annabelle Tuttle, Cara Forster, Johanna Striesow, Richard Golnik, Damara Ortiz, Laura Jenkins, Jill A Rosenfeld, Alban Ziegler, Clara Houdayer, Dominique Bonneau, Erin Torti, Amber Begtrup, Kristin G Monaghan, Sureni V Mullegama, Catharina M L Nienke Volker-Touw, Koen L I Van Gassen, Renske Oegema, Mirjam S De Pagter, Katharina Steindl, Anita Rauch, Ivan Ivanovski, Kimberly Mcdonald, Emily Boothe, Andrew Dauber, Janice Baker, Noelle Andrea V Fabie, Raphael A Bernier, Tychele N Turner, Siddharth Srivastava, Kira A Dies, Lindsay C Swanson, Carrie Costin, Alali Abdulrazak, Rebekah K Jobling, John Pappas, Rachel Rabin, Dmitriy Niyazov, Anne Chun-Hui Tsai, Karen Kovak, David B Beck, May Christine V Malicdan, David R Adams, Lynne Wolfe, Rebecca D Ganetzky, Colleen C Muraresku, Davit Babikyan, Zdeněk Sedláček, Miroslava Hančárová, Andrew T Timberlake, Hind Al Saif, Berkley Nestler, Kayla King, M J Hajianpour, Gregory Costain, D'Arcy Prendergast, Chumei Li, David Geneviève, Antonio Vitobello, Arthur Sorlin, Christophe Philippe, Tamar Harel, Ori Toker, Ataf Sabir, Derek Lim, Mark J Hamilton, Lisa J Bryson, Elaine Cleary, Sacha Weber, Trevor L Hoffman, Anna M Cueto-González, Eduardo F Tizzano, David Gómez-Andrés, Marta Codina-Solà, Athina Ververi, Efterpi Pavlidou, Alexandros Lambropoulos, Kyriakos Garganis, Marlène Rio, Jonathan Levy, Sarah J Langas, Anne M Mcrae, Mathieu K Lessard, Maria Daniela D'Agostino, Isabelle De Bie, Meret Wegler, Rami Abou Jamra, Susanne B Kamphausen, Viktoria Bothe, Lorraine Potocki, Eric Olinger, Yves Sznajer, Elsa Wiame, Michelle L Thompson, Molly C Schroeder, Catherine Gooch, Raphael A Smith, Arti Pandya, Larissa M Busch, Uwe Völker, Elke Hammer, Kristian Wende, Benjamin Cogné, Bertrand Isidor, Jens Meiler, Clémentine Ripoll, Stéphanie Bigou, Frédéric Laumonnier, Peter W Hildebrand, Evan E Eichler, Kirsty Mcwalter, Peter M Krawitz, Florence Roux-Dalvai, Ype Elgersma, Julien Marcoux, Marie-Pierre Bousquet, Arnaud Droit, Jeremie Poschmann, Andreas M Grabrucker, Francois V Bolduc, Stéphane Bézieau, Frédéric Ebstein, Elke Krüger

Faculty, Staff and Students Publications

Neurodevelopmental proteasomopathies are a group of disorders caused by variants in proteasome subunit genes, that disrupt protein homeostasis and brain development through poorly characterized mechanisms. Here, we report 26 distinct variants in PSMC5, encoding the AAA⁺ ATPase subunit PSMC5/RPT6, in individuals with syndromic neurodevelopmental conditions. Combining genetic, multi-omics and biochemical approaches across cellular models and Drosophila, we unveil the essential role of proteasomes in sustaining key cellular processes. Loss of PSMC5/RPT6 function impairs proteasome activity, leading to protein aggregation, disruption of mitochondrial homeostasis, and dysregulation of lipid metabolism and immune signaling. It also compromises synaptic balance, neuritogenesis, and neural progenitor …

Transcription-Replication Collisions Trigger High-Fidelity Replication Reset, Matthew B Cooke, Kobie T Welch, Laura Deus Ramirez, Katelin M Hagstrom, Alice X Wen, Jennifer A Halliday, Susan M Rosenberg, Christophe Herman

Faculty, Staff and Students Publications

Double-stranded DNA ends arise from external agents or cellular processes like transcription-replication collisions (TRCs), threatening genome stability. Here, we performed genomic CRISPRi screens to uncover DNA end formation factors in Escherichia coli. We discovered that translation-transcription decoupling causes DNA end formation through a TRC-dependent pathway, which is lethal when DNA end processing by RecBCD is disrupted, but not when recombination is disrupted. We find that TRCs cause replisome stalling followed by "rear-ending" from trailing replisomes which generates free DNA ends, rather than strand breaks. Surprisingly, these DNA ends are resolved through a process we call "replication reset", where the stalled …

Dna Extrusion Size Determines Pathway Choice During Cag Repeat Expansion, Mayuri Bhatia, Ashutosh S. Phadte, Anna Lakhina, Anthony R. Monte Carloi Iii, Sarah Barndt, Anna Pluciennik

Department of Biochemistry and Molecular Biology Faculty Papers

DNA triplet repeat expansion causes several primarly neurological disorders like Huntington's disease, myotonic dystrophy type 1, and fragile-X related disorders. There is general consensus that recognition of extrahelical extrusions or hairpin-loop structures (formed by strand slippage) by the DNA mismatch repair protein MutSβ leads to repeat expansion by a mutagenic process. By contrast, the FAN1 nuclease attenuates triplet repeat expansion, the molecular basis of which was explained by our recent finding that FAN1 nuclease cleaves and initiates removal of extrahelical extrusions. Here we show that extrusions containing two or more triplet repeats are subject to recognition and processing by either …