Medicine and Health Sciences Commons^™

Real-World Dosing And Persistence Of Oral Treprostinil Initiation Strategies In Patients With Pulmonary Arterial Hypertension, Daniel J Lachant, Ali Ataya, H James Ford, Meredith Broderick, Scott Seaman, Benjamin Wu, Murali M Chakinala

2020-Current year OA Pubs

In patients with pulmonary arterial hypertension (PAH), limited real-world data are available on persistence to oral treprostinil therapy, particularly while transitioning from parenteral prostacyclins. We compared persistence to oral treprostinil and total daily dose (TDD) achieved among patients with PAH initiating oral treprostinil de novo or while transitioning from parenteral prostacyclins using two real-world datasets: specialty pharmacy shipment records (Analysis 1) and ADAPT registry (Analysis 2). In Analysis 1, patients receiving oral treprostinil in 2017, 2020, and 2023 were included. In Analysis 2, de-identified data of patients enrolled in ADAPT from July 2017 to January 2022 were included. We conducted …

Chimeric Antigen Receptor Natural Killer (Car-Nk) Cells: From Preclinical Promise To Clinical Reality In Cancer Immunotherapy, Hunter Cassidy Cochran, Kevin Ashkan Ghobadi, Armin Ghobadi

2020-Current year OA Pubs

Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents an emerging frontier in cancer immunotherapy. CAR-NK cells offer the potential for "off-the-shelf" treatments with a favorable safety profile, due in part to their innate capacity for HLA-unrestricted tumor targeting and an absence of graft-versus-host disease. Landmark clinical studies using cord blood - derived CAR-NK cells and another employing iPSC-derived CAR-NK cells have reported impressive response rates, durable remissions, and minimal toxicity. Furthermore, a growing landscape of ongoing clinical trials is exploring innovative strategies to enhance persistence, overcome solid tumor challenges, and prevent antigen escape. These advances collectively underscore the …

Nrf2 Immunobiology In Cancer: Implications For Immunotherapy And Therapeutic Targeting, Harit Panda, Natalie G Rowland, Caroline M Krall, Brittany M Bowman, Michael B Major, Paul Zolkind

2020-Current year OA Pubs

Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that acts as a key regulator in cellular defense mechanisms against oxidative stress and xenobiotics. NRF2 modulates the expression of over 200 genes involved in antioxidant response, drug metabolism, and cellular resilience. Constitutive activation of NRF2 is a common event in cancer and recent advances provide remarkable insights into the role of NRF2 in oncogenesis, immune evasion, and treatment resistance. This review aims to provide a comprehensive overview of the role of NRF2 in shaping the tumor immune microenvironment and the impact this has on clinical outcomes and treatment …

The Triglyceride-Glucose Index And Risk Of End-Stage Renal Disease Across Different Durations Of Type 2 Diabetes Mellitus: A Longitudinal Cohort Study, Mi-Sook Kim, Kyu-Na Lee, Jeongmin Lee, Jeongeun Kwak, Seung-Hwan Lee, Hyuk-Sang Kwon, Jing Hughes, Kyung-Do Han, Eun Young Lee

2020-Current year OA Pubs

BACKGRUOUND: This study investigated the association between the triglyceride-glucose (TyG) index, a marker of insulin resistance, and the risk of end-stage renal disease (ESRD) in individuals with type 2 diabetes mellitus (T2DM), focusing on variations by diabetes duration.

METHODS: We analyzed 1,219,148 Korean adults with T2DM from National Health Insurance Service data who underwent biennial health evaluations (2015 to 2016). ESRD was defined using specific procedural codes (V codes), and Cox proportional hazard models were employed to estimate hazard ratios (HRs) for ESRD across TyG index quartiles and diabetes duration categories, adjusting for various confounders.

RESULTS: Over 6,967,381 person-years of …

Family Income And Polygenic Scores Are Independently But Not Interactively Associated With Cognitive Performance Among Youth Genetically Similar To European Reference Populations, S E Paul, N M Elsayed, S M C Colbert, R Bogdan, A S Hatoum, D M Barch

2020-Current year OA Pubs

Cognitive abilities are heritable and influenced by socioeconomic status (SES). It is critical to understand the association between SES and cognition beyond genetic propensity to inform potential benefits of SES-based interventions and to determine if such associations vary across (i) cognitive domains, (ii) facets of SES, and/or (iii) genetic propensity for different aspects of cognition. We examined the contributions of neighborhood socioeconomic advantage, family income, and polygenic scores (PGS) for domains of cognition (i.e., general cognitive ability, executive function, learning and memory, fluid reasoning) in a sample of children (ages 9-10;

Motivations, Facilitators, And Barriers Of Donation-Based Interventions In Hiv And Sexually Transmitted Infection Research: A Systematic Review, Dorian Ho, Ye Liu, Jamie Conklin, Thomas Fitzpatrick, Jiayu Wang, Suzanne Day, Takhona G Hlatshwako, Rohit Ramaswamy, Ruby Congjiang Wang, Eneyi E Kpokiri, Weiming Tang, Elvin Geng, Joseph D Tucker

2020-Current year OA Pubs

IMPORTANCE: Donation-based prosocial interventions involve someone receiving a free health service and then distributing or donating to support health services for others; examples within the HIV and sexually transmitted infection (STI) literature include secondary distribution of HIV self-tests, secondary syringe exchange, and pay it forward for STI testing. These interventions answer research and policy recommendations to incorporate prosocial behaviors into HIV/STI services.

OBJECTIVE: To describe motivations, facilitators, and barriers of donation-based interventions in HIV and STI research using data from qualitative studies.

EVIDENCE REVIEW: In this systematic review, 5 databases (PubMed, CINAHL, Embase, PsycInfo, and Scopus) and references were searched …

Succinate Dehydrogenase B (Sdhb) Overexpression With Enzymatic Dysfunction Defines A Distinct Subtype Of Undifferentiated Pleomorphic Sarcoma, Miguel Esperança-Martins, Brian A Van Tine, Alliny C S Bastos, Et Al.

2020-Current year OA Pubs

UNLABELLED: Undifferentiated pleomorphic sarcoma (UPS) remains one of the most clinically aggressive and poorly characterized soft-tissue sarcoma subtypes. To uncover distinctive molecular traits for UPS, a multiomics analysis of UPS compared with leiomyosarcoma (LMS) and liposarcoma (LPS) was performed. Transcriptomic profiling revealed that UPS exhibits overexpression of genes encoding succinate dehydrogenase (SDH) subunits, particularly SDHB, SDHC, and SDHD, distinguishing it from LMS and dedifferentiated LPS. This finding was validated using The Cancer Genome Atlas Sarcoma dataset. High SDHB expression in UPS was significantly associated with shorter overall survival, shorter recurrence-free survival, and shorter overall survival from the date of first …

Dissecting Real-World Memory Clinical Cohort Heterogeneity: Analysis Of Neuroanatomical Subtypes Using Hydra, Gordon Zhaoqi An, Yunchang Xie, Tammie L S Benzinger, Brian A Gordon, Aristeidis Sotiras

2020-Current year OA Pubs

BACKGROUND: There is significant evidence for neuroanatomical heterogeneity in neurodegenerative disorders, which has been demonstrated predominantly through analyses of well-characterized research cohorts. Despite the known diversity in clinical presentations among patients attending memory clinics, studies exploring neuroanatomical heterogeneity in such clinically diverse groups remain sparse.

METHODS: To address this gap, we applied the semi-supervised Heterogeneity through Discriminative Analysis (HYDRA) (Neuroimage 145:346-364 2017) machine learning method to magnetic resonance imaging (MRI) data from the Open Access Series of Imaging Studies (OASIS) (NeuroImage 26:102248 2020) to uncover patterns of neurostructural heterogeneity in memory clinic attendees. Cross-validation was used to assess clustering stability …

Using Implementation Mapping To Optimize The Impact Of Universal School Meals: A Type Iii Hybrid Implementation-Effectiveness Study Protocol, Gabriella M Mcloughlin, Angel Smith, Alex R Dopp, Resa Jones, Omar Martinez, Shiriki Kumanyika, Recai Yucel, Ross C Brownson, Jennifer Orlet Fisher

2020-Current year OA Pubs

BACKGROUND: Provision of government subsidized school meals at no charge to all students in income-eligible schools (Universal School Meals) is a critical policy approach to address food insecurity and risk for obesity in school-aged children. However, despite documented benefits, implementation challenges remain, which limit the uptake and associated impact of this provision. To ensure the longevity of this policy approach, equity-focused solutions that center the needs of those tasked with implementation and the most vulnerable Universal School Meals recipients are necessary. The aims of this study are to develop equity-focused implementation strategies and test them through a hybrid type III …

Do Complex Psychometric Analyses Really Matter? Comparing Multiple Approaches Using Individual Participant Data From Antidepressant Trials, David Byrne, Frank Doyle, Susan Brannick, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth E Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Emma Wallace, Fiona Boland

2020-Current year OA Pubs

BACKGROUND: Psychometric methods are used to remove underperforming items and reduce error in existing measures, albeit different approaches can produce different results. This study aimed to determine the implications of applying different psychometric methods for clinical trial outcomes.

METHODS: Individual participant data from 15 antidepressant treatment trials from Vivli.org were analyzed. Baseline (pretreatment) and 8-week (range 4-12 weeks) outcome data from the Montgomery-Asberg Depression Rating Scale were subjected to best-practice factor analysis (FA), item response theory (IRT), and network analysis (NA) approaches. Trial outcomes for the original summative scores and psychometric-model scores were assessed using multilevel models. Percentage differences in …

Aging And The Spectral Properties Of Brain Hemodynamics, Ki Yun Park, Abraham Z Snyder, Manu S Goyal, Timothy O Laumann, John J Lee, Babatunde Adeyemo, Nicholas Metcalf, Andrei G Vlassenko, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

Cerebral glucose metabolism (CMRGlc) systematically decreases with advancing age. We sought to identify correlates of decreased CMRGlc in the spectral properties of fMRI signals imaged in the task-free state. Lifespan resting-state fMRI data acquired in 455 healthy adults (ages 18-87 years) and cerebral metabolic data acquired in a separate cohort of 94 healthy adults (ages 25-45 years, 65-85 years) were analyzed. The spectral properties of the fMRI data were characterized in terms of the relative predominance of slow versus fast activity using the spectral slope (SS) measure. We found that the relative proportion of fast activity increases with advancing age …

Dominant Negative Atp5f1a Variants Disrupt Oxidative Phosphorylation Causing Neurological Disorders, Sara M Fielder, Jessie R Zhang, Liana M Valin, Tara Samson, Sarah Govert, Sara Dacunha, Weimin Yuan, Jian Chen, Jacob Lesinski, Hieu Hoang, Stephanie A Morrison, Eric Tycksen, Dustin Baldridge, Gary A Silverman, Lisa Emrick, William J Craigen, Stephen M Sykes, Tim Schedl, Stephen C Pak, Et Al.

2020-Current year OA Pubs

ATP5F1A encodes the α-subunit of complex V of the respiratory chain, which is responsible for mitochondrial ATP synthesis. We describe 6 probands with heterozygous de novo missense ATP5F1A variants that presented with developmental delay, intellectual disability, and movement disorders. All variants were located at the contact points between the α- and β-subunits. Functional studies in C. elegans revealed that the variants were damaging via a dominant negative genetic mechanism. Biochemical and proteomics studies of proband-derived cells showed a marked reduction in complex V abundance and activity. Mitochondrial physiology studies revealed increased oxygen consumption, yet decreased mitochondrial membrane potential and ATP …

A Modification To The Brand Transfer For Claw Hand: The Four-Tailed Extensor Carpi Radialis Brevis To Lateral Band Transfer, Lauren E Wessel, Nirbhay S Jain, Ambika E Paulson, Carrie Bettlach, Mitchell A Pet, Amy M Moore

2020-Current year OA Pubs

BACKGROUND: Claw deformity is a devastating consequence of low ulnar nerve palsy, resulting in loss of finger function. Traditionally, the Brand transfer is a favored intervention but requires lengthy grafts and bulky tenorrhaphies, risking adhesions in the lumbrical canal. We present a modified Brand tendon transfer, which extends the extensor carpi radialis brevis (ECRB) into 4 tails for individual grafting into the lateral band, decreasing adhesion risk and graft length need.

METHODS: Nine consecutive patients with claw hand were examined in detail to confirm the diagnosis and appropriateness for claw-correction surgery by the senior author. All patients underwent our modified …

Gut Complement System: A New Frontier In Microbiota-Host Communication And Intestinal Homeostasis, Xianbin Tian, Lan Zhang, Xinyang Qian, Yangqing Peng, Fengyixin Chen, Sarah Bengtson, Zhiqing Wang, Meng Wu

2020-Current year OA Pubs

The gut microbiota plays a crucial role in maintaining intestinal homeostasis and influencing various aspects of host physiology, including immune function. Recent advances have highlighted the emerging importance of the complement system, particularly the C3 protein, as a key player in microbiota-host interactions. Traditionally known for its role in innate immunity, the complement system is now recognized for its interactions with microbial communities within the gut, where it promotes immune tolerance and protects against enteric infections. This Review explores the gut complement system as a possibly novel frontier in microbiota-host communication and examines its role in shaping microbial diversity, modulating …

Spatial Multiomics Of Acute Myocardial Infarction Reveals Immune Cell Infiltration Through The Endocardium, Florian Wünnemann, Junedh M Amrute, Kory J Lavine, Et Al.

2020-Current year OA Pubs

Myocardial infarction (MI) continues to be a leading cause of death worldwide. Even though it is well established that the complex interplay between different cell types determines the overall healing response after MI, the precise changes in the tissue architecture are still poorly understood. In this study, we generated an integrative cellular map of the acute phase after murine MI using a combination of imaging-based transcriptomics (Molecular Cartography) and antibody-based highly multiplexed imaging (Sequential Immunofluorescence). This enabled us to evaluate cell type compositions and changes at subcellular resolution over time. We observed the recruitment of leukocytes to the infarcted heart …

Identification Of Surrogate Outcome Biomarkers In Lung Allograft Recipients With Bronchiolitis Obliterans: Implications For Randomized Controlled Trials, Derek E. Byers, Suresh Vedantham, Mary Clare Derfler, Paul Commean, Andrew Atkinson, Jeff Atkinson, Alexey Prokudin, John Mccarthy, George Despotis, Et Al.

2020-Current year OA Pubs

BACKGROUND: We developed a prospective, multicenter "registry" to evaluate the effect of extracorporeal photopheresis for lung transplant recipients who develop chronic lung allograft dysfunction (CLAD) with the bronchiolitis obliterans syndrome (BOS) phenotype (CLAD/BOS) and who are refractory to conventional standard-of-care therapy.

METHODS: Data from 258 lung transplant recipients enrolled in the Registry between April 2015 and April 2022 were included in this analysis. All recorded parameters (eg, demographics), including forced expiratory volume in 1 s (FEV

RESULTS: Mortality at 6 and 12 mo after CLAD/BOS diagnosis was 5% and 14%, whereas mortality at 6 and 12 mo after enrollment was …

Brugia Malayi And Other Filarial Parasite Species In Animals In Areas Endemic For Lymphatic Filariasis In Belitung District, Indonesia, Irina Diekmann, Taniawati Supali, Kerstin Fischer, Elisa Iskandar, Noviani Sugianto, Yossi Destani, Rahmat Alfian, Gary J. Weil, Peter U. Fischer

2020-Current year OA Pubs

BACKGROUND: Brugia malayi is the most common cause of lymphatic filariasis (LF) in Indonesia. A zoophilic ecotype that infects both humans and animals occur in Belitung District in Indonesia. The district received five annual rounds of mass drug administration (MDA) between 2006 and 2010 and passed three transmission assessment surveys (TAS) in subsequent years. However, a survey in five villages in 2021 showed a microfilaria (Mf) prevalence of 2.1% in humans. The reappearance of B. malayi infection in humans may be due to reintroduction from animal reservoirs. The goal of this study was to determine B. malayi prevalence in potential …

Peroxisomal Metabolism Of Branched Fatty Acids Regulates Energy Homeostasis, Xuejing Liu, Anyuan He, Dongliang Lu, Donghua Hu, Min Tan, Parniyan Goodarzi, Bilal Ahmad, Brian Kleiboeker, Brian N Finck, Mohamed Zayed, Jonathan R Brestoff, Ali Javaheri, Fong-Fu Hsu, Clay F Semenkovich, Irfan J Lodhi, Et Al.

2020-Current year OA Pubs

Brown and beige adipocytes express uncoupling protein 1 (UCP1), a mitochondrial protein that dissociates respiration from ATP synthesis and promotes heat production and energy expenditure. However, UCP1

Upper And Lower Airway Microbiota Across Infancy And Childhood, Ariel J Hernandez-Leyva, Anne L Rosen, Christopher P Tomera, Elaina E Lin, Elikplim H Akaho, Allison M Blatz, William R Otto, Joey Logan, Lisa R Young, Rebecca M Harris, Samantha A Whiteside, Andrew L Kau, Audrey R Odom John

2020-Current year OA Pubs

BACKGROUND: The upper and lower respiratory tracts feature distinct environments and responses affecting microbial colonization but investigating the relationship between them is technically challenging. We aimed to identify relationships between taxa colonizing the nasopharynx and trachea across childhood.

METHODS: We employed V4 16S rRNA gene sequencing to profile nasopharyngeal swabs and tracheal aspirates collected from 172 subjects between 20 weeks and 18 years of age. These samples were collected prior to elective procedures over the course of 20 weeks in 2020 from subjects enrolled in a cross-sectional study. After extraction, sequencing, and quality control, we studied the remaining 147 of …

The Critical Human Pathogen Acinetobacter Baumannii Exhibits Light-Regulated Circadian Rhythms, Valentín Permingeat, Bárbara Edith Perez Mora, María Laura Migliori, Natalia Arana, Julia Fernández, María Belén Allasia, Melisa Luciana Lamberti, Gisela Di Venanzio, Ramiro Esteban Rodriguez, Mario Federico Feldman, Diego Andrés Golombek, María Alejandra Mussi

2020-Current year OA Pubs

Acinetobacter baumannii is recognized as the paradigm of multidrug-resistant superbug, topping the WHO priority list of critical human pathogens. Interestingly, it senses and responds to blue light, which modulates global aspects of its physiology, including pathogenicity. We hypothesized that light could serve as a signal to synchronize the bacterial physiology to the host's behavior and/or to the environment. At environmental temperatures, light regulation is mainly governed by the photoreceptor BlsA. In this work, we identified the existence of daily rhythms in blsA promoter activity displaying a robust response to light, as well as endogenous circadian rhythms in A. baumannii. In …

Life-Moms: Effects Of Multicomponent Lifestyle Randomized Control Trial On Physical Activity During Pregnancy In Women With Overweight And Obesity, Hannah E Cabre, Debra Haire-Joshu, Alison G Cahill, Samuel Klein, Et Al.

2020-Current year OA Pubs

BACKGROUND: This report details the effect of LIFE-Mom's multicomponent lifestyle interventions on physical activity (PA) and inactivity time across pregnancy (2nd and 3rd trimesters) and their effect on gestational weight gain (GWG) and maternal/neonatal outcomes, a pre-specified secondary analysis.

METHODS: Pregnant people with BMI ≥ 25 kg/m

RESULTS: Although there were statistically significant differences in vigorous activity between the intervention and control group (p = .024), there were no clinically meaningful differences in PA. In the combined sample, moderate to vigorous PA (MVPA) significantly decreased across pregnancy (mean ± SD: 72.9 ± 29.1 min/day vs 63.9 ± 28.1 min/day; p …

Ebola Virus Vp35 Nnlns Motif Modulates Viral Rna Synthesis And Mib2-Mediated Signaling, Grace Uwase, Priya Luthra, Olivia A Vogel, Jyoti Batra, Bruno A La Rosa, Kathleen C F Sheehan, Oam Khatavkar, Jacqueline E Payton, Robert A Davey, Nevan J Krogan, Christopher F Basler, Daisy W Leung, Gaya K Amarasinghe

2020-Current year OA Pubs

Ebola virus (EBOV) is a nonsegmented, negative-sense virus (NNSV) with a single-stranded RNA genome. EBOV encodes for a limited number of proteins and thus depends on host factors to facilitate viral replication and pathogenesis. Of the virus-encoded proteins, multifunctional EBOV VP35 (eVP35) is necessary for host immune evasion and viral RNA synthesis. Previous proteomics studies identified an interaction between eVP35 and the host E3 ubiquitin ligase Mindbomb 2 (MIB2). Here, we show how an NNLNS (Asn-Asn-Leu-Asn-Ser) motif (residues 201 to 205) within eVP35 serves as a binding site for MIB2. This motif is critical for eVP35-dependent inhibition of MIB2-mediated interferon …

Long-Acting Recombinant Il-7 (Rhil-7-Hyfc) Enhances The Primary And Memory Neoantigen-Specific Immune Response To Breast Cancer Personalized Cancer Vaccines, Michael Chen, Thomas Kane, Ina Chen, Suangson Supabphol, Xiuli Zhang, Alexandra A Wolfarth, Donghoon Choi, Lijin Li, S Peter Goedegebuure, William E Gillanders

2020-Current year OA Pubs

No abstract provided.

Motion Impact Score For Detecting Spurious Brain-Behavior Associations, Benjamin P Kay, David F Montez, Scott Marek, Joshua S Siegel, Babatunde Adeyemo, Timothy O Laumann, Athanasia Metoki, Roselyne J Chauvin, Andrew N Van, Vahdeta Suljic, Samuel R Krimmel, Ryland L Miller, Dillan J Newbold, Annie Zheng, Nicole A Seider, Kristen M Scheidter, Julia S Monk, Jarod L Roland, Evan M Gordon, Abraham Z Snyder, Deanna M Barch, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

In-scanner head motion introduces systematic bias to resting-state fMRI functional connectivity (FC) not completely removed by denoising algorithms. Researchers studying traits associated with motion (e.g. psychiatric disorders) need to know if their trait-FC relationships are impacted by residual motion to avoid reporting false positive results. We devised Split Half Analysis of Motion Associated Networks (SHAMAN) to assign a motion impact score to specific trait-FC relationships. SHAMAN distinguishes between motion causing overestimation or underestimation of trait-FC effects. We assessed 45 traits from n = 7270 participants in the Adolescent Brain Cognitive Development (ABCD) Study. After standard denoising with ABCD-BIDS and without …

In Vivo Crispr Screening In Head And Neck Cancer Reveals Uchl5 As An Immunotherapy Target, Cong Fu, Zahra Alipour, Douglas R Adkins, Rebecca D Chernock, Et Al.

2020-Current year OA Pubs

Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with a significant unmet need for enhancing immunotherapy response given current modest efficacy. Here, we perform an in vivo CRISPR screen in an HNSCC mouse model to identify immune evasion genes. We identify several regulators of immune checkpoint blockade (ICB) response, including the ubiquitin C-terminal hydrolase 5 (UCHL5). Loss of Uchl5 in tumors increases CD8

Current States In Understanding Oligodendroglia-Mediated Neurological Issues In Neurofibromatosis Type 1 (Nf1), Benjamin E Aghoghovwia, Cheng-En Shen, Sabiha Bano, Nandini Shyamala, Alesandra Echeandia Marrero, Khushboo Irshad, Samer Sharafaldin, Nicole M Brossier, Yuan Pan

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1) is among the most common neurogenetic disorders and is associated with an increased risk of developing tumors in the nervous system. Additionally, up to 80% of patients with NF1 experience neurological complications, including deficits in attention, memory, and executive function. Significant effort has been dedicated to studying how NF1 mutations autonomously dysregulate neuronal function. Increasing evidence indicates that NF1 mutations also dysregulate the oligodendroglial lineage that contributes to neurological issues in NF1. Here, we summarize our current understanding of how NF1 mutations impact the oligodendroglial lineage homeostasis and plasticity. We also discuss gaps in knowledge, potential …

Lysosomal Lrrc8 Complex Impacts Lysosomal Ph, Morphology, And Systemic Glucose Metabolism, Ashutosh Kumar, Yonghui Zhao, Litao Xie, Rahul Chadda, John D Tranter, Ryan T Mikami, Nihil Abraham, Juan Hong, Ethan Feng, David R Rawnsley, Haiyan Liu, Gretchen Meyer, Abhinav Diwan, Rajan Sah, Et Al.

2020-Current year OA Pubs

The lysosome integrates anabolic signaling and nutrient sensing to regulate intracellular growth pathways. The leucine-rich repeat-containing 8 (LRRC8) channel complex forms a lysosomal anion channel and regulates PI3K-AKT-mTOR signaling, skeletal muscle differentiation, growth, and systemic glucose metabolism. Here, we define the endogenous LRRC8 subunits localized to a subset of lysosomes in differentiated myotubes. We show that LRRC8A affects leucine-stimulated mTOR; lysosome size; number; pH; expression of lysosomal proteins LAMP2, P62, and LC3B; and lysosomal function. Mutating an LRRC8A lysosomal targeting dileucine motif sequence (LRRC8A-L706A;L707A) in myotubes recapitulates the abnormal AKT signaling and altered lysosomal morphology and pH observed in LRRC8A …

Genetic Susceptibility To Oral And Atherosclerotic Cardiovascular Diseases Based On Dental And Heart Score Studies, Mariana Bezamat, Dylan J Baxter, Nandita Mukhopadhyay, Anum Saeed, Lei Liu, Lisa De Las Fuentes, Betsy Foxman, John R Shaffer, Daniel W Mcneil, Steven E Reis, Mary L Marazita

2020-Current year OA Pubs

Periodontal disease and dental caries are two oral conditions that have been associated with atherosclerotic cardiovascular disease (ASCVD). However, it is unclear if one of the key mechanisms involved in this association could be a shared genetic susceptibility. The goal of this study was to explore whether there is an intersection of genetic loci among individuals with comprehensive oral examinations and subclinical ASCVD screenings. We leveraged data from oral and medical examinations obtained from the Dental and Heart Strategies Concentrating on Risk Evaluation (Dental/Heart SCORE) projects. Genome-wide association studies (GWASs) were performed independently in 552 participants (aged 45-75 years). The …

Aggrebots: Configuring Ciliabots Through Guided, Modular Tissue Aggregation, Dhruv Bhattaram, Kian Golestan, Xuanshuo Zhang, Shihong Yang, Zhuowei Gong, Steven L Brody, Amjad Horani, Victoria A Webster-Wood, Amir Barati Farimani, Xi Ren

2020-Current year OA Pubs

Ciliated biobots (CiliaBots) are engineered tissues capable of self-actuated propulsion via exterior motile cilia. While correlations have been observed between CiliaBot motility and morphology, direct control of morphological features to deliver desired motility outcomes remains unexplored. Here, we describe the engineering of aggregated CiliaBots (AggreBots) to augment control over CiliaBot structural parameters and, consequently, motility patterns through guided, modular aggregation of human airway epithelial spheroids [referred to as CiliaBot building blocks (CBBs)]. Multi-CBB aggregation generated rod-, triangle-, and diamond-shaped AggreBots, altering tissue geometry without sacrificing surface cilia density or inter-CBB boundary fidelity. The further introduction of

Health And Climate At Cop29: Advancing Integration And Bridging Research Gaps, Rupa R Patel, Yevheniia Varyvoda, Hiba Baroud, Philip J Landrigan, Aminata Kilungo

2020-Current year OA Pubs

Climate and health science is a rapidly growing, interdisciplinary field and holds importance during intergovernmental climate adaptation and mitigation policy negotiations. The 29th session of the Conference of the Parties (COP) to the United Nations Framework Convention on Climate Change (UNFCCC) convened stakeholders for negotiations and scientific discourse. This viewpoint presents insights gained by the authors' participation at COP29 focused on health and climate. The authors analyze the evolving integration of health into the UNFCCC process, dissect the contributions and the role of the Research and Independent Non‑Governmental Organizations (RINGOs), a constituency to achieve this endeavor, and identify the key …