bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergency surgery for gastrointestinal cancer: A nationwide study in Japan based on the National Clinical Database
Authors: Hoshino Nobuaki , Endo Hideki , Hida Koya , Ichihara Nao , Takahashi Yoshimitsu , Hasegawa Hiroshi , Kimura Toshimoto , Kitagawa Yuko , Kakeji Yoshihiro , Miyata Hiroaki , Nakayama Takeo , Sakai Yoshiharu 
Published: June 2020

AbstractBackgroundEmergency gastrointestinal surgery, although rare, is known for its high mortality and morbidity. However, the risks of emergency surgery for gastrointestinal cancer have not been investigated in depth. This study aimed to investigate the impact of emergency surgery on mortality and morbidity in patients with gastrointestinal cancers and to identify associated risk factors.MethodsWe extracted data from the National Clinical Database, a nationwide surgery registration system in Japan, for patients with gastrointestinal cancer who underwent esophageal resection, total gastrectomy, distal gastrectomy, right hemicolectomy, or low anterior resection between 2012 and 2017. The impacts of emergency surgery on 30‐day mortality and incidence of overall postoperative complications were compared with those of non‐emergency surgery. Risk factors for mortality and overall postoperative complications were then sought in patients who underwent emergency surgery.ResultsThirty‐day mortality and incidence of overall postoperative complications were significantly higher in emergency surgeries for gastric, colon, and rectal cancers than in non‐emergency surgeries (odds ratios 4.86‐6.98 and 1.68‐2.18, respectively; all P < .001). Various risk factors were identified in the group that underwent emergency surgery, including preoperative sepsis and lower body mass index. Some of the risk factors were common to all types of surgery and others were specific to a certain type of surgery.ConclusionThe actual risk of emergency surgery and the risk factors for overall postoperative complications in emergency cases are shown to serve as a reference for postoperative management. Emergency surgery had an additional burden on patients depending on the type of surgery.
Reduction in Osteoarthritis Risk After Treatment With Ticagrelor Compared to Clopidogrel: A Propensity Score–Matching Analysis
Authors: Baker Matthew C. , Weng Yingjie , Robinson William H. , Ahuja Neera , Rohatgi Nidhi 
Published: June 2020

ObjectiveOsteoarthritis (OA) is a common cause of joint pain and disability, and effective treatments are lacking. Extracellular adenosine has antiinflammatory effects and can prevent and treat OA in animal models. Ticagrelor and clopidogrel are both used in patients with coronary artery disease, but only ticagrelor increases extracellular adenosine levels. This study was undertaken to determine whether treatment with ticagrelor was associated with a lower risk of OA.MethodsWe conducted a 1:2 propensity score–matching analysis using data from 2011–2017 in the Optum Clinformatics Data Mart. Patients who had received either ticagrelor or clopidogrel for ≥90 days were included in our study, and patients with a prior diagnosis of OA or inflammatory arthritis were excluded. OA was identified using International Classification of Diseases codes. The primary outcome was the time to diagnosis of OA after treatment with ticagrelor versus clopidogrel.ResultsOur propensity score–matched cohort consisted of 7,007 ticagrelor‐treated patients and 14,014 clopidogrel‐treated patients, with a median number of days receiving treatment of 287 and 284, respectively. For both groups, the mean age was 64 years, and 73% of the patients were male. Multivariate Cox regression analysis estimated a hazard ratio for developing OA of 0.71 (95% confidence interval 0.64–0.79) (P < 0.001) after treatment with ticagrelor compared to clopidogrel.ConclusionTreatment with ticagrelor was associated with a 29% lower risk of developing OA compared to treatment with clopidogrel over 5 years of follow‐up. We hypothesize that the reduction in OA seen in patients who received ticagrelor may in part be due to increased extracellular adenosine levels.
How Computer‐Assisted Learning Influences Medical Students' Performance in Anatomy Courses
Authors: Santos Raquel Sofia , Carvalho Ana Cristina , Tsisar Stanislav , Bastos Ana Raquel , Ferreira Diogo , Ferreira Maria Amélia , Povo Ana , Guimarães Bruno 
Published: June 2020

Anatomy is an essential subject of the medical curriculum. Despite its relevance, the curricular time and logistical resources devoted to teaching anatomy are in decline, favoring the introduction of new pedagogical approaches based on computer‐assisted learning (CAL). This new pedagogical approach provides an insight into students' learning profiles and features, which are correlated with knowledge acquisition. The aim of this study was to understand how training with CAL platforms can influence medical students' anatomy performance. A total of 611 medical students attending Musculoskeletal Anatomy (MA) and Cardiovascular Anatomy (CA) courses were allocated to one of three groups (MA Group, CA Group, and MA + CA Group). An association between the performance in these anatomy courses and the number of CAL training sessions was detected. In the MA Group (r = 0.761, P < 0.001) and the MA + CA Group (r = 0.786, P < 0.001), a large positive correlation was observed between musculoskeletal anatomy performance and the number of CAL training sessions. Similarly, in the CA Group (r = 0.670, P < 0.001) and the MA + CA Group (r = 0.772, P < 0.001), a large positive correlation was observed between cardiovascular anatomy performance and the number of CAL training sessions. Multiple linear regression models were performed, considering either musculoskeletal or cardiovascular anatomy performance as the dependent variable. The results suggest that using CAL platforms to study has a positive dose‐dependent effect on anatomy performance. Understanding students' individual features and academic background may contribute to the optimization of the learning process.
Quantitative determination of canagliflozin in human plasma samples using a validated HPTLC method and its application to a pharmacokinetic study in rats
Authors: Alam Prawez , Iqbal Muzaffar , Foudah Ahmed I. , Alqarni Mohammad H. , Shakeel Faiyaz 
Published: June 2020

AbstractCanagliflozin (CNZ) is the first sodium–glucose co‐transporter‐2 inhibitor approved for treatment of type 2 diabetes mellitus. In the proposed work, a sensitive, rapid and validated high‐performance thin‐layer chromatography (HPTLC) method was established for the estimation of CNZ in human plasma for the first time. HPTLC analysis of CNZ and internal standard (sildenafil) was performed on glass coated silica gel 60 F254 HPTLC plates using a binary mixture of chloroform–methanol 9:1 (%, v/v) as the mobile phase. Densitometric detection was done at 295 nm. Retardation factor values were obtained as 0.22 and 0.52 for the CNZ and the IS, respectively. The linearity range of CNZ was obtained as 200–3,200 ng/ml. A simple protein precipitation method was used for the extraction of analyte from plasma using methanol. The proposed HPTLC technique was validated for linearity, accuracy, precision and robustness. The proposed HPTLC technique was successfully utilized for the assessment of pharmacokinetic profile of CNZ in rats after oral administration. After oral administration, the peak plasma concentration of CNZ was obtained as 1458.01 ng/ml in 2 h. The proposed HPTLC method could be applied to the study of the pharmacokinetic profile of pharmaceutical formulations containing CNZ.
In Vitro Effects of Ginseng and the Seed of Zizyphus jujuba var. spinosa on Gut Microbiota of Rats with Spleen Deficiency
Authors: Li Fang‐Tong , Yang Di , Song Feng‐Yuan , Liu Ming , Dai Yu‐Lin , Zheng Fei , Yue Hao 
Published: June 2020

AbstractGinseng and the seed of Zizyphus jujuba var. spinosa, which are traditional Chinese medicinal materials, were often used in ancient Chinese recipes as a pair of medicines. They can replenish the primordial qi and tonify the spleen. This study investigated the effects of ginseng and the seed of Zizyphus jujuba var. spinosa (GS) extract on gut microbiota diversity in rats with spleen deficiency syndrome (SDS). A total of 52 compounds (including 16 flavonoids, 35 saponins, and 1 alkaloid) were identified and analyzed from the GS extract by UPLC‐Q‐Orbitrap‐MS/MS. The GS extract significantly increased the relative abundance of Firmicutes and Bacteroidetes in rats with SDS but decreased that of Proteobacteria and Actinobacteria. At the genus level, the GS extract significantly increased the relative abundance of Lactobacillus and Bifidobacterium in rats with SDS but decreased that of Streptococcus, Escherichia‐Shigella, Veillonella, and Enterococcus. In addition, the GS extract influenced glucose and amino acid metabolism. In summary, the results showed that the GS extract changed the structure and diversity of gut microbiota in rats with SDS and balanced the metabolic process.
Effect of sugar type and concentration on pasting and textural properties of corn starch in water and skim milk
Authors: Köse Şenol 
Published: June 2020

AbstractBackground and objectivesPasting and textural characteristics of corn starch in water and skim milk were prepared with different types of sugars (glucose, fructose, sucrose, and maltose) and different concentrations (0, 2, 4, 6, and 8%) were examined using Rapid Visco and Texture Analyzer.FindingsPasting parameters such as pasting temperature, peak time, peak, breakdown, trough, final and setback viscosities of corn starch–water and milk were influenced with the addition of sugar type and concentrations. Also, addition of sugar significantly influenced textural properties such as hardness, springiness, gumminess, adhesiveness, chewiness, cohesiveness, and resilience values of samples.ConclusionsThe results showed that addition of sugar to corn starch should be done carefully in terms of textural and pasting properties.Significance and NoveltySugar type and concentration directly influenced the product of corn starch samples.
Mob grazing increases trampling but not litter deposition on a Nebraska Sandhills subirrigated meadow
Authors: Guretzky John A. , Mamo Martha , Schacht Walter H. , Volesky Jerry D. , Wingeyer Ana B. 
Published: June 2020

AbstractHigh cattle stocking densities may enhance trampling, litter deposition, and soil organic matter (OM) formation in grasslands. To test this, we measured aboveground vegetation production, standing live and dead mass before and after grazing, vegetation utilization, trampling, litter accumulation, and spring standing dead mass across 2014 and 2015, comparing high [210,343 lb live weight (LW) acre–1] and low (7,011 lb LW acre–1) stocking densities in a Nebraska Sandhills subirrigated meadow. Pregrazing live mass in the cool‐season grass‐dominated meadow averaged 3,722 and 4,128 lb acre–1 under the low and high densities, respectively. Utilization was greater under the high (93%) than the low (85%) stocking density, resulting in less postgrazing live mass (272 and 521 lb acre–1, respectively). The high stocking density also increased trampling (41%) of live vegetation relative to the low density (25%) but did not affect annual litter accumulation, which averaged 1,957 lb acre–1. Trampling accounted for 97% of annual litter accumulation under the high stocking density but 51% under the low density, indicating the importance of senescence and fall of standing plant material under the latter. Transfer of trampled tissue to the litter pool was 931 and 1,762 lb acre–1 at maximum, whereas the transfer of senescent and detached standing plant material to the litter pool was 1,085 and 136 lb acre–1 at minimum under the low and high densities, respectively. We reject the hypothesis that high stocking densities enhances annual litter deposition and, in turn, soil OM formation in grasslands.
An Eight‐Step Total Synthesis of Pyrroloquinolone‐TypeLycopodium Alkaloid via a Tandem Annulation Approach†
Authors: Zhong Lin‐Rui , Yang Yuanjie , Huang Bing‐Bing , Yao Zhu‐Jun 
Published: June 2020

Summary of main observation and conclusionA total synthesis of 6,7,9,10,12,12a‐hexahydro‐2‐methyl‐(2R,4aS,12aS)‐2H,5H‐benzo[e]pyrrolo[3,2,1‐ij]quinolone‐4,11(1H,3H)‐dione (1), a unique pyrroloquinolone‐type Lycopodium alkaloid containing a complex 6/6/6/5 tetracyclic core, has been disclosed in eight steps and 38% overall yield. The reported synthesis features a short, efficient synthesis of the crucial multi‐substituted cyclohexanone intermediate with three stereogenic centers, and one‐pot generation of the complex 6/6/6/5 tetracyclic core in a single tandem step.
A biomechanical analysis of 3D stress and strain patterns in patellar tendon during knee flexion
Authors: Wang Kunyang , Hosseinnejad Soroosh H. , Jabran Ali , Baltzopoulos Vasilios , Ren Lei , Qian Zhihui 
Published: June 2020

AbstractPatellar tendinopathy is among the most widespread patellar tendon diseases in athletes that participate in activities involving running and jumping. Although their symptoms can be detected, especially at the inferior pole of the patella, their biomechanical cause remains unknown. In this study, a three‐dimensional finite element model of knee complex was developed to investigate principal stress and strain distributions in the patellar tendon during 0° to 90° knee flexion and slow and fast level‐ground walking. Results indicate that the patellar tendon is subjected to tensile stress and strains during all three activities. During flexion, its central proximal posterior region exhibited highest peak stress and strain, followed by central distal posterior, central distal anterior and central proximal anterior region. Similar trends and magnitudes were reported during slow and fast walking. The region with highest principal stresses and strains, central proximal anterior region, also corresponds to the most commonly reported patellar tendinopathy lesion site, suggesting that principal stress and strain are good indicators of lesion site location. Additional factors such as regional variations in material properties and frequency and duration of cyclic loading also need to be considered when determining the biomechanical aetiology of patellar tendinopathy.
Relationship Between Progression‐Free Survival, Objective Response Rate, and Overall Survival in Clinical Trials of PD‐1/PD‐L1 Immune Checkpoint Blockade: A Meta‐Analysis
Authors: Ye Jiabu , Ji Xiang , Dennis Phillip A. , Abdullah Hesham , Mukhopadhyay Pralay 
Published: June 2020

PD‐1/PD‐L1 immune checkpoint blockade (ICB) has improved overall survival (OS) in solid tumor trials; however, parallel improvements in Response Evaluation Criteria in Solid Tumors (RECIST)‐based surrogate end points, progression‐free survival (PFS), and objective response rate (ORR), are not always observed. Here, we assess the surrogacy of PFS/ORR for OS with ICB therapy across advanced/metastatic tumors. In a trial‐level analysis (N = 40 randomized trials), PFS, ORR, and OS treatment effects were correlated (Spearman's rho). In a patient‐level analysis, data were extracted from available trials of durvalumab; the correlation of PFS and OS was evaluated (Bayesian normal‐induced‐copula‐estimation model) and the ordinal association between objective response and OS hazard ratio (HR) were assessed with concordance index measures. High correlation was observed between PFS HR and OS HR in intention‐to‐treat (ITT; rho = 0.76) and PD‐L1‐enriched populations (0.74); modest (or limited) benefit in PFS was associated with meaningful improvement in OS. Moderate correlations were observed between ΔORR and OS HR: ITT, −0.63; PD‐L1‐enriched, −0.53. At the patient level, a positive association was observed between PFS and OS in non‐small cell lung cancer (Kendall’s Tau = 0.793; 95% confidence interval, 0.789–0.797), head and neck squamous cell carcinoma (0.794; 0.789–0.798), and bladder cancer (0.872; 0.869–0.875). Objective responders had significantly better OS (concordance index > 0.9) than nonresponders across these tumor types. Modest (or limited) improvement in RECIST‐based end points did not rule out meaningful OS benefit, indicating they are imperfect surrogates and do not fully capture ICB clinical benefit. Therefore, caution is advised when basing early discontinuation of novel ICB agents on these end points.
HucMSC‐exosomes carrying miR‐326 inhibit neddylation to relieve inflammatory bowel disease in mice
Authors: Wang Gaoying , Yuan Jintao , Cai Xiu , Xu Zhiwei , Wang Jingyan , Ocansey Dickson K.W. , Yan Yongmin , Qian Hui , Zhang Xu , Xu Wenrong , Mao Fei 
Published: June 2020

AbstractBackgroundInflammatory bowel disease (IBD) is a group of chronic intestinal inflammation that is a risk factor for many gastrointestinal cancers. Exosomes are gradually gaining attention as an emerging treatment method for IBD due to their important biological characteristics. NF‐κB is an important pro‐inflammatory transcription factor kept inactive by IκB protein in the cytoplasm by masking the nuclear localization signal of NF‐κB. The deterioration of IκB is mainly ubiquitination, and this depends on neddylation.MethodsIn this study, we established a dextran sulfate sodium (DSS)‐induced IBD model in BABL/C mice to evaluate the effect of human umbilical cord mesenchymal stem cell‐derived exosomes (hucMSC‐exosomes, hucMSC‐Ex) on the repair of IBD. At the same time, human colorectal mucosa cells (FHC) were stimulated by LPS (lipopolysaccharide) in vitro to activate the inflammatory environment to study the mechanism of hucMSC‐Ex regulating neddylation. The microRNA (miRNA) obtained by sequencing and transfection with hucMSC‐Ex was used to verify the role of miR‐326/neddylation/IκB/NF‐κB signaling pathway in IBD repair.ResultsHucMSC‐Ex inhibited the process of neddylation in relieving DSS‐induced IBD in mice. The binding of NEDD8 (neural precursor cell‐expressed, developmentally downregulated gene 8) to cullin 1 and the activation of NF‐κB signaling pathway were suppressed along with reduced expression levels of neddylation‐related enzyme molecules. The same phenomenon was observed in FHC cells. The miRNA comparison results showed that miR‐326 was highly expressed in hucMSC‐Ex and played an important role in inhibiting the neddylation process. The therapeutic effect of hucMSC‐Ex with high expression of miR‐326 on IBD mice was significantly stronger than that of ordinary hucMSC‐Ex.ConclusionsHucMSC‐Ex relieves DSS‐induced IBD in a mouse model by inhibiting neddylation through miR‐326.
Evidence for endothelial‐to‐mesenchymal transition in human brain arteriovenous malformations
Authors: Shoemaker Lorelei D. , McCormick Aaron K. , Allen Breanna M. , Chang Steven D. 
Published: June 2020

AbstractBackgroundBrain arteriovenous malformations (AVMs) are rare, potentially devastating cerebrovascular lesions that can occur in both children and adults. AVMs are largely sporadic and the basic disease biology remains unclear, limiting advances in both detection and treatment. This study aimed to investigate human brain AVMs for endothelial‐to‐mesenchymal transition (EndMT), a process recently implicated in cerebral cavernous malformations (CCMs).MethodsWe used 29 paraffin‐embedded and 13 fresh/frozen human brain AVM samples to profile expression of panels of EndMT‐associated proteins and RNAs. CCMs, a cerebrovascular disease also characterized by abnormal vasculature, were used as a primary comparison, given that EndMT specifically contributes to CCM disease biology. AVM‐derived cell lines were isolated from three fresh, surgical AVM samples and characterized by protein expression.ResultsWe observed high collagen deposition, high PAI‐1 expression, and expression of EndMT‐associated transcription factors such as KLF4, SNAI1, and SNAI2 and mesenchymal‐associated markers such as VIM, ACTA2, and S100A4. SMAD‐dependent TGF‐β signaling was not strongly activated in AVMs and this pathway may be only partially involved in mediating EndMT. Using serum‐free culture conditions, we isolated myofibroblast‐like cell populations from AVMs that expressed a unique range of proteins associated with mature cell types and with EndMT. Conditioned medium from these cells led to increased proliferation of HUVECs and SMCs.ConclusionsCollectively, our results suggest a role for EndMT in AVM disease. This may lead to new avenues for disease models to further our understanding of disease mechanisms, and to the development of improved diagnostics and therapeutics.
Understanding embryonic development for cell‐based therapies of intervertebral disc degeneration: Toward an effort to treat disc degeneration subphenotypes
Authors: Tessier Steven , Risbud Makarand V. 
Published: June 2020

AbstractChronic low back and neck pain are associated with intervertebral disc degeneration and are major contributors to the global burden of disability. New evidence now suggests that disc degeneration comprises a spectrum of subphenotypes influenced by genetic background, age, and environmental factors, which may be contributing to the mixed outcomes seen in clinical trials of cell‐based therapies that aim to treat disc degeneration. This problem is further compounded by the fact that disc degeneration and aging coincide with an exhaustion of endogenous progenitor cells, imposing limitations on the regenerative capacity of the disc. At the bench‐side, current work is focused on applying our knowledge of embryonic disc development to direct and refine differentiation of adult and human‐induced pluripotent stem cells into notochord‐like and nucleus pulposus‐like cells for use in novel cell‐based therapies. Accordingly, this review presents the salient features of intervertebral disc development, post‐natal maintenance, and regeneration, with emphasis on recent advancements. We also discuss how a stratified approach can be undertaken for the development of future cell‐based therapies to bring emerging subphenotypes into consideration.
Marine water environmental DNA metabarcoding provides a comprehensive fish diversity assessment and reveals spatial patterns in a large oceanic area
Authors: Fraija‐Fernández Natalia , Bouquieaux Marie‐Catherine , Rey Anaïs , Mendibil Iñaki , Cotano Unai , Irigoien Xabier , Santos María , Rodríguez‐Ezpeleta Naiara 
Published: June 2020

AbstractCurrent methods for monitoring marine fish (including bony fishes and elasmobranchs) diversity mostly rely on trawling surveys, which are invasive, costly, and time‐consuming. Moreover, these methods are selective, targeting a subset of species at the time, and can be inaccessible to certain areas. Here, we used environmental DNA (eDNA), the DNA present in the water column as part of shed cells, tissues, or mucus, to provide comprehensive information about fish diversity in a large marine area. Further, eDNA results were compared to the fish diversity obtained in pelagic trawls. A total of 44 5 L‐water samples were collected onboard a wide‐scale oceanographic survey covering about 120,000 square kilometers in Northeast Atlantic Ocean. A short region of the 12S rRNA gene was amplified and sequenced through metabarcoding generating almost 3.5 million quality‐filtered reads. Trawl and eDNA samples resulted in the same most abundant species (European anchovy, European pilchard, Atlantic mackerel, and blue whiting), but eDNA metabarcoding resulted in more detected bony fish and elasmobranch species (116) than trawling (16). Although an overall correlation between fishes biomass and number of reads was observed, some species deviated from the common trend, which could be explained by inherent biases of each of the methods. Species distribution patterns inferred from eDNA metabarcoding data coincided with current ecological knowledge of the species, suggesting that eDNA has the potential to draw sound ecological conclusions that can contribute to fish surveillance programs. Our results support eDNA metabarcoding for broad‐scale marine fish diversity monitoring in the context of Directives such as the Common Fisheries Policy or the Marine Strategy Framework Directive.