Medicine and Health Sciences Commons^™

Perioperative Durvalumab Plus Chemotherapy Plus New Agents For Resectable Non-Small-Cell Lung Cancer: The Platform Phase 2 Neocoast-2 Trial, Tina Cascone, Laura Bonanno, Florian Guisier, Amelia Insa, Moishe Liberman, Olivier Bylicki, Lorenzo Livi, Thomas Egenod, Romain Corre, Dong-Wan Kim, Maria Rosario Garcia Campelo, Mariano Provencio Pulla, Byoung Yong Shim, Giulio Metro, Jaafar Bennouna, Agata A Bielska, Alula R Yohannes, Yun He, Adam Dowson, Gozde Kar, Lara Mcgrath, Rakesh Kumar, Italia Grenga, Jonathan Spicer, Patrick M Forde

Faculty, Staff and Student Publications

In the phase II NeoCOAST-2 platform study, 202 patients with untreated, resectable stage IIA–IIIB non-small-cell lung cancer (NSCLC) were randomized to receive neoadjuvant durvalumab plus platinum-doublet chemotherapy with oleclumab, a CD73 inhibitor (Arm 1), or with monalizumab, a NKG2A inhibitor (Arm 2), or neoadjuvant durvalumab plus single-agent platinum chemotherapy with the TROP-2 antibody–drug conjugate (ADC) datopotamab deruxtecan (Arm 4), followed by surgical resection and adjuvant durvalumab with oleclumab or monalizumab (Arms 1 and 2) or durvalumab alone (Arm 4). Primary endpoints were pathological complete response (pCR) rate and safety; secondary endpoints included feasibility of surgery and major pathological response (mPR) …

A Phase 2 Trial Of Cpx-351 Combined With Venetoclax In Relapsed Or Refractory Acute Myeloid Leukemia, Tapan M Kadia, Wei-Ying Jen, Alex Bataller, Alexandre Bazinet, Gautam Borthakur, Elias Jabbour, Wei Qiao, Nicholas J Short, Koichi Takahashi, Ghayas C Issa, Courtney D Dinardo, Guillermo Montalban-Bravo, Naveen Pemmaraju, Andrew Tran, Vanthana Bharathi, Sanam Loghavi, Amin M Alousi, Uday Popat, Naval G Daver, Farhad Ravandi, Hagop M Kantarjian

Faculty, Staff and Student Publications

Outcomes in patients with relapsed/refractory (RR) AML are poor. We sought to investigate if CPX-531 in combination with venetoclax (CPX + VEN) was tolerable and effective in RR AML. This was a single institution phase 1b/2 trial of CPX + VEN. Patients aged ≥ 18 years with RR AML who were fit for intensive chemotherapy were eligible. Prior venetoclax exposure was allowed. The phase 1b portion followed a 3 + 3 design to identify the recommended phase 2 dose (RP2D) for the expansion cohort. At the starting dose level of −1, prolonged myelosuppression was observed, leading to dose level −2 …

Excellent Response Following Palliative Radiation For Locally Advanced Epidemic/Aids-Associated Kaposi Sarcoma Of The Lower Extremity: A Case Report, Anushka S Mandalapu, Alison K Yoder, Xin Wang, Devarati Mitra, Andrew J Bishop, B Ashleigh Guadagnolo, Ahsan S Farooqi

Faculty, Staff and Student Publications

No abstract provided.

Acquired Resistance In Cancer: Towards Targeted Therapeutic Strategies, Alice Soragni, Erik S Knudsen, Thomas N O'Connor, Cristina E Tognon, Jeffrey W Tyner, Beatrice Gini, Donghwa Kim, Trever G Bivona, Xingxing Zang, Agnieszka K Witkiewicz, David W Goodrich, Dadi Jiang, Seth T Gammon, Christopher D Willey, Paul C Boutros, Vlad C Sandulache, Abdullah A Osman, Jeffrey N Myers, Kamiya Mehla, Pankaj K Singh, Keith S Chan, Hongbo Gao, Himangi Marathe

Faculty, Staff and Student Publications

Development of acquired therapeutic resistance limits the efficacy of cancer treatments and accounts for therapeutic failure in most patients. How resistance arises, varies across cancer types and differs depending on therapeutic modalities is incompletely understood. Novel strategies that address and overcome the various and complex resistance mechanisms necessitate a deep understanding of the underlying dynamics. We are at a crucial time when innovative technologies applied to patient-relevant tumour models have the potential to bridge the gap between fundamental research into mechanisms and timing of acquired resistance and clinical applications that translate these findings into actionable strategies to extend therapy efficacy. …

Molecular Determinants Of Sotorasib Clinical Efficacy In Krasg12c-Mutated Non-Small-Cell Lung Cancer, Ferdinandos Skoulidis, Bob T Li, Adrianus Johannes De Langen, David S Hong, Herve Lena, Juergen Wolf, Grace K Dy, Alessandra Curioni Fontecedro, Pascale Tomasini, Vamsidhar Velcheti, Anthonie J Van Der Wekken, Christophe Dooms, Luis Paz-Ares Rodriguez, Giannis Mountzios, Adrian Sacher, Ernest Nadal, Sebastien Couraud, Sang-We Kim, Kenneth O'Byrne, Danilo Rocco, Ryo Toyozawa, Izabela Chmielewska, Colin R Lindsay, Antreas Hindoyan, Lata Mukundan, Tomasz Wilmanski, Abraham Anderson, Christine Ardito-Abraham, Amrita Pati, Anita Reddy, Bhakti Mehta, Martin Schuler

Faculty, Staff and Student Publications

Molecular determinants of KRAS(G12C)inhibitor efficacy in KRASG12C-mutated non-small-cell lung cancer (NSCLC) remain poorly characterized. Here we report one of the largest integrated analyses to date of sotorasib clinical efficacy biomarkers from the phase 2 CodeBreaK 100 and phase 3 CodeBreaK 200 studies. We reveal differential sotorasib activity and relative benefit compared to docetaxel across KRASG12C-mutated NSCLC co-mutational subsets and transcriptional subtypes. We also identify low expression of TTF1 and KEAP1 co-mutations/NRF2 activation as major determinants of sotorasib anti-tumor efficacy and adverse prognostic features. Exploratory analyses highlight potential tumor cell-extrinsic contributors to sotorasib anti-tumor activity and suggest …

Intention To Take Pre-Exposure Prophylaxis (Prep) As An Hiv Preventive Medication: An Application Of The Health Belief Model And Theory Planned Behavior, Besuthu Nakekelwa Nkambule

Graduate Theses and Dissertations

South Africa (SA) has 7.7 million citizens (12.6% of its 2023 population) living with human immunodeficiency virus (HIV). The use of pre-exposure prophylaxis (PrEP) as an antiretroviral medication for HIV-negative individuals is a promising HIV prevention strategy in SA that can help the attainment of an HIV free generation. PrEP offers greater than 90% protection against HIV acquisition. Despite SA’s efforts in increasing PrEP coverage for its citizens, primarily to those at substantial risk, its adoption remains relatively low. Structural barriers related to access, costs, lack of awareness, and, more recently, US funding cuts exacerbate the challenges of PrEP’s potential …

Computed Tomography Radiomics-Based Cross-Sectional Detection Of Mandibular Osteoradionecrosis In Head And Neck Cancer Survivors, Serageldin Kamel, Laia Humbert-Vidan, Zaphanlene Kaffey, Sarah Mirbahaeddin, Abdulrahman Abusaif, David T A Fuentes, Kareem Wahid, Cem Dede, Mohamed A Naser, Renjie He, Ahmed W Moawad, Khaled M Elsayes, Melissa M Chen, Adegbenga O Otun, Jillian Rigert, Mark S Chambers, Andrew Hope, Erin Watson, Kristy K Brock, Katherine Hutcheson, Lisanne Van Dijk, Amy C Moreno, Stephen Y Lai, Clifton D Fuller, Abdallah S R Mohamed, Md Anderson Head And Neck Cancer Symptom Working Group

Faculty, Staff and Student Publications

Purpose: This study aims to identify radiomic features from contrast-enhanced CT (CECT) scans that differentiate osteoradionecrosis (ORN) from normal mandibular bone in head and neck cancer (HNC) patients treated with radiotherapy (RT).

Materials and methods: CECT images from 150 patients with confirmed ORN diagnosis (2008-2018) at MD Anderson Cancer Center (MDACC) were analyzed (80 % train, 20 % test). Radiomic features were extracted using PyRadiomics from manually segmented ORN regions and automated contralateral healthy mandible regions. Correlation analysis (r > 0.95) reduced features for model training. A random Forest (RF) classifier with Recursive Feature Elimination identified discriminative features. Explainability was assessed …

Characterization Of The Germline Pathogenic Mutational Landscape And Oncologic Outcomes Among 877 Patients With Invasive Lobular Carcinoma, Victoria D Huynh, Jason Mouabbi, Henry M Kuerer, Kerollos Nashat Wanis, Hiam M Abdel-Salam, Angelica M Gutierrez, Helen M Johnson, Anthony Lucci, Kelly K Hunt, Banu K Arun

Faculty, Staff and Student Publications

Purpose: There is a paucity of literature on germline pathogenic variants (gPVs) in patients with invasive lobular carcinoma (ILC). This study characterizes the landscape and compares clinicopathologic variables and treatment outcomes between those with and without gPVs.

Methods: A prospectively maintained institutional database was used to identify all patients diagnosed with nonmetastatic ILC who had germline genetic testing. Clinicopathologic characteristics and time to recurrence, contralateral cancer, and death were compared for patients with and without gPVs. Conditional hazard ratios, computed by Cox proportional hazards models, described associations between clinicopathologic factors, including gPV status, and cancer events.

Results: Of 4398 patients …

Mitophagy’S Impacts On Cancer And Neurodegenerative Diseases: Implications For Future Therapies, Jason Huang, Vincent Truong Pham, Shaozi Fu, Gang Huang, Ya-Guang Liu, Lei Zheng

Faculty, Staff and Student Publications

Substantial evidence supports an inverse relationship between cancer and neurodegenerative diseases (NDDs), but few studies investigate the biological mechanisms underlying this phenomenon. While previous explanations-such as inflammation, reactive oxygen species (ROS), genetic mutations, and cell death-remain significant, they ultimately converge on mitophagy. This review identifies mitophagy as a pivotal factor in the development of both cancer and NDDs, while also evaluating specific mechanisms and processes to clarify how mitophagy connects these opposing disease trajectories. By examining these factors, we aim to uncover the underlying mechanisms that explain the inverse relationship between cancer and NDDs, which will help develop therapeutic strategies …

Seeking Existential Meaning In The “Sea Of Trees:” A Qualitative Exploration In The Depths Of Japan’S Aokigahara “Suicide” Forest, Sophia Bates

Masters Theses, 2020-current

This thesis explores the intercultural perceptions of suicidality and the role that these perceptions have on meaning of life in Japanese culture through an exploratory, autoethnographic analysis of my journey walking through Japan’s Aokigahara “suicide” Forest. In June 2024, I traveled to Fujikawaguchiko, Japan to conduct an autoethnographic analysis of my experiences walking through Aokigahara Forest using shinrin-yoku and mindful walking (Jung, 2014) as supplemental research methodologies to make empirical observations and take notes on my journey walking through suicide forest as an embodied sensory experience. Drawing upon the research and ideas of cultural anthropologist and existential philosopher Ernest Becker, …

A Comprehensive Narrative Review Of The Challenges Surrounding Cutaneous Scc., Sarah C Beach, Austin S Cusick, Aaron S Farberg, Shannon C Trotter

Ambulatory and Primary Care Articles

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer (NMSC) and is predominantly found in the head and neck region. With an annual increase in NMSC diagnoses, cSCC presents significant diagnostic and therapeutic challenges. This review discusses the many risk factors for the development of cSCC, outlines the criteria for defining high-risk cSCC, and examines treatment approaches of these tumors based on risk stratification. While most cSCCs are treatable with surgical excision, approximately 5% metastasize, with head and neck cSCC showing poor prognosis once metastasis occurs. High-risk cSCCs, which are more likely to recur or metastasize, …

Sex-Related Measurement Bias In Autism Spectrum Disorder Symptoms In The Baby Siblings Research Consortium, Catherine A Burrows, Natasha Marrus, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Disparities exist in age of diagnosis and prevalence of autism spectrum disorder (ASD) for female compared with male children. Correcting for sources of bias is critical for improving equitable ASD identification.

OBJECTIVE: To determine whether sex differences exist in measurement of ASD symptoms using the Autism Diagnostic Observation Schedule (ADOS) among young children at high familial likelihood (HFL) and low familial likelihood (LFL) of ASD.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study collected longitudinal, prospective data from the Baby Siblings Research Consortium between January 1, 2003, and December 31, 2021. Participants included 3106 children who had an older sibling …

Screening Programmes And Breast Cancer Mortality: An Observational Study Of 194 Countries, Syed Mahfuz Al Hasan, Debbie L Bennett, Adetunji T Toriola

2020-Current year OA Pubs

OBJECTIVE: To investigate the associations between national breast cancer screening programmes and breast cancer mortality globally.

METHODS: We collected data on breast cancer screening programmes and breast cancer mortality from the World Health Organization's Global Health Observatory, the Global Burden of Diseases 2021 study and the Eurostat database. We assessed differences in breast cancer mortality between countries with regular and irregular screening programmes, adjusting for sociodemographic index. We calculated annual changes in breast cancer mortality from 2015 to 2021 and assessed differences in mortality changes between countries with regular and irregular screening programmes.

FINDINGS: Between 2015 and 2021, 94 of …

Implementation Outcomes Of A Patient Decision-Aid In A Diverse Population With Systemic Lupus Erythematosus In 15 Us Rheumatology Clinics, Jasvinder A Singh, Seth Eisen, Alfred Kim, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The objective of this study was to examine the clinical outcomes during the implementation of a self-administered patient decision-aid (PtDA) for lupus.

METHODS: We provided an effective computerized lupus PtDA in 15 rheumatology outpatient clinics 2019-2024 (including the COVID pandemic). We undertook Organizational Readiness to Implement Change Surveys (ORICs) and Team Learning and Psychological Safety Surveys (TLPSSs) at baseline. The primary study outcome objective measure, percent penetration/reach, was defined as the number of patients who viewed the lupus PtDA at the end of the study, divided by the total number of eligible patients (times 100). We used validated clinical …

Benefit Of Early Oseltamivir Therapy For Adults Hospitalized With Influenza A: An Observational Study, Nathaniel M Lewis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Clinical guidelines recommend initiation of antiviral therapy as soon as possible for patients hospitalized with confirmed or suspected influenza.

METHODS: A multicenter US observational sentinel surveillance network prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during 1 October 2022-21 July 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), …

Dissemination And Implementation Of A Telehealth-Enabled Program For Providing Infectious Disease Expertise In Rural Settings, Robin L P Jump, Jason P Burnham, Et Al.

2020-Current year OA Pubs

BACKGROUND: Telehealth can facilitate improving antibiotic use and related antimicrobial stewardship activities in facilities underserved by infectious diseases (IDs) expertise. We describe implementation of the Department of Veterans Affairs (VA) videoconference antimicrobial stewardship team (VAST) to connect multidisciplinary teams from rural VA medical centers (VAMCs) with geographically distant ID experts.

METHODS: We implemented VASTs at 10 rural VAMCs from September 2021 to February 2024. VASTs consisted of regular meetings between rural VAMCs and an off-site ID expert who met by videoconference to discuss clinical cases, emphasizing recommendations for antibiotic prescribing. The VA Corporate Data Warehouse was used to collect information …

The Global Neurodegeneration Proteomics Consortium: Biomarker And Drug Target Discovery For Common Neurodegenerative Diseases And Aging, Farhad Imam, Muhammad Ali, Carlos Cruchaga, Chengran Yang, Et Al.

2020-Current year OA Pubs

More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions. High-dimensional molecular studies in biofluids ('omics') offer promise for scalable biomarker discovery, but challenges in assembling large, diverse datasets hinder progress. To address this, the Global Neurodegeneration Proteomics Consortium (GNPC)-a public-private partnership-established one of the …

Integrative Genomic Reconstruction Reveals Heterogeneity In Carbohydrate Utilization Across Human Gut Bifidobacteria, Aleksandr A Arzamasov, Dmitry A Rodionov, Matthew C Hibberd, Janaki L Guruge, James E Kent, Marat D Kazanov, Semen A Leyn, Marinela L Elane, Kristija Sejane, Annalee Furst, Lars Bode, Michael J Barratt, Jeffrey I Gordon, Andrei L Osterman

2020-Current year OA Pubs

Bifidobacteria are beneficial saccharolytic microbes that are widely used as probiotics or in synbiotic formulations, yet individual responses to supplementation can vary with strain type, microbiota composition, diet and lifestyle, underscoring the need for strain-level insights into glycan metabolism. Here we reconstructed 68 pathways for the utilization of mono-, di-, oligo- and polysaccharides by analysing the distribution of 589 curated metabolic gene functions (catabolic enzymes, transporters and transcriptional regulators) across 3,083 non-redundant Bifidobacterium genomes of human origin. Thirty-eight predicted phenotypes were validated in vitro for 30 geographically diverse strains, supporting genomics-based predictions. Our analysis uncovered extensive inter- and intraspecies functional …

Germline Genetic Variation Impacts Clonal Hematopoiesis Landscape And Progression To Malignancy, Jie Liu, Duc Tran, Brian J Wiley, Irenaeus C C Chan, Indraniel Das, Li Ding, Yin Cao, Matthew J Walter, Daniel C Link, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

With age, clonal expansions occur pervasively across normal tissues yet only in rare instances lead to cancer, despite being driven by well-established cancer drivers. Characterization of the factors that influence clonal progression is needed to inform interventional approaches. Germline genetic variation influences cancer risk and shapes tumor mutational profile, but its influence on the mutational landscape of normal tissues is not well known. Here we studied the impact of germline genetic variation on clonal hematopoiesis (CH) in 731,835 individuals. We identified 22 new CH-predisposition genes, most of which predispose to CH driven by specific mutational events. CH-predisposition genes contribute to …

Impact Of Transcatheter Aortic Valve Replacement Use Ratio On Outcomes In Patients With Aortic Valve Disease, Theodore Marghitu, Sophia H Roberts, June He, Nicholas Kouchoukos, Puja Kachroo, Harold Roberts, Ralph Damiano, Alan Zajarias, Marc Sintek, John Lasala, Alexander A Brescia, Tsuyoshi Kaneko

2020-Current year OA Pubs

OBJECTIVE: Use of the Heart Team has been the standard of care for the treatment of aortic valve disease; however, its efficacy has not been evaluated. We sought to analyze its impact using the transcatheter aortic valve replacement (TAVR) use ratio (number of TAVR/total aortic valve replacement [AVR] volume) on TAVR, surgical aortic valve replacement (SAVR), and overall AVR outcomes.

METHODS: We analyzed all TAVRs and SAVRs sampled by the National Readmissions Database between 2016 and 2020. Hospitals were stratified into quartiles on the basis of their TAVR/AVR ratio. Centers with a ratio below the first quartile were considered "low …

Medicaid Accessibility For Ophthalmologists And Optometrists In Florida: A Pilot Study, Darby D Miller, Isabella V. Wagner, Michael W. Stewart, Abhimanyu S. Ahuja, Syril Dorairaj, Richard D. Ten Hulzen, Aaron Y. Lee

2020-Current year OA Pubs

OBJECTIVE AND METHODS: This study aimed to evaluate Medicaid accessibility for ophthalmologists and optometrists in Florida. A cross-sectional telephone survey was conducted between February and March 2018 using a geographically uniform sample of 22 ophthalmologists and 80 optometrists registered with Medicaid. Providers were asked whether they accepted new Medicaid patients (adult and/or pediatric) and for the earliest available appointment. Categorical variables were compared using Fisher's exact test, and time to next appointment was analyzed using the Wilcoxon rank-sum test (α = 0.05).

RESULTS: Across all age groups, a greater proportion of ophthalmologists (95.4%) accepted some form of Medicaid compared to …

A Three-Stage Matheuristic For The Blood Stochastic Inventory Routing Problem, Vincent F. Yu, Nabila Salsabila, Aldy Gunawan, Aldy Gunawan, Nurhadi Siswanto

Research Collection School Of Computing and Information Systems

This research introduces a blood distribution system under vendor-managed inventory that considers uncertain supply and demand. We present it as the Blood Stochastic Inventory Routing Problem, formulating it as a two-stage stochastic programming model. To solve this problem, this study proposes a three-stage matheuristic that combines a perturbation heuristic, Adaptive Large Neighborhood Search, and an exact approach. From historical data of Surabaya Blood Center in Indonesia, six sets of new instances are generated under different settings. Computational results show that our proposed three-stage matheuristic outperforms CPLEX and a two-stage matheuristic by gaining optimal or better solutions within a significantly shorter …

Disruption Of The Cerebrospinal Fluid-Plasma Protein Balance In Cognitive Impairment And Aging, Amelia Farinas, Daniel Western, Jigyasha Timsina, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

The brain barrier system, including the choroid plexus, meninges and brain vasculature, regulates substrate transport and maintains differential protein concentrations between blood and cerebrospinal fluid (CSF). Aging and neurodegeneration disrupt brain barrier function, but proteomic studies of the effects on blood-CSF protein balance are limited. Here we used SomaScan proteomics to characterize paired CSF and plasma samples from 2,171 healthy or cognitively impaired older individuals from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium. We identified proteins with correlated CSF and plasma levels that are produced primarily outside the brain and are enriched for structural domains that may enable their …

Echollm: Extracting Echocardiogram Entities With Light-Weight, Open-Source Large Language Models, Jonathan Chi, Yazan Rouphail, Ethan Hillis, Ningning Ma, An Nguyen, Jane Wang, Mackenzie Hofford, Aditi Gupta, Patrick G Lyons, Adam Wilcox, Albert M Lai, Philip R O Payne, Marin H Kollef, Caitlin Dreisbach, Andrew P Michelson

2020-Current year OA Pubs

OBJECTIVES: Large language models (LLMs) have demonstrated high levels of performance in clinical information extraction compared to rule-based systems and traditional machine-learning approaches, offering scalability, contextualization, and easier deployment. However, most studies rely on proprietary models with privacy concerns and high costs, limiting accessibility. We aim to evaluate 14 publicly available open-source LLMs for extracting clinically relevant findings from free-text echocardiogram reports and examine the feasibility of their implementation in information extraction workflows.

MATERIALS AND METHODS: We used 14 open-source LLM models to extract clinically relevant entities from echocardiogram reports (

RESULTS: In aggregate, Gemma2:9b-instruct had the highest precision, recall, …

Combination Effect Of Finerenone And Empagliflozin In Participants With Chronic Kidney Disease And Type 2 Diabetes Using A Uacr Endpoint (Confidence) Trial: Baseline Clinical Characteristics, Rajiv Agarwal, Janet B Mcgill, Et Al.

2020-Current year OA Pubs

BACKGROUND: Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitors (SGLT2is) both reduce chronic kidney disease (CKD) progression and improve kidney/cardiovascular (CV) outcomes. The CONFIDENCE (COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint) study (NCT05254002; EudraCT 2021-003037-11) hypothesis is that early combination of finerenone and empagliflozin, an SGLT2i, is superior to either drug alone in reducing urine albumin-to-creatinine ratio (UACR) over 6 months.

METHODS: CONFIDENCE is an ongoing, fully enrolled, randomized, controlled, double-blind, multicentre phase 2 clinical trial in adults (≥18 years of age) with …

Tau Pet Positivity In Individuals With And Without Cognitive Impairment Varies With Age, Amyloid-Β Status, Apoe Genotype And Sex, Rik Ossenkoppele, Tammy L S Benzinger, Et Al.

2020-Current year OA Pubs

Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia. We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU …

Shared And Disease-Specific Pathways In Frontotemporal Dementia And Alzheimer's And Parkinson's Diseases, Muhammad Ali, Yike Chen, Ying Xu, Katherine Gong, Menghan Liu, Jigyasha Timsina, Daniel Western, Chengran Yang, Gyujin Heo, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD) and frontotemporal dementia (FTD), exhibit distinct yet overlapping pathological mechanisms. Leveraging large-scale plasma proteomics data from the Global Neurodegeneration Proteomics Consortium, we analyzed 10,527 plasma samples (1,936 AD, 525 PD, 163 FTD, 1,638 dementia and 6,265 controls) to identify disease-specific and shared proteins across NDs. We identified 5,187 proteins significantly associated with AD, 3,748 with PD and 2,380 with FTD that revealed both common and divergent proteomic signatures, which were confirmed by multiple analytical approaches and orthogonal validation. PD and FTD showed the highest overlap (r

Do Risk Factors For Hcc Impact The Association Of Ct/Mri Lirads Major Features With Hcc? An Individual Participant Data Meta-Analysis, Robert G Adamo, Daniel R Ludwig, Tyler J Fraum, Et Al.

2020-Current year OA Pubs

No abstract provided.

The Microrna Mir-30a Blocks Adipose Tissue Fibrosis Accumulation In Obesity, Pradip K Saha, Robert Sharp, Aaron R. Cox, Rabie Habib, Michael J. Bolt, Jessica B. Felix, Claudia E. Ramirez Bustamante, Xin Li, Sung Yun Jung, Kang Ho Kim, Kai Sun, Huaizhu Wu, Samuel Klein, Sean M. Hartig

2020-Current year OA Pubs

White adipose tissue (WAT) fibrosis occurring in obesity contributes to the inflammatory and metabolic comorbidities of insulin resistance and type 2 diabetes, yet the mechanisms involved remain poorly understood. Here, we report a role for the broadly conserved miRNA miR-30a as a regulator of WAT fibrosis and systemic glucose metabolism. Mice modified to express miR-30a at elevated levels in adipose tissues maintain insulin sensitivity coupled with reduced fatty liver disease when fed a high-fat diet. These effects were attributable to cell-autonomous functions of miR-30a that potently increase expression of adipocyte-specific genes. Proteomic screening revealed miR-30a limits profibrotic programs in subcutaneous …

Active Dna Demethylation Upstream Of Rod-Photoreceptor Fate Determination Is Required For Retinal Development, Ismael Hernández-Núñez, Alaina Urman, Xiaodong Zhang, William Jacobs, Christy Hoffmann, Ellen G. Harding, Shiming Chen, Meelad M. Dawlaty, Philip A. Ruzycki, John R. Edwards, Brian S. Clark

2020-Current year OA Pubs

Retinal cell fate specification from multipotent retinal progenitors is governed by dynamic changes in chromatin structure and gene expression. Methylation at cytosines in DNA (5mC) is actively regulated for proper control of gene expression and chromatin architecture. Numerous genes display active DNA demethylation across retinal development; a process that requires oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) and is controlled by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. Using an allelic series of conditional TET enzyme mutants in mice, we determine that DNA demethylation is required upstream of NRL and NR2E3 expression for the establishment of rod-photoreceptor fate. Using histological, behavioral, …