bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiotherapy for geriatric head-and-neck cancer patients: what is the value of standard treatment in the elderly?
Authors: Haehl Erik , Rühle Alexander , David Hélène , Kalckreuth Tobias , Sprave Tanja , Stoian Raluca , Becker Christoph , Knopf Andreas , Grosu Anca-Ligia , Nicolay Nils H. 
Published: February 2020

AbstractBackgroundHead-and-neck squamous cell carcinoma (HNSCC) is one of the most common malignancies globally, and the number of elderly patients diagnosed with HNSCC is increasing. However, as elderly HNSCC patients are underrepresented in clinical trials, current clinical decision making for this cohort largely lacks clinical evidence.MethodsElderly patients (≥65 years) with HNSCC undergoing (chemo)radiotherapy from 2010 to 2018 at Freiburg University Medical Center were assessed for patterns of care, locoregional control (LRC), progression-free (PFS) and overall survival (OS) regarding definitive and adjuvant treatments. Acute and late therapy-associated toxicities were quantified according to CTCAE v5.0.ResultsTwo hundred forty-six patients were included in this analysis, of whom 166 received definitive and 80 adjuvant treatment. Two-year rates for OS, PFS and LRC were 56.9, 44.9 and 75.5%, respectively. Survival differed significantly between age groups with an OS of 40 and 22 months and a PFS of 23 and 12 months for patients aged 65–74 or ≥ 75 years, respectively (p < 0.05). Concomitant chemotherapy resulted in improved OS in patients aged 65–74 years compared to radiotherapy alone (p < 0.05) for definitive treatments, while patients ≥75 years did not benefit (p = 0.904). For adjuvant chemoradiotherapy, a trend towards superior OS rates was observed for patients aged 65–74 years (p = 0.151). Low performance status (HR = 2.584, 95% CI 1.561–4.274;p < 0.001) and smoking (HR = 1.960, 95% CI 1.109–3.464,p < 0.05) were the strongest independent prognostic factor in the multivariate analysis for decreased OS. One hundred thirty-eight patients (56.1%) experienced acute grade 3/4 and 45 patients (19.9%) chronic grade 3 toxicities.ConclusionRadiotherapy is a feasible treatment modality for elderly HNSCC patients. The relatively low OS compared to high LRC may reflect age and comorbidities. Concomitant chemotherapy should be critically discussed in elderly HNSCC patients.
Effects of inhaled nitric oxide for postoperative hypoxemia in acute type A aortic dissection: a retrospective observational study
Authors: Zhang Hang , Liu Yaoyang , Meng Xiangdong , Yang Dicheng , Shi Sheng , Liu Jian , Yuan Zhongxiang , Gu Tongtong , Han Lin , Lu Fanglin , Xu Zhiyun , Liu Yang , Yu Min 
Published: February 2020

Abstract
Background
Postoperative hypoxemia in acute type A aortic dissection (AADA) is a common complication and is associated with negative outcomes. This study aimed to analyze the efficacy of low-dose (5–10 ppm) inhaled nitric oxide (iNO) in the management of hypoxemia after AADA surgery.

Methods
In this retrospective observational study, Medical records of patients who underwent AADA surgery at two institutions between January 2015 and January 2018 were collected. Patients with postoperative hypoxemia were classified as iNO and control groups. Clinical characteristics and outcomes were compared using a propensity score-matched (PSM) analysis.

Results
Among 436 patients who underwent surgical repair, 187 (42.9%) had hypoxemia and 43 were treated with low-dose iNO. After PSM, patients were included in the iNO treatment (n = 40) and PSM control (n = 94) groups in a 1:3 ratio. iNO ameliorated hypoxemia at 6, 24, 48, and 72 h after initiation, and shortened the durations of ventilator support (39.0 h (31.3–47.8) vs. 69.0 h (47.8–110.3), p < 0.001) and ICU stay (122.0 h (80.8–155.0) vs 179.5 h (114.0–258.0), p < 0.001). There were no significant between-group differences in mortality, complications, or length of hospital stay.

Conclusions
In this study, we found that low-dose iNO improved oxygenation in patients with hypoxemia after AADA surgery and shortened the durations of mechanical ventilation and ICU stay. No significant side effects or increase in postoperative mortality or morbidities were observed with iNO treatment. These findings warrant a randomized multicenter controlled trial to assess the exact efficiency of iNO for hypoxemia after AADA.
Efficacy and safety of endoscopic submucosal tunnel dissection for superficial esophageal neoplastic lesions: a systematic review and meta-analysis
Authors: Peng Wei , Tan Shali , Ren Yutang , Li Huan , Peng Yan , Fu Xiangsheng , Tang Xiaowei 
Published: February 2020

Abstract
Background
Presently, endoscopic submucosal tunnel dissection (ESTD) has been a novel therapy for superficial esophageal neoplastic lesions (SENL), especially for circumferential neoplastic lesions. A number of studies have reported the clinical application of ESTD with promising outcomes. Therefore, we conducted a systematic review and meta-analysis to evaluated the efficacy and safety of ESTD for SENL .

Methods
From 2013 to November 2018, Pubmed, Embase and Cochrane databases were searched to determine studies reporting ESTD treatment of SENL. Weighted pooled rates (WPR) were calculated for en bloc resection, R0 resection and complication of ESTD. Risk ratios (RR) were calculated and pooled to compare the clinical outcomes of ESTD with ESD for SENL.

Results
A total of 9 studies involving 494 patients with 518 esophageal neoplastic lesions were included in our study. WPR for en bloc resection and R0 resection of ESTD was 97.0% (95% CI: 94.7–98.3%) and 84.1% (95% CI: 80.5–87.1%), respectively. WPR for complication was 40.0% (95% CI: 25.8–56.1%). Two studies with 265 patients compared the performance of ESTD with ESD. Pooled RR for en bloc resection and R0 resection was 1.04 (95% CI: 0.95–1.14, P = 0.42) and 1.01 (95% CI: 0.93–1.10, P = 0.73), respectively. Pooled RR for complication was 0.68 (95% CI: 0.46–1.01, P = 0.05).

Conclusion
Our study showed that ESTD is effective for treating SENL with high en bloc resection rate and R0 resection rate, but accompanying by a relatively high complications.
13-Methylberberine improves endothelial dysfunction by inhibiting NLRP3 inflammasome activation via autophagy induction in human umbilical vein endothelial cells
Authors: Peng Zhihua , Zhan Hong , Shao Yijia , Xiong Yan , Zeng Lijin , Zhang Cong , Liu Zhihao , Huang Zhenhua , Su Huanxing , Yang Zhen 
Published: February 2020

Abstract
Background
Atherosclerosis, the underlying cause of the majority of cardiovascular diseases, is a lipid-driven, inflammatory disease of the large arteries. Atherosclerotic cardiovascular disease (ASCVD) threatens human lives due to high morbidity and mortality. Many studies have demonstrated that atherosclerosis is accelerated via activation of the NLRP3 inflammasome. The NLRP3 inflammasome plays a critical role in the development of vascular inflammation and atherosclerosis. In atherosclerotic plaques, excessive generation of reactive oxygen species (ROS) activates the NLRP3 inflammasome. 13-Methylberberine (13-MB) is a newly synthesized compound used in traditional Chinese medicine that has outstanding antibacterial, antitumor, and antiobesity activities, especially anti-inflammatory activity. However, the role of 13-MB in atherosclerosis needs to be explored.

Methods
CCK-8 assays and flow cytometry were conducted to determine the cell viability and apoptotic profiles of human umbilical vein endothelial cells (HUVECs) treated with 13-MB. Carboxy-DCFH-DA and JC-10 assays were used to measure ROS and determine mitochondrial membrane potential. Western blot analysis was performed to investigate proteins that are associated with the NLRP3 inflammasome and autophagy. ELISA was used to detect and quantify inflammatory cytokines related to the NLRP3 inflammasome. Transfection and confocal microscopy were conducted to observe autophagy.

Results
Pretreatment with 13-MB markedly reduced cytotoxicity and apoptosis, as well as intracellular ROS production, in H2O2-induced HUVECs. Moreover, 13-MB showed a protective effect in maintaining mitochondrial membrane potential. 13-MB also suppressed NLRP3 inflammasome activation and promoted autophagy induction in HUVECs.

Conclusion
13-MB exerts cytoprotective effects in an H2O2-induced cell injury model by inhibiting NLRP3 inflammasome activation via autophagy induction in HUVECs. These anti-inflammatory and autophagy induction activities may provide valuable evidence for further investigating the potential role of 13-MB in atherosclerosis.
Significantly different clinical phenotypes associated with mutations in synthesis and transamidase+remodeling glycosylphosphatidylinositol (GPI)-anchor biosynthesis genes
Authors: Carmody Leigh C. , Blau Hannah , Danis Daniel , Zhang Xingman A. , Gourdine Jean-Philippe , Vasilevsky Nicole , Krawitz Peter , Thompson Miles D. , Robinson Peter N. 
Published: February 2020

Abstract
Background
Defects in the glycosylphosphatidylinositol (GPI) biosynthesis pathway can result in a group of congenital disorders of glycosylation known as the inherited GPI deficiencies (IGDs). To date, defects in 22 of the 29 genes in the GPI biosynthesis pathway have been identified in IGDs. The early phase of the biosynthetic pathway assembles the GPI anchor (Synthesis stage) and the late phase transfers the GPI anchor to a nascent peptide in the endoplasmic reticulum (ER) (Transamidase stage), stabilizes the anchor in the ER membrane using fatty acid remodeling and then traffics the GPI-anchored protein to the cell surface (Remodeling stage).

Results
We addressed the hypothesis that disease-associated variants in either the Synthesis stage or Transamidase+Remodeling-stage GPI pathway genes have distinct phenotypic spectra. We reviewed clinical data from 58 publications describing 152 individual patients and encoded the phenotypic information using the Human Phenotype Ontology (HPO). We showed statistically significant differences between the Synthesis and Transamidase+Remodeling Groups in the frequencies of phenotypes in the musculoskeletal system, cleft palate, nose phenotypes, and cognitive disability. Finally, we hypothesized that phenotypic defects in the IGDs are likely to be at least partially related to defective GPI anchoring of their target proteins. Twenty-two of one hundred forty-two proteins that receive a GPI anchor are associated with one or more Mendelian diseases and 12 show some phenotypic overlap with the IGDs, represented by 34 HPO terms. Interestingly, GPC3 and GPC6, members of the glypican family of heparan sulfate proteoglycans bound to the plasma membrane through a covalent GPI linkage, are associated with 25 of these phenotypic abnormalities.

Conclusions
IGDs associated with Synthesis and Transamidase+Remodeling stages of the GPI biosynthesis pathway have significantly different phenotypic spectra. GPC2 and GPC6 genes may represent a GPI target of general disruption to the GPI biosynthesis pathway that contributes to the phenotypes of some IGDs.
Epidemiological and advanced therapeutic approaches to treatment of uveitis in pediatric rheumatic diseases: a systematic review and meta-analysis
Authors: Jari Mohsen , Shiari Reza , Salehpour Omid , Rahmani Khosro 
Published: February 2020

AbstractBackgroundDespite the low prevalence of uveitis in pediatric rheumatic diseases, potential problems as well as high disease burden can complicate its management. In this review, we systematically assessed the epidemiological, etiological, and managerial aspects of uveitis in pediatric rheumatic diseases.MethodsThis current study was conducted in accordance with the established methods and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). We searched the manuscript databases, including Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane for all eligible studies in line with the considered keywords. We also conducted the statistical analysis using the Stata software.ResultsConsidering studies focusing on uveitis in Juvenile Idiopathic Arthritis (JIA) yielded a pooled prevalence of 11.8% (95%CI: 11.2 to 12.4%) for uveitis following JIA. In this regard, the prevalence rate of uveitis related to Behçet,s disease and Systemic Lupus Erythematosus (SLE( was estimated to be 15.0 and 0.8%, respectively. The pooled response rate to Adalimumab and Infliximab was estimated to be 68.0% (95%CI: 65.4 to 70.6%), 64.7% (95%CI: 59.8 to 69.3%), respectively. The documents for the systematical assessment of other biological medications (e.g. Tocilizumab, Daclizumab and Rituximab) were inadequate; however, the mean response rate for these drugs was 59, 75 and 80%, respectively. Our meta-analysis showed a pooled response rate of 40.0% (95%CI, 36.0% to 44.2) to Methotrexate. Significant heterogeneity and significant diffusion bias were demonstrated by reviewing studies.ConclusionsThe pooled prevalence of uveitis in pediatric rheumatic diseases widely varied based on the underlying disease requiring more investigations in different subtypes of rheumatic diseases. The biologic medications, especially Adalimumab are the most effective treatments for uveitis in pediatric rheumatic diseases; however, a combination of the safe, available alternatives is preferred to achieve the most desirable treatment response.
Rugby Fans in Training New Zealand (RUFIT-NZ): protocol for a randomized controlled trial to assess the effectiveness and cost-effectiveness of a healthy lifestyle program for overweight men delivered through professional rugby clubs in New Zealand
Authors: Maddison Ralph , Hargreaves Elaine Anne , Jiang Yannan , Calder Amanda Jane , Wyke Sally , Gray Cindy M. , Hunt Kate , Lubans David , Eyles Helen , Draper Nick , Heke Ihirangi , Kara Stephen , Sundborn Gerhard , Arandjus Claire , Jenkins Matthew , Marsh Samantha 
Published: February 2020

Abstract
Background
A healthy lifestyle program that appeals to, and supports, obese New Zealand (NZ) European, Māori (indigenous) and Pasifika men to achieve weight loss is urgently needed. In Scotland, Football Fans in Training (FFIT), a weight management and healthy lifestyle program for overweight and obese men aged 35–65 years , delivered by community coaching staff at professional football clubs, has been shown to be beneficial and cost-effective. A pilot program inspired by FFIT but delivered by professional rugby clubs in NZ (n = 96) was shown to be effective in weight loss, improved physiological outcomes, and adherence to healthy lifestyle behaviors in overweight and obese men. The objective of this trial is to determine the effectiveness and cost-effectiveness of the Rugby Fans in Training New Zealand (RUFIT-NZ) program.

Methods
A pragmatic, two-arm, multi-center, randomized controlled trial involving 308 overweight and obese men aged 30–65 years, randomized to either an intervention group (n = 154) or a wait-list control group (n = 154). The intervention-group participated in the 12-week RUFIT-NZ program, a gender-sensitized, healthy lifestyle intervention adapted to the environment and cultural diversity of NZ and delivered through professional rugby clubs. Participants in the intervention group undergo physical training sessions, in addition to workshop-based sessions to learn about nutrition, physical activity, sleep, sedentary behavior, and a range of behavior-change strategies for sustaining a healthier lifestyle. The control group receives the program after 52 weeks. The primary outcome is change in body weight from baseline to 52 weeks. Secondary outcomes include change in body weight at 12 weeks; waist circumference, blood pressure, fitness, and lifestyle behaviors at 12 and 52 weeks; and cost-effectiveness. A process evaluation informed by the RE-AIM framework will evaluate potential implementation of RUFIT-NZ as an ongoing program in NZ after the trial.

Discussion
This trial will investigate the effectiveness and cost-effectiveness of the RUFIT-NZ program in overweight and obese NZ men.

Trial registration
Australia New Zealand Clinical Trials Registry, ACTRN12619000069156. Registered on 18 January 2019, according to the World Health Organization Trial Registration Data Set. Universal Trial Number, U1111-1245-0645.
Preventing early childhood caries with silver diamine fluoride: study protocol for a randomised clinical trial
Authors: Gao Sherry Shiqian , Chen Kitty Jieyi , Duangthip Duangporn , Wong May Chun Mei , Lo Edward Chin Man , Chu Chun Hung 
Published: February 2020

Abstract
Background
Silver diamine fluoride (SDF) solution is effective in arresting early childhood caries (ECC). Previous studies have suggested that it might exert a preventive effect in managing ECC. However, no well-designed clinical trials have yet been performed to study the effect of SDF on caries prevention. The objective of this randomised clinical trial is to determine whether 38% SDF solution is superior to 5% sodium fluoride (NaF) varnish in preventing new carious lesions in primary anterior teeth.

Methods/design
This is a phase II, single-centre, randomised, double-blind, active-controlled, parallel-group pragmatic trial. The hypothesis tested is that 38% SDF would be more effective than 5% NaF in preventing new caries development in primary anterior teeth. Approximately 730 3-year-old children who are generally healthy and with parental consent will be recruited from Hong Kong kindergartens. This sample size will be sufficient for appropriate statistical analysis of a superiority trial with 90% power, allowing for a 20% drop-out rate. Stratified randomisation will be adopted for allocating the intervention. The intervention will either be 38% SDF or 5% NaF (as a positive control) therapy on primary upper anterior teeth. A single trained examiner will conduct a dental examination every 6 months until 30 months in kindergarten. Another operator will provide fluoride therapy immediately after each dental examination. The examiner, children and children’s parents will be blinded to the treatment allocation. A questionnaire survey will be conducted to study the children’s oral health-related behaviours and socioeconomic backgrounds. Chi-square tests, t tests, regression analyses and survival analyses will be adopted for data analysis.

Discussion
The effectiveness of 38% SDF in preventing ECC remains uncertain. If the results are as anticipated, care standards using 5% NaF for ECC prevention will be changed. In addition, the results will be widely available and increase the adoption of SDF in other countries to reduce the global burden of ECC.

Trial registration
ClinicalTrials.gov, NCT04075474. Registered on 30 Aug 2019.
Fed-batch enzymatic hydrolysis of alkaline organosolv-pretreated corn stover facilitating high concentrations and yields of fermentable sugars for microbial lipid production
Authors: Gong Zhiwei , Wang Xuemin , Yuan Wei , Wang Yanan , Zhou Wenting , Wang Guanghui , Liu Yi 
Published: February 2020

Abstract
Background
Lignocellulosic biomass has been commonly regarded as a potential feedstock for the production of biofuels and biochemicals. High sugar yields and the complete bioconversion of all the lignocellulosic sugars into valuable products are attractive for the utilization of lignocelluloses. It is essential to pretreat and hydrolyze lignocelluloses at high solids loadings during industrial processes, which is more economical and environmentally friendly as capital cost, energy consumption, and water usage can be reduced. However, oligosaccharides are inevitably released during the high solids loading enzymatic hydrolysis and they are more recalcitrant than monosaccharides for microorganisms.

Results
A fed-batch enzymatic hydrolysis of corn stover pretreated by the sodium hydroxide–methanol solution (SMs) at high solids loading was demonstrated to reach the high concentrations and yields of fermentable sugars. Glucose, xylose, cello-oligosaccharides, and xylo-oligosaccharides achieved 146.7 g/L, 58.7 g/L, 15.6 g/L, and 24.7 g/L, respectively, when the fed-batch hydrolysis was started at 12% (w/v) solids loading, and 7% fresh substrate and a standardized blend of cellulase, β-glucosidase, and hemicellulase were fed consecutively at 3, 6, 24, and 48 h to achieve a final solids loading of 40% (w/v). The total conversion of glucan and xylan reached 89.5% and 88.5%, respectively, when the oligosaccharides were taken into account. Then, a fed-batch culture on the hydrolysates was investigated for lipid production by Cutaneotrichosporon oleaginosum. Biomass, lipid content, and lipid yield were 50.7 g/L, 61.7%, and 0.18 g/g, respectively. The overall consumptions of cello-oligosaccharides and xylo-oligosaccharides reached 74.1% and 68.2%, respectively.

Conclusions
High sugars concentrations and yields were achieved when the enzyme blend was supplemented simultaneously with the substrate at each time point of feeding during the fed-batch enzymatic hydrolysis. Oligosaccharides were co-utilized with monosaccharides during the fed-batch culture of C. oleaginosum. These results provide a promising strategy to hydrolyze alkaline organosolv-pretreated corn stover into fermentable sugars with high concentrations and yields for microbial lipid production.
Cardiac point-of-care ultrasound reveals unexpected, life-threatening findings in two children
Authors: Doniger Stephanie J. , Ng Nicholas 
Published: February 2020

Abstract
Background
The diagnosis of pericardial effusion with cardiac tamponade can at times be elusive in pediatric patients since it is relatively uncommon. Point-of-care ultrasound (POCUS) can readily be performed at the bedside to assess for the presence of a pericardial effusion, tamponade, and can occasionally yield unexpected results.

Case presentation
Two cases where POCUS unexpectedly identified pericardial effusions, with one patient who also had an anterior mediastinal mass.

Conclusions
Though underutilized, cardiac POCUS in children can be immediately life-saving and drastically change the clinical management at the patient’s bedside.
Autologous plasma versus fetal calf serum as a supplement for the culture of neutrophils
Authors: Alipour Razieh , Fatemi Alimohammad , Alsahebfosul Fereshteh , Andalib Alireza , Pourazar Abbasali 
Published: February 2020

AbstractObjectiveCurrently, the replacement of fetal calf serum (FCS) by a more suitable alternative is a sought aim in the field of tissue and cell culture research. Autologous plasma (AP) and especially autologous serum (AS) have been shown to be effective substitutes of FCS in culture media for some of the cell types. Nevertheless, there is no comparative data on the most appropriate supplement for cell media in neutrophil studies, it is now unclear whether AP have a relatively equal, superior or inferior performance to FCS in neutrophil cell culture. In the present study, human blood neutrophils were isolated and cultured in FCS- or AP-supplemented medium. After 12, 36 and 60 h of incubation, cell viability, oxidative burst and CD11b expression were determined by flow cytometry.ResultsCompared to the culture of neutrophils in FCS 10% medium, the culture of neutrophils in a medium with AP 10% could prolong their life span without affecting their function. The findings introduce AP as a better supplement for human neutrophil cell culture than FCS and propose a simple and economical procedure for neutrophil isolation and culture.