bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial patterns and associated factors of HIV Seropositivity among adults in Ethiopia from EDHS 2016: a spatial and multilevel analysis
Authors: Hailu Bayuh Asmamaw , Tadese Fentaw , Bogale Getahun Gebre , Molla Asressie , Miheretu Birhan Asmame , Beyene Joseph 
Published: October 2020

Abstract
Background
HIV is a major public health issue, especially in developing countries. It is important to track and design successful intervention programs to explore the spatial pattern, distribution, and associated factors of HIV Seropositivity. This study therefore showed the spatial variation of HIV Seropositivity and related factors in Ethiopia.

Methods
A total sample of 25,774 individual data collected from the 2016 EDHS data were primarily HIV biomarkers, IR, MR, and GPS. Spatial heterogeneity analysis was used with methods such as Morans I, Interpolation, and Kulldorff ‘s scan statistic. Spatial analysis was conducted using open source tools (QGIS, GeoDa, SaTScan). Multilevel logistic regression analysis was performed using Stata14 to identify HIV-associated factors. Finally, the AOR with a 95% confidence interval was used to report the mixed-effect logistic regression result in the full model.

Result
The prevalence of HIV / AIDS at national level was 0.93%. The highest prevalence regions were Gambela, Addis Abeba, Harari and Diredawa, accounting for 4.79, 3.36, 2.65 and 2.6%, respectively. Higher HIV seropositive spatial clusters have been established in the Gambela and Addis Ababa regions. Multilevel analysis at the individual level being married [AOR = 2.19 95% CI: (1.11–4.31)] and previously married [AOR = 6.45, 95% CI: (3.06–13.59)], female [AOR = 1.8, 95% CI: (1.19–2.72)], first-sex at age ≤15 [AOR = 4.39, 95% CI: (1.70–11.34)], 18—19 [AOR = 2.67 95% CI: (1.05–6.8)], middle age group (25-34) [AOR = 6.53, 95% CI: (3.67–11.75)], older age group (>34) [AOR = 2.67 95% CI: (1.05–6.8)], primary school [AOR = 3.03, 95% CI: (1.92–4.79)], secondary school [AOR = 3.37, 95% CI: (1.92–5.92) were significantly associated with serropositivity. Regarding household level, place of residence [urban: AOR = 6.13 CI: (3.12, 12.06)], female-headed households (AOR = 2.24 95% CI: (1.57–3.73), media exposure [low exposure (AOR = 0.53 95% CI: (0.33–0.86), no exposure AOR = 0.39 95% CI: (0.23–0.65)] and increased household size [AOR = 0.72 95% CI: (0.65–0.8)] were associated with HIV Seropositivity.

Conclusion
High cluster HIV cases were found in Gambela, Addis Abeba, Harari, and Diredawa. Having a history of married, start sex at a younger age, female-headed household, urban residence, and lower household size is more affected by HIV/AIDS. So any concerned body work around this risk group and area can be effective in the reduction of transmission.
Six-year follow-up of a survivor of cervical spine fracture and dislocation with oesophageal perforation following long scarf syndrome - a case report and literature review
Authors: Li Xiang , Wang Fangyong , Zhang Junwei , Hong Yi , Yang Yong 
Published: October 2020

Abstract
Background
Accidental strangulation due to scarf getting caught in the wheels of a vehicle or machine was called “Isadora Duncan Syndrome” or “Long Scarf Syndrome”. Survival of concomitant fracture dislocation of cervical spine and oesophageal perforation following Long Scarf Syndrome was rarely described and medium-term follow-up for this lesion has not been reported.

Case presentation
We present a 39-year-old female who suffered accidental strangulation caused by the scarf around her neck getting trapped in the wheels of the a vehicle and was referred to our hospital forty days post injury. The CT examination showed a fracture dislocation at C5/6 levels with complete dissociation of the supporting structures. She developed paravertebral abscesses, cutaneous fistulas and oesophageal perforation confirmed by oesophagoscope. The patient was treated conservatively because of poor general condition and inappropriate initial treatment. Halo-vest was used to immobilize the cervical spine. The oesophagus-cutaneous fistula was managed with enteral tube feeding and repeated local care. The patient survived despite such severe injury. Nine months after the injury, the oesophageal perforation closed spontaneously and fixed malunion of the cervical spine was achieved. Six-year follow-up demonstrated that the patient survived with complete C5 tetraplegia. Literature associated with this lesion was reviewed and factors contributing to the survival were discussed.

Conclusions
Concomitant fracture dislocation of cervical spine and oesophageal perforation following Long Scarf Syndrome is extremely rare with high risk of mortality. Though surgical intervention is always necessary, the optimal management for this kind of lesion should be made on an individual basis through a multidisciplinary approach.
CASCADE: a phase 2, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effect of tezepelumab on airway inflammation in patients with uncontrolled asthma
Authors: Emson Claire , Diver Sarah , Chachi Latifa , Megally Ayman , Small Cherrie , Downie John , Parnes Jane R. , Bowen Karin , Colice Gene , Brightling Chris E. 
Published: October 2020

Abstract
Background
Patients with severe, uncontrolled asthma, particularly those with a non-eosinophilic phenotype, have a great unmet need for new treatments that act on a broad range of inflammatory pathways in the airway. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine. In the PATHWAY phase 2b study (NCT02054130), tezepelumab reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline eosinophilic inflammatory status. This article reports the design and objectives of the phase 2 CASCADE study.

Methods
CASCADE is an ongoing exploratory, phase 2, randomized, double-blind, placebo-controlled, parallel-group study aiming to assess the anti-inflammatory effects of tezepelumab 210 mg administered subcutaneously every 4 weeks for 28 weeks in adults aged 18–75 years with uncontrolled, moderate-to-severe asthma. The primary endpoint is the change from baseline to week 28 in airway submucosal inflammatory cells (eosinophils, neutrophils, T cells and mast cells) from bronchoscopic biopsies. Epithelial molecular phenotyping, comprising the three-gene-mean technique, will be used to assess participants’ type 2 (T2) status to enable evaluation of the anti-inflammatory effect of tezepelumab across the continuum of T2 activation. Other exploratory analyses include assessments of the impact of tezepelumab on airway remodelling, including reticular basement membrane thickening and airway epithelial integrity. At the onset of the COVID-19 pandemic, the protocol was amended to address the possibility that site visits would be limited. The amendment allowed for: at-home dosing of study drug by a healthcare professional, extension of the treatment period by up to 6 months so patients are able to attend an onsite visit to undergo the end-of-treatment bronchoscopy, and replacement of final follow-up visits with a virtual or telephone visit.

Discussion
CASCADE aims to determine the mechanisms by which tezepelumab improves clinical asthma outcomes by evaluating the effect of tezepelumab on airway inflammatory cells and remodelling in patients with moderate-to-severe, uncontrolled asthma. An important aspect of this study is the evaluation of the anti-inflammatory effect of tezepelumab across patients with differing levels of eosinophilic and T2 inflammation.

Trial registration
NCT03688074 (ClinicalTrials.gov). Registered 28 September 2018.
NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma
Authors: Menzies-Gow Andrew , Colice Gene , Griffiths Janet M. , Almqvist Gun , Ponnarambil Sandhia , Kaur Primal , Ruberto Gennaro , Bowen Karin , Hellqvist Åsa , Mo May , Garcia Gil Esther 
Published: October 2020

Abstract
Background
Patients with severe, uncontrolled asthma have a significant unmet need for new treatments that have broader effects on airway inflammation, and that provide greater improvements in asthma outcomes than currently approved biologics and standard-of-care therapies. Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. In the PATHWAY phase 2b study (NCT02054130), tezepelumab significantly reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline disease phenotype. This article reports the design and objectives of the pivotal phase 3 NAVIGATOR study.

Methods
NAVIGATOR (NCT03347279) is an ongoing randomized, double-blind, placebo-controlled trial in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids (N = 1061). The study population includes approximately equal proportions of patients with high (≥ 300 cells/μL) and low (< 300 cells/μL) blood eosinophil counts. The study comprises a 5–6-week screening period, a 52-week treatment period and a 12-week post-treatment follow-up period. All patients will receive their prescribed controller medications without change throughout the study. The primary efficacy endpoint is the annualized asthma exacerbation rate during the 52-week treatment period. Key secondary endpoints include the effect of tezepelumab on lung function, asthma control and health-related quality of life.

Discussion
NAVIGATOR is evaluating the effect of tezepelumab in patients with a broad range of severe asthma phenotypes at baseline, including those with low blood eosinophil counts. The target sample size for NAVIGATOR (N = 1060) was achieved, and it is the largest clinical study of tezepelumab in severe, uncontrolled asthma to date. NAVIGATOR aims to further investigate the effect of tezepelumab on exacerbations and build on observations from the phase 2b PATHWAY study, and to demonstrate further the potential of tezepelumab to provide patients with severe, uncontrolled asthma with improvements in lung function, asthma control and health-related quality of life.

Trial registration
NCT03347279 (ClinicalTrials.gov). Registered 20 November 2017.
The correlation between the Th17/Treg cell balance and bone health
Authors: Zhu Lei , Hua Fei , Ding Wenge , Ding Kai , Zhang Yige , Xu Chenyang 
Published: October 2020

AbstractWith the ageing of the world population, osteoporosis has become a problem affecting quality of life. According to the traditional view, the causes of osteoporosis mainly include endocrine disorders, metabolic disorders and mechanical factors. However, in recent years, the immune system and immune factors have been shown to play important roles in the occurrence and development of osteoporosis. Among these components, regulatory T (Treg) cells and T helper 17 (Th17) cells are crucial for maintaining bone homeostasis, especially osteoclast differentiation. Treg cells and Th17 cells originate from the same precursor cells, and their differentiation requires involvement of the TGF-β regulated signalling pathway. Treg cells and Th17 cells have opposite functions. Treg cells inhibit the differentiation of osteoclasts in vivo and in vitro, while Th17 cells promote the differentiation of osteoclasts. Therefore, understanding the balance between Treg cells and Th17 cells is anticipated to provide a new idea for the development of novel treatments for osteoporosis.
Evaluation on the application of transcranial Doppler (TCD) and electroencephalography (EEG) in patients with vertebrobasilar insufficiency
Authors: Ke Changmin , Zheng Chu-na , Wang Juan , Yao Dongying , Fang Xiaojuan , Luo Yan , Wu Jianglin , Zheng Xiaoqing , Wang Peiping 
Published: October 2020

Abstract
Background
To evaluate the diagnostic value of transcranial Doppler (TCD) and electroencephalography (EEG) in patients with vertebrobasilar insufficiency (VBI) during clinical diagnosis and treatment

Methods
Eighty patients diagnosed with VBI in our hospital from June 2018 to December 2019 were randomly selected as the observation group, and 80 healthy people who received physical examination in the same period were selected as the control group. The abnormal rate, main performance and results, and the peak velocity of blood flow and vertebrobasilar artery blood flow of the two groups were compared.

Results
The abnormal rate of EEG and TCD in VBI patients was 38.75% (31/80) and the 93.75% (75/80), respectively. In TCD examination, ACA, PCA, MCA, and VA of both sides of the observation group were higher than those of the control group, while BA was lower than that of the control group (P < 0.05). The Vs, Vd, and Vm on both sides of BA and VA in the observation group were lower than those in the control group, while PI and RI were higher than those in the control group (P < 0.05).

Conclusions
TCD examination is highly sensitive to the degree and pattern of cerebral ischemia in VBI patients. EEG examination will define the changes of brain cell function after cerebral ischemia. Therefore, EEG and TCD have their own advantages. The application of TCD and EEG can be considered in the early diagnosis, curative effect, and prognosis evaluation of VBI patients, so as to improve the accuracy of diagnosis and prognosis.
Performance and community structure dynamics of microbial electrolysis cells operated on multiple complex feedstocks
Authors: Satinover Scott J. , Rodriguez Miguel , Campa Maria F. , Hazen Terry C. , Borole Abhijeet P. 
Published: October 2020

Abstract
Background
Microbial electrolysis is a promising technology for converting aqueous wastes into hydrogen. However, substrate adaptability is an important feature, seldom documented in microbial electrolysis cells (MECs). In addition, the correlation between substrate composition and community structure has not been well established. This study used an MEC capable of producing over 10 L/L-day of hydrogen from a switchgrass-derived bio-oil aqueous phase and investigated four additional substrates, tested in sequence on a mature biofilm. The additional substrates included a red oak-derived bio-oil aqueous phase, a corn stover fermentation product, a mixture of phenol and acetate, and acetate alone.

Results
The MECs fed with the corn stover fermentation product resulted in the highest performance among the complex feedstocks, producing an average current density of 7.3 ± 0.51 A/m2, although the acetate fed MECs outperformed complex substrates, producing 12.3 ± 0.01 A/m2. 16S rRNA gene sequencing showed that community structure and community diversity were not predictive of performance, and replicate community structures diverged despite identical inoculum and enrichment procedure. The trends in each replicate, however, were indicative of the influence of the substrates. Geobacter was the most dominant genus across most of the samples tested, but its abundance did not correlate strongly to current density. High-performance liquid chromatography (HPLC) showed that acetic acid accumulated during open circuit conditions when MECs were fed with complex feedstocks and was quickly degraded once closed circuit conditions were applied. The largest net acetic acid removal rate occurred when MECs were fed with red oak bio-oil aqueous phase, consuming 2.93 ± 0.00 g/L-day. Principal component analysis found that MEC performance metrics such as current density, hydrogen productivity, and chemical oxygen demand removal were closely correlated. Net acetic acid removal was also found to correlate with performance. However, no bacterial genus appeared to correlated to these performance metrics strongly, and the analysis suggested that less than 70% of the variance was accounted for by the two components.

Conclusions
This study demonstrates the robustness of microbial communities to adapt to a range of feedstocks and conditions without relying on specific species, delivering high hydrogen productivities despite differences in community structure. The results indicate that functional adaptation may play a larger role in performance than community composition. Further investigation of the roles each microbe plays in these communities will help MECs to become integral in the 21st-century bioeconomy to produce zero-emission fuels.
Cord blood DNA methylome in newborns later diagnosed with autism spectrum disorder reflects early dysregulation of neurodevelopmental and X-linked genes
Authors: Mordaunt Charles E. , Jianu Julia M. , Laufer Benjamin I. , Zhu Yihui , Hwang Hyeyeon , Dunaway Keith W. , Bakulski Kelly M. , Feinberg Jason I. , Volk Heather E. , Lyall Kristen , Croen Lisa A. , Newschaffer Craig J. , Ozonoff Sally , Hertz-Picciotto Irva , Fallin M. Daniele , Schmidt Rebecca J. , LaSalle Janine M. 
Published: October 2020

AbstractBackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder with complex heritability and higher prevalence in males. The neonatal epigenome has the potential to reflect past interactions between genetic and environmental factors during early development and influence future health outcomes.MethodsWe performed whole-genome bisulfite sequencing of 152 umbilical cord blood samples from the MARBLES and EARLI high-familial risk prospective cohorts to identify an epigenomic signature of ASD at birth. Samples were split into discovery and replication sets and stratified by sex, and their DNA methylation profiles were tested for differentially methylated regions (DMRs) between ASD and typically developing control cord blood samples. DMRs were mapped to genes and assessed for enrichment in gene function, tissue expression, chromosome location, and overlap with prior ASD studies. DMR coordinates were tested for enrichment in chromatin states and transcription factor binding motifs. Results were compared between discovery and replication sets and between males and females.ResultsWe identified DMRs stratified by sex that discriminated ASD from control cord blood samples in discovery and replication sets. At a region level, 7 DMRs in males and 31 DMRs in females replicated across two independent groups of subjects, while 537 DMR genes in males and 1762 DMR genes in females replicated by gene association. These DMR genes were significantly enriched for brain and embryonic expression, X chromosome location, and identification in prior epigenetic studies of ASD in post-mortem brain. In males and females, autosomal ASD DMRs were significantly enriched for promoter and bivalent chromatin states across most cell types, while sex differences were observed for X-linked ASD DMRs. Lastly, these DMRs identified in cord blood were significantly enriched for binding sites of methyl-sensitive transcription factors relevant to fetal brain development.ConclusionsAt birth, prior to the diagnosis of ASD, a distinct DNA methylation signature was detected in cord blood over regulatory regions and genes relevant to early fetal neurodevelopment. Differential cord methylation in ASD supports the developmental and sex-biased etiology of ASD and provides novel insights for early diagnosis and therapy.
Treatment variables associated with outcome in emergency department patients with suspected sepsis
Authors: Sivayoham Narani , Blake Lesley A. , Tharimoopantavida Shafi E. , Chughtai Saad , Hussain Adil N. , Rhodes Andrew 
Published: October 2020

Abstract
Background
Early treatment is advocated in the management of patients with suspected sepsis in the emergency department (ED). We sought to understand the association between the ED treatments and outcome in patients admitted with suspected sepsis. The treatments studied were: (i) the time to antibiotics, where time zero is the time the patient was booked in which is also the triage time; (ii) the volume of intravenous fluid (IVF); (iii) mean arterial pressure (MAP) after 2000 ml of IVF and (iv) the final MAP in the ED.

Methods
We performed a retrospective analysis of the ED database of patients aged ≥ 18 year who met two SIRS criteria or one red flag sepsis criteria on arrival, received intravenous antibiotics for a suspected infection and admitted between 8th February 2016 and 31st August 2017. The primary outcome measure was all-cause in-hospital mortality. The four treatments stated above were controlled for severity of illness and subject to multivariate logistic regression and Cox proportional-hazard regression to identify independent predictors of mortality.

Results
Of the 2,066 patients studied 272 (13.2%) died in hospital. The median time to antibiotics was 48 (interquartile range 30–82) minutes. The time to antibiotics was an independent predictor of mortality only in those who developed refractory hypotension (RH); antibiotics administered more than 55 mins after arrival was associated with an odds ratio (OR) for mortality of 2.75 [95% confidence interval (CI) 1.22–6.14]. The number-needed-to-treat was 4. IVF > 2000 ml (95% CI > 500– > 2100), except in RH, and a MAP ≤ 66 mmHg after 2000 ml of IVF were also independent predictors of mortality. The OR for mortality of IVF > 2,000 ml in non-RH was 1.80 (95% CI 1.15–2.82); Number-needed-to-harm was 14. The OR for morality for a MAP ≤ 66 mmHg after 2000 ml of IVF was 3.42 (95% CI 2.10–5.57). A final MAP < 75 mmHg in the ED was associated with, but not an independent predictor of mortality. An initial systolic blood pressure of < 100 mmHg has a sensitivity of 63.3% and specificity of 88.4% for the development of RH.

Conclusion
In this study, antibiotics were found to be time-critical in RH. Intravenous fluids > 2000 ml (except in RH) and a MAP ≤ 66 mmHg after 2000 ml of IVF were also independent predictors of mortality.
pCLIF-SOFA is a reliable outcome prognostication score of critically ill children with cirrhosis: an ESPNIC multicentre study
Authors: Claude Caroline , Deep Akash , Kneyber Martin , Siddiqui Salman , Renolleau Sylvain , Morin Luc , Jacquemin Emmanuel , Teglas Jean-Paul , Gajdos Vincent , Tissières Pierre , Durand Philippe ,   the ESPNIC liver failure, support working group
Published: October 2020

Abstract
Background and aims
Data on outcome of critically ill children with cirrhosis are scarce. We aimed to evaluate the prognostic accuracy of sequential organs scoring systems in children with cirrhosis admitted to Paediatric Intensive Care Units (PICU).

Methods
We performed a multicentre retrospective analysis of children with cirrhosis admitted into four European PICUs between 2011 and 2016. Investigators were members of the ESPNIC liver failure and support working group. Paediatric End-Stage Liver Disease (PELD) and paediatric chronic liver failure sequential organ failure assessment score (pCLIF-SOFA) diagnostic accuracy for 28- and 60-day liver transplantation, 28-day mortality and 60-day composite outcome (ie. death or liver transplantation) were tested.

Results
One-hundred-and-thirty children were included. The main causes for PICU admission were acute-on-chronic liver failure (ACLF), gastrointestinal bleeding and sepsis. Twenty-nine percent died and 22.3% were transplanted by day-60 after PICU admission. On multivariable analysis, pCLIF-SOFA was the only predictor of mortality at day-28 and of composite outcome. Both pCLIF-SOFA and ACLF were independently associated with emergent liver transplantation. The pCLIF-SOFA score higher than 9 well predicted a 28-day mortality with a sensitivity of 87.8% and a specificity of 77.3%. A pCLIF-SOFA score higher than 7 was independently associated with liver transplantation on day-60. Stage 3 AKI assessed with KDIGO classification was significantly associated with 28-day mortality.

Conclusions
Half of critically ill cirrhotic children admitted to PICU either died or were transplanted within the initial 28-day period. On admission pCLIF-SOFA score accurately identify patients transplanted at day-28 and day-60 to those alive without LT and is associated with 28-day mortality and composite outcome at day-60.