Medicine and Health Sciences Commons^™

An Essential Endoplasmic Reticulum-Resident N-Acetyltransferase Ortholog In Plasmodium Falciparum, Alexander J Polino, Muhammad M Hasan, Katherine Floyd, Yolotzin Avila-Cruz, Yujuan Yang, Daniel E Goldberg

2020-Current year OA Pubs

N-terminal acetylation is a common eukaryotic protein modification that involves the addition of an acetyl group to the N-terminus of a polypeptide. This modification is largely performed by cytosolic N-terminal acetyltransferases (NATs). Most associate with the ribosome, acetylating nascent polypeptides co-translationally. In the malaria parasite Plasmodium falciparum, exported effectors are thought to be translated into the endoplasmic reticulum (ER), processed by the aspartic protease plasmepsin V and then N-acetylated, despite having no clear access to cytosolic NATs. Here, we used inducible gene deletion and post-transcriptional knockdown to investigate the primary ER-resident NAT candidate, Pf3D7_1437000. We found that it localizes to …

The Thin Line Between Conventional Dendritic Cells (Cdcs) And Group 3 Innate Lymphoid Cells (Ilc3s) In The Gut, Alina Ulezko Antonova, José Luís Fachi, Susan Gilfillan, Marco Colonna

2020-Current year OA Pubs

Dendritic cells (DCs) express major histocompatibility complex class II (MHC-II) and are best known for proficiently presenting antigens to T cells, thereby eliciting specific adaptive T cell responses. Moreover, conventional DCs (cDCs) are specifically adept at handling intestinal antigens. Relatively recent discoveries and investigations have proven the existence of a new group of innate lymphocytes that reside in tissues like the intestine. They lack specific antigen receptors and can express MHC-II. These group 3 innate lymphoid cells (ILC3s) comprise a subset of heterogeneous innate lymphocytes that mirror the phenotype and functions of T-helper cells and act in the first line …

Noninvasive Electromyometrial Imaging Of Human Uterine Maturation During Term Labor, Hui Wang, Zichao Wen, Wenjie Wu, Zhexian Sun, Zulfia Kisrieva-Ware, Yiqi Lin, Sicheng Wang, Hansong Gao, Haonan Xu, Peinan Zhao, Qing Wang, Alan L Schwartz, Phillip Cuculich, Yong Wang, Et Al.

2020-Current year OA Pubs

Electromyometrial imaging (EMMI) was recently developed to image the three-dimensional (3D) uterine electrical activation during contractions noninvasively and accurately in sheep. Herein we describe the development and application of a human EMMI system to image and evaluate 3D uterine electrical activation patterns at high spatial and temporal resolution during human term labor. We demonstrate the successful integration of the human EMMI system during subjects' clinical visits to generate noninvasively the uterine surface electrical potential maps, electrograms, and activation sequence through an inverse solution using up to 192 electrodes distributed around the abdomen surface. Quantitative indices, including the uterine activation curve, …

Clinicopathological Classification Of Immune Checkpoint Inhibitor-Associated Myocarditis: Possible Refinement By Measuring Macrophage Abundance, Jesus Jimenez, Nicolas Kostelecky, Joshua D Mitchell, Kathleen W Zhang, Chieh-Yu Lin, Daniel J Lenihan, Kory J Lavine

2020-Current year OA Pubs

BACKGROUND: Immune checkpoint inhibitor (ICI) myocarditis is associated with high morbidity and mortality. While endomyocardial biopsy (EMB) is considered a gold standard for diagnosis, the sensitivity of EMB is not well defined. Additionally, the pathological features that correlate with the clinical diagnosis of ICI-associated myocarditis remain incompletely understood.

METHODS: We retrospectively identified and reviewed the clinicopathological features of 26 patients with suspected ICI-associated myocarditis based on institutional major and minor criteria. Seventeen of these patients underwent EMB, and the histopathological features were assessed by routine hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for CD68, a macrophage marker.

RESULTS: …

A Gap-Free Genome Assembly Of Chlamydomonas Reinhardtii And Detection Of Translocations Induced By Crispr-Mediated Mutagenesis, Zachary L Payne, Gervette M Penny, Tychele N Turner, Susan K Dutcher

2020-Current year OA Pubs

Genomic assemblies of the unicellular green alga Chlamydomonas reinhardtii have provided important resources for researchers. However, assembly errors, large gaps, and unplaced scaffolds as well as strain-specific variants currently impede many types of analysis. By combining PacBio HiFi and Oxford Nanopore long-read technologies, we generated a de novo genome assembly for strain CC-5816, derived from crosses of strains CC-125 and CC-124. Multiple methods of evaluating genome completeness and base-pair error rate suggest that the final telomere-to-telomere assembly is highly accurate. The CC-5816 assembly enabled previously difficult analyses that include characterization of the 17 centromeres, rDNA arrays on three chromosomes, and …

Allopregnanolone Effects On Inhibition In Hippocampal Parvalbumin Interneurons, Xinguo Lu, Peter Lambert, Ann Benz, Charles F. Zorumski, Steven J. Mennerick

2020-Current year OA Pubs

Allopregnanolone (AlloP) is a neurosteroid that potentiates ionotropic GABAergic (GABA

Intravenously Administered Interleukin-7 To Reverse Lymphopenia In Patients With Septic Shock: A Double-Blind, Randomized, Placebo-Controlled Trial, Thomas Daix, Armelle Mathonnet, Scott Brakenridge, Pierre-François Dequin, Jean-Paul Mira, Frederique Berbille, Michel Morre, Robin Jeannet, Teresa Blood, Jacqueline Unsinger, Jane Blood, Andrew Walton, Lyle L Moldawer, Richard Hotchkiss, Bruno François

2020-Current year OA Pubs

BACKGROUND: Profound lymphopenia is an independent predictor of adverse clinical outcomes in sepsis. Interleukin-7 (IL-7) is essential for lymphocyte proliferation and survival. A previous phase II study showed that CYT107, a glycosylated recombinant human IL-7, administered intramuscularly reversed sepsis-induced lymphopenia and improved lymphocyte function. Thepresent study evaluated intravenous administration of CYT107. This prospective, double-blinded, placebo-controlled trial was designed to enroll 40 sepsis patients, randomized 3:1 to CYT107 (10 µg/kg) or placebo, for up to 90 days.

RESULTS: Twenty-one patients were enrolled (fifteen CYT107 group, six placebo group) at eight French and two US sites. The study was halted early because …

Individualized Precision Targeting Of Dorsal Attention And Default Mode Networks With Rtms In Traumatic Brain Injury-Associated Depression, Shan H Siddiqi, Sridhar Kandala, Carl D Hacker, Nicholas T Trapp, Eric C Leuthardt, Alexandre R Carter, David L Brody

2020-Current year OA Pubs

At the group level, antidepressant efficacy of rTMS targets is inversely related to their normative connectivity with subgenual anterior cingulate cortex (sgACC). Individualized connectivity may yield better targets, particularly in patients with neuropsychiatric disorders who may have aberrant connectivity. However, sgACC connectivity shows poor test-retest reliability at the individual level. Individualized resting-state network mapping (RSNM) can reliably map inter-individual variability in brain network organization. Thus, we sought to identify individualized RSNM-based rTMS targets that reliably target the sgACC connectivity profile. We used RSNM to identify network-based rTMS targets in 10 healthy controls and 13 individuals with traumatic brain injury-associated depression …

Molecular Mechanism Of Biased Signaling At The Kappa Opioid Receptor, Amal El Daibani, Joseph M Paggi, Kuglae Kim, Yianni D Laloudakis, Petr Popov, Sarah M Bernhard, Brian E Krumm, Reid H J Olsen, Jeffrey Diberto, F Ivy Carroll, Vsevolod Katritch, Bernhard Wünsch, Ron O Dror, Tao Che

2020-Current year OA Pubs

The κ-opioid receptor (KOR) has emerged as an attractive drug target for pain management without addiction, and biased signaling through particular pathways of KOR may be key to maintaining this benefit while minimizing side-effect liabilities. As for most G protein-coupled receptors (GPCRs), however, the molecular mechanisms of ligand-specific signaling at KOR have remained unclear. To better understand the molecular determinants of KOR signaling bias, we apply structure determination, atomic-level molecular dynamics (MD) simulations, and functional assays. We determine a crystal structure of KOR bound to the G protein-biased agonist nalfurafine, the first approved KOR-targeting drug. We also identify an arrestin-biased …

Synthesis And Characterization Of Pt(Ii) And Pd(Ii) Complexes With Planar Aromatic Oximes, Mikala Meadows, Lei Yang, Cody Turner, Mikhail Berezin, Sergiy Tyukhtenko, Nikolay Gerasimchuk

2020-Current year OA Pubs

No abstract provided.

Text Messages Exchanged Between Individuals With Opioid Use Disorder And Their Mhealth E-Coaches: Content Analysis Study, Yerina S Ranjit, Warren M Davis, Andrea Fentem, Raven Riordan, Rikki Roscoe, Patricia Cavazos-Rehg

2020-Current year OA Pubs

BACKGROUND: Opioid use disorder (OUD) has affected 2.2 million people in the United States. About 7.2 million people reported using illicit drugs in 2019, which contributed to over 70,000 overdose deaths. SMS text messaging interventions have been shown to be effective in OUD recovery. However, the interpersonal communication between individuals in OUD treatment and a support team on digital platforms has not been well examined.

OBJECTIVE: This study aims to understand the communication between participants undergoing OUD recovery and their e-coaches by examining the SMS text messages exchanged from the lens of social support and the issues related to OUD …

Mechanism Of Kmt5b Haploinsufficiency In Neurodevelopment In Humans And Mice, Sarah E Sheppard, Marisa Andrews, Dustin Baldridge, John Constantino, Et Al.

2020-Current year OA Pubs

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Eus-Guided Vascular Interventions, Michelle Baliss, Devan Patel, Mahmoud Y Madi, Ahmad Najdat Bazarbashi

2020-Current year OA Pubs

Endoscopic ultrasound (EUS) has numerous advanced applications as a diagnostic and therapeutic modality in contemporary medicine. Through intraluminal placement, EUS offers a real-time Doppler-guided endoscopic visualization and access to intra-abdominal vasculature, which were previously inaccessible using historical methods. We aim to provide a comprehensive review of key studies on both current and future EUS-guided vascular applications. This review details EUS-based vascular diagnostic techniques of portal pressure measurements in the prognostication of liver disease and portal venous sampling for obtaining circulating tumor cells in the diagnosis of cancer. From an interventional perspective, we describe effective EUS-guided treatments via coiling and cyanoacrylate …

Prevalence Of Potentially Traumatic Events And Symptoms Of Depression, Anxiety, Hazardous Alcohol Use, And Post-Traumatic Stress Disorder Among People With Hiv Initiating Hiv Care In Cameroon, Angela M Parcesepe, Lindsey M Filiatreau, Peter Vanes Ebasone, Anastase Dzudie, Brian W Pence, Milton Wainberg, Marcel Yotebieng, Kathryn Anastos, Eric Pefura-Yone, Denis Nsame, Rogers Ajeh, Denis Nash

2020-Current year OA Pubs

BACKGROUND: This study explored the relationship between specific types of potentially traumatic events (PTEs) and symptoms of mental health disorders among people with HIV (PWH) in Cameroon.

METHODS: We conducted a cross-sectional study with 426 PWH in Cameroon between 2019-2020. Multivariable log binominal regression was used to estimate the association between exposure (yes/no) to six distinct types of PTE and symptoms of depression (Patient Health Questionnaire-9 score > 9), PTSD (PTSD Checklist for DSM-5 score > 30), anxiety (Generalized Anxiety Disorder-7 scale score > 9), and hazardous alcohol use (Alcohol Use Disorders Identification Test score > 7 for men; > 6 for women).

RESULTS: A …

Nirogacestat, A Γ-Secretase Inhibitor For Desmoid Tumors, Mrinal Gounder, Brian A Van Tine, Et Al.

2020-Current year OA Pubs

BACKGROUND: Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments.

METHODS: We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral γ-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival.

RESULTS: From May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit …

Neurofibromatosis Type 1-Dependent Alterations In Mouse Microglia Function Are Not Cell-Intrinsic, Francesca Logiacco, Laura Cathleen Grzegorzek, Elizabeth C Cordell, Oliver Popp, Philipp Mertins, David H Gutmann, Helmut Kettenmann, Marcus Semtner

2020-Current year OA Pubs

We previously discovered a sex-by-genotype defect in microglia function using a heterozygous germline knockout mouse model of Neurofibromatosis type 1 (Nf1 ± mice), in which only microglia from male Nf1 ± mice exhibited defects in purinergic signaling. Herein, we leveraged an unbiased proteomic approach to demonstrate that male, but not female, heterozygous Nf1 ± microglia exhibit differences in protein expression, which largely reflect pathways involved in cytoskeletal organization. In keeping with these predicted defects in cytoskeletal function, only male Nf1 ± microglia had reduced process arborization and surveillance capacity. To determine whether these microglial defects were cell autonomous or reflected …

The Tetraspanin Cd53 Protects Stressed Hematopoietic Stem Cells Via Promotion Of Dream Complex-Mediated Quiescence, Zev J Greenberg, Luana Chiquetto Paracatu, Darlene A Monlish, Qian Dong, Michael Rettig, Nate Roundy, Rofaida Gaballa, Weikai Li, Wei Yang, Cliff J Luke, Laura G Schuettpelz

2020-Current year OA Pubs

The hematopoietic stem cell (HSC) cycle responds to inflammatory and other proliferative stressors; however, these cells must quickly return to quiescence to avoid exhaustion and maintain their functional integrity. The mechanisms that regulate this return to quiescence are not well understood. Here, we show that tetraspanin CD53 is markedly upregulated in HSCs in response to a variety of inflammatory and proliferative stimuli and that the loss of CD53 is associated with prolonged cycling and reduced HSC function in the context of inflammatory stress. Mechanistically, CD53 promotes the activity of the dimerization partner, RB-like, E2F, and multi-vulva class B (DREAM) transcriptional …

Role Of Klotho And Age/Rage-Wnt/Β-Catenin Signalling Pathway On The Development Of Cardiac And Renal Fibrosis In Diabetes, Beatriz Martín-Carro, Julia Martín-Vírgala, Sara Fernández-Villabrille, Alejandra Fernández-Fernández, Marcos Pérez-Basterrechea, Juan F Navarro-González, Javier Donate-Correa, Carmen Mora-Fernández, Adriana S Dusso, Natalia Carrillo-López, Sara Panizo, Manuel Naves-Díaz, José L Fernández-Martín, Jorge B Cannata-Andía, Cristina Alonso-Montes

2020-Current year OA Pubs

Fibrosis plays an important role in the pathogenesis of long-term diabetic complications and contributes to the development of cardiac and renal dysfunction. The aim of this experimental study, performed in a long-term rat model, which resembles type 1 diabetes mellitus, was to investigate the role of soluble Klotho (sKlotho), advanced glycation end products (AGEs)/receptor for AGEs (RAGE), fibrotic Wnt/β-catenin pathway, and pro-fibrotic pathways in kidney and heart. Diabetes was induced by streptozotocin. Glycaemia was maintained by insulin administration for 24 weeks. Serum and urine sKlotho, AGEs, soluble RAGE (sRAGE) and biochemical markers were studied. The levels of Klotho, RAGEs, ADAM10, …

Adipose-Targeted Swell1 Deletion Exacerbates Obesity- And Age-Related Nonalcoholic Fatty Liver Disease, Susheel K. Gunasekar, John Heebink, Danielle H Carpenter, Ashutosh Kumar, Litao Xie, Haixia Zhang, Joel D. Schilling, Rajan Sah

2020-Current year OA Pubs

Healthy expansion of adipose tissue is critical for the maintenance of metabolic health, providing an optimized reservoir for energy storage in the form of triacylglycerol-rich lipoproteins. Dysfunctional adipocytes that are unable to efficiently store lipid can result in lipodystrophy and contribute to nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. Leucine-rich repeat containing protein 8a/SWELL1 functionally encodes the volume-regulated anion channel complex in adipocytes, is induced in early obesity, and is required for normal adipocyte expansion during high-fat feeding. Adipose-specific SWELL1 ablation (Adipo KO) leads to insulin resistance and hyperglycemia during caloric excess, both of which are associated with NAFLD. …

How I Prescribe Prolonged Intermittent Renal Replacement Therapy, Edward G Clark, Anitha Vijayan

2020-Current year OA Pubs

Prolonged Intermittent Renal Replacement Therapy (PIRRT) is the term used to define 'hybrid' forms of renal replacement therapy. PIRRT can be provided using an intermittent hemodialysis machine or a continuous renal replacement therapy (CRRT) machine. Treatments are provided for a longer duration than typical intermittent hemodialysis treatments (6-12 h vs. 3-4 h, respectively) but not 24 h per day as is done for continuous renal replacement therapy (CRRT). Usually, PIRRT treatments are provided 4 to 7 times per week. PIRRT is a cost-effective and flexible modality with which to safely provide RRT for critically ill patients. We present a brief …

Microbiology Clinical Culture Diagnostic Yields And Antimicrobial Resistance Proportions Before And During The Covid-19 Pandemic In An Indian Community Hospital And Two Us Community Hospitals, Sumanth Gandra, Gerardo Alvarez-Uria, Dustin Stwalley, Katelin B Nickel, Kimberly A Reske, Jennie H Kwon, Erik R Dubberke, Margaret A Olsen, Jason P Burnham

2020-Current year OA Pubs

Studies comparing the impact of the COVID-19 pandemic on diagnostic microbiology culture yields and antimicrobial resistance proportions in low-to-middle-income and high-income countries are lacking. A retrospective study using blood, respiratory, and urine microbiology data from a community hospital in India and two community hospitals (Hospitals A and B) in St. Louis, MO, USA was performed. We compared the proportion of cultures positive for selected multi-drug-resistant organisms (MDROs) listed on the WHO's priority pathogen list both before the COVID-19 pandemic (January 2017-December 2019) and early in the COVID-19 pandemic (April 2020-October 2020). The proportion of blood cultures contaminated with coagulase-negative

Social Determinants, Cardiovascular Disease, And Health Care Cost: A Nationwide Study In The United States Using Machine Learning, Feinuo Sun, Jie Yao, Shichao Du, Feng Qian, Allison A Appleton, Cui Tao, Hua Xu, Lei Liu, Qi Dai, Brian T Joyce, Drew R Nannini, Lifang Hou, Kai Zhang

2020-Current year OA Pubs

Background Existing studies on cardiovascular diseases (CVDs) often focus on individual-level behavioral risk factors, but research examining social determinants is limited. This study applies a novel machine learning approach to identify the key predictors of county-level care costs and prevalence of CVDs (including atrial fibrillation, acute myocardial infarction, congestive heart failure, and ischemic heart disease). Methods and Results We applied the extreme gradient boosting machine learning approach to a total of 3137 counties. Data are from the

The Implementation Playbook: Study Protocol For The Development And Feasibility Evaluation Of A Digital Tool For Effective Implementation Of Evidence-Based Innovations, Melanie Barwick, Jacquie Brown, Kadia Petricca, Bonnie Stevens, Byron J Powell, Alexia Jaouich, Jill Shakespeare, Emily Seto

2020-Current year OA Pubs

BACKGROUND: Evidence-based innovations can improve health outcomes, but only if successfully implemented. Implementation can be complex, highly susceptible to failure, costly and resource intensive. Internationally, there is an urgent need to improve the implementation of effective innovations. Successful implementation is best guided by implementation science, but organizations lack implementation know-how and have difficulty applying it. Implementation support is typically shared in static, non-interactive, overly academic guides and is rarely evaluated. In-person implementation facilitation is often soft-funded, costly, and scarce. This study seeks to improve effective implementation by (1) developing a first-in-kind digital tool to guide pragmatic, empirically based and self-directed …

Molnupiravir And Risk Of Hospital Admission Or Death In Adults With Covid-19: Emulation Of A Randomized Target Trial Using Electronic Health Records, Yan Xie, Benjamin Bowe, Ziyad Al-Aly

2020-Current year OA Pubs

OBJECTIVE: To emulate a randomized target trial to estimate the association between the antiviral drug molnupiravir and hospital admission or death in adults with SARS-CoV-2 infection in the community during the omicron predominant era who were at high risk of progression to severe covid-19.

DESIGN: Emulation of a randomized target trial using electronic health records.

SETTING: US Department of Veterans Affairs.

PARTICIPANTS: 85 998 adults with SARS-CoV-2 infection between 5 January and 30 September 2022 and at least one risk factor for progression to severe covid-19: 7818 participants were eligible for and treated with molnupiravir and 78 180 received no …

Long-Term Gastrointestinal Outcomes Of Covid-19, Evan Xu, Yan Xie, Ziyad Al-Aly

2020-Current year OA Pubs

A comprehensive evaluation of the risks and 1-year burdens of gastrointestinal disorders in the post-acute phase of COVID-19 is needed but is not yet available. Here we use the US Department of Veterans Affairs national health care databases to build a cohort of 154,068 people with COVID-19, 5,638,795 contemporary controls, and 5,859,621 historical controls to estimate the risks and 1-year burdens of a set of pre-specified incident gastrointestinal outcomes. We show that beyond the first 30 days of infection, people with COVID-19 exhibited increased risks and 1-year burdens of incident gastrointestinal disorders spanning several disease categories including motility disorders, acid …

Rethinking The Difficult Patient: Formative Qualitative Study Using Participatory Theater To Improve Physician-Patient Communication In Rheumatology, Jerik Leung, Avira Som, Lily Mcmorrow, Lisa Zickuhr, John Wolbers, Karen Bain, Julia Flood, Elizabeth A Baker

2020-Current year OA Pubs

BACKGROUND: Effective physician-patient communication is crucial for positive health outcomes for patients with chronic diseases. However, current methods of physician education in communication are often insufficient to help physicians understand how patients' actions are influenced by the contexts within which they live. An arts-based participatory theater approach can provide the necessary health equity framing to address this deficiency.

OBJECTIVE: The aim of this study was to develop, pilot, and conduct a formative evaluation of an interactive arts-based communication skills intervention for graduate-level medical trainees grounded in a narrative representative of the experience of patients with systemic lupus erythematosus.

METHODS: We …

Charge-Voltage Curves Of Shaker Potassium Channel Are Not Hysteretic At Steady State, John Cowgill, Baron Chanda

2020-Current year OA Pubs

Charge-voltage curves of many voltage-gated ion channels exhibit hysteresis but such curves are also a direct measure of free energy of channel gating and, hence, should be path-independent. Here, we identify conditions to measure steady-state charge-voltage curves and show that these are curves are not hysteretic. Charged residues in transmembrane segments of voltage-gated ion channels (VGICs) sense and respond to changes in the electric field. The movement of these gating charges underpins voltage-dependent activation and is also a direct metric of the net free-energy of channel activation. However, for most voltage-gated ion channels, the charge-voltage (Q-V) curves appear to be …

Application Of Artificial Intelligence In Measuring Novel Ph-Impedance Metrics For Optimal Diagnosis Of Gerd, Ming-Wun Wong, Benjamin D Rogers, Min-Xiang Liu, Wei-Yi Lei, Tso-Tsai Liu, Chih-Hsun Yi, Jui-Sheng Hung, Shu-Wei Liang, Chiu-Wang Tseng, Jen-Hung Wang, Ping-An Wu, Chien-Lin Chen

2020-Current year OA Pubs

Novel metrics extracted from pH-impedance monitoring can augment the diagnosis of gastroesophageal reflux disease (GERD). Artificial intelligence (AI) is being widely used to improve the diagnostic capabilities of various diseases. In this review, we update the current literature regarding applications of artificial intelligence in measuring novel pH-impedance metrics. AI demonstrates high performance in the measurement of impedance metrics, including numbers of reflux episodes and post-reflux swallow-induced peristaltic wave index and, furthermore, extracts baseline impedance from the entire pH-impedance study. AI is expected to play a reliable role in facilitating measuring novel impedance metrics in patients with GERD in the near …

Association Between Community-Level Social Risk And Spending Among Medicare Beneficiaries: Implications For Social Risk Adjustment And Health Equity, Brian W Powers, Jose F Figueroa, Melanie Canterberry, Suhas Gondi, Stephanie M Franklin, William H Shrank, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: Payers are increasingly using approaches to risk adjustment that incorporate community-level measures of social risk with the goal of better aligning value-based payment models with improvements in health equity.

OBJECTIVE: To examine the association between community-level social risk and health care spending and explore how incorporating community-level social risk influences risk adjustment for Medicare beneficiaries.

DESIGN, SETTING, AND PARTICIPANTS: Using data from a Medicare Advantage plan linked with survey data on self-reported social needs, this cross-sectional study estimated health care spending health care spending was estimated as a function of demographics and clinical characteristics, with and without the inclusion …

Insights Into Pulmonary Phosphate Homeostasis And Osteoclastogenesis Emerge From The Study Of Pulmonary Alveolar Microlithiasis, Yasuaki Uehara, Steven L Teitelbaum, Et Al.

2020-Current year OA Pubs

Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a pulmonary alveolar microlithiasis lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes and other proteins suggested a role for osteoclast-like cells in the host response to microliths. While investigating the mechanisms of microlith clearance, we found …