bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac Rehabilitation Participation in Heart Failure Over Time: An Analysis of the Colorado All Payer Claims Database
Authors: Deng Lubin R. , Polsinelli Vincenzo B. , Kini Vinay , Wilson Morgan , Peterson Pamela , Bekelman David B. , Flint Kelsey M. 
Published: March 2023

AbstractBackgroundDespite CMS coverage expansion supporting cardiac rehabilitation (CR) in patients with heart failure (HF) in 2014, data suggest that utilization among patients with HF is low. We describe CR participation and adherence among HF patients in Colorado.MethodsData from the Colorado All-Payer Claims Database from 2010-2018 were used. Patients with HF were identified by ≥2 claims with a HF diagnosis code, then grouped by type of HF (HFrEF, HFpEF, unspecified). CR participation and adherence were identified using CR CPT codes. Participation rates were calculated by quarter of each year. Cochran-Armitage tests determined whether temporal trends were significant. Association between CR participation and payer source was examined in adjusted logistic regression models.Results263,476 patients with HF were identified. 4.77% of all HF patients attended CR at least once; this result was similar for HFpEF (4.35%), unspecified HF (4.15%), and higher in the HFrEF group (8.25%). Overall adherence was poor (median 8 visits, IQR 3-18; full adherence=36 visits). CR participation over time increased (P<0.01) for all HF patients. Compared to patients with commercial insurance, patients with Medicare, Medicaid, or Medicare Advantage were less likely to have participated in CR at least once (P<0.01). Race, sex and presence of another indication for CR were also associated with at least one CR visit (P<0.01).ConclusionsIn the state of Colorado, CR participation improved from 2010-2018 among all patients with HF. Our data suggest that payer source, race, sex and presence of another indication for CR drive CR participation in patients with HF.
Leveraging genetic diversity to identify small molecules that reverse mouse skeletal muscle insulin resistance
Authors: Masson Stewart W.C. , Madsen Søren , Cooke Kristen C. , Potter Meg , Diaz-Vegas Alexis , Carroll Luke , Thillainadesan Senthil , Cutler Harry B. , Walder Ken , Cooney Gregory J. , Morahan Grant , Stöckli Jacqueline , James David E. 
Published: March 2023

AbstractSystems genetics has begun to tackle the complexity of insulin resistance by capitalising on computational advances to study high-diversity populations. “Diversity Outbred in Australia (DOz)” is a population of genetically unique mice with profound metabolic heterogeneity. We leveraged this variance to explore skeletal muscle’s contribution to whole-body insulin action through metabolic phenotyping and skeletal muscle proteomics of 215 DOz mice. Linear modelling identified 553 proteins that associated with whole-body insulin sensitivity (Matsuda Index) including regulators of endocytosis and muscle proteostasis. To enrich for causality, we refined this network by focussing on negatively associated, genetically regulated proteins, resulting in a 76-protein fingerprint of insulin resistance. We sought to perturb this network and restore insulin action with small molecules by integrating the Broad Institute Connectivity Map platform andin vitroassays of insulin action using the Prestwick chemical library. These complimentary approaches identified the antibiotic thiostrepton as an insulin resistance reversal agent. Subsequent validation inex vivoinsulin resistant mouse muscle, and palmitate induced insulin resistant myotubes demonstrated potent insulin action restoration, potentially via up-regulation of glycolysis. This work demonstrates the value of a drug-centric framework to validate systems level analysis by identifying potential therapeutics for insulin resistance.
Decoding Duchenne muscular dystrophy transcriptome to single nuclei level reveals clinical-genetic correlations
Authors: Suárez-Calvet Xavier , Fernández-Simón Esther , Natera Daniel , Jou Cristina , Pinol-Jurado Patricia , Villalobos Elisa , Ortez Carlos , Monceau Alexandra , Schiava Marianela , Verdu-Díaz José , Clark James , Laidler Zoe , Mehra Priyanka , Gokul-Nath Rasya , Alonso-Perez Jorge , Marini-Bettolo Chiara , Tasca Giorgio , Straub Volker , Guglieri Michela , Nascimento Andrés , Diaz-Manera Jordi 
Published: March 2023

AbstractThe cellular and molecular consequences of lack of dystrophin in humans are only partially known, which is crucial for the development of new therapies aiming to slow or stop the progression Duchenne and Becker muscular dystrophies. We analyzed muscle biopsies of DMD patients and controls using single nuclei RNA sequencing (snRNAseq) and correlated the results with clinical data. DMD samples displayed an increase in regenerative fibers, satellite cells and fibro-adipogenic progenitor cells (FAPs) and a decrease in slow fibers and smooth muscle cells. Samples from patients with stable mild weakness were characterized by an increase in regenerative fibers, while those from patients with progressive weakness had fewer muscle fibers and increased FAPs. DMD muscle fibers displayed a strong regenerative signature, while DMD FAPs upregulated genes producing extracellular matrix and molecules involved in several signaling pathways. An analysis of intercellular communication profile identified FAPs as a key regulator of cell signaling in DMD samples. We show significant differences in the gene expression profiled of the different cell populations present in DMD muscle samples compared to controls.
KIF16B mediates anterograde transport and modulates lysosomal degradation of the HIV-1 envelope glycoprotein
Authors: Weaver Nicholas , Hammonds Jason , Ding Lingmei , Lerner Grigoriy , Dienger-Stambaugh Krista , Spearman Paul 
Published: March 2023

ABSTRACTThe human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) is incorporated into virions at the site of particle assembly on the plasma membrane (PM). The route taken by Env to reach the site of assembly and particle incorporation remains incompletely understood. Following initial delivery to the PM through the secretory pathway, Env is rapidly endocytosed, suggesting that recycling is required for particle incorporation. Endosomes marked by the small GTPase Rab14 have been previously shown to play a role in Env trafficking. Here we examined the role of KIF16B, the molecular motor protein that directs outward movement of Rab14-dependent cargo, in Env trafficking. Env colocalized extensively with KIF16B+ endosomes at the cellular periphery, while expression of a motor-deficient mutant of KIF16B redistributed Env to a perinuclear location. The half-life of Env labeled at the cell surface was markedly reduced in the absence of KIF16B, while a normal half-life was restored through inhibition of lysosomal degradation. In the absence of KIF16B, Env expression on the surface of cells was reduced, leading to a reduction in Env incorporation into particles and a corresponding reduction in particle infectivity. HIV-1 replication in KIF16B knockout cells was substantially reduced as compared to wildtype cells. These results indicate that KIF16B regulates an outward sorting step involved in Env trafficking, thereby limiting lysosomal degradation and enhancing particle incorporation.IMPORTANCEThe HIV-1 envelope glycoprotein is an essential component of HIV-1 particles. The cellular pathways that contribute to incorporation of envelope into particles are not fully understood. Here we identify KIF16B, a motor protein that directs movement from internal compartments toward the plasma membrane, as a host factor that prevents envelope degradation and enhances particle incorporation. This is the first host motor protein identified that contributes to HIV-1 envelope incorporation and replication.
Frequent emergence of resistance mutations following complex intra-host genomic dynamics in SARS-CoV-2 patients receiving Sotrovimab
Authors: Palomino-Cabrera Rosalía , Tejerina Francisco , Molero-Salinas Andrea , Ferris María , Veintimilla Cristina , Catalán Pilar , Rodríguez Macias Gabriela , Alonso Roberto , Muñoz Patricia , de Viedma Darío García , Pérez-Lago Laura 
Published: March 2023

AbstractThe emergence of the Omicron variant of SARS-CoV-2 represented a challenge to the treatment of COVID-19 with monoclonal antibodies. Only Sotrovimab maintained partial activity, allowing it to be used in high-risk patients infected with the Omicron variant. However, the reports of resistance mutations to Sotrovimab call for efforts to better understand the intra-patient emergence of this resistance. A retrospective genomic analysis was conducted on respiratory samples from immunocompromised patients infected with SARS-CoV-2 who received Sotrovimab at our hospital between December 2021 and August 2022. The study involved 95 sequential specimens from 22 patients (1-12 samples/patient; 3-107 days post-infusion (Ct ≤ 32)). Resistance mutations (in P337, E340, K356, and R346) were detected in 68% of cases; the shortest time to detection of a resistance mutation was 5 days after Sotrovimab infusion. The dynamics of resistance acquisition were highly complex, with up to 11 distinct amino acid changes in specimens from the same patient. In two patients, the mutation distribution was compartmentalized in respiratory samples from different sources. This is the first study to examine the acquisition of resistance to Sotrovimab in the BA.5 lineage, enabling us to determine the lack of genomic or clinical differences between Sotrovimab resistance in BA.5 relative to BA.1/2. Across all Omicron lineages, the acquisition of resistance delayed SARS-CoV-2 clearance (40.67 vs 19.5 days). Close, real-time genomic surveillance of patients receiving Sotrovimab should be mandatory to facilitate early therapeutic interventions.
Stitch with Which? Absorbable vs Nonabsorbable Suture for Skin Closure – A meta-analysis
Authors: Desai Dev 
Published: March 2023

AbstractBackgroundIt has been taught as a fundamental value that for skin sutures and wound closure, non-absorbable sutures should be used without many research papers supporting its higher efficacy with decreased would infection, decreased wound dehiscence and decreased skin scarring. The optimal suture material type still remains a myth.ObjectiveThis study aimed to compare the outcomes of absorbable versus non-absorbable sutures for skin closureMethodsA Systemic-review was performed with randomized controlled trials (RCTs) and Cohort studies that compared outcomes of absorbable versus non-absorbable sutures for skin closure.ResultsA total of 5096 patients in 27 RCTs analyzed. There was no significant difference between absorbable sutures and non-absorbable sutures in the incidence of wound infections, scar formation and wound dehiscence. The results of both groups are quite comparable with nil heterogeneity.ConclusionsAbsorbable sutures for skin closure were not inferior to nonabsorbable sutures. It should be recommended due to its great cost and time savings. Well-designed RCTs with sufficient follow-ups are needed to adequately clarify whether better cosmetic results can be achieved using intradermal absorbable sutures.
Mobile Stroke Unit Treatment Times and Transport Frequency in a Suburban Setting
Authors: Vargas Alejandro , Zobel Rebecca , Cherian Laurel J. , Dafer Rima M. , Osteraas Nicholas D. , Song Sarah Y. , Cichon Mark E. , Conners James J. 
Published: March 2023

AbstractBackgroundThe majority of Mobile Stoke Units (MSUs) operate in European and United States urban cities. Questions remain on the cost-effectiveness, setting (urban, suburban, or rural), infrastructure and support, and reimbursement of these units. We present our experiences of a single-center MSU in a suburban setting, with treatment times, challenges, and possible future directions of alternative methods of care.MethodsRetrospective analysis of prospectively collected data from Mobile Stroke Unit calls for service and Get With The Guidelines-Stroke data from two primary stroke centers from December 2017 through February 2020 comparing patients receiving intravenous thrombolysis and treatment times.ResultsThere were no differences in age, sex, medical history, or stroke severity between MSU transport when compared to standard transport. There were differences in patient racial and ethnic demographics between groups, with higher white race and Hispanic ethnicity. Door-to-needle time was 48.9 minutes for patients seen on the Rush MSU versus 67.2 minutes for patients seen via traditional EMS transport (p=0.04).ConclusionsThe Rush MSU demonstrated significant reduction of acute ischemic stroke treatment time with intravenous thrombolysis, but did not demonstrate the patient volume necessary to justify continued operation. Suburban and rural regions do benefit from pre-hospital stroke evaluation, however the ideal method for a cost-effective strategy is still unknown.
Association of Nirmatrelvir/Ritonavir Treatment with Long COVID Symptoms in an Online Cohort of Non-Hospitalized Individuals Experiencing Breakthrough SARS-CoV-2 Infection in the Omicron Era
Authors: Durstenfeld Matthew S. , Peluso Michael J. , Lin Feng , Peyser Noah D. , Isasi Carmen , Carton Thomas W. , Henrich Timothy J. , Deeks Steven G. , Olgin Jeffrey E. , Pletcher Mark J. , Beatty Alexis L. , Marcus Gregory M. , Hsue Priscilla Y. 
Published: March 2023

AbstractBackgroundOral nirmatrelvir/ritonavir is a treatment for COVID-19, but whether treatment during the acute phase reduces the risk of developing Long COVID is unknown.MethodsUsing the Covid Citizen Science (CCS) online cohort, we surveyed individuals who reported their first SARS-CoV-2 positive test between March and August 2022 regarding Long COVID symptoms. We excluded those who were pregnant, unvaccinated, hospitalized for COVID-19, or received other antiviral therapy. The primary exposure was oral nirmatrelvir/ritonavir. The primary outcome was the presence of any Long COVID symptoms reported on cross-sectional surveys in November and December 2022. We used propensity-score models and inverse probability of treatment weighting to adjust for differences in treatment propensity. Our secondary question was whether symptom or test positivity rebound were associated with Long COVID.Results4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the survey. Median age was 55 years and 66% were female. We did not identify an association between nirmatrelvir/ritonavir treatment and Long COVID symptoms (OR 1.15; 95%CI 0.80-1.64). Among n=666 treated with nirmatrelvir/ritonavir who responded who responded to questions about rebound, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR 1.34; 95%CI 0.74-2.41; p=0.33).ConclusionsWithin this cohort, treatment with nirmatrelvir/ritonavir among vaccinated, non-hospitalized individuals was not associated with lower prevalence of Long COVID symptoms or severity of Long COVID. Experiencing rebound symptoms or test positivity is not strongly associated with developing Long COVID.
Astrocyte glypican 5 regulates synapse maturation and stabilization
Authors: Bosworth AP , Contreras M , Weiser Novak S , Sancho L , Salas IH , Manor U , Allen NJ 
Published: March 2023

SummaryThe maturation and stabilization of appropriate synaptic connections is a vital step in the development of neuronal circuits, however the molecular signals underlying these processes are not fully understood. We show that astrocytes, through production of glypican 5 (GPC5), are required for maturation and refinement of synapses in the developing mouse cortex. In the absence of astrocyte GPC5 thalamocortical synapses in the visual cortex show structural immaturity during the critical period, including smaller presynaptic terminals, decreased postsynaptic density area, and presence of more postsynaptic partners at multisynaptic connections. This structural immaturity is accompanied by a delay in developmental incorporation of GLUA2-containing calcium impermeable AMPARs at intracortical synapses. The functional impact of this is that mice lacking astrocyte GPC5 exhibit increased levels of ocular dominance plasticity in adulthood. This shows astrocyte GPC5 is necessary for maturation and stabilization of synaptic connections in typical development, with implications for understanding disorders with altered synaptic function, including Alzheimer’s disease, where GPC5 levels are altered.
Environmentally stressed human nucleus pulposus cells trigger the onset of discogenic low back pain
Authors: Jiang Wensen , Glaeser Juliane D , Kaneda Giselle , Sheyn Julia , Wechsler Jacob T , Stephan Stephen , Salehi Khosrowdad , Chan Julie L. , Tawackoli Wafa , Avalos Pablo , Johnson Christopher , Castaneda Chloe , Kanim Linda EA , Tanasansomboon Teerachat , Burda Joshua , Shelest Oksana , Yameen Haneen , Perry Tiffany G , Kropf Michael , Cuellar Jason M , Seliktar Dror , Bae Hyun W , Stone Laura S , Sheyn Dmitriy 
Published: March 2023

AbstractLow back pain (LBP) is often associated with the degeneration of human intervertebral discs (IVDs). However, the pain-inducing mechanism in degenerating discs remains to be elucidated. Here, we identified a subtype of locally residing nucleus pulposus cells (NPCs), generated by the environmental stress in degenerating discs, that triggered the onset of discogenic LBP. Single-cell transcriptomic analysis of human tissues showed a strong correlation between this specific pain-triggering subtype and the pain conditions in human degenerated discs. Next, we recreated this pain-triggering subtype by applying known exogenous stressors to healthy NPCsin vitro. The recreated pain phenotype activated functional sensory neurons responsein vitroand induced local inflammatory responses, hyperalgesia, and mechanical sensitivity in a healthy rat IVDin vivo. Our findings provide strong evidence of a previously unknown pain-inducing mechanism mediated by NPCs in degenerating IVDs. This newly defined pathway will aid in the development of NPC-targeted therapeutic strategies for clinically unmet need to attenuate discogenic LBP.One Sentence SummaryDiscogenic low back pain can be initiated by a stress-induced subtype of nucleus pulposus cells present in human degenerating intervertebral discs
Identifying the environmental drivers of corridors and predicting connectivity between seasonal ranges in multiple populations of Alpine ibex (Capra ibex) as tools for conserving migration
Authors: Chauveau Victor , Garel Mathieu , Toïgo Carole , Anderwald Pia , Beurier Mathieu , Bunz Yoann , Bouche Michel , Cagnacci Francesca , Canut Marie , Cavailhes Jérôme , Champly Ilka , Filli Flurin , Frey-Roos Alfred , Gressmann Gunther , Herfindal Ivar , Jurgeit Florian , Martinelli Laura , Papet Rodolphe , Petit Elodie , Ramanzin Maurizio , Semenzato Paola , Vannard Eric , Loison Anne , Coulon Aurélie , Marchand Pascal 
Published: March 2023

ABSTRACTSeasonal migrations are central ecological processes connecting populations, species and ecosystems in time and space. Land migrations, such as those of ungulates, are particularly threatened by habitat transformations and fragmentation, climate change and other environmental changes caused by anthropogenic activities. Mountain ungulate migrations are neglected because they are relatively short, although traversing highly heterogeneous altitudinal gradients particularly exposed to anthropogenic threats. Detecting migration routes of these species and understanding their drivers is therefore of primary importance to predict connectivity and preserve ecosystem functions and services. The populations of Alpine ibexCapra ibex, an iconic species endemic to the Alps, have all been reintroduced from the last remnant source population. Because of their biology and conservation history, Alpine ibex populations are mostly disconnected. Hence, despite a general increase in abundance and overall distribution range, their conservation is strictly linked to the interplay between external threats and related behavioral responses, including space use and migration. By using 337 migratory tracks from 425 GPS-collared individuals from 15 Alpine ibex populations distributed across their entire range, we (i) identified the environmental drivers of movement corridors in both spring and autumn and (ii) compared the abilities of three modeling approaches to predict migratory movements between seasonal ranges of the 15 populations. Trade-offs between energy expenditure, food, and cover seemed to be the major driver of migration routes: steep south-facing snow-free slopes were selected while high elevation changes were avoided. This revealed the importance of favorable resources and an attempt to limit energy expenditures and perceived predation risk. Based on these findings, we provided efficient connectivity models to inform conservation of Alpine ibex and its habitats, and a framework for future research investigating connectivity in migratory species.
Early Differentiation Signatures in Human Induced Pluripotent Stem Cells Determined by Non-Targeted Metabolomics Analysis
Authors: Abdalkader Rodi , Chaleckis Romanas , Fujita Takuya 
Published: March 2023

AbstractHuman induced pluripotent stem cells (hiPSCs) possess immense potential as a valuable source for the generation of a wide variety of human cells yet monitoring the early cell differentiation towards a specific lineage remains challenging. In this study, we employed a non-targeted metabolomic analysis technique to analyze the extracellular metabolites present in samples as small as one microliter. The hiPSCs were subjected to differentiation by initiating culture under the basal medium E6 in combination with chemical inhibitors that have been previously reported to direct differentiation towards the ectodermal lineage such as Wnt/β- catenin and TGF-β kinase/activin receptor alone or in combination with bFGF, and the inhibition of glycogen kinase 3 (GSK-3), which is commonly used for the diversion of hiPSCs towards mesodermal lineage. At 0 hr and 48 hrs 107 metabolites were identified, including biologically relevant metabolites such as lactic acid, pyruvic acid, and amino acids. By determining the expression of the pluripotency marker OCT3/4, we were able to correlate the differentiation status of cells with the shifted metabolites. The group of cells undergoing ectodermal differentiation showed a greater reduction in OCT3/4 expression. Moreover, metabolites such as pyruvic acid and kynurenine showed dramatic change under ectodermal differentiation conditions where pyruvic acid consumption increased 1-2-folds, while kynurenine secretion decreased 2-folds. Further metabolite analysis uncovered a group of metabolites specifically associated with ectodermal lineage, highlighting the potential of our findings to determine the characteristics of hiPSCs during cell differentiation, particularly under ectodermal lineage conditions.Graphical abstract