bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Retinal Microvasculature and Immune Restoration Among South Eastern Asian Patients With HIV/AIDS Over a 9-Month Antiretroviral Therapy
Authors: Li Ling-Jun , Tan Petrina , Hee Owen , Agrawal Rupesh , Lim Tock-Han , Wong Tien-Yin , Teoh Stephen C 
Published: February 2022

Background:
Longitudinal evidence on retinal microvasculature and subsequent systemic inflammatory alteration is lacking. We investigated the association between retinal microvasculature and immune response among patients with HIV/AIDS over a 9-month antiretroviral therapy.

Methods:
We conducted a prospective cohort study on patients with HIV/AIDS at Singapore Communicable Disease Centre since June 2011. We recruited all eligible patients and then reviewed them every 3 months over a 9-month follow-up, including performing blood tests (CD4+/CD8+ T-cell counts and HIV viral load), blood pressure, anthropometry measurements, and retinal photography at each visit. We assessed retinal vascular indexes using a semiautomated computer-based program. Finally, we applied a linear mixed model to analyze associations between baseline retinal vascular indexes and 9-month changes of CD4+/CD8+ T-cell counts and HIV viral load throughout study observation, after adjusting for major confounders.

Results:
We found that narrower arteriolar caliber (per 10 μm decrease), wider venular caliber (per 10 μm increase), and larger arteriolar branching angle (per 10° increase) in the retina assessed at baseline were significantly associated with 9-month reductions in CD4+ T-cell count by 52.97 cells/μL (P = 0.006), 33.55 cells/μL (P = 0.01), and 39.09 cells/μL (P = 0.008), accordingly.

Conclusion:
Patients with HIV/AIDS with a suboptimal retinal microvascular morphology tended to fail immune restoration undertaking a 9-month antiretroviral therapy.
A Multicomponent Intervention to Reduce Readmissions Among People With HIV
Authors: Nijhawan Ank E. , Zhang Song , Chansard Matthieu , Gao Ang , Jain Mamta K. , Halm Ethan A. 
Published: February 2022

Background:
Hospital readmissions are common, costly, and potentially preventable, including among people with HIV (PWH). We present the results of an evaluation of a multicomponent intervention aimed at reducing 30-day readmissions among PWH.

Methods:
Demographic, socioeconomic, and clinical variables were collected from the electronic health records of PWH or those with cellulitis (control group) hospitalized at an urban safety-net hospital before and after (from September 2012 to December 2016) the implementation of a multidisciplinary HIV transitional care team. After October 2014, hospitalized PWH could receive a medical HIV consultation ± a transitional care nurse intervention. The primary outcome was readmission to any hospital within 30 days of discharge. Multivariate logistic regression and propensity score analyses were conducted to compare readmissions before and after intervention implementation in PWH and people with cellulitis.

Results:
Overall, among PWH, 329 of the 2049 (16.1%) readmissions occurred before and 329 of the 2023 (16.3%) occurred after the transitional care team intervention. After including clinical and social predictors, the adjusted odds ratio of 30-day readmissions for postintervention for PWH was 0.81 (95% confidence interval: 0.66 to 0.99, P= 0.04), whereas little reduction was identified for those with cellulitis (adjusted odds ratio 0.91 (95% confidence interval: 0.81 to 1.02, P= 0.10). A dose–response effect was not observed for receipt of different HIV intervention components.

Conclusions:
A multicomponent intervention reduced the adjusted risk of 30-day readmissions in PWH, although no dose–response effect was detected. Additional efforts are needed to reduce overall hospitalizations and readmissions among PWH including increasing HIV prevention, early diagnosis and engagement in care, and expanding the availability and spectrum of transitional care services.
Hospital readmission after blunt traumatic rib fractures
Authors: Marthy Andrew G. , Mounsey Molly , Ata Ashar , Stain Steven C. , Tafen Marcel 
Published: February 2022

BACKGROUND
Hospital readmissions are resource intensive, associated with increased morbidity, and often used as hospital-level quality indicators. The factors that determine hospital readmission after blunt thoracic trauma have not been sufficiently defined. We sought to identify predictors of hospital readmission in patients with traumatic rib fractures.

METHODS
We performed an 8-year (2011–2019) retrospective chart review of patients with traumatic rib fractures who required unplanned readmission within 30 days of discharge at a Level 1 trauma center. Patient characteristics, injury severity, and hospital complications were examined using quantitative analysis to identify readmission risk factors.

RESULTS
There were 13,046 trauma admissions during the study period. The traumatic rib fracture cohort consisted of 3,720 patients. The cohort included 206 patients who were readmitted within 30 days of discharge. The mean age of the traumatic rib fracture cohort was 57 years, with a 6-day median length of stay. The 30-day mortality rate was 5%. Use of anticoagulation (11.0 vs. 5.4; p = 0.029), diagnosis of a psychiatric disorder (10.2 vs. 5.3; p = 0.01), active smoking (7.3 vs. 5.0; p = 0.008), associated hemothorax (8.3 vs. 5.2; p = 0.010), higher abdominal Abbreviated Injury Scale (33.3 vs. 8.4 vs. 6.5; p = 0.002), rapid response activation (8.9 vs. 5.2; p = 0.005), admission to intensive care unit (7.7 vs. 4.5; p = 0.001), and diagnosis of in-hospital pneumonia (10.1 vs. 5.4; p = 0.022) were predictors of hospital readmission. On multivariate analysis, prescribed anticoagulation (odds ratio [OR], 2.22; p = 0.033), active smoking (OR, 1.58; p = 0.004), higher abdominal Abbreviated Injury Scale (OR, 1.50; p = 0.054), and diagnosis of a psychiatric disorder (OR, 2.00; p = 0.016) predicted hospital readmission.

CONCLUSION
In patients with traumatic rib fractures, those with anticoagulant use, those who actively smoke, those with a psychiatric diagnosis, or those with associated abdominal injuries are at the highest risk of rehospitalization following discharge. Quality improvement should focus on strategies and protocols directed toward these groups to reduce nonelective readmissions.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
ECMO Long Haulers: A Distinct Phenotype of COVID-19–Associated ARDS With Implications for Lung Transplant Candidacy
Authors: Mohanka Manish R. , Joerns John , Lawrence Adrian , Bollineni Srinivas , Kaza Vaidehi , Cheruku Sreekanth , Leveno Matthew , Chen Catherine , Terada Lance S. , Kershaw Corey D. , Torres Fernando , Peltz Matthias , Wait Michael A. , Hackmann Amy E. , Banga Amit 
Published: February 2022

Background.
Studies indicate that the recovery from coronavirus disease 2019 (COVID-19)–associated acute respiratory distress syndrome may be slower than other viral pneumonia. There are limited data to guide decisions among patients who need extracorporeal membrane oxygenation (ECMO) support, especially the expected time of recovery and considering lung transplantation (LT).

Methods.
This was a retrospective chart review of patients with COVID-19–associated acute respiratory distress syndrome placed on ECMO between March 1, 2020, and September 15, 2021 (n = 20; median age, 44 y; range, 22–62 y; male:female, 15:5). We contrasted the baseline variables and clinical course of patients with and without the need for ECMO support >30 d (ECMO long haulers, n = 10).

Results.
Ten patients met the criteria for ECMO long haulers (median duration of ECMO, 86 d; range, 42–201 d). The long haulers were healthier at baseline with fewer comorbidities but had worse pulmonary compliance and higher partial pressure of CO2. They had a significantly higher number of membrane oxygenator failures, changes to their cannulation sites, and suffer more complications on ECMO. One of the long hauler was bridged to LT while another 6 patients recovered and were discharged. Overall survival was better among the ECMO long haulers (70% versus 20%; 9.3, 1.2–73; P = 0.03).

Conclusions.
Despite worse pulmonary physiology, frequent complications, and a tortuous hospital course that may appear to portend a poor prognosis, ECMO long haulers have the potential to recover and be weaned off ECMO without the need for LT. A customized approach comprising a more conservative timeline for the consideration of LT may be prudent among these patients.
Antimicrobial susceptibility and risk factors for resistance amongEscherichia coliisolated from canine specimens submitted to a diagnostic laboratory in Indiana, 2010-2019
Authors: Ekakoro John E. , Hendrix G. Kenitra , Guptill Lynn F. , Ruple Audrey 
Published: February 2022

AbstractEscherichia coli(E. coli) is the most common Gram-negative pathogen isolated in human infections. Antimicrobial resistant (AMR)E. colioriginating from dogs may directly or indirectly cause disease in humans. The objective of this study was to calculate the proportion of antimicrobial susceptibleE. coliisolated from canine specimens submitted to the Indiana Animal Disease Diagnostic Laboratory and to identify temporal patterns of susceptibility among these isolates. Susceptibility data of 2,738E. coliisolates from dogs from 2010 through 2019 were used in this study. Proportions of isolates susceptible to the various antimicrobials were calculated using SAS statistical software and the Cochran-Armitage trend test was used to investigate the temporal trends in susceptibility. A multivariable binary logistic regression model was built to investigate the association between host factors and AMR. Overall, 553/2,738 (20.2%) of the isolates were susceptible to 17 of the 27 antimicrobials examined. Of the 2,638 isolates examined for amikacin susceptibility, 2,706 (97.5%) were susceptible, 2,657/2,673 (99.4%) isolates were susceptible to imipenem, and 2,099/2,670 (78.6%) were susceptible to marbofloxacin. A significant decreasing trend in susceptibility was observed for amoxicillin-clavulanic acid (P<0.0001), ampicillin (P<0.0001), Cefazolin (P<0.0001), ceftazidime (P=0.0067), chloramphenicol (P<0.0001), and orbifloxacin (P=0.008). The overall percentage of AMR isolates (isolates not susceptible to at least one antimicrobial) was 61.7% (1,690/2,738) and 29.3 % (801/2,738) of isolates were multidrug resistant. Multivariable regression analyses showed significant associations between AMR and age (P=0.0091), breed (P=0.0008), and sample isolation site/source (P<0.0001). The decreasing trend in the proportion of isolates susceptible to several beta-lactam antimicrobials suggests that resistance ofEscherichia coliin dogs to these antimicrobials could be increasing in Indiana. The decreasing trend in susceptibility to these drugs could be due to selection pressure from antimicrobial use.
The Role of Genetic Testing in Diagnosis and Care of Inherited Cardiac Conditions in a Specialised Multidisciplinary Clinic
Authors: Stafford Fergus , Krishnan Neesha , Richardson Ebony , Butters Alexandra , Hespe Sophie , Burns Charlotte , Gray Belinda , Medi Caroline , Nowak Natalie , Isbister Julia C , Raju Hariharan , Richmond David , Ryan Mark P , Singer Emma S , Sy Raymond W , Yeates Laura , Bagnall Richard D , Semsarian Christopher , Ingles Jodie 
Published: February 2022

ABSTRACTBackgroundThe diagnostic yield of genetic testing for inherited cardiac diseases is up to 40% and primarily indicated for screening of at-risk relatives. Here we evaluate the role of genomics in diagnosis and management among consecutive individuals attending a specialised clinic and identify those with highest likelihood of having a monogenic disease.MethodsRetrospective audit of 1697 consecutive, unrelated probands referred to a specialised, multidisciplinary clinic between 2002 and 2020. A concordant clinical and genetic diagnosis was considered solved. Cases were classified as likely monogenic based on a score comprising a positive family history, young age at onset and severe phenotype, whereas low scoring cases were considered to have a likely complex aetiology. The impact of a genetic diagnosis was evaluated.ResultsA total of 888 probands fulfilled inclusion criteria, and genetic testing identified likely pathogenic or pathogenic (LP/P) variants in 330 individuals (37%), and suspicious variants of uncertain significance (VUS) in 73 (8%). Research-focused efforts identified 46 (5%) variants, missed by conventional genetic testing. Where a variant was identified, this changed or clarified the final diagnosis in a clinically useful way for 51 (13%). The yield of suspicious VUS across ancestry groups ranged from 15-20%, compared to only 10% among Europeans. Even when the clinical diagnosis was uncertain, those with the most monogenic disease features had the greatest diagnostic yield from genetic testing.ConclusionResearch-focused efforts can increase the diagnostic yield by up to 5%. Where a variant is identified, this will have clinical utility beyond family screening in 13%. We demonstrate the value of genomics in reaching an overall diagnosis, and highlight inequities based on ancestry. Acknowledging our incomplete understanding of disease phenotypes, we propose a framework for prioritising likely monogenic cases to solve their underlying cause of disease.
The Heart’s Pacemaker Mimics Brain Cytoarchitecture and Function: Autonomic innervation, a peripheral glial cell web, and a novel S100B expressing interstitial cell type impart structural and functional complexity to the sinoatrial node
Authors: Bychkov Rostislav , Juhaszova Magdalena , Calvo-Rubio Miguel , Donald Lorenzo A. H. , Coletta Chris , Shumaker Chad , Moorman Kayla , Sirenko Syevda Tagirova , Maltsev Alex V. , Sollott Steven J. , Lakatta Edward G. 
Published: February 2022

AbstractObjectivesThis study sought to describe the 3D cytoarchitecture of sinoatrial node tissue, including autonomic innervation, peripheral glial cells, and pacemaker cells.BackgroundThe sinoatrial node of the heart produces rhythmic action potentials (AP), generated via calcium signaling within and among pacemaker cells. Our previous work has described the SAN as composed of an HCN4-expressing pacemaker cell meshwork, which merges with a network of CX43+/F-actin+ cells. It is also known that sympathetic and parasympathetic innervation from epicardial ganglia create an autonomic plexus in the sinoatrial node, which modulates heart rate and rhythm. However, the anatomical details of the interaction of this plexus with the pacemaker cell meshwork have yet to be described.Methods3D confocal laser-scanning microscopy of triple immunolabeled SAN whole mount preparations with combinations of antibodies for HCN4, S100B, GFAP, ChAT or VAChT, and TH, and transmission electron microscopy (TEM).ResultsThe SAN exhibited heterogeneous autonomic innervation, which was accompanied by a web of peripheral glial cells (PGCs). Further, we identified a novel S100B+/GFAP- interstitial cell population, with unique morphology and distinct distribution pattern, creating complex interactions with other cell types in the node. TEM images showed a similar population of cells, here identified as telocytes, which appeared to secrete vesicles towards pacemaker cells. Application of S100B protein to SAN preparations induced distinct changes in rhythmogenic calcium signaling.ConclusionsThe autonomic plexus and its associated peripheral glial cell web, a novel network of S100B expressing interstitial cells resembling telocytes, and a meshwork of HCN4+ cells interact to impart structural complexity to the sinoatrial node.Summary Table
LRLoop: Feedback loops as a design principle of cell-cell communication
Authors: Xin Ying , Lyu Pin , Jiang Junyao , Zhou Fengquan , Wang Jie , Blackshaw Seth , Qian Jiang 
Published: February 2022

ABSTRACTGenome-wide gene expression profiling, and single-cell RNA-seq in particular, allows the predictions of molecular mechanisms regulating cell-cell communication based on the expression of known ligand-receptor pairs. Currently available techniques for predicting ligand-receptor interactions are one-directional from sender to receiver cells. Here we describe LRLoop, a new method for analyzing cell-cell communication that is based on bi-directional ligand-receptor interactions, where two pairs of ligand-receptor interactions are identified that are responsive to each other, and thereby form a closed feedback loop. We assessed LRLoop using both bulk and single-cell datasets and found our method significantly reduces the false positive rate seen with existing methods. Finally, we applied LRLoop to the single-cell datasets obtained from retinal development and discovered many new bi-directional ligand-receptor interactions among individual cell types that potentially control proliferation, neurogenesis and/or cell fate specification.
SpatialCorr: Identifying Gene Sets with Spatially Varying Correlation Structure
Authors: Bernstein Matthew N. , Ni Zijian , Prasad Aman , Brown Jared , Mohanty Chitrasen , Stewart Ron , Newton Michael A. , Kendziorski Christina 
Published: February 2022

AbstractRecent advances in spatially resolved transcriptomics technologies enable both the measurement of genome-wide gene expression profiles and their mapping to spatial locations within a tissue. A first step in spatial transcriptomics data analysis is identifying genes with expression that varies spatially, and robust statistical methods exist to address this challenge. While useful, these methods do not detect spatial changes in the coordinated expression within a group of genes. To this end, we present SpatialCorr, a method for identifying sets of genes with spatially varying correlation structure. Given a collection of gene sets pre-defined by a user, SpatialCorr tests for spatially induced differences in the correlation of each gene set within tissue regions, as well as between and among regions. An application to cutaneous squamous cell carcinoma demonstrates the power of the approach for revealing biological insights not identified using existing methods.
Time-Optimal Adaptation in Metabolic Network Models
Authors: Köbis Markus A. , Bockmayr Alexander , Steuer Ralf 
Published: February 2022

AbstractAnalysis of metabolic models using constraint-based optimization has emerged as an important computational technique to elucidate and eventually predict cellular metabolism and growth. In this work, we introduce time-optimal adaptation (TOA), a new constraint-based modeling approach that allows us to evaluate the fastest possible adaptation to a pre-defined cellular state while fulfilling a given set of dynamic and static constraints. TOA falls into the mathematical problem class of time-optimal control problems, and, in its general form, can be applied in a broad sense and thereby extends most existing constraint-based modeling frameworks. Specifically, We introduce a general mathematical framework that captures many existing constraint-based methods and define TOA within this framework. We then exemplify TOA using a coarse-grained self-replicator model and demonstrate that TOA allows us to explain several well known experimental phenomena that are difficult to explore using existing constraint-based analysis methods. We show that TOA can explain accumulation of storage compounds in constant environments, as well as overshoot uptake metabolism after a period of nutrient scarcity. TOA reveals that organisms with internal temporal degrees of freedom, such as storage, can in most environments outperform organisms with a static intracellular composition. Furthermore, TOA shows that organisms adapted to better growth conditions than present in the environment (“optimists”) typically outperform organisms adapted to poorer growth conditions (“pessimists”).
Impacts of climate change on California’s rangeland production: sensitivity and future projection
Authors: Liu Han , Jin Yufang , Roche Leslie M. , O’Geen Anthony T. , Dahlgren Randy A. 
Published: February 2022

AbstractRangelands support many important ecosystem services and are highly sensitive to climate change. Understanding temporal dynamics in rangeland gross primary production (GPP) and how it may change under projected climate change, including more frequent and severe droughts, is critical for ranching communities to cope with future changes. Covering ~10% of California’s climatologically and topographically diverse landscapes, annual rangelands express varying sensitivity to precipitation fluctuation and warming. Herein, we examined how climate regulates temporal dynamics of annual GPP in California’s annual rangeland across scales, based on 20 years of satellite record derived GPP at 500-meter resolution since 2001. We built gradient boosted regression tree models for 23 ecoregion subsections in our study area, relating annual GPP with 30 climatic variables and disentangling the partial dependence of GPP on each climate variable. Our analysis showed that GPP was most sensitive to growing season precipitation amount; GPP decrease as much as 200 g C/m2/yr when growing season precipitation decreased from 400 to 100 mm/yr in one of the driest subsections. We also found that years with more evenly distributed growing season precipitation had higher GPP. Warmer winter minimum air temperature enhanced GPP in approximately two-thirds of the subsections. In contrast, average growing season mean and maximum air temperatures showed a negative relationship with annual GPP. When forced by downscaled future climate projections, changes in future rangeland productivity at the ecoregion subsection scale were more remarkable than at the state level; this suggests rangeland productivity responses to climate change will be highly variable at the local level. Further, we found large uncertainty in precipitation projections among the four climate models used in this study. Specifically, drier models predicted a larger degree of reduction in GPP, especially in drier subsections. Our machine learning-based analysis highlights key regional differences in GPP vulnerability to climate and provides insights into the intertwining and potentially counteracting effects of seasonal temperature and precipitation regimes. This work demonstrates the potential of using remote sensing to enhance field-based rangeland monitoring and, combined with machine learning, to inform adaptive management and conservation within the context of weather extremes and climate change.
Fate tracing reveals differences between Reelin+ HSCs and Desmin+ HSCs in activation, migration, and proliferation activities
Authors: Chen Ning , Liu Shenghui , Qin Dan , Guan Dian , Chen Yaqing , Hou Chenjiao , Zheng Songyun , Wang Liqiang , Chen Xiangmei , Zhang Lisheng 
Published: February 2022

AbstractThe activation of hepatic stellate cells (HSCs) which comprise distinct clusters, is the main cause of liver fibrogenesis in response to different etiologies of chronic liver injuries. In this study, we constructed a novel ReelinCreERT2 transgenic mouse in which cells expressing Reelin were fully marked and demonstrated that about 50% HSCs were labeled. These ReelinCreERT2-labeled HSCs displayed distinct characteristics in migration, activation and proliferation compared to Desmin+ HSCs (total HSCs) in cholestatic (bile duct ligation; BDL) or hepatotoxic (carbon tetrachloride; CCl4) liver injuries. In BDL-induced fibrotic livers, Desmin+ HSCs were activated with increased proliferation and accumulation activities around the portal triad, but mGFP+ HSCs did not show proliferation or accumulation activity around the portal triad, and only a small part was activated. In CCl4-induced fibrotic livers, most of Desmin+ and mGFP+ HSCs were activated along with proliferation and accumulation potential around the central vein, however fewer mGFP+ HSCs were activated compared to Desmin+ HSCs. Moreover, in the regression of CCl4-induced fibrosis, mGFP+ HSCs were apoptosed whereas Desmin+ HSCs recovered to normal state. Besides, we didn’t find evidence that mGFP+ HSCs transdifferentiated into hepatocytes or cholangiocytes through mesenchymal-epithelial transition (MET).