Digital Commons Network^™

Adapt Vr In Dental Education: Boosting Preclinical Skill And Self-Confidence, Shehabeldin Mohamed Saber Prof.Dr.

Dentistry

Introduction: Preclinical dental training requires extensive feedback and repetition, which traditional manikin exercises often lack. Adapt VR is a cost-effective, immersive system that delivers interactive, adaptive training with real-time feedback. Methods: This comparative study aimed to evaluate the effectiveness of the Adapt VR system in preclinical training. A total of 126 third-year dental students were randomly assigned to an Adapt VR Group 1 (n = 63), acquiring VR learning experience before practicing on laboratory simulators, or a control group (n = 63) who started their training on simulators directly. After practising Class I and II cavity preparations, laboratory performance was …

Phase 1b Pilot Study Of Itacitinib With Alemtuzumab In Patients With T-Cell Prolymphocytic Leukemia, Tapan M Kadia, Akhil Jain, Caitlin R Rausch, Alex Bataller, Farhad Ravandi, Elias Jabbour, Wei Qiao, Gautam Borthakur, Nicholas Short, Guillermo Montalban-Bravo, Andres E Quesada, Jan Burger, Alessandra Ferrajoli, William Wierda, Chitra Hosing, Hagop Kantarjian

Faculty, Staff and Student Publications

T-cell prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm with an aggressive clinical course. Overall prognosis is poor, and treatment relies on alemtuzumab because of inadequate response to conventional chemotherapy. Three-quarters of cases harbor activating mutations in the JAK-STAT pathway (JAK1, JAK3, STAT5B, IL2RG). We report safety and efficacy from a phase 1B study evaluating the combination of the JAK1 inhibitor itacitinib with alemtuzumab. Patients (N = 15) were aged >18 years, with treatment-naïve (n = 8) or relapsed/refractory (n = 7) T-PLL with adequate organ function, European Cooperative Oncology Group Performance Status ≤2, and …

First Report Of Response To Tarlatamab In A Patient With Histologic-Transformed Sclc From Alk-Rearranged Nsclc: Case Report, Kaiwen Wang, Ceylan Altintas Taslic, Patricia De Groot, Mitchell A Parma, Alvaro Guimaraes Paula, Melody Caranto, Komal Shah, Mukulika Bose, Cole Ruoff, Loukia G Karacosta, Lauren A Byers, Carl M Gay, Jianjun Zhang, John V Heymach, Bingnan Zhang

Faculty, Staff and Student Publications

Small cell transformation has been described as a resistance mechanism to targeted therapy treated in patients with EGFR-mutated NSCLC and less often reported with those with other actionable oncogenic alterations, including ALK-rearranged NSCLC. Given lack of standard-of-care treatments for patients with actionable oncogenic alteration NSCLC transformed to SCLC, this remains a challenge and unmet need for treating these patients.

Here, we present a case of a patient with ALK-rearranged NSCLC with transformation to SCLC, who has progressed on several lines of therapies and successfully treated with tarlatamab to elicit and maintain clinical benefit, including intracranial response.

Fireproof: Intricacies Of Microglial Biology, Wei Cao

Faculty, Staff and Student Publications

No abstract provided.

Outcomes Of Therapy-Related Non-Core Binding Factor Acute Myeloid Leukemia With Venetoclax-Based Therapies, Jayastu Senapati, Jennifer Croden, Guillermo Garcia-Manero, Koichi Takahashi, Naval G Daver, Tapan M Kadia, Gautam Borthakur, Nicholas James Short, Elias Jabbour, Fadi Haddad, Jennifer Marvin-Peek, Hussein A Abbas, Prithviraj Bose, Guilin Tang, Sanam Loghavi, Elizabeth J Shpall, Jeremy Ramdial, Uday R Popat, Richard E Champlin, Farhad Ravandi, Hagop M Kantarjian, Courtney D Dinardo

Faculty, Staff and Student Publications

Prognosis in therapy‐related acute myeloid leukemia (T‐AML) remains poor, but understanding outcomes with venetoclax (VEN)‐based therapy is relevant. We retrospectively analyzed 317 adult patients with newly diagnosed T‐AML focusing on lower intensity therapy (LIT) VEN‐containing regimens. Patients with an antecedent myeloid disorder before AML diagnosis were excluded. The median age was 69 years (range 21–92); 50% evaluated patients had a complex karyotype, and 40% evaluated patients had a TP53 mutation. Composite complete response rates were higher with LIT + VEN compared to LIT (58% vs. 40%, P = 0.003) but were similar in intensive chemotherapy (IC) + VEN versus IC …

Circulating Fatty Acid Binding Protein 4 (Fabp-4) Concentrations And Mortality In Individuals With Colorectal Cancer In The European Prospective Investigation Into Cancer And Nutrition Study, Thu Thi Pham, Katharina Nimptsch, Krasimira Aleksandrova, Mazda Jenab, Veronika Fedirko, Anja Olsen, Anne Tjønneland, Claire Cadeau, Gianluca Severi, Matthias B Schulze, Renée Turzanski Fortner, Verena Katzke, Claudia Agnoli, Carlotta Sacerdote, Rosario Tumino, Simona Signoriello, Camino Trobajo-Sanmartín, Jesús-Humberto Gómez, María-Dolores Chirlaque, Maria-Jose Sánchez, Marta Crous-Bou, Anne May, Alicia Heath, Dagfinn Aune, Elisabete Weiderpass, Tobias Pischon

Faculty, Staff and Student Publications

Human fatty acid binding protein‐4 (FABP‐4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity–mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC‐specific, non‐CRC‐specific, and all‐cause mortality by FABP‐4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC …

Introducing A New Frontier In The Journal Of Pediatric Rehabilitation Medicine: An Interdisciplinary Approach Throughout The Lifespan: The Pediatric Brain Injury Section, Michael Green, Glendaliz Bosques, Kimberly Davis, Brenda Eagan-Johnson, Carty Husted

Faculty, Staff and Student Publications

No abstract provided.

Unravelling The Molecular Mechanisms Causal To Type 2 Diabetes Across Global Populations And Disease-Relevant Tissues, Ozvan Bocher, Ana Luiza Arruda, Satoshi Yoshiji, Chi Zhao, Alicia Huerta-Chagoya, Chen-Yang Su, Xianyong Yin, Davis Cammann, Henry J Taylor, Jingchun Chen, Ken Suzuki, Ravi Mandla, Ta-Yu Yang, Fumihiko Matsuda, Josep M Mercader, Jason Flannick, James B Meigs, Alexis C Wood, Marijana Vujkovic, Benjamin F Voight, Cassandra N Spracklen, Jerome I Rotter, Andrew P Morris, Eleftheria Zeggini

Children’s Nutrition Research Center Staff Publications

Type 2 diabetes (T2D) is a prevalent disease arising from complex molecular mechanisms. Here we leverage T2D genetic associations to identify causal molecular mechanisms in an ancestry-aware and tissue-aware manner. Using two-sample Mendelian randomization corroborated by colocalization across four global ancestries, we analyse 20,307 gene and 1,630 protein expression levels using blood-derived cis-quantitative trait loci (QTLs). We detect causal effects of genetically predicted levels of 335 genes and 46 proteins on T2D risk, with 16.4% and 50% replication in independent cohorts, respectively. Using gene expression cis-QTLs derived from seven T2D-relevant tissues, we identify causal links between the expression of 676 …

Population-Scale Sequencing Resolves Determinants Of Persistent Ebv Dna, Sherry S Nyeo, Erin M Cumming, Oliver S Burren, Meghana S Pagadala, Jacob C Gutierrez, Thahmina A Ali, Laura C Kida, Yifan Chen, Hoyin Chu, Fengyuan Hu, Xueqing Zoe Zou, Benjamin Hollis, Margarete A Fabre, Stewart Macarthur, Quanli Wang, Leif S Ludwig, Kushal K Dey, Slavé Petrovski, Ryan S Dhindsa, Caleb A Lareau

Duncan NRI Faculty and Staff Publications

Epstein–Barr virus (EBV) is an endemic herpesvirus implicated in autoimmunity, cancer and neurological disorders. Although primary infection is often subclinical, persistent EBV infection can drive immune dysregulation and long-term complications. Despite the ubiquity of infection, the determinants of EBV persistence following primary exposure remain poorly understood, although human genetic variation partially contributes to this phenotypic spectrum1–3. Here we demonstrate that existing whole genome sequencing (WGS) data of human populations can be used to quantify persistent EBV DNA. Using WGS and health record data from the UK Biobank (n = 490,560) and All of Us ( …

Children's Experiences Of Functional Constipation: A Qualitative Reflexive Thematic Analysis, Gunilla Flankegård, Patrik Rytterström, Berit M. Gustafsson, Evalotte Mörelius

Research outputs 2022 to 2026

Background: Childhood functional constipation, a common concern within child healthcare, necessitates oral and rectal medical treatments, that are mostly administered by parents in the home environment. It is important to gather children's perspectives in child- and family-centred care. The private nature of toileting, bowel movements, and faecal incontinence are areas of taboo and stigmatisation. Research is scarce on how children perceive this common but private situation of oral and rectal constipation treatment. Objective: To explore children's experiences of functional constipation and its treatments. Design: A qualitative interview study with a constructionist epistemology and a predominantly experiential orientation. Setting: Individual interviews …

Contemporary Structures, Processes, And Outcomes Of Critical Care Nursing Education: An Integrative Review, Farida Saghafi, Carol Grech, Belinda Causby, Angelique Clarke, Jacqueline Jauncey-Cooke, Deb Massey, Kaye Rolls, Kylie Thompson, Melanie Greenwood

Research outputs 2022 to 2026

Objective: The critical care workforce requires nurses who are specialised, educated, and adaptable to manage complex situations, with the capability to make informed decisions for optimal patient care. The Australian College of Critical Care Nurses supports evidence-based practice through an education position statement, which is periodically updated to reflect evolving needs. In this review, our aim was to inform revisions to the position statement on critical care nurse education by examining the structure, processes, and outcomes of contemporary education programs designed to enhance the capability of registered nurses working in critical care environments internationally. Review method used: An integrative review …

Intrapartum Experiences Of Gestational Surrogates And Intended Parents In Australia: A Qualitative Study, Jutharat Attawet, Leo Ng, Evie Kendal, Yunjing Qiu, Myles Ojabo, Sarah Jefford, Micah D.J. Peters

Research outputs 2022 to 2026

Background Gestational surrogacy is an increasingly visible, though tightly regulated, pathway to parenthood in Australia, yet intrapartum care remains under-examined. Existing maternity models are grounded in woman-centred care and offer limited guidance for births involving surrogates and intended parents within a triadic care relationship. Objectives To describe the intrapartum experiences of gestational surrogates and intended parents in Australia and to identify care processes that support or hinder respectful, inclusive practice. Methods A descriptive qualitative study was conducted with purposive sampling. Seventeen participants took part between December 2024 and May 2025, comprising nine gestational surrogates and eight intended parents who had …

Feasibility And Implementation Of Interval-Gap4: A Global Randomised Controlled Trial Of Intense Hybrid-Supervised/Self-Managed Versus Self-Directed Exercise For Metastatic Prostate Cancer, Stacey A. Kenfield, Nicolas H. Hart, Kerry S. Courneya, Rosemary Greenwood, June M. Chan, Jennette Sison, Li Zhang, Sarah Rudman, Leah Ung, Moritz Schumann, Erin L. Van Blarigan, Sam Mckeown, Charles J. Ryan, James Catto, Daniel A. Galvão, Robert U. Newton, Fred Saad

Research outputs 2022 to 2026

Background and objective: Physical activity is associated with a lower risk of mortality in men with prostate cancer (PC); yet, randomised controlled trials with survival endpoints are nonexistent. INTense ExeRcise for surviVAL-Global Action Plan 4 (INTERVAL-GAP4) was a global phase 3 trial designed to test whether structured, hybrid-supervised/self-managed exercise improves survival in men with metastatic PC. The trial was stopped early due to poor accrual. This paper reports feasibility and implementation outcomes. Methods: Men with metastatic PC were randomised (1:1) to a supervised/self-managed moderate- to high-intensity resistance and aerobic programme (three sessions per week for 2 yr) or to self-directed …

Making It Up As We Go: Midwives’ Perceptions Of Preparedness And Role Clarity In Surrogacy Birth Care, Jutharat Attawet, Leo Ng, Yunjing Qiu, Evie Kendal, Myles Ojabo, Sarah Jefford, Micah D.J. Peters

Research outputs 2022 to 2026

Background Surrogacy poses unique clinical, psychosocial, and organisational challenges. Midwives, often with limited experience, education, and guidance, may feel uncertain about providing appropriate care, potentially affecting the quality of care and experiences of surrogates, intended parents, and newborns. Objective This study explored how midwives navigate surrogacy birth care, with a focus on role clarity, involvement of intended parents, and preparedness across the intrapartum and postnatal continuum. Method An interpretative phenomenological design was adopted. Five midwives with experience in surrogacy births were recruited through professional networks and the Australian College of Midwives newsletter. In-depth interviews were conducted and analysed using reflexive …

Peak Lower Limb Joint Angles Are Weak Predictors Of Hamstring Length Change During Sprinting, Shayne Vial, Jodie Cochrane Wilkie, Anthony J. Blazevich, Daniel Kadlec

Research outputs 2022 to 2026

Non-contact hamstring injuries (HSIs) commonly occur during the late swing phase of sprinting, when muscle–tendon units (MTUs) approach maximum length. Although sagittal-plane pelvis, hip and knee angles are often used as surrogate measures of overall hamstring lengthening, their predictive validity remains uncertain. This study investigated whether peak three-dimensional lower limb joint angles predict length change in the biarticular hamstring MTUs from peak hip flexion through to toe off (0–100 %) in fourteen intermediate-level male soccer players sprinting at maximal speed (8.56 ± 0.47 m·s−1). Participant-specific musculoskeletal models were used to compute MTU lengths for the biceps femoris long head (BFlh), …

Carbohydrate Restriction Drives Greater Perturbations In Circulating Metabolites Than Low Energy Availability In Elite Male Athletes, Kyle A. Dunlop, Nathan G. Lawler, Jamie Whitfield, Alannah K.A. Mckay, Nicolin Tee, Megan L. Ross, Stacey N. Reinke, John A. Hawley, David Broadhurst, Louise M. Burke

Research outputs 2022 to 2026

Periods of low energy availability (LEA) are common in elite athletes and typically arise from reduced energy intake, often involving some degree of carbohydrate (CHO) restriction. Whether the metabolic profile created by energy restriction per se is distinct compared to that driven by CHO restriction is unknown. Using untargeted metabolomics, we examined metabolic perturbations linked to CHO restriction and energy restriction in plasma from elite male endurance athletes. In a semi-randomized controlled trial, athletes (n = 20) completed one of three 5-day dietary interventions: high energy-high CHO (HCHO); LEA (energy-restricted, CHO-reduced); or low-CHO, high-fat (LCHF; energy-matched, CHO-restricted). Plasma samples were …

Harmonizing Neuropsychological Test Data Across Prospective Studies, Rosita Shishegar, James D. Doecke, Yen Ying Lim, Pierrick Bourgeat, Vincent Dore, Bhargav Tallapragada, Simon M. Laws, Tenielle Porter, Samantha Burnham, Azadeh Feizpour, Ashley Gillman, Michael Weiner, Jason Hassenstab, Christopher C. Rowe, Victor L. Villemagne, Colin L. Masters, Jurgen Fripp, Hamid Sohrabi, Paul Maruff

Research outputs 2022 to 2026

Introduction: Alzheimer's disease (AD) research relies on large datasets and advanced statistical models. However, individual population studies often lack sufficient sample size for conclusive results. Harmonizing cognitive test data across studies can address this gap, despite differences in testing protocols. This study harmonizes cognitive data from three major AD cohorts to support robust clinical–pathological modelling. Methods: Information from the Alzheimer's Disease Neuroimaging Initiative (N = 1446); Australian Imaging, Biomarkers and Lifestyle (N = 1764); and Open Access Series of Imaging Studies-3 (N = 440) were integrated, including cognitive scores, demographics, genetics, and clinical and neuroimaging data. Neuropsychological tests relevant to …

Increasing Phytochemical-Rich Foods And Lactobacillus Probiotics In Men With Low-Risk Prostate Cancer – A Randomised, Double-Blind, Placebo-Controlled Trial, Robert J. Thomas, Stacey A. Kenfield, Madeleine Williams, Robert U. Newton, Jeffrey Aldous, Anita Mitra, Zahoor Fazili

Research outputs 2022 to 2026

Men on active surveillance (AS), with prostate cancer, are very interested in dietary strategies that could improve their symptoms and help prevent progression of their disease. In this real-world trial involving 208 men, intake of phytochemical-rich food capsules helped slow prostate-specific antigen (PSA) progression significantly, and improved urinary symptoms and erectile function. What was novel about this study was that men randomised to take an additional blend of five Lactobacillus probiotics had a further three-fold slowing of PSA progression as well as reduction of inflammation. Currently, nearly 50% of men opt out of AS within 5 yr. If confirmed with …

A Scalable Organoid Model Of Urothelial Aging For Metabolic Interrogation, Infection Modeling, And Reversal Of Age-Associated Changes, Adwaita R Parab, Arnold M Salazar, Steven J Bark, Margarita Divenko, Vasanta Putluri, D'Feau J Lieu, Aadya S Singh, Nagireddy Putluri, Indira U Mysorekar

Faculty, Staff and Students Publications

Aging leads to a progressive decline in overall bladder function resulting in lower urinary tract symptoms and increased susceptibility to infections. However, tissue-specific mechanisms of aging, specifically the contributions of the urothelium, remain elusive. Here, we introduce mouse bladder epithelium-derived organoids (mBEDOs) as a scalable platform to model urothelial aging. mBEDOs from aged mice recapitulate key features of age-associated cellular reprogramming, including oxidative stress, senescence, and DNA damage. We demonstrate the utility of mBEDOs for modeling Uropathogenic Escherichia coli (UPEC) infection, generating assembloids between mBEDOs and macrophages to model epithelial-immune interactions, and genetic perturbation. Using the mBEDO platform, we also …

Analysis Of Failure To Rescue In Adult Patients Who Undergo Open, Proximal Aortic Repair, Kyle W Blackburn, Joseph S Coselli, Armin Farazdaghi, Lynna Nguyen, Susan Y Green, Anna Xue, Vicente Orozco-Sevilla, Scott M Leikin, Marc R Moon, Subhasis Chatterjee

Faculty, Staff and Students Publications

Objective: Failure to rescue (FTR) is a metric of postoperative care, measuring a center's ability to prevent operative death after a surgical complication. We evaluated trends in and contributors to FTR after proximal aortic surgery at a high-volume institution.

Methods: Of 4180 patients in our single practice who underwent open proximal aortic repair from 1990 to 2024, 1304 (31.2%) had at least 1 of 4 FTR-related complications identified by the Society of Thoracic Surgeons (STS). Operative death was defined as death within 30 days of surgery or before hospital discharge or transfer. We analyzed FTR rate by specific complication, including …

Prospective Evaluation Of The European Society Of Cardiology 0/1h-Algorithm’S Safety And Efficacy For Triage Of Patients With Suspected Myocardial Infarction (Presc1se-Mi): Rationale And Design Of A Prospective International Multicenter Stepped-Wedge Cluster Randomized Controlled Trial, Jasper Boeddinghaus, Paolo Bima, Luca Crisanti, Dagmar I Keller, Ksenija Slankamenac, Michael Christ, Philipp Schuetz, Andrea Wiencierz, Ivo Strebel, Julia Reinhardt, Iryna Vyshnevska, Tzu-Ying Tsao, Felix Mahfoud, Maria Pia Ruggieri, Stephan Steuer, Òscar Miró, Veli-Pekka Harjola, Fulvio Morello, Peiman Nazerian, Dominik Roth, José Luis Zamorano, Deborah Erica Gannon, Jason Pott, Mohammed Oa Abubakr, Hyun Suk Yang, Joe Young, Richina Bicette, Andreea Cuculici, Héctor Bueno, Juan Sanchis, Christian Mueller

Faculty, Staff and Students Publications

Background: International practice guidelines recommend the more rapid European Society of Cardiology (ESC) 0/1h-algorithm for the triage of patients with suspected myocardial infarction (MI) as the preferred option and consider the ESC 0/3h-algorithm as an alternative. However, many centers worldwide have not yet adopted the ESC 0/1h-algorithm in clinical practice due to uncertainty which approach best balances safety and efficacy.

Methods: PRESC1SE-MI (PRospective Evaluation of the European Society of Cardiology 0/1h-algorithm`s Safety and Efficacy for Triage of Patients with Suspected Myocardial Infarction) is an international, investigator-initiated multicenter, stepped-wedge, cluster randomized controlled trial. At least 52,156 consecutive adult patients with nontraumatic …

Cyclic Amp-Dependent Regulation Of Ryanodine Receptors In Healthy And Diseased Hearts, Mohit M Hulsurkar, Isabelle Ong, Joshua A Keefe, Issam H Abu-Taha, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

Cyclic adenosine monophosphate (cAMP) is a critical second messenger in cardiomyocytes, regulating essential cellular functions. Upon G-protein-coupled receptor stimulation, adenylyl cyclase (AC) synthesizes cAMP, which phosphodiesterase (PDE) enzymes subsequently degrade. Recent studies challenge the traditional view of uniform cAMP signaling, revealing nanodomain-specific regulation within cardiomyocytes. This localized cAMP signaling modulates key Ca2+-handling proteins, including ryanodine receptor type-2 (RyR2), through channel-bound protein kinases and PDEs. Additionally, nucleoside-diphosphate kinases (NDPKs), particularly NDPK-C, contribute to cAMP synthesis and RyR2 regulation. Elevated NDPK-C levels in failing hearts correlate with increased cAMP levels, enhanced sarcoplasmic reticulum Ca2+ release, and cardiac arrhythmias. Furthermore, cAMP influences the …

Recognising Type 5 Diabetes – Authors’ Reply, Meredith Hawkins, Peter Schwarz, Chittaranjan S Yajnik, Mandeep Bajaj, Alvin C Powers, Michael S Boyne, Sarah Wild, Dirk L Christensen, Silver Bahendeka, Angus G Jones, Satinath Mukhopadhyay, Kaushik Ramaiya, David Phillips, Sylvia Kehlenbrink, Davis Kibirige, Charlotte Bavuma, Noel P Somasundaram, Debbie S Thompson, Jacko Abodo, Shitaye Alemu, Prasad Katulanda, Faruque Pathan, Shahjada Selim, Sarah Mathai, Mini Joseph, Mahindra Sonawane, Sandeep Mathur, Shajith Anoop, Sadishkumar Kamalanathan, Prosenjit Mondal, Dukhabandhu Naik, Ullas Kolthur-Seetharam, Riddhi Dasgupta, Felix Jebasingh, Nihal Thomas, Pradnyashree Wadivkar, Allan A Vaag

Faculty, Staff and Students Publications

No abstract provided.

Baseline Characteristics In The Synchronize™-2 Randomized Phase 3 Trial Of Survodutide, A Glucagon Receptor/Glp-1 Receptor Dual Agonist, For Obesity In People With Type 2 Diabetes, Sean Wharton, Carel W Le Roux, Biykem Bozkurt, Elke Platz, Gabriele Bleckert, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Isabel M Kloer, Lee M Kaplan

Faculty, Staff and Students Publications

Aims: Survodutide is an investigational glucagon receptor/glucagon-like peptide-1 receptor dual agonist that has shown promise for treating obesity and its complications in Phase 2 trials. Two double-blind, randomized, global Phase 3 trials are designed to assess the efficacy and safety of survodutide for treatment of obesity-SYNCHRONIZE™-1 in people with obesity without type 2 diabetes (T2D) and SYNCHRONIZE™-2 in people with obesity and T2D. This paper describes the baseline characteristics of participants in SYNCHRONIZE-2 (ClinicalTrials.gov identifier NCT06066528).

Materials and methods: Participants aged ≥18 years with a body mass index (BMI) ≥27 kg/m2 and T2D were randomized 1:1:1 to weekly subcutaneous …

Icosapent Ethyl Reduces Cvd Risk In Cardiovascular-Kidney-Metabolic Syndrome: Reduce-It Ckm, Michael Miller, Deepak L Bhatt, Eliot A Brinton, Terry A Jacobson, Ph Gabriel Steg, Steven B Ketchum, Armando Lira Pineda, Jean-Claude Tardif, Christie M Ballantyne

Faculty, Staff and Students Publications

Background/introduction: Cardiovascular-kidney-metabolic (CKM) syndrome was recently identified as a cardiometabolic disorder that incorporates chronic kidney disease with the metabolic syndrome (MetS). REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was an international, double-blind, placebo-controlled trial that randomized hypertriglyceridemic (TG, 150-499 mg/dL) statin-treated patients with established cardiovascular disease (CVD) or diabetes and multiple CVD risk factors to icosapent ethyl (IPE) or placebo (4 grams/day). It is unknown if renal insufficiency added to MetS confers incremental CVD risk in secondary prevention patients without diabetes and if IPE lowers that risk.

Methods: The current study evaluated the secondary prevention patient subgroup with …

Multi-Trait And Multi-Ancestry Genetic Analysis Of Comorbid Lung Diseases And Traits Improves Genetic Discovery And Polygenic Risk Prediction, Yixuan He, Wenhan Lu, Yon Ho Jee, Mu-Yi Shih, Ying Wang, Kristin Tsuo, David C Qian, James A Diao, Hailiang Huang, Chirag J Patel, Jinyoung Byun, Bogdan Pasaniuc, Elizabeth G Atkinson, Christopher I Amos, Yen-Chen Anne Feng, Matthew Moll, Michael H Cho, Alicia R Martin

Faculty, Staff and Students Publications

While respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma share many risk factors, most studies investigate them in isolation and in predominantly European-ancestry populations. Here, we conducted the most powerful multi-trait and multi-ancestry genetic analysis of respiratory diseases and auxiliary traits to date, identifying 25 new loci associated with lung function in individuals of East Asian ancestry. Using these results, we developed PRSxtra (cross-trait and cross-ancestry), a multi-trait and multi-ancestry polygenic risk score (PRS) approach that leverages shared components of heritable risk via pleiotropic effects. PRSxtra significantly improved the prediction of asthma, COPD and lung cancer compared …

Validation Of The French Translation Of The Movement Disorder Society Non-Motor Symptoms Scale (Mds-Nms) In Parkinson's Disease, Clément Desjardins, Stéphan Grimaldi, Sheng Luo, Luowen Yu, Christopher G Goetz, Glenn T Stebbins, Pablo Martinez-Martin, Monica M Kurtis, Tiago A Mestre, Alvaro Sanchez-Ferro, Michelle H S Tosin, Roberta Balestrino, Chi-Ying R Lin, Carmen Gasca-Salas, Tatiana Witjas, Olivier Colin, David Maltete, Luc Defebvre, Caroline Giordana, Mahmoud Charif, Claire Thiriez, Chloé Laurencin, Mélissa Tir, Gwendoline Dupont, Philippe Remy, Christine Tranchant, Sophie Drapier, Alexandra Samier, Isabelle Benatru, Sara Sambin, Jean-Christophe Corvol, Fatma Khelifi, Margherita Fabbri, Olivier Rascol, Ns‐Part Cohort Study Group And The Mds Coa Translation Steering Committee

Faculty, Staff and Students Publications

No abstract provided.

Minifast: A Sensitive And Fast Miniaturized Microscope For In Vivo Neural Recording, Jill Juneau, Guillaume Duret, Joshua P Chu, Blake Madruga, Conor C Dorian, Alexander V Rodriguez, Savva Morozov, Daniel Aharoni, Jacob T Robinson, François St-Pierre, Peyman Golshani, Caleb Kemere

Faculty, Staff and Students Publications

Significance: Observing the activity of large populations of neurons in vivo is critical for understanding brain function and dysfunction. The use of fluorescent genetically encoded calcium indicators (GECIs) in conjunction with miniaturized microscopes is an exciting emerging toolset for recording neural activity in unrestrained animals. Despite their potential, current miniaturized microscope designs are limited using image sensors with low frame rates, sensitivity, and resolution. Beyond GECIs, there are many neuroscience applications that would benefit from the use of other emerging neural indicators, such as fluorescent genetically encoded voltage indicators (GEVIs) that have faster temporal resolution to match neuron spiking, yet …

Rethinking The Centrality Of Brain Areas In Understanding Functional Organization, Benjamin Yost Hayden, Sarah R Heilbronner, Seng Bum Michael Yoo

Faculty, Staff and Students Publications

Parcellation of the cerebral cortex into functionally modular brain areas is foundational to cognitive and systems neuroscience. Here, we question the central status of brain areas from the perspectives of neuroanatomy and electrophysiology. We argue that the major ostensible determinants of brain function, such as cytoarchitecture and connectivity, seldom produce convergent parcellations. Brain areas themselves are just one of several equally important organizing principles; others include macroscale gradients, distributed networks, layers, columns and patches. We further argue that the evidence for a close correspondence between areal parcellation and cognitive function is weaker than is generally supposed. Indeed, many important cognitive …

Deep Brain Stimulation Response Circuits In Obsessive-Compulsive Disorder, Andreas Horn, Ningfei Li, Garance M Meyer, Ron Gadot, Nicole R Provenza, Sameer A Sheth

Faculty, Staff and Students Publications

In the field of deep brain stimulation (DBS), two major themes are currently making significant progress. First, the framework of connectomic DBS, in which circuits that are associated with improvements of specific symptoms are described and targeted to improve and potentially personalize treatment. Second, the concept of brain sensing and adaptive DBS, which aims at identifying neural biomarkers that may guide stimulation in a closed-loop fashion.

In DBS for Obsessive Compulsive Disorder (OCD), substantial progress has been made on both ends, over the last five years. Together, results begin to draw a picture of exactly which circuit is …