bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined oral 5-azacytidine and romidepsin are highly effective in patients with PTCL: a multicenter phase 2 study
Authors: Falchi Lorenzo , Ma Helen , Klein Sandra , Lue Jennifer K. , Montanari Francesca , Marchi Enrica , Deng Changchun , Kim Hye A. , Rada Aishling , Jacob Alice T. , Kinahan Cristina , Francescone Mark M. , Soderquist Craig R. , Park David C. , Bhagat Govind , Nandakumar Renu , Menezes Daniel , Scotto Luigi , Sokol Lubomir , Shustov Andrei R. , O’Connor Owen A. 
Published: November 2020

Abstract
Peripheral T-cell lymphomas (PTCLs) are uniquely vulnerable to epigenetic modifiers. We demonstrated in vitro synergism between histone deacetylase inhibitors and DNA methyltransferase inhibitors in preclinical models of T-cell lymphoma. In a phase 1 trial, we found oral 5-azacytidine and romidepsin to be safe and effective, with lineage-selective activity among patients with relapsed/refractory (R/R) PTCL. Patients who were treatment naïve or who had R/R PTCL received azacytidine 300 mg once per day on days 1 to 14, and romidepsin 14 mg/m2 on days 8, 15, and 22 every 35 days. The primary objective was overall response rate (ORR). Targeted next-generation sequencing was performed on tumor samples to correlate mutational profiles and response. Among 25 enrolled patients, the ORR and complete response rates were 61% and 48%, respectively. However, patients with T-follicular helper cell (tTFH) phenotype exhibited higher ORR (80%) and complete remission rate (67%). The most frequent grade 3 to 4 adverse events were thrombocytopenia (48%), neutropenia (40%), lymphopenia (32%), and anemia (16%). At a median follow-up of 13.5 months, the median progression-free survival, duration of response, and overall survival were 8.0 months, 20.3 months, and not reached, respectively. The median progression-free survival and overall survival were 8.0 months and 20.6 months, respectively, in patients with R/R disease. Patients with tTFH enjoyed a particularly long median survival (median not reached). Responders harbored a higher average number of mutations in genes involved in DNA methylation and histone deacetylation. Combined azacytidine and romidepsin are highly active in PTCL patients and could serve as a platform for novel regimens in this disease. This trial was registered at www.clinicaltrials.gov as #NCT01998035.
Estrogen receptors α, β and GPER in the CNS and trigeminal system - molecular and functional aspects
Authors: Warfvinge Karin , Krause Diana N. , Maddahi Aida , Edvinsson Jacob C. A. , Edvinsson Lars , Haanes Kristian A. 
Published: November 2020

AbstractBackgroundMigraine occurs 2–3 times more often in females than in males and is in many females associated with the onset of menstruation. The steroid hormone, 17β-estradiol (estrogen, E2), exerts its effects by binding and activating several estrogen receptors (ERs). Calcitonin gene-related peptide (CGRP) has a strong position in migraine pathophysiology, and interaction with CGRP has resulted in several successful drugs for acute and prophylactic treatment of migraine, effective in all age groups and in both sexes.MethodsImmunohistochemistry was used for detection and localization of proteins, release of CGRP and PACAP investigated by ELISA and myography/perfusion arteriography was performed on rat and human arterial segments.ResultsERα was found throughout the whole brain, and in several migraine related structures. ERβ was mainly found in the hippocampus and the cerebellum. In trigeminal ganglion (TG), ERα was found in the nuclei of neurons; these neurons expressed CGRP or the CGRP receptor in the cytoplasm. G-protein ER (GPER) was observed in the cell membrane and cytoplasm in most TG neurons. We compared TG from males and females, and females expressed more ER receptors. For neuropeptide release, the only observable difference was a baseline CGRP release being higher in the pro-estrous state as compared to estrous state. In the middle cerebral artery (MCA), we observed similar dilatory ER-responses between males and females, except for vasodilatory ERβ which we observed only in female arteries.ConclusionThese data reveal significant differences in ER receptor expression between male and female rats. This contrasts to CGRP and PACAP release where we did not observe discernable difference between the sexes. Together, this points to a hypothesis where estrogen could have a modulatory role on the trigeminal neuron function in general rather than on the acute CGRP release mechanisms and vasomotor responses.
Characterization and Fabrication of the CFM-JTE for 4H-SiC Power Device with High-Efficiency Protection and Increased JTE Dose Tolerance Window
Authors: Wen Yi , Xu Xiao-jie , Tao Meng-ling , Lu Xiao-fei , Deng Xiao-chuan , Li Xuan , Li Jun-tao , Li Zhi-qiang , Zhang Bo 
Published: November 2020

Abstract
A 13.5 kV 4H-SiC PiN rectifier with a considerable active area of 0.1 cm2 is fabricated in this paper. Charge-field-modulated junction termination extension (CFM-JTE) has been proposed for satisfying the requirement of ultra-high reverse voltage, which enlarges the JTE dose tolerance window, making it approximately 2.8 times that of the conventional two-zone JTE. Besides, the CFM-JTE can be implemented through the conventional two-zone JTE process. The measured forward current is up to 100 A @ VF = 5.2 V in the absence of carrier lifetime enhancement technology. The CFM-JTE structure accomplishes 96% of the theoretical breakdown voltage of the parallel plane junction with a relatively small terminal area of 400 μm, which contributes to achieving the Baliga’s figure of merit of 58.8 GW/cm2.
Mobility-as-a-service (MaaS) digital marketplace impact on EU passengers’ rights
Authors: Murati Erion 
Published: November 2020

AbstractIntegrated and seamless mobility has been a futuristic vision of mobility for a few years already. Today, Mobility as a Service (MaaS) embodies that vision through the integration of existing and new mobility services into one single digital platform, providing customised door-to-door transport and offering personalised trip or packages planning and payment options. The MaaS concept enable a practical shift from a fragmented and unimodal transport towards a harmonized, centralized and multimodal one, yet the current EU transport law, which is based on the principle of unimodality transport regulation, does not cover any passenger multimodal transport. Thus, as MaaS providers generate multimodal travel chains, it’s problematic that under EU law there is no harmonised legal base for multimodal passenger travel. Moreover, passenger rights cannot be guaranteed when an event occurring during one transport segment affects the following one, if the latter segment is operated with another operator of transport. In light of this, the knowledge gaps that this paper aims to fulfil are to comprehend, on the one hand, the status quo of EU passenger legislation and, on the other hand, the impact of MaaS concept on EU passenger’s rights. This will be achieved by analysing the EU transport law and its adequacy to cover passenger’s rights through a MaaS multimodal journey, as well as the position of a MaaS provider in a travel chain.
Transcriptome analysis of genes and pathways associated with metabolism in Scylla paramamosain under different light intensities during indoor overwintering
Authors: Li Na , Zhou Junming , Wang Huan , Mu Changkao , Shi Ce , Liu Lei , Wang Chunlin 
Published: November 2020

Abstract

Background
Scylla paramamosain is one of the commercially crucial marine crustaceans belonging to the genus Scylla, which is commonly distributed along the coasts of China, Vietnam, and Japan. Genomic and transcriptomic data are scarce for the mud crab. Light intensity is one of the ecological factors that affect S. paramamosain during indoor overwintering. To understand the energy metabolism mechanism adapted to light intensity, we analyzed the transcriptome of S. paramamosain hepatopancreas in response to different light intensities (0, 1.43, 40.31 μmol·m− 2·s− 1).

Results
A total of 5052 differentially expressed genes were identified in low light group (LL group, 3104 genes were up-regulated and 1948 genes were down-regulated). A total of 7403 differentially expressed genes were identified in high light group (HL group, 5262 genes were up-regulated and 2141 genes were down-regulated). S. paramamosain adapts to different light intensity environments through the regulation of amino acids, fatty acids, carbon and energy metabolism. Different light intensities had a strong impact on the energy generation of S. paramamosain by influencing oxygen consumption rate, aerobic respiration, glycolysis/gluconeogenesis pathway, the citrate cycle (TCA cycle) and fatty acid degradation.

Conclusion
Low light is more conducive to the survival of S. paramamosain, which needs to produce and consume relatively less energy to sustain physiological activities. In contrast, S. paramamosain produced more energy to adapt to the pressure of high light intensities. The findings of the study add to the knowledge of regulatory mechanisms related to S. paramamosain metabolism under different light intensities.
Integrated analysis of lncRNAs and mRNAs reveals key trans-target genes associated with ETEC-F4ac adhesion phenotype in porcine small intestine epithelial cells
Authors: Augustino Serafino M. A. , Xu Qinglei , Liu Xueqin , Mi Siyuan , Shi Liangyu , Liu Yibing , Wen Hui , Wang Di , Liu Lei , Zhang Qin , Yu Ying 
Published: November 2020

Abstract

Background
Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation at the transcriptional and post-transcriptional levels. LncRNAs are belonging to a large class of transcripts with ≥200 nt in length which do not code for proteins, have been widely investigated in various physiological and pathological contexts by high-throughput sequencing techniques and bioinformatics analysis. However, little is known about the regulatory mechanisms by which lncRNAs regulate genes that are associated with Enterotoxigenic Escherichia coli F4 fimbriae (ETEC-F4ac) adhesion phenotype in small intestine epithelial cells of Large White piglets. To address this, we used RNA sequencing to profile lncRNAs and mRNAs of small intestine epithelial cells in Large White piglets differing in their ETEC-F4 adhesion phenotypes and ITGB5 genotypes. Eight male piglets were used in this study and were divided into two groups on the basis of their adhesion phenotype and ITGB5 genotypes, a candidate gene for F4ac receptor. Non-adhesive group (n = 4) with CC genotype and adhesive group (n = 4) with TT genotype.

Results
In total, 78 differentially expressed lncRNAs (DE-lncRNA) and 223 differentially expressed mRNAs (log2 |FC| > 1, P < 0.05) were identified in the comparison of non-adhesive vs. adhesive small intestine epithelial cells. Furthermore, cis- and trans-regulatory target genes of DE-lncRNAs were identified, then interaction networks of lncRNAs and their cis- and trans-target differentially expressed genes (DEGs) were constructed separately. A total of 194 cis-targets were involved in the lncRNAs-cis genes interaction network and 61 trans-targets, were involved in lncRNA-trans gene interaction network that we constructed. We determined that cis-target genes were involved in alcoholism, systemic lupus erythematosus, viral carcinogenesis and malaria. Whereas trans-target DEGs were engaged in three important pathways related to the ETEC-F4 adhesion phenotype namely cGMP-PKG signaling pathway, focal adhesion, and adherens junction. The trans-target DEGs which directly involved in these pathways are KCNMB1 in cGMP-PKG signaling pathway, GRB2 in focal adhesion pathway and ACTN4 in focal adhesion and adherens junction pathways.

Conclusion
The findings of the current study provides an insight into biological functions and epigenetic regulatory mechanism of lncRNAs on porcine small intestine epithelial cells adhesion to ETEC-F4-ac and piglets’ diarrhea susceptibility/resistance.
Exploring patient willingness to accept hepatitis C-infected kidneys for transplantation
Authors: Edwards Gretchen C. , Shipe Maren E. , Smith Lindsay , Gamble Christianna , Shaffer David , Concepcion Beatrice P. , Forbes Rachel 
Published: November 2020

Abstract

Background
As organs infected with Hepatitis C virus (HCV) provide an opportunity to expand the donor pool, the primary aim of this study is to explore patient willingness to accept a kidney from HCV-infected donors compared to other high-risk donors.

Methods
An anonymous, electronic survey was sent to all active kidney transplant waitlist patients at a single large volume transplant center. Patients were asked to respond to three hypothetical organ offers from the following: 1) HCV-infected donor 2) Donor with active intravenous drug use and 3) Donor with longstanding diabetes and hypertension.

Results
The survey was sent to 435 patients of which 125 responded (29% response rate). While 86 out of 125 patients (69%) were willing to accept an HCV-infected kidney, only a minority of respondents were willing to accept a kidney from other high-risk donors. In contrast to other studies, by multivariable logistic regression, age and race were not associated with willingness to accept an HCV-infected kidney.

Conclusions
In this exploratory study, utilization of kidneys from HCV-infected donors to expand the donor pool appears to be an acceptable option to patients.
Evidence supporting the use of a subjective staff evaluation to assess the benefit of rehabilitation in hemodialysis patients undergoing inpatient rehabilitation
Authors: Shimoda Takahiro , Alston Helen , Chai Angelique , Jassal Sarbjit V. 
Published: November 2020

Abstract

Background
We questioned whether the introduction of a subjective evaluation of patient-specific goals, could be used as a valid method to assess the effectiveness of inpatient rehabilitation.

Methods
In this prospective cohort study, all admissions to the UHN hemodialysis rehabilitation service between April 2013 and August 2016 were included. We introduced a system of subjective assessment, performed by the team at the time of admission and discharge. We evaluated Functional Independence Measure (FIM®) score and KDQoL for objective measures of physical function and patient-reported quality of life.

Results
A total of 201 patients were included. The median FIM score at discharge correlated well with the subjective staff evaluation. FIM score changes for those with evaluations for Success, Partial success, and Not Successful were 28 [interquartile range (IQR) 20–34], 24 [IQR18–31], 16 [IQR 11–34] respectively. The median PCS at discharge for those deemed to have Success was 37.4 [IQR31.0, 44.7], and for those with Partial success & Not Successful 28.8 [IQR 22.4, 39.2]. There was no correlation with MCS scores (55.2 [IQR 51.2, 60.2], 58.4 [IQR 50.1, 63.1] respectively).

Conclusions
These results suggest the subjective staff evaluation is a brief but valid assessment of patient outcome for dialysis patients undergoing inpatient rehabilitation.
COVID-19 and maintenance hemodialysis: a systematic scoping review of practice guidelines
Authors: Akbarialiabad Hossein , Kavousi Shahin , Ghahramani Aria , Bastani Bahar , Ghahramani Nasrollah 
Published: November 2020

AbstractBackgroundCoronavirus Disease 2019 (COVID-19) has substantially impacted the provision of medical services. During the pandemic, many medical services, including facilities providing care to patients with end stage renal disease faced challenges in safeguarding patients and staff while providing clinical care. This study aims to identify the extent, range, and nature of articles related to COVID-19 and maintenance hemodialysis to understand the research gaps and propose recommendations for future research.MethodsUsing the terms: “Dialysis” OR “RRT” OR “Renal replacement therapy” AND “SARS-COV-2” OR “COVID-19” OR “novel coronavirus” OR “2019-nCov”, we performed a multi-step systematic search of the literature in the English language in Pubmed, Scopus, Embase, and Web of Science published from December 1, 2019, to May 13, 2020. Two authors separately screened the title and abstracts of the documents and ruled out irrelevant articles. We obtained a full report of the papers that met our inclusion criteria and screened the full texts. We conducted a descriptive analysis of the characteristics of the included articles and performed a narrative synthesis of the results. We conducted this scoping review in accordance with the PRISMA-ScR Checklist.ResultsWe included 22 articles in this scoping review. Perspectives (n = 9), editorials (n = 4), and case series (n = 5) were the most common types of articles. Most articles were from Italy and the United States. Seventeen (77.3%) of the articles focused on the topic of recommendation for outpatient hemodialysis units. While many of the recommendations overlapped in several articles, there were also many unique recommendations.Conclusionsmost of the articles are based on single-center experience, which spontaneously developed best practices. Many of these practices have formed the basis for policies and guidelines that will guide future prevention of infection and management of patients with End Stage Renal Disease (ESRD) and COVID-19.
Comparison of two different optical coherence tomography angiography devices in detecting healthy versus glaucomatous eyes – an observational cross-sectional study
Authors: Kee A. R. , Yip V. C. H. , Tay E. L. T. , Lim C. W. , Cheng J. , Teo H. Y. , Chua C. H. , Yip L. W. L. 
Published: November 2020

Abstract

Background
To understand the differences between two different optical coherence tomography angiography (OCTA) devices in detecting glaucomatous from healthy eyes by comparing their vascular parameters, diagnostic accuracy and test-retest reliability.

Methods
A cross-sectional observational study was performed on healthy and glaucoma subjects, on whom two sets of OCTA images of optic disc and macula were acquired using both AngioVue (Optovue, USA) and Swept Source (Topcon, Japan) OCTA devices during one visit. A novel in-house software was used to calculate the vessel densities. Diagnostic accuracy of the machines in differentiating healthy versus glaucomatous eyes was determined using area under the receiver operating characteristic curve (AUROC) and test-retest repeatability of the machines was also evaluated.

Results
A total of 80 healthy and 38 glaucomatous eyes were evaluated. Glaucomatous eyes had reduced mean vessel density compared to healthy controls in all segmented layers of the optic disc and macula using AngioVue (p ≤ 0.001). However, glaucomatous eyes had higher mean vessel density on optic disc scans using Swept Source, with lack of statistically significant difference between healthy and glaucomatous eyes. The AUROC showed better diagnostic accuracy of AngioVue (0.761–1.000) compared to Swept Source (0.113–0.644). The test-retest reliability indices were generally better using AngioVue than Swept Source.

Conclusions
AngioVue showed better diagnostic capability and test-retest reliability compared to Swept Source. Further studies need to be undertaken to evaluate if there is any significant difference between the various machines in diagnosing and monitoring glaucoma.
Using the drug repositioning approach to develop a novel therapy, tipepidine hibenzate sustained-release tablet (TS-141), for children and adolescents with attention-deficit/hyperactivity disorder
Authors: Saito Takuya , Yamashita Yushiro , Tomoda Akemi , Okada Takashi , Umeuchi Hideo , Iwamori Saki , Shinoda Satoru , Mizuno-Yasuhira Akiko , Urano Hidetoshi , Nishino Izumi , Saito Kazuhiko 
Published: November 2020

Abstract

Background
Asverin® (tipepidine hibenzate) has been used as an antitussive for > 50 years in Japan. Studies revealed that tipepidine modulates monoamine levels, by inhibiting G-protein-activated inwardly rectifying potassium (GIRK) channels, expecting the potential therapeutic effects of tipepidine for attention-deficit/hyperactivity disorder (ADHD) in recent years. In this study, TS-141, a sustained-release tablet of tipepidine, was developed for the treatment of ADHD through a drug repositioning approach.

Methods
The sustained-release profile of TS-141 in healthy adults was investigated, and tipepidine exposure in the plasma after the TS-141 administration was compared to that of Asverin in the phase I study. Phase II study was conducted to examine the effects of TS-141 30 (once a day), 60 (once a day), 120 mg (60 mg twice a day), or placebo, that is within the exposure in the maximum dosage of Asverin, in children and adolescents with ADHD, and was designed as an 8-week treatment, randomized, parallel group, double-blind, placebo-controlled trial recruiting 6–17-year-old children and adolescents diagnosed with ADHD. A total of 216 patients were randomized according to the CYP2D6 phenotype. The primary end-point was ADHD Rating Scale IV-J changes. Furthermore, effects of CYP2D6 phenotype on the efficacy in the subgroup analysis were investigated.

Results
TS-141 had the sustained-release profile, and the CYP2D6 phenotype had effects on the plasma exposure of tipepidine. ADHD RS-IV-J scores in all TS-141 dosages decreased from their baseline scores; however, no significant difference was observed in ADHD RS-IV-J score changes between the placebo and TS-141-administered groups. In patients with intermediate metabolizer CYP2D6, ADHD RS-IV-J score changes in the 120 mg group tended to be larger than that in the placebo group.

Conclusions
ADHD RS-IV-J changes on TS-141 may depend on the interaction between the TS-141 dose and CYP2D6 phenotype, suggesting that further clinical trials should be conducted with careful consideration of polymorphism. Drug repositioning approach of TS-141 was attempted at the same dose as that of antitussive; however, dose setting according to the indication was necessary.

Trial registration
Phase I study: JapicCTI-205235 (Registered 25 March 2020), Phase II study: JapicCTI-163244 (Registered 9 May 2016), https://www.clinicaltrials.jp/cti-user/trial/Show.jsp