bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isavuconazole for treatment of rare invasive fungal diseases
Authors: Cornely Oliver A. , Mullane Kathleen M. , Ostrosky‐Zeichner Luis , Maher Rochelle M. , Croos‐Dabrera Rodney , Lu Qiaoyang , Lademacher Christopher , Perfect John R. , Oren Ilana , Schmitt‐Hoffmann Anne‐Hortense , Giladi Michael , Marty Francisco M. , Rahav Galia 
Published: April 2018

SummaryData regarding treatment of rare invasive fungal diseases (IFDs) are scarce. We documented the efficacy and safety of isavuconazole for treatment of uncommonly diagnosed IFDs. VITAL was a single‐arm, international, open‐label study evaluating the efficacy and safety of isavuconazole (200 mg orally or intravenously every 8 hours for 48 hours, then once daily). The primary outcome was overall response at Day 42; key secondary outcomes were overall responses at Day 84 and end of treatment (EOT), mortality at Days 42 and 84, and safety. This analysis includes patients with IFD caused by rare or unidentified pathogens. Twenty‐six patients with IFDs caused by rare moulds (n = 17), non‐Candida yeasts (n = 2), or unidentified moulds (n = 7) were enrolled (median treatment duration [range], 114.5 [1‐496]) days. Overall treatment success was observed in 11/26 (42.3%), 10/26 (38.5%), and 15/26 (57.7%) patients at Days 42, 84, and EOT, respectively. All‐cause mortality rates were 2/26 patients (7.7%) at Day 42 and 4/26 patients (15.4%) at Day 84; another two patients died after Day 84. All patients had ≥1 treatment‐emergent adverse event (TEAE); 15 patients (57.7%) had serious TEAEs, and TEAEs led to discontinuation of isavuconazole in four patients (15.4%). Isavuconazole may be efficacious for treatment of a range of rare IFDs.
Determination of leaf respiration in the light: comparison between an isotopic disequilibrium method and the Laisk method
Authors: Gong Xiao Ying , Tcherkez Guillaume , Wenig Johannes , Schäufele Rudi , Schnyder Hans 
Published: April 2018

Summary

Quantification of leaf respiration is important for understanding plant physiology and ecosystem biogeochemical processes. Leaf respiration continues in the light (RL) but supposedly at a lower rate than in the dark (RDk). However, there is no method for direct measurement of RL and the available methods require nonphysiological measurement conditions.

A method based on isotopic disequilibrium quantified RL (RL 13C) and mesophyll conductance of young and old fully expanded leaves of six species. RL 13C was compared to RL determined by the Laisk method (RL Laisk) on the very same leaves with a minimum time lag.

RL 13C and RL Laisk were generally lower than RDk, and were not significantly affected by leaf ageing. RL Laisk and RL 13C were positively correlated (r2 = 0.35), and both were positively correlated with RDk (r2 ≥ 0.6). RL Laisk was systematically lower than RL 13C by 0.4 μmol m−2 s−1. Using A/Cc instead of A/Ci curves, a higher photocompensation point Γ* (by 5 μmol mol−1) was found but no influence on RL Laisk estimates was observed.

The results imply that the Laisk method underestimates actual RL significantly, probably related to the measurement condition of low CO2 and irradiance. The isotopic disequilibrium method is useful for assessing responses of RL to irradiance and CO2, improving our mechanistic understanding of RL.
Group B Streptococcus Vaginal Carriage in Pregnant Women as Deciphered by Clustered Regularly Interspaced Short Palindromic Repeat Analysis
Authors: Beauruelle Clemence , Pastuszka Adeline , Mereghetti Laurent , Lanotte Philippe 
Published: April 2018

ABSTRACT

We evaluated the diversity of group B
Streptococcus
(GBS) vaginal carriage populations in pregnant women. For this purpose, we studied each isolate present in a primary culture of a vaginal swab using a new approach based on clustered regularly interspaced short palindromic repeats (CRISPR) locus analysis. To evaluate the CRISPR array composition rapidly, a restriction fragment length polymorphism (RFLP) analysis was performed. For each different pattern observed, the CRISPR array was sequenced and capsular typing and multilocus sequence typing (MLST) were performed. A total of 970 isolates from 10 women were analyzed by CRISPR-RFLP. Each woman carrying GBS isolates presented one to five specific “personal” patterns. Five women showed similar isolates with specific and unique restriction patterns, suggesting the carriage of a single GBS clone. Different patterns were observed among isolates from the other five women. For three of these, CRISPR locus sequencing highlighted low levels of internal modifications in the locus backbone, whereas there were high levels of modifications for the last two women, suggesting the carriage of two different clones. These two clones were closely related, having the same ancestral spacer(s), the same capsular type and, in one case, the same ST, but showed different antibiotic resistance patterns in pairs. Eight of 10 women were colonized by a single GBS clone, while two of them were colonized by two strains, leading to a risk of selection of more-virulent and/or more-resistant clones during antibiotic prophylaxis. This CRISPR analysis made it possible to separate isolates belonging to a single capsular type and sequence type, highlighting the greater discriminating power of this approach.
Cost-effectiveness of interventions to control cardiovascular diseases and diabetes mellitus in South Asia: a systematic review
Authors: Singh Kavita , Chandrasekaran Ambalam M , Bhaumik Soumyadeep , Chattopadhyay Kaushik , Gamage Anuji Upekshika , Silva Padmal De , Roy Ambuj , Prabhakaran Dorairaj , Tandon Nikhil 
Published: April 2018

ObjectivesMore than 80% of cardiovascular diseases (CVD) and diabetes mellitus (DM) burden now lies in low and middle-income countries. Hence, there is an urgent need to identify and implement the most cost-effective interventions, particularly in the resource-constraint South Asian settings. Thus, we aimed to systematically review the cost-effectiveness of individual-level, group-level and population-level interventions to control CVD and DM in South Asia.MethodsWe searched 14 electronic databases up to August 2016. The search strategy consisted of terms related to ‘economic evaluation’, ‘CVD’, ‘DM’ and ‘South Asia’. Per protocol two reviewers assessed the eligibility and methodological quality of studies using standard checklists, and extracted incremental cost-effectiveness ratios of interventions.ResultsOf the 2949 identified studies, 42 met full inclusion criteria. Critical appraisal of studies revealed 15 excellent, 18 good and 9 poor quality studies. Most studies were from India (n=37), followed by Bangladesh (n=3), Pakistan (n=2) and Bhutan (n=1). The economic evaluations were based on observational studies (n=9), randomised trials (n=12) and decision models (n=21). Together, these studies evaluated 301 policy or clinical interventions or combination of both. We found a large number of interventions were cost-effective aimed at primordial prevention (tobacco taxation, salt reduction legislation, food labelling and food advertising regulation), and primary and secondary prevention (multidrug therapy for CVD in high-risk group, lifestyle modification and metformin treatment for diabetes prevention, and screening for diabetes complications every 2–5 years). Significant heterogeneity in analytical framework and outcome measures used in these studies restricted meta-analysis and direct ranking of the interventions by their degree of cost-effectiveness.ConclusionsThe cost-effectiveness evidence for CVD and DM interventions in South Asia is growing, but most evidence is from India and limited to decision modelled outcomes. There is an urgent need for formal health technology assessment and policy evaluations in South Asia using local research data.PROSPERO registration numberCRD42013006479.
Piloting the addition of contingency management to best practice counselling as an adjunct treatment for rural and remote disordered gamblers: study protocol
Authors: Christensen Darren R , Witcher Chad S G , Leighton Trent , Hudson-Breen Rebecca , Ofori-Dei Samuel 
Published: April 2018

IntroductionProblematic gambling is a significant Canadian public health concern that causes harm to the gambler, their families, and society. However, a significant minority of gambling treatment seekers drop out prior to the issue being resolved; those with higher impulsivity scores have the highest drop-out rates. Consequently, retention is a major concern for treatment providers. The aim of this study is to investigate the efficacy of internet-delivered cognitive behavioural therapy (CBT) and internet-delivered CBT and contingency management (CM+) as treatments for gambling disorder in rural Albertan populations. Contingency management (CM) is a successful treatment approach for substance dependence that uses small incentives to reinforce abstinence. This approach may be suitable for the treatment of gambling disorder. Furthermore, internet-delivered CM may hold particular promise in rural contexts, as these communities typically struggle to access traditional clinic-based counselling opportunities.Methods and analysis54 adults with gambling disorder will be randomised into one of two conditions: CM and CBT (CM+) or CBT alone (CBT). Gambling will be assessed at intake, every treatment session, post-treatment, and follow-up. The primary outcome measures are treatment attendance, gambling abstinence, gambling, gambling symptomatology, and gambling urge. In addition, qualitative interviews assessing study experiences will be conducted with the supervising counsellor, graduate student counsellors, study affiliates, and a subset of treatment seekers. This is the first study to use CM as a treatment for gambling disorder in rural and remote populations.Ethics and disseminationThis study was approved by the University of Lethbridge’s Human Subject Research Committee (#2016–080). The investigators plan to publish the results from this study in academic peer-reviewed journals. Summary information will be provided to the funder.Trial registration numberNCT02953899; Pre-results.
Effect of pasta in the context of low-glycaemic index dietary patterns on body weight and markers of adiposity: a systematic review and meta-analysis of randomised controlled trials in adults
Authors: Chiavaroli Laura , Kendall Cyril W C , Braunstein Catherine R , Blanco Mejia Sonia , Leiter Lawrence A , Jenkins David J A , Sievenpiper John L 
Published: April 2018

ObjectiveCarbohydrate staples such as pasta have been implicated in the obesity epidemic. It is unclear whether pasta contributes to weight gain or like other low-glycaemic index (GI) foods contributes to weight loss. We synthesised the evidence of the effect of pasta on measures of adiposity.DesignSystematic review and meta-analysis using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.Data sourcesMEDLINE, Embase, CINAHL and the Cochrane Library were searched through 7 February 2017.Eligibility criteria for selecting studiesWe included randomised controlled trials ≥3 weeks assessing the effect of pasta alone or in the context of low-GI dietary patterns on measures of global (body weight, body mass index (BMI), body fat) and regional (waist circumference (WC), waist-to-hip ratio (WHR), sagittal abdominal diameter (SAD)) adiposity in adults.Data extraction and synthesisTwo independent reviewers extracted data and assessed risk of bias. Data were pooled using the generic inverse-variance method and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2statistic). GRADE assessed the certainty of the evidence.ResultsWe identified no trial comparisons of the effect of pasta alone and 32 trial comparisons (n=2448 participants) of the effect of pasta in the context of low-GI dietary patterns. Pasta in the context of low-GI dietary patterns significantly reduced body weight (MD=−0.63 kg; 95% CI −0.84 to –0.42 kg) and BMI (MD=−0.26 kg/m2; 95% CI −0.36 to –0.16 kg/m2) compared with higher-GI dietary patterns. There was no effect on other measures of adiposity. The certainty of the evidence was graded as moderate for body weight, BMI, WHR and SAD and low for WC and body fat.ConclusionsPasta in the context of low-GI dietary patterns does not adversely affect adiposity and even reduces body weight and BMI compared with higher-GI dietary patterns. Future trials should assess the effect of pasta in the context of other ‘healthy’ dietary patterns.Trial registration numberNCT02961088; Results.
A protocol for a prospective observational study using chest and thumb ECG: transient ECG assessment in stroke evaluation (TEASE) in Sweden
Authors: Magnusson Peter , Koyi Hirsh , Mattsson Gustav 
Published: April 2018

IntroductionAtrial fibrillation (AF) causes ischaemic stroke and based on risk factor evaluation warrants anticoagulation therapy. In stroke survivors, AF is typically detected with short-term ECG monitoring in the stroke unit. Prolonged continuous ECG monitoring requires substantial resources while insertable cardiac monitors are invasive and costly. Chest and thumb ECG could provide an alternative for AF detection poststroke.The primary objective of our study is to assess the incidence of newly diagnosed AF during 28 days of chest and thumb ECG monitoring in cryptogenic stroke. Secondary objectives are to assess health-related quality of life (HRQoL) using short-form health survey (SF-36) and the feasibility of the Coala Heart Monitor in patients who had a stroke.MethodsStroke survivors in Region Gävleborg, Sweden, will be eligible for the study from October 2017. Patients with a history of ischaemic stroke without documented AF before or during ECG evaluation in the stroke unit will be evaluated by the chest and thumb ECG system Coala Heart Monitor. The monitoring system is connected to a smartphone application which allows for remote monitoring and prompt advice on clinical management. Over a period of 28 days, patients will be monitored two times a day and may activate the ECG recording at symptoms. On completion, the system is returned by mail. This system offers a possibility to evaluate the presence of AF poststroke, but the feasibility of this system in patients who recently suffered from a stroke is unknown. In addition, HRQoL using SF-36 in comparison to Swedish population norms will be assessed. The feasibility of the Coala Heart Monitor will be assessed by a self-developed questionnaire.Ethics and disseminationThe study was approved by The Regional Ethical Committee in Uppsala (2017/321). The database will be closed after the last follow-up, followed by statistical analyses, interpretation of results and dissemination to a scientific journal.Trial registration numberNCT03301662; Pre-results.
Multiple balloon-like lesions in the small intestine of an adult with chronic diarrhoea
Authors: Zhou Cheng-Bei , Lu Hong , Chen Ying-Xuan , Fang Jing-Yuan 
Published: April 2018

Clinical presentationA 28-year-old woman presented with a 3-year history of chronic watery diarrhoea along with abdominal pain and bloating, which could mostly be alleviated after defecation. Her symptom of diarrhoea, at least three times a day, could be relieved by neither probiotics nor antidiarrhoeal agents. She had also lost 5 kg in the last month. She denied family history, poor vaccine responses or significant infections in early childhood except for an allergy history to intravenous immunoglobulin (Ig) with immediate dyspnoea, palpitations and hypotension. Laboratory investigations suggested that the stool specimens were negative for viruses, parasites or bacteria. Laboratory evaluation revealed a low serum globulin level, 14.5 (reference range, 20–30 g/L); serum Ig levels were significantly abnormal: IgA <0.27 (0.7–4 g/L), IgM 0.24 (0.4–2.3 g/L), IgG 1.3 (7–16 g/L); white cell count 15.4×109/L (3.69–9.16×109/L); C-reactive protein (CRP) 20.5 (normal <10 mg/L); CD4+ lymphocyte/CD8+ lymphocyte 1.09% (1.5%–2%). Other laboratory findings were unremarkable, for example, tumour markers, autoantibodies and HIV, and so on. CT showed mesenteric nodule-like images and thickening of the wall and mucosa in small intestine. Peroral and transanal enteroscopy respectively demonstrated swelling mucosa and continuous granular lesions from duodenum to middle jejunum, and from middle ileum to terminal ileum (figure 1A–D).Figure 1Endoscopic images show swelling mucosa, dense nodular lesions in duodenum (A), upper jejunum (B), upper ileum (C) and terminal ileum (D).QuestionWhat is the most likely diagnosis?
How adolescent health influences education and employment: investigating longitudinal associations and mechanisms
Authors: Hale Daniel R , Viner Russell M 
Published: April 2018

BackgroundEducation is recognised as a strong determinant of health. Yet there is increasing concern that health in adolescence may also influence educational attainments and future life chances. We examined associations between health in early adolescence and subsequent academic and employment outcomes, exploring potential mediators of these relationships to inform intervention strategies.MethodsWe used data from the Longitudinal Study of Young People in England. Adolescent health was measured at waves 1 and 2. Outcomes included educational attainment at age 16 years and being NEET (not in education, employment or training) at age 19 years. Associations were adjusted for ethnicity, area-level deprivation and early adolescent academic attainment. Where significant associations were identified, we examined the role of hypothesised mediators including attendance and truancy, classroom behaviour, substance use and psychological distress.ResultsHealth conditions in early adolescence predicted poor subsequent education and employment outcomes (ORs ranged from 1.25 to 1.72) with the exception of long-term chronic conditions and NEET status, which were unassociated. The most consistent mediating variable was social exclusion. School behaviour, truancy and substance use were significant mediators for mental health. Long-term absences mediated associations between mental health and physical health and later outcomes.ConclusionsHealth is a key component of academic and vocational achievement. Investment in health is a way of improving life chances. The identification of key mediators such as social exclusion and truancy indicate areas where screening for health conditions and provision of targeted support could improve educational, employment and health outcomes.
Molecular Diagnosis of Diffuse Gliomas through Sequencing of Cell-Free Circulating Tumor DNA from Cerebrospinal Fluid
Authors: Martínez-Ricarte Francisco , Mayor Regina , Martínez-Sáez Elena , Rubio-Pérez Carlota , Pineda Estela , Cordero Esteban , Cicuéndez Marta , Poca Maria A. , López-Bigas Nuria , Ramon y Cajal Santiago , Vieito María , Carles Joan , Tabernero Josep , Vivancos Ana , Gallego Soledad , Graus Francesc , Sahuquillo Juan , Seoane Joan 
Published: April 2018

Abstract
Purpose: Diffuse gliomas are the most common primary tumor of the brain and include different subtypes with diverse prognosis. The genomic characterization of diffuse gliomas facilitates their molecular diagnosis. The anatomical localization of diffuse gliomas complicates access to tumor specimens for diagnosis, in some cases incurring high-risk surgical procedures and stereotactic biopsies. Recently, cell-free circulating tumor DNA (ctDNA) has been identified in the cerebrospinal fluid (CSF) of patients with brain malignancies.
Experimental Design: We performed an analysis of IDH1, IDH2, TP53, TERT, ATRX, H3F3A, and HIST1H3B gene mutations in two tumor cohorts from The Cancer Genome Atlas (TCGA) including 648 diffuse gliomas. We also performed targeted exome sequencing and droplet digital PCR (ddPCR) analysis of these seven genes in 20 clinical tumor specimens and CSF from glioma patients and performed a histopathologic characterization of the tumors.
Results: Analysis of the mutational status of the IDH1, IDH2, TP53, TERT, ATRX, H3F3A, and HIST1H3B genes allowed the classification of 79% of the 648 diffuse gliomas analyzed, into IDH-wild-type glioblastoma, IDH-mutant glioblastoma/diffuse astrocytoma and oligodendroglioma, each subtype exhibiting diverse median overall survival (1.1, 6.7, and 11.2 years, respectively). We developed a sequencing platform to simultaneously and rapidly genotype these seven genes in CSF ctDNA allowing the subclassification of diffuse gliomas.
Conclusions: The genomic analysis of IDH1, IDH2, TP53, ATRX, TERT, H3F3A, and HIST1H3B gene mutations in CSF ctDNA facilitates the diagnosis of diffuse gliomas in a timely manner to support the surgical and clinical management of these patients. Clin Cancer Res; 24(12); 2812–9. ©2018 AACR.
ZIP4 Promotes Pancreatic Cancer Progression by Repressing ZO-1 and Claudin-1 through a ZEB1-Dependent Transcriptional Mechanism
Authors: Liu Mingyang , Yang Jingxuan , Zhang Yuqing , Zhou Zhijun , Cui Xiaobo , Zhang Liyang , Fung Kar-Ming , Zheng Wei , Allard Felicia D. , Yee Eric U. , Ding Kai , Wu Huanwen , Liang Zhiyong , Zheng Lei , Fernandez-Zapico Martin E. , Li Yi-Ping , Bronze Michael S. , Morris Katherine T. , Postier Russell G. , Houchen Courtney W. , Yang Jing , Li Min 
Published: April 2018

Abstract
Purpose: ZIP4 is overexpressed in human pancreatic cancer and promotes tumor growth. However, little is known about the role of ZIP4 in advanced stages of this dismal neoplasm. Our goal is to study the underlying mechanism and define a novel signaling pathway controlled by ZIP4-modulating pancreatic tumor metastasis.
Experimental Design: The expression of ZIP4, ZO-1, claudin-1, and ZEB1 in human pancreatic cancer tissues, genetically engineered mouse model, xenograft tumor model, and pancreatic cancer cell lines were examined, and the correlations between ZIP4 and those markers were also analyzed. Functional analysis of ZO-1, claudin-1, and ZEB1 was investigated in pancreatic cancer cell lines and orthotopic xenografts.
Results: Genetic inactivation of ZIP4 inhibited migration and invasion in pancreatic cancer and increased the expression of ZO-1 and claudin-1. Conversely, overexpression of ZIP4 promoted migration and invasion and increased the expression of ZEB1 and downregulation of the aforementioned epithelial genes. ZIP4 downregulation of ZO-1 and claudin-1 requires the transcriptional repressor ZEB1. Further analysis demonstrated that ZIP4-mediated repression of ZO-1 and claudin-1 leads to upregulation of their targets FAK and Paxillin. Silencing of ZIP4 caused reduced phosphorylation of FAK and Paxillin, which was rescued by simultaneous blocking of ZO-1 or claudin-1. Clinically, we demonstrated that ZIP4 positively correlates with the levels of ZEB1 and inversely associates with the expression of ZO-1 and claudin-1.
Conclusions: These findings suggest a novel pathway activated by ZIP4-controlling pancreatic cancer invasiveness and metastasis, which could serve as a new therapeutic target for this devastating disease. Clin Cancer Res; 24(13); 3186–96. ©2018 AACR.
A new combination in Tulista, T. minor (Alooideae, Asphodelaceae)
Authors: SMITH GIDEON F. , FIGUEIREDO ESTRELA , MOLTENO STEVEN 
Published: April 2018

Tulista Rafinesque (1840: 137) is the smallest of the three haworthioid genera recognised in the Asphodelaceae subfam. Alooideae, and widely considered to include four, or five, species [depending on whether T. opalina (Hayashi 2001: 17) Breuer (2016: 7) is accepted] (Smith et al. 2017).