bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic performance of D-dimer in predicting venous thromboembolism and acute aortic dissection
Authors: Koch Vitali , Biener Moritz , Müller-Hennessen Matthias , Vafaie Mershad , Staudacher Ingo , Katus Hugo A , Giannitsis Evangelos 
Published: March 2020

Abstract

Background
D-dimer is elevated in a variety of conditions. The purpose of this study was to assess the positive predictive value of D-dimer to rule in patients with confirmed pulmonary embolism, deep vein thrombosis, acute aortic dissection or thrombosis of the upper extremity in comparison to patients with elevated D-dimer for other reasons.

Methods and results
We studied 1334 patients presenting to the emergency department with pulmonary embolism (n=193), deep vein thrombosis (n=73), acute aortic dissection (n=22), thrombosis of the upper extremity (n=8) and 1038 controls. The positive predictive value was increased with higher D-dimer concentrations improving the ability to identify diseases with high thrombus burden. Patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity showed a maximum positive predictive value of 85.2% at a D-dimer level of 7.8 mg/L (95% confidence interval (CI) 78.1 to 90.4). The maximum positive predictive value was lower in cancer patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity, reaching 68.9% at a D-dimer level of 7.5 mg/L (95% CI 57.4 to 78.4). The positive likelihood ratio was very consistent with the positive predictive value. Using a cut-off level of 0.5 mg/L, D-dimer showed a high sensitivity of at least 93%, but a very low specificity of nearly 0%. Conversely, an optimised cut-off value of 4.6 mg/L increased specificity to 95% for the detection of life-threatening venous thromboembolism, acute aortic dissection or thrombosis of the upper extremity at the costs of moderate sensitivities (58% for pulmonary embolism, 41% for deep vein thrombosis, 65% for pulmonary embolism with co-existent deep vein thrombosis, 50% for acute aortic dissection and 13% for thrombosis of the upper extremity). Using the same cut-off in cancer patients, higher values were observed for sensitivity at a specificity level of more than 95%. The area under the curve for the discrimination of venous thromboembolism/acute aortic dissection/thrombosis of the upper extremity from controls was significantly higher in cancer versus non-cancer patients (area under the curve 0.905 in cancer patients, 95% CI 0.89 to 0.92, vs. area under the curve 0.857 in non-cancer patients, 95% CI 0.84 to 0.88; P=0.0349).

Conclusion
D-dimers are useful not only to rule out but also to rule in venous thromboembolism and acute aortic dissection with an at least moderate discriminatory ability, both in patients with and without cancer.
Time to debridement in open high-grade lower limb fractures and its effect on union and infections: A prospective study in a tropical setting
Authors: Joseph Christina Marie , Jepegnanam Thilak Samuel , Ramasamy Boopalan , Cherian Vinoo Mathew , Nithyananth Manasseh , Sudarsanam Thambu David , Premkumar Prasanna Samuel 
Published: March 2020

Purpose: To prospectively evaluate whether time to debridement has any correlation with union, infection, and quality of life in high-grade lower limb fractures in a tropical setting. Methods: A prospective cohort study was conducted at a tertiary care center in South India. Two hundred fifty-four adult skeletally mature patients with 301 grade 3 fractures involving the femur, tibia, or fibula were recruited. The cohort was empirically divided into two groups (early and late) based on the time to debridement (less than or more than 12 h from injury). Outcome: The primary outcome was nonunion. Secondary outcomes were deep infection rates and patients’ quality of life. Short form-36 (SF-36) and short musculoskeletal functional assessment (SMFA) questionnaires were also used. Patients were followed up for 9 months. Results: The follow-up rate was 93%. The late group had a significantly higher risk of nonunion (odds ratio(OR): 6.5, 95% confidence interval (CI): 2.82–14.95) and infections (OR: 6.05, 95% CI: 2.85–12.82). There was a 4% increase in the infection risk for each hour of delay for the initial 50 h ( p < 0.0001). SF-36 and SMFA scores were superior in the early group ( p < 0.0001). Conclusion: The study contradicts findings reported in the literature from the West. Our study was in agreement with our hypothesis and proved that debridement within 12 h resulted in significantly lower rates of nonunion and infections and an overall improved quality of life in high-grade open lower limb fractures in a developing country. Level of evidence: Level II Trial registration: German Clinical Trials Register DRKS00015186
FcRn augments induction of tissue factor activity by IgG-containing immune complexes
Authors: Cines Douglas B. , Zaitsev Sergei , Rauova Lubica , Rux Ann H. , Stepanova Victoria , Krishnaswamy Sriram , Sarkar Amrita , Kowalska M. Anna , Zhao Guohua , Mast Alan E. , Blumberg Laurence J. , McCrae Keith R. , Poncz Mortimer , Hubbard Jonathan J. , Pyzik Michal , Blumberg Richard S. 
Published: March 2020

AbstractThromboembolism complicates disorders caused by immunoglobulin G (IgG)–containing immune complexes (ICs), but the underlying mechanisms are incompletely understood. Prior evidence indicates that induction of tissue factor (TF) on monocytes, a pivotal step in the initiation, localization, and propagation of coagulation by ICs, is mediated through Fcγ receptor IIa (FcγRIIa); however, the involvement of other receptors has not been investigated in detail. The neonatal Fc receptor (FcRn) that mediates IgG and albumin recycling also participates in cellular responses to IgG-containing ICs. Here we asked whether FcRn is also involved in the induction of TF-dependent factor Xa (FXa) activity by IgG-containing ICs by THP-1 monocytic cells and human monocytes. Induction of FXa activity by ICs containing IgG antibodies to platelet factor 4 (PF4) involved in heparin-induced thrombocytopenia (HIT), β-2-glycoprotein-1 implicated in antiphospholipid syndrome, or red blood cells coated with anti-(α)-Rh(D) antibodies that mediate hemolysis in vivo was inhibited by a humanized monoclonal antibody (mAb) that blocks IgG binding to human FcRn. IgG-containing ICs that bind to FcγR and FcRn induced FXa activity, whereas IgG-containing ICs with an Fc engineered to be unable to engage FcRn did not. Infusion of an α-FcRn mAb prevented fibrin deposition after microvascular injury in a murine model of HIT in which human FcγRIIa was expressed as a transgene. These data implicate FcRn in TF-dependent FXa activity induced by soluble and cell-associated IgG-containing ICs. Antibodies to FcRn, now in clinical trials in warm autoimmune hemolytic anemia to lower IgG antibodies and IgG containing ICs may also reduce the risk of venous thromboembolism.
TRIM33 prevents pulmonary fibrosis by impairing TGF-β1 signalling
Authors: Boutanquoi Pierre-Marie , Burgy Olivier , Beltramo Guillaume , Bellaye Pierre-Simon , Dondaine Lucile , Marcion Guillaume , Pommerolle Lenny , Vadel Aurélie , Spanjaard Maximilien , Demidov Oleg , Mailleux Arnaud , Crestani Bruno , Kolb Martin , Garrido Carmen , Goirand Françoise , Bonniaud Philippe 
Published: March 2020

BackgroundIdiopathic pulmonary fibrosis (IPF) is a devastating disease characterised by myofibroblast proliferation and abnormal extracellular matrix accumulation in the lungs. Transforming growth factor (TGF)-β1 initiates key profibrotic signalling involving the SMAD pathway and the small heat shock protein B5 (HSPB5). Tripartite motif-containing 33 (TRIM33) has been reported to negatively regulate TGF-β/SMAD signalling, but its role in fibrogenesis remains unknown. The objective of this study was to elucidate the role of TRIM33 in IPF.MethodsTRIM33 expression was assessed in the lungs of IPF patients and rodent fibrosis models. Bone marrow-derived macrophages (BMDM), primary lung fibroblasts and 3D lung tissue slices were isolated fromTrim33-floxed mice and cultured with TGF-β1 or bleomycin (BLM).Trim33expression was then suppressed by adenovirus Cre recombinase (AdCre). Pulmonary fibrosis was evaluated in haematopoietic-specificTrim33knockout mice and inTrim33-floxed mice that received AdCre and BLM intratracheally.ResultsTRIM33 was overexpressed in alveolar macrophages and fibroblasts in IPF patients and rodent fibrotic lungs.Trim33inhibition in BMDM increased TGF-β1 secretion upon BLM treatment. Haematopoietic-specificTrim33knockout sensitised mice to BLM-induced fibrosis. In primary lung fibroblasts and 3D lung tissue slices,Trim33deficiency increased expression of genes downstream of TGF-β1. In mice, AdCre-Trim33inhibition worsened BLM-induced fibrosis.In vitro, HSPB5 was able to bind directly to TRIM33, thereby diminishing its protein level and TRIM33/SMAD4 interaction.ConclusionOur results demonstrate a key role of TRIM33 as a negative regulator of lung fibrosis. Since TRIM33 directly associates with HSPB5, which impairs its activity, inhibitors of TRIM33/HSPB5 interaction may be of interest in the treatment of IPF.
Respiratory surveillance in mineral dust-exposed workers
Authors: Wood Clare , Yates Deborah 
Published: March 2020

Recently, there has been a worldwide resurgence in pneumoconiosis, or pulmonary fibrosis due to occupational mineral dust exposure. In Queensland, Australia, there has been a re-emergence of coal workers' pneumoconiosis and silicosis. Some coal mining communities have experienced a resurgence of progressive massive fibrosis in the USA and a worldwide epidemic is occurring of accelerated silicosis due to exposure to artificial stone.These diseases are all preventable and should not be occurring in the 21st century. Best practice prevention includes reduction of exposure to mineral dusts or, ideally, prevention of exposure altogether. However, where dust exposure has occurred, respiratory surveillance can provide a strategy for early disease detection. It is important to identify early signs of occupational lung disease at a stage where intervention may be beneficial, though it must be acknowledged that progression may occur even after cessation of exposure to dusts. Respiratory surveillance should be distinguished from population screening and case finding, which are different methods used for disease investigation and control. Designing an ideal respiratory surveillance programme is challenging, as there is no single test that accurately identifies early disease. Several different respiratory disorders may occur related to the same exposure(s). Physicians organising and interpreting tests used in respiratory surveillance must be aware of the broad range of potential work-related respiratory conditions, complexities in diagnosis, and appropriate interpretation of the exposure history, as well as current management options. A working knowledge of the compensation and medicolegal avenues available to workers in individual jurisdictions is also useful.Key pointsMineral dust exposure causes a number of conditions, including those specific to dust exposures, such as the pneumoconioses (or pulmonary fibroses due to mineral dust exposure), and others that may additionally be related to other causes, such as COPD.Identification of multiple conditions using respiratory investigations requires expert interpretation and understanding of the range of potential conditions.The frequency and content of a respiratory surveillance programme will vary according to the relevant occupational exposures, and be affected by both medical and nonmedical factors, including the background prevalence of local diseases. A programme will also need to consider other factors such as local legislation, availability of resources, worker convenience and cost.Educational aimsTo identify the large range of respiratory diseases caused by exposure to mineral dusts and identify the range of tests that may be used in a surveillance programme for occupational respiratory disorders.To highlight difficulties that might be experienced by medical practitioners in designing and operating an effective surveillance programme, while incorporating rapidly advancing medical technology and practice.
Screening for obstructive sleep apnoea in professional drivers
Authors: Schiza Sophia E. , Bouloukaki Izolde 
Published: March 2020

Professional drivers show a higher prevalence of obstructive sleep apnoea (OSA) compared with the general population. Furthermore, there is concern about the association between OSA and car crash risk given that drivers with OSA show an increased risk for car accidents. Despite this risk, OSA is often underdiagnosed and undertreated in this population, mainly due to lack of appropriate screening and sleep study referrals. Polysomnography (PSG), the gold standard test, is inappropriate for systematic screening because of its high expense, complexity and relative inaccessibility in this population. Therefore, there is a strong demand for good screening tools, including both subjective and objective data that may assist in early identification of possible OSA among professional drivers and, thus, aid in PSG examination referral and OSA management in an accredited sleep centre. However, there is considerable disagreement over screening methods and criteria for triggering a sleep study referral in different countries. There is also a strong need for further research in the area of OSA screening of commercial drivers in order to improve the diagnostic accuracy of screening tools and ensure that patients with OSA are accurately identified.Key pointsObstructive sleep apnoea (OSA) is often undiagnosed and undertreated in professional drivers.Professional drivers often under-report and are reluctant to report OSA symptoms.Barriers to OSA diagnosis include appropriate screening and sleep study referrals.Screening tools including both subjective and objective data may assist in early identification of possible OSA among professional drivers.Educational aimsTo evaluate screening instruments currently used to identify OSA risk in professional drivers.To provide guidance for developing an assessment strategy for OSA by professional driver medical examiners.
Revealing hidden information in osteoblast’s mechanotransduction through analysis of time patterns of critical events
Authors: Ascolani Gianluca , Skerry Timothy M. , Lacroix Damien , Dall’Ara Enrico , Shuaib Aban 
Published: March 2020

Abstract
Background
Mechanotransduction in bone cells plays a pivotal role in osteoblast differentiation and bone remodelling. Mechanotransduction provides the link between modulation of the extracellular matrix by mechanical load and intracellular activity. By controlling the balance between the intracellular and extracellular domains, mechanotransduction determines the optimum functionality of skeletal dynamics. Failure of this relationship was suggested to contribute to bone-related diseases such as osteoporosis.

Results
A hybrid mechanical and agent-based model (Mech-ABM), simulating mechanotransduction in a single osteoblast under external mechanical perturbations, was utilised to simulate and examine modulation of the activation dynamics of molecules within mechanotransduction on the cellular response to mechanical stimulation. The number of molecules and their fluctuations have been analysed in terms of recurrences of critical events. A numerical approach has been developed to invert subordination processes and to extract the direction processes from the molecular signals in order to derive the distribution of recurring events. These predict that there are large fluctuations enclosing information hidden in the noise which is beyond the dynamic variations of molecular baselines. Moreover, studying the system under different mechanical load regimes and altered dynamics of feedback loops, illustrate that the waiting time distributions of each molecule are a signature of the system’s state.

Conclusions
The behaviours of the molecular waiting times change with the changing of mechanical load regimes and altered dynamics of feedback loops, presenting the same variation of patterns for similar interacting molecules and identifying specific alterations for key molecules in mechanotransduction. This methodology could be used to provide a new tool to identify potent molecular candidates to modulate mechanotransduction, hence accelerate drug discovery towards therapeutic targets for bone mass upregulation.
Cathepsin K regulates localization and secretion of Tartrate-Resistant Acid Phosphatase (TRAP) in TRAP-overexpressing MDA-MB-231 breast cancer cells
Authors: Reithmeier Anja , Norgård Maria , Ek-Rylander Barbro , Näreoja Tuomas , Andersson Göran 
Published: March 2020

AbstractBackgroundTartrate–resistant acid phosphatase (TRAP/ ACP5) belongs to the binuclear metallophosphatase family and is present in two isoforms. The primary translation product is an uncleaved TRAP 5a isoform with low phosphatase activity. TRAP 5a can be post-translationally processed to a cleaved TRAP 5b isoform with high phosphatase activity by e.g. cysteine proteinases, such as Cathepsin K (CtsK). The relevance of the phosphatase activity of TRAP 5b has been demonstrated for proliferation, migration and invasion of cancer cells. TRAP-overexpressing MDA-MB-231 breast cancer cells displayed higher levels of TRAP 5a and efficient processing of TRAP 5a to TRAP 5b protein, but no changes in levels of CtsK when compared to mock-transfected cells. In TRAP-overexpressing cells colocalization of TRAP 5a and proCtsK was augmented, providing a plausible mechanism for generation of TRAP 5b. CtsK expression has been associated with cancer progression and has been pharmacologically targeted in several clinical studies.ResultsIn the current study, CtsK inhibition with MK-0822/Odanacatib did not abrogate the formation of TRAP 5b, but reversibly increased the intracellular levels of a N-terminal fragment of TRAP 5b and reduced secretion of TRAP 5a reversibly. However, MK-0822 treatment neither altered intracellular TRAP activity nor TRAP-dependent cell migration, suggesting involvement of additional proteases in proteolytic processing of TRAP 5a. Notwithstanding, CtsK was shown to be colocalized with TRAP and to be involved in the regulation of secretion of TRAP 5a in a breast cancer cell line, while it still was not essential for processing of TRAP 5a to TRAP 5b isoform.ConclusionIn cancer cells multiple proteases are involved in cleaving TRAP 5a to high-activity phosphatase TRAP 5b. However, CtsK-inhibiting treatment was able to reduce secretion TRAP 5a from TRAP-overexpressing cancer cells.
Genome of the webworm Hyphantria cunea unveils genetic adaptations supporting its rapid invasion and spread
Authors: Chen Qi , Zhao Hanbo , Wen Ming , Li Jiaxin , Zhou Haifeng , Wang Jiatong , Zhou Yuxin , Liu Yulin , Du Lixin , Kang Hui , Zhang Jian , Cao Rui , Xu Xiaoming , Zhou Jing-Jiang , Ren Bingzhong , Wang Yinliang 
Published: March 2020

AbstractBackgroundThe fall webwormHyphantria cuneais an invasive and polyphagous defoliator pest that feeds on nearly any type of deciduous tree worldwide. The silk web ofH. cuneaaids its aggregating behavior, provides thermal regulation and is regarded as one of causes for its rapid spread. In addition, both chemosensory and detoxification genes are vital for host adaptation in insects.ResultsHere, a high-quality genome ofH. cuneawas obtained. Silk-web-related genes were identified from the genome, and successful silencing of the silk protein geneHcunFib-Hresulted in a significant decrease in silk web shelter production. The CAFE analysis showed that some chemosensory and detoxification gene families, such asCSPs,CCEs,GSTsandUGTs, were expanded. A transcriptome analysis using the newly sequencedH. cuneagenome showed that most chemosensory genes were specifically expressed in the antennae, while most detoxification genes were highly expressed during the feeding peak. Moreover, we found that many nutrient-related genes and one detoxification gene,HcunP450(CYP306A1), were under significant positive selection, suggesting a crucial role of these genes in host adaptation inH. cunea. At the metagenomic level, several microbial communities inH. cuneagut and their metabolic pathways might be beneficial toH. cuneafor nutrient metabolism and detoxification, and might also contribute to its host adaptation.ConclusionsThese findings explain the host and environmental adaptations ofH. cuneaat the genetic level and provide partial evidence for the cause of its rapid invasion and potential gene targets for innovative pest management strategies.
CuAS: a database of annotated transcripts generated by alternative splicing in cucumbers
Authors: Sun Ying , Zhang Quanbao , Liu Bing , Lin Kui , Zhang Zhonghua , Pang Erli 
Published: March 2020

Abstract
Background
Alternative splicing (AS) plays a critical regulatory role in modulating transcriptome and proteome diversity. In particular, it increases the functional diversity of proteins. Recent genome-wide analysis of AS using RNA-Seq has revealed that AS is highly pervasive in plants. Furthermore, it has been suggested that most AS events are subject to tissue-specific regulation.

Description
To reveal the functional characteristics induced by AS and tissue-specific splicing events, a database for exploring these characteristics is needed, especially in plants. To address these goals, we constructed a database of annotated transcripts generated by alternative splicing in cucumbers (CuAS: http://cmb.bnu.edu.cn/alt_iso/index.php) that integrates genomic annotations, isoform-level functions, isoform-level features, and tissue-specific AS events among multiple tissues. CuAS supports a retrieval system that identifies unique IDs (gene ID, isoform ID, UniProt ID, and gene name), chromosomal positions, and gene families, and a browser for visualization of each gene.

Conclusion
We believe that CuAS could be helpful for revealing the novel functional characteristics induced by AS and tissue-specific AS events in cucumbers. CuAS is freely available at http://cmb.bnu.edu.cn/alt_iso/index.php.