bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association mapping reveals potential novel loci controlling stripe rust resistance in a Chinese wheat landrace diversity panel from the southern autumn-sown spring wheat zone
Authors: Wang Yuqi , Yu Can , Cheng Yukun , Yao Fangjie , Long Li , Wu Yu , Li Jing , Li Hao , Wang Jirui , Jiang Qiantao , Li Wei , Pu Zhien , Qi Pengfei , Ma Jian , Deng Mei , Wei Yuming , Chen Xianming , Chen Guoyue , Kang Houyang , Jiang Yunfeng , Zheng Youliang 
Published: January 2021

AbstractBackgroundStripe rust, caused by the fungal pathogenPuccinia striiformisf. sp.tritici(Pst), is a serious foliar disease of wheat. Identification of novel stripe rust resistance genes and cultivation of resistant cultivars are considered to be the most effective approaches to control this disease. In this study, we evaluated the infection type (IT), disease severity (DS) and area under the disease progress curve (AUDPC) of 143 Chinese wheat landrace accessions for stripe rust resistance. Assessments were undertaken in five environments at the adult-plant stage withPstmixture races under field conditions. In addition, IT was assessed at the seedling stage with two prevalentPstraces (CYR32 and CYR34) under a controlled greenhouse environment.ResultsSeventeen accessions showed stable high-level resistance to stripe rust across all environments in the field tests. Four accessions showed resistance to thePstraces CYR32 and CYR34 at the seedling stage. Combining phenotypic data from the field and greenhouse trials with 6404 markers that covered the entire genome, we detected 17 quantitative trait loci (QTL) on 11 chromosomes for IT associated with seedling resistance and 15 QTL on seven chromosomes for IT, final disease severity (FDS) or AUDPC associated with adult-plant resistance. Four stable QTL detected on four chromosomes, which explained 9.99–23.30% of the phenotypic variation, were simultaneously associated with seedling and adult-plant resistance. Integrating a linkage map of stripe rust resistance in wheat, 27 QTL overlapped with previously reported genes or QTL, whereas four and one QTL conferring seedling and adult-plant resistance, respectively, were mapped distantly from previously reported stripe rust resistance genes or QTL and thus may be novel resistance loci.ConclusionsOur results provided an integrated overview of stripe rust resistance resources in a wheat landrace diversity panel from the southern autumn-sown spring wheat zone of China. The identified resistant accessions and resistance loci will be useful in the ongoing effort to develop new wheat cultivars with strong resistance to stripe rust.
Phylogenomic and evolutionary dynamics of inverted repeats across Angelica plastomes
Authors: Wang Mengli , Wang Xin , Sun Jiahui , Wang Yiheng , Ge Yang , Dong Wenpan , Yuan Qingjun , Huang Luqi 
Published: January 2021

AbstractBackgroundAngelicaL. (family Apiaceae) is an economically important genus comprising ca. One hundred ten species.Angelicaspecies are found on all continents of the Northern Hemisphere, and East Asia hosts the highest number of species. Morphological characters such as fruit anatomy, leaf morphology and subterranean structures ofAngelicaspecies show extreme diversity. Consequently, the taxonomic classification ofAngelicaspecies is complex and remains controversial, as the classifications proposed by previous studies based on morphological data and molecular data are highly discordant. In addition, the phylogenetic relationships of major clades in theAngelicagroup, particularly in theAngelicas. s. clade, remain unclear. Chloroplast (cp) genome sequences have been widely used in phylogenetic studies and for evaluating genetic diversity.ResultsIn this study, we sequenced and assembled 28 complete cp genomes from 22 species, two varieties and two cultivars ofAngelica. Combined with 36 available cp genomes in GenBank from representative clades of the subfamily Apioideae, the characteristics and evolutionary patterns ofAngelicacp genomes were studied, and the phylogenetic relationships ofAngelicaspecies were resolved. TheAngelicacp genomes had the typical quadripartite structure including a pair of inverted repeats (IRs: 5836–34,706 bp) separated by a large single-copy region (LSC: 76,657–103,161 bp) and a small single-copy region (SSC: 17,433–21,794 bp). Extensive expansion and contraction of the IR region were observed among cp genomes ofAngelicaspecies, and the pattern of the diversification of cp genomes showed high consistency with the phylogenetic placement ofAngelicaspecies. Species ofAngelicawere grouped into two major clades, with most species grouped in theAngelicagroup andA. omeiensisandA. sinensisgrouped in theSinodielsiawithLigusticum tenuissimum.ConclusionsOur results further demonstrate the power of plastid phylogenomics in enhancing the phylogenetic reconstructions of complex genera and provide new insights into plastome evolution acrossAngelicaL.
Cardiovascular risk factors and mortality in hospitalized patients with COVID-19: systematic review and meta-analysis of 45 studies and 18,300 patients
Authors: Silverio Angelo , Di Maio Marco , Citro Rodolfo , Esposito Luca , Iuliano Giuseppe , Bellino Michele , Baldi Cesare , De Luca Giuseppe , Ciccarelli Michele , Vecchione Carmine , Galasso Gennaro 
Published: January 2021

AbstractBackgroundA high prevalence of cardiovascular risk factors including age, male sex, hypertension, diabetes, and tobacco use, has been reported in patients with Coronavirus disease 2019 (COVID-19) who experienced adverse outcome. The aim of this study was to investigate the relationship between cardiovascular risk factors and in-hospital mortality in patients with COVID-19.MethodsMEDLINE, Cochrane, Web of Sciences, and SCOPUS were searched for retrospective or prospective observational studies reporting data on cardiovascular risk factors and in-hospital mortality in patients with COVID-19.Univariable and multivariable age-adjusted analyses were conducted to evaluate the association between cardiovascular risk factors and the occurrence of in-hospital death.ResultsThe analysis included 45 studies enrolling 18,300 patients. The pooled estimate of in-hospital mortality was 12% (95% CI 9–15%). The univariable meta-regression analysis showed a significant association between age (coefficient: 1.06; 95% CI 1.04–1.09; p < 0.001), diabetes (coefficient: 1.04; 95% CI 1.02–1.07; p < 0.001) and hypertension (coefficient: 1.01; 95% CI 1.01–1.03; p = 0.013) with in-hospital death. Male sex and smoking did not significantly affect mortality. At multivariable age-adjusted meta-regression analysis, diabetes was significantly associated with in-hospital mortality (coefficient: 1.02; 95% CI 1.01–1.05; p = 0.043); conversely, hypertension was no longer significant after adjustment for age (coefficient: 1.00; 95% CI 0.99–1.01; p = 0.820). A significant association between age and in-hospital mortality was confirmed in all multivariable models.ConclusionsThis meta-analysis suggests that older age and diabetes are associated with higher risk of in-hospital mortality in patients infected by SARS-CoV-2. Conversely, male sex, hypertension, and smoking did not independently correlate with fatal outcome.
The M310T mutation in the GATA4 gene is a novel pathogenic target of the familial atrial septal defect
Authors: Bu Haisong , Sun Guowen , Zhu Yun , Yang Yifeng , Tan Zhiping , Zhao Tianli , Hu Shijun 
Published: January 2021

AbstractBackgroundAlthough most cases of atrial septal defect (ASD) are sporadic, familial cases have been reported, which may be caused by mutation of transcription factor GATA binding protein 4 (GATA4). Herein we combined whole-exome sequencing and bioinformatics strategies to identify a novel mutation inGATA4accounting for the etiology in a Chinese family with ASD.MethodsWe identified kindred spanning 3 generations in which 3 of 12 (25.0%) individuals had ASD. Punctilious records for the subjects included complete physical examination, transthoracic echocardiography, electrocardiograph and surgical confirming. Whole-exome capture and high-throughput sequencing were performed on the proband III.1. Sanger sequencing was used to validate the candidate variants, and segregation analyses were performed in the family members.ResultsDirect sequencing ofGATA4from the genomic DNA of family members identified a T-to-C transition at nucleotide 929 in exon 5 that predicted a methionine to threonine substitution at codon 310 (M310T) in the nuclear localization signal (NLS) region. Two affected members (II.2 and III.3) and the proband (III.1) who was recognized as a carrier exhibited this mutation, whereas the other unaffected family members or control individuals did not. More importantly, the mutationGATA4(c.T929C: p.M310T) has not been reported previously in either familial or sporadic cases of congenital heart defects (CHD).ConclusionsWe identified for the first time a novel M310T mutation in theGATA4gene that is located in the NLS region and leads to family ASD with arrhythmias. However, the mechanism by which this pathogenic mutation contributes to the development of heart defect and tachyarrhythmias remains to be ascertained.
Effect of PCSK9 inhibitor on lipoprotein particles in patients with acute coronary syndromes
Authors: Li Tingting , Zhang Yingyi , Cong Hongliang 
Published: January 2021

AbstractBackgroundTo assess the effects of proprotein convertase subtilisin/kexin type 9 inhibitor (evolocumab) on lipoprotein particles subfractions with Nuclear Magnetic Resonance spectroscopy in patients with acute coronary syndromes.MethodsA total of 99 consecutive patients with ACS were enrolled and assigned to either the experimental group (n = 54) or the control group (n = 45). The combination therapy of PCSK9 inhibitor (Repatha®, 140 mg, q2w) and moderate statin (Rosuvastatin, 10 mg, qn) was administered in the experimental group, with statin monotherapy (Rosuvastatin, 10 mg, qn) in the control group. The therapeutic effects on lipoprotein particle subfractions were assessed with NMR spectroscopy after 8 weeks treatment, and the achievement of LDL-C therapeutic target in both groups were analyzed.ResultsIn the experimental group, after 8 weeks of evolocumab combination treatment, the concentrations of blood lipids (TC, LDL-C and its subfractions [LDL-1 to 6], VLDL-C and its subfractions [VLDL-1 to 5], IDL-C, and HDL-C), lipoprotein particles, and their subfractions [VLDL-P, IDL-P, LDL-P, and its subfractions [LDL-P1 to 6], apoB, and LP(a)] demonstrated therapeutic benefits with statistical significance (P < 0.05). The decrease in total LDL-P concentrations was mainly due to a decreased concentration of small-sized LDL particles (LDL-P 5 + 6), which was significantly more prominent than the decrease in medium-sized LDL-P (LDL-P3 + 4) and large-sized LDL-P (LDL-P1 + 2) (P < 0.001). According to lipid control target recommended by the latest China Cholesterol Education Program Expert Consensus in 2019, after 8 weeks treatment, 96.3% patients in the experimental group and 13.3% in the control group had achieved the LDL-C therapeutic target (P < 0.01).ConclusionsEvolocumab combination treatment for 8 weeks significantly improves the plasma lipid profiles in ACS patients, and significantly decrease the concentration of lipoprotein particles which might contribute to the pathonesis of atherosclerosis.
The utility of the rapid emergency medicine score (REMS) compared with SIRS, qSOFA and NEWS for Predicting in-hospital Mortality among Patients with suspicion of Sepsis in an emergency department
Authors: Ruangsomboon Onlak , Boonmee Phetsinee , Limsuwat Chok , Chakorn Tipa , Monsomboon Apichaya 
Published: January 2021

Abstract
Background
Many early warning scores (EWSs) have been validated to prognosticate adverse outcomes secondary to sepsis in the Emergency Department (ED). These EWSs include the Systemic Inflammatory Response Syndrome criteria (SIRS), the quick Sequential Organ Failure Assessment (qSOFA) and the National Early Warning Score (NEWS). However, the Rapid Emergency Medicine Score (REMS) has never been validated for this purpose. We aimed to assess and compare the prognostic utility of REMS with that of SIRS, qSOFA and NEWS for predicting mortality in patients with suspicion of sepsis in the ED.

Methods
We conducted a retrospective study at the ED of Siriraj Hospital Mahidol University, Thailand. Adult patients suspected of having sepsis in the ED between August 2018 and July 2019 were included. Their EWSs were calculated. The primary outcome was all-cause in-hospital mortality. The secondary outcome was 7-day mortality.

Results
A total of 1622 patients were included in the study; 457 (28.2%) died at hospital discharge. REMS yielded the highest discrimination capacity for in-hospital mortality (the area under the receiver operator characteristics curves (AUROC) 0.62 (95% confidence interval (CI) 0.59, 0.65)), which was significantly higher than qSOFA (AUROC 0.58 (95%CI 0.55, 0.60); p = 0.005) and SIRS (AUROC 0.52 (95%CI 0.49, 0.55); p < 0.001) but not significantly superior to NEWS (AUROC 0.61 (95%CI 0.58, 0.64); p = 0.27). REMS was the best EWS in terms of calibration and association with the outcome. It could also provide the highest net benefit from the decision curve analysis. Comparison of EWSs plus baseline risk model showed similar results. REMS also performed better than other EWSs for 7-day mortality.

Conclusion
REMS was an early warning score with higher accuracy than sepsis-related scores (qSOFA and SIRS), similar to NEWS, and had the highest utility in terms of net benefit compared to SIRS, qSOFA and NEWS in predicting in-hospital mortality in patients presenting to the ED with suspected sepsis.
Pattern-mixture model in network meta-analysis of binary missing outcome data: one-stage or two-stage approach?
Authors: Spineli Loukia M. , Papadimitropoulou Katerina , Kalyvas Chrysostomos 
Published: January 2021

AbstractBackgroundTrials with binary outcomes can be synthesised using within-trial exact likelihood or approximate normal likelihood in one-stage or two-stage approaches, respectively. The performance of the one-stage and the two-stage approaches has been documented extensively in the literature. However, little is known about how these approaches behave in the presence of missing outcome data (MOD), which are ubiquitous in clinical trials. In this work, we compare the one-stage versus two-stage approach via a pattern-mixture model in the network meta-analysis using Bayesian methods to handle MOD appropriately.MethodsWe used 29 published networks to empirically compare the two approaches concerning the relative treatment effects of several competing interventions and the between-trial variance (τ2), while considering the extent and level of balance of MOD in the included trials. We additionally conducted a simulation study to compare the competing approaches regarding the bias and width of the 95% credible interval of the (summary) log odds ratios (OR) andτ2in the presence of moderate and large MOD.ResultsThe empirical study did not reveal any systematic bias between the compared approaches regarding the log OR, but showed systematically larger uncertainty around the log OR under the one-stage approach for networks with at least one small trial or low event risk and moderate MOD. For these networks, the simulation study revealed that the bias in log OR for comparisons with the reference intervention in the network was relatively higher in the two-stage approach. Contrariwise, the bias in log OR for the remaining comparisons was relatively higher in the one-stage approach. Overall, bias increased for large MOD. For these networks, the empirical results revealed slightly higherτ2estimates under the one-stage approach irrespective of the extent of MOD. The one-stage approach also led to less precise log OR andτ2when compared with the two-stage approach for large MOD.ConclusionsDue to considerable bias in the log ORs overall, especially for large MOD, none of the competing approaches was superior. Until a more competent model is developed, the researchers may prefer the one-stage approach to handle MOD, while acknowledging its limitations.
Perspectives of family physicians towards access to lung cancer screening for individuals living with low income – a qualitative study
Authors: Sayani Ambreen , Vahabi Mandana , O’Brien Mary Ann , Liu Geoffrey , Hwang Stephen W. , Selby Peter , Nicholson Erika , Lofters Aisha 
Published: January 2021

AbstractBackgroundIndividuals living with low income are less likely to participate in lung cancer screening (LCS) with low-dose computed tomography. Family physicians (FPs) are typically responsible for referring eligible patients to LCS; therefore, we sought to understand their perspectives on access to lung cancer screening for individuals living with low income in order to improve equity in access to LCS.MethodsA theory-informed thematic analysis was conducted using data collected from 11 semi-structured interviews with FPs recruited from three primary care sites in downtown Toronto. Data was coded using the Systems Model of Clinical Preventative Care as a framework and interpretation was guided by the synergies of oppression analytical lens.ResultsFour overarching themes describe FP perspectives on access to LCS for individuals living with low income: the degree of social disadvantage that influences lung cancer risk and opportunities to access care; the clinical encounter, where there is often a mismatch between the complex health needs of low income individuals and structure of health care appointments; the need for equity-oriented health care, illustrated by the neglect of structural origins of health risk and the benefits of a trauma-informed approach; and finally, the multiprong strategies that will be needed in order to improve equity in health outcomes.ConclusionAn equity-oriented and interdisciplinary team based approach to care will be needed in order to improve access to LCS, and attention must be given to the upstream determinants of lung cancer in order to reduce lung cancer risk.
Design and rationale of a routine clinical care pathway and prospective cohort study in older patients needing intensive treatment
Authors: van Holstein Yara , van Deudekom Floor J. , Trompet Stella , Postmus Iris , Uit den Boogaard Anna , van der Elst Marjan J. T. , de Glas Nienke A. , van Heemst Diana , Labots Geert , Altena Mariëtte , Slingerland Marije , Liefers Gerrit Jan , van den Bos Frederiek , van der Bol Jessica M. , Blauw Gerard J. , Portielje Johanneke E. A. , Mooijaart Simon P. 
Published: January 2021

Abstract
Background
Treatment decisions concerning older patients can be very challenging and individualised treatment plans are often required in this very heterogeneous group. In 2015 we have implemented a routine clinical care pathway for older patients in need of intensive treatment, including a comprehensive geriatric assessment (CGA) that was used to support clinical decision making. An ongoing prospective cohort study, the Triaging Elderly Needing Treatment (TENT) study, has also been initiated in 2016 for participants in this clinical care pathway, to study associations between geriatric characteristics and outcomes of treatment that are relevant to older patients. The aim of this paper is to describe the implementation and rationale of the routine clinical care pathway and design of the TENT study.

Methods
A routine clinical care pathway has been designed and implemented in multiple hospitals in the Netherlands. Patients aged ≥70 years who are candidates for intensive treatments, such as chemotherapy, (chemo-)radiation therapy or major surgery, undergo frailty screening based on the Geriatric 8 (G-8) questionnaire and the Six-Item Cognitive Impairment Test (6CIT). If screening reveals potential frailty, a CGA is performed. All patients are invited to participate in the TENT study. Clinical data and blood samples for biomarker studies are collected at baseline. During follow-up, information about treatment complications, hospitalisations, functional decline, quality of life and mortality is collected. The primary outcome is the composite endpoint of functional decline or mortality at 1 year.

Discussion
Implementation of a routine clinical care pathway for older patients in need of intensive treatment provides the opportunity to study associations between determinants of frailty and outcomes of treatment. Results of the TENT study will support individualised treatment for future patients.

Trial registration
The study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22-10-2019.
Continuous elevation of procalcitonin in cirrhosis combined with hepatic carcinoma: a case report
Authors: Lu Juan , Chen Chun-lei , Jin Jian-di , Chen Jun , Yu Cheng-bo 
Published: January 2021

Abstract
Background
Serum levels of procalcitonin (PCT) are considered a useful biomarker for the diagnosis of bacterial infection or inflammation. There are few reports of high PCT levels in end-stage liver disease regardless of bacterial infection. Here, we present a case of extremely high PCT levels (> 100 ng/mL) in a patient with severe cirrhosis combined with hepatic carcinoma.

Case presentation
A 65-year-old man developed end-stage cirrhosis with hepatic carcinoma. Radiographic imaging showed a massive hepatocellular carcinoma with multiple loci lack of indications of resection. Hence, transcatheter hepatic arterial chemoembolization was performed three times over a period of 4 months. Before and after interventional therapies, the biochemistry laboratory results were only slightly abnormal except for persistently high PCT concentrations (> 100 ng/mL), irrespective of the evidence for bacterial infection or sepsis.

Conclusions
This case suggests that continuously high levels of PCT (> 100 ng/mL) may be present in advanced liver disease, particularly in complex situations such as decompensated cirrhosis and liver cancer, in the absence of severe infection or sepsis. This knowledge could expand the significance of PCT in liver disease.