bluuebunny/crossref_metadata_2025_split huggingface dataset:
Msx1 haploinsufficiency modifies the Pax9-deficient cardiovascular phenotype
Authors: Khasawneh Ramada R. , Kist Ralf , Queen Rachel , Hussain Rafiqul , Coxhead Jonathan , Schneider Jürgen E. , Mohun Timothy J. , Zaffran Stéphane , Peters Heiko , Phillips Helen M. , Bamforth Simon D. 
Published: October 2021

Abstract
Background
Successful embryogenesis relies on the coordinated interaction between genes and tissues. The transcription factors Pax9 and Msx1 genetically interact during mouse craniofacial morphogenesis, and mice deficient for either gene display abnormal tooth and palate development. Pax9 is expressed specifically in the pharyngeal endoderm at mid-embryogenesis, and mice deficient for Pax9 on a C57Bl/6 genetic background also have cardiovascular defects affecting the outflow tract and aortic arch arteries giving double-outlet right ventricle, absent common carotid arteries and interruption of the aortic arch.

Results
In this study we have investigated both the effect of a different genetic background and Msx1 haploinsufficiency on the presentation of the Pax9-deficient cardiovascular phenotype. Compared to mice on a C57Bl/6 background, congenic CD1-Pax9–/– mice displayed a significantly reduced incidence of outflow tract defects but aortic arch defects were unchanged. Pax9–/– mice with Msx1 haploinsufficiency, however, have a reduced incidence of interrupted aortic arch, but more cases with cervical origins of the right subclavian artery and aortic arch, than seen in Pax9–/– mice. This alteration in arch artery defects was accompanied by a rescue in third pharyngeal arch neural crest cell migration and smooth muscle cell coverage of the third pharyngeal arch arteries. Although this change in phenotype could theoretically be compatible with post-natal survival, using tissue-specific inactivation of Pax9 to maintain correct palate development whilst inducing the cardiovascular defects was unable to prevent postnatal death in the mutant mice. Hyoid bone and thyroid cartilage formation were abnormal in Pax9–/– mice.

Conclusions
Msx1 haploinsufficiency mitigates the arch artery defects in Pax9–/– mice, potentially by maintaining the survival of the 3rd arch artery through unimpaired migration of neural crest cells to the third pharyngeal arches. With the neural crest cell derived hyoid bone and thyroid cartilage also being defective in Pax9–/– mice, we speculate that the pharyngeal endoderm is a key signalling centre that impacts on neural crest cell behaviour highlighting the ability of cells in different tissues to act synergistically or antagonistically during embryo development.
AutoCNV: a semiautomatic CNV interpretation system based on the 2019 ACMG/ClinGen Technical Standards for CNVs
Authors: Fan Chunna , Wang Zhonghua , Sun Yan , Sun Jun , Liu Xi , Kang Licheng , Xu Yingshuo , Yang Manqiu , Dai Wentao , Song Lijie , Wei Xiaoming , Xiang Jiale , Huang Hui , Zhou Meizhen , Zeng Fanwei , Huang Lin , Xu Zhengfeng , Peng Zhiyu 
Published: October 2021

Abstract
Background
The American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) presented technical standards for interpretation and reporting of constitutional copy-number variants in 2019 (the standards). Although ClinGen developed a web-based CNV classification calculator based on scoring metrics, it can only track and tally points that have been assigned based on observed evidence. Here, we developed AutoCNV (a semiautomatic automated CNV interpretation system) based on the standards, which can automatically generate predictions on 18 and 16 criteria for copy number loss and gain, respectively.

Results
We assessed the performance of AutoCNV using 72 CNVs evaluated by external independent reviewers and 20 illustrative case examples. Using AutoCNV, it showed that 100 % (72/72) and 95 % (19/20) of CNVs were consistent with the reviewers’ and ClinGen-verified classifications, respectively. AutoCNV only required an average of less than 5 milliseconds to obtain the result for one CNV with automated scoring. We also applied AutoCNV for the interpretation of CNVs from the ClinVar database and the dbVar database. We also developed a web-based version of AutoCNV (wAutoCNV).

Conclusions
AutoCNV may serve to assist users in conducting in-depth CNV interpretation, to accelerate and facilitate the interpretation process of CNVs and to improve the consistency and reliability of CNV interpretation.
Map-based cloning and promoter variation analysis of the lobed leaf gene BoLMI1a in ornamental kale (Brassica oleracea L. var. acephala)
Authors: Zhang Bin , Chen Wendi , Li Xing , Ren Wenjing , Chen Li , Han Fengqing , Fang Zhiyuan , Yang Limei , Zhuang Mu , Lv Honghao , Wang Yong , Zhang Yangyong 
Published: October 2021

Abstract
Background
Leaf shape is an important agronomic trait in ornamental kale (Brassica oleracea L. var. acephala). Although some leaf shape-related genes have been reported in ornamental kale, the detailed mechanism underlying leaf shape formation is still unclear. Here, we report a lobed-leaf trait in ornamental kale, aiming to analyze its inheritance and identify the strong candidate gene.

Results
Genetic analysis of F2 and BC1 populations demonstrate that the lobed-leaf trait in ornamental kale is controlled by a single dominant gene, termed BoLl-1 (Brassica oleracea lobed-leaf). By performing whole-genome resequencing and linkage analyses, the BoLl-1 gene was finely mapped to a 127-kb interval on chromosome C09 flanked by SNP markers SL4 and SL6, with genetic distances of 0.6 cM and 0.6 cM, respectively. Based on annotations of the genes within this interval, Bo9g181710, an orthologous gene of LATE MERISTEM IDENTITY 1 (LMI1) in Arabidopsis, was predicted as the candidate for BoLl-1, and was renamed BoLMI1a. The expression level of BoLMI1a in lobed-leaf parent 18Q2513 was significantly higher compared with unlobed-leaf parent 18Q2515. Sequence analysis of the parental alleles revealed no sequence variations in the coding sequence of BoLMI1a, whereas a 1737-bp deletion, a 92-bp insertion and an SNP were identified within the BoLMI1a promoter region of parent 18Q2513. Verification analyses with BoLMI1a-specific markers corresponding to the promoter variations revealed that the variations were present only in the lobed-leaf ornamental kale inbred lines.

Conclusions
This study identified a lobed-leaf gene BoLMI1a, which was fine-mapped to a 127-kb fragment. Three variations were identified in the promoter region of BoLMI1a. The transcription level of BoLMI1a between the two parents exhibited great difference, providing new insight into the molecular mechanism underlying leaf shape formation in ornamental kale.
The bayberry database: a multiomic database for Myrica rubra, an important fruit tree with medicinal value
Authors: Ren Haiying , He Yuanhao , Qi Xingjiang , Zheng Xiliang , Zhang Shuwen , Yu Zheping , Hu Fengrong 
Published: October 2021

Abstract
Background
Chinese bayberry (Myrica rubra Sieb. & Zucc.) is an important fruit tree in China, and has high medicinal value. At present, the genome, transcriptome and germplasm resources of bayberry have been reported. In order to make more convenient use of these data, the Bayberry Database was established.

Results
The Bayberry Database is a comprehensive and intuitive data platform for examining the diverse annotated genome and germplasm resources of this species. This database contains nine central functional domains to interact with multiomic data: home, genome, germplasm, markers, tools, map, expression, reference, and contact. All domains provide pathways to a variety of data types composed of a reference genome sequence, transcriptomic data, gene patterns, phenotypic data, fruit images of Myrica rubra varieties, gSSR data, gene maps with annotation and evolutionary analyses. The tools module includes BLAST search, keyword search, sequence fetch and enrichment analysis functions.

Conclusions
The web address of the database is as follows http://www.bayberrybase.cn/. The Myrica rubra database is an intelligent, interactive, and user-friendly system that enables researchers, breeders and horticultural personnel to browse, search and retrieve relevant and useful information and thus facilitate genomic research and breeding efforts concerning Myrica rubra. This database will be of great help to bayberry research and breeding in the future.
Efficiency of different flows for apneic oxygenation when using high flow nasal oxygen application – a technical simulation
Authors: Wetsch W. A. , Herff H. , Schroeder D. C. , Sander D. , Böttiger B. W. , Finke S. R. 
Published: October 2021

Abstract
Background
Preoxygenation and application of apneic oxygenation are standard to prevent patients from desaturation e.g. during emergency intubation. The time before desaturation occurs can be prolonged by applying high flow oxygen into the airway. Aim of this study was to scientifically assess the flow that is necessary to avoid nitrogen entering the airway of a manikin model during application of pure oxygen via high flow nasal oxygen.

Methods
We measured oxygen content over a 20-min observation period for each method in a preoxygenated test lung applied to a human manikin, allowing either room air entering the airway in control group, or applying pure oxygen via high flow nasal oxygen at flows of 10, 20, 40, 60 and 80 L/min via nasal cannula in the other groups. Our formal hypothesis was that there would be no difference in oxygen fraction decrease between the groups.

Results
Oxygen content in the test lung dropped from 97 ± 1% at baseline in all groups to 43 ± 1% in the control group (p < 0.001 compared to all other groups), to 92 ± 1% in the 10 L/min group, 92 ± 1% in the 20 L/min group, 90 ± 1% in the 40 L/min group, 89 ± 0% in the 60 L/min group and 87 ± 0% in the 80 L/min group. Apart from comparisons 10 l/ min vs. 20 L/min group (p = .715) and 10/L/min vs. 40 L/min group (p = .018), p was < 0.009 for all other comparisons.

Conclusions
Simulating apneic oxygenation in a preoxygenated manikin connected to a test lung over 20 min by applying high flow nasal oxygen resulted in the highest oxygen content at a flow of 10 L/min; higher flows resulted in slightly decreased oxygen percentages in the test lung.
The predictive role of early recurrences of atrial arrhythmias after pulmonary vein cryoballoon ablation. Is blanking period an outdated concept? Insights from 12-month continuous cardiac monitoring
Authors: Davtyan Karapet V. , Topchyan Arpi H. , Brutyan Hakob A. , Kalemberg Elena N. , Kharlap Maria S. , Simonyan Georgiy Yu. , Kalemberg Andrey A. , Kuznetsova Maria V. 
Published: October 2021

Abstract
Background
Early recurrences of atrial arrhythmias (ERAA) after atrial fibrillation (AF) catheter ablation do not predict procedural failure. A well-demarcated homogeneous lesion delivered by cryoballoon is less arrhythmogenic, and the recommended three-months blanking period may not refer to cryoballoon ablation (CBA).

Objective
We aimed to evaluate the predictive role of ERAA after second-generation CBA using an implantable loop recorder.

Methods
This prospective observational study enrolled 100 patients (58 males, median age 58) with paroxysmal/persistent AF undergoing pulmonary vein (PV) CBA using second-generation cryoballoon with simultaneous ECG loop recorder implantation. The duration of follow-up was 12 months, with scheduled visits at 3, 6 and 12 months.

Results
99 patients from 100 completed the 12-month follow-up period. ERAA occurred in 31.3 % of patients. 83.9 % of patients with ERAA also developed late recurrences. The 12-month freedom from AF in patients with ERAA was significantly lower than in those without ERAA (p < 0.0001). Non-paroxysmal AF and longer arrhythmia history were associated with increased risk of both early (HR 3.27; 95 % CI 1.32–8.08; p = 0.010 and HR 1.0147; 95 % CI 1.008–1.086; p = 0.015, respectively) and late recurrences (HR 3.89; 95 % CI 1.67–9.04; p = 0.002 and HR 1.0142; 95 % CI 1.007–1.078; p = 0.019, respectively) of AF. ERAA were another predictor for procedural failure (HR 15.2; 95 % CI (6.42–35.99; p = 0.019).

Conclusions
ERAA occurred in the third of the patients after PV second-generation CBA and are strongly associated with procedural failure. Longer duration of AF history and persistent AF are independent predictors of AF’s early and late recurrence.
Osteopathy in Germany: attitudes, beliefs and handling among general practitioners – results of a nationwide cross-sectional questionnaire survey
Authors: Schmid Gordian L. , Kluge Jeremias , Deutsch Tobias , Geier Anne-Kathrin , Bleckwenn Markus , Unverzagt Susanne , Frese Thomas 
Published: October 2021

AbstractBackgroundOsteopathy is a type of complementary medicine based on specific manual techniques. In many countries, including Germany, the profession is not officially regulated, and evidence for the effectiveness of osteopathy is insufficient for most diseases. Nevertheless, many health insurances in Germany offer reimbursement for therapy costs, if osteopathy is recommended by a physician.This cross-sectional survey of German general practitioners (GPs) explored beliefs and attitudes towards osteopathic medicine and described their daily interactions with it.MethodsA random sample of 1000 GPs from all federal states was surveyed by mail using a self-designed questionnaire. We collected data on sociodemographics, personal experiences with osteopathy, and attitudes and expectations towards osteopathy. In particular, participants were asked about indications for osteopathic treatment and their beliefs about its effectiveness for different patient groups and diagnoses. A self-designed score was used to estimate general attitudes towards osteopathy and identify factors correlated with greater openness. Additionally, we performed logistic regression to reveal factors associated with the frequency of recommending osteopathy to patients.ResultsResponse rate was 34.4%. 46.5% of participants were women, and the median age was 56.0 years. 91.3% of GPs had referred patients to an osteopath, and 88.0% had recommended osteopathy to their patients. However, 57.5% acknowledged having little or no knowledge about osteopathy. Most frequent reasons for a recommendation were spinal column disorders (46.2%), other complaints of the musculoskeletal system (18.2%) and headaches (9.8%). GPs estimated the highest benefit for chronically ill and middle-aged adults. Female gender (OR 2.09; 95%CI 1.29–3.38) and personal treatment experiences (OR 5.14; 95%CI 2.72–9.72) were independently positively associated with more frequent treatment recommendation.ConclusionGPs in Germany have frequent contact with osteopathy, and the vast majority have recommended osteopathic treatment to some extent in their practice, with foci and opinions comparable to other Western countries. The discrepancy between GPs making frequent referrals for osteopathic treatment while self-assessing to have little knowledge about it demonstrates need for intensified research on the collaboration with osteopaths and how to best integrate osteopathic treatments. Our results may help to focus future effectiveness studies on most relevant clinical conditions in general practice.
The clinical significance of preoperative serum fibrinogen levels and platelet counts in patients with gallbladder carcinoma
Authors: Cao Peng , Jiang Lei , Zhou Liang-Yi , Chen Yan-Ling 
Published: October 2021

Abstract
Background
Gallbladder carcinoma (GBC) was the most common malignancy of biliary tract. Patients with malignancies frequently present with activated coagulation pathways, which might potentially related to tumor progression and prognosis. The purpose of the study was to investigate the clinical significance of preoperative serum fibrinogen levels and platelet counts in GBC patients.

Methods

The preoperative fasting serum fibrinogen levels and platelet counts of 58 patients with GBC were measured by AUV2700 automatic biochemical analyzer, as well as 60 patients with cholesterol polyps and 60 healthy volunteers. Kaplan–Meier survival analysis was applied to show the correction between fibrinogen levels and outcome after surgery.

Results
The fibrinogen levels of patients with GBC were significantly higher than healthy gallbladder and cholesterol polyp of gallbladder (p < 0.001 and p < 0.001, respectively). In GBC, fibrinogen levels were associated with tumor depth (p = 0.001), lymph node metastasis (p = 0.002), distant metastasis (p < 0.001) and Tumor Node Metastasis (TNM) stage (p < 0.001). The levels in TNM stage IV disease were significantly higher than stage III or stage I + II disease (p = 0.048 and p < 0.001, respectively), and in TNM stage III disease were significantly higher than stage I + II disease (p = 0.002). Furthermore, the overall survival was better in low fibrinogen level group than in high fibrinogen level group (p < 0.001). However, thrombocytosis was not significantly associated with overall survivals (p > 0.05) in multivariate analysis.

Conclusions
The preoperative serum fibrinogen levels and platelet counts might be reliable biomarkers for the occurance of disease, tumor depth, lymph node metastasis, distant metastasis and advanced TNM stage in patients with GBC. The serum fibrinogen levels might be a prognostic factor to predict outcome for GBC patients suffering from surgery treatment. Anticoagulation therapy might be considered to control cancer progression in future studies.
Prevalence and characteristics of chronic Pain in the Chinese community-dwelling elderly: a cross-sectional study
Authors: Li Xiahui , Zhu Wei , Li Jiping , Huang Chan , Yang Fan 
Published: October 2021

Abstract
Background
Chronic pain adversely affects health and daily life in the elderly. Gaining insight into chronic pain that affects the community-dwelling elderly is crucial for pain management in China, which possesses the largest elderly population in the world.

Methods
This is a cross-sectional design study that followed the STROBE Guideline. A randomized cluster sampling method was used to recruit participants in the Sichuan Province from Dec 2018 to May 2019. In addition, face-to-face interviews were conducted to collect socio-demographic data, characteristics and health-seeking behaviors of chronic pain through a self-designed questionnaire.

Results
A total of 1381 older adults participated in this study. Among these participants, 791 (57.3%) had chronic pain. Here, prevalence and pain intensity were both found to increase from the 60–69 group to the 70–79 group, which then decreased in the ≥80 group with no significant differences in sex (p > 0.05). The most common pain locations were observed in the legs/feet (53.5%), head (23.6) and abdomen/pelvis (21.1%). Among the elderly suffering from chronic pain, 29.4% sought medical help, 59.2% received medication and 59.7% adopted non-drug therapy.

Conclusion
Chronic pain is a common health concern in the Chinese community-dwelling elderly, which possesses different characteristics than other countries’ populations. Therefore, easier access to medication assistance and provision of scientific guidance for non-drug therapy may serve as satisfactory approaches in improving pain management.
Improvements in six aspects of quality of care of incident hemodialysis patients – a real-world experience
Authors: Drozdz Maciej , Frazão João , Silva Fatima , Das Partha , Kleophas Werner , Al Badr Wisam , Brzosko Szymon , Jacobson Stefan H. 
Published: October 2021

Abstract
Background
The transition from chronic kidney disease stage 5 to initiation of hemodialysis has gained increased attention in recent years as this period is one of high risk for patients with an annual mortality rate exceeding 20%. Morbidity and mortality in incident hemodialysis patients are partially attributed to failure to attain guideline-based targets. This study focuses on improvements in six aspects of quality of dialysis care (adequacy, anemia, nutrition, chronic kidney disease-mineral bone disorder (CKD-MBD), blood pressure and vascular access) aligning with KDIGO guidelines, during the first 6 months of hemodialysis.

Methods
We analyzed patient demographics, practice patterns and laboratory data in all 3 462 patients (mean age 65.9 years, 41% females) on hemodialysis (incident <90 days on hemodialysis, n=603, prevalent ≥90 days on hemodialysis, mean 55 months, n=2 859) from all 56 DaVita centers in Poland (51 centers) and Portugal (5 centers). 80% of patients had hemodialysis and 20% hemodiafiltration. Statistical analyses included unpaired and paired Students t-test, Chi-2 analyses, McNemar test and logistic regression analysis.

Results
Incident patients had lower Kt/V (1.4 vs 1.7, p<0.001), lower serum albumin (37 vs 40 g/l, p=0.001), lower Hb (9.9 vs 11.0 g/dl, p<0.001), lower TSAT (26 vs 31%, p<0.001), lower iPTH (372 vs 496 pg/ml, p<0.001), more often a central venous catheter (68 vs 26%, p<0.001), less often an AV fistula (34 vs 70 %, p<0.001) compared with all prevalent patients. Significantly more prevalent patients achieved international treatment targets.
Improvements in quality of care was also analyzed in a subgroup of 258 incident patients who were followed prospectively for 6 months. We observed significant improvements in Kt/V (p<0.001), albumin (p<0.001), Hb (p<0.001) transferrin saturation (TSAT, p<0.001), iPTH (p=0.005) and an increased use of AV fistula (p<0.001). Furthermore, logistic regression analyses identified treatment time and TSAT as major factors influencing the attainment of adequacy and anemia treatment targets.

Conclusion
This large real-world European multicenter analysis of representative incident hemodialysis patients indicates that the use of medical protocols and medical targets assures significant improvements in quality of care, which may correspond to better outcomes. A selection bias of survivors with less comorbidities in prevalent patients may have influenced the results.
Online clinical pathway for chronic kidney disease management in primary care: a retrospective cohort study
Authors: Donald Maoliosa , Smekal Michelle D. , Elliott Meghan J. , McBrien Kerry , Weaver Robert G. , Manns Braden J. , Tonelli Marcello , Bello Aminu , Straus Sharon E. , Scott-Douglas Nairne , Jindal Kailash , Hemmelgarn Brenda R. 
Published: October 2021

Abstract
Background
Clinical pathways aim to improve patient care. We sought to determine whether an online chronic kidney disease (CKD) clinical pathway was associated with improvements in CKD management.

Methods
We conducted a retrospective pre/post population-based cohort study using linked health data from Alberta, Canada. We included adults 18 years or older with mean estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2. The primary outcome was measurement of an outpatient urine albumin creatinine ratio (ACR) in a 28-day period, among people without a test in the prior year. Secondary outcomes included use of guideline-recommended drug therapies (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and statins).

Results
The study period spanned October 2010 to March 2017. There were 84 independent 28-day periods (53 pre, 31 post pathway implementation) including 345,058 adults. The population was predominantly female (56%) with median age 77 years; most had category 3A CKD (67%) and hypertension (82%). In adjusted segmented regression models, the increase in the rate of change of ACR testing was greatest in Calgary zone (adjusted OR 1.19 per year, 95% CI 1.16–1.21), where dissemination of the pathway was strongest; this increase was more pronounced in those without diabetes (adjusted OR 1.25 per year, 95% CI 1.21–1.29). Small improvements in guideline-concordant medication use were also observed.

Conclusions
Following implementation of an online CKD clinical pathway, improvements in ACR testing were evident in regions where the pathway was most actively used, particularly among individuals without diabetes.