bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study identifies new loci associated with risk of HBV infection and disease progression
Authors:   the HBVstudy consortium, Zeng Zheng , Liu Hankui , Xu Huifang , Lu Haiying , Yu Yanyan , Xu Xiaoyuan , Yu Min , Zhang Tao , Tian Xiulan , Xi Hongli , Guan Liping , Zhang Jianguo , O’Brien Stephen J. 
Published: March 2021

Abstract
Background
Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes.

Methods
Collected samples from different outcomes of HBV infection and performed genotyping by Affymetrix 500 k SNP Array. GCTA tool, PLINK, and Bonferroni method were applied for analysis of genotyping and disease progression. ANOVA was used to evaluate the significance of the association between biomarkers and genotypes in healthy controls. PoMo, FST, Vcftools and Rehh package were used for building the racial tree and population analysis. FST statistics accesses 0.15 was used as a threshold to detect the signature of selection.

Results
There are 1031 participants passed quality control from 1104 participants, including 275 HBV clearance, 92 asymptomatic persistence infection (ASPI), 93 chronic hepatitis B (CHB), 188 HBV-related decompensated cirrhosis (DC), 214 HBV-related hepatocellular carcinoma (HCC) and 169 healthy controls (HC). In the case–control study, one novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57 × 10−6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62 × 10−6; SNP: rs4661093, Gene: ETV3, P = 2.26 × 10−6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85 × 10−6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Underlying the evolutionary study of HBV-related genes in public database, the derived allele of two HBV clearance related loci, rs3077 and rs9277542, are under strong selection in European population.

Conclusions
In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression.
Factors supporting retention of health and wellbeing staff in Aboriginal health services: a strength-based case study
Authors: Deroy Sara , Schütze Heike 
Published: March 2021

Abstract
Background
Aboriginal Community Controlled Health Services are fundamental to improving the health and welfare of Aboriginal peoples. A key element that contributes to the effectiveness of these services are Aboriginal health and wellbeing staff. However, Aboriginal health and wellbeing staff often suffer high rates of stress and burnout. Current literature focuses on proposed strategies to increase staff retention in Aboriginal Health Services, yet, there is limited information available showcasing what has actually worked.

Method
This was an intrinsic strengths-based case study of one regional Aboriginal Community Controlled Health Service. Semi-structured research yarning interviews were conducted with past and present staff employed in health and wellbeing roles to highlight the factors that staff felt contributed to their retention.

Results
Ten interviews were conducted between February and April 2018. Six key themes emerged: social accountability, teamwork and collaboration, cultural safety, supervision, professional advancement, and recognition. We add to the literature by identifying the importance of bi-directional communication, and showing that social accountability, teamwork and collaboration, cultural safety, supervision, professional advancement, and recognition continue to be important factors that contribute to health and wellbeing staff retention in Aboriginal Health Services.

Conclusion
This exemplar Aboriginal Health Service may provide insights into future strategies to improve staff retention in other health services.
Systematic review of the correlates of outdoor play and time among children aged 3-12 years
Authors: Lee Eun-Young , Bains Ajaypal , Hunter Stephen , Ament Alyssa , Brazo-Sayavera Javier , Carson Valerie , Hakimi Shawn , Huang Wendy Y. , Janssen Ian , Lee Mikyung , Lim Heejun , Silva Diego Augusto Santos , Tremblay Mark S. 
Published: March 2021

Abstract
Background
Due to the myriad of benefits of children’s outdoor play and time, there is increasing concern over its decline. This systematic review synthesized evidence on the correlates of outdoor play and outdoor time among children aged 3-12 years.

Methods
A total of 12 electronic databases in five different languages (Chinese, English, Korean, Spanish, Portuguese) were searched between October 28, 2019 and July 27, 2020. Covidence software was used for screening and Microsoft Excel with a predesigned coding form was used for data extraction. Evidence was synthesized and correlates were categorized using the socioecological model framework.

Results
Based on 107 studies representing 188,498 participants and 422 childcare centers from 29 countries, 85 studies examined potential correlates of outdoor play while 23 studies examined that of outdoor time (one examined both). The duration of outdoor play and outdoor time ranged between 60 and 165 min/d and 42-240 min/d, respectively. Out of 287 (outdoor play) and 61 (outdoor time) potential correlates examined, 111 correlates for outdoor play and 33 correlates for outdoor time were identified as significant correlates. Thirty-three variables were identified as key/common correlates of outdoor play/time, including eight correlates at the individual level (e.g., sex/gender, race/ethnicity, physical activity), 10 correlates at the parental level (e.g., parental attitude/support/behavior, parenting practice), nine at the microsystem level (e.g., proximal home/social environment such as residence type, peer influence), three at the macrosystem/community level (e.g., availability of space children can play), and three at the physical ecology/pressure for macrosystem change level (e.g., seasonality, rurality). No key correlates were found at the institutional level.

Conclusions
Individual, parental, and proximal physical (home) and social environments appear to play a role in children’s outdoor play and time. Ecological factors (i.e., seasonality, rurality) also appear to be related to outdoor play/time. Evidence was either inconsistent or lacking at institutional and macrosystem/community levels. Standardizing terminology and measures of outdoor play/time is warranted. Future work should investigate the interactions and processes of multiple variables across different levels of socioecological modelling to better understand the mechanisms through which outdoor play/time opportunities can be optimized for children while paying special attention to varying conditions in which children are born, live, and play.
Stable, simultaneous and proportional 4-DoF prosthetic hand control via synergy-inspired linear interpolation: a case series
Authors: Lukyanenko Platon , Dewald Hendrik Adriaan , Lambrecht Joris , Kirsch Robert F. , Tyler Dustin J. , Williams Matthew R. 
Published: March 2021

Abstract
Background
Current commercial prosthetic hand controllers limit patients’ ability to fully engage high Degree-of-Freedom (DoF) prosthetic hands. Available feedforward controllers rely on large training data sets for controller setup and a need for recalibration upon prosthesis donning. Recently, an intuitive, proportional, simultaneous, regression-based 3-DoF controller remained stable for several months without retraining by combining chronically implanted electromyography (ciEMG) electrodes with a K-Nearest-Neighbor (KNN) mapping technique. The training dataset requirements for simultaneous KNN controllers increase exponentially with DoF, limiting the realistic development of KNN controllers in more than three DoF. We hypothesize that a controller combining linear interpolation, the muscle synergy framework, and a sufficient number of ciEMG channels (at least two per DoF), can allow stable, high-DoF control.

Methods
Two trans-radial amputee subjects, S6 and S8, were implanted with percutaneously interfaced bipolar intramuscular electrodes. At the time of the study, S6 and S8 had 6 and 8 bipolar EMG electrodes, respectively. A Virtual Reality (VR) system guided users through single and paired training movements in one 3-DoF and four different 4-DoF cases. A linear model of user activity was built by partitioning EMG feature space into regions bounded by vectors of steady state movement EMG patterns. The controller evaluated online EMG signals by linearly interpolating the movement class labels for surrounding trained EMG movements. This yields a simultaneous, continuous, intuitive, and proportional controller. Controllers were evaluated in 3-DoF and 4-DoF through a target-matching task in which subjects controlled a virtual hand to match 80 targets spanning the available movement space. Match Percentage, Time-To-Target, and Path Efficiency were evaluated over a 10-month period based on subject availability.

Results and conclusions
In 3-DoF, S6 and S8 matched most targets and demonstrated stable control after 8 and 10 months, respectively. In 4-DoF, both subjects initially found two of four 4-DoF controllers usable, matching most targets. S8 4-DoF controllers were stable, and showed improving trends over 7–9 months without retraining or at-home practice. S6 4-DoF controllers were unstable after 7 months without retraining. These results indicate that the performance of the controller proposed in this study may remain stable, or even improve, provided initial viability and a sufficient number of EMG channels. Overall, this study demonstrates a controller capable of stable, simultaneous, proportional, intuitive, and continuous control in 3-DoF for up to ten months and in 4-DoF for up to nine months without retraining or at-home use with minimal training times.
In vitro evaluation of cerebrospinal fluid velocity measurement in type I Chiari malformation: repeatability, reproducibility, and agreement using 2D phase contrast and 4D flow MRI
Authors: Williams Gwendolyn , Thyagaraj Suraj , Fu Audrey , Oshinski John , Giese Daniel , Bunck Alexander C. , Fornari Eleonora , Santini Francesco , Luciano Mark , Loth Francis , Martin Bryn A. 
Published: March 2021

Abstract
Background
Phase contrast magnetic resonance imaging, PC MRI, is a valuable tool allowing for non-invasive quantification of CSF dynamics, but has lacked adoption in clinical practice for Chiari malformation diagnostics. To improve these diagnostic practices, a better understanding of PC MRI based measurement agreement, repeatability, and reproducibility of CSF dynamics is needed.

Methods
An anatomically realistic in vitro subject specific model of a Chiari malformation patient was scanned three times at five different scanning centers using 2D PC MRI and 4D Flow techniques to quantify intra-scanner repeatability, inter-scanner reproducibility, and agreement between imaging modalities. Peak systolic CSF velocities were measured at nine axial planes using 2D PC MRI, which were then compared to 4D Flow peak systolic velocity measurements extracted at those exact axial positions along the model.

Results
Comparison of measurement results showed good overall agreement of CSF velocity detection between 2D PC MRI and 4D Flow (p = 0.86), fair intra-scanner repeatability (confidence intervals ± 1.5 cm/s), and poor inter-scanner reproducibility. On average, 4D Flow measurements had a larger variability than 2D PC MRI measurements (standard deviations 1.83 and 1.04 cm/s, respectively).

Conclusion
Agreement, repeatability, and reproducibility of 2D PC MRI and 4D Flow detection of peak CSF velocities was quantified using a patient-specific in vitro model of Chiari malformation. In combination, the greatest factor leading to measurement inconsistency was determined to be a lack of reproducibility between different MRI centers. Overall, these findings may help lead to better understanding for application of 2D PC MRI and 4D Flow techniques as diagnostic tools for CSF dynamics quantification in Chiari malformation and related diseases.
Astrocyte-specific hypoxia-inducible factor 1 (HIF-1) does not disrupt the endothelial barrier during hypoxia in vitro
Authors: Baumann Julia , Tsao Chih-Chieh , Huang Sheng-Fu , Gassmann Max , Ogunshola Omolara O. 
Published: March 2021

AbstractBackgroundAstrocytes (AC) are essential for brain homeostasis. Much data suggests that AC support and protect the vascular endothelium, but increasing evidence indicates that during injury conditions they may lose their supportive role resulting in endothelial cell activation and BBB disturbance. Understanding the triggers that flip this switch would provide invaluable information for designing new targets to modulate the brain vascular compartment. Hypoxia-inducible factor-1 (HIF-1) has long been assumed to be a culprit for barrier dysfunction as a number of its target genes are potent angiogenic factors. Indeed AC themselves, reservoirs of an array of different growth factors and molecules, are frequently assumed to be the source of such molecules although direct supporting evidence is yet to be published. Being well known reservoirs of HIF-1 dependent angiogenic molecules, we asked if AC HIF-1 dependent paracrine signaling drives brain EC disturbance during hypoxia.MethodsFirst we collected conditioned media from control and siRNA-mediated HIF-1 knockdown primary rat AC that had been exposed to normoxic or hypoxic conditions. The conditioned media was then used to culture normoxic and hypoxic (1% O2) rat brain microvascular EC (RBE4) for 6 and 24 h. Various activation parameters including migration, proliferation and cell cycling were assessed and compared to untreated controls. In addition, tight junction localization and barrier stability per se (via permeability assay) was evaluated.ResultsAC conditioned media maintained both normoxic and hypoxic EC in a quiescent state by suppressing EC metabolic activity and proliferation. By FACs we observed reduced cell cycling with an increased number of cells in G0 phase and reduced cell numbers in M phase compared to controls. EC migration was also blocked by AC conditioned media and in correlation hypoxic tight junction organization and barrier functionality was improved. Surprisingly however, AC HIF-1 deletion did not impact EC responses or barrier stability during hypoxia.ConclusionsThis study demonstrates that AC HIF-1 dependent paracrine signaling does not contribute to AC modulation of EC barrier function under normoxic or hypoxic conditions. Thus other cell types likely mediate EC permeability in stress scenarios. Our data does however highlight the continuous protective effect of AC on the barrier endothelium. Exploring these protective mechanisms in more detail will provide essential insight into ways to prevent barrier disturbance during injury and disease.
Comparison of the prognosis of four different treatment strategies for acute left malignant colonic obstruction: a systematic review and network meta-analysis
Authors: Tan Ling , Liu Zi-lin , Ran Meng-ni , Tang Ling-han , Pu Yan-jun , Liu Yi-lei , Ma Zhou , He Zhou , Xiao Jiang-wei 
Published: March 2021

Abstract
Background
There is controversy regarding the efficacy of different treatment strategies for acute left malignant colonic obstruction. This study investigated the 5-year overall survival (OS) and disease-free survival (DFS) of several treatment strategies for acute left malignant colonic obstruction.

Methods
We searched for articles published in PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and Cochrane Library between January 1, 2000, and July 1, 2020. We screened out the literature comparing different treatment strategies. Evaluate the primary and secondary outcomes of different treatment strategies. The network meta-analysis summarizes the hazard ratio, odds ratio, mean difference, and its 95% confidence interval.

Results
The network meta-analysis involved 48 articles, including 8 (randomized controlled trials) RCTs and 40 non-RCTs. Primary outcomes: the 5-year overall survival (OS) and disease-free survival (DFS) of the CS-BTS strategy and the DS-BTS strategy were significantly better than those of the ES strategy, and the 5-year OS of the DS-BTS strategy was significantly better than that of CS-BTS. The long-term survival of TCT-BTS was not significantly different from those of CS-BTS and ES. Secondary outcomes: compared with emergency resection (ER) strategies, colonic stent-bridge to surgery (CS-BTS) and transanal colorectal tube-bridge to surgery (TCT-BTS) strategies can significantly increase the primary anastomosis rate, CS-BTS and decompressing stoma-bridge to surgery (DS-BTS) strategies can significantly reduce mortality, and CS-BTS strategies can significantly reduce the permanent stoma rate. The hospital stay of DS-BTS is significantly longer than that of other strategies. There was no significant difference in the anastomotic leakage levels of several treatment strategies.

Conclusion
Comprehensive literature research, we find that CS-BTS and DS-BTS strategies can bring better 5-year OS and DFS than ER. DS-BTS strategies have a better 5-year OS than CS-BTS strategies. Without considering the hospital stays, DS-BTS strategy is the best choice.
Prediction of functional loss in emergency surgery is possible with a simple frailty screening tool
Authors: Zattoni Davide , Montroni Isacco , Saur Nicole Marie , Garutti Anna , Bacchi Reggiani Maria Letizia , Ghignone Federico , Taffurelli Giovanni , Ugolini Giampaolo 
Published: March 2021

Abstract
Background
Senior adults fear postoperative loss of independence the most, and this might represent an additional burden for families and society. The number of geriatric patients admitted to the emergency room requiring an urgent surgical treatment is rising, and the presence of frailty is the main risk factor for postoperative morbidity and functional decline. Frailty assessment in the busy emergency setting is challenging. The aim of this study is to verify the effectiveness of a very simple five-item frailty screening tool, the Flemish version of the Triage Risk Screening Tool (fTRST), in predicting functional loss after emergency surgery among senior adults who were found to be independent before surgery.

Methods
All consecutive individuals aged 70 years and older who were independent (activity of daily living (ADL) score ≥5) and were admitted to the emergency surgery unit with an urgent need for abdominal surgery between December 2015 and May 2016 were prospectively included in the study. On admission, individuals were screened using the fTRST and additional metrics such as the age-adjusted Charlson Comorbidity Index (CACI) and the ASA score. Thirty- and 90-day complications and postoperative decline in the ADL score where recorded. Regression analysis was performed to identify preoperative predictors of functional loss.

Results
Seventy-eight patients entered the study. Thirty-day mortality rate was 12.8% (10/78), and the 90-day overall mortality was 15.4% (12/78). One in every four patients (17/68) experienced a significant functional loss at 30-day follow-up. At 90-day follow-up, only 3/17 patients recovered, 2 patients died, and 12 remained permanently dependent. On the regression analysis, a statistically significant correlation with functional loss was found for fTRST, CACI, and age≥85 years old both at 30 and 90 days after surgery. fTRST≥2 showed the highest effectiveness in predicting functional loss at 90 days with AUC 72 and OR 6.93 (95% CI 1.71–28.05). The institutionalization rate with the need to discharge patients to a healthcare facility was 7.6% (5/66); all of them had a fTRST≥2.

Conclusion
fTRST is an easy and effective tool to predict the risk of a postoperative functional decline and nursing home admission in the emergency setting.
Real-time ultrasound for tip location of umbilical venous catheter in neonates: a pre/post intervention study
Authors: Rubortone Serena Antonia , Costa Simonetta , Perri Alessandro , D’Andrea Vito , Vento Giovanni , Barone Giovanni 
Published: March 2021

Abstract
Background
Recent guidelines advocate the use of real-time ultrasound to locate umbilical venous catheter tip. So far, training programs are not well established.

Methods
A pre/post interventional study was carried out in our tertiary neonatal intensive care unit centre to evaluate the efficacy of a training protocol in the use of real-time ultrasound. Primary outcome was the percentage in the use of real-time ultrasound.

Results
Fifty-four patients were enrolled. The use of real-time ultrasound for tip location significantly increased after the training program (15.3% vs 89.2%, p <  0.0001). After the training the tip of the catheters was more frequently placed at the junction of the inferior vena cava and right atrium (75% vs 30.7%, p = 0.0023). Twenty-two catheters were also evaluated with serial scans during the intervention phase to assess migration rate which was 50%.

Conclusion
a multimodal, targeted training on the use of real-time ultrasound for umbilical venous catheter placement is feasible. Real-time ultrasound is easily teachable, increases the number of umbilical venous catheters placed in a correct position, reduces the number of line manipulations and the need of chest-x-rays.
Galectin-3 in septic acute kidney injury: a translational study
Authors: Sun Haibing , Jiang Huiping , Eliaz Amity , Kellum John A. , Peng Zhiyong , Eliaz Isaac 
Published: March 2021

Abstract
Background
Galectin-3 (Gal-3) is a pleiotropic glycan-binding protein shown to be involved in sepsis and acute kidney injury (AKI). However, its role has never been elucidated in sepsis-associated AKI (S-AKI). We aimed to explore Gal-3’s role and its potential utility as a therapeutic target in S-AKI.

Methods
In 57 patients admitted to the intensive care unit (ICU) with sepsis, serum Gal-3 was examined as a predictor of ICU mortality and development of AKI. In a rat model of S-AKI induced by cecal ligation and puncture (CLP), 7-day mortality and serum Gal-3, Interleukin-6 (IL-6), and creatinine were examined at 2, 8, and 24 hours (h) post-CLP. Two experimental groups received the Gal-3 inhibitor modified citrus pectin (P-MCP) at 400 mg/kg/day and 1200 mg/kg/day, while the control group received water only (n = 18 in each group).

Results
Among 57 patients, 27 developed AKI and 8 died in the ICU. Serum Gal-3 was an independent predictor of AKI (OR = 1.2 [95% CI 1.1–1.4], p = 0.01) and ICU mortality (OR = 1.4 [95% CI 1.1–2.2], p = 0.04) before and after controlling for age, AKI, and acute physiology and chronic health evaluation (APACHE II) score. In the CLP rat experiment, serum Gal-3 peaked earlier than IL-6. Serum Gal-3 was significantly lower in both P-MCP groups compared to control at 2 h post-CLP (400 mg: p = 0.003; 1200 mg: p = 0.002), and IL-6 was significantly lower in both P-MCP groups at all time points with a maximum difference at 24 h post-CLP (400 mg: p = 0.015; 1200 mg: p = 0.02). In the Gal-3 inhibitor groups, 7-day mortality was significantly reduced from 61% in the control group to 28% (400 mg P-MCP: p = 0.03) and 22% (1200 mg P-MCP: p = 0.001). Rates of AKI per RIFLE criteria were significantly reduced from 89% in the control group to 44% in both P-MCP groups (400 mg: p = 0.007; 1200 mg: p = 0.007).

Conclusions
This translational study demonstrates the importance of Gal-3 in the pathogenesis of S-AKI, and its potential utility as a therapeutic target.

Graphic abstract