bluuebunny/crossref_metadata_2025_split huggingface dataset:
Added value of metastatic cervical lymph node group V in nodal staging of nasopharyngeal cancer
Authors: Setakornnukul Jiraporn , Thephamongkhol Kullathorn , Chaysiri Panid 
Published: June 2020

AbstractBackgroundPrognostic significance of posterior cervical lymph node metastasis in nasopharyngeal cancer is largely unknown. This study aims to determine the added prognostic significance of cervical lymph node group V to the standard American Joint Committee on Cancer (AJCC) staging system (eighth edition AJCC) of nasopharyngeal patients with cancer treated with intensity‐modulated radiation therapy (IMRT) in terms of overall survival (OS), distant metastatic‐free survival (DMFS), and disease‐free survival (DFS).Methods and MaterialsA retrospective cohort of 199 consecutively diagnosed nasopharyngeal patients with cancer treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) in the era of IMRT in a large university hospital in endemic area of Southeast Asia. Pre‐treatment imaging studies were thoroughly re‐evaluated and re‐staged by a board‐certified radiologist using radiographic criteria for cervical lymph node metastasis. T and N classifications were reclassified according to the eighth AJCC staging system. Group V (Va and Vb) cervical node was evaluated for its added prognostic significance. Cox's proportional hazard model was used to retrieve hazard ratio (HR), 95% confidence interval and P value for N classification. Harrell's C‐statistic (concordance index) was used for test of discrimination and internal validation was calculated by bootstrap method.ResultsThis study demonstrated greater separation of OS with HR of 6.75 (95%CI 1.94‐23.51, P = .003) by using group Vb only as N3 compared to HR of 4.70 (95%CI 1.37‐16.13, P = .014) by using current standard N3 disease (groups IV and Vb). Similarly, N2 with presence of Va shows worsened DFS with HR of 8.70 (95%CI 1.08‐69.67, P = .042) compared to N2 without Va with HR of 5.93 (95%CI 0.76‐46.00, P = .089). After incorporating cervical group V into nodal staging, the HR and 95%CI among each group was better separated than the eighth AJCC staging system but without significant improvement in C‐index.ConclusionCervical lymph node group V is a potentially added prognostic factor to standard TNM staging.
Crafting job demands and employee creativity: A diary study
Authors: Sun Shuhua , Wang Nan , Zhu Jinlong , Song Zhaoli 
Published: June 2020

AbstractPeople are more creative on some days than others. Studying how individuals generate creative ideas from day to day could contribute to knowledge regarding the causes of such within‐person variations and have practical implications for improving employee creativity across time. By adopting a dynamic resource allocation perspective and a repeated‐measure diary design, we developed and examined a theoretical model focusing on the within‐person processes of employee creativity. Specifically, we hypothesized that momentary role‐breadth self‐efficacy predicts daily changes in increasing job challenges, which, in turn, predicts daily changes in employee creativity, and that the latter relationship is accentuated by decreasing hindering demands. Results, based on 818 pairs of matched morning–afternoon observations from 91 employees over 10 workdays, provided support for our predictions. We discuss the theoretical and practical implications of these results for improving employee daily creativity.
Real‐world outcomes of advanced melanoma patients not represented in phase III trials
Authors: van Zeijl Michiel C. T. , Ismail Rawa K. , de Wreede Liesbeth C. , van den Eertwegh Alfonsus J. M. , de Boer Anthonius , van Dartel Maaike , Hilarius Doranne L. , Aarts Maureen J. B. , van den Berkmortel Franchette W. P. J. , Boers‐Sonderen Marye J. , de Groot Jan‐Willem B. , Hospers Geke A. P. , Kapiteijn Ellen , Piersma Djura , van Rijn Rozemarijn S. , Suijkerbuijk Karijn P. M. , ten Tije Albert J. , van der Veldt Astrid A. M. , Vreugdenhil Gerard , Haanen John B. A. G. , Wouters Michel W. J. M 
Published: June 2020

AbstractThe aim was to provide evidence on systemically treated patients with advanced melanoma not represented in phase III trials to support clinical decision‐making. Analysis were performed on advanced melanoma patients diagnosed between 2014 and 2017 in the Netherlands, treated with immune‐ or targeted therapy, who met ≥1 trial exclusion criteria. These criteria were derived from the KEYNOTE‐006 and CHECKMATE‐067/‐066 phase III trials. Prognostic importance of factors associated with overall survival (OS) was assessed with the Kaplan‐Meier method, Cox models, predicted OS probabilities of prognostic subgroups and a conditional inference survival tree (CIST). A nationwide population‐based registry was used as data source. Of 2536 systemically treated patients with advanced melanoma, 1004 (40%) patients were ineligible for phase IIII trials. Ineligible patients had a poorer median OS (mOS) compared to eligible patients (8.8 vs 23 months). Eligibility criteria strongly associated with OS in systemically treated ineligible patients were Eastern Cooperative Oncology Group Performance Score (ECOG PS) ≥2, brain metastases (BM) and lactate dehydrogenase (LDH) of >500 U/L. Patients with ECOG PS of ≥2 with or without symptomatic BM had a predicted mOS of 6.5 and 11.3 months and a 3‐year survival probability of 9.3% and 23.6%, respectively. The CIST showed the strongest prognostic covariate for survival was LDH, followed by ECOG PS. The prognosis of patients with LDH of >500 U/L is poor, but long‐term survival is possible. The prognosis of ineligible patients with advanced melanoma in real‐world was very heterogeneous and highly dependent on LDH value, ECOG PS and symptomatic BM.
Challenges in RNA Regulation in Huntington's Disease: Insights from Computational Studies
Authors: Palomino‐Hernandez Oscar , Margreiter Michael A. , Rossetti Giulia 
Published: June 2020

AbstractNovel therapeutic approaches are being developed to tackle neurodegenerative diseases, due to the lack of efficiency of the known druggable targets. For Huntington's disease, a promising approach is the regulation of the RNA product. This target would allow for a selective and effective inhibition of the toxic effects exerted by the final nucleic product and the coded protein. In this review, the current state of the art of RNA regulation is discussed, with a brief but insightful view on novel plausible targets. After this, an emphasis on successful computational and experimental approaches tailored in modeling and regulating RNA aberrant behavior are extensively presented. Finally, the application and limitations of current computational methods are discussed, and possible avenues for improvement are outlined.
Testicular sperm extraction in a patient with ejaculatory dysfunction after combined androgen blockade therapy for prostate cancer
Authors: Amano Toshiyasu , Suzuki Chihiro , Shimojima Yuji , Imao Tetsuya , Earle Carolyn 
Published: June 2020

IntroductionProstate cancer is the most prevalent urological cancer for older men. However, there is still a possibility that a few prostate cancer patients may still wish to have children.Case presentationA 49‐year‐old male was diagnosed with low‐risk prostate cancer. Combined anti‐androgen blockade therapy was performed for 8 months prior to radiation therapy. However, he suffered from ejaculatory dysfunction and wished to conceive with his partner. Hormonal therapy was discontinued and he was referred to our clinic for sperm preservation. His ejaculatory function did not recover after 4 months discontinuation of hormonal therapy, subsequently micro‐testicular sperm extraction for sperm preservation was successfully performed.ConclusionSperm preservation in patients with prostate cancer is unusual but it should be considered if the patient’s fertility is an issue.
Structural and electronic properties of defective 2D transition metal dichalcogenide heterostructures
Authors: Pecoraro Adriana , Schiavo Eduardo , Maddalena Pasqualino , Muñoz‐García Ana B. , Pavone Michele 
Published: June 2020

AbstractWe present a first‐principles study on the structure‐property relationships in MoS2 and WS2 monolayers and their vertically stacked hetero‐bilayer, with and without Sulfur vacancies, in order to dissect the electronic features behind their photocatalytic water splitting capabilities. We also benchmark the accuracy of three different exchange‐correlation density functionals for both minimum‐energy geometries and electronic structure. The best compromise between computational cost and qualitative accuracy is achieved with the HSE06 density functional on top of Perdew–Burke–Ernzerhof minima, including dispersion with Grimme's D3 scheme. This computational approach predicts the presence of mid‐gap states for defective monolayers, in accordance with the present literature. For the heterojunction, we find unexpected vacancy‐position dependent electronic features: the location of the defects leads either to mid‐gap trap states, detrimental for photocatalyst or to a modification of characteristic type II band alignment behavior, responsible for interlayer charge separation and low recombination rates.
Vaccine development and therapeutic design for 2019‐nCoV/SARS‐CoV‐2: Challenges and chances
Authors: Ghaebi Mahnaz , Osali Abdolreza , Valizadeh Hamed , Roshangar Leila , Ahmadi Majid 
Published: June 2020

AbstractThe ongoing outbreak of the recently emerged 2019 novel coronavirus (nCoV), which has seriously threatened global health security, is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with high morbidity and mortality. Despite the burden of the disease worldwide, still, no licensed vaccine or any specific drug against 2019‐nCoV is available. Data from several countries show that few repurposed drugs using existing antiviral drugs have not (so far) been satisfactory and more recently were proven to be even highly toxic. These findings underline an urgent need for preventative and therapeutic interventions designed to target specific aspects of 2019‐nCoV. Again the major factor in this urgency is that the process of data acquisition by physical experiment is time‐consuming and expensive to obtain. Scientific simulations and more in‐depth data analysis permit to validate or refute drug repurposing opportunities predicted via target similarity profiling to speed up the development of a new more effective anti‐2019‐nCoV therapy especially where in vitro and/or in vivo data are not yet available. In addition, several research programs are being developed, aiming at the exploration of vaccines to prevent and treat the 2019‐nCoV. Computational‐based technology has given us the tools to explore and identify potentially effective drug and/or vaccine candidates which can effectively shorten the time and reduce the operating cost. The aim of the present review is to address the available information on molecular determinants in disease pathobiology modules and define the computational approaches employed in systematic drug repositioning and vaccine development settings for SARS‐CoV‐2.
Asprosin promotes β‐cell apoptosis by inhibiting the autophagy of β‐cell via AMPK‐mTOR pathway
Authors: Wang Rui , Hu Wenchao 
Published: June 2020

AbstractAsprosin is a newly discovered adipokine. A recent study showed that asprosin promoted the β‐cell apoptosis of MIN6 cells. This study aims to determine whether asprosin induces the apoptosis in β‐cell via regulating autophagy. Mouse insulinoma MIN6 cells were divided into the following four groups: control, vehicle, high glucose, and asprosin groups. MIN6 cells in the asprosin group were transfected with recombinant asprosin‐T2A‐GFP vector. MIN6 cells in the vehicle group were transfected with vector only. Then the apoptosis of MIN6 cells was detected using flow cytometry. Real‐time polymerase chain reaction and western blot were used to determine the expression of caspase 3, LC3‐I, LC3‐II, beclin 1, P62, AMP activated protein kinase (AMPK), and mammalian target of rapamycin (mTOR). AMPK pathway was enhanced using AMPK agonist AICAR. High glucose and asprosin induced the apoptosis of MIN6 cells and elevated expression of caspase 3. In addition, high glucose and asprosin resulted in reduced expression of LC3‐II/LC3‐I, beclin 1, and increased expression of P62. p‐AMPK expression was decreased and p‐mTOR expression was increased after high glucose and asprosin treatment. AMPK agonist AICAR was used to activate the AMPK pathway. Treatment with AICAR significantly partly restored decreased autophagy and increased apoptosis of β‐cell, which was induced by asprosin. Asprosin promotes the apoptosis of β‐cell by inhibiting the autophagy of β‐cell via AMPK‐mTOR pathway.
A Comprehensive Review of Tocilizumab in COVID‐19 Acute Respiratory Distress Syndrome
Authors: Khiali Sajad , Khani Elnaz , Entezari‐Maleki Taher 
Published: June 2020

AbstractCurrently, the world is facing the pandemic of a novel strain of beta‐coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Acute respiratory distress syndrome (ARDS) is the most devastating complication of SARS‐CoV‐2. It was indicated that cytokine‐release syndrome and dominantly interleukin (IL)‐6 play a central role in the pathophysiology of ARDS related to the novel 2019 coronavirus disease (COVID‐19). Despite the global emergency of the disease, at this time, there are no proven therapies for the management of the disease. Tocilizumab is a potential recombinant monoclonal antibody against IL‐6 and currently is under investigation for the management of ARDS in patients with COVID‐19. Given these points, we reviewed the current evidence regarding the potential therapeutic role of tocilizumab and its important clinical issues in the treatment of ARDS related to COVID‐19.
Subtypes of physical frailty and their long‐term outcomes: a longitudinal cohort study
Authors: Huang Shih‐Tsung , Tange Chikako , Otsuka Rei , Nishita Yukiko , Peng Li‐Ning , Hsiao Fei‐Yuan , Tomida Makiko , Shimokata Hiroshi , Arai Hidenori , Chen Liang‐Kung 
Published: June 2020

AbstractBackgroundComponents of physical frailty cluster into subtypes, but it remains unknown how these might be associated with age‐related functional declines and multimorbidities. This study aims to investigated associations of physical frailty subtypes with functional declines and multimorbidity in a 10 year longitudinal cohort survey.MethodsComplementary longitudinal cohort study used group‐based multitrajectory modelling to verify whether frailty subtypes discovered in Taiwan are presented in another aging cohort, then investigated associations of these subtypes with cognitive decline and multimorbidity. Participants aged ≥50 years were recruited from the third to sixth waves (May 2002 to July 2010) of the National Institute for Longevity Sciences‐Longitudinal Study of Aging, in Japan. People with incomplete data, pre‐frail/frail status before their index wave, and those with incomplete data or who died during follow‐up, were excluded. Group‐based trajectory analysis denoted five established physical frailty criteria as time‐varying binary variables in each wave during follow‐up. Incident frailty was classified as mobility subtype (weakness/slowness), non‐mobility subtype (weight loss/exhaustion), or low physical activity subtype. General linear modelling investigated associations of these frailty subtypes with activities of daily living, digit symbol substitution test (DSST) and Charlson Comorbidity Index (CCI) at 2 year follow‐up.ResultsWe identified four longitudinal trajectories of physical frailty, which corroborated the distinct subtypes we discovered previously. Among 940 eligible participants, 38.0% were robust, 18.4% had mobility subtype frailty, 20.7% non‐mobility subtype, and 20.1% low physical activity subtype. People with mobility subtype frailty were older than those with other frailty subtypes or robust status and had higher prevalence of hypertension, diabetes, and heart failure. In the multivariable‐adjusted general linear models, mobility‐subtype frailty was associated with a significantly lower DSST score (point estimate −2.28, P = 0.03) and higher CCI (point estimate 0.82, P < 0.01) than the other groups.ConclusionsMobility‐subtype frailty was associated with functional declines and progression of multimorbidity; the long‐term effects of physical frailty subtypes deserve further investigation.
COMMD8 changes expression during initial phase of wasp venom immunotherapy
Authors: Kempiński Karol , Romantowski Jan , Maciejewska Agnieszka , Pawłowski Ryszard , Chełmińska Marta , Jassem Ewa , Niedoszytko Marek 
Published: June 2020

AbstractBackgroundHymenoptera venom allergy (HVA) is of great concern because of the possibility of anaphylaxis, which may be fatal. Venom immunotherapy (VIT) is the only disease‐modifying treatment in HVA and, although efficient, its mechanism remains partially unknown. Gene expression analysis may be helpful for establishing a proper model of tolerance induction during the build‐up phase of VIT. The present study aimed to analyze how the start of VIT changes the expression of 15 selected genes.MethodsForty‐five patients starting VIT with a wasp venom allergy were enrolled. The diagnosis was established based on anaphylaxis history (third or fourth grade on the Mueller scale) and positive soluble immunoglobulin E and/or skin tests. Two blood collections were performed in the patient group: before and after 3 months of VIT. One sample was taken in the control group. Gene expression analysis was performed using a reverse transcriptase‐polymerase chain reaction with microfluidic cards and normalized to the 18S housekeeping gene.ResultsCommd8 was the only gene that changed expression significantly after the start of VIT (p = 0.012). Its expression decreased towards the levels observed in the healthy controls. Twelve out of 15 genes (commd8, cldn1, cngb3, fads1, hes6, hla‐drb5, htr3b, prlr, slc16a4, snx33, socs3 and twist2) revealed a significantly different expression compared to the healthy controls.ConclusionsThe present study shows that commd8 changes significantly its expression during initial phase of VIT. This gene might be a candidate for VIT biomarker in future studies.
Epstein‐Barr virus‐immortalized B lymphocytes exacerbate experimental autoimmune encephalomyelitis in xenograft mice
Authors: Polepole Pascal , Bartenslager Alison , Liu Yutong , Petro Thomas M. , Fernando Samodha , Zhang Luwen 
Published: June 2020

AbstractMultiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system. Epstein‐Barr virus (EBV) is a causative agent for infectious mononucleosis (IM) that is associated with MS pathogenesis. However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV‐infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans and is a well‐established rodent model for human MS. We have found that xenografts of EBV‐immortalized B lymphocytes, which partially resemble the hyperproliferation of EBV‐infected cells in IM, exacerbate autoimmune responses in myelin oligodendrocyte glycoprotein‐induced EAE in C57BL/6 mice. After remission, an additional challenge with EBV‐immortalized cells induces a relapse in EAE. Moreover, xenografts with EBV‐immortalized cells tighten the integrity of the blood‐brain barrier (BBB) in the thalamus and hypothalamus areas of the mouse brains. Genomic sequences of prokaryotic 16S ribosomal RNA presented in the feces reveal that EBV‐immortalized cells significantly change the diversities of microbial populations. Our data collectively suggest that EBV‐mediated proliferation of B lymphocytes may be a risk factor for the exacerbation of MS, which are associated with gut microbiome changes and BBB modulations. Furthermore, multiple xenografts of EBV‐immortalized cells into C57BL/6 mice could serve as a useful model for human relapsing‐remitting MS with predictable severity and timing.
A case series of COVID‐19 patients with chronic hepatitis B virus infection
Authors: Li Yang , Li Chunyang , Wang Jian , Zhu Chuanwu , Zhu Li , Ji Fang , Liu Longgen , Xu Tianmin , Zhang Biao , Xue Leyang , Yan Xiaomin , Huang Rui , Wu Chao , Yan Xuebing 
Published: June 2020

AbstractPrevious studies reported that coronavirus disease 2019 (COVID‐19) was likely to result in liver injury. However, few studies reported the impacts of COVID‐19 on liver function in patients with chronic liver diseases. We aimed to describe a case series of COVID‐19 patients with chronic hepatitis B virus (HBV) infection. Confirmed hospitalized COVID‐19 patients from hospitals in 10 cities of Jiangsu province, China, were retrospectively included between 18 January 2020 and 26 February 2020. Demographic information, epidemiologic data, clinical features, and treatment data were extracted from medical records. Seven COVID‐19 patients with chronic HBV infection were included. Six (85.7%) patients were male. The patients aged from 33 to 49 years. Two patients had HBV‐related cirrhosis. One patient (14.3%) was positive for serum HBV e‐antigen. On admission, 1 (14.3%) patient had mildly elevated alanine aminotransferase (ALT) level (>40 U/L) and 1 (14.3%) had elevated aspartate aminotransferase (AST) level (>40 U/L). The serum albumin level and platelet counts were decreased in two patients with HBV‐related liver cirrhosis. Three (42.9%) patients had elevated ALT level and 2 (28.6%) patients had elevated AST level in hospitalization. However, the peak ALT and AST level during hospitalization was 51 U/L and 44 U/L, respectively. As of 29 February 2020, all patients were discharged. No patient was admitted to the intensive care units or developed liver failure during hospitalization. The abnormalities of liver function are not uncommon on COVID‐19 patients with chronic HBV infection in our case series. However, no patient developed severe liver‐related complications during hospitalization.
High‐density mapping of multiple atypical atrial flutter. First HD GRID mapping experience among The Commonwealth of Independent States
Authors: Bakytzhanuly Abay , Abdrakhmanov Ayan , Seisembekov Telman , Smagulova Aliya , Blyalova Dariga 
Published: June 2020

AbstractMapping of multiple atrial tachycardias after previous cryoballoon pulmonary vein isolations and multiple radiofrequency ablations can be challenging even for experienced specialists. HD Grid high‐density mapping catheter is one of the catheters, which helps not only to precisely identify the mechanisms of macro‐reentry tachycardia but also to avoid unnecessary radiofrequency applications. Accordingly, we present two cases of complex atrial arrhythmia with the use of HD Grid, which showed clear visualization of mechanisms and target ablations with the termination of tachycardia.