Medicine and Health Sciences Commons^™

The Crossroads Between Osteosarcopenia And Intrinsic Capacity—A Narrative Review, Nailton J. Neto, Guy Hajj-Boutros, Wayne Lok Ok Choo, Miguel G. Borda, Konstantinos Prokopidis, Hassan Rammal, Daniel Rivas, Hussein Samhat, Ivan Baltasar-Fernandez, Mahdi Imani, Cristiano Dos Santos Gomes, Oscar Rosas Carrasco, Marc Sim, Julie A. Pasco, Julia Chabot, Ana M. Ayala-Copete, Francisco J. García-García, Claire Godard-Sebillotte, Raman Agnihotram, Lana J. Williams, Anna Andrianova, Robinson Ramirez-Vélez, Emma Connolly, Harmehr Sekhon, Hidenori Arai, Liang-Kung Chen, Andréa Faust, Howard Bergman, Alexandra Papaioannou, Pierrette Gaudreau, Tiago Alexandre, Leocadio Rodriguez-Mañas, Ricardo Oliveira Guerra, Gustavo Duque

Research outputs 2022 to 2026

Intrinsic capacity (IC) is defined as the composite of physical and mental abilities an individual possesses, encompassing 5 domains: cognition, psychological health, sensory function, vitality, and locomotion. This construct is central to the World Health Organization’s framework for assessing functional ability in older adults. Growing evidence highlights the critical role of the musculoskeletal system in maintaining these domains, while conditions such as sarcopenia, osteoporosis, and their coexistence as osteosarcopenia (OS) are increasingly associated with IC decline. This narrative review compiles current evidence on the modulatory role of muscles and bones in IC and the impacts of sarcopenia, osteoporosis, and OS. …

The Life Study: A Cross-Sectional Study Protocol For Lifestyle Risk Factors For Chronic Disease Across The Stages Of Reproductive Ageing, Laura E. Pernoud, Jamie L. Noll, Paul A. Gardiner, Melinda Dean, Kathryn M. Broadhouse, Meegan Anne Walker, Hattie H. Wright, Anthony Villani, Joseph Scott, Alexandra P. Metse, Mia A. Schaumberg

Research outputs 2022 to 2026

Introduction: The dynamic physiological and hormonal changes through the menopause transition predispose women to an increased risk of chronic diseases including cardiovascular disease, metabolic disease, depression and dementia. The underlying mechanisms remain unclear, yet it is thought that chronic systemic inflammation and changes to lifestyle behaviours play important roles. The LIfestyle risk Factors for chronic disease across the stagEs of reproductive ageing (LIFE study) is a cross-sectional study aimed to characterise how hormonal and lifestyle (physical activity, diet and sleep) differences across pre, peri and postmenopause influence chronic systemic inflammation, visceral adiposity, cognitive function and sleep health. Methods and analysis: …

Defining Varus Thrust Assessment And Measurement: A Scoping Review, Haonan Shen, Nicole D'Souza, Claire E. Hiller, Marnee J. Mckay, Kun Hu, Zhiyong Wang, Milena Simic

Research outputs 2022 to 2026

Objective: The primary aim of this scoping review was to identify and evaluate the methodologies used for classifying and quantifying varus thrust of the knee during walking. The secondary aim was to report outcomes of reliability, validity, prevalence, and quantitative cutoffs of varus thrust in existing studies. Methods: A systematic literature search was conducted across five electronic databases from inception to April 2024. Studies that reported varus thrust during gait in adults were included. Two independent reviewers extracted data, and data were synthesized based on thrust classification methods, prevalence, reliability, and validity results. Results: A total of 59 studies were …

Factors Impacting Western Australian Midwives' Intention To Stay: A Mixed Methods Study, Christine Atkinson, Dianne Bloxsome, Zoe Bradfield, Kate Buchanan, Sarah Dawson, Frances Finch, Sadie Geraghty, Sara Bayes

Research outputs 2022 to 2026

Problem Midwifery workforce sustainability remains a critical concern for maternity services. Existing literature predominantly focuses on burnout and attrition, offering limited insight into what influences midwives’ decisions to remain within specific workplaces. Background Midwives consistently report strong professional commitment alongside growing workforce instability. National data indicate that uncertainty about current roles does not necessarily reflect disengagement from the profession. Understanding workplace-level influences on retention is therefore essential for targeted workforce strategy. Aim To examine how workplace stress and satisfaction with the practice environment are associated with Western Australian midwives’ intention to stay in their current job and in the profession. …

The Interplay Between Osteosarcopenia And Intrinsic Capacity: Insights And Associations With All-Cause Mortality In The Toledo Study For Healthy Aging, Ivan Baltasar-Fernandez, Pedro L. Valenzuela, Irene Rodríguez-Gómez, Fabio Quiñonez-Bareiro, Luis M. Alegre, Konstantinos Prokopidis, Leocadio Rodriguez-Mañas, Ignacio Ara, Oscar Rosas-Carrasco, Lana J. Williams, Robinson Ramirez-Vélez, Julie A. Pasco, Guy Hajj-Boutros, Raman Agnihotram, Marc Sim, Wayne Lok Ok Choo, Mahdi Imani, Ana M. Ayala-Copete, Julia Chabot, Miguel G. Borda, Nailton J. Neto, Claire Godard-Sebillotte, Howard Bergman, Anna Andrianova, Hidenori Arai, Pierrette Gaudreau

Research outputs 2022 to 2026

Background: Osteosarcopenia—the coexistence of osteopenia/osteoporosis and sarcopenia—is associated with numerous adverse health outcomes, but its association with intrinsic capacity (IC) remains unknown. We aimed to explore the associations of osteosarcopenia with IC and all-cause mortality in older adults. Methods: We conducted a cross-sectional analysis of IC and a prospective analysis of all-cause mortality in 1142 participants from the Toledo Study for Healthy Aging (75.1 ± 6.0 years, 53.1% women). Participants were classified as having no musculoskeletal disorders, osteopenia/osteoporosis, sarcopenia, or osteosarcopenia (DXA- and EWGSOP2-based criteria). IC was operationalized as a composite score integrating locomotion, cognition, psychological, vitality, and sensory domains. …

Peripheral Neuromuscular Fatigue Responses Of The Knee Extensors To Distinct Concurrent Training Protocols: A Preliminary Study, Tomás T. Freitas, Elena Marín-Cascales, Cristian Marín-Pagán, Linda H. Chung, Antonio Martínez-Serrano, Nicola A. Maffiuletti, Anthony J. Blazevich, Pedro E. Alcaraz

Research outputs 2022 to 2026

Background: This study aimed to investigate the extent and time course of peripheral neuromuscular fatigue of the knee extensors following different concurrent training protocols in recreationally active men. Methods: In a randomized, counterbalanced, crossover design, ten participants completed one exercise session of three concurrent exercise protocols in consecutive weeks and in similar resting conditions: traditional concurrent training (TCT), sprint interval training (SIT), and high-intensity resistance circuit training (HRC). Maximal voluntary isometric contraction (MVIC) and electrically evoked tetanic force of the knee extensors were assessed before, immediately after, and at 24 and 48 h following each exercise session. Linear mixed models …

A Qualitative Exploration Of Unanticipated Effects Experienced By People With Chronic Obstructive Pulmonary Disease Who Participated In Interventions Designed To Reduce Sedentary Behaviour, Fiona Coll, Vinicius Cavalheri, Daniel F. Gucciardi, Kylie Hill

Research outputs 2022 to 2026

Introduction: This study explored the lived experiences of people with chronic obstructive pulmonary disease (COPD) who participated in interventions designed to reduce the accumulation of sedentary behaviour in prolonged uninterrupted bouts. Methods: Ten participants with stable COPD participated in a multi-component intervention that spanned over 9 months and was designed to address the intervention message ‘If you have been sitting or resting continuously for 30 min, stand up and move’. Interventions comprised participation in an 8-week programme of supervised exercise training coupled with behaviour change techniques. Throughout the intervention period the person delivering the intervention kept detailed notes of their …

Age-Related Increase In Plasma P-Tau217 In Amyloid-Beta–Negative Cognitively Unimpaired Individuals Affects Diagnostic Interpretation, Anna E. Mammel, Fernando Gonzalez-Ortiz, Ali Mousavi, Kelsey Hallett, Mary Encarnacion, Don Biehl, Pradip Gill, Sazan Ismael, Christopher Fowler, James D. Doecke, Larry Ward, Hans Frykman

Research outputs 2022 to 2026

Introduction: The extent to which non-pathological aging influences plasma biomarkers remains unclear. Here, we investigate factors influencing plasma p-tau217 levels in cognitively unimpaired (CU), amyloid-beta–negative (Aβ-) individuals. Methods: Plasma p-tau217 was measured in CU Aβ- positron emission tomography–negative (PET-) participants using two immunoassays (ALZpath n = 360 and LUMIPULSE G1200 n = 73). Associations between p-tau217 and age groups (60–69, 70–79, and 80+ years), apolipoprotein E (APOE) genotype, and gender were evaluated. Results: ALZpath plasma p-tau217 showed a non-pathological age-related increase (p < 0.001), and increased percentage within the intermediate zone with age. Lumipulse p-tau217 showed an increase in the percentage of subjects with positive results with age, however, this trend was not significant (p > 0.05). Men had higher levels of p-tau217 only with the ALZpath assay (p = 0.02; Lumipulse: p = …

Assessing Shifts In Research Priority Areas From The Neurological Community Before And After The Covid-19 Pandemic, Leah Dempsey, Travis Cruickshank, Mitchell Turner, Manja Laws, Danielle Bartlett, Barby Singer, Onno Van Der Groen, Moira Sim, Mandy Stanley

Research outputs 2022 to 2026

Introduction: People living with a neurological condition face many difficulties in daily life, impacting their function and quality of life (QoL). There is currently no cure to many neurological conditions, therefore identifying interventions to improve QoL is of high importance. COVID-19 changed society in many ways and understanding the research priorities from the neurological community post pandemic is urgently needed to ensure resources are used efficiently and aligned with the needs and priorities of the community. To better understand the priority areas, it is essential for individuals with lived experience to have input into priority areas for research. Therefore, the …

Public Attitudes Toward Cascade Genetic Screening In The United States, Hadley Stevens Smith, Emilie S Zoltick, Madison R Hickingbotham, Emily S Bonkowski, Stacey Pereira, Tara A Lavelle, David L Veenstra, Amy L Mcguire, Katherine E Bonini, Leila Jamal

Center for Medical Ethics and Health Policy Staff Publications

Introduction: After a patient receives genetic test results that indicate an actionable health condition, cascade genetic screening (CGS) is the process of evaluating the patient's relatives for a potentially elevated genetic risk of disease. The United States primarily relies on patients to communicate with their relatives, resulting in suboptimal rates of risk communication, familial genetic testing uptake, and risk-reducing interventions. There is ongoing debate about whether and how best to inform relatives of a potentially increased genetic risk.

Methods: We conducted a nationally representative survey of US adults to assess attitudes toward informing at-risk relatives, acceptability of system-mediated communication, and …

Corneal Innervation Research At A Crossroads: A Tool-Driven Roadmap For The Future, Anna Matynia, Ian D Meng, Brian M Davis, Stephen C Pflugfelder, Anat Galor, Victor L Perez, Elizabeth R Felix, Pedram Hamrah, Pantelimon Rompolas, Raul E Ruiz-Lozano, Shamsuddin A Bhuiyan, Kaveh Moghbeli, Evangelia Semizoglou, William Renthal, Harinder Singh, Jishnu Das, Marcin Golczak, Mary Ann Stepp, Catherine W Morgans, Cintia S De Paiva, Carl Y Saab, Igor Spigelman, Rony R Sayegh, Tally M Largent-Milnes, Hao Wu, Wenqin Luo, Sreya Mitra, Heesuk Yoo, Sina Farsiu, Sejiro Littleton, Eden Jacob, Matthew T Mcpheeters, Maryse Lapierre-Landry, Jordan J Smith, Xi Wang, Roxana Florea, Made Airanthi K Widjaja-Adhi, Scott Holmes, Zane Zemborain, Kate E T Laise, Nicholas J Pondelis, Ki-Soo Jeong, Rui Chen, Michael W Jenkins, Vivian Lee, Eric A Moulton, Deborah S Jacobs, Sue A Aicher, Anthony J St Leger, Daniel R Saban

Faculty, Staff and Students Publications

Corneal innervation research has faced long-standing clinical challenges that only recent technological breakthroughs now make tractable. Advances in single-cell analysis, viral vectors, clinical imaging, and artificial intelligence provide integrated approaches for uncovering molecular mechanisms underlying functional outcomes and facilitating clinical applications. The National Eye Institute's U01-funded consortium on ocular surface innervation addresses major knowledge gaps in characterizing corneal-projecting neurons, understanding neuroimmune and epithelial interactions in the cornea, and translating animal model findings to human pathology. The unique properties of the cornea (transparent, avascular, and densely innervated) make it ideal for neurobiology research on peripheral and central sensory processing. Through a …

Disease-Specific Growth Charts Capture Characteristic Growth Patterns In Children With Pmm2 – Cdg, Kyriakie Sarafoglou, Christina Lam, Andrew C Edmondson, Andrea Miller, Rodrigo T Starosta, Aziza Zeighami, Seishu Horikoshi, Hayden Vreugdenhil, Fernando Scaglia, Tamas Kozicz, Queenie K G Tan, Bradley S Miller, Iván Martínez-Duncker, Gerard T Berry, Peter Mcwilliams, Eva Morava, Yaw Addo

Faculty, Staff and Students Publications

Background: Growth faltering is prevalent in 96% of children with Phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG). Published long-term growth data is extremely limited. Growth and weight patterns of PMM2-CDG children differ from the general population limiting the utility of existing normative growth charts to track development trajectory in comparison to peers with PMM2-CDG.

Objective: Create PMM2-CDG disease-specific height-, weight-, and BMI-for-age reference growth charts (0-20 years).

Methods: De-identified growth data was provided by Frontiers in Congenital Disorders of Glycosylation Consortium, CDG Care, Minnesota Partnership for Biotechnology and Medical Genomics, and Glycomine, Inc. Semi-parametric modeling techniques were used to develop PMM2-CDG-specific …

Hematologic Markers And Machine Learning In Predicting Placenta Accreta: A Case-Control Study, Michael D Jochum, Kelly D Albrecht, Yamely Mendez Martinez, Victoria Zhang, Sanmay Sarada, Brian Burnett, Christina C Reed, Karin A Fox, Amir A Shamshirsaz, Michael A Belfort, Jessian L Munoz, Hennie A Lombaard

Faculty, Staff and Students Publications

Objective: This study aims to enhance antenatal detection of placenta accreta spectrum (PAS) and predict severe hemorrhage at delivery using machine learning by evaluating the association between antenatal hematologic index trends across trimesters, imaging markers, and patient history.

Methods: We retrospectively analyzed 2017-2023 data from a PAS referral center, including demographics, laboratory results, ultrasounds, and outcomes. Patients with confirmed PAS (cases) were compared to those with antenatal risk but no histopathologic evidence of PAS (controls). Statistical analyses and machine learning models were developed to predict PAS. We also used machine learning to predict severe hemorrhage (>1500 mL) in the …

A Randomized Double-Masked Study Evaluating Safety And Efficacy Of A Novel Topical Cooling Device For Chronic Ocular Surface Pain, Anat Galor, Christopher Rapuano, Alice Epitropoulos, Jayne Weiss, Stephen Pflugfelder, Preeya Gupta, Deepinder Dhaliwal, Laura Periman, Bonnie An Henderson, Thanh T Nguyen, Chameen Samarawickrama, Helen Wu, Tomasz Stryjewski, James A Stefater, Mark Hinds, Pooja Bhindi, Cristos Ifantides

Faculty, Staff and Students Publications

Introduction: No therapy is currently FDA approved to treat ocular pain. This study evaluated the safety and efficacy of a novel topical ocular cooling device for chronic ocular surface pain (COSP).

Methods: This was a prospective, randomized, double-masked, multicenter clinical feasibility study in adults aged 22-90 years with COSP. The intervention was a handheld device that applied cold temperatures to the conjunctival surface above the long ciliary nerves via two metallic contact surfaces at the 3 and 9 o'clock positions. Subjects were randomized 2:1 to a one-time, 4-min treatment with the active (frozen) or sham (refrigerated) device and followed for …

Investigating The Correlation Between Scleral Spur Angle And Intraocular Lens Tilt, Dylan Mcbee, Karim Kozhaya, Li Wang, Douglas D Koch, Allison J Chen, Mitchell P Weikert

Faculty, Staff and Students Publications

Purpose: To evaluate the correlation between the preoperative vertex-scleral spur angle (Vtx-SSA) and postoperative horizontal intraocular lens (IOL) tilt after routine cataract surgery.

Setting: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas.

Design: Prospective case series.

Methods: This study enrolled patients who underwent uneventful phacoemulsification cataract extraction with IOL implantation. The Anterion and Eyestar 900 swept-source optical coherence tomographers (SS-OCTs) were used to determine Vtx-SSA and lens tilt (crystalline and IOL) measurements, respectively. Tilt vectors were decomposed into orthogonal, vertical, and horizontal components to explore preoperative correlations independently. The Pearson correlation coefficient and linear regression analysis were used to …

Higher Sodium Intake Is Associated With Episodic Memory Decline In Cognitively Unimpaired Older Males: A 6-Year Longitudinal Study, Francisca Chuwa, Stephanie R. Rainey-Smith, Hilal Salim Said Al Shamsi, Hamid Sohrabi, Kevin Taddei, Colin L. Masters, Ralph N. Martins, Samantha L. Gardener

Research outputs 2022 to 2026

Recent evidence has suggested an association between high sodium intake and development of cognitive impairment. However, while animal studies demonstrate consistent relationships between sodium intake and cognitive impairment, this relationship remains less clear in humans. Our aim was to investigate the relationship between self-reported baseline sodium intake and cognitive decline over 72 months. Cognitively unimpaired participants (n = 1208) from the Australian Imaging, Biomarkers and Lifestyle study were included (70.87 years of age; 41 % male). Participants completed a food frequency questionnaire to quantify sodium intake and underwent comprehensive neuropsychological assessment at baseline and four additional timepoints, 18 months apart. …

Exploring The Fidelity Of Resistance Training Interventions In Regional, Rural, And Remote Cancer Care: A Systematic Scoping Review, Christopher W. Rowe, Nicolas H. Hart, Julia Carlino, James Murray

Research outputs 2022 to 2026

Resistance-based exercise interventions are an integral part of supportive cancer care, though their high quality and high-fidelity implementation with people with cancer living in non-metropolitan locations is challenging. This systematic scoping review aimed to identify how exercise prescription principles and measures of fidelity are reported in resistance-based exercise interventions delivered to people with cancer living in regional, rural and remote areas. A systematic scoping review was conducted in accordance with the PRISMA-ScR guidelines. Five electronic databases were searched (MEDLINE/PubMed, Embase, CINAHL, SCOPUS and SportDiscus) for peer-reviewed studies published in English, that delivered a resistance-based exercise intervention to adult cancer survivors …

Recruitment And Retention Of Rural-Dwelling Young Adults Into A Digital Healthy Eating Intervention: Lessons Learned From A Randomized Controlled Trial Of The Veg4me Study, Katherine M. Livingstone, Stephanie R. Partridge, Jonathan C. Rawstorn, Kathleen M. Dullaghan, Yuxin Zhang, Stephanie L. Godrich, Sarah A. Mcnaughton, Gilly A. Hendrie, Lauren C. Blekkenhorst, Ralph Maddison, John C. Mathers, Laura Alston

Research outputs 2022 to 2026

Background/objectives: The study aimed to identify the key methodological challenges and solutions related to recruitment and retention of rural-dwelling young adults into a randomized controlled trial that tests the feasibility of a digital healthy eating intervention (Veg4Me). Methods: Digital registration for a 12-week study was set up as a one-step process without researcher involvement. Participant registrations and recruitment rates were monitored daily using predetermined online preventative measures to identify fraudulent responses and to amend the digital registration process where necessary. Retention rates were monitored daily to identify any necessary amendments to the follow-up protocol. Results: During data collection, n = …

The Effect Of Boosting Dietary Lactobacillus And Phytochemical Rich Foods On Biomarkers Of Longevity—A Phase Ii Randomised Placebo Controlled Trial, Robert J. Thomas, Madeleine Williams, Jeffrey W.F. Aldous, Stacey A. Kenfield, Robert U. Newton

Research outputs 2022 to 2026

As men age, systemic inflammation increases, whereas grip strength (GS) and testosterone levels tend to fall. This rate of decline is known to be influenced by gut microbial health, lifestyle and diet but the role for interventions to slow this decline are less well established. This double-blind randomised controlled trial evaluated the impact, and explored the synergistic potential, of boosting phytochemical rich foods and Lactobacillus probiotics on these physical and biological markers. Two hundred and eight men with untreated early prostate cancer managed with observation only (average age 74 years) received a phytochemical rich supplement (PRS) containing concentrated broccoli, green …

Validation Of The Immune-Mediated Colitis Endoscopic Score Using A Retrospective Cohort Of Patients With Immune-Mediated Colitis, Malek Shatila, Carolina Colli Cruz, Krishnavathana Varatharajalu, Andres Caleb Urias Rivera, Kian Abdul-Baki, Kei Takigawa, Tanvi Gupta, Elliot Baerman, Linfeng Lu, Irene Jeong-Ah Lee, Hamza Salim, Raakhi Menon, Andrew Sullivan, Varun Vemulapalli, Cristina Natha, Ayesha Khan, Petros Grivas, David Faleck, Michael Dougan, Anusha Shirwaiker Thomas, Yinghong Wang

Faculty, Staff and Students Publications

Background and aims: Immune-mediated colitis (IMC) is a challenging adverse effect of immune checkpoint inhibitor therapy, often leading to treatment interruption or discontinuation. Current IMC endoscopic scoring systems were adapted from those used for inflammatory bowel disease but fail to fully capture IMC. The newly proposed IMC endoscopic score (IMCES) seeks to help guide prognosis and treatment. We aimed to validate IMCES and explore its association with IMC clinical severity and outcomes.

Methods: This single-center retrospective study included patients with IMC who received immune checkpoint inhibitors and underwent endoscopic evaluation. IMCESs were calculated on the basis of 10 gross endoscopic …

Classification Of Gck-Mody In A Child With Mild Hyperglycemia And Islet Autoantibody Positivity: A Diagnostic Challenge, Aman N Yarlagadda, Maria J Redondo, Toni I Pollin, Mustafa Tosur, Colleen O Jodarski, Jennifer J Bell

Faculty, Staff and Students Publications

We report a 9-year-old female who presented with mild, persistent hyperglycemia, with hemoglobin A1c and oral glucose tolerance test results in the prediabetes range, relatively preserved C-peptide, and mildly positive glutamate decarboxylase 65 autoantibody levels. A strong family history of lean, noninsulin-dependent diabetes suggested a possible monogenic cause. Genetic testing with a 28-gene maturity-onset diabetes of the young (MODY) panel identified a heterozygous variant of uncertain significance in GCK (NM_000162.5:c.179C>T [p.Thr60Ile]). Following review by the ClinGen Monogenic Diabetes Variant Curation Expert Panel, the GCK variant was reclassified as pathogenic, confirming a diagnosis of glucokinase (GCK)-MODY/GCK-hyperglycemia, a stable …

Lingo4 Coordinates Ilc3-Intrinsic Il-22 Production And Microbiota-Mediated Ilc3 Homeostasis, José L Fachi, Tihana Trsan, Cristiane Sécca, Sarah De Oliveira, Vinícius R Rodovalho, Patrick Fernandes Rodrigues, Wandy L Beatty, Raki Sudan, Shitong Wu, Bishan Bhattarai, Santosh K Panda, Marina Cella, Susan Gilfillan, Marco Colonna

2020-Current year OA Pubs

LINGO4 is a leucine-rich repeat and immunoglobulin-like domain-containing transmembrane protein encoded immediately adjacent to Rorc, the gene for RORγt, raising the possibility that it contributes to the biology of RORγt+ lymphocytes. However, its impact on these cells and resistance to enteric infections has remained unknown. Here, we identify LINGO4 as a critical regulator of group 3 innate lymphoid cells (ILC3s). Lingo4-/- ILC3s exhibit a profound, cell-intrinsic defect in IL-22 production linked to impaired STAT3 activation, mitochondrial dysfunction, elevated ROS, and increased apoptosis. In vivo, Lingo4 deficiency also drives a dysbiotic gut microbiota, resulting in an additional, microbiota-dependent loss of ILC3s. …

Wayfindr: Investigating Feedback In Biological Pathways, Polina Bombina, Reginald L Mcgee Ii, Jake Reed, Zachary B Abrams, Lynne V Abruzzo, Kevin R Coombes

2020-Current year OA Pubs

Understanding biological pathways requires more than static diagrams. We present WayFindR, an R package that converts pathway data from WikiPathways and KEGG into graph structures using igraph, enabling computational analysis of regulatory features such as negative feedback loops. Rooted in control theory, negative feedback is essential for system stability, yet it is often underrepresented in curated pathway data. In this study, we systematically analyzed pathway information from both databases across multiple species and found that feedback loops-particularly negative ones-are rarely captured. This gap likely reflects both biological and technical challenges. Biologically, feedback mechanisms are inherently complex and often remain uncharted …

Activation Of The Human Β3 Gabaa Receptor By Combinations Of Receptor Protonation With Chemical Agonists And Gain-Of-Function Mutations, Allison L Germann, Spencer R Pierce, Joe Henry Steinbach, Gustav Akk

2020-Current year OA Pubs

Native GABA

Human Stem Cell-Based Embryo Models: Innovation, Ethics, And Policy, Alfonso Martinez Arias, Thorold Theunissen, Et Al.

2020-Current year OA Pubs

The aim of this White Paper is to establish a foundational framework for research, technological development, and regulation in the emerging field of stem cell-based embryo models (SCBEMs). These models, generated from Pluripotent Stem Cells, are designed to recapitulate essential events in early stages of human development. They have the potential to illuminate the early stages of embryo development and implantation and hold promise as an avenue to address global health challenges, including infertility and pregnancy loss, congenital, neonatal and adult conditions, and the need for organ transplants. While SCBEMs are not a substitute for human embryos, their tractability for …

Noninvasive Enrichment Of Circulating Tumor Biomarkers In A Mouse Model Of Diffuse Midline Glioma Using Focused Ultrasound, Dingyue Zhang, Yimei Yue, Yan Gong, Leqi Yang, Kevin Xu, Jinyun Yuan, Hong Chen

2020-Current year OA Pubs

BACKGROUND: Diagnosing diffuse midline glioma (DMG) through invasive tissue biopsies is challenging due to the tumor's eloquent location at the pons. Liquid biopsies offer a promising noninvasive alternative; however, their limited detection sensitivity and lack of information on the source of biomarkers pose great challenges. This study aimed to evaluate the feasibility and safety of using focused ultrasound (FUS) with microbubbles to enrich circulating DMG tumor biomarkers in blood and cerebrospinal fluid (CSF) using a mouse model.

METHODS: Murine DMG cells, transfected with enhanced green fluorescent protein (EGFP) and firefly luciferase (Fluc) genes, were orthotopically injected into the mouse brain. …

Routine Transfusion Of Rh(D)-Positive Rbcs To Rh(D)-Negative Patients Designated As Do Not Resuscitate Conserves Rh(D)-Negative Red Blood Cell Inventory, Julie Katz Karp, Jovanna Everetts, Juliana Guarente, Angelica Vivero, Tiffany Bohr, Mary Harach

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: A minority of blood donors are Rh(D)-negative, and Rh(D)-negative red blood cell (RBC) products are often overutilized. As such, Rh(D)-negative RBCs may be difficult to maintain in blood bank inventory.

Study design and methods: We changed our blood bank laboratory policy to approve non-alloimmunized Rh(D)-negative patients to receive Rh(D)-positive RBCs for routine transfusion under defined criteria. Those criteria included Rh(D)-negative males (all ages) and females (aged >50 years) who were designated as do not resuscitate (DNR), either with or without intubation, in the electronic medical record.

Results: From August 15, 2024 through August 15, 2025, a total of 204 …

Variation In Chronic Automated Red Cell Exchange Practices For Sickle Cell Disease: Insights Into Isovolemic Hemodilution Use, Jennifer M. Jones, Fatima Aldarweesh, Nicole Aqui, Aleh Bobr, Patricia Brunker, Mischa L. Covington, Juliana Guarente, Robert Hagar, Matthew Karafin, Divjot Singh Lamba, Grace Lee, Wen Lu, Ethan A. Mack, Gagan Muthur, Saadiya Nazli, Halima Olaniyan, Chinelo P. Onyenekwu, Jay S. Raval, Divya Setya, Yvette C. Tanhehco, Mamie Thant, Angelica Vivero, Yanyun Wu, Edward C. C. Wong, Nalan Yurtsever, Yan Zheng, Patricia A. Shi, Jennifer Webb

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Prior surveys of chronic automated red blood cell exchange (RCE) for patients with sickle cell disease (SCD) have identified considerable procedural variability, especially with the use of isovolemic hemodilution red blood cell exchange (IHD-RCE). We conducted a survey of chronic RCE practices among American Society for Apheresis (ASFA) members to identify opportunities for practice harmonization and future studies. The ASFA SCD Research Subcommittee developed a 72-item survey of chronic RCE practices, with a focus on IHD-RCE. The survey was validated internally and distributed by email to all ASFA members from September 2024 to February 2025. One survey response from each …

Trastuzumab Deruxtecan In Hormone Receptor-Positive, Her2-Low/-Ultralow Metastatic Breast Cancer (Destiny-Breast06): Outcome Analyses By Time To Progression On Prior First-Line Endocrine Therapy With Cdk4/6 Inhibitor And Baseline Burden Of Disease, G Curigliano, N A Bagegni, Et Al.

2020-Current year OA Pubs

BACKGROUND: In DESTINY-Breast06, trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) versus physician's choice of chemotherapy (TPC) for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-low/-ultralow metastatic breast cancer (mBC), without new safety signals. We report additional analyses exploring outcomes for patients with characteristics that affect prognosis.

PATIENTS AND METHODS: Patients were randomly assigned 1 : 1 to receive T-DXd (5.4 mg/kg) once every 3 weeks or TPC. Subgroups were specified post hoc from the intent-to-treat population (N = 866). Outcomes were PFS, objective response rate (ORR), and duration of response (DOR) by blinded independent central review …

Biomedgraphica: An All-In-One Platform For Joint Textual Biomedical Prior Knowledge And Numeric Graph Generation, Heming Zhang, Shunning Liang, Tim Xu, Wenyu Li, Di Huang, Yuhan Dong, Philip Miller, Peter Goedegebuure, Marco Sardiello, Jonathan Cooper, William Buchser, Patricia Dickson, Ryan C Fields, Carlos Cruchaga, Yixin Chen, Michael Province, Philip Payne, Fuhai Li, Et Al.

2020-Current year OA Pubs

MOTIVATION: Multiomics data analysis is essential for scientific discovery in precision medicine. However, translating analysis results of omics data analysis into novel scientific hypotheses remains a significant challenge. Human experts must manually review analysis results and generate new hypotheses based on extensive and interconnected biomedical prior knowledge, which is subjective and not scalable. While large language models can accelerate the discovery, their reasoning improves when grounded in structured, auditable, and comprehensive biomedical prior knowledge. However, biomedical knowledge is scattered across heterogeneous databases that use diverse and inconsistent nomenclature systems, making it difficult to integrate resources into a unified format for …