bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acquired multi‐segment foot kinematics in haemophilic children, adolescents and young adults with or without haemophilic ankle arthropathy
Authors: Lobet Sebastien , Peerlinck Kathelijne , Hermans Cedric , Van Damme An , Staes Filip , Deschamps Kevin 
Published: June 2020

AbstractIntroduction and aimThe ankle joint remains vulnerable in children with haemophilia and is the primary joint affected. The purpose of this study was to dynamically characterize the segmental foot and ankle kinematics of male children, adolescents and young adults with or without ankle arthropathy.MethodsThe barefoot multi‐segment foot kinematics of 70 ankles from 35 haemophilia subjects between 6 and 20 years old were captured with the Rizzoli Multi‐Segment Foot Model. Joint damage of the tibiotalar and subtalar joints was scored using the IPSG‐MRI score. The feet of patients with or without evidence of ankle arthropathy were compared with those of matched typically developing boys via a nonpaired comparison. The differences between the affected and nonaffected sides of patients with unilateral ankle arthropathy were assessed using a paired comparison.ResultsSubjects without arthropathy demonstrated a nonsignificant trend towards a higher frontal plane range of motion (RoM) at the midfoot upon loading response and a lower sagittal plane RoM at the midfoot during midstance. No differences were observed between the affected side group and their matched control group. The affected side of unilaterally affected subjects exhibited a nonsignificant tendency towards a higher frontal plane RoM at the ankle joint upon loading response and terminal stance compared to the healthy side.ConclusionMost patients maintained physiological rocker function of the ankle and had no (mal)adaptive motion patterns in the more distal joints of the foot. Therefore, established structural lesions may remain subclinical with respect to moderate functional activities like walking.
Benign infiltrative myofibroblastic neoplasms of childhood with USP6 gene rearrangement
Authors: Malik Faizan , Wang Lu , Yu Zhongxin , Edelman Morris C , Miles Lili , Clay Michael R , Hedges Dale , Brennan Rachel C , Nichols Kim E , Beth McCarville M , Bahrami Armita 
Published: June 2020

AimsSeveral morphologically overlapping (myo)fibroblastic neoplasms harbour USP6 fusions, including aneurysmal bone cysts, nodular fasciitis, myositis ossificans, cranial fasciitis, fibro‐osseous pseudotumour of the digits, and cellular fibroma of the tendon sheath. USP6‐induced neoplasms are almost universally benign and cured by local excision. We aim to highlight the diagnostic value of USP6 fusion detection in a series of aggressive‐appearing paediatric myofibroblastic tumours.Methods and resultsThree deep‐seated, radiographically aggressive, and rapidly growing childhood myofibroblastic neoplasms were morphologically and molecularly characterised by USP6 break‐apart fluorescence in‐situ hybridisation (FISH), transcriptome sequencing, and targeted capture analysis. Each tumour occurred in the lower‐extremity deep soft tissue of a child presenting with pain, limping, or a mass. In all three patients, imaging studies showed a solid mass that infiltrated into surrounding skeletal muscle or involved/eroded underlying bone. The biopsied tumours consisted of variably cellular myofibroblastic proliferations with variable mitotic activity that lacked overt malignant cytological features. FISH showed that all tumours had USP6 rearrangements. On the basis of these results, all three patients were treated with conservative excision with positive margins. The excised tumours had foci resembling nodular fasciitis, fibromatosis, and pseudosarcomatous proliferation. Next‐generation sequencing revealed COL1A1–USP6 fusions in two tumours and a COL3A1–USP6 fusion in the third tumour. One tumour had a subclonal somatic APC in‐frame deletion. No recurrence was observed during follow‐up (8–40 months).ConclusionWe present a series of benign, but aggressive‐appearing, USP6‐rearranged myofibroblastic tumours. These deep‐seated tumours had concerning clinical and radiographic presentations and did not fit into one distinct histological category. These cases highlight the diagnostic value of USP6 fusion detection to identify benign nondescript tumours of this group, especially those with aggressive features, to avoid overtreatment.
The role of innate immunity in Alzheimer's disease
Authors: Ennerfelt Hannah E. , Lukens John R. 
Published: June 2020

AbstractThe amyloid hypothesis has dominated Alzheimer's disease (AD) research for almost 30 years. This hypothesis hinges on the predominant clinical role of the amyloid beta (Aβ) peptide in propagating neurofibrillary tangles (NFTs) and eventual cognitive impairment in AD. Recent research in the AD field has identified the brain‐resident macrophages, known as microglia, and their receptors as integral regulators of both the initiation and propagation of inflammation, Aβ accumulation, neuronal loss, and memory decline in AD. Emerging studies have also begun to reveal critical roles for distinct innate immune pathways in AD pathogenesis, which has led to great interest in harnessing the innate immune response as a therapeutic strategy to treat AD. In this review, we will highlight recent advancements in our understanding of innate immunity and inflammation in AD onset and progression. Additionally, there has been mounting evidence suggesting pivotal contributions of environmental factors and lifestyle choices in AD pathogenesis. Therefore, we will also discuss recent findings, suggesting that many of these AD risk factors influence AD progression via modulation of microglia and immune responses.
Densification, mechanical, and tribological properties of ZrB2‐ZrCx composites produced by reactive hot pressing
Authors: Kannan Rajaguru , Rangaraj Lingappa 
Published: June 2020

AbstractZrB2‐ZrCx composites were produced using Zr:B4C powder mixtures in the molar ratios of 3:1, 3.5:1, 4:1, and 5:1 by reactive hot pressing (RHP) at 4‐7 MPa, 1200°C for 60 minutes. X‐ray diffraction analyses confirmed the formation of nonstoichiometric zirconium carbide (ZrCx) with different lattice parameters and enhanced carbide formation by increasing the Zr mole fraction. An increase in applied pressure from 4 to 7 MPa was responsible for the improved relative density (RD) of 4Zr:B4C composition from 86% to 99%. Microstructural studies on Zr‐rich composites showed a reduction in unreacted B4C particles and enriched elongated ZrB2 platelets. Reaction and densification mechanism in 4Zr:B4C composition were studied as a function of temperature increased from 600 to 1200°C at an applied constant pressure of 7 MPa. After 1000°C, <40 vol.% of unreacted Zr was observed during the densification process. Concurrently, low energies of carbon diffusion and carbon vacancy formation were found to enhance nonstoichiometric ZrCx formation, which was found to be responsible for the completion of the reaction. The plastic deformation of unreacted Zr was responsible for the densification of the ZrB2‐ZrCx composite. The results clearly showed that the applied pressure is five times lower than the reported values. Moreover, a temperature of 1200°C was sufficient to produce dense ZrB2‐ZrCx composites. The improved microhardness, flexural strength, fracture toughness, and specific wear rate were 8.2‐15 GPa, 265‐590 MPa, 2.82‐6.33 MPa.m1/2, and 1.43‐0.376 × 10−2 mm2/N, respectively.
Outcomes of incident atrial fibrillation in heart failure with preserved or reduced ejection fraction: A community‐based study
Authors: Zhang Pei , Chamberlain Alanna M. , Hodge David O. , Cai Cheng , Xiao Pei L. , Han Jie , Jiang Chen‐Yang , Redfield Margaret M. , Roger Veronique L. , Cha Yong‐Mei 
Published: June 2020

AbstractIntroductionThe best management strategy for patients with atrial fibrillation (AF) with heart failure (HF) and preserved left ventricular ejection fraction (LVEF) is unknown.Methods and ResultsThis cohort study was conducted in Olmsted County, Minnesota, with resources of the Rochester Epidemiology Project. Patients with incident AF occurring between 2000 and 2014 with a prior or concurrent HF were included. Patients with LVEF ≥ 50% were designated as HF and preserved ejection fraction (HFpEF) and those with LVEF < 50% were designated as HF and reduced ejection fraction (HFrEF). Rhythm control in the first year after AF diagnosis was defined as prescriptions for an antiarrhythmic drug, catheter ablation, or maze procedure. The primary endpoint was all‐cause mortality. The secondary endpoints were cardiovascular death, cardiovascular hospitalization, and stroke or transient ischemic attack. Of 859 patients (age, 77.2 ± 12.1 years; 49.2%, female), 447 had HFpEF‐AF, and 412 had HFrEF‐AF. There was no difference in all‐cause mortality (10‐year mortality, 83% vs 79%; p = .54) or secondary endpoints between the HFpEF‐AF and HFrEF‐AF, respectively. Compared with the rate control strategy, rhythm control in HFpEF‐AF patients (n = 40, 15.9%) offered no survival benefits (adjusted HR, 0.70; 95% CI, 0.42–1.16; p = .16), whereas rhythm control in HFrEF‐AF patients (n = 52, 22.5%) decrease cardiovascular mortality (HR, 0.38; 95% CI, 0.17–0.86; p = .02).ConclusionsPatients with HFpEF‐AF and HFrEF‐AF had similar poor prognoses. Rhythm control strategy was seldom adopted in community care in patients with HF and AF. A rhythm control strategy may provide survival benefit for patients with HFrEF‐AF and the benefit of rhythm control in patients with HFpEF‐AF warrants further study.
Growth differentiation factor 11 promotes differentiation of MSCs into endothelial‐like cells for angiogenesis
Authors: Zhang Chi , Lin Yinuo , Liu Qi , He Junhua , Xiang Pingping , Wang Dianliang , Hu Xinyang , Chen Jinghai , Zhu Wei , Yu Hong 
Published: June 2020

AbstractGrowth differentiation factor 11 (GDF11) is a member of the transforming growth factor‐β super family. It has multiple effects on development, physiology and diseases. However, the role of GDF11 in the development of mesenchymal stem cells (MSCs) is not clear. To explore the effects of GDF11 on the differentiation and pro‐angiogenic activities of MSCs, mouse bone marrow–derived MSCs were engineered to overexpress GDF11 (MSCGDF11) and their capacity for differentiation and paracrine actions were examined both in vitro and in vivo. Expression of endothelial markers CD31 and VEGFR2 at the levels of both mRNA and protein was significantly higher in MSCGDF11 than control MSCs (MSCVector) during differentiation. More tube formation was observed in MSCGDF11 as compared with controls. In an in vivo angiogenesis assay with Matrigel plug, MSCGDF11 showed more differentiation into CD31+ endothelial‐like cells and better pro‐angiogenic activity as compared with MSCVector. Mechanistically, the enhanced differentiation by GDF11 involved activation of extracellular‐signal‐related kinase (ERK) and eukaryotic translation initiation factor 4E (EIF4E). Inhibition of either TGF‐β receptor or ERK diminished the effect of GDF11 on MSC differentiation. In summary, our study unveils the function of GDF11 in the pro‐angiogenic activities of MSCs by enhancing endothelial differentiation via the TGFβ‐R/ERK/EIF4E pathway.
Exosomal MiR‐500a‐3p promotes cisplatin resistance and stemness via negatively regulating FBXW7 in gastric cancer
Authors: Lin Hao , Zhang Liang , Zhang Caihua , Liu Pengpeng 
Published: June 2020

AbstractChemoresistance has been a major challenge in advanced gastric cancer (GC) therapy. Exosomal transfer of oncogenic miRNAs implicates important effects in mediating recipient cell chemoresistance by transmitting active molecules. In this study, we found that microRNA‐500a‐3p was highly expressed in cisplatin (DDP) resistant GC cells (MGC803/DDP and MKN45/DDP) and their secreted exosomes than that in the corresponding parental cells. MGC803/DDP‐derived exosomes enhance DDP resistance and stemness properties of MGC803 recipient cells via exosomal delivery of miR‐500a‐3p in vitro and in vivo through targeting FBXW7. However, reintroduction of FBXW7 in MGC803 cells reverses miR‐500a‐3p‐mediated DDP resistance as well as stemness properties. Furthermore, elevated miR‐500a‐3p in the plasma exosomes of GC patients is correlated with DDP resistance and thereby results in poor progression‐free prognosis. Our finding highlights the potential of exosomal miR‐500a‐3p as an potential modality for the prediction and treatment of GC with chemoresistance.
TIPE1‐mediated autophagy suppression promotes nasopharyngeal carcinoma cell proliferation via the AMPK/mTOR signalling pathway
Authors: Liu Yongliang , Qi Xiangqin , Zhao Zhenan , Song Daoliang , Wang Lianqing , Zhai Qiaoli , Zhang Xiaoning , Zhao Peiqing , Xiang Xinxin 
Published: June 2020

AbstractRecent studies have shown that tumour necrosis factor‐α–induced protein 8 like‐1(TIPE1) plays distinct roles in different cancers. TIPE1 inhibits tumour proliferation and metastasis in a variety of tumours but acts as an oncogene in cervical cancer. The role of TIPE1 in nasopharyngeal carcinoma (NPC) remains unknown. Interestingly, TIPE1 expression was remarkably increased in NPC tissue samples compared to adjacent normal nasopharyngeal epithelial tissue samples in our study. TIPE1 expression was positively correlated with that of the proliferation marker Ki67 and negatively correlated with patient lifespan. In vitro, TIPE1 inhibited autophagy and induced cell proliferation in TIPE1‐overexpressing CNE‐1 and CNE‐2Z cells. In addition, knocking down TIPE1 expression promoted autophagy and decreased proliferation, whereas overexpressing TIPE1 increased the levels of pmTOR, pS6 and P62 and decreased the level of pAMPK and the LC3B. Furthermore, the decrease in autophagy was remarkably rescued in TIPE1‐overexpressing CNE‐1 and CNE‐2Z cells treated with the AMPK activator AICAR. In addition, TIPE1 promoted tumour growth in BALB/c nude mice. Taken together, results indicate that TIPE1 promotes NPC progression by inhibiting autophagy and inducing cell proliferation via the AMPK/mTOR signalling pathway. Thus, TIPE1 could potentially be used as a valuable diagnostic and prognostic biomarker for NPC.
The influence of processing conditions on kinetics, anthocyanin profile and antioxidant activity of purple sweet potato subjected to hot air drying
Authors: Wang Junmin , Wu Guangxu , Wang Zhineng , Shu Bin , Li Li , Zhang Ruifen , Huang Fei , Dong Lihong , Zhang Mingwei , Chen Suo , Su Dongxiao 
Published: June 2020

AbstractPurple sweet potato is rich in anthocyanins. The influence of hot air drying on the physical properties, anthocyanin profile and antioxidant capacity of purple sweet potato was explored at six different temperatures (60, 70, 80, 90, 100, and 110°C), three different paving densities and six different dimensions. The results show that the hot air drying kinetics of purple sweet potato were best described by the Page model. The samples dried at 60°C had the highest rehydration rate (2.64), and there was no significant difference between 80 and 60°C. There were no significant differences among the colors of the samples dried at 60, 70, 80, and 90°C, but they were quite different from that dried at 110°C. Four anthocyanins were identified by HPLC–MS/MS as cyanidin 3‐sophoroside‐5‐glucoside, peonidin 3‐sophoroside‐5‐glucoside, cyanidin 3‐p‐hydroxybenzoylsophoroside‐5‐glucoside and peonidin 3‐p‐hydroxybenzoylsophoroside‐5‐glucoside and determined by HPLC‐DAD, and the anthocyanin contents of the samples dried at 80°C were 609.08 ± 3.26, 82.75 ± 0.33, 265.88 ± 0.93, and 179.74 ± 1.35 mg/100 g DW, respectively. The highest ORAC antioxidant capacity was found in samples dried at 80°C (130.94 ± 2.59 μmol TE/g). Based on these studies, 80°C is most suitable for the hot air drying of purple sweet potato.Practical applicationsPurple sweet potatoes have good antioxidant capacity, which is good for health and loved by consumers. Fresh purple sweet potatoes are not easy to store, but the storage time can be prolonged after hot air drying. This study detected the influence of hot air drying on the drying kinetic, color, rehydration, microstructure, and anthocyanin content of purple sweet potato. Compared with dimension and paving density, the influence of drying temperature is greater. Among six temperatures, 80°C is most suitable for the hot air drying of purple sweet potato. This study provides a theoretical basis for the development and utilization of purple sweet potato as a functional food.
Estimating design flood runoff volume
Authors: Vesuviano Gianni , Stewart Elizabeth , Young Andrew R. 
Published: June 2020

AbstractStandard flood risk estimation methods in the United Kingdom have largely focused on peak flows at ungauged locations. However, the importance of whole‐hydrograph and event volume estimation in a design context is increasing with the application of unsteady‐state hydraulic models and construction of sustainable drainage systems. Here, we explore the relationship between peak flow estimation accuracy and flood volume estimation accuracy across 780 events in 81 catchments. Runoff hydrographs are modelled using ReFH2, a rainfall‐runoff model widely used by practitioners for design flood estimation in the UK. We find that strong performance in peak flow estimation is highly correlated with strong performance in event volume estimation, and that between‐event variation in performance is greater than the typical reduction in performance when moving from calibrated to design (regression‐based) model parameters. Unfortunately, evaluating model performance in terms of runoff volume is complicated by the fact that measured rainfall hyetographs and runoff hydrographs are themselves estimates that can disagree with each other for legitimate reasons. We demonstrate that it is not always possible, expected or realistic to close the water balance over an event in a topographically defined river catchment. Hence, ‘errors’ in modelled hydrographs cannot be solely attributed to modelling deficiencies.
In vitro metabolic characterization of orbitazine, a novel derivative of the PAC-1 anticancer agent
Authors: Li Fang , Han Xuhua , Chen Yanfen , Wang Shanshan , Cheng Zeneng , Hu Gaoyun , Liu Wenjie , Zhu Qubo 
Published: June 2020

Abstract

Objectives
The in vitro evaluation of new drugs is an important step in the drug development pipeline. Orbitazine is a derivative of PAC-1 that has substituted the functional group homopiperazine ring with a piperazine ring. The purpose of this study was to assess the metabolic profile of orbitazine.

Methods
Metabolism was characterized in vitro by incubating liver microsomes with metabolize orbitazine or the classical metabolic enzyme substrates. High performance liquid chromatography (HPLC) and LC-MS/MS were used to identify the parent drugs and metabolites of orbitazine or metabolic enzyme substrates.

Key findings
There was no difference in metabolic stability or metabolites across different species. The metabolites included a debenzyl compound and several hydroxyl compounds, defined as M1(316), M2(440), M3(422), M4(422) and M5(422). We found that orbitazine was metabolized by CYP3A4, CYP2C9 and CYP2D6 in a human liver microsomes incubation system. Orbitazine had no significant inhibitory effect on CYP1A2, CYP2B6, CYP2C9, or CYP2C19 in human liver microsomes, but showed a dose-dependent inhibition of CYP2C8, CYP2D6 and CYP3A4; and there was no orbitazine-mediated induction of CYP1A2, CYP2B6, CYP3A4 or mRNA expression in hepatocytes.

Conclusions
This in vitro data on the metabolism of orbitazine may provide valuable information to support further clinical progression as a potential therapeutic molecule.
Prevalence and management of chronic insomnia in Swiss primary care: Cross‐sectional data from the “Sentinella” practice‐based research network
Authors: Maire Micheline , Linder Stefanie , Dvořák Charles , Merlo Christoph , Essig Stefan , Tal Kali , Del Giovane Cinzia , Syrogiannouli Lamprini , Duss Simone B. , Heinzer Raphael , Nissen Christoph , Bassetti Claudio L. A. , Auer Reto 
Published: June 2020

AbstractWe investigated the prevalence and treatment of patients with chronic insomnia presenting to Swiss primary care physicians (PCPs) part of “Sentinella”, a nationwide practice‐based research network. Each PCP consecutively asked 40 patients if they had sleep complaints, documented frequency, duration, comorbidities, and reported ongoing treatment. We analysed data of 63% (83/132) of the PCPs invited. The PCPs asked 76% (2,432/3,216) of included patients about their sleep (51% female); 31% (761/2,432) of these had had insomnia symptoms; 36% (875/2,432) had current insomnia symptoms; 11% (269/2,432) met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐5) criteria for chronic insomnia (61% female). In all, 75% (201/269) of patients with chronic insomnia had comorbidities, with 49% (99/201) reporting depression. Chronic insomnia was treated in 78% (209/269); 70% (188/268) took medication, 38% (102/268) benzodiazepines or benzodiazepine receptor agonists, 32% (86/268) took antidepressants. Only 1% (three of 268) had been treated with cognitive behavioural therapy for insomnia (CBT‐I). A third of patients presenting for a non‐urgent visit in Swiss primary care reported insomnia symptoms and 11% met the DSM‐5 criteria for chronic insomnia. Hypnotics were the most common treatment, but almost no patients received first‐line CBT‐I. Reducing the burden of insomnia depends on disseminating knowledge about and access to CBT‐I, and encouraging PCPs to discuss it with and offer it as a first‐line treatment to patients with chronic insomnia.
Dysbiosis is not present in horses with fecal water syndrome when compared to controls in spring and autumn
Authors: Schoster Angelika , Weese J. Scott , Gerber Vinzenz , Nicole Graubner Claudia 
Published: June 2020

AbstractBackgroundFecal water syndrome (FWS) is long‐standing and common in horses, particularly in central Europe. No large epidemiological data sets exist, and the cause remains elusive. Dysbiosis could play a role in pathogenesis.ObjectivesTo evaluate whether dysbiosis is present in horses with FWS when compared to stable‐matched control horses in spring and autumn.AnimalsFecal samples were collected from horses with FWS (n = 16; 9 mares, 7 geldings) and controls (n = 15; 8 mares, 7 geldings).MethodsThe bacterial microbiome of samples collected in spring and autumn of 2016 was analyzed using high‐throughput sequencing. Differences in relative abundance of bacterial taxa, alpha diversity, and beta diversity indices were assessed between horses with FWS and controls based on season.ResultsDifferences in microbial community composition based on time point and health status were not observed on any taxonomic level. Limited differences were seen on linear discriminant analysis effect size analysis. No difference in alpha diversity indices was observed including richness, diversity based on health status, or time point. No effect of health status on microbial community membership structure was observed.Conclusions and Clinical ImportanceLimited differences were found in the bacterial microbiota of horses with and without FWS, regardless of season. Further research is needed to elucidate the role of microbiota in the development of FWS.