bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving primary care management of asthma: do we know what really works?
Authors: Fletcher Monica J. , Tsiligianni Ioanna , Kocks Janwillem W. H. , Cave Andrew , Chunhua Chi , Sousa Jaime Correia de , Román-Rodríguez Miguel , Thomas Mike , Kardos Peter , Stonham Carol , Khoo Ee Ming , Leather David , van der Molen Thys 
Published: June 2020

AbstractAsthma imposes a substantial burden on individuals and societies. Patients with asthma need high-quality primary care management; however, evidence suggests the quality of this care can be highly variable. Here we identify and report factors contributing to high-quality management. Twelve primary care global asthma experts, representing nine countries, identified key factors. A literature review (past 10 years) was performed to validate or refute the expert viewpoint. Key driving factors identified were: policy, clinical guidelines, rewards for performance, practice organisation and workforce. Further analysis established the relevant factor components. Review evidence supported the validity of each driver; however, impact on patient outcomes was uncertain. Single interventions (e.g. healthcare practitioner education) showed little effect; interventions driven by national policy (e.g. incentive schemes and teamworking) were more effective. The panel’s opinion, supported by literature review, concluded that multiple primary care interventions offer greater benefit than any single intervention in asthma management.
Lineage dynamics of the endosymbiotic cell type in the soft coral Xenia
Authors: Hu Minjie , Zheng Xiaobin , Fan Chen-Ming , Zheng Yixian 
Published: June 2020

AbstractMany corals harbour symbiotic dinoflagellate algae. The algae live inside coral cells in a specialized membrane compartment known as the symbiosome, which shares the photosynthetically fixed carbon with coral host cells while host cells provide inorganic carbon to the algae for photosynthesis1. This endosymbiosis—which is critical for the maintenance of coral reef ecosystems—is increasingly threatened by environmental stressors that lead to coral bleaching (that is, the disruption of endosymbiosis), which in turn leads to coral death and the degradation of marine ecosystems2. The molecular pathways that orchestrate the recognition, uptake and maintenance of algae in coral cells remain poorly understood. Here we report the chromosome-level genome assembly of a Xenia species of fast-growing soft coral3, and use this species as a model to investigate coral–alga endosymbiosis. Single-cell RNA sequencing identified 16 cell clusters, including gastrodermal cells and cnidocytes, in Xenia sp. We identified the endosymbiotic cell type, which expresses a distinct set of genes that are implicated in the recognition, phagocytosis and/or endocytosis, and maintenance of algae, as well as in the immune modulation of host coral cells. By coupling Xenia sp. regeneration and single-cell RNA sequencing, we observed a dynamic lineage progression of the endosymbiotic cells. The conserved genes associated with endosymbiosis that are reported here may help to reveal common principles by which different corals take up or lose their endosymbionts.
Serial scanning electron microscopy of anti-PKHD1L1 immuno-gold labeled mouse hair cell stereocilia bundles
Authors: Ivanchenko Maryna V. , Cicconet Marcelo , Jandal Hoor Al , Wu Xudong , Corey David P. , Indzhykulian Artur A. 
Published: June 2020

AbstractSerial electron microscopy techniques have proven to be a powerful tool in biology. Unfortunately, the data sets they generate lack robust and accurate automated segmentation algorithms. In this data descriptor publication, we introduce a serial focused ion beam scanning electron microscopy (FIB-SEM) dataset consisting of six outer hair cell (OHC) stereocilia bundles, and the supranuclear part of the hair cell bodies. Also presented are the manual segmentations of stereocilia bundles and the gold bead labeling of PKHD1L1, a coat protein of hair cell stereocilia important for hearing in mice. This depository includes all original data and several intermediate steps of the manual analysis, as well as the MATLAB algorithm used to generate a three-dimensional distribution map of gold labels. They serve as a reference dataset, and they enable reproduction of our analysis, evaluation and improvement of current methods of protein localization, and training of algorithms for accurate automated segmentation.
Combination of variations in inflammation- and endoplasmic reticulum-associated genes as putative biomarker for bevacizumab response in KRAS wild-type colorectal cancer
Authors: Barat Ana , Smeets Dominiek , Moran Bruce , Zhang Wu , Cao Shu , Das Sudipto , Klinger Rut , Betge Johannes , Murphy Verena , Bacon Orna , Kay Elaine W. , Van Grieken Nicole C. T. , Verheul Henk M. W. , Gaiser Timo , Schulte Nadine , Ebert Matthias P. , Fender Bozena , Hennessy Bryan T. , McNamara Deborah A. , O’Connor Darran , Gallagher William M. , Cremolini Chiara , Loupakis Fotios , Parikh Aparna , Mancao Christoph , Ylstra Bauke , Lambrechts Diether , Lenz Heinz-Josef , Byrne Annette T. , Prehn Jochen H. M. 
Published: June 2020

AbstractChemotherapy combined with the angiogenesis inhibitor bevacizumab (BVZ) is approved as a first-line treatment in metastatic colorectal cancer (mCRC). Limited clinical benefit underpins the need for improved understanding of resistance mechanisms and the elucidation of novel predictive biomarkers. We assessed germline single-nucleotide polymorphisms (SNPs) in 180 mCRC patients (Angiopredict [APD] cohort) treated with combined BVZ + chemotherapy and investigated previously reported predictive SNPs. We further employed a machine learning approach to identify novel associations. In the APD cohortIL8rs4073 any A carriers, compared to TT carriers, were associated with worse progression-free survival (PFS) (HR = 1.51, 95% CI:1.03–2.22,p-value = 0.037) andTBK1rs7486100 TT carriers, compared to any A carriers, were associated with worse PFS inKRASwild-type (wt) patients (HR = 1.94, 95% CI:1.04–3.61,p-value = 0.037), replicating previous findings. Machine learning identified novel associations in genes encoding the inflammasome proteinNLRP1and the ER protein Sarcalumenin (SRL). A negative association between PFS and carriers of any A atNLRP1rs12150220 and AA forSRLrs13334970 in APDKRASwild-type patients (HR = 4.44, 95% CI:1.23–16.13,p-value = 0.005), which validated in two independent clinical cohorts involving BVZ, MAVERICC and TRIBE. Our findings highlight a key role for inflammation and ER signalling underpinning BVZ + chemotherapy responsiveness.
Erythroderma: a prospective study of 309 patients followed for 12 years in a tertiary center
Authors: Miyashiro Denis , Sanches José Antonio 
Published: June 2020

AbstractErythroderma is characterized by erythema and scaling affecting more than 80% of the body surface area. It is potentially life-threatening, and diagnosis of the underlying disease is a challenge. Despite laboratory improvements, many cases remain idiopathic. We aimed to analyze clinical and laboratory findings of 309 erythrodermic patients to find clues to the etiologic diagnosis. We performed a prospective study at the University of São Paulo Medical School, from 2007 to 2018, with patients with acquired erythroderma. Clinical, laboratory, histology, and molecular biology data were collected. The median age at diagnosis was 57 years, with a male-to-female ratio of 2.2. Eczema was the most frequent etiology (20.7%), followed by psoriasis (16.8%), Sézary syndrome (12.3%), drug eruption (12.3%), atopic dermatitis (8.7%), and mycosis fungoides (5.5%). Other diagnoses (6.8%) included pemphigus foliaceous, paraneoplastic erythroderma, adult T-cell leukemia/lymphoma, dermatomyositis, pityriasis rubra pilaris, lichen planus, bullous pemphigoid, and leprosy. In 52 patients (16.8%), it was not possible to elucidate erythroderma etiology. Atopic dermatitis developed erythroderma at an earlier age (median 25 years; P = 0.0001). Acute onset was associated with drug reactions and atopic dermatitis (median time from erythroderma to diagnosis of 1 and 1.5 months, respectively; P = 0.0001). Higher immunoglobulin E levels were observed in atopic dermatitis (median 24,600 U/L; P = 0.0001). Histopathology was helpful and was consistent with the final diagnosis in 72.4%. Monoclonal T-cell proliferation in the skin was observed in mycosis fungoides (33.3%) and Sézary syndrome (90.9%). At the last assessment, 211 patients (69.3%) were alive with disease, 65 (21.7%) were alive without disease, and 27 (9.1%) died with active disease. Erythroderma is a challenging syndrome with a difficult diagnostic approach. Younger age and higher immunoglobulin E levels are associated with atopic dermatitis; acute onset is observed in drug eruptions and atopic dermatitis. Histopathology and molecular biology tests are essential tools in the investigation of erythroderma.
Temporal X-ray Reconstruction using Temporal and Spectral Measurements at LCLS
Authors: Christie Florian , Lutman Alberto Andrea , Ding Yuantao , Huang Zhirong , Jhalani Vatsal A. , Krzywinski Jacek , Maxwell Timothy J. , Ratner Daniel , Rönsch-Schulenburg Juliane , Vogt Mathias 
Published: June 2020

AbstractTransverse deflecting structures (TDSs) are widely used in accelerator physics to measure the longitudinal density of particle bunches. When used in combination with a dispersive section, the whole longitudinal phase space density can be imaged. At the Linac Coherent Light Source (LCLS), the installation of such a device downstream of the undulators enables the reconstruction of the X-ray temporal intensity profile by comparing longitudinal phase space distributions with lasing on and lasing off. However, the resolution of this TDS is limited to around 1 fs rms (root mean square), and therefore, it is not possible to resolve single self-amplified spontaneous emission (SASE) spikes within an X-ray photon pulse. By combining the power spectrum from a high resolution photon spectrometer and the temporal structure from the TDS, the overall resolution is enhanced, thus allowing the observation of temporal, single SASE spikes. The combined data from the spectrometer and the TDS is analysed using an iterative algorithm to obtain the actual intensity profile. In this paper, we present some improvements to the reconstruction algorithm as well as real data taken at LCLS.
Quantitative Analysis of Enhancement Intensity and Patterns on Contrast-enhanced Spectral Mammography
Authors: Liu Ying , Zhao Shuang , Huang Juan , Zhang Xueqin , Qin Yun , Zhong Huanhuan , Yu Jianqun 
Published: June 2020

AbstractCESM is an emerging digital mammography technology with a high breast cancer detection and a limited diagnostic specificity. In order to improve specificity, we quantitatively assessed enhancement intensity of breast lesions with different pathological types and hormonal receptor status and evaluated the consistency of enhancement patterns between CESM and DCE-MRI. A total of 145 lesions were enrolled, consisting of 43 malignant (17 non-infiltrating cancers and 26 infiltrating cancers) and 99 benign lesions. The diagnostic performance of enhancement intensity in the former positions was significantly higher than that in the latter positions (AUC: 0.834 vs. 0.755, p = 0.0008). Infiltrating cancers showed the highest enhancement intensity, while benign lesions the lowest (mean CNR1: 7.6% vs. 2.7%; median CNR1: 6.8% vs. 2.7%). Enhancement intensity of ER or PR positive group was weaker than negative group, while HER-2 positive group was stronger than negative group. 28 patients with 28 lesions performed both CESM and DCE-MRI examinations, showing a coincidence rate of 64.2% and moderate agreement (k = 0.515) between CESM and DCE-MRI. In conclusion, quantitative analysis of enhancement characteristics is feasible to the diagnosis practice on CESM.
Theoretical insights on helix repacking as the origin of P-glycoprotein promiscuity
Authors: Bonito Cátia A. , Ferreira Ricardo J. , Ferreira Maria-José. U. , Gillet Jean-Pierre , Cordeiro M. Natália D. S. , dos Santos Daniel J. V. A. 
Published: June 2020

AbstractP-glycoprotein (P-gp, ABCB1) overexpression is, currently, one of the most important multidrug resistance (MDR) mechanisms in tumor cells. Thus, modulating drug efflux by P-gp has become one of the most promising approaches to overcome MDR in cancer. Yet, more insights on the molecular basis of drug specificity and efflux-related signal transmission mechanism between the transmembrane domains (TMDs) and the nucleotide binding domains (NBDs) are needed to develop molecules with higher selectivity and efficacy. Starting from a murine P-gp crystallographic structure at the inward-facing conformation (PDB ID: 4Q9H), we evaluated the structural quality of the herein generated human P-gp homology model. This initial human P-gp model, in the presence of the “linker” and inserted in a suitable lipid bilayer, was refined through molecular dynamics simulations and thoroughly validated. The best human P-gp model was further used to study the effect of four single-point mutations located at the TMDs, experimentally related with changes in substrate specificity and drug-stimulated ATPase activity. Remarkably, each P-gp mutation is able to induce transmembrane α-helices (TMHs) repacking, affecting the drug-binding pocket volume and the drug-binding sites properties (e.g. volume, shape and polarity) finally compromising drug binding at the substrate binding sites. Furthermore, intracellular coupling helices (ICH) also play an important role since changes in the TMHs rearrangement are shown to have an impact in residue interactions at the ICH-NBD interfaces, suggesting that identified TMHs repacking affect TMD-NBD contacts and interfere with signal transmission from the TMDs to the NBDs.
The role of low Gd concentrations on magnetisation behaviour in rare earth:transition metal alloy films
Authors: Inyang O. , Rafiq A. , Swindells C. , Ali S. , Atkinson D. 
Published: June 2020

AbstractThe magnetisation reversal behaviour as a function of composition was studied in low rare earth concentration alloys. 30 nm thick rare earth:transition-metal films of composition GdxCo100−x, GdxFe100−x and Gdx(Co50Fe50)100−x were prepared by magnetron sputtering, where x ranged from 4 to 13 atomic%. Magnetisation behaviour was studied using MOKE and Hall hysteresis measurements. The magnetic reversal behaviour as a function of Gd content is strongly dependent on the transition metal. With increasing Gd content the film structure transitions from crystalline to amorphous and the saturation magnetisation decreases linearly. For GdCo, the reversal field, Hc, increases by less than a factor of two with Gd doping of 11%, while for Fe, the coercivity falls by a factor of ten with 8% Gd. This may be attributed to changes in the crystalline morphology. GdCoFe shows a similar trend with Gd doping for the in-plane reversal field to that of GdFe. With 13% Gd in Fe there is evidence indicating the presence of a weak perpendicular magnetic anisotropy, PMA. With Gd doping the anomalous Hall resistivity of Co, Fe and CoFe increases significantly with the largest increase observed for GdCoFe.
Distribution of nerve fibers and nerve-immune cell association in mouse spleen revealed by immunofluorescent staining
Authors: Hu Dailun , Al-Shalan Huda A. M. , Shi Zhongli , Wang Penghao , Wu Yongkang , Nicholls Philip K. , Greene Wayne K. , Ma Bin 
Published: June 2020

AbstractThe central nervous system regulates the immune system through the secretion of hormones from the pituitary gland and other endocrine organs, while the peripheral nervous system (PNS) communicates with the immune system through local nerve-immune cell interactions, including sympathetic/parasympathetic (efferent) and sensory (afferent) innervation to lymphoid tissue/organs. However, the precise mechanisms of this bi-directional crosstalk of the PNS and immune system remain mysterious. To study this kind of bi-directional crosstalk, we performed immunofluorescent staining of neurofilament and confocal microscopy to reveal the distribution of nerve fibers and nerve-immune cell associations inside mouse spleen. Our study demonstrates (i) extensive nerve fibers in all splenic compartments including the splenic nodules, periarteriolar lymphoid sheath, marginal zones, trabeculae, and red pulp; (ii) close associations of nerve fibers with blood vessels (including central arteries, marginal sinuses, penicillar arterioles, and splenic sinuses); (iii) close associations of nerve fibers with various subsets of dendritic cells, macrophages (Mac1+ and F4/80+), and lymphocytes (B cells, T helper cells, and cytotoxic T cells). Our data concerning the extensive splenic innervation and nerve-immune cell communication will enrich our knowledge of the mechanisms through which the PNS affects the cellular- and humoral-mediated immune responses in healthy and infectious/non-infectious states.
Simulating dissolved 90Sr concentrations within a small catchment in the Chernobyl Exclusion Zone using a parametric hydrochemical model
Authors: Igarashi Yasunori , Onda Yuichi , Smith Jim , Obrizan Sergey , Kirieiev Serhii , Demianovych Volodymyr , Laptev Gennady , Bugai Dmitri , Lisovyi Hlib , Konoplev Alexei , Zheleznyak Mark , Wakiyama Yoshifumi , Nanba Kenji 
Published: June 2020

AbstractStrontium-90 (90Sr) is the major long-lived radionuclide derived from the Chernobyl accident, and is still being detected in the heavily contaminated catchments of the Chernobyl Exclusion Zone. This study examines the long-term decrease in the dissolved-phase 90Sr concentration and the concentration–discharge (90Sr-Q) relationship in stream water since the accident. We show that the slow decline in 90Sr follows a double-exponential function, and that there is a clear relationship between 90Sr and Q. This study is the first to reveal that the log(90Sr)-log(Q) slope has been gradually decreasing since the accident. This trend persists after decay correction. Thus, it is not caused by the physical decay of 90Sr and environmental diffusion, but implies that the concentration formation processes in stream water have been changing over a long period. We propose a hydrochemical model to explain the time-dependency of the 90Sr-Q relationship. This paper presents a mathematical implementation of the new concept and describes the model assumptions. Our model accurately represents both the long-term 90Sr trend in stream water and the time-dependency of the 90Sr-Q relationship. Although this paper considers a small catchment in Chernobyl, the conceptual model is shown to be applicable to other accidental releases of radionuclides.
The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unresponsive to standard heart failure therapy
Authors: Eijgenraam Tim R. , Boukens Bastiaan J. , Boogerd Cornelis J. , Schouten E. Marloes , van de Kolk Cees W. A. , Stege Nienke M. , te Rijdt Wouter P. , Hoorntje Edgar T. , van der Zwaag Paul A. , van Rooij Eva , van Tintelen J. Peter , van den Berg Maarten P. , van der Meer Peter , van der Velden Jolanda , Silljé Herman H. W. , de Boer Rudolf A. 
Published: June 2020

AbstractPhospholamban (PLN) plays a role in cardiomyocyte calcium handling as primary inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). The p.(Arg14del) pathogenic variant in the PLN gene results in a high risk of developing dilated or arrhythmogenic cardiomyopathy with heart failure. There is no established treatment other than standard heart failure therapy or heart transplantation. In this study, we generated a novel mouse model with the PLN-R14del pathogenic variant, performed detailed phenotyping, and tested the efficacy of established heart failure therapies eplerenone or metoprolol. Heterozygous PLN-R14del mice demonstrated increased susceptibility to ex vivo induced arrhythmias, and cardiomyopathy at 18 months of age, which was not accelerated by isoproterenol infusion. Homozygous PLN-R14del mice exhibited an accelerated phenotype including cardiac dilatation, contractile dysfunction, decreased ECG potentials, high susceptibility to ex vivo induced arrhythmias, myocardial fibrosis, PLN protein aggregation, and early mortality. Neither eplerenone nor metoprolol administration improved cardiac function or survival. In conclusion, our novel PLN-R14del mouse model exhibits most features of human disease. Administration of standard heart failure therapy did not rescue the phenotype, underscoring the need for better understanding of the pathophysiology of PLN-R14del-associated cardiomyopathy. This model provides a great opportunity to study the pathophysiology, and to screen for potential therapeutic treatments.
SPOCK1 is a novel inducer of epithelial to mesenchymal transition in drug-induced gingival overgrowth
Authors: Alshargabi Rehab , Sano Tomomi , Yamashita Akiko , Takano Aiko , Sanada Taiki , Iwashita Misaki , Shinjo Takanori , Fukuda Takao , Sanui Terukazu , Kishida Shosei , Nishimura Fusanori 
Published: June 2020

AbstractFew studies have investigated the role of extracellular-matrix proteoglycans in the pathogenesis of drug-induced gingival overgrowth (DIGO). SPOCK1 is an extracellular proteoglycan that induces epithelial to mesenchymal transition (EMT) in several cancer cell lines and exhibits protease-inhibitory activity. However, the role of SPOCK1 in non-cancerous diseases such as DIGO has not been well-addressed. We demonstrated that the expression of SPOCK1, TGF-β1, and MMP-9 in calcium channel blocker-induced gingival overgrowth is higher than that in non-overgrowth tissues. Transgenic mice overexpressingSpock1 developed obvious gingival-overgrowth and fibrosis phenotypes, and positively correlated with EMT-like changes. Furthermore,in vitrodata indicated a tri-directional interaction between SPOCK1, TGF-β1, and MMP-9 that led to gingival overgrowth. Our study shows that SPOCK1 up-regulation in a noncancerous disease and SPOCK1-induced EMT in gingival overgrowth occurs via cooperation and crosstalk between several potential signaling pathways. Therefore, SPOCK1 is a novel therapeutic target for gingival overgrowth and its expression is a potential risk of EMT induction in cancerous lesions.
Comorbidities of Patients with Functional Somatic Syndromes Before, During and After First Diagnosis: A Population-based Study using Bavarian Routine Data
Authors: Donnachie Ewan , Schneider Antonius , Enck Paul 
Published: June 2020

AbstractFunctional somatic syndromes (FSS) are characterised by the presence of one or multiple chronic symptoms that cannot be attributed to a known somatic disease. They are thought to arise though a complex interaction of biological and psychosocial factors, but it is unclear whether they share a common aetiology. One hypothesis supported by recent studies is that the FSS are postinfectious disorders, as is widely recognised for a subset of patients with irritable bowel syndrome. Our study used claims data submitted by office-based physicians to compare groups of patients with different FSS in the five years before and after the point of first diagnosis. Even five years prior to diagnosis, FSS patients consulted more frequently for a range of psychological and somatic conditions than did controls. Following diagnosis, consultation rates increased further and remained persistently high. Five years after diagnosis, between 34% (somatization disorder) and 66% (fibromyalgia) of patients were still being treated for the condition. Both prior gastrointestinal and upper-respiratory infection were associated with an increased risk of developing an FSS. We therefore recommend that patients at risk should be identified at an early stage and the underlying psychosocial and somatic issues addressed to prevent progression of the condition.