bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and effectiveness of riociguat for chronic thromboembolic pulmonary hypertension in real‐world clinical practice: interim data from post‐marketing surveillance in Japan
Authors: Tanabe Nobuhiro , Ogo Takeshi , Hatano Masaru , Kigawa Ayaka , Sunaya Toshiyuki , Sato Shoichiro 
Published: July 2020

This multicenter, prospective, non‐interventional study (ClinicalTrials.gov: NCT02117791) evaluated the safety and effectiveness of riociguat for chronic thromboembolic pulmonary hypertension in Japanese clinical practice, registering all patients with chronic thromboembolic pulmonary hypertension treated with riociguat following its launch in Japan in April 2014. Safety was assessed by analyzing the adverse drug reactions. Effectiveness measurements included the assessment of change in World Health Organization functional class, six‐minute walk test, and hemodynamics. Overall, 1031 patients were included in the safety analysis with 811 (78.7%) patients in World Health Organization functional class II/III. The mean treatment duration was 591.4 days (median 441.0 days). Adverse drug reactions were reported in 19.5% of patients, the most common being hypotension (5.9%), headache (3.0%), dizziness (1.9%), and gastroesophageal reflux disease (1.5%). Serious adverse drug reactions were reported in 2.1% of patients. Estimated survival was 97.0% at one year, 95.8% at two years, and 94.4% at three years. The effectiveness analysis (n = 1027) showed significant increases from baseline in six‐minute walking distance, and significant reductions from baseline in mean pulmonary arterial pressure and pulmonary vascular resistance. These interim results of riociguat in Japanese patients with chronic thromboembolic pulmonary hypertension demonstrated a safety profile that was generally consistent with those of pivotal clinical studies. The study is ongoing, and will continue to provide insights into the safety and effectiveness of riociguat in real‐world practice.
Radiofrequency denervation of the lumbar facet joints: guidelines for the RADICAL randomised controlled trial
Authors: Price Cathy , Reeves Barney , Ahmad Alia , Baloch Mohjir , Baranidharan Ganesan , Correa Robin , McCormick Tim , Sharma Manohar , Veemarajan Bala , Grimwood Margot , Pirie Katrina Ishbel , Wylde Vikki 
Published: July 2020

Background and aim: The RADICAL trial has been funded by the National Institute for Health Research (NIHR) to evaluate the clinical and cost-effectiveness of radiofrequency denervation (RFD) for low back pain. Recommendations have been published which aim to standardise selection of patients and RFD technique. However, it is important to ensure these recommendations are acceptable to clinicians within the context of the trial. The aim of this work was to develop standardised criteria for the trial entry and RFD technique for implementation within the RADICAL trial. Methods: Fourteen pain clinicians completed a survey, which involved reviewing the current recommendations and indicating whether they disagreed with any of the recommendations and if so why. Responses were collated and presented at a half-day workshop with 14 attendees. During the workshop, the National Low Back and Radicular Pain Pathway (NLBRPP) guidelines for patient selection and an article by Eldabe and colleagues presenting recommendations on the RFD technique were reviewed. Attendees discussed whether each component of the recommendations should be mandatory, mandatory with alteration or clarification or optional within the RADICAL trial. Results: Attendees agreed during the workshop that 5 of the 10 criteria for patient selection described in the NLBRPP should be mandatory within the RADICAL trial. Three were agreed as mandatory criteria but required further clarification, one of which involved defining a positive response to a diagnostic medial branch block as ⩾60% pain relief. Two criteria had optional components. After reviewing the recommendations on the RFD technique from Eldabe and colleagues, seven components were agreed as mandatory, three were mandatory with alterations and three were optional. Conclusion: When evaluating complex interventions, such as RFD, it is important to ensure agreement and clarity on the clinical protocol, so that the intervention can be reproduced, if found to be effective.
Characterization of the effluents condensated by volatile organic compounds during heat-treated rubberwood process
Authors: Li Tongtong , Li Guanjun , Li Jianing , Li Xiaowen , Lu Quanji , Li Min 
Published: July 2020

AbstractHeat treatment was an eco-friendly modification technology for rubberwood, without the addition of chemical reagents into the wood and wood performance has been improved remarkably. Many effluents are generated from heat-treated rubberwood process, which were rarely researched. The effluents contain relatively high content of volatile organic compounds, which may seriously threaten the environment and human health. In this study, effluents condensated during different heat-treated stages (125 ℃, 145 ℃, 175 ℃, 185 ℃, 215 ℃) and frequently used industrial heat treatment production technology (185 ℃/3 h, 215 ℃/3 h) were characterized by gas chromatography–mass spectrometry (GC–MS). The effluents were classified as aldehydes, phenols, esters, ketones, acids, alcohols, alkanes, anhydride, aromatics and compounds released the most during all heat-treated stages were aldehydes. With the temperature increased, the relative amounts of aldehydes decreased, while the ketones, esters and aromatics increased under acidic constituents (pH ranged from 4.17 to 2.47) and high moisture condition. The vanillin and coniferyl aldehyde accounted for much higher proportion in the aldehydes. The mass loss of rubberwood was larger under 215 ℃/3 h (16.61%), correspondingly the effluents had more kinds of compounds at 215 ℃. These results would provide guidance for research of effluent disposal and transform biomass residues into valuable things.
Machine learning based imputation techniques for estimating phylogenetic trees from incomplete distance matrices
Authors: Bhattacharjee Ananya , Bayzid Md. Shamsuzzoha 
Published: July 2020

Abstract
Background
With the rapid growth rate of newly sequenced genomes, species tree inference from genes sampled throughout the whole genome has become a basic task in comparative and evolutionary biology. However, substantial challenges remain in leveraging these large scale molecular data. One of the foremost challenges is to develop efficient methods that can handle missing data. Popular distance-based methods, such as NJ (neighbor joining) and UPGMA (unweighted pair group method with arithmetic mean) require complete distance matrices without any missing data.

Results
We introduce two highly accurate machine learning based distance imputation techniques. These methods are based on matrix factorization and autoencoder based deep learning architectures. We evaluated these two methods on a collection of simulated and biological datasets. Experimental results suggest that our proposed methods match or improve upon the best alternate distance imputation techniques. Moreover, these methods are scalable to large datasets with hundreds of taxa, and can handle a substantial amount of missing data.

Conclusions
This study shows, for the first time, the power and feasibility of applying deep learning techniques for imputing distance matrices. Thus, this study advances the state-of-the-art in phylogenetic tree construction in the presence of missing data. The proposed methods are available in open source form at https://github.com/Ananya-Bhattacharjee/ImputeDistances.
Integrating RNA-Seq with GWAS reveals novel insights into the molecular mechanism underpinning ketosis in cattle
Authors: Yan Ze , Huang Hetian , Freebern Ellen , Santos Daniel J. A. , Dai Dongmei , Si Jingfang , Ma Chong , Cao Jie , Guo Gang , Liu George E. , Ma Li , Fang Lingzhao , Zhang Yi 
Published: July 2020

Abstract
Background
Ketosis is a common metabolic disease during the transition period in dairy cattle, resulting in long-term economic loss to the dairy industry worldwide. While genetic selection of resistance to ketosis has been adopted by many countries, the genetic and biological basis underlying ketosis is poorly understood.

Results
We collected a total of 24 blood samples from 12 Holstein cows, including 4 healthy and 8 ketosis-diagnosed ones, before (2 weeks) and after (5 days) calving, respectively. We then generated RNA-Sequencing (RNA-Seq) data and seven blood biochemical indicators (bio-indicators) from leukocytes and plasma in each of these samples, respectively. By employing a weighted gene co-expression network analysis (WGCNA), we detected that 4 out of 16 gene-modules, which were significantly engaged in lipid metabolism and immune responses, were transcriptionally (FDR < 0.05) correlated with postpartum ketosis and several bio-indicators (e.g., high-density lipoprotein and low-density lipoprotein). By conducting genome-wide association signal (GWAS) enrichment analysis among six common health traits (ketosis, mastitis, displaced abomasum, metritis, hypocalcemia and livability), we found that 4 out of 16 modules were genetically (FDR < 0.05) associated with ketosis, among which three were correlated with postpartum ketosis based on WGCNA. We further identified five candidate genes for ketosis, including GRINA, MAF1, MAFA, C14H8orf82 and RECQL4. Our phenome-wide association analysis (Phe-WAS) demonstrated that human orthologues of these candidate genes were also significantly associated with many metabolic, endocrine, and immune traits in humans. For instance, MAFA, which is involved in insulin secretion, glucose response, and transcriptional regulation, showed a significantly higher association with metabolic and endocrine traits compared to other types of traits in humans.

Conclusions
In summary, our study provides novel insights into the molecular mechanism underlying ketosis in cattle, and highlights that an integrative analysis of omics data and cross-species mapping are promising for illustrating the genetic architecture underpinning complex traits.
Characterization of the bacterial communities of psyllids associated with Rutaceae in Bhutan by high throughput sequencing
Authors: Morrow Jennifer L. , Om Namgay , Beattie George A. C. , Chambers Grant A. , Donovan Nerida J. , Liefting Lia W. , Riegler Markus , Holford Paul 
Published: July 2020

Abstract
Background
Several plant-pathogenic bacteria are transmitted by insect vector species that often also act as hosts. In this interface, these bacteria encounter plant endophytic, insect endosymbiotic and other microbes. Here, we used high throughput sequencing to examine the bacterial communities of five different psyllids associated with citrus and related plants of Rutaceae in Bhutan: Diaphorina citri, Diaphorina communis, Cornopsylla rotundiconis, Cacopsylla heterogena and an unidentified Cacopsylla sp.

Results
The microbiomes of the psyllids largely comprised their obligate P-endosymbiont ‘Candidatus Carsonella ruddii’, and one or two S-endosymbionts that are fixed and specific to each lineage. In addition, all contained Wolbachia strains; the Bhutanese accessions of D. citri were dominated by a Wolbachia strain first found in American isolates of D. citri, while D. communis accessions were dominated by the Wolbachia strain, wDi, first detected in D. citri from China. The S-endosymbionts from the five psyllids grouped with those from other psyllid taxa; all D. citri and D. communis individuals contained sequences matching ‘Candidatus Profftella armatura’ that has previously only been reported from other Diaphorina species, and the remaining psyllid species contained OTUs related to unclassified Enterobacteriaceae. The plant pathogenic ‘Candidatus Liberibacter asiaticus’ was found in D. citri but not in D. communis. Furthermore, an unidentified ‘Candidatus Liberibacter sp.’ occurred at low abundance in both Co. rotundiconis and the unidentified Cacopsylla sp. sampled from Zanthoxylum sp.; the status of this new liberibacter as a plant pathogen and its potential plant hosts are currently unknown. The bacterial communities of Co. rotundiconis also contained a range of OTUs with similarities to bacteria previously found in samples taken from various environmental sources.

Conclusions
The bacterial microbiota detected in these Bhutanese psyllids support the trends that have been seen in previous studies: psyllids have microbiomes largely comprising their obligate P-endosymbiont and one or two S-endosymbionts. In addition, the association with plant pathogens has been demonstrated, with the detection of liberibacters in a known host, D. citri, and identification of a putative new species of liberibacter in Co. rotundiconis and Cacopsylla sp.
Calcium regulates the mycophagous ability of Burkholderia gladioli strain NGJ1 in a type III secretion system-dependent manner
Authors: Yadav Sunil Kumar , Das Joyati , Kumar Rahul , Jha Gopaljee 
Published: July 2020

Abstract
Background
A rice associated bacterium Burkholderia gladioli strain NGJ1 demonstrates mycophagy, a phenomenon wherein bacteria feed on fungi. Previously, we have reported that NGJ1 utilizes type III secretion system (T3SS) to deliver a prophage tail-like protein (Bg_9562) into fungal cells to establish mycophagy.

Results
In this study, we report that calcium ion concentration influences the mycophagous ability of NGJ1 on Rhizoctonia solani, an important fungal pathogen. The calcium limiting condition promotes mycophagy while high calcium environment prevents it. The expression of various T3SS apparatus encoding genes of NGJ1 was induced and secretion of several potential T3SS effector proteins (including Bg_9562) into extracellular milieu was triggered under calcium limiting condition. Using LC-MS/MS proteome analysis, we identified several calcium regulated T3SS effector proteins of NGJ1. The expression of genes encoding some of these effector proteins was upregulated during mycophagous interaction of NGJ1 with R. solani. Further, mutation of one of these genes (endo-β-1, 3- glucanase) rendered the mutant NGJ1 bacterium defective in mycophagy while complementation with full length copy of the gene restored its mycophagous activity.

Conclusion
Our study provides evidence that low calcium environment triggers secretion of various T3SS effectors proteins into the extracellular milieu and suggests the importance of cocktail of these proteins in promoting mycophagy.
WHO Trial Registration Data Set (TRDS) extension for traditional Chinese medicine 2020: recommendations, explanation, and elaboration
Authors: Zhang Xuan , Lan Liang , Chan Jacky C. P. , Zhong Linda L. D. , Cheng Chung-Wah , Lam Wai-Ching , Tian Ran , Zhao Chen , Wu Tai-Xiang , Shang Hong-Cai , Lyu Ai-Ping , Bian Zhao-Xiang 
Published: July 2020

AbstractBackgroundAlthough the WHO Trial Registration Data Set (TRDS) has been published for many years, the quality of clinical trial registrations with traditional Chinese medicine (TCM) is still not satisfactory, especially about the inadequate reporting on TCM interventions. The development of the WHO TRDS for TCM Extension 2020 (WHO TRDS-TCM 2020) aims to address this inadequacy.MethodsA group of clinical experts, methodologists, epidemiologists, and editors has developed this WHO TRDS-TCM 2020 through a comprehensive process, including the baseline survey, draft of the initial items, three-round of Delphi survey, solicitation of comments, revision, and finalization.ResultsThe WHO TRDS-TCM 2020 statement extends the latest version (V.1.3.1) of TRDS published in November 2017. The checklist includes 11 extended items (including subitems), namely Source(s) of Monetary or Material Support (Item 4), Scientific Title (Item 10a and 10b), Countries of Recruitment (Item 11), Health Condition(s) or Problem(s) Studied (Item 12), Intervention(s) (Item 13a, 13b and 13c), Key Inclusion and Exclusion Criteria (Item 14), Primary and Key Secondary Outcomes (Item 19 to 20), and Lay Summary (Item B1). For Item 13 (Interventions), three common TCM interventions--i.e., Chinese herbal medicine formulas, acupuncture and moxibustion—are elaborated.ConclusionsThe group hopes that the WHO TRDS-TCM 2020 can improve the reporting quality and transparency of TCM trial registrations, assist registries in assessing the registration quality of TCM trials, and help readers understand TCM trial design.
Plasma Lipidome, PNPLA3 polymorphism and hepatic steatosis in hereditary hemochromatosis
Authors: Seeßle Jessica , Gan-Schreier Hongying , Kirchner Marietta , Stremmel Wolfgang , Chamulitrat Walee , Merle Uta 
Published: July 2020

Abstract
Background
Hereditary hemochromatosis (HH) is an autosomal recessive genetic disorder with increased intestinal iron absorption and therefore iron Overload. iron overload leads to increased levels of toxic non-transferrin bound iron which results in oxidative stress and lipid peroxidation. The impact of iron on lipid metabolism is so far not fully understood. The aim of this study was to investigate lipid metabolism including lipoproteins (HDL, LDL), neutral (triglycerides, cholesterol) and polar lipids (sphingo- and phospholipids), and PNPLA3 polymorphism (rs738409/I148M) in HH.

Methods
We conducted a cohort study of 54 subjects with HH and 20 healthy subjects. Patients were analyzed for their iron status including iron, ferritin, transferrin and transferrin saturation and serum lipid profile on a routine follow-up examination.

Results
HH group showed significantly lower serum phosphatidylcholine (PC) and significantly higher phosphatidylethanolamine (PE) compared to healthy control group. The ratio of PC/PE was clearly lower in HH group indicating a shift from PC to PE. Triglycerides were significantly higher in HH group. No differences were seen for HDL, LDL and cholesterol. Hepatic steatosis was significantly more frequent in HH. PNPLA3 polymorphism (CC vs. CG/GG) did not reveal any significant correlation with iron and lipid parameters including neutral and polar lipids, grade of steatosis and fibrosis.

Conclusion
Our study strengthens the hypothesis of altered lipid metabolism in HH and susceptibility to nonalcoholic fatty liver disease. Disturbed phospholipid metabolism may represent an important factor in pathogenesis of hepatic steatosis in HH.
Not so FAST. Commentary on the article “Appraisal of the faecal haemoglobin, age and sex test (FAST) score in assessment of patients with lower bowel symptoms: an observational study”
Authors: Cubiella Joaquín 
Published: July 2020

AbstractA recent study by Digby et al. in BMC Gastroenterology evaluated the faecal haemoglobin, age and sex test (FAST) score in the assessment of patients with lower bowel symptoms attended in primary healthcare. This article is a valuable source of information but the conclusions must be carefully assessed. Authors evaluated the FAST score threshold with a 99% sensitivity (≥ 2.12) for colorectal cancer (CRC). Although the number of patients meeting this criteria is high, 53.5% of the patients not referred initially to secondary healthcare, the results on the patients referred to colonoscopy validate the prediction model. The sensitivity and the specificity for CRC detection were 99.0 and 23.2% with a positive and negative predictive value of 8.0 and 99.7%. Additionally, the sensitivity and the specificity for significant bowel disease were 96.1 and 26.2% with a positive and negative predictive value of 24.3 and 96.1%, consistent with our initial results. To conclude, although we need the information regarding the risk of CRC in those patients not referred to colonoscopy, a FAST Score < 2.12 allows to determine a group of patients with a low risk of CRC detection that requires no further evaluation.
Endoscopic severe mucosal atrophy indicates the presence of gastric cancer after Helicobacter pylori eradication -analysis based on the Kyoto classification
Authors: Ohno Akiko , Miyoshi Jun , Kato Atsushi , Miyamoto Naohiko , Yatagai Takahito , Hada Yu , Kusuhara Mitsunori , Jimbo Yoko , Ida Yosuke , Tokunaga Kengo , Okamoto Susumu , Hisamatsu Tadakazu 
Published: July 2020

Abstract
Background
Gastric cancer after Helicobacter pylori (HP) eradication is a crucial clinical challenge today as HP eradication therapy is widely performed. Detecting gastric cancer after HP eradication tends to be difficult with normal white-light endoscopy. In the present study, we aimed to identify easily-evaluated endoscopic findings that indicate the presence of gastric cancer after HP eradication so that endoscopists can consider additional detailed examinations at the site.

Methods
We analyzed the endoscopic images of 43 patients who underwent endoscopic submucosal dissection for early gastric cancer after HP eradication and 119 patients with an HP eradication history who underwent esophagogastroduodenoscopy for a medical checkup. Endoscopic findings were evaluated according to the Kyoto classification of gastritis (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness) and map-like redness.

Results
Patients with gastric cancer had significantly higher total Kyoto risk scores; more atrophy, intestinal metaplasia, and diffuse redness; and a significantly higher prevalence of map-like redness compared with those without gastric cancer, in the univariate analyses. We used logistic regression analysis with forward selection based on the likelihood ratio to develop a model using atrophy and diffuse redness. Receiver operating characteristic analysis showed that a score of A2 in the Kyoto classification of gastritis (open-type atrophic pattern in the Kimura–Takemoto classification) was an endoscopic marker for the presence of post-HP-eradication gastric cancer.

Conclusions
Endoscopic severe gastric mucosal atrophy is useful to screen patients for gastric cancer after HP eradication.
Dysbiosis, gut barrier dysfunction and inflammation in dementia: a pilot study
Authors: Stadlbauer Vanessa , Engertsberger Lara , Komarova Irina , Feldbacher Nicole , Leber Bettina , Pichler Gerald , Fink Nicole , Scarpatetti Monika , Schippinger Walter , Schmidt Reinhold , Horvath Angela 
Published: July 2020

AbstractBackgroundDementia is an increasing public health threat worldwide. The pathogenesis of dementia has not been fully elucidated yet. Inflammatory processes are hypothesized to play an important role as a driver for cognitive decline but the origin of inflammation is not clear. We hypothesize that disturbances in gut microbiome composition, gut barrier dysfunction, bacterial translocation and resulting inflammation are associated with cognitive dysfunction in dementia.MethodsTo test this hypothesis, a cohort of 23 patients with dementia and 18 age and sex matched controls without cognitive impairments were studied. Gut microbiome composition, gut barrier dysfunction, bacterial translocation and inflammation were assessed from stool and serum samples. Malnutrition was assessed by Mini Nutritional Assessment Short Form (MNA-SF), detailed information on drug use was collected. Microbiome composition was assessed by 16S rRNA sequencing, QIIME 2 and Calypso 7.14 tools.ResultsDementia was associated with dysbiosis characterized by differences in beta diversity and changes in taxonomic composition. Gut permeability was increased as evidenced by increased serum diamine oxidase (DAO) levels and systemic inflammation was confirmed by increased soluble cluster of differentiation 14 levels (sCD14). BMI and statin use had the strongest impact on microbiome composition.ConclusionDementia is associated with changes in gut microbiome composition and increased biomarkers of gut permeability and inflammation.Lachnospiraceae NK4A136 groupas potential butyrate producer was reduced in dementia. Malnutrition and drug intake were factors, that impact on microbiome composition. Increasing butyrate producing bacteria and targeting malnutrition may be promising therapeutic targets in dementia.Trial registrationNCT03167983.