bluuebunny/crossref_metadata_2025_split huggingface dataset:
Japanese Society of Medical Oncology Clinical Guidelines: Molecular Testing for Colorectal Cancer Treatment, 4th edition
Authors: Ebi Hiromichi , Bando Hideaki , Taniguchi Hiroya , Sunakawa Yu , Okugawa Yoshinaga , Hatanaka Yutaka , Hosoda Waki , Kumamoto Kensuke , Nakatani Kaname , Yamazaki Kentaro 
Published: July 2020

AbstractMolecular testing to select the appropriate targeted and standard of care therapies is essential for managing patients with colorectal cancer (CRC). The Japanese Society of Medical Oncology previously published clinical guidelines for molecular testing in CRC. In the third edition published in 2018, RAS and BRAF V600E mutations should be tested prior to first‐line chemotherapy to assess the benefit of anti–epidermal growth factor receptor (EGFR) antibody therapy in patients with unresectable CRC. Microsatellite instability (MSI) testing was recommended in patients with curatively resected stage II CRC because deficient mismatch repair is associated with low risk of recurrence. MSI testing was also recommended in patients with CRC suspected to be Lynch syndrome. The main aim of this fourth edition is to reflect recent advances in comprehensive genomic profiling (CGP) tests and liquid biopsy. Here, CGP tests performed on tumor tissues are strongly recommended to assess the benefit of molecular targeted drugs in patients with CRC. Circulating tumor DNA (ctDNA)‐based CGP tests are also proposed. ctDNA testing is recommended to determine the optimal treatment based on the risk of recurrence for curatively resected CRC and evaluate the suitability and monitor the therapeutic effects of anti–EGFR antibodies in patients with unresectable CRC. While both MSI testing and immunohistochemistry are strongly recommended to determine the indication of immune checkpoint inhibitors in patients with unresectable CRC, next‐generation sequencing‐based tests are weakly recommended because these tests have not been validated in clinical trials.
Combined in vitro and in silico analyses of FGFR1 variants: genotype‐phenotype study in idiopathic hypogonadotropic hypogonadism
Authors: Wang Daoqi , Niu Yonghua , Tan Jiahong , Chen Yinwei , Xu Hao , Ling Qing , Gong Jianan , Ling Le , Wang Jiaxin , Wang Tao , Liu Jihong 
Published: July 2020

AbstractFibroblast growth factor receptor 1 (FGFR1) is an idiopathic hypogonadotropic hypogonadism (IHH)‐associated gene, mutated in approximately 10% of the patients with this condition. Through targeted gene sequencing of 153 males with IHH and 100 healthy controls, we identified 10 mutations in FGFR1 from IHH patients with a frequency of 5.9% in the Chinese population of central China. These included nine missense mutations(NM_023110.2, p.Gly687Arg, p.Ala608Asp, p.Gly348Glu, p.Asn296Ser, p.Gly226Asp, p.Arg209Cys, p.Gly97Arg, p.Val71Met, p.Gly70Arg) and a splicing mutation c.1430 + 1G > T. in vitro and in silico analyses of FGFR1 variants were conducted to study the impact of the identified mutations. Our findings indicated that the splicing mutation dramatically affected premRNA processing, causing exon 10 and 6 nucleotides in the 3′ end of exon 9 to be completely skipped. Two variants (p.Gly687Arg and p.Ala608Asp) markedly impaired tyrosine kinase activity, while the other variants had limited impact on the mitogen‐activated protein kinase (MAPK) signaling pathway. However, the functional impairment of the mutant receptors was not always consistent with the phenotypes, indicating that FGFR1 mutations might cause IHH in conjunction with other mutant genes. In this study, we expanded the knowledge on the mutation spectrum of FGFR1 in IHH patients and explored the genotype‐phenotype relationship.
Real time three‐dimensional echocardiographic quantification of left atrial volume in orthotopic heart transplant recipients: Comparisons with cardiac magnetic resonance imaging
Authors: Zhu Shuangshuang , Sun Wei , Qiao Weihua , Li Meng , Li Yuman , Liang Bo , Wang Jing , Dong Nianguo , Zhang Li , Xie Mingxing 
Published: July 2020

AbstractIntroductionThe accuracy of real time three‐dimensional echocardiography (RT‐3DE) in evaluating left atrial volume (LAV) of heart transplant recipients against cardiac magnetic resonance (CMR) has not been reported. The aim of this study was to compare LAV with RT‐3DE with respect to CMR in heart transplant recipients.MethodsThirty‐one heart transplant recipients who received echocardiogram and CMR examination on the same day were prospectively enrolled. The maximal LAV, minimal LAV by RT‐3DE, and two‐dimensional echocardiography (2DE) were compared with CMR measurements. Inter‐technique comparisons included Pearson's correlation coefficient and Bland–Altman analysis. Reproducibility of 2DE and RT‐3DE technique was assessed by intra‐class correlation coefficient (ICC).ResultsRT‐3DE‐derived LAV values showed higher correlation with CMR than 2DE measurements in heart transplant recipients (r = .93 vs r = .76 for maximal LAV; r = .91 vs r = .81 for minimal LAV). Two‐dimensional echocardiography underestimated maximal LAV by 10 ± 31 mL and minimal LAV by 26 ± 26 mL. Although RT‐3DE underestimated minimal LAV 15 ± 19 mL, no significant difference between RT‐3DE and CMR was observed in maximal LAV (RT‐3DE: 86 ± 22 mL; CMR: 89 ± 23 mL, P = .079), with a negligible bias of 3 mL. Inter‐observer and intra‐observer agreement were excellent for 2DE and RT‐3DE parameters.ConclusionCompared with CMR reference, RT‐3DE‐derived LAV measurements are more accurate than 2DE‐based analysis in heart transplant recipients, especially with regard to the assessment of maximal LAV. RT‐3DE may be a valid alternative to CMR for quantification LAV in heart transplant recipients.
Severe acute respiratory syndrome coronavirus 2 may be an underappreciated pathogen of the central nervous system
Authors: Alam S. B. , Willows S. , Kulka M. , Sandhu J. K. 
Published: July 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes a highly contagious respiratory disease referred to as COVID‐19. However, emerging evidence indicates that a small but growing number of COVID‐19 patients also manifest neurological symptoms, suggesting that SARS‐CoV‐2 may infect the nervous system under some circumstances. SARS‐CoV‐2 primarily enters the body through the epithelial lining of the respiratory and gastrointestinal tracts, but under certain conditions this pleiotropic virus may also infect peripheral nerves and gain entry into the central nervous system (CNS). The brain is shielded by various anatomical and physiological barriers, most notably the blood–brain barrier (BBB) which functions to prevent harmful substances, including pathogens and pro‐inflammatory mediators, from entering the brain. The BBB is composed of highly specialized endothelial cells, pericytes, mast cells and astrocytes that form the neurovascular unit, which regulates BBB permeability and maintains the integrity of the CNS. In this review, potential routes of viral entry and the possible mechanisms utilized by SARS‐CoV‐2 to penetrate the CNS, either by disrupting the BBB or infecting the peripheral nerves and using the neuronal network to initiate neuroinflammation, are briefly discussed. Furthermore, the long‐term effects of SARS‐CoV‐2 infection on the brain and in the progression of neurodegenerative diseases known to be associated with other human coronaviruses are considered. Although the mechanisms of SARS‐CoV‐2 entry into the CNS and neurovirulence are currently unknown, the potential pathways described here might pave the way for future research in this area and enable the development of better therapeutic strategies.
Spectrum of Headaches Associated With SARS‐CoV‐2 Infection: Study of Healthcare Professionals
Authors: Porta‐Etessam Jesús , Matías‐Guiu Jordi A. , González‐García Nuria , Gómez Iglesias Patricia , Santos‐Bueso Enrique , Arriola‐Villalobos Pedro , García‐Azorín David , Matías‐Guiu Jorge 
Published: July 2020

BackgroundSeries of patients with SARS‐CoV‐2 infection report headache in 6%‐15% of cases, although some data suggest that the actual frequency is higher, and that headache is not associated with fever. No study published to date has analyzed the characteristics of headache in these patients.ObjectiveTo analyze the characteristics of COVID‐19 related headaches.MethodsWe conducted a survey of Spaniard healthcare professionals who have been infected by SARS‐CoV‐2 and presented headache during the course of the disease. The survey addressed respondents’ medical history and headache characteristics, and we analyzed the association between both.ResultsWe analyzed the responses of a sample of 112 healthcare professionals. History of migraine was reported by 20/112 (17.9%) of respondents, history of tension‐type headache by 8/112 (7.1%), and history of cluster headache was reported by a single respondent; 82/112(73.2%) of respondents had no history of headache. Headache presented independently of fever, around the third day after symptom onset. The previous history of migraine was associated with a higher frequency of pulsating headache (20% in patients with previous migraine vs 4.3% in those with no history of migraine, P = .013).ConclusionHeadache is often holocranial, hemicranial, or occipital, pressing, and worsens with physical activity or head movements. Because the characteristics of the headache and the associated symptoms are heterogeneous in our survey, we suggest that several patterns with specific pathophysiological mechanisms may underlie the headache associated with COVID‐19.
Design of an inhibitor of Helicobacter pylori cholesteryl‐α‐glucoside transferase critical for bacterial colonization
Authors: Pal Soumiya , Sarker Nishat , Qaria Majjid , Tandon Kshitij , Akhter Yusuf , Ahmed Niyaz 
Published: July 2020

AbstractBackgroundFifty percent of the world's population surves as a host for Helicobacter pylori, gastric cancer causing bacteria, that colonizes the gastric region of digestive tract. It has a remarkable capacity to infect the host stomach for the entire lifetime despite an activated host immune response.MethodsIn this study, we have performed the virtual screening analysis of protein‐inhibitor binding between the glycosyl transferase enzymes of Helicobacter pylori (CapJ or HP0421) and a corresponding library of inhibitors in the known substrate‐binding pockets. We have docked our library of ligands consisting of cholesterol backbone with CapJ protein and identified several ligands’ interacting amino acid residues present in active site pocket(s) of the protein.ResultsIn most of the cases, the ligands showed an interaction with the residues of the same pocket of the enzyme. Top three (03) hits were filtered out from the whole data set, which might act as potent inhibitors of the enzyme‐substrate reaction.ConclusionsThis study describes a new possibility by which colonization of H. pylori can be limited. The reported evidence suggests that comprehensive knowledge and wet laboratory validation of these inhibitors are needed in order to develop them as lead molecules.
Is it enough to be willing to win or do you have to be smart? The relationship between competitive worldviews, cognitive abilities, and applicant faking in personality tests
Authors: Schilling Michael , Sparfeldt Jörn R. , Becker Nicolas , Engel Marie , Levacher Julie , Sebastian Tilman F. P. , Schäfer Juliane , Schwabe Sarah , König Cornelius J. 
Published: July 2020

AbstractRecent research has highlighted competitive worldviews as a key predictor of faking—the intentional distortion of answers by candidates in the selection context. According to theoretical assumptions, applicants’ abilities, and especially their cognitive abilities, should influence whether faking motivation, triggered by competitive worldviews, can be turned into successful faking behavior. Therefore, we examined the influence of competitive worldviews on faking in personality tests and investigated a possible moderation of this relationship by cognitive abilities in three independent high school and university student samples (N1 = 133, N2 = 137, N3 = 268). Our data showed neither an influence of the two variables nor of their interaction on faking behavior. We discuss possible reasons for these findings and give suggestions for further research.
Motivational Drivers of Extensive Work Effort: Are Long Hours Always Detrimental to Well‐being?
Authors: Avgoustaki Argyro , Cañibano Almudena 
Published: July 2020

Is extensive work effort always detrimental to professionals’ well‐being? We argue that the link between extensive work effort and well‐being depends on the reasons why professionals work extended hours. Drawing on self‐determination theory and data from an international consultancy firm, we show that extrinsically driven work effort is negatively related to well‐being, while intrinsically driven work effort is positively related to well‐being. A reinforcing effect seems to exist between the two types of motivators, revealing that intrinsically driven work effort has both a direct and an indirect link to well‐being, mitigating the downsides of extrinsically driven work effort.
Genotypic yield responses of lowland rice in high‐altitude cropping systems
Authors: Razafindrazaka Ando , Stuerz Sabine , Cotter Marc , Rajaona Arisoa , Asch Folkard 
Published: July 2020

AbstractRising global mean temperatures open opportunities in high‐altitude production systems for temperature‐sensitive crops such as lowland rice. Currently, the cropping window for rice in higher altitudes is still narrow, and thus, genotypes that tolerate a certain degree of chilling are needed to achieve their potential yield. Final yield depends on the interaction between genotype and environmental conditions. Exposing the genotype to a wide range of environments is a way to evaluate its adaptability into an expanding cropping calendar. Over a 2‐year period, an experiment was conducted in lowland rice systems in Madagascar at two locations differing in altitude. Twenty genotypes with contrasting levels of tolerance to low temperature were sown monthly in a non‐replicated rice garden trial. Plant development was monitored and yield and yield components were determined. Yield stability across the different growing environments was investigated. While crop duration was affected by sowing dates and altitude, yield was mainly determined by sowing date. Panicle number per m2 and number of spikelets per panicle were the most limiting factors for yield potential in mid‐altitude, while in high altitude, yield was mainly limited by spikelet fertility. Resulting cropping calendar and genotype recommendations are discussed.
Season‐specific varietal management as an option to increase rainfed lowland rice production in East African high altitude cropping systems
Authors: Abera Bayuh Belay , Stuerz Sabine , Senthilkumar Kalimuthu , Cotter Marc , Rajaona Arisoa , Asch Folkard 
Published: July 2020

AbstractDue to land expansion and an increase in productivity, rice production in sub‐Saharan Africa has been growing at a rate of 6% in the past decade. Rainfed rice production systems have accounted for a large share of this expansion. In these systems, the potential growing period not only depends on the length of the rainy season and thus water availability, but is often, especially in the highlands of East Africa, bordered by the onset of the cool period of the year, when low minimum temperatures compromise rice yields. The objective of this study was to investigate the yield potential of 30 rice varieties contrasting in crop duration and cold tolerance in the highlands of East Africa, with its limited length of growing period. A field trial was conducted in the cropping seasons in 2016 and 2017 at the Fogera rice research station, Ethiopia. As a function of the onset of rains, rice was sown mid‐July in 2016 and early July in 2017. Early sowing in 2017 led to an extended crop duration and significantly lower yields of the short‐duration varieties, and to a shortened duration and significantly higher yields of the medium‐ and long‐duration varieties, when compared to late sowing in 2016. Late sowing compromised yield of the medium‐ and long‐duration varieties because of low temperatures during booting stage, which led to high spikelet sterility. Early sowing resulted in low yields of the short‐duration varieties, probably due to low solar radiation during the cloudy rainy season, which coincided with the vegetative stage. Therefore, choice of variety should be a function of the variable onset of the rainy season and related sowing date. However, crop models precisely calibrated for potential varieties and the respective environmental conditions could fully support the selection of a suitable variety, depending on the date of sowing, for example with the help of online tools or smartphone applications.
Clinical outcome of pulmonary vein isolation alone ablation strategy using VISITAG SURPOINT in nonparoxysmal atrial fibrillation
Authors: Yamaguchi Junji , Takahashi Yoshihide , Yamamoto Tasuku , Amemiya Miki , Sekigawa Masahiro , Shirai Yasuhiro , Tao Susumu , Hayashi Tatsuya , Yagishita Atsuhiko , Takigawa Masateru , Goya Masahiko , Sasano Tetsuo 
Published: July 2020

AbstractBackgroundRecent studies have shown the improvement in long‐term effectiveness with standardized pulmonary vein isolation (PVI) aimed at creating durable and contiguous lesions with VISITAG SURPOINT (VS) in paroxysmal atrial fibrillation (PAF).ObjectiveWe aimed to assess efficacy of PVI alone strategy using VS in non‐PAF patients and evaluate factors associated with corresponding clinical outcomes.MethodsConsecutive patients who underwent PVI for persistent/long‐standing persistent AF between May 2017 to July 2019 were studied retrospectively. PVI was performed with 30–50 W guided by VS (posterior target: 400–500, anterior target: 500). Left atrial voltage maps were created during atrial pacing after PVI.ResultsA total of 140 patients (119 males, age 62 ± 10 years, long‐standing persistent AF: 35) were included and followed for median of 454 days. No adverse events were reported in any patients during periprocedural and follow‐up period of up to 28 months. Kaplan–Meier analysis estimated that freedom from atrial tachycardia or AF (AT/AF) without antiarrhythmics at 1‐year was 70%. Radiofrequency delivery with higher power was associated with increased first‐pass isolation rate, but not with freedom from AT/AF. In multivariate analysis, long‐standing persistent AF and % low‐voltage zone (%LVZ) were independent predictors of clinical outcome. The best cut‐off value of %LVZ for predicting AT/AF recurrence was 3.24%. Freedom from AT/AF was 88% in patients with persistent AF and %LVZ < 3.24%, while 27% in those with long‐standing persistent AF and %LVZ ≥ 3.24%.ConclusionsPVI alone using VS was associated with excellent 1‐year success in patients with persistent AF and %LVZ < 3.24%, but was insufficient in those with long‐standing persistent AF and/or %LVZ ≥ 3.24%.
Sequential His bundle and left ventricular pacing for cardiac resynchronization
Authors: Deshmukh Amrish , Sattur Sudhakar , Bechtol Tim , Heckman Luuk I. B. , Prinzen Frits W. , Deshmukh Pramod 
Published: July 2020

AbstractIntroductionFusion of left ventricular pacing with intrinsic conduction provides superior resynchronization compared to biventricular pacing. His bundle pacing (HBP) preserves intrinsic conduction and allows for constant fusion with left ventricular pacing. This study evaluated sequential His bundle and left ventricular pacing for cardiac resynchronization therapy (CRT).MethodsIn patients referred for CRT, sequential His bundle and left ventricular pacing was performed when HBP did not correct the QRS. At implant, QRS duration and area were compared between biventricular pacing and His bundle and left ventricular pacing. Devices were programmed for His and left ventricular pacing. Functional status and echocardiography were evaluated in follow up.ResultsTwenty‐one patients, seven female, 70.7 ± 9.9 years, 57% with nonischemic cardiomyopathy were included. Baseline QRS duration was 170 ± 21 ms and was 157 ± 16 ms with HBP. Biventricular pacing resulted in a QRS duration of 141 ± 15 ms and decreased to 110 ± 14 ms with His bundle and left ventricular pacing (p < .0005). His bundle and left ventricular pacing resulted in a smaller paced QRS area (38.5 ± 22.6 µVs) compared to biventricular pacing (67.5 ± 24.0 µVs) and baseline (78.1 ± 28.1 µVs; p < .0005). Left ventricular ejection fraction increased from 27.6 ± 6.4% to 41.1 ± 12.5 (at 25 mean months, p = .001) and functional class improved from 3.1 ± 0.5 to 2.1 ± 0.8 (at mean 32 months, p < .001).ConclusionsSequential His bundle and left ventricular pacing results in superior electrical synchrony in patients with indication for CRT when HBP does not correct the QRS and resulted in promising clinical and echocardiographic response rates.
Exogenous neuritin treatment improves survivability and functions of Schwann cells with improved outgrowth of neurons in rat diabetic neuropathy
Authors: Xi Chunhong , Zhang Yingduan , Yan Mei , Lv Qing , Lu Huan , Zhou Jun , Wang Yucheng , Li Jianbo 
Published: July 2020

AbstractPathogenesis and treatment for diabetic neuropathy are still complex. A deficit of neurotrophic factors affecting Schwann cells is a very important cause of diabetic neuropathy. Neuritin is a newly discovered potential neurotrophic factor. In this study, we explored the effect of exogenous neuritin on survivability and functions of diabetic Schwann cells of rats with experimental diabetic neuropathy. Diabetic neuropathy was induced in rats. 12‐week diabetic rats contrasted with non‐diabetic normal rats had decreased levels of serum neuritin and slowed nerve conduction velocities (NCVs). Schwann cells isolated from these diabetic rats and cultured in high glucose showed reduced cell neuritin mRNA and protein and supernatant neuritin protein, increased apoptosis rates, increased caspase‐3 activities and progressively reduced viability. In contrast, exogenous neuritin treatment reduced apoptosis and improved viability, with elevated Bcl‐2 levels (not Bax) and decreased caspase‐3 activities. Co‐cultured with diabetic Schwann cells pre‐treated with exogenous neuritin in high glucose media, and diabetic DRG neurons showed lessened decreased neurite outgrowth and supernatant NGF concentration occurring in co‐culture of diabetic cells. Exogenous neuritin treatment ameliorated survivability and functions of diabetic Schwann cells of rats with diabetic neuropathy. Our study may provide a new mechanism and potential treatment for diabetic neuropathy.
The use of mechanistic reasoning in assessing coronavirus interventions
Authors: Aronson Jeffrey K. , Auker‐Howlett Daniel , Ghiara Virginia , Kelly Michael P. , Williamson Jon 
Published: July 2020

AbstractRationaleEvidence‐based medicine (EBM), the dominant approach to assessing the effectiveness of clinical and public health interventions, focuses on the results of association studies. EBM+ is a development of EBM that systematically considers mechanistic studies alongside association studies.Aims and objectivesTo explore examples of the importance of mechanistic evidence to coronavirus research.MethodsWe have reviewed the mechanistic evidence in four major areas that are relevant to the management of COVID‐19.Results and conclusions(a) Assessment of combination therapy for MERS highlights the need for systematic assessment of mechanistic evidence. (b) That hypertension is a risk factor for severe disease in the case of SARS‐CoV‐2 suggests that altering hypertension treatment might alleviate disease, but the mechanisms are complex, and it is essential to consider and evaluate multiple mechanistic hypotheses. (c) Confidence that public health interventions will be effective requires a detailed assessment of social and psychological components of the mechanisms of their action, in addition to mechanisms of disease. (d) In particular, if vaccination programmes are to be effective, they must be carefully tailored to the social context; again, mechanistic evidence is crucial. We conclude that coronavirus research is best situated within the EBM+ evaluation framework.