bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal mesenchymal cells regulate immune responses and promote epithelial regeneration in vitro and in dextran sulfate sodium‐induced experimental colitis in mice
Authors: Hidalgo‐Garcia Laura , Molina‐Tijeras José Alberto , Huertas‐Peña Francisco , Ruiz‐Malagón Antonio Jesús , Diez‐Echave Patricia , Vezza Teresa , Rodríguez‐Sojo María Jesús , Morón Rocío , Becerra‐Massare Patricia , Rodríguez‐Nogales Alba , Gálvez Julio , Rodríguez‐Cabezas María Elena , Anderson Per 
Published: June 2021

AbstractAimDisruption of the intestinal mucosal tolerance, that is, the immunological unresponsiveness to innocuous food antigens and the commensal microbiota, in the colon is associated with several chronic diseases including inflammatory bowel disease (IBD). Understanding the mechanisms responsible for intestinal mucosal tolerance has potential translational value for its therapy and management. Human intestinal mesenchymal cells (iMCs) play important roles in colonic mucosal tolerance, but further studies on their tissue regenerative and immunomodulatory capacities are necessary in order to fully understand their function in health and disease.MethodsIn this study, we have isolated and analysed the capacity of human iMCs to promote wound healing and modulate immune responses in vitro and in vivo, using the dextran sulfate sodium (DSS)‐induced colitis model.ResultsCultured iMCs were CD45−CD73+CD90+CD105+ and accelerated the wound closure in a normal colon mucosa (NCM) 356 human epithelial cell wound healing assay. Furthermore, iMCs blocked the LPS‐mediated induction of TNF‐α in THP‐1 macrophages and inhibited the proliferation of peripheral blood mononuclear cells, partly through the induction of indoleamine‐2,3‐dioxygenase. In DSS colitic mice, iMCs administration reduced the disease activity index and ameliorated intestinal tissue damage and permeability. Furthermore, iMCs reduced intestinal inflammation, evidenced by a decreased mRNA expression of pro‐inflammatory cytokines, reduced IL‐1β secretion by intestinal explants and inhibited colonic iNOS protein expression.ConclusionsOur data show that human iMCs isolated from the noninflamed intestine possess tissue‐regenerative and immunomodulatory capacities that could potentially be harnessed/restored in order to reduce IBD severity.
High‐intensity exercise in hypoxia improves endothelial function via increased nitric oxide bioavailability in C57BL/6 mice
Authors: Lavier Jessica , Beaumann Manon , Menétrey Steeve , Bouzourène Karima , Rosenblatt‐Velin Nathalie , Pialoux Vincent , Mazzolai Lucia , Peyter Anne‐Christine , Pellegrin Maxime , Millet Grégoire P. 
Published: June 2021

AbstractAimThe optimal exercise intensity to improve endothelial function remains unclear, as well as whether the addition of hypoxia could potentiate this function. Therefore, the aim of this study was to compare the effects of different exercise intensities in normoxia and hypoxia on vascular reactivity and nitric oxide (NO) bioavailability in mice.MethodsC57BL/6 mice underwent treadmill running three times per week, for 4 weeks at either low, maximal or supramaximal intensity in normoxia or hypoxia (inspire oxygen fraction = 0.13). Vascular reactivity and expression of genes and proteins involved in NO production/bioavailability were assessed in aorta using isolated vessel tension experiments, RT‐qPCR and western blot, respectively. Circulating NO metabolites and pro‐/antioxidant markers were measured.ResultsHypoxic exercise improved both acetylcholine‐induced vasorelaxation and phenylephrine‐induced vasoconstriction compared to normoxic exercise, independently of intensity. In hypoxia, a higher acetylcholine‐induced vasorelaxation was observed with high intensities (supramaximal and maximal) compared to low intensity. Exercise protocols modulated endothelial nitric oxide synthase (eNOS) and α1‐adrenergic receptor (α1‐AR) mRNA level, but not superoxide dismutase 3 (SOD3) and p47phox. No significant differences were observed for protein expression of α1‐AR, total eNOS, phosphorylated eNOS, SOD isoforms and p47phox. However, plasma SOD and catalase activities were significantly increased in hypoxic supramaximal compared to hypoxic low intensity, while concentration of nitrotyrosine significantly decreased. The latter was also observed in hypoxic maximal and supramaximal compared to the same intensities in normoxia.ConclusionHypoxic high‐intensity exercise increases NO bioavailability and improves vascular function, opening promising clinical perspectives for cardiovascular disease prevention.
Reliable kidney size determination by magnetic resonance imaging in pathophysiological settings
Authors: Gladytz Thomas , Millward Jason M. , Cantow Kathleen , Hummel Luis , Zhao Kaixuan , Flemming Bert , Periquito Joāo S. , Pohlmann Andreas , Waiczies Sonia , Seeliger Erdmann , Niendorf Thoralf 
Published: June 2021

AbstractAimKidney diseases constitute a major health challenge, which requires noninvasive imaging to complement conventional approaches to diagnosis and monitoring. Several renal pathologies are associated with changes in kidney size, offering an opportunity for magnetic resonance imaging (MRI) biomarkers of disease. This work uses dynamic MRI and an automated bean‐shaped model (ABSM) for longitudinal quantification of pathophysiologically relevant changes in kidney size.MethodsA geometry‐based ABSM was developed for kidney size measurements in rats using parametric MRI (T2, T2* mapping). The ABSM approach was applied to longitudinal renal size quantification using occlusion of the (a) suprarenal aorta or (b) the renal vein, (c) increase in renal pelvis and intratubular pressure and (d) injection of an X‐ray contrast medium into the thoracic aorta to induce pathophysiologically relevant changes in kidney size.ResultsThe ABSM yielded renal size measurements with accuracy and precision equivalent to the manual segmentation, with >70‐fold time savings. The automated method could detect a ~7% reduction (aortic occlusion) and a ~5%, a ~2% and a ~6% increase in kidney size (venous occlusion, pelvis and intratubular pressure increase and injection of X‐ray contrast medium, respectively). These measurements were not affected by reduced image quality following administration of ferumoxytol.ConclusionDynamic MRI in conjunction with renal segmentation using an ABSM supports longitudinal quantification of changes in kidney size in pathophysiologically relevant experimental setups mimicking realistic clinical scenarios. This can potentially be instrumental for developing MRI‐based diagnostic tools for various kidney disorders and for gaining new insight into mechanisms of renal pathophysiology.
A drug screen with approved compounds identifies amlexanox as a novel Wnt/β‐catenin activator inducing lung epithelial organoid formation
Authors: Costa Rita , Wagner Darcy E. , Doryab Ali , De Santis Martina M. , Schorpp Kenji , Rothenaigner Ina , Lehmann Mareike , Baarsma Hoeke A. , Liu Xueping , Schmid Otmar , Campillos Monica , Yildirim Ali Önder , Hadian Kamyar , Königshoff Melanie 
Published: June 2021

Background and PurposeEmphysema is an incurable disease characterized by loss of lung tissue leading to impaired gas exchange. Wnt/β‐catenin signalling is reduced in emphysema, and exogenous activation of the pathway in experimental models in vivo and in human ex vivo lung tissue improves lung function and structure. We sought to identify a pharmaceutical able to activate Wnt/β‐catenin signalling and assess its potential to activate lung epithelial cells and repair.Experimental ApproachWe screened 1216 human‐approved compounds for Wnt/β‐catenin signalling activation using luciferase reporter cells and selected candidates based on their computationally predicted protein targets. We further performed confirmatory luciferase reporter and metabolic activity assays. Finally, we studied the regenerative potential in murine adult epithelial cell‐derived lung organoids and in vivo using a murine elastase‐induced emphysema model.Key ResultsThe primary screen identified 16 compounds that significantly induced Wnt/β‐catenin‐dependent luciferase activity. Selected compounds activated Wnt/β‐catenin signalling without inducing cell toxicity or proliferation. Two compounds were able to promote organoid formation, which was reversed by pharmacological Wnt/β‐catenin inhibition, confirming the Wnt/β‐catenin‐dependent mechanism of action. Amlexanox was used for in vivo evaluation, and preventive treatment resulted in improved lung function and structure in emphysematous mouse lungs. Moreover, gene expression of Hgf, an important alveolar repair marker, was increased, whereas disease marker Eln was decreased, indicating that amlexanox induces pro‐regenerative signalling in emphysema.Conclusion and ImplicationsUsing a drug screen based on Wnt/β‐catenin activity, organoid assays and a murine emphysema model, amlexanox was identified as a novel potential therapeutic agent for emphysema.
A novel embedded system design for the detection and classification of cardiac disorders
Authors: Riaz Umair , Aziz Sumair , Umar Khan Muhammad , Zaidi Syed Azhar Ali , Ukasha Muhammad , Rashid Aamir 
Published: June 2021

AbstractPhonocardiogram (PCG) signals hold significant prognostic and diagnostic information about cardiac health. Numerous PCG or heart sound based automated detection algorithms were previously proposed to assist the disease diagnosis process. Most of the previous studies only focused on algorithmic development. This study presents an intelligent, portable, and low‐cost embedded system for the classification of cardiac disorders associated with heart murmurs. Different stages corresponding to the developed embedded system implementation are summarized as follows: The first stage consists of the acquisition of PCG signals of both normal and patients from various hospitals with a customized and low‐cost stethoscope. The second stage describes the preprocessing, localization of S1 and S2 heart sounds, and the extraction of systole and diastole from a heart signal with an empirical mode decomposition integrated with the self‐developed algorithm. In the third stage, discriminant features are extracted to represent various cardiac classes of PCG signals in a compact manner. In the final stage of the algorithm, the k‐nearest neighbors classifier is trained and tested to distinguish between normal and four cardiac disorders. The proposed algorithm achieved 94% mean accuracy through comprehensive experimentation. The cardiac disorders classification algorithm is implemented on a RP‐based embedded system. Software application with an interactive graphical interface is also designed to assist users. The developed intelligent system is portable, low‐cost, and it enables regular patient‐monitoring. The proposed system has the potential to be employed at remote locations where the availability of doctors remains challenging.
Secretory carcinoma of the breast limited to the dermis: Cutaneous or breast primary?
Authors: Grinnell Madison , Yanala Ujwal , DiMaio Dominick 
Published: June 2021

AbstractWe offer a case of a 22‐year‐old woman who presented with a painless breast mass. Physical examination of the breast was unrevealing other than a palpable mass in close proximity to the nipple areolar region. No lymphadenopathy was noticed in the axilla or supraclavicular region. Sonographic assessment was performed and the findings were classified as Breast Imaging Reporting and Data System category 4. Because of the proximity of the mass to the skin surface, an excisional biopsy was performed. Final pathology disclosed a 5‐mm invasive carcinoma. On pathologic examination, histopathology and immunophenotyping supported the diagnosis of secretory carcinoma; however, whether the origin was from the breast parenchyma or skin tissue was not clearly discernable. Therefore, the patient was scheduled for sentinel lymph node biopsy with plans for axillary dissection if positive. While the overall prognosis for secretory carcinoma is good, with a low chance of metastasis, any ambiguity in breast mass diagnosis should be discussed in a multidisciplinary tumor board and should be treated aggressively particularly in younger patients.
An unusual case of T‐cell prolymphocytic leukemia mimicking a cutaneous vasculitis
Authors: Edmonds Nicole , Guerra Ricardo , Noland Mary‐Margaret B. , Schenck Olivia , Krasner Brett , Gru Alejandro A. 
Published: June 2021

AbstractT‐cell prolymphocytic leukemia (T‐PLL) is an aggressive post‐thymic T‐cell malignancy, which accounts for 2% of mature lymphocytic leukemias in adults. Though typically presenting with a brief history of B symptoms, hepatosplenomegaly, and marked lymphocytosis, erythematous or nodular skin rashes involving the trunk or limbs may be seen in 25% to 30% of patients, as well as a purpuric rash in a periorbital distribution. Cutaneous involvement typically presents in the context of patients with an established history of T‐PLL, but it can less frequently present as an initial symptom heralding the diagnosis. An unusual case of T‐PLL is described, presenting initially as palmoplantar ulcerated nodules with an initial biopsy suggestive of perniosis, followed by rapid progression of dark violaceous and bright red papules throughout the body after initiation of obinutuzumab. The diagnosis of T‐PLL was subsequently fully supported by the clinical, laboratory, cytologic, and immunophenotypic findings. This case highlights the importance of a multidisciplinary team approach to address such rare and atypical presentations.
Significant contributions of combustion‐related NH3 and non‐fossil fuel NOx to elevation of nitrogen deposition in southwestern China over past five decades
Authors: Huang Hao , Song Wei , Liu Xue‐Yan 
Published: June 2021

AbstractAnthropogenic nitrogen (N) emissions and deposition have been increasing over past decades. However, spatiotemporal variations of N deposition levels and major sources remain unclear in many regions, which hinders making strategies of emission mitigation and evaluating effects of elevated N deposition. By investigating moss N contents and δ15N values in southwestern (SW) China in 1954–1964, 1970–1994, and 2005–2015, we reconstructed fluxes and source contributions of atmospheric ammonium () and nitrate () deposition and evaluated their historical changes. For urban and non‐urban sites, averaged moss N contents did not differ between 1954–1964 and 1970–1994 (1.2%–1.3%) but increased distinctly in 2005–2015 (1.6%–2.3%), and averaged moss δ15N values decreased from +0.4‰ to +3.3‰ in 1954–1964 to −1.9‰ to −0.7‰ in 1974–1990, and to −4.8‰ to −3.6‰ in 2005–2015. Based on quantitative estimations, N deposition levels from the 1950s to the 2000s did not change in the earlier 20 years but were elevated substantially in the later 30 years. Moreover, the elevation of deposition (by 12.2 kg‐N/ha/year at urban sites and 4.6 kg‐N/ha/year at non‐urban sties) was higher than that of deposition (by 6.0 and 2.9 kg‐N/ha/year, respectively) in the later 30 years. This caused a shifted dominance from to in N deposition. Based on isotope source apportionments, contributions of combustion‐related NH3 sources (vehicle exhausts, coal combustion, and biomass burning) to the elevation of deposition were two times higher than volatilization NH3 sources (wastes and fertilizers) in the later 30 years. Meanwhile, non‐fossil fuel NOx sources (biomass burning, microbial N cycles) contributed generally more than fossil fuel NOx sources (vehicle exhausts and coal combustion) to the elevation of deposition. These results revealed significant contributions of combustion‐related NH3 and non‐fossil fuel NOx emissions to the historical elevation of N deposition in SW China, which is useful for emission mitigation and ecological effect evaluation of atmospheric N loading.
Ancient geological dynamics impact neutral biodiversity accumulation and are detectable in phylogenetic reconstructions
Authors: Herrera‐Alsina Leonel , Algar Adam C. , Bocedi Greta , Gubry‐Rangin Cecile , Lancaster Lesley T. , Mynard Poppy , Osborne Owen G. , Papadopulos Alexander S. T. , Creer Simon , Nangoy Meis , Fahri Fahri , Lupiyaningdyah Pungki , Sudiana I Made , Juliandi Berry , Travis Justin M. J. 
Published: June 2021

AbstractAimLandmasses have been continuously modified by tectonic activity, the breakup and collision of landmasses is thought to have generated or suppressed ecological opportunities, altering the rates of speciation, dispersal and extinction. However, the extent to which the signatures of past geological events are retained in modern biodiversity patterns—or obliterated by recent ecological dynamics—remains unresolved. We aim to identify the fingerprint of different scenarios of geological activity on phylogenetic trees and geographic range size distributions.LocationGlobal.Time periodGeological time.Major taxa studiedTheoretical predictions for any taxa.MethodsWe conducted spatially explicit simulations under a neutral model of range evolution, speciation and extinction for three different geological scenarios that differed in their geological histories. We set a limit on the number of populations that locally can coexist, which, along with the geographic boundaries of landmasses, influences the rate of range expansion.ResultsOur results demonstrate regions of similar size, age and ecological limits will differ in richness and macroevolutionary patterns based solely on the geological history of landmass breakup and collision even in the absence of species’ ecological differences, that is, neutrality. When landmasses collide, regional richness is higher, lineages exhibit more similar rates of speciation and phylogenetic trees are more balanced than in the geologically static scenario. Stringent local limits to coexistence yield lower regional diversity but in general do not affect our ability to distinguish geological scenarios.Main conclusionsThese findings provide an alternative explanation for existence of some hotspots of diversity in areas of high geological activity. Although a limit on the number of coexisting species largely influences regional diversity, its contribution to phylogenetic patterns is lower than variation in per‐capita rates of speciation and extirpation. Importantly, these findings demonstrate the potential for inferring past geological history from distributions of phylogenies and range sizes.
Use of electronic self‐administered bleeding assessment tool in diagnosis of paediatric bleeding disorders
Authors: Kaur Dominder , Kerlin Bryce A. , Stanek Joseph R. , O'Brien Sarah H. 
Published: June 2021

AbstractIntroductionIn the era of electronic medical records, pen‐and‐paper‐based physician‐administered bleeding assessment tools (BAT) remain under‐utilized in the clinical setting, as they are noted to be time‐consuming.AimThe current study reviews the use of an electronic self‐administered bleeding assessment tool (eBAT) prospectively in a paediatric haematology clinic and in comparison with a physician administered BAT (pBAT).Materials and MethodsThis was reviewed and approved in the current form because the aims statement includes the method regarding comparison of 2 groups. So no additional section required.ResultsA total of 94 BAT response pairs were available for analysis. The median time required for patients or parents to complete the eBAT was 8 min, with less than a third of the patients requiring over 10 min. The median bleeding scores noted in this study were 4 for both the BATs, with strong positive correlation between the eBAT and the physician administered bleeding questionnaire. The eBAT had a sensitivity of 93.8% (95% CI 82.8%–98.7%), a specificity of 34.8% (95% CI 21.4%–50.3%), a positive predictive value (PV) of 60.0% (95% CI 54.5%–65.2%) and a negative PV of 84.2% (95% CI 62.5%–94.5%) for identifying a bleeding disorder.ConclusionsFindings indicate that eBAT is a valid and time‐efficient screening tool for evaluating patients’ bleeding symptoms, which can improve clinical applicability of BATs by reducing time for bleeding history review.
Pharmacokinetic, efficacy and safety evaluation of B‐domain‐deleted recombinant FVIII (SCT800) for prophylactic treatment in adolescent and adult patients with severe haemophilia A
Authors: Xue Feng , Zhao Xielan , Sun Jing , Zeng Xiaojing , Yang Fenge , Xu Ming , Yu Ziqiang , Gu Weiying , Feng Ying , Li Wenqian , Zheng Changcheng , Bi Hui , Xie Liangzhi , Gai Wenlin , Yang Renchi 
Published: June 2021

AbstractIntroductionSCT800 is a recombinant human B‐domain‐deleted coagulation factor VIII (BDDrFVIII) developed in China.AimTo evaluate the repeat pharmacokinetics (PKs), efficacy, and safety of SCT800 in previously treated Chinese adolescent and adult patients with severe haemophilia A.MethodsA phase III, multicentre, prospective, open‐label, single‐arm trial was conducted at 12 medical centres. Subjects received treatment for 24 weeks. PKs were assessed at the initial and repeated dosing 24 weeks later. The primary endpoint was annualized bleeding rate (ABR). Breakthrough bleeding episodes and inhibitor development were assessed.ResultsA total of 71 of 73 patients completed the study, and 18 were enrolled for the repeat PK investigation. Total exposure was 5643 exposure days. Overall, SCT800 showed comparable repeat PK profiles. The total ABR was 2.82 (95% confidence interval 2.01‐3.96). During prophylaxis, 43.8% of patients had no bleeding episodes. The majority (89.4%) of bleeding episodes were controlled with 1–2 injections of SCT800, the success rate (defined as ‘excellent’ or ‘good’ haemostatic response) for the treatment of bleeding episodes was 92.6%. The incidence of treatment‐related adverse events was 53.4%. Drug‐related AE incidence was 4.1%. The observed AEs were similar to those of other coagulation factor VIII, but lower in frequency. No subject developed an inhibitor, and no other safety concerns were identified.ConclusionsSCT800 has robust PK characteristics, and is safe and efficacious for the prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult patients with severe haemophilia A.