bluuebunny/crossref_metadata_2025 huggingface dataset:
Home vs hospital treatment of low-risk venous thromboembolism: a systematic review and meta-analysis
Authors: Khatib Rasha , Ross Stephanie , Kennedy Sean Alexander , Florez Ivan D. , Ortel Thomas L. , Nieuwlaat Robby , Neumann Ignacio , Witt Daniel M. , Schulman Sam , Manja Veena , Beyth Rebecca , Clark Nathan P. , Wiercioch Wojtek , Schünemann Holger J. , Zhang Yuqing
Published: February 2020

Increasing evidence supports the safety and effectiveness of managing low-risk deep vein thrombosis (DVT) or pulmonary embolism (PE) in outpatient settings. We performed a systematic review to assess safety and effectiveness of managing patients with DVT or PE at home compared with the hospital. Medline, Embase, and Cochrane databases were searched up to July 2019 for relevant randomized clinical trials (RCTs), and prospective cohort studies. Two investigators independently screened titles and abstracts of identified citations and extracted data from relevant full-text papers. Risk ratios (RRs) were calculated, and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Seven RCTs (1922 patients) were included in meta-analyses on managing patients with DVT. Pooled estimates indicated decreased risk of PE (RR = 0.64; 95% confidence interval [CI], 0.44-0.93) and recurrent DVT (RR = 0.61; 95% CI, 0.42-0.90) for home management, both with moderate certainty of the evidence. Reductions in mortality and major bleeding were not significant, both with low certainty of the evidence. Two RCTs (445 patients) were included in meta-analyses on home management of low-risk patients with PE. Pooled estimates indicated no significant difference in all-cause mortality, recurrent PE, and major bleeding, all with low certainty of the evidence. Results of pooled estimates from 3 prospective cohort studies (234 patients) on home management of PE showed similar results. Our findings indicate that low-risk DVT patients had similar or lower risk of patient-important outcomes with home treatment compared with hospital treatment. In patients with low-risk PE, there was important uncertainty about a difference between home and hospital treatment.
The stability of the ADO score among UK COPD patients from The Health Improvement Network
Authors: Keene Spencer J. , Adab Peymane , de Vries Frank , Franssen Frits M.E. , Sitch Alice , Martin James , Marshall Tom , Jordan Rachel
Published: February 2020

The ADO (age, dyspnoea, airflow obstruction) score predicts 3-year overall mortality among chronic obstructive pulmonary disease (COPD) patients. Information on the changes in COPD prognostic scores is sparse and it is unclear if the ADO score should be measured serially.

We followed 4804 UK COPD patients with three or more ADO measurements from The Health Improvement Network (2005–2014) in a retrospective open cohort design. Patient's ADO scores were calculated once per year unless an obstruction or dyspnoea measurement was missing. Cox regression models assessed the independent role of serial ADO scores on mortality. The associations between baseline patient characteristics and long-term change in ADO scores were assessed using linear mixed effect models.

Fewer than 7% of patients had worsened (i.e.increased) by ≥1 point per year after a median follow-up of 4.4 years. There was strong evidence that patients with more rapid worsening in ADO scores had increased mortality (hazard ratio 2.00 (95% CI 1.59–2.52) per 1 point increase in ADO per year). More rapid ADO score worsening was seen among current smokers (rate difference 0.059 (95% CI 0.031–0.087); p=0.001) and ex-smokers (0.028 (95% CI 0.003–0.054); p=0.032) and patients with depression (0.038 (95% CI 0.005–0.071); p=0.022), while overweight (−0.0347 (95% CI −0.0544– −0.0150); p=0.001) and obese (−0.0412 (95% CI −0.0625– −0.0198); p<0.001) patients had a less rapid ADO score worsening.

Serial assessment of the ADO score can identify patients with worsening disease and update their prognosis, especially for patients who smoke, are depressed or have lower body mass index.
Mechanically ventilated patients exhibit decreased particle flow in exhaled breath as compared to normal breathing patients
Authors: Broberg Ellen , Andreasson Jesper , Fakhro Mohammed , Olin Anna-Carin , Wagner Darcy , Hyllén Snejana , Lindstedt Sandra
Published: February 2020

Introduction

In this cohort study, we evaluated whether the particles in exhaled air (PExA) device can be used in conjunction with mechanical ventilation during surgery. The PExA device consists of an optical particle counter and an impactor that collects particles in exhaled air. Our aim was to establish the feasibility of the PExA device in combination with mechanical ventilation (MV) during surgery and if collected particles could be analysed. Patients with and without nonsmall cell lung cancer (NSCLC) undergoing lung surgery were compared to normal breathing (NB) patients with NSCLC.

Methods

A total of 32 patients were included, 17 patients with NSCLC (MV-NSCLC), nine patients without NSCLC (MV-C) and six patients with NSCLC and not intubated (NB). The PEx samples were analysed for the most common phospholipids in surfactant using liquid-chromatography-mass-spectrometry (LCMS).

Results

MV-NSCLC and MV-C had significantly lower numbers of particles exhaled per minute (particle flow rate; PFR) compared to NB. MV-NSCLC and MV-C also had a siginificantly lower amount of phospholipids in PEx when compared to NB. MV-NSCLC had a significantly lower amount of surfactant A compared to NB.

Conclusion

We have established the feasibility of the PExA device. Particles could be collected and analysed. We observed lower PFR from MV compared to NB. High PFR during MV may be due to more frequent opening and closing of the airways, known to be harmful to the lung. Online use of the PExA device might be used to monitor and personalise settings for mechanical ventilation to lower the risk of lung damage.
Performance of pulmonary artery dimensions measured on high-resolution computed tomography scan for identifying pulmonary hypertension
Authors: Ratanawatkul Pailin , Oh Andrea , Richards J. Caleb , Swigris Jeffrey J.
Published: February 2020

Background

On high-resolution computed tomography (HRCT), pulmonary artery (PA) dimensions may hint at the presence of pulmonary hypertension. We aimed to determine how accurately various measures of the PA, as viewed on HRCT, predict right heart catheterisation (RHC)-confirmed pulmonary hypertension.

Methods

We retrospectively reviewed patients who had HRCT and RHC between 2010 and 2018. Analyses considered respiratory cycle, pulmonary hypertension diagnostic criteria, time between HRCT and RHC, and subgroup analysis in interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD).

Results

Of 620 patients, 375 had pulmonary hypertension. For pulmonary hypertension (defined as mean PA pressure (mPAP) ≥25 mmHg) and from HRCT performed within 60 days of RHC, main PA diameter (MPAD) ≥29 mm had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 88%, 42%, 0.70 and 0.70, respectively, while ratio of the diameter of the PA to the diameter of the ascending aorta (PA:Ao) ≥1.0 showed 53%, 85%, 0.84 and 0.54, respectively. In general, results were similar when the interval between HRCT and RHC varied from 7 to 60 days and when measured on expiratory images. In ILD, the sensitivity of MPAD was higher; in COPD, the specificity of PA:Ao was higher. There was moderately positive correlation between mPAP and inspiratory MPAD, PA:Ao, right PA diameter (RPAD), left PA diameter (LPAD) and (RPAD+LPAD)/2 (r=0.48, 0.51, 0.34, 0.34 and 0.36, respectively), whereas there was weak negative correlation between mPAP and PA angle (r= −0.24).

Conclusions

Findings on HRCT may assist in the diagnosis of RHC-confirmed pulmonary hypertension. MPAD ≥29 mm had high sensitivity and PA:Ao ≥1.0 had high specificity. Compared with the entire cohort, MPAD had greater sensitivity in ILD and PA:Ao had higher specificity in COPD.
The role of RICTOR amplification in targeted therapy and drug resistance
Authors: Zhao Deze , Jiang Man , Zhang Xiaochun , Hou Helei
Published: February 2020

The emergence of tyrosine kinase inhibitors (TKIs) has changed the current treatment paradigm and achieved good results in recent decades. However, an increasing number of studies have indicated that the complex network of receptor tyrosine kinase (RTK) co-activation could influence the characteristic phenotypes of cancer and the tumor response to targeted treatments. One of strategies to blocking RTK co-activation is targeting the downstream factors of RTK, such as PI3K-AKT-mTOR pathway. RICTOR, a core component of mTORC2, acts as a key effector molecule of the PI3K-AKT pathway; its amplification is often associated with poor clinical outcomes and resistance to TKIs. Here, we discuss the biology of RICTOR in tumor and the prospects of targeting RICTOR as a complementary therapy to inhibit RTK co-activation.
Position within the hospital and role in the emergency department of emergency physicians in the Netherlands: a national survey
Authors: Coppes Sarah , Veugelers Rebekka , Hessels Roger A. P. A. , van den Brand Crispijn L. , Gaakeer Menno I.
Published: February 2020

Objectives

Emergency medicine (EM) in the Netherlands has developed rapidly and initially without central guidance. This has led to heterogeneity in current EM practice. Our aim was to quantify this heterogeneity by answering the following questions: (1) What is the current position of emergency physicians (EPs) within hospital organizations? (2) Which roles and responsibilities do EPs have across emergency departments (EDs)?

Methods

During 2018, we conducted a survey among all EM consultant bodies (CBs,n = 56) in the Netherlands. Data was analyzed using descriptive statistics.

Results

The response rate was 91.1%. Presence of EPs has been realized 24/7 in 23.1% of EDs. EPs were the main consultants for all ED patients in 9.8% of CBs, but never had this role in 13.7% of CBs. EPs supervised EM junior doctors in 78.5% of EDs, GPs in training in 80.0% of EDs, and junior doctors of other specialties in 41.5% of EDs. Procedures such as lumbar puncture (LP), procedural sedation and analgesia (PSA), and emergency ultrasound (US) were performed by all EPs in the CB in a range between 5.9 and 78.4%. In 36.9% of EDs, EPs did not analyze patients with presumed cardiac pathology due to a separateFirst Heart Aid.

Conclusion

We conclude that there is a high degree of heterogeneity between emergency CBs in regard to the position in the hospital and the role or responsibilities in the ED. Lack of uniformity might inhibit emancipation of the profession.
Influence of seat-belt use on the severity of injury in traffic accidents
Authors: Febres Juan Diego , García-Herrero Susana , Herrera Sixto , Gutiérrez J. M. , López-García J. R. , Mariscal Miguel A.
Published: February 2020

Background

About 1.35 million people died in traffic accidents around the world in 2018, make this type of accidents the 8th cause of death in the world. Particularly, in Spain, there were 204,596 traffic accidents during 2016 and 2017, out of which 349,810 drivers were injured. The objective of this study was to understand to what extent seat belt non-use and human factors contribute to drivers injury severity.

Methodology

The results are based on the information and 2016–17 data provided by the Spain national traffic department “Dirección General de Tráfico” (DGT). The discretization model and Bayesian Networks were developed based on important variables from the literature. These variables were classified as; human factor, demographic factor, conditioning factor and seat belt use.

Results

The results showed that failure to wear the seat belt by drivers are likely to increase the risk of fatal and sever injury significantly. Moreover, distraction and road type road can contribute to the accident severity.
SeqBreed: a python tool to evaluate genomic prediction in complex scenarios
Authors: Pérez-Enciso Miguel , Ramírez-Ayala Lino C. , Zingaretti Laura M.
Published: February 2020

Background

Genomic prediction (GP) is a method whereby DNA polymorphism information is used to predict breeding values for complex traits. Although GP can significantly enhance predictive accuracy, it can be expensive and difficult to implement. To help design optimum breeding programs and experiments, including genome-wide association studies and genomic selection experiments, we have developed SeqBreed, a generic and flexible forward simulator programmed in python3.

Results

SeqBreed accommodates sex and mitochondrion chromosomes as well as autopolyploidy. It can simulate any number of complex phenotypes that are determined by any number of causal loci. SeqBreed implements several GP methods, including genomic best linear unbiased prediction (GBLUP), single-step GBLUP, pedigree-based BLUP, and mass selection. We illustrate its functionality with Drosophila genome reference panel (DGRP) sequence data and with tetraploid potato genotype data.

Conclusions

SeqBreed is a flexible and easy to use tool that can be used to optimize GP or genome-wide association studies. It incorporates some of the most popular GP methods and includes several visualization tools. Code is open and can be freely modified. Software, documentation, and examples are available athttps://github.com/miguelperezenciso/SeqBreed.
Deep learning improves the ability of sgRNA off-target propensity prediction
Authors: Liu Qiaoyue , Cheng Xiang , Liu Gan , Li Bohao , Liu Xiuqin
Published: February 2020

Background

CRISPR/Cas9 system, as the third-generation genome editing technology, has been widely applied in target gene repair and gene expression regulation. Selection of appropriate sgRNA can improve the on-target knockout efficacy of CRISPR/Cas9 system with high sensitivity and specificity. However, when CRISPR/Cas9 system is operating, unexpected cleavage may occur at some sites, known as off-target. Presently, a number of prediction methods have been developed to predict the off-target propensity of sgRNA at specific DNA fragments. Most of them use artificial feature extraction operations and machine learning techniques to obtain off-target scores. With the rapid expansion of off-target data and the rapid development of deep learning theory, the existing prediction methods can no longer satisfy the prediction accuracy at the clinical level.

Results

Here, we propose a prediction method named CnnCrispr to predict the off-target propensity of sgRNA at specific DNA fragments. CnnCrispr automatically trains the sequence features of sgRNA-DNA pairs with GloVe model, and embeds the trained word vector matrix into the deep learning model including biLSTM and CNN with five hidden layers. We conducted performance verification on the data set provided by DeepCrispr, and found that the auROC and auPRC in the “leave-one-sgRNA-out” cross validation could reach 0.957 and 0.429 respectively (the Pearson value and spearman value could reach 0.495 and 0.151 respectively under the same settings).

Conclusion

Our results show that CnnCrispr has better classification and regression performance than the existing states-of-art models. The code for CnnCrispr can be freely downloaded from https://github.com/LQYoLH/CnnCrispr.
Phylogeographic history of flat periwinkles, Littorina fabalis and L. obtusata
Authors: Sotelo Graciela , Duvetorp Mårten , Costa Diana , Panova Marina , Johannesson Kerstin , Faria Rui
Published: February 2020

Background

The flat periwinkles,Littorina fabalisandL. obtusata, are two sister species widely distributed throughout the Northern Atlantic shores with high potential to inform us about the process of ecological speciation in the intertidal. However, whether gene flow has occurred during their divergence is still a matter of debate. A comprehensive assessment of the genetic diversity of these species is also lacking and their main glacial refugia and dispersal barriers remain largely unknown. In order to fill these gaps, we sequenced two mitochondrial genes and two nuclear fragments to perform a phylogeographic analysis of flat periwinkles across their distribution range.

Results

We identified two main clades largely composed by species-specific haplotypes corresponding toL. obtusataandL. fabalis, with moderate to strong support, respectively. Importantly, a model of divergence with gene flow between the two species (fromL. obtusata to L. fabalis) was better supported, both in Iberia and in northern-central Europe. Three mitochondrial clades were detected withinL. fabalisand two withinL. obtusata, with strong divergence between Iberia and the remaining populations. The largest component of the genetic variance within each species was explained by differences between geographic regions associated with these clades. Our data suggests that overall intraspecific genetic diversity is similar between the two flat periwinkle species and that populations from Iberia tend to be less diverse than populations from northern-central Europe.

Conclusions

The phylogeographic analysis of this sister-species pair supports divergence with gene flow. This system thus provides us with the opportunity to study the contribution of gene flow and natural selection during diversification. The distribution of the different clades suggests the existence of glacial refugia in Iberia and northern-central Europe for both species, with a main phylogeographic break between these regions. Although the genetic diversity results are not fully conclusive, the lower diversity observed in Iberia could reflect marginal conditions at the southern limit of their distribution range during the current interglacial period.
Genomic measures of inbreeding coefficients and genome-wide scan for runs of homozygosity islands in Iranian river buffalo, Bubalus bubalis
Authors: Ghoreishifar Seyed Mohammad , Moradi-Shahrbabak Hossein , Fallahi Mohammad Hossein , Jalil Sarghale Ali , Moradi-Shahrbabak Mohammad , Abdollahi-Arpanahi Rostam , Khansefid Majid
Published: February 2020

Background

Consecutive homozygous fragments of a genome inherited by offspring from a common ancestor are known as runs of homozygosity (ROH). ROH can be used to calculate genomic inbreeding and to identify genomic regions that are potentially under historical selection pressure. The dataset of our study consisted of 254 Azeri (AZ) and 115 Khuzestani (KHZ) river buffalo genotyped for ~ 65,000 SNPs for the following two purposes: 1) to estimate and compare inbreeding calculated using ROH (FROH), excess of homozygosity (FHOM), correlation between uniting gametes (FUNI), and diagonal elements of the genomic relationship matrix (FGRM); 2) to identify frequently occurring ROH (i.e. ROH islands) for our selection signature and gene enrichment studies.

Results

In this study, 9102 ROH were identified, with an average number of 21.2 ± 13.1 and 33.2 ± 15.9 segments per animal in AZ and KHZ breeds, respectively. On average in AZ, 4.35% (108.8 ± 120.3 Mb), and in KHZ, 5.96% (149.1 ± 107.7 Mb) of the genome was autozygous. The estimated inbreeding values based on FHOM, FUNIand FGRMwere higher in AZ than they were in KHZ, which was in contrast to the FROHestimates. We identified 11 ROH islands (four in AZ and seven in KHZ). In the KHZ breed, the genes located in ROH islands were enriched for multiple Gene Ontology (GO) terms (P ≤ 0.05). The genes located in ROH islands were associated with diverse biological functions and traits such as body size and muscle development (BMP2), immune response (CYP27B1), milk production and components (MARS, ADRA1A, and KCTD16), coat colour and pigmentation (PMEL and MYO1A), reproductive traits (INHBC, INHBE, STAT6 and PCNA), and bone development (SUOX).

Conclusion

The calculated FROHwas in line with expected higher inbreeding in KHZ than in AZ because of the smaller effective population size of KHZ. Thus, we find that FROHcan be used as a robust estimate of genomic inbreeding. Further, the majority of ROH peaks were overlapped with or in close proximity to the previously reported genomic regions with signatures of selection. This tells us that it is likely that the genes in the ROH islands have been subject to artificial or natural selection.
Transcriptional profiling and physiological roles of Aedes aegypti spermathecal-related genes
Authors: Pascini Tales Vicari , Ramalho-Ortigão Marcelo , Ribeiro José Marcos , Jacobs-Lorena Marcelo , Martins Gustavo Ferreira
Published: February 2020

Background

Successful mating of female mosquitoes typically occurs once, with the male sperm being stored in the female spermatheca for every subsequent oviposition event. The female spermatheca is responsible for the maintenance, nourishment, and protection of the male sperm against damage during storage.Aedes aegyptiis a major vector of arboviruses, including Yellow Fever, Dengue, Chikungunya, and Zika. Vector control is difficult due to this mosquito high reproductive capacity.

Results

Following comparative RNA-seq analyses of spermathecae obtained from virgin and inseminated females, eight transcripts were selected based on their putative roles in sperm maintenance and survival, including energy metabolism, chitin components, transcriptional regulation, hormonal signaling, enzymatic activity, antimicrobial activity, and ionic homeostasis. In situ RNA hybridization confirmed tissue-specific expression of the eight transcripts. Following RNA interference (RNAi), observed outcomes varied between targeted transcripts, affecting mosquito survival, egg morphology, fecundity, and sperm motility within the spermathecae.

Conclusions

This study identified spermatheca-specific transcripts associated with sperm storage inAe. aegypti. Using RNAi we characterized the role of eight spermathecal transcripts on various aspects of female fecundity and offspring survival. RNAi-induced knockdown of transcriptAeSigP-66,427,coding for a Na+/Ca2+protein exchanger, specifically interfered with egg production and reduced sperm motility. Our results bring new insights into the molecular basis of sperm storage and identify potential targets forAe. aegypticontrol.
A combined microRNA and transcriptome analyses illuminates the resistance response of rice against brown planthopper
Authors: Tan Jiaoyan , Wu Yan , Guo Jianping , Li Huimin , Zhu Lili , Chen Rongzhi , He Guangcun , Du Bo
Published: February 2020

Background

The brown planthopper (BPH, Nilaparvata lugens Stål) is a kind of phloem-feeding pest that adversely affects rice yield. Recently, the BPH-resistance gene, BPH6, was cloned and applied in rice breeding to effectively control BPH. However, the molecular mechanisms underlying BPH6 are poorly understood.

Results

Here, an integrated miRNA and mRNA expression profiling analysis was performed on BPH6-transgenic (BPH6G) and Nipponbare (wild type, WT) plants after BPH infestation, and a total of 217 differentially expressed miRNAs (DEMs) and 7874 differentially expressed mRNAs (DEGs) were identified. 29 miRNAs, including members of miR160, miR166 and miR169 family were opposite expressed during early or late feeding stages between the two varieties, whilst 9 miRNAs were specifically expressed in BPH6G plants, suggesting involvement of these miRNAs in BPH6-mediated resistance to BPH. In the transcriptome analysis, 949 DEGs were opposite expressed during early or late feeding stages of the two genotypes, which were enriched in metabolic processes, cellular development, cell wall organization, cellular component movement and hormone transport, and certain primary and secondary metabolite synthesis. 24 genes were further selected as candidates for BPH resistance. Integrated analysis of the DEMs and DEGs showed that 34 miRNAs corresponding to 42 target genes were candidate miRNA-mRNA pairs for BPH resistance, 18 pairs were verified by qRT-PCR, and two pairs were confirmed by in vivo analysis.

Conclusions

For the first time, we reported integrated small RNA and transcriptome sequencing to illustrate resistance mechanisms against BPH in rice. Our results provide a valuable resource to ascertain changes in BPH-induced miRNA and mRNA expression profiles and enable to comprehend plant-insect interactions and find a way for efficient insect control.
Transcriptomic study of pedicels from GA3-treated table grape genotypes with different susceptibility to berry drop reveals responses elicited in cell wall yield, primary growth and phenylpropanoids synthesis
Authors: Meneses Marco , García-Rojas Miguel , Muñoz-Espinoza Claudia , Carrasco-Valenzuela Tomás , Defilippi Bruno , González-Agüero Mauricio , Meneses Claudio , Infante Rodrigo , Hinrichsen Patricio
Published: February 2020

Background

Gibberellins (GA3) are the most sprayed growth regulator for table grape production worldwide, increasing berry size of seedless varieties through pericarp cell expansion. However, these treatments also exacerbate berry drop, which has a detrimental effect on the postharvest quality of commercialized clusters. Several studies have suggested that pedicel stiffening caused by GA3would have a role in this disorder. Nevertheless, transcriptional and phenotypic information regarding pedicel responses to GA3is minimal.

Results

Characterization of responses to GA3treatments using the lines L23 and Thompson Seedless showed that the former was up to six times more susceptible to berry drop than the latter. GA3also increased the diameter and dry matter percentage of the pedicel on both genotypes. Induction of lignin biosynthesis-related genes by GA3has been reported, so the quantity of this polymer was measured. The acetyl bromide method detected a decreased concentration of lignin 7 days after GA3treatment, due to a higher cell wall yield of the isolated fractions of GA3-treated pedicel samples which caused a dilution effect. Thus, an initial enrichment of primary cell wall components in response to GA3was suggested, particularly in the L23 background. A transcriptomic profiling was performed to identify which genes were associated with these phenotypic changes. This analysis identified 1281 and 1787 genes differentially upregulated by GA3in L23 and cv. Thompson Seedless, respectively. Concomitantly, 1202 and 1317 downregulated genes were detected in L23 and cv. Thompson Seedless (FDR < 0.05). Gene ontology analysis of upregulated genes showed enrichment in pathways including phenylpropanoids, cell wall metabolism, xylem development, photosynthesis and the cell cycle at 7 days post GA3application. Twelve genes were characterized by qPCR and striking differences were observed between genotypes, mainly in genes related to cell wall synthesis.

Conclusions

High levels of berry drop are related to an early strong response of primary cell wall synthesis in the pedicel promoted by GA3treatment. Genetic backgrounds can produce similar phenotypic responses to GA3, although there is considerable variation in the regulation of genes in terms of which are expressed, and the extent of transcript levels achieved within the same time frame.
Identification of two recessive etiolation genes (py1, py2) in pakchoi (Brassica rapa L. ssp. chinensis)
Authors: Zhang Kun , Mu Yu , Li Weijia , Shan Xiaofei , Wang Nan , Feng Hui
Published: February 2020

Background

Leaf color is a major agronomic trait, which has a strong influence on crop yields. Isolating leaf color mutants can represent valuable materials for research in chlorophyll (Chl) biosynthesis and metabolism regulation.

Results

In this study, we identified a stably inherited yellow leaf mutant derived from ‘Huaguan’ pakchoi variety via isolated microspore culture and designated aspylm. This mutant displayed yellow leaves after germination. Its etiolated phenotype was nonlethal and stable during the whole growth period. Its growth was weak and its hypocotyls were markedly elongated. Genetic analysis revealed that two recessive nuclear genes, namedpy1andpy2, are responsible for the etiolation phenotype. Bulked segregant RNA sequencing (BSR-Seq) showed thatpy1andpy2were mapped on chromosomes A09 and A07, respectively. The genes were single Mendelian factors in F3:4populations based on a 3:1 phenotypic segregation ratio. Thepy1was localized to a 258.3-kb interval on a 34-gene genome. The differentially expressed geneBraA09004189was detected in thepy1mapping region and regulated heme catabolism. One single-nucleotide polymorphism (SNP) ofBraA09004189occurred inpylm.A candidate gene-specific SNP marker in 1520 F3:4yellow-colored individuals co-segregated withpy1. Forpy2, 1860 recessive homozygous F3:4individuals were investigated and localizedpy2to a 4.4-kb interval. Of the five genes in this region,BraA07001774was predicted as a candidate forpy2.It encoded anembryo defective 1187and a phosphotransferase related to chlorophyll deficiency and hypocotyl elongation. One SNP ofBraA07001774occurred inpylm.It caused a single amino acid mutation from Asp to Asn. According to quantitative real-time polymerase chain reaction (qRT-PCR),BraA07001774was downregulated inpylm.

Conclusions

Our study identified a Chl deficiency mutantpylmin pakchoi. Two recessive nuclear genes namedpy1andpy2had a significant effect on etiolation. Candidate genes regulating etiolation were identified asBraA09004189andBraA07001774, respectively. These findings will elucidate chlorophyll metabolism and the molecular mechanisms of the gene interactions controlling pakchoi etiolation.
Simultaneous pacing from two branches of coronary sinus in a patient with prosthetic tricuspid valve and complete heart block
Authors: Yolcu Mustafa
Published: February 2020

Background

Complete heart blocks underwent to permanent pacemaker placement are a common complication of tricuspid valve replacement (TVR). If indicated, endocardial placement of a right ventricular (RV) lead is precluded in the presence of mechanical TVR.

Case presentation

A 20-year-old female patient firstly underwent metallic prosthetic valve operation with tricuspid valve endocarditis in 2014. Three years after the operation, echocardiography revealed dysfunction of the prosthetic valve thus reoperation was decided. In the second operation, the patient underwent a bioprosthesis valve and AV complete block developed in the postoperative period. Left ventricular ejection fraction (EF) was 45% was found on echocardiography. Pacemaker dependence of the patient, it was aimed to place two electrodes into the left ventricle. Electrodes were placed the target two branches in coronary sinus (CS) and right atrium. Univentricular bifocal pacing was enabled to work.

Conclusion

Electrode placement in the CS is a very good alternative to epicardial surgical lead placement in cases where endocardial lead placement from the right atrium to the RV is contraindicated. In patients with lower left ventricular EF who will be pacemaker dependent, the insertion of two electrodes into the CS to prevent pacemaker is a safe and effective treatment.
Prognostic value of plasma von Willebrand factor levels in major adverse cardiovascular events: a systematic review and meta-analysis
Authors: Fan Mengge , Wang Xia , Peng Xun , Feng Shuo , Zhao Junyu , Liao Lin , Zhang Yong , Hou Yinglong , Liu Ju
Published: February 2020

Background

Prediction of major adverse cardiovascular events (MACEs) may offer great benefits for patients with coronary artery disease (CAD). Von Willebrand factor (vWF) is stored in endothelial cells and released into blood plasma upon vascular dysfunction. This meta-analysis was performed to evaluate the prognostic value of plasma vWF levels in CAD patients with MACEs.

Methods

A total of 15 studies were included in this meta-analysis through the search in PubMed, Embase and CNKI. Data were collected from 960 patients who had MACEs after CAD and 3224 controls nested without the adverse events. The standard mean difference (SMD) and 95% confidence intervals (95% CI) were calculated using random-effects model.

Results

The plasma vWF levels examined at 24 h and 48 h after admission were significantly higher in CAD patients with MACEs than those without. The pooled SMD among the MACEs group and the non-MACEs group was 0.55 (95% CI = 0.30–0.80, P < 0.0001) and 0.70 (95% CI = 0.27–1.13, P = 0.001), respectively. However, no significant difference was found in plasma vWF levels on admission between the two groups.

Conclusion

Plasma vWF level in CAD patients examined at 24 h and 48 h after admission might be an independent prognostic factor for MACE.
Patient and Public Involvement (PPI) in evidence synthesis: how the PatMed study approached embedding audience responses into the expression of a meta-ethnography
Authors: Park S. , Khan N. , Stevenson F. , Malpass A.
Published: February 2020

Background

Patient and public involvement (PPI) has become enshrined as an important pillar of health services empirical research, including PPI roles during stages of research development and analysis and co-design approaches. Whilst user participation has been central to qualitative evidence synthesis (QES) for decades, as seen in the Cochrane consumer network and guidelines, meta-ethnography has been slow to incorporate user participation and published examples of this occurring within meta-ethnography are sparse.

In this paper, drawing upon our own experience of conducting a meta-ethnography, we focus on what it means in practice to ‘express a synthesis’ (stage 7). We suggest the methodological importance of ‘expression’ in Noblit and Hare’s seven stage process (Noblit, GW and Hare, RD. Meta-ethnography: synthesizing qualitative studies, 1988) has been overlooked, and in particular, opportunities for PPI user participation within it.

Methods

Meta-ethnography comprises a seven-stage process of evidence synthesis. Noblit and Hare describe the final 7th stage of the meta-ethnography process as ‘expression of synthesis’, emphasizing co-construction of findings with the audience. In a previous study we conducted a meta-ethnography exploring patient and student experience of medical education within primary care contexts. We subsequently presented and discussed initial meta-ethnography findings with PPI (students and patients) in focus groups and interviews. We transcribed patient and student PPI interpretations of synthesis findings. As a research team, we then translated these into our existing meta-ethnography findings.

Results

We describe, with examples, the process of involving PPI in stage 7 of meta-ethnography and discuss three methodological implications of incorporating PPI within an interpretative approach to QES: (1) we reflect on the construct hierarchy of user participants’ interpretations and consider whether incorporating these additional 1st order, 2nd level constructs implies an additional logic of 3rd order 2nd level constructs of the QES team; (2) we discuss the link between PPI user participation and what Noblit and Hare may have meant by ideas of ‘expression’ and ‘audience’ as integral to stage 7; and (3) we link PPI user participation to Noblit and Hare’s underlying theory of social explanation, i.e. how expression of the synthesis is underpinned by ideas of translation and that the synthesis must be ‘translated in the audience’s (user participants) particular language’.

Conclusions

The paper aims to complement recent attempts in the literature to refine and improve guidance on conducting a meta-ethnography, highlighting opportunities for PPI user participation in the processes of interpretation, translation and expression. We discuss the implications of user participation in meta-ethnography on ideas of ‘generalisability’.
Prevalence and correlates of Alzheimer’s disease and related dementias in rural Uganda: cross-sectional, population-based study
Authors: Mubangizi Vincent , Maling Samuel , Obua Celestino , Tsai Alexander C.
Published: February 2020

Background

There is a paucity of data on the prevalence and correlates of Alzheimer’s disease and related dementias in sub-Saharan Africa. The aim of the study was to estimate the prevalence and correlates of Alzheimer’s disease and related dementias in rural Uganda.

Methods

We conducted a cross-sectional, population-based study in a rural region of southwestern Uganda. The Brief Community Screening Instrument for Dementia was administered to a multi-stage area probability sample of 400 people aged 60 years and over. Multivariable logistic regression was used to estimate correlates of probable dementia.

Results

Overall, 80 (20%) of the sample screened positive for dementia. On multivariable regression, we estimated the following correlates of probable dementia: age (adjusted odds ratio [AOR], 1.02 per year; 95% confidence interval [CI], 1.10–1.03, p<0.001), having some formal education (AOR, 0.57; 95% CI, 0.41–0.81, p = 0.001), exercise (AOR, 0.44; 95% CI, 0.27–0.72, p = 0.001), and having a ventilated kitchen (AOR, 0.43; (95% CI, 0.24–0.77, p = 0.001).

Conclusions

In this population-based sample of older-age adults in rural Uganda, nearly one-fifth screened positive for dementia.
Long-term impact of the adoption of bedaquiline-containing regimens on the burden of drug-resistant tuberculosis in China
Authors: Agnarson Abela Mpobela , Wang Xiao Chun , Potluri Ravi , Bhandari Hitesh , Dhir Amit , Kambili Chrispin , Metz Laurent
Published: February 2020

Background

Currently available injectable agents are inadequate to address the high drug-resistant tuberculosis (DR-TB) burden in China. Regimens including the oral agent bedaquiline have been shown to be efficacious and safe, leading to its incorporation into multiple national TB treatment programs. This analysis evaluated the impact of increased adoption of bedaquiline-containing regimens on the DR-TB burden in China.

Methods

A state-transition model was developed that permits movement and interaction between susceptible, latent, and active TB disease states, while distinguishing between drug-sensitive (DS) and DR-TB. Model inputs were obtained from the published literature or derived such that model metrics approximated those published by the WHO. Expected improvements in infrastructure were built into the model to forecast the epidemiology of DR-TB in China through 2040 in the absence of bedaquiline (baseline forecast). The impact of higher utilization of bedaquiline-containing regimens (85% peak share) was then assessed in two scenarios that differed with regard to treatment success rates of the regimens: 61% (reflecting findings of clinical trials) and 80% (reflecting data from observational studies), versus the 44% success rate associated with standard-of-care treatment.

Results

In the baseline scenario, the model predicted increases in annual incidence of DR-TB by 6–8% during each five-year period between 2020 and 2040, with an increase of 30% over the entire study duration. Adoption of bedaquiline-based regimens limits the incidence increases to only 1–3% in each five-year period and to 8% over the study duration in the 61% success rate scenario. Incidence declines by 1–6% during each five-year period and by 12% over the study duration in the 80% success rate scenario. Similar effects on DR-TB prevalence (4–5% increase in baseline, 0–7% decline in scenario 1, and 4–19% decline in scenario 2) and mortality (5–7% increase in baseline, 0–16% decline in scenario 1, and 6–40% decline in scenario 2) were seen following bedaquiline adoption.

Conclusions

Incorporation of bedaquiline into DR-TB treatment regimens will significantly reduce the DR-TB burden in China, helping to counter the expected increase in burden in the absence of bedaquiline. The study will provide valuable information to public health policy planners.
Prioritising pathogens for the management of severe febrile patients to improve clinical care in low- and middle-income countries
Authors: Osborn Jennifer , Roberts Teri , Guillen Ethan , Bernal Oscar , Roddy Paul , Ongarello Stefano , Sprecher Armand , Page Anne-Laure , Ribeiro Isabela , Piriou Erwan , Tamrat Abiy , de la Tour Roberto , Rao V. Bhargavi , Flevaud Laurence , Jensen Tomas , McIver Lachlan , Kelly Cassandra , Dittrich Sabine
Published: February 2020

Background

Severe febrile illness without a known source (SFWS) is a challenge for clinicians when deciding how to manage a patient, particularly given the wide spectrum of potential aetiologies that contribute to fever. These infections are difficult to distinguish clinically, and accurate diagnosis requires a plethora of diagnostics including blood cultures, imaging techniques, molecular or serological tests, and more. When laboratory services are available, a limited test menu hinders clinical decision-making and antimicrobial stewardship, leading to empiric treatment and suboptimal patient outcomes. To specifically address SFWS, this work aimed to identify priority pathogens for a globally applicable panel for fever causing pathogens.

Method

A pragmatic two-pronged approach combining currently available scientific data in an analytical hierarchy process and systematically gathered expert input, was designed to address the lack of comprehensive global aetiology data. The expert re-ranked list was then further adapted for a specific use case to focus on community acquired infections in whole blood specimens. The resulting list was further analysed to address different geographical regions (Asia, Africa, and Latin America), and Cohen kappa scores of agreement were calculated.

Results

The expert ranked prioritized pathogen list generated as part of this two-pronged approach included typhoidalSalmonella,Plasmodiumspecies andMycobacterium tuberculosisas the top 3 pathogens. This pathogen list was then further adapted for the SFWS use case to develop a final pathogen list to inform product development. Subsequent analysis comparing the relevance of the SFWS pathogen list to multiple populations and geographical regions showed that the SFWS prioritized list had considerable utility across Africa and Asia, but less so for Latin America. In addition, the list showed high levels of agreement across different patient sub-populations, but lower relevance for neonates and symptomatic HIV patients.

Conclusion

This work highlighted once again the challenges of prioritising in global health, but it also shows that taking a two-pronged approach, combining available prevalence data with expert input, can result in a broadly applicable priority list. This comprehensive utility is particularly important in the context of product development, where a sufficient market size is essential to achieve a sustainable commercialized diagnostic product to address SFWS.
A strategy to account for noise in the X-variable to reduce underestimation in Logan graphical analysis for quantifying receptor density in positron emission tomography
Authors: Shigwedha Paulus K. , Yamada Takahiro , Hanaoka Kohei , Ishii Kazunari , Kimura Yuichi , Fukuoka Yutaka
Published: February 2020

Background

The Logan graphical analysis (LGA) algorithm is widely used to quantify receptor density for parametric imaging in positron emission tomography (PET). Estimating receptor density, in terms of the non-displaceable binding potential (BPND), from the LGA using the ordinary least-squares (OLS) method has been found to be negatively biased owing to noise in PET data. This is because OLS does not consider errors in the X-variable (predictor variable). Existing bias reduction methods can either only reduce the bias slightly or reduce the bias accompanied by increased variation in the estimates. In this study, we addressed the bias reduction problem by applying a different regression method.

Methods

We employed least-squares cubic (LSC) linear regression, which accounts for errors in both variables as well as the correlation of these errors. Noise-free PET data were simulated, for 11C-carfentanil kinetics, with known BPND values. Statistical noise was added to these data and the BPNDs were re-estimated from the noisy data by three methods, conventional LGA, multilinear reference tissue model 2 (MRTM2), and LSC-based LGA; the results were compared. The three methods were also compared in terms of beta amyloid (A β) quantification of 11C-Pittsburgh compound B brain PET data for two patients with Alzheimer’s disease and differing A β depositions.

Results

Amongst the three methods, for both synthetic and actual data, LSC was the least biased, followed by MRTM2, and then the conventional LGA, which was the most biased. Variations in the LSC estimates were smaller than those in the MRTM2 estimates. LSC also required a shorter computational time than MRTM2.

Conclusions

The results suggest that LSC provides a better trade-off between the bias and variability than the other two methods. In particular, LSC performed better than MRTM2 in all aspects; bias, variability, and computational time. This makes LSC a promising method for BPND parametric imaging in PET studies.
Husbands’ experience and perception of supporting their wives during childbirth in Tanzania
Authors: Kashaija Denis Kampayana , Mselle Lilian Teddy , Mkoka Dickson Ally
Published: February 2020

Background

In order improve the quality of birth care and women satisfaction with birthing process it is recommended that every woman should be offered the option to experience labour and childbirth with a companion of her choice. Involving husbands who are decision makers in the household may a play role in reducing maternal mortality which is unacceptably high despite the targeted goal to reduce this mortality up to three quarters as targeted in the MDGs by 2015. This is still addressed in the Sustainable Development Goals (SDGs) of 2015/30. This study aimed to explore the experiences and perceptions of husbands’ support of their wives during pregnancy, labour and deliveries in Tanzania.

Methods

Qualitative descriptive study design was employed; involving men aged between 24 and 63 years. Participants were selected purposefully at the clinic and in labour ward of SekouToure Regional Referral Hospital (SRRH). The in-depth interview, guided by semi structured interview guide was used to collect the audio recorded and hand written information. Data were analysed using qualitative content analysis.

Results

Nine semi-structured interviews were conducted with husbands of women attended for antenatal care and those came for deliveries. Four themes emerged; Demonstrating care, love and affection, adopting modern life style, observing women’s right and meeting social economic difficulties. Husbands’ support to their partners is a good behaviour practiced during matrimonial lives. Husbands who support their partners during pregnancy and delivery consider themselves as being modern men as they at home take duties beside their usual tasks to let their wives have adequate time to rest during pregnancy. Poor road infrastructure makes difficult to get transport to the healthcare facility especially when labour is imminent. Also ward infrastructure is not supportive to accommodate husbands when they accompany their wives to the healthcare facility.

Conclusions

The healthcare settings in low income countries need to accommodate men during the routine antenatal and intranatal care for the positive outcome of labour and delivery.

Educating men on importance of active involvement in reproductive and child health services is important. Exploratory research should be conducted to understand how education and urbanisation affects men involvement in maternal and child health specifically in the low income countries.