bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the performance of GIS methodologies for quantifying spatial accessibility to healthcare in Multi-Island Micro States (MIMS)
Authors: Brizan-St. Martin Roxanne , Paul Juel 
Published: January 2022

Abstract
There has been limited information on spatial accessibility to healthcare in Multi-island Micro States (MIMS). This is partly due to the application of methodologies that do not sufficiently consider the dynamic or unique characteristics of MIMS. The objective of the paper is to evaluate the performance of different Geographic Information Systems (GIS) methodologies for quantifying spatial accessibility to public healthcare in Multi-island States (MIMS). Spatial accessibility was measured using three GIS-based methodologies: Temporally Available Two-Step Floating Catchment Area (TA2SFCA) and traditional models [Two-Step Floating Catchment Area (2SFCA) and the Gravity Model]. Unlike the Gravity Model and the 2SFCA which only used population and health facilities locations along with travel times to quantify spatial accessibility, the TA2SFCA also included information on the hours of operations and health schedules in its assessment. These additional variables were used to develop the time windows to assess differences in capacity among available service sites. TA2SFCA results showed that spatial accessibility was linked to a ‘traveling doctor’ dynamic with access to healthcare services reflecting changes in the supply of services. As such, the Gravity Model and 2SFCA which did not account for this peculiarity were inadequate for measuring spatial accessibility in MIMS. The TA2SFCA addressed both the temporal and spatial aspects of health which were most reflective of the health system of these islands. Given the spatial-temporal dynamics, improving accessibility to healthcare requires periodic assessments and reassessments of health service delivery since this is affected by operating times and changes in capacity. Furthermore, there is the need for more research to develop methodologies that are more reflective or sensitive to MIMS dynamics.
Making health public: a philosophy café in a disadvantaged neighbourhood
Authors: Raap Sanne , Knibbe Mare , Horstman Klasien 
Published: January 2022

Summary
Community Based Participatory Research (CBPR) provides important insights in how to mobilize a community for health promotion. This article explores the possibilities for shifting the frame from community to publics for building new forms of public health engagement in disadvantaged neighbourhoods. We present the results of an ethnographic research project on health and resilience in three low-income neighbourhoods in Maastricht, the Netherlands. In the context of a broader University–Citizens collaboration, citizens and researchers organized a monthly philosophy café to discuss subjects related to health and wellbeing. We analyse this in terms of public building and argue that shifting the perspective from community to publics strengthens the emancipatory tradition within CBPR. By creating an open setting, accommodating diversity and disagreements between its participants, the philosophy café constituted a local epistemic public, generating knowledge on health and wellbeing in disadvantaged neighbourhoods.
Loss-of-function and gain-of-function studies refute the hypothesis that tau protein is causally involved in the pathogenesis of Huntington’s disease
Authors: Mees Isaline , Li Shanshan , Beauchamp Leah C , Barnham Kevin J , Dutschmann Mathias , Hannan Anthony J , Renoir Thibault 
Published: January 2022

Abstract
Tubulin-associated unit (Tau) is a microtubule-associated protein, whose abnormal phosphorylation and deposition in the brain characterizes a range of neurodegenerative diseases called tauopathies. Recent clinical (post-mortem) and pre-clinical evidence suggests that Huntington’s disease (HD), an autosomal dominant neurodegenerative disorder, could be considered as a tauopathy. Studies have found the presence of hyperphosphorylated tau, altered tau isoform ratio and aggregated tau in HD brains. However, little is known about the implication of tau in the development of HD pathophysiology, which includes motor, cognitive and affective symptoms. To shine a light on the involvement of tau in HD, our present study aimed at (i) knocking out tau expression and (ii) expressing a transgene encoding mutant human tau in the R6/1 mouse model of HD. We hypothesized that expression of the mutant human tau transgene in HD mice would worsen the HD phenotype, while knocking out endogenous mouse tau in HD mice would improve some behavioral deficits displayed by HD mice. Our data suggest that neither the expression of a tau transgene nor the ablation of tau expression impacted the progression of the HD motor, cognitive and affective phenotypes. Supporting these behavioral findings, we also found that modulating tau expression had no effect on brain weights in HD mice. We also report that expression of the tau transgene increased the weight of WT and HD male mice, whereas tau ablation increased the weight of HD females only. Together, our results indicate that tau might not be as important in regulating the onset and progression of HD symptomatology as previously proposed.
Host, Microbiome, and Complex Space: Applying Population and Landscape Genetic Approaches to Gut Microbiome Research in Wild Populations
Authors: Couch Claire E , Epps Clinton W 
Published: January 2022

Abstract
In recent years, emerging sequencing technologies and computational tools have driven a tidal wave of research on host-associated microbiomes, particularly the gut microbiome. These studies demonstrate numerous connections between the gut microbiome and vital host functions, primarily in humans, model organisms, and domestic animals. As the adaptive importance of the gut microbiome becomes clearer, interest in studying the gut microbiomes of wild populations has increased, in part due to the potential for discovering conservation applications. The study of wildlife gut microbiomes holds many new challenges and opportunities due to the complex genetic, spatial, and environmental structure of wild host populations, and the potential for these factors to interact with the microbiome. The emerging picture of adaptive coevolution in host–microbiome relationships highlights the importance of understanding microbiome variation in the context of host population genetics and landscape heterogeneity across a wide range of host populations. We propose a conceptual framework for understanding wildlife gut microbiomes in relation to landscape variables and host population genetics, including the potential of approaches derived from landscape genetics. We use this framework to review current research, synthesize important trends, highlight implications for conservation, and recommend future directions for research. Specifically, we focus on how spatial structure and environmental variation interact with host population genetics and microbiome variation in natural populations, and what we can learn from how these patterns of covariation differ depending on host ecological and evolutionary traits.
Comparison of surgical outcomes after robot-assisted laparoscopic partial nephrectomy between patients continuing and discontinuing aspirin therapy: a Japanese single-centre study
Authors: Wada Arisa , Omae Kenji , Yoshida Kazuhiko , Kondo Tsunenori , Tanabe Kazunari , Takagi Toshio 
Published: January 2022

Abstract

Purpose
To investigate the feasibility of continuing aspirin therapy in patients with renal tumours undergoing robot-assisted laparoscopic partial nephrectomy.

Methods
This retrospective, single-centre study included 106 patients receiving aspirin therapy who underwent robot-assisted laparoscopic partial nephrectomy. The patients were divided into two groups, including those continuing and discontinuing aspirin therapy, and their surgical outcomes were compared. To minimise potential bias, variables including patient and tumour characteristics were adjusted using 1:1 propensity score matching.

Results
Aspirin therapy was used for ischaemic heart disease in 38 patients (36%), cerebrovascular disease in 21 (20%) and others in 47 (44%). Of the 106 patients, 49 were classified to the continuing group and 57 to the discontinuing group. After matching, 24 patients were included in each group. The surgical outcomes, such as changes in the estimated glomerular filtration rate, estimated blood loss, and surgical margin positivity rate, were not significantly different between the groups. In addition, no significant difference was observed in haemoglobin level changes during surgery (continuing: −2.3 g/dl; discontinuing: −1.7 g/dl, P = 0.0676) and haemorrhagic complications (continuing: 8%; discontinuing: 4%, P = 0.500). Multivariate analysis of predictors for haemoglobin level decrease &gt;2 g/dl or haemorrhagic complications showed that, whereas tumour complexity was an independent predictor, continuation or discontinuation of aspirin therapy was not.

Conclusion
The surgical outcomes of robot-assisted laparoscopic partial nephrectomy between patients continuing and discontinuing aspirin therapy were not significantly different, thus suggesting the feasibility of continuing aspirin therapy in selected Japanese patients.
Detection of low-frequency breaks in power density spectrum of GX 339−4 in faint low/hard state observations using AstroSat data
Authors: Husain Nazma , Misra Ranjeev , Sen Somasri 
Published: January 2022

ABSTRACT
We present the spectro-timing analysis of the black hole binary system GX 339−4 using AstroSat data extracted at the beginning of outbursts in 2017 and 2019. The joint spectral fitting of Large Area X-ray Proportional Counter (LAXPC) and Soft X-ray Telescope (SXT) data revealed that the source was in a faint low/hard state for both 2017 and 2019 observations, with nearly equal photon indexes of ∼1.57 and ∼1.58 and Eddington ratios, L/LEdd, of 0.0011 and 0.0046, respectively. The addition of a reflection component into the spectral modelling improved the fit (Δχ2 ≈ 6 for 2017 and Δχ2 ≈ 7 for 2019), pointing towards the presence of weak reflection features arising due to irradiation of the accretion disc. The power density spectrum consisted of strong band-limited noise with a break at low frequencies, described by a combination of a few zero-centred Lorentzians. The fitting revealed a low-frequency break at ∼6 mHz for 2017 and ∼11 mHz for 2019 observations, whose detection is validated by results from independent detectors (LAXPCs and SXT). The break frequency is roughly consistent with results obtained from earlier observations that showed an evolution of the frequency with flux, which is in accordance with the truncated disc model. Associating the break frequency with the viscous time-scale of the accretion disc, we estimated a truncation radius of ∼93 and ∼61 gravitational radius for 2017 and 2019 observations, respectively.
Nuclear and cytoplasmic RNA exosomes and PELOTA1 prevent miRNA-induced secondary siRNA production in Arabidopsis
Authors: Vigh Maria L , Bressendorff Simon , Thieffry Axel , Arribas-Hernández Laura , Brodersen Peter 
Published: January 2022

Abstract
Amplification of short interfering RNA (siRNAs) via RNA-dependent RNA polymerases (RdRPs) is of fundamental importance in RNA silencing. Plant microRNA (miRNA) action generally does not involve engagement of RdRPs, in part thanks to a poorly understood activity of the cytoplasmic exosome adaptor SKI2. Here, we show that inactivation of the exosome subunit RRP45B and SKI2 results in similar patterns of miRNA-induced siRNA production. Furthermore, loss of the nuclear exosome adaptor HEN2 leads to secondary siRNA production from miRNA targets largely distinct from those producing siRNAs in ski2. Importantly, mutation of the Release Factor paralogue PELOTA1 required for subunit dissociation of stalled ribosomes causes siRNA production from miRNA targets overlapping with, but distinct from, those affected in ski2 and rrp45b mutants. We also show that in exosome mutants, miRNA targets can be sorted into producers and non-producers of illicit secondary siRNAs based on trigger miRNA levels and miRNA:target affinity rather than on presence of 5′-cleavage fragments. We propose that stalled RNA-Induced Silencing Complex (RISC) and ribosomes, but not mRNA cleavage fragments released from RISC, trigger siRNA production, and that the exosome limits siRNA amplification by reducing RISC dwell time on miRNA target mRNAs while PELOTA1 does so by reducing ribosome stalling.
Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control
Authors: Hormazabal Juan , Saavedra Francisco , Espinoza-Arratia Claudia , Martinez Nicolas W , Cruces Tatiana , Alfaro Iván E , Loyola Alejandra 
Published: January 2022

Abstract
Although there are several pathways to ensure that proteins are folded properly in the cell, little is known about the molecular mechanisms regulating histone folding and proteostasis. In this work, we identified that chaperone-mediated autophagy (CMA) is the main pathway involved in the degradation of newly synthesized histones H3 and H4. This degradation is finely regulated by the interplay between HSC70 and tNASP, two histone interacting proteins. tNASP stabilizes histone H3 levels by blocking the direct transport of histone H3 into lysosomes. We further demonstrate that CMA degrades unfolded histone H3. Thus, we reveal that CMA is the main degradation pathway involved in the quality control of histone biogenesis, evidencing an additional mechanism in the intricate network of histone cellular proteostasis.
Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy*
Authors: Wacker David A. , Burton Susan L. , Berger John P. , Hegg A. J. , Heisdorffer Jamie , Wang Qi , Medcraft Emily J. , Reilkoff Ronald A. 
Published: January 2022

OBJECTIVES:
To determine whether IV vitamin C therapy reduces 28-day mortality in patients with septic shock.

DESIGN:
Multicenter, double-blinded, randomized controlled trial.

SETTING:
One academic medical ICU and four community ICUs.

PATIENTS:
Of 167 adult patients within 24 hours of vasopressor initiation for septic shock, 126 consented to participation, and 124 received study drug and were included in analysis.

INTERVENTIONS:
IV vitamin C (10 mg/mL in normal saline) administered as a 1,000-mg bolus over 30 minutes followed by continuous infusion of 250 mg/hr for 96 hours or placebo of equal volumes of normal saline.

MEASUREMENTS AND MAIN RESULTS:
Of 124 subjects receiving study drug and included in analysis, 60 received vitamin C and 64 placebo. The primary outcome of all-cause 28-day mortality (vitamin C, 26.7%; placebo, 40.6%; p = 0.10) was lower in the vitamin C arm but did not reach statistical significance. Initiation of renal replacement therapy was higher in the vitamin C arm (vitamin C, 16.7%; placebo, 3.3%; p = 0.015), as was volume of fluid administration within 6 hours of study drug initiation (vitamin C, 1.07 L; placebo, 0.76 L; p = 0.03). There were no statistically significant differences in other secondary outcomes. In post hoc subgroup analysis, there was a decrease in 28-day mortality in the vitamin C arm among patients requiring positive-pressure ventilation at the time of enrollment (vitamin C, 36.3%; placebo, 60.0%; p = 0.05). This trial is registered at clinicaltrials.gov under identifier NCT03338569.

CONCLUSIONS:
Vitamin C monotherapy failed to significantly reduce mortality in septic shock patients as hypothesized. Our findings do not support its routine clinical use for this purpose.
Blood pressure undulation of peripheral thrombolysis period in acute ischemic stroke is associated with prognosis
Authors: He Mingli , Wang Hongrui , Tang Yi , Wang Jin’e , Cui Bing , Xu Bingchao , Sun Yongan , Zhang Guanghui , He Xiaobing , Niu Xiaoqin , Wang Bei , Xu Bei , Li Zaipo , Zhang Yu , Wang Yibo 
Published: January 2022

Background:
Evidence suggests that patients with higher blood pressure variability (BPV) have a higher risk for stroke but the relationship between BPV and stroke outcomes is unknown in those who underwent intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). The objective of this study is to investigate the association among BPV, BP values and stroke outcomes.

Methods:
A retrospective analysis of about 510 consecutive thrombolysis cases for AIS from January 2015 to March 2019 in a single-center database were done. Then, these patients were followed-up for 3 months. We used univariate and multivariable models to evaluate the relationship between mean BP values, BPV and the risk of stroke outcomes from prior IVT to 72 h after IVT. Meanwhile, we also used COX regression to assess the hazard ratios of stroke outcomes with BPV within 3 months. Furthermore, we tested the effect of BP level at various time-points (prior to IVT and at 0, 2, 4, 8, 12, 24, 48 and 72 h after IVT) on development of postthrombolytic stroke outcomes.

Results:
Higher BPV from prior IVT to 72 h after IVT was associated with higher risk of stroke outcomes within 3 months [SBPV of recurrent stroke: odds ratios (OR) = 5.298, 95% confidence interval (CI) 1.339–10.968, P = 0.018; DBPV of recurrent stroke: OR = 6.397, 95% CI 1.576–25.958, P = 0.009, respectively]. In addition, patients with recurrent stroke had significantly higher mean SBP (OR=1.037, 95% CI 1.006–1.069, P = 0.019). Furthermore, higher BP at different time points were associated with greater risk of recurrent stroke from prior IVT to 72 h after IVT.

Conclusion:
Higher BPV and SBP from prior IVT to 72 h after IVT was associated with higher risk of stroke outcomes within 3 months.
Clinical Redesign: An Innovative Approach to Leading Change at an Academic Healthcare System
Authors: Li Luming , Davis Melissa , Kim Nancy , Lipka Susan , Branson Brittany , Amport Stephanie , Schwartz Ian , Sussman Scott 
Published: January 2022

SUMMARY

Goal:
We characterized the core elements of a clinical redesign program (CRDP) to represent both a team and a methodology to rapidly improve outcomes important to patients and hospitals (e.g., length of stay, unnecessary care, and cost). Unique features of our CRDP included a clinician lead, engagement from senior leadership, formal project management, and rapid cycle implementation. We aimed to examine the effectiveness of this strategy across three different project examples.

Methods:
Using an observational pre–post study design, we compared the patient-level data for three representative projects applying the core elements of the CRDP: (1) optimizing telemetry utilization, (2) creating a high flow nasal cannula protocol in the pediatric intensive care unit, and (3) standardizing care for patients with chronic obstructive pulmonary disease and pneumonia.

Principal Findings:
The primary metrics for all three projects were a project-specific clinical outcome and cost per case. Telemetry utilization was reduced from a peak of 26.0% to 19.6% with a $1,075 reduction in cost per case. Creation of a high flow nasal cannula protocol led to a decrease in median pediatric intensive care unit length of stay from 77.3 to 75.8 hours with a $2,020 decrease in cost per case. Decreasing variation of care for patients with chronic obstructive pulmonary disease and pneumonia diagnoses led to a $371 decrease in cost per case.

Applications to Practice:
The CRDP adds to existing clinical quality improvement models using a structured process for a 90-day rapid cycle project turnaround. In addition, the CRDP incorporates project management and defined team members for the completion and sustainability of projects. The CRDP also facilitates the scalable translation of projects from local to systemwide and incorporates tracking of clinical and financial outcomes through interval internal auditing. These elements provide prioritization, resource allocation, and expertise for improved patient care and high-value care delivery. The CRDP can be adapted for other contexts to lead and foster momentum and drive rapid and successful completion of clinical improvement projects.
Point-of-Care Ultrasonography for Ankle Injuries in Children
Authors: Nadler Ariella , Tsung James W. , Rabiner Joni E. 
Published: January 2022

Objectives
The aim of the study was to determine whether point-of-care ultrasound (US) can decrease x-rays in children with ankle injuries. Secondary objectives were to determine the test performance characteristics for ankle US, analyze diagnostic errors, and compare US with the Ottawa Ankle Rules (OAR).

Methods
This was a prospective study of children younger than 21 years presenting to an emergency department with an ankle injury requiring x-rays. Pediatric emergency medicine physicians received a 1-hour training session, performed ankle US with a standardized scanning protocol of the distal tibia and fibula, and described the US as positive, negative, or equivocal for fracture. Ankle x-ray interpretation by a radiologist was the reference standard for fracture.

Results
One hundred twenty patients with a mean age of 13.5 (±4.0) years were enrolled. Nine patients (7.5%) had an ankle fracture on x-ray, and 56 patients (47%) had open physes. Ankle US would reduce x-rays by 81 (67.5%), missing 2 intra-articular, nondisplaced, tibial fractures in patients with open physes. Ankle US had a sensitivity of 78% (95% confidence interval [CI], 40%–97%), specificity of 71% (95% CI, 62%–79%), likelihood ratio for a positive test of 2.7 (95% CI, 1.7–4.3), and likelihood ratio for a negative test of 0.31 (95% CI, 0.09–1.07). The OAR would reduce x-rays by 21 (17.5%), missing one fracture. Ultrasound with OAR would reduce x-rays by 20 (17%) with no missed fractures.

Conclusions
Point-of-care US has the potential to reduce x-rays for children with ankle injuries; however, nondisplaced, intra-articular tibial fractures may be missed. Ultrasound with OAR may reduce radiographs without missed fractures in this population.
Phosphoantigens are Molecular Glues that Promote Butyrophilin 3A1/2A1 Association Leading to Vγ9Vδ2 T Cell Activation
Authors: Yuan Linjie , Ma Xianqiang , Yang Yunyun , Li Xin , Ma Weiwei , Yang Haoyu , Huang Jian-Wen , Xue Jing , Yi Simin , Zhang Mengting , Cai Ningning , Ding Qingyang , Li Liping , Duan Jianxin , Malwal Satish , Chen Chun-Chi , Oldfield Eric , Guo Rey-Ting , Zhang Yonghui 
Published: January 2022

AbstractTumor cells and pathogen-infected cells are presented to human γδ T cells based on “inside-out” signaling in which metabolites called phosphoantigens (pAgs) inside target cells are recognized by the intracellular domain of a butyrophilin protein (BTN3A1), leading to an extracellular conformational change. Here, we report that pAgs function as molecular “glues” that initiate a heteromeric association between the intracellular domains of BTN3A1 and the structurally similar BTN2A1. Working with both exogenous and endogenous pAgs, we used x-ray crystallography, mutational studies, cellular assays, synthetic probe as well as molecular dynamics investigations to determine how pAgs glue intracellular BTN3A1 and BTN2A1 together for the “inside-out” signaling that triggers γδ T cell activation. This γδ T cell-specific mode of antigen sensing creates opportunities for the development of alternative immunotherapies against cancer and infectious diseases that do not involve αβ T cells.One Sentence SummaryThe responses of gamma-delta T cells to cancer cells or pathogens are initiated via the intracellular association of heteromeric butyrophilins that are glued together by isoprenoid metabolites.