bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparison of Home Health Utilization, Outcomes, and Cost Between Medicare Advantage and Traditional Medicare
Authors: Casebeer Adrianne W. , Ronning David , Schwartz Richard , Long Charron , Bhattacharya Rituparna , Uribe Claudia , Brown Courtney R. , Cameron Joy , Painter Phil , Sharma Anup , Spitale Sandy , Powers Brian , Stemple Chuck , Shrank William 
Published: November 2021

Background:
Home health use is rising rapidly in the United States as the population ages, the prevalence of chronic disease increases, and older Americans express their desire to age at home. Enrollment in Medicare Advantage (MA) plans rather than Traditional Medicare (TM) has grown as well, from 13% of total Medicare enrollment in 2004 to 39% in 2020. Despite these shifts, little is known about outcomes and costs following home health in MA as compared with TM.

Objective:
The objective of this study was to measure the association of MA enrollment with outcomes and costs for patients using home health.

Design:
This was a retrospective cohort study.

Participants:
Patients enrolled in plans offered by 1 large, national MA organization and patients enrolled in TM, with at least 1 home health visit between January 1, 2017, and June 30, 2018.

Exposure:
MA enrollment.

Main Measures:
We compared the intensity of home health services and types of care delivered. The main outcome measures were hospitalization, the proportion of days in the home, and total allowed costs during the 180-day period following the first qualifying home health visit during the study period.

Key Results:
Among patients who used home health, our models demonstrated enrollment in MA was associated with 14%, and 6% decreased odds of 60- and 180-day hospitalization, respectively, a 12.8% and 14.7% decrease in medical costs exclusive and inclusive of home health costs, respectively, and a 0.27% increase in the proportion of days at home during the 180-day follow-up, equivalent to an additional half-day at home. There were few differences in home health care delivered for MA and TM [mean number of visits in the first episode of care (17.1 vs. 17.3) and mean visits per week (3.2 vs. 3.3)]. The mean number of visits by visit type and percent of patients with each type was similar between MA and TM as well.

Conclusions:
Compared with enrollment in TM, enrollment in MA was associated with improved patient-centered outcomes and lower cost and utilization, despite few differences in the way home health was delivered. These findings might be explained by structural components of MA that encourage better care management, but further investigation is needed to clarify the mechanisms by which MA enrollment may lead to higher value home health care.
Kidney dysfunction requiring dialysis is a heterogeneous syndrome: we should treat it like one
Authors: Murea Mariana , Flythe Jennifer E. , Anjay Rastogi , Emaad Abdel-Rahman M. , Gupta Nupur , Kovach Cassandra , Vachharajani Tushar J. , Kalantar-Zadeh Kamyar , Casino Francesco G. , Basile Carlo 
Published: November 2021

Purpose of review
Advanced kidney failure requiring dialysis, commonly labeled end-stage kidney disease or chronic kidney disease stage 5D, is a heterogeneous syndrome –a key reason that may explain why: treating advanced kidney dysfunction is challenging and many clinical trials involving patients on dialysis have failed, thus far. Treatment with dialytic techniques – of which maintenance thrice-weekly hemodialysis is most commonly used – is broadly named kidney ‘replacement’ therapy, a term that casts the perception of a priori abandonment of intrinsic kidney function and subsumes patients into a single, homogeneous group.

Recent findings
Patients with advanced kidney failure necessitating dialytic therapy may have ongoing endogenous kidney function, and differ in their clinical manifestations and needs. Different terminology, for example, kidney dysfunction requiring dialysis (KDRD) with stages of progressive severity could better capture the range of phenotypes of patients who require kidney ‘assistance’ therapy.

Summary
Classifying patients with KDRD based on objective, quantitative levels of endogenous kidney function, as well as patient-reported symptoms and quality of life, would facilitate hemodialysis prescriptions tailored to level of kidney dysfunction, clinical needs, and personal priorities. Such classification would encourage clinicians to move toward personalized, physiological, and adaptive approach to hemodialysis therapy.
Hypertonic Dextrose Prolotherapy, an Alternative to Intra-Articular Injections With Hyaluronic Acid in the Treatment of Knee Osteoarthritis
Authors: Arias-Vázquez Pedro Iván , Tovilla-Zárate Carlos Alfonso , Castillo-Avila Rosa Giannina , Legorreta-Ramírez Blanca Gabriela , López-Narváez María Lilia , Arcila-Novelo Russell , González-Castro Thelma Beatriz 
Published: November 2021

Abstract
Intra-articular injections with hyaluronic acid are recommended in the treatment of knee osteoarthritis; however, hypertonic dextrose prolotherapy has been reported as effective and safe. The aim was to evaluate the effectiveness of hypertonic dextrose prolotherapy for pain reduction and improvement of function in individuals with knee osteoarthritis in comparison with hyaluronic acid by meta-analysis. The search was performed in electronic databases. Six studies were included (395 participants). No statistically significant differences were found between prolotherapy and hyaluronic acid in pain control in the short-term; however, in the subanalysis that included only the studies that used intra-articular injection within the prolotherapy scheme, an effect was found in favor of the prolotherapy groups (d = −1.33; 95% confidence interval, −2.50 to −0.16; P (z) = 0.03). Also, an effect was found in favor of the prolotherapy group in the improvement in function (d = −1.05; 95% confidence interval, −2.03 to −0.08; P (z) = 0.03). No major adverse reactions or side effects were reported in any of the studies. Hypertonic dextrose prolotherapy seems to be an effective intervention to decrease pain and improve function in knee osteoarthritis, with efficacy similar to intra-articular injections with hyaluronic acid in the short-term follow-up. Nonetheless, better-quality clinical trials are necessary.
δPKC-Mediated DRP1 Phosphorylation Impacts Macrophage Mitochondrial Function and Inflammatory Response to Endotoxin
Authors: Lin Amanda J. , Joshi Amit U. , Mukherjee Riddhita , Tompkins Carly A. , Vijayan Vijith , Mochly-Rosen Daria , Haileselassie Bereketeab 
Published: November 2021

ABSTRACT

Background:
Recent studies have demonstrated that alterations in mitochondrial dynamics can impact innate immune function. However, the upstream mechanisms that link mitochondrial dynamics to innate immune phenotypes have not been completely elucidated. This study asks if Protein Kinase C, subunit delta (δPKC)-mediated phosphorylation of dynamin-related protein 1 (Drp1), a key driver of mitochondrial fission, impacts macrophage pro-inflammatory response following bacterial-derived lipopolysaccharide (LPS) stimulation.

Methods:
Using RAW 264.7 cells, bone marrow-derived macrophages from C57BL/6J mice, as well as human monocyte-derived macrophages, we first characterized changes in δPKC-mediated phosphorylation of Drp1 following LPS stimulation. Next, using rationally designed peptides that inhibit δPKC activation (δV1-1) and δPKC-Drp1 interaction (ψDrp1), we determined whether δPKC-mediated phosphorylation of Drp1 impacts LPS-induced changes in mitochondrial morphology, mitochondrial function, and inflammatory response.

Results:
Our results demonstrated that δPKC-dependent Drp1 activation is associated with increased mitochondrial fission, impaired cellular respiration, and increased mitochondrial reactive oxygen species in LPS-treated macrophages. This is reversed using a rationally designed peptide that selectively inhibits δPKC phosphorylation of Drp1 (ψDrp1). Interestingly, limiting excessive mitochondrial fission using ψDrp1 reduced LPS-triggered pro-inflammatory response, including a decrease in NF-κB nuclear localization, decreased iNOS induction, and a reduction in pro-inflammatory cytokines (IL-1β, TNFα, IL-6).

Conclusion:
These data suggest that inhibiting Drp1 phosphorylation by δPKC abates the excessive mitochondrial fragmentation and mitochondrial dysfunction that is seen following LPS treatment. Furthermore, these data suggest that limiting δPKC-dependent Drp1 activation decreases the pro-inflammatory response following LPS treatment. Altogether, δPKC-dependent Drp1 phosphorylation might be an upstream mechanistic link between alterations in mitochondrial dynamics and innate immune phenotypes, and may have therapeutic potential.
The Impact of Indocyanine Green Fluorescence Angiography on Intraoperative Decision Making in Right Hemicolectomy: A Case-Control Study
Authors: Aawsaj Yousif , Mustafa Abdalla , Winstanley Joseph , O’loughlin Paul 
Published: November 2021

Introduction:
Anastomotic leak (AL) after right hemicolectomy remains a significant clinical challenge with an incidence of 4.2% to 8.2% in European series. Near infrared imaging with indocyanine green (NIR-ICG) allows real-time assessment of bowel perfusion. However, there is a lack of published data assessing the clinical utility of this new technology in right sided colonic resection.

Materials and Methods:
Data from electronic records were retrospectively analyzed for consecutive patients undergoing right hemicolectomy in a single center between March 1, 2016 and October 31, 2019. Primary outcomes were the incidence of AL and the frequency with which ICG-NIR imaging altered the intraoperative course.

Results:
Our study included 127 patients, with 65 in the NIR-ICG group and 62 in the control group. Median length of follow-up was 24 months. There was no significant difference in demographic or pathologic characteristics between the 2 cohorts. There was no significant difference in operation length between the NIR-ICG and control groups (164.7 vs. 162.9 min, P=0.88). The use of NIR-ICG altered the intraoperative course in 4/65 (6.2%) patients. The rate of AL was lower in the NIR-ICG group (1.5% vs. 4.8%), although this did not reach statistical significance.

Conclusion:
The use of NIR-ICG altered the intraoperative course for notable subset of patients undergoing right hemicolectomy without prolonging operative time. Larger prospective studies are required to evaluate the potential for the routine use of this technology to reduce AL rate in right hemicolectomy.
A new trauma frontier: Exploratory pilot study of platelet transcriptomics in trauma patients
Authors: Fields Alexander T. , Lee Man-Cheung , Mayer Fahima , Santos Yale A. , Bainton Cedric M.V. , Matthay Zachary A. , Callcut Rachael A. , Mayer Nasima , Cuschieri Joseph , Kober Kord M. , Bainton Roland J. , Kornblith Lucy Zumwinkle 
Published: November 2021

BACKGROUND
The earliest measurable changes to postinjury platelet biology may be in the platelet transcriptome, as platelets are known to carry messenger ribonucleic acids (RNAs), and there is evidence in other inflammatory and infectious disease states of differential and alternative platelet RNA splicing in response to changing physiology. Thus, the aim of this exploratory pilot study was to examine the platelet transcriptome and platelet RNA splicing signatures in trauma patients compared with healthy donors.

METHODS
Preresuscitation platelets purified from trauma patients (n = 9) and healthy donors (n = 5) were assayed using deep RNA sequencing. Differential gene expression analysis, weighted gene coexpression network analysis, and differential alternative splicing analyses were performed. In parallel samples, platelet function was measured with platelet aggregometry, and clot formation was measured with thromboelastography.

RESULTS
Differential gene expression analysis identified 49 platelet RNAs to have differing abundance between trauma patients and healthy donors. Weighted gene coexpression network analysis identified coexpressed platelet RNAs that correlated with platelet aggregation. Differential alternative splicing analyses revealed 1,188 splicing events across 462 platelet RNAs that were highly statistically significant (false discovery rate <0.001) in trauma patients compared with healthy donors. Unsupervised principal component analysis of these platelet RNA splicing signatures segregated trauma patients in two main clusters separate from healthy controls.

CONCLUSION
Our findings provide evidence of finetuning of the platelet transcriptome through differential alternative splicing of platelet RNA in trauma patients and that this finetuning may have relevance to downstream platelet signaling. Additional investigations of the trauma platelet transcriptome should be pursued to improve our understanding of the platelet functional responses to trauma on a molecular level.
Patient-reported outcomes 6 to 12 months after isolated rib fractures: A nontrivial injury pattern
Authors: Heindel Patrick , Ordoobadi Alexander , El Moheb Mohamad , Serventi-Gleeson Jessica , Garvey Shannon , Heyman Annie , Patel Nikita , Sanchez Sabrina , Kaafarani Haytham M.A. , Herrera-Escobar Juan , Salim Ali , Nehra Deepika 
Published: November 2021

BACKGROUND
Despite the ubiquity of rib fractures in patients with blunt chest trauma, long-term outcomes for patients with this injury pattern are not well described.

METHODS
The Functional Outcomes and Recovery after Trauma Emergencies (FORTE) project has established a multicenter prospective registry with 6- to 12-month follow-up for trauma patients treated at participating centers. We combined the FORTE registry with a detailed retrospective chart review investigating admission variables and injury characteristics. All trauma survivors with complete FORTE data and isolated chest trauma (Abbreviated Injury Scale score of ≤1 in all other regions) with rib fractures were included. Outcomes included chronic pain, limitation in activities of daily living, physical limitations, exercise limitations, return to work, and both inpatient and discharge pain control modalities. Multivariable logistic regression models were built for each outcome using clinically relevant demographic and injury characteristic univariate predictors.

RESULTS
We identified 279 patients with isolated rib fractures. The median age of the cohort was 68 years (interquartile range, 56–78 years), 59% were male, and 84% were White. Functional and quality of life limitations were common among survivors of isolated rib fractures even 6 to 12 months after injury. Forty-three percent of patients without a preexisting pain disorder reported new daily pain, and new chronic pain was associated with low resilience. Limitations in physical functioning and exercise capacity were reported in 56% and 51% of patients, respectively. Of those working preinjury, 28% had not returned to work. New limitations in activities of daily living were reported in 29% of patients older than 65 years. Older age, higher number of rib fractures, and intensive care unit admission were independently associated with higher odds of receiving regional anesthesia. Receiving a regional nerve block did not have a statistically significant association with any patient-reported outcome measures.

CONCLUSION
Isolated rib fractures are a nontrivial trauma burden associated with functional impairment and chronic pain even 6 to 12 months after injury.

LEVEL OF EVIDENCE
Prognostic/epidemiologic, level III.
Social determinants of health and patient-level mortality prediction after trauma
Authors: Phelos Heather M. , Kass Nicolas M. , Deeb Andrew-Paul , Brown Joshua B. 
Published: November 2021

BACKGROUND
Social determinants of health (SDOH) impact patient outcomes in trauma. Census data are often used to account for SDOH; however, there is no consensus on which variables are most important. Social vulnerability indices offer the advantage of combining multiple constructs into a single variable. Our objective was to determine if incorporation of SDOH in patient-level risk-adjusted outcome modeling improved predictive performance.

METHODS
We evaluated two social vulnerability indices at the zip code level: Distressed Community Index (DCI) and National Risk Index (NRI). Individual variable combinations from Agency for Healthcare Research and Quality's SDOH data set were used for comparison. Patients were obtained from the Pennsylvania Trauma Outcomes Study 2000 to 2020. These measures were added to a validated base mortality prediction model with comparison of area under the curve and Bayesian information criterion. We performed center benchmarking using risk-standardized mortality ratios to evaluate change in rank and outlier status based on SDOH. Geospatial analysis identified geographic variation and autocorrelation.

RESULTS
There were 449,541 patients included. The DCI and NRI were associated with an increase in mortality (adjusted odds ratio, 1.02; 95% confidence interval, 1.01–1.03 per 10% percentile rank increase; p < 0.01, respectively). The DCI, NRI, and seven Agency for Healthcare Research and Quality variables also improved base model fit but discrimination was similar. Two thirds of centers changed mortality ranking when accounting for SDOH compared with the base model alone. Outlier status changed in 7% of centers, most representing an improvement from worse-than-expected to nonoutlier or nonoutlier to better-than-expected. There was significant geographic variation and autocorrelation of the DCI and NRI (DCI; Moran's I 0.62, p = 0.01; NRI; Moran's I 0.34, p = 0.01).

CONCLUSION
Social determinants of health are associated with an individual patient's risk of mortality after injury. Accounting for SDOH may be important in risk adjustment for trauma center benchmarking.

LEVEL OF EVIDENCE
Prognostic/Epidemiologic, level IV.
Health-related quality of life and functional outcome measures for pediatric multiple injury: A systematic review and narrative synthesis
Authors: Collins Kathryn C. , Burdall Oliver , Kassam Jamila , Firth Gregory , Perry Daniel , Ramachandran Manoj 
Published: November 2021

BACKGROUND
Pediatric multiple injury is a major cause of mortality and morbidity worldwide, with varied long-term sequelae. To improve care, a better understanding of the outcome tools used following multiple injury is needed.

OBJECTIVES
This study aimed to (1) identify the outcome tools used to assess functional and health-related quality of life outcomes in pediatric multiple injury and to (2) describe the tool domains and validity.

METHODS
Eligible studies were those that included pediatric participants aged 0 to 17 years who experienced multiple injury or severe trauma based on Injury Severity Score/Abbreviated Injury Scale score and a functional outcome tool was used to assess outcomes (e.g., physical, psychological, quality of life). Excluded study designs were editorials, narrative, and systematic reviews.

RESULTS
Twenty-two papers were included encompassing 16,905 participants and 34 different outcome tools. Ten tools were validated in children of which 4 were multiple injury specific; 18 were validated in adults of which 8 were trauma specific, and 6 were previously unvalidated. The tools were a mixture of patient reported (7 of 10 validated in children and 13 of 18 validated in adults) and clinician reported (3 of 10 validated in children and 2 of 13 validated in adults). Pediatric tool domains assessed were function, mobility, activities of daily living, pain, school, cognition, emotional domains, mental health, behavior, and high-risk behaviors. Using adult-validated tools to assess children may not capture the children's true function and health-related quality of life.

CONCLUSION
There was a lack of consistency in the outcome tools used following multiple injury in children. Adult-validated measures may not accurately capture pediatric outcomes after multiple injury. To fully understand the impact of pediatric multiple injury and make comparisons between studies, development of a core outcome set is required.

LEVEL OF EVIDENCE
Quantitative observational studies, level III.
Proteomics of spatially identified tissues in whole organs
Authors: Bhatia Harsharan Singh , Brunner Andreas-David , Rong Zhouyi , Mai Hongcheng , Thielert Marvin , Al-Maskari Rami , Paetzold Johannes Christian , Kofler Florian , Todorov Mihail Ivilinov , Ali Mayar , Molbay Muge , Kolabas Zeynep Ilgin , Kaltenecker Doris , Müller Stephan , Lichtenthaler Stefan F. , Menze Bjoern H. , Theis Fabian J. , Mann Matthias , Ertürk Ali 
Published: November 2021

SUMMARYSpatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of biological specimens imaged in 3D as a whole are lacking. Here, we present DISCO-MS, a technology combining whole-organ imaging, deep learning-based image analysis, and ultra-high sensitivity mass spectrometry. DISCO-MS yielded qualitative and quantitative proteomics data indistinguishable from uncleared samples in both rodent and human tissues. Using DISCO-MS, we investigated microglia activation locally along axonal tracts after brain injury and revealed known and novel biomarkers. Furthermore, we identified initial individual amyloid-beta plaques in the brains of a young familial Alzheimer’s disease mouse model, characterized the core proteome of these aggregates, and highlighted their compositional heterogeneity. Thus, DISCO-MS enables quantitative, unbiased proteome analysis of target tissues following unbiased imaging of entire organs, providing new diagnostic and therapeutic opportunities for complex diseases, including neurodegeneration.Graphical AbstractHighlightsDISCO-MS combines tissue clearing, whole-organ imaging, deep learning-based image analysis, and ultra-high sensitivity mass spectrometryDISCO-MS yielded qualitative and quantitative proteomics data indistinguishable from fresh tissuesDISCO-MS enables identification of rare pathological regions & their subsequent molecular analysisDISCO-MS revealed core proteome of plaques in 6 weeks old Alzheimer‘s disease mouse model Supplementary Video can be seen at: http://discotechnologies.org/DISCO-MS/
Fast and robust imputation for miRNA expression data using constrained least squares
Authors: Webber James W. , Elias Kevin M. 
Published: November 2021

AbstractHigh dimensional transcriptome profiling, whether through next generation sequencing techniques or high-throughput arrays, may result in scattered variables with missing data. Data imputation is a common strategy to maximize the inclusion of samples by using statistical techniques to fill in missing values. However, many data imputation methods are cumbersome and risk introduction of systematic bias. Here we present a new data imputation method using constrained least squares and algorithms from the inverse problems literature and present applications for this technique in miRNA expression analysis. The proposed technique is shown to offer an imputation orders of magnitude faster, with greater than or equal accuracy when compared to similar methods from the literature.