bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory modules of human thermogenic adipocytes: functional genomics of large cohort and Meta-analysis derived marker-genes
Authors: B. Tóth Beáta , Barta Zoltán , Barta Ákos Barnabás , Fésüs László 
Published: December 2021

Abstract
Background
Recently, ProFAT and BATLAS studies identified brown and white adipocytes marker genes based on analysis of large databases. They offered scores to determine the thermogenic status of adipocytes using the gene-expression data of these markers. In this work, we investigated the functional context of these genes.

Results
Gene Set Enrichment Analyses (KEGG, Reactome) of the BATLAS and ProFAT marker-genes identified pathways deterministic in the formation of brown and white adipocytes. The collection of the annotated proteins of the defined pathways resulted in expanded white and brown characteristic protein-sets, which theoretically contain all functional proteins that could be involved in the formation of adipocytes. Based on our previously obtained RNA-seq data, we visualized the expression profile of these proteins coding genes and found patterns consistent with the two adipocyte phenotypes. The trajectory of the regulatory processes could be outlined by the transcriptional profile of progenitor and differentiated adipocytes, highlighting the importance of suppression processes in browning. Protein interaction network-based functional genomics by STRING, Cytoscape and R-Igraph platforms revealed that different biological processes shape the brown and white adipocytes and highlighted key regulatory elements and modules including GAPDH-CS, DECR1, SOD2, IL6, HRAS, MTOR, INS-AKT, ERBB2 and 4-NFKB, and SLIT-ROBO-MAPK. To assess the potential role of a particular protein in shaping adipocytes, we assigned interaction network location-based scores (betweenness centrality, number of bridges) to them and created a freely accessible platform, the AdipoNET (https//adiponet.com), to conveniently use these data. The Eukaryote Promoter Database predicted the response elements in the UCP1 promoter for the identified, potentially important transcription factors (HIF1A, MYC, REL, PPARG, TP53, AR, RUNX, and FoxO1).

Conclusion
Our integrative approach-based results allowed us to investigate potential regulatory elements of thermogenesis in adipose tissue. The analyses revealed that some unique biological processes form the brown and white adipocyte phenotypes, which presumes the existence of the transitional states. The data also suggests that the two phenotypes are not mutually exclusive, and differentiation of thermogenic adipocyte requires induction of browning as well as repressions of whitening. The recognition of these simultaneous actions and the identified regulatory modules can open new direction in obesity research.
Genome-wide association of single nucleotide polymorphism loci and candidate genes for frogeye leaf spot (Cercospora sojina) resistance in soybean
Authors: Gu Xin , Huang Shanshan , Zhu Zhiguo , Ma Yansong , Yang Xiaohe , Yao Liangliang , Gao Xuedong , Zhang Maoming , Liu Wei , Qiu Lei , Zhao Haihong , Wang Qingsheng , Li Zengjie , Li Zhimin , Meng Qingying , Yang Shuai , Wang Chao , Hu Xiping , Ding Junjie 
Published: December 2021

Abstract
Background
Frogeye leaf spot (FLS) is a destructive fungal disease that affects soybean production. The most economical and effective strategy to control FLS is the use of resistant cultivars. However, the use of a limited number of resistant loci in FLS management will be countered by the emergence of new high-virulence Cercospora sojina races. Therefore, we identified quantitative trait loci (QTL) that control resistance to FLS and identified novel resistant genes using a genome-wide association study (GWAS) on 234 Chinese soybean cultivars.

Results
A total of 30,890 single nucleotide polymorphism (SNP) markers were used to estimate linkage disequilibrium (LD) and population structure. The GWAS results showed four loci (p < 0.0001) distributed over chromosomes (Chr.) 5 and 20, that are significantly associated with FLS resistance. No previous studies have reported resistance loci in these regions. Subsequently, 45 genes in the two resistance-related haplotype blocks were annotated. Among them, Glyma20g31630 encoding pyruvate dehydrogenase (PDH), Glyma05g28980, which encodes mitogen-activated protein kinase 7 (MPK7), and Glyma20g31510, Glyma20g31520 encoding calcium-dependent protein kinase 4 (CDPK4) in the haplotype blocks deserves special attention.

Conclusions
This study showed that GWAS can be employed as an effective strategy for identifying disease resistance traits in soybean and narrowing SNPs and candidate genes. The prediction of candidate genes in the haplotype blocks identified by disease resistance loci can provide a useful reference to study systemic disease resistance.
Non-conveyance of older adult patients and association with subsequent clinical and adverse events after initial assessment by ambulance clinicians: a cohort analysis
Authors: Lederman Jakob , Lindström Veronica , Elmqvist Carina , Löfvenmark Caroline , Ljunggren Gunnar , Djärv Therese 
Published: December 2021

Abstract
Background
Older adults (age ≥ 65 years) represent a significant proportion of all patients who are not transported to hospital after assessment by ambulance clinicians (non-conveyed patients). This study aimed to fill the knowledge gap in the understanding of the prevalence of older adult non-conveyed patients and investigate their characteristics and risk factors for subsequent and adverse events with those of younger non-conveyed patients comparatively.

Methods
This population-based retrospective cohort study included all adult non-conveyed patients who availed the ambulance service of Region Stockholm, Sweden in 2015; they were age-stratified into two groups: 18–64 and ≥ 65 years. Inter-group differences in short-term outcomes (i.e. emergency department visits, hospitalisations, and mortality within 7 days following non-conveyance) were assessed using multivariate regression analyses.

Results
Older adult patients comprised 48% of the 17,809 non-conveyed patients. Dispatch priority levels were generally lower among older non-conveyed patients than among younger patients. Non-conveyance among older patients occurred more often during daytime, and they were more frequently assessed by ambulance clinicians with nonspecific presenting symptoms. Approximately one in five older adults was hospitalised within 7 days following non-conveyance. Patients presenting with infectious symptoms had the highest mortality risk following non-conveyance. Oxygen saturation level < 95% or systolic blood pressure > 160 mmHg had significantly higher associations with hospitalisation within 7 days following non-conveyance in older adult patients.

Conclusions
Older adult patients have an increased risk for adverse events following non-conveyance. In combination with a complex and variating presentation of symptoms and vital signs proved difficult for dispatch operators and ambulance clinicians to identify and assess, the identified risks raise questions on the patient safety of older adult non-conveyed patients. The results indicate a system failure that need to be managed within the ambulance service organisation to achieve higher levels of patient safety for older non-conveyed patients.
COPD – do the right thing
Authors: Sandelowsky Hanna , Weinreich Ulla Møller , Aarli Bernt B. , Sundh Josefin , Høines Kristian , Stratelis Georgios , Løkke Anders , Janson Christer , Jensen Christian , Larsson Kjell 
Published: December 2021

AbstractA gap exists between guidelines and real-world clinical practice for the management and treatment of chronic obstructive pulmonary disease (COPD). Although this has narrowed in the last decade, there is room for improvement in detection rates, treatment choices and disease monitoring. In practical terms, primary care practitioners need to become aware of the huge impact of COPD on patients, have non-judgemental views of smoking and of COPD as a chronic disease, use a holistic consultation approach and actively motivate patients to adhere to treatment.This article is based on discussions at a virtual meeting of leading Nordic experts in COPD (the authors) who were developing an educational programme for COPD primary care in the Nordic region. The article aims to describe the diagnosis and lifelong management cycle of COPD, with a strong focus on providing a hands-on, practical approach for medical professionals to optimise patient outcomes in COPD primary care.
Printed educational materials directed at Ontario family physicians do not improve adherence to guideline recommendations for diabetes management: a pragmatic, factorial, cluster randomized controlled trial [ISRCTN72772651]
Authors: Howie Alison H. , Klar Neil , Nash Danielle M. , Reid Jennifer N. , Zwarenstein Merrick 
Published: December 2021

Abstract
Background
Printed educational materials (PEMs) have long been used to inform clinicians on evidence-based practices. However, the evidence for their effects on patient care and outcomes is unclear. In Ontario, despite widely available clinical practice guidelines recommending antihypertensives and cholesterol-lowering agents for patients with diabetes, prescriptions remain low. We aimed to determine whether PEMs can influence physicians to intensify prescribing of these medications.

Methods
A pragmatic, 2 × 2 factorial, cluster randomized controlled trial was designed to ascertain the effect of two PEM formats on physician prescribing: a postcard-sized message (“outsert”) or a longer narrative article (“insert”). Ontario family physician practices (clusters) were randomly allocated to receive the insert, outsert, both or neither. Physicians were eligible if they were in active practice and their patients were included if they were over 65 years with a diabetes diagnosis; both were unaware of the trial. Administrative databases at ICES (formerly the Institute for Clinical Evaluative Sciences) were used to link patients to their physician and to analyse prescribing patterns at baseline and 1 year following PEM mailout. The primary outcome was intensification defined as the addition of a new antihypertensive or cholesterol-lowering agent, or dose increase of a current drug, measured at the patient level. Analyses were by intention-to-treat and accounted for the clustering of patients to physicians.

Results
We randomly assigned 4231 practices (39% of Ontario family physicians) with a total population of 185,526 patients (20% of patients with diabetes in Ontario primary care) to receive the insert, outsert, both, and neither; among these, 4118 practices were analysed (n = 1025, n = 1037, n = 1031, n = 1025, respectively). No significant treatment effect was found for the outsert (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.98 to 1.04) or the insert (OR 0.99, 95% CI 0.96 to 1.02). Percent of intensification in the four arms was similar (approximately 46%). Adjustment for physician characteristics (e.g., age, sex, practice location) had no impact on these findings.

Conclusions
PEMs have no effect on physician’s adherence to recommendations for the management of diabetes-related complications in Ontario. Further research should investigate the effect of other strategies to narrow this evidence-to-practice gap.

Trial registration
ISRCTN72772651. Retrospectively registered 21 July 2005.
A case of primary intestinal lymphangiectasia with non-Hodgkin lymphoma
Authors: Hu Doudou , Cui Xianghua , Ren Wanlei , Zhang Jian , Guan Xin , Jiang Xiangjun 
Published: December 2021

Abstract
Background
Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by the loss of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. Increasing evidence has demonstrated an association between PIL and lymphoma.

Case presentation
A 54-year-old man with a 20-year history of abdominal distension and bilateral lower limb edema was admitted. Laboratory investigations revealed lymphopenia, hypoalbuminemia, decreased triglyceride and cholesterol level. Colonoscopy showed multiple smooth pseudo polyps in the ileocecal valve and terminal ileum and histological examination showed conspicuous dilation of the lymphatic channels in the mucosa and submucosa. A diagnosis of PIL was made. Three years later colonoscopy of the patient showed an intraluminal proliferative mass in the ascending colon and biopsy examination confirmed a malignant non-Hodgkin lymphoma. Then the patient was been underwent chemotherapy, and his clinical condition is satisfactory.

Conclusion
Our report supports the hypothesis that PIL is associated with lymphoma development.
Changing socio-economic and ethnic disparities in influenza/A/H1N1 infection early in the 2009 UK epidemic: a descriptive analysis
Authors: Munday James D. , Pebody Richard , Atkins Katherine E. , van Hoek Albert Jan 
Published: December 2021

Abstract
Background
Higher incidence of and risk of hospitalisation and death from Influenza A(H1N1)pdm09 during the 2009 pandemic was reported in ethnic minority groups in many high-income settings including in the United Kingdom (UK). Many of these studies rely on geographical and temporal aggregation of cases and can be difficult to interpret due to the spatial and temporal factors in outbreak spread. Further, it can be challenging to distinguish between disparities in health outcomes caused by variation in transmission risk or disease severity.

Methods
We used anonymised laboratory confirmed and suspected case data, classified by ethnicity and deprivation status, to evaluate how disparities in risk between socio-economic and ethnic groups vary over the early stages of the 2009 Influenza A(H1N1)pdm09 epidemic in Birmingham and London, two key cities in the emergence of the UK epidemic. We evaluated the relative risk of infection in key ethnic minority groups and by national and city level deprivation rank.

Results
We calculated higher incidence in more deprived areas and in people of South Asian ethnicity in both Birmingham and London, although the magnitude of these disparities reduced with time. The clearest disparities existed in school-aged children in Birmingham, where the most deprived fifth of the population was 2.8 times more likely to be infected than the most affluent fifth of the population.

Conclusions
Our analysis shows that although disparities in reported cases were present in the early phase of the Influenza A(H1N1)pdm09 outbreak in both Birmingham and London, they vary substantially depending on the period over which they are measured. Further, the development of disparities suggest that clustering of social groups play a key part as the outbreak appears to move from one ethnic and socio-demographic group to another. Finally, high incidence and large disparities between children indicate that they may hold an important role in driving inequalities.
Quantitative contrast enhanced dual energy CT to predict avascular necrosis: a feasibility study of proximal humerus fractures
Authors: Hoover Kevin B. , Starks Alexandria O. , Robila Valentina , Riddle Daniel L. 
Published: December 2021

Abstract
Background
Avascular necrosis is a delayed complication of proximal humerus fractures that increases the likelihood of poor clinical outcomes. CT scans are routinely performed to guide proximal humerus fracture management. We hypothesized iodine concentration on post-contrast dual energy CT scans identifies subjects who develop avascular necrosis and ischemia due to compromised blood flow.

Materials and methods
55 patients with proximal humerus fractures enrolled between 2014 and 2017 underwent clinical, radiographic and contrast enhanced dual energy CT assessment. Iodine densities of the humeral head and the glenoid (control) were measured on CT. Subjects managed with open reduction internal fixation or conservatively (non-surgical) were followed for up to two years for radiographic evidence of avascular necrosis. Arthroplasty subjects underwent histopathologic evaluation for ischemia of the resected humeral head.

Results
17 of 55 subjects (30.9%) were treated conservatively, 21 (38.2%) underwent open reduction internal fixation and 17 of 55 (30.9%) underwent arthroplasty. Of the 38 subjects treated conservatively or with ORIF, 20 (52.6%) completed 12 months of follow up and 14 (36.8%) 24 months of follow up. At 12 months follow up, two of 20 subjects (10%) and at 24 months 3 of 14 subjects (21.4%) developed avascular necrosis. At 12 months, the mean humerus/glenoid iodine ratio was 1.05 (standard deviation 0.24) in subjects with AVN compared to 0.91 (0.24) in those who did not. At 24 months, subjects with avascular necrosis had a mean humerus/glenoid iodine concentration ratio of 1.06 (0.17) compared to 0.924 (0.21) in those who did not. Of 17 arthroplasty subjects, 2 had severe ischemia and an iodine ratio of 1.08 (0.30); 5 had focal ischemia and a ratio of 1.00 (0.36); and 8 no ischemia and a ratio of 0.83 (0.08).

Conclusions
Quantifying iodine using dual energy CT in subjects with proximal humerus fractures is technically feasible. Preliminary data suggest higher humeral head iodine concentration may increase risk of avascular necrosis; however, future studies must enroll and follow enough subjects managed with open reduction internal fixation or conservatively for two or more years to provide statistically significant results.
Trial Registrations NCT02170545 registered June 23, 2014, ClinicalTrials.gov.
First diagnosis of thrombotic thrombocytopenic purpura after SARS-CoV-2 vaccine – case report
Authors: Osmanodja Bilgin , Schreiber Adrian , Schrezenmeier Eva , Seelow Evelyn 
Published: December 2021

Abstract
Background
We report a case of a 25-year-old male patient, who developed acquired thrombotic thrombocytopenic purpura (aTTP) after receiving a first dose of mRNA-based SARS-CoV-2 vaccine Spikevax (mRNA-1273, Moderna Biotech, USA). While this is the first case in literature describing a case of aTTP after receiving the Spikevax vaccine, there are two other cases after mRNA-based Covid-19 vaccine and two after adenoviral SARS-CoV-2 vaccine.

Case presentation
The patient presented with persisting malaise, fever, headache, word-finding difficulties, nausea, vomiting, petechial bleeding, and hematuria 13 days after receiving a first dose of vaccination. Laboratory testing showed low platelet count, Coombs-negative hemolytic anemia, and mild acute kidney injury. We excluded vaccine induced immune thrombotic thrombocytopenia (VITT) as another important differential diagnosis and the final diagnosis was established after ADAMTS-13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) activity was found to be < 1% (reference range > 40%) and ADAMTS-13 antibodies being 72.2 IU/L (reference range < 12 IU/L).
We initiated empiric therapy of plasmapheresis and corticosteroids on admission and started caplacizumab the day after. The patient’s thrombocyte count normalized 3 days after admission, hemolysis and acute kidney injury resolved after 2 weeks. The patient received 2 doses of rituximab (1 g each) after the diagnosis of immune TTP was established. One month after the initial presentation, the patient is in good overall condition, but still receives daily caplacizumab due to ADAMTS-13 activity of < 1%.

Conclusions
Low platelet count after vaccination against SARS-CoV-2 has gained attraction after vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described as a rare but severe complication of adenoviral-based vaccines. Thrombotic thrombocytopenic purpura (TTP) is an important differential diagnosis, but there are only few reports of TTP following SARS-CoV-2 vaccination. Despite pathophysiological and clinical differences of both entities, diagnostic uncertainty can result in the acute setting, since they share main symptoms such as headache and neurological alterations in addition to thrombocytopenia. In difference to other cases reported, this patient developed first symptoms of TTP as early as 4 days after vaccination, which suggests that vaccination merely acted as trigger for occult TTP, instead of truly inducing an autoimmunological process.
CASP5 and CR1 as potential biomarkers for Kawasaki disease: an Integrated Bioinformatics-Experimental Study
Authors: Rahmati Yazdan , Mollanoori Hasan , Najafi Sajad , Esmaeili Sajjad , Alivand Mohammad Reza 
Published: December 2021

Abstract
Background
Kawasaki disease (KD) is a pediatric inflammatory disorder causes coronary artery complications. The disease overlapping manifestations with a set of symptomatically like diseases such as bacterial and viral infections, juvenile idiopathic arthritis, Henoch-Schönlein purpura, infection of unknown etiology, group-A streptococcal and adenoviral infections, and incomplete KD could lead to misdiagnosis of the disease.

Methods
In the present study, we applied weighted gene co-expression network analysis (WGCNA) to identify network modules of co-expressed genes in GSE73464 and also, limma package was used to identify the differentially expressed genes (DEGs) in KD expression arrays composed of GSE73464, GSE18606, GSE109351, and GSE68004. By merging the results of WGCNA and limma, we detected hub genes. Then, analyzed the peripheral blood mononuclear cells (PBMCs) of 16 patients and 8 control subjects using Real-Time Polymerase Chain Reaction (RT-PCR) to evaluate the previous results.

Results
We assessed the diagnostic potency of the screened genes by plotting the area under curve (AUC). We finally identified 2 genes CASP5(Caspase 5) and CR1(Complement C3b/C4b Receptor 1) which were shown to potentially discriminate KD from other similar diseases and also from healthy people.

Conclusions
The results of RT-PCR and AUC confirmed the diagnostic potentials of two suggested biomarkers for KD.