bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to prioritise in quality improvement? Targeted implementation as a key for quality improvement in Kenyan health facilities
Authors: Nitschke Christine , Nafula Maureen , Brodowski Marc , Marx Irmgard , Kandie Charles , Omogi Irene , Paul-Fariborz Friederike , Szecsenyi Joachim , Brugnara Lucia , Marx Michael 
Published: November 2020

BackgroundData from national surveys of low- and middle income countries indicates that there is still a need to improve the quality of healthcare in resource-poor settings. This study aims to understand the benefit of an integral, facility-driven, indicator-based approach used as a decision-making tool to define effective quality improvement interventions in Kenya.ObjectiveThe aim of the study is to understand whether the integral approach developed leads to effective interventions.MethodsCategorical data is collected from ten health facilities covered by the Integrated Quality Management System (IQMS) project in Kenya. First the information on concrete improvement interventions implemented within the facilities is collected and merged into five different intervention topics. Second, groups of facilities with similar quality improvement interventions are selected to compare between the first and second quality assessment rounds. Those IQMS indicators matching the content of the intervention topic are extracted from the software VISOTOOL. In a third step, the data is summarised using means and SD. A one sample T-test is applied on the mean changes and SD. Frequency counts and percentages were used for the presentation of categorical data.ResultsAll improvement interventions resulted in positive and higher change values (T2-T1). Four of five intervention topics, show statistically significant improvements including neonatal mortality (42%; p<0.0001), waiting time (39%; p=0.0490), infection prevention control (28%; p=0.0007) and with shortages of staffing and transport in remote areas (32%; p=0.0194).ConclusionsIn all facilities the interventions selected have a positive impact, some of which markedly improved. It demonstrates that this integral quality improvement approach in Kenya can serve as an effective decision-making tool for identification and prioritisation of interventions. Those targeted interventions, being performed under institutionalisation in form of coaching and tutoring, effectively contribute to improving the quality of care in resource poor settings.
Neutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis
Authors: Takeuchi Masahiro , Vidigal Paula T , Guerra Mateus T , Hundt Melanie A , Robert Marie E , Olave-Martinez Maria , Aoki Satoshi , Khamphaya Tanaporn , Kersten Remco , Kruglov Emma , de la Rosa Rodriguez Randolph , Banales Jesus M , Nathanson Michael H , Weerachayaphorn Jittima 
Published: November 2020

Background & objectivesAlcoholic hepatitis (AH) is a common but life-threatening disease with limited treatment options. It is thought to result from hepatocellular damage, but the presence of cholestasis worsens prognosis, so we examined whether bile ducts participate in the pathogenesis of this disease.DesignCholangiocytes derived from human bile ducts were co-cultured with neutrophils from patients with AH or controls. Loss of type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), an apical intracellular calcium channel necessary for cholangiocyte secretion, was used to reflect cholestatic changes. Neutrophils in contact with bile ducts were quantified in liver biopsies from patients with AH and controls and correlated with clinical and pathological findings.ResultsLiver biopsies from patients with AH revealed neutrophils in contact with bile ducts, which correlated with biochemical and histological parameters of cholestasis. Cholangiocytes co-cultured with neutrophils lost ITPR3, and neutrophils from patients with AH were more potent than control neutrophils. Biochemical and histological findings were recapitulated in an AH animal model. Loss of ITPR3 was attenuated by neutrophils in which surface membrane proteins were removed. RNA-seq analysis implicated integrin β1 (ITGB1) in neutrophil-cholangiocyte interactions and interference with ITGB1 on cholangiocytes blocked the ability of neutrophils to reduce cholangiocyte ITPR3 expression. Cell adhesion molecules on neutrophils interacted with ITGB1 to trigger RAC1-induced JNK activation, causing a c-Jun-mediated decrease in ITPR3 in cholangiocytes.ConclusionsNeutrophils bind to ITGB1 on cholangiocytes to contribute to cholestasis in AH. This previously unrecognised role for cholangiocytes in this disease alters our understanding of its pathogenesis and identifies new therapeutic targets.
Eftilagimod alpha, a soluble lymphocyte activation gene-3 (LAG-3) protein plus pembrolizumab in patients with metastatic melanoma
Authors: Atkinson Victoria , Khattak Adnan , Haydon Andrew , Eastgate Melissa , Roy Amitesh , Prithviraj Prashanth , Mueller Christian , Brignone Chrystelle , Triebel Frederic 
Published: November 2020

BackgroundTo evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, in combination with the programmed cell death-1 (PD-1) antagonist pembrolizumab.MethodsThe study was divided into two parts; parts A and B, where part A was the dose escalation part and part B was an extension part of the study. Patients with metastatic melanoma were treated with efti plus the standard dose of pembrolizumab. Blood samples were assayed to determine plasma pharmacokinetic parameters, detect efti antibody formation and determine long-lived CD8 T cell responses and associated pharmacodynamic parameters.ResultsTwenty-four patients with melanoma received pembrolizumab and bi-weekly subcutaneous (s.c.) injections of efti at doses 1 mg, 6 mg or 30 mg/injection for up to 6 months (part A) or 30 mg/injection for up 12 months (part B). No dose-limiting toxicities were reported and the main adverse event for efti was injection site reactions. Sustained systemic exposure to the product was obtained in all patients following s.c. injections of 30 mg dose. Treatment induced an increase in activated CD8 and CD4 T cell counts, and in some of the soluble biomarkers, particularly interferon (IFN)-γ, a Th1 signature cytokine. An overall response rate (ORR) of 33% was observed in patients partly with pembrolizumab-refractory of part A and ORR of 50% was observed in patients with PD-1 naïve of part B.ConclusionsEfti was well tolerated in combination with pembrolizumab with encouraging antitumor activity. This warrants further clinical studies of this new combination therapy combining an antigen-presenting cell activator with an immune checkpoint inhibitor.
Screening of CNVs using NGS data improves mutation detection yield and decreases costs in genetic testing for hereditary cancer
Authors: Moreno-Cabrera José Marcos , del Valle Jesús , Feliubadaló Lidia , Pineda Marta , González Sara , Campos Olga , Cuesta Raquel , Brunet Joan , Serra Eduard , Capellà Gabriel , Gel Bernat , Lázaro Conxi 
Published: November 2020

IntroductionGermline CNVs are important contributors to hereditary cancer. In genetic diagnostics, multiplex ligation-dependent probe amplification (MLPA) is commonly used to identify them. However, MLPA is time-consuming and expensive if applied to many genes, hence many routine laboratories test only a subset of genes of interest.Methods and resultsWe evaluated a next-generation sequencing (NGS)-based CNV detection tool (DECoN) as first-tier screening to decrease costs and turnaround time and expand CNV analysis to all genes of clinical interest in our diagnostics routine. We used DECoN in a retrospective cohort of 1860 patients where a limited number of genes were previously analysed by MLPA, and in a prospective cohort of 2041 patients, without MLPA analysis. In the retrospective cohort, 6 new CNVs were identified and confirmed by MLPA. In the prospective cohort, 19 CNVs were identified and confirmed by MLPA, 8 of these would have been lost in our previous MLPA-restricted detection strategy. Also, the number of genes tested by MLPA across all samples decreased by 93.0% in the prospective cohort.ConclusionIncluding an in silico germline NGS CNV detection tool improved our genetic diagnostics strategy in hereditary cancer, both increasing the number of CNVs detected and reducing turnaround time and costs.
Risk of chronic opioid use after simultaneous versus staged bilateral knee arthroplasty
Authors: Wilson Lauren , Fiasconaro Megan , Liu Jiabin , Poeran Jashvant , Poultsides Lazaros , Memtsoudis Stavros G 
Published: November 2020

BackgroundSeveral studies have identified excess risk associated with undergoing simultaneous (compared with unilateral or staged) bilateral total knee arthroplasty (BTKA). However, few have addressed subsequent chronic opioid use. Given the substantial morbidity and mortality associated with prolonged opioid use, we evaluated the incidence of postoperative chronic opioid use following simultaneous versus staged BTKA, based on the different timing strategies of staged procedures.MethodsIn this retrospective cohort study, patients who underwent BTKA procedures (2012–2016; Truven Health MarketScan; n=14 407) were classified as having undergone simultaneous or staged BTKA (<3 months, 3–6 months or 6–12 months apart). Outcomes were postoperative chronic opioid use and oral morphine equivalents prescribed on discharge. Multivariable regression models measured associations between type/timing of BTKA and outcomes. ORs and 95% CIs were reported.ResultsUnadjusted frequency of chronic opioid use did not differ between groups, (Simultaneous: 11.3%, staged <3 months: 10.7%, staged 3–6 months: 11.7%, staged >6 months: 10.2%; p=0.247). In an adjusted model, there was no significant difference in the odds of becoming chronic opioid users between staged and simultaneous BTKA (staged <3 months OR 1.03, 95% CI 0.88 to 1.21/staged 3–6 months OR 0.94, 95% CI 0.79 to 1.12/staged >6 months OR 0.96, 95% CI 0.82 to 1.13; p=0.755). Patients undergoing staged BTKAs <6 months apart (compared with simultaneous) were prescribed slightly greater oral morphine equivalents on hospital discharge (staged <3 months 6% increase, 95% CI 3% to 10%; staged 3–6 months 4%, 95% CI 1% to 8%; p=0.002).ConclusionAlthough patients undergoing staged BTKA <6 months apart were prescribed greater quantities of opioids on discharge, there was no significant difference in the odds of postoperative chronic opioid use compared with simultaneous BTKA. The timing of BTKA procedures does not appear to influence the likelihood of postoperative chronic opioid dependence.
Characterisation of the novel clinical isolate X-4 containing a new
tp0548
sequence-type
Authors: Liu Dan , Tong Man-Li , Liu Li-Li , Lin Li-Rong , Zhang Hui-Lin , Yang Tian-Ci 
Published: November 2020

Objectives

A novel
tp0548
sequence-type was identified in one clinical isolate (X-4) from a patient diagnosed with primary syphilis in Xiamen, China. To precisely define and characterise a new clinical isolate, we performed further genome-scale molecular analysis.

Methods
The pooled segment genome sequencing method followed by Illumina sequencing was performed.

Results
This novel sequence-type contained a unique nucleotide substitution ‘T’ at position 167 and belonged to the SS14-like clade of TPA strains, as determined by phylogenetic analysis. Multi-locus sequence analysis of nine chromosomal loci demonstrated that the X-4 isolate was clustered within a monophyletic group of TPA strains. Whole-genome phylogenetic analysis subsequently corroborated the TPA strain classification of the X-4 isolate and revealed that the isolate was closely related to the SS14 strain, with 42 single-nucleotide variations and 12 insertions/deletions. In addition, high intrastrain heterogeneity in the length of the poly G/C tracts was found in the TPAChi_0347 locus, which might indicate that this gene of the X-4 isolate is likely involved in phase variation events. The length heterogeneity of the poly A/T tracts was lower than the genetic variability of the poly G/C tracts, and all the observed intrastrain variations fell within coding regions.

Conclusion

The novel
tp0548
sequence-type was determined to belong to a new TPA isolate, X-4. The identification of variable length in homopolymetic tracts (G/C and A/T) could provide a snapshot of the genes that potentially involved in genotype–phenotype variations. These findings provide an unequivocal characterisation for better understanding the molecular variation of this emerging isolate.
Effects of nutrition supplementation and physical exercise on muscle mass, muscle strength and fat mass among sarcopenic elderly: a randomized controlled trial
Authors: Li Zhuo , Cui Min , Yu Kang , Zhang Xiao-wei , Li Chun-wei , Nie Xiao-dong , Wang Fang 
Published: November 2020

This study aimed to determine the impact of nutrition supplementation (whey protein, fish oil, vitamin D) and physical exercise (resistance and aerobic exercise) on muscle mass, muscle strength and fat mass among sarcopenic elderly. Participants (N = 241) with sarcopenia (aged ≥ 60 y) enrolled from 2 centers were randomized into groups undergoing nutrition supplementation (Nutr), physical exercise (Ex), nutrition combined with exercise (Nutr+Ex), or routine consultation for 12 weeks. Muscle-related indicators, grip strength as well as fat-related indicators were compared pre- and post-intervention. The per-protocol analysis showed that all indicators were significantly different between groups (P < 0.001). Further pairwise comparisons showed that compared with controls, appendicular muscle mass and grip strength were significantly higher in Nutr (P < 0.001, 95% CI: 0.578, 1.475; P < 0.001, 95% CI: 3.614∼9.118), Ex (P = 0.010, 95% CI: 0.157, 1.153; P < 0.001, 95% CI: 2.904, 8.732), and Nutr+Ex (P < 0.001, 95% CI: 0.564, 1.471; P < 0.001, 95% CI: 3.441, 8.907) groups, while fat mass was significantly lower in the Nutr (P < 0.001, 95% CI: −4.676, −2.358) and Nutr+Ex (P < 0.001, 95% CI: −4.717,−1.790) groups. When compared with Ex, fat mass decreased significantly in the Nutr (P = 0.001, 95% CI: −4.856,−1.359) and Nutr+Ex (P = 0.005, 95% CI: −4.810, −0.878) groups. The findings indicate that nutrition supplementation and physical exercise could improve muscle mass, strength and fat mass among sarcopenic elderly. Nutrition supplementation might be better at decreasing fat mass in this population. ClinicalTrials.gov registration no.: NCT02873676. Novelty: Nutrition supplementation improved muscle mass, strength and fat mass among sarcopenic elderly. Aerobic and resistance exercise improved muscle mass and strength in sarcopenic elderly. Combined nutrition supplementation and physical exercise improved muscle mass, strength and fat mass among sarcopenic elderly.
Individualized, Intraoperative Dosing of Fibrinogen Concentrate for the Prevention of Bleeding in Neonatal and Infant Cardiac Surgery Using Cardiopulmonary Bypass (FIBCON)
Authors: Siemens Kristina , Hunt Beverley J. , Harris Julia , Nyman Andrew G. , Parmar Kiran , Tibby Shane M. 
Published: November 2020

Background:Mediastinal bleeding is common following pediatric cardiopulmonary bypass surgery for congenital heart disease. Fibrinogen concentrate (FC) represents a potential therapy for preventing bleeding.Methods:We performed a single-center, phase 1b/2a, randomized controlled trial on infants 2.5 to 12 kg undergoing cardiopulmonary bypass surgery, aimed at (1) demonstrating the feasibility of an intraoperative point-of-care test, rotational thromboelastometry, to screen out patients at low risk of postoperative bleeding and then guide individualized FC dosing in high-risk patients and (2) determining the dose, safety, and efficacy of intraoperative FC supplementation. Screening occurred intraoperatively 1-hour before bypass separation using the rotational thromboelastometry variable fibrinogen thromboelastometry maximum clot firmness (FibTEM-MCF; fibrinogen contribution to clot firmness). If FibTEM-MCF ≥7 mm, patients entered the monitoring cohort. If FibTEM-MCF ≤6 mm, patients were randomized to receive FC/placebo (2:1 ratio). Individualized FC dose calculation included weight, bypass circuit volume, hematocrit, and intraoperative measured and desired FibTEM-MCF. The coprimary outcomes, measured 5 minutes post-FC administration were FibTEM-MCF (desired range, 8–13 mm) and fibrinogen levels (desired range, 1.5–2.5 g/L). Secondary outcomes were thrombosis and thrombosis-related major complications and postoperative 24-hour mediastinal blood loss.Results:We enrolled 111 patients (cohort, n=21; FC, n=60; placebo, n=30); mean (SD) age, 6.4 months (5.8); weight, 5.9 kg (2.0). Intraoperative rotational thromboelastometry screening effectively excluded low-risk patients, in that none in the cohort arm (FibTEM-MCF, ≥7 mm) demonstrated clinically significant early postoperative bleeding (>10 mL/kg per 4 hours). Among randomized patients, the median (range) FC administered dose was 114 mg/kg (51–218). Fibrinogen levels increased from a mean (SD) of 0.91 (0.22) to 1.7 g/L (0.41). The postdose fibrinogen range was 1.2 to 3.3 g/L (72% within the desired range). The corresponding FibTEM-MCF values were as follows: pre-dose, 5.3 mm (1.9); post-dose, 13 mm (3.2). Ten patients (8 FC and 2 placebo) exhibited 12 possible thromboses; none were clearly related to FC. There was an overall difference in mean (SD) 24-hour mediastinal drain loss: cohort, 12.6 mL/kg (6.4); FC, 11.6 mL/kg (5.2); placebo, 17.1 mL/kg (14.3; ANOVAP=0.02).Conclusions:Intraoperative, individualized dosing of FC appears feasible. The need for individualized dosing is supported by the finding that a 4-fold variation in FC dose is required to achieve therapeutic fibrinogen levels.Registration:URL:https://eudract.ema.europa.eu/; Unique identifier: 2013-003532-68. URL:https://www.isrctn.com/; Unique identifier: 50553029.
Behavioral and Neural Correlates of Speech Motor Sequence Learning in Stuttering and Neurotypical Speakers: An fMRI Investigation
Authors: Masapollo Matthew , Segawa Jennifer A. , Beal Deryk S. , Tourville Jason A. , Nieto-Castañón Alfonso , Heyne Matthias , Frankford Saul A. , Guenther Frank H. 
Published: November 2020

AbstractStuttering is a neurodevelopmental disorder characterized by impaired production of coordinated articulatory movements needed for fluent speech. It is currently unknown whether these abnormal production characteristics reflect disruptions to brain mechanisms underlying the acquisition and/or execution of speech motor sequences. To dissociate learning and control processes, we used a motor sequence learning paradigm to examine the behavioral and neural correlates of learning to produce novel phoneme sequences in adults who stutter (AWS) and neurotypical controls. Participants intensively practiced producing pseudowords containing non-native consonant clusters (e.g., “GVAZF”) over two days. The behavioral results indicated that although the two experimental groups showed comparable learning trajectories, AWS performed significantly worse on the task prior to and after speech motor practice. Using functional magnetic resonance imaging (fMRI), the authors compared brain activity during articulation of the practiced words and a set of novel pseudowords (matched in phonetic complexity). FMRI analyses revealed no differences between AWS and controls in cortical or subcortical regions; both groups showed comparable increases in activation in left-lateralized brain areas implicated in phonological working memory and speech motor planning during production of the novel sequences compared to the practiced sequences. Moreover, activation in left-lateralized basal ganglia sites was negatively correlated with in-scanner mean disfluency in AWS. Collectively, these findings demonstrate that AWS exhibit no deficit in constructing new speech motor sequences but do show impaired execution of these sequences before and after they have been acquired and consolidated.
Distinguishing Syntactic Operations in the Brain: Dependency and Phrase-Structure Parsing
Authors: Lopopolo Alessandro , van den Bosch Antal , Petersson Karl-Magnus , Willems Roel M. 
Published: November 2020

AbstractFinding the structure of a sentence—the way its words hold together to convey meaning—is a fundamental step in language comprehension. Several brain regions, including the left inferior frontal gyrus, the left posterior superior temporal gyrus, and the left anterior temporal pole, are supposed to support this operation. The exact role of these areas is nonetheless still debated. In this paper we investigate the hypothesis that different brain regions could be sensitive to different kinds of syntactic computations. We compare the fit of phrase-structure and dependency structure descriptors to activity in brain areas using fMRI. Our results show a division between areas with regard to the type of structure computed, with the left anterior temporal pole and left inferior frontal gyrus favouring dependency structures and left posterior superior temporal gyrus favouring phrase structures.
Preservation or Correction?
Authors: Perng Hsin-Chih 
Published: November 2020

Abstract
The manuscript Heb. 110 of the National Library in Paris (=Ms Paris 110) has long been considered by many targumic scholars to be the best manuscript for the Aramaic targums to the Hagiographa, mainly due to its many prominent and consistent Palestinian linguistic features. This article discusses the peculiarities of Ms Paris 110 in comparison with many other earlier manuscripts, and shows that many of its Palestinian and other features do not reflect the original language of the targums, but rather a late tradition characterised by ‘Palestinianisation’ and linguistic editing. This has serious implications for current trends in targumic studies.
The Month ʾdr in Safaitic and the Status of Spirantisation in ‘Arabian’ Aramaic
Authors: Al-Jallad Ahmad 
Published: November 2020

Abstract
This article discusses the status of spirantisation in the Aramaic of Arabia based on transcriptions in Safaitic and other ancient Arabian languages. I suggest that ‘Arabian’ Aramaic pronunciation stems from an archaic variety of the language introduced by the Babylonians and Achaemenids in the mid-first millennium BCE. This variety lacked post-vocalic spirantisation and formed the basis for the local pronunciation of later Aramaic varieties, accounting for the archaic phonology of Aramaic loans into Arabian languages.
On the Emergence of Maragha Avicennism
Authors: Wisnovsky Robert 
Published: November 2020

Abstract
This article examines the earliest surviving commentary on Avicenna’s Kitāb al-Shifāʾ: ʿAllāmah al-Ḥillī’s (d. 726/1325) Kitāb Kashf al-khifāʾ min Kitāb al-Shifāʾ, composed when Ḥillī was working with the Īlkhānid vizier Rashīd al-Dīn al-Hamadānī (d. 718/1318). Only part of this work—covering the initial chapters from the Maqūlāt (Categories) of the Manṭiq (Logic) section of the Shifāʾ—is extant. After describing the manuscript (Chester Beatty Ar. 5151), the article situates the Kashf al-khifāʾ within the history of kalām appropriations of Avicenna’s metaphysics. Ḥillī’s commentary contains evidence of a tug-of-war between Sunni and Shiite mutakallimūn over proprietorship of the Avicennian legacy.