bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significance of KDM6A Mutation in Bladder Cancer Immune Escape
Authors: Chen Xingxing , Lin Xuehua , Pang Guofu , Deng Jian , Xie Qun , Zhang Zhengrong 
Published: September 2020

Abstract
Background: Bladder cancer (BC) is the fourth most prevalent neoplasm in men and is associated with high tumour recurrence rates, leading to major treatment challenges. Lysine-specific demethylase 6A (KDM6A) is frequently mutated in several cancer types; however, its effects on tumour progression and clinical outcome in BC remain unclear. Here, we explored the potential role of KDM6A in regulating the antitumor immune response. Methods: We mined The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases for somatic mutation and clinical data in patients with BC. Results: We found frequent mutations in 12 genes in both cohorts, including TP53, KDM6A, CSMD3, MUC16, STAG2, PIK3CA, ARID1A, RB1, EP300, ERBB2, ERBB3, and FGFR3. The frequency of KDM6A mutations in the TCGA and ICGC datasets was 25.97% and 24.27%, respectively. In addition, KDM6A mutation was associated with a lower number of tumour-infiltrating lymphocytes and indicated a state of immune tolerance. KDM6A mutation was associated with lower KDM6A expression level compared with that in samples carrying the wild-type gene. Further, survival analysis showed that the prognosis of patients with low KDM6A expression was worse than that with high KDM6A expression. Using the CIBERSORT algorithm, Tumor Immune Estimation Resource site, and Gene Set Enrichment Analysis, we found that KDM6A mutation downregulated nine signalling pathways that participate in the immune system and attenuated the tumour immune response. Conclusion: Overall, we conclude that KDM6A mutation is frequent in BC and promotes tumour immune escape, which may serve as a novel biomarker to predict the immune response. Key Words: KDM6A, bladder cancer, mutation, immune
Tailoring of a Visible-Light-Absorbing Biaxial Ferroelectric towards Broadband Self-Driven Photodetection
Authors: Han Shiguo , Li Maofan , Liu Yi , Guo Wuqian , Hong Mao-Chun , Sun Zhihua , Luo Junhua 
Published: September 2020

Abstract
In term of strong light-polarization coupling, ferroelectric materials with bulk photovoltaic effects (BPVEs) afford a promising avenue for newly-conceptual optoelectronic devices. However, due to severe polarization deterioration caused by leakage current of photoexcited carriers, most of ferroelectrics are merely capable of absorbing 8 ~ 20% of visible-light spectra. BPVE-active ferroelectrics with the narrow bandgap (Eg < 2.0 eV) are still scarce, hindering their practical applications. Here, we present a new 2D lead-iodide hybrid biaxial ferroelectric, [(CH3)2CH(CH2)2NH3]2(CH3CH2NH3)2Pb3I10 (1), which shows large spontaneous polarization (Ps = 5.2 µC/cm2) and the narrow direct bandgap (Eg = 1.80 eV). To the best of our knowledge, this Eg value of 1 is the smallest figure ever observed for the existing molecular ferroelectrics. Particularly, the symmetry breaking of 4/mmmFmm2 species results in its biaxial attributes, that is, four equivalent Ps directions for 1. Accordingly, exceptional in-plane BPVEs are exploited along the crystallographic [001] and [010] axes directions inside the crystallographic bc-plane, of which the directions can be facilely switched through external electric poling. At zero bias, the intriguing self-driven photoactivities were created in a wide range of 365–670 nm, including large switching ratio (> 105), high-density photocurrent (~ 1.5 µA/cm2) and ultrafast transient responding time (~ 2.7 ns). It is the coupling between ferroelectricity and in-plane BPVEs that endows great potentials of 1 toward broadband self-driven photodetection. This innovative study on in-plane ferroelectric BPVEs is unprecedent, which sheds light on new properties for their future optoelectronic device applications.
Future flood risk exacerbated by the dynamic impacts of sea level rise
Authors: Bilskie Matthew , Angel Diana Del , Yoskowitz David , Hagen Scott 
Published: September 2020

Abstract
A growing concern of coastal communities is an increase in flood risk and non-monetary consequences as a result of climate-induced impacts such as sea level rise (SLR). While previous studies have outlined the importance of quantifying future flood risk, most have focused on broad aggregations of monetary loss using bathtub SLR-type models. Here we quantify, for the first time at the multi-state scale, actual impacts to coastal communities at the census block level using a dynamic, high-resolution, biogeophysical modeling framework that accounts for future sea-levels and coastal landscapes. We demonstrate that future SLR can increase the number of damaged residential buildings by 600%, the population of displaced people by 500% and the need for shelter assistance of up to 460% from present-day conditions. An exponential increase in flood damage associated with increasing sea level deems it essential for stakeholders to plan for plausible future conditions rather than the current reality.
Diagnostic value of plasma neurofilament light: A multicentre validation study
Authors: Ashton Nicholas , Janelidze Shorena , Khleifat Ahmad Al , Leuzy Antoine , Ende Emma van der , Karikari Thomas , Benedet Andrea , Pascoal Tharick , Lleó Alberto , Parnetti Lucilla , Galimberti Daniela , Bonanni Laura , Pilotto Andrea , Padovani Alessandro , Lycke Jan , Novakova Lenka , Axelsson Markus , Velayudhan Latha , Rabinovici Gil , Miller Bruce , Pariante Carmine , Nikkheslat Naghmeh , Resnick Susan , Thambisetty Madhav , Schöll Michael , Fernandez-Eulate Gorka , Gil-Bea Francisco , de Munain Adolfo López , Al-Chalabi Ammar , Rosa-Neto Pedro , Strydom Andre , Svenningsson Per , Stomrud Erik , Santillo Alexander , Aarsland Dag , Swieten John van , Palmqvist Sebastian , Zetterberg Henrik , Blennow Kaj , Hye Abdul , Hansson Oskar 
Published: September 2020

Abstract
Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in fifteen neurodegenerative diseases from two multicenter cohorts: King’s College London (n = 847) and the Swedish BioFINDER study (n = 1464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We further demonstrate that plasma NfL is clinically useful in identifying, i) atypical parkinsonian disorders in patients with parkinsonism, ii) dementia in individuals with Down Syndrome, iii) detect cases of frontotemporal dementia among psychiatric disorders such as moderate and severe depression, iv) identify frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related plasma NfL cut-offs for disorders with a younger age of onset. Finally, our findings suggest that plasma NfL performs best when a concentration cut-off is applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
99mTc-HMPAO SPECT imaging reveals brain hypoperfusion during status epilepticus
Authors: Bascuñana Pablo , Wolf Bettina J. , Jahreis Ina , Brackhan Mirjam , García-García Luis , Ross Tobias L. , Bengel Frank M. , Bankstahl Marion , Bankstahl Jens P. 
Published: September 2020

Abstract
Status epilepticus (SE) is a clinical emergency with high mortality. SE can trigger neuronal death or injury and alteration of neuronal networks resulting in long-term cognitive decline or epilepsy. Among the multiple factors contributing to this damage, imbalance between oxygen and glucose requirements and brain perfusion during SE has been proposed. Herein, we aimed to quantify by neuroimaging the spatiotemporal course of brain perfusion during and after lithium-pilocarpine-induced SE in rats. To this purpose, animals underwent 99mTc-HMPAO SPECT imaging at different time points during and after SE using a small animal SPECT/CT system. 99mTc-HMPAO regional uptake was normalized to the injected dose. In addition, voxel-based statistical parametric mapping was performed. SPECT imaging showed an increase of cortical perfusion before clinical seizure activity onset followed by regional hypo-perfusion starting with the first convulsive seizure and during SE. Twenty-four hours after SE, brain 99mTc-HMPAO uptake was widely decreased. Finally, chronic epileptic animals showed regionally decreased perfusion affecting hippocampus and cortical sub-regions. Despite elevated energy and oxygen requirements, brain hypo-perfusion is present during SE. Our results suggest that insufficient compensation of required blood flow might contribute to the neuronal damage and neuroinflammation, and ultimately to chronic epilepsy generated by SE.
A case report of Salmonella meningitis in three Chinese children and a literature review
Authors: Zhao Jingli , Hua Chunzhen , Zhou Mingming , Wang Hongjiao , Xie Yongping , Wang Gaoliang 
Published: September 2020

Abstract
Background: Salmonella is a common pathogen for gastroenteritis, but it rarely causes intracranial infection in China. To improve the understanding of pediatric Salmonella meningitis, we report three cases of Salmonella meningitis in Chinese children.Case presentation: The patients were aged from 1 day to 14 months. Fever was the first symptom in two patients, while loose stool with a little mucus occurred in one patient during the course of disease. Peripheral white blood cell count, neutrophils count, and C-reactive protein were 20.08 - 25.2 *109/L, 15.4 - 19.7 *109/L, and 1.6 - >160 mg/L, respectively. CSF analysis showed that white blood cell count, glucose, and protein were 70 - 1473 *106/L, 0.18 - 3.19 mmol/L, and 598.1 - 6639.0 mg/L, respectively. Three isolates of Salmonella were detected in cerebrospinal fluid cultures, including Salmonella newport, Salmonella paratyphi, and Salmonella typhimurium (one case per each). All strains were sensitive to ceftriaxone, ceftazidime, cefoperazone / sulbactam, meropenem, and imipenem, while one strain was resistant to ampicillin. The blood cultures were all negative. All patients were treated with carbapenems after failed therapies of cefotaxime or ceftriaxone, for a total duration of 3 - 5 weeks. One patient died, and subdural effusion occurred in one of the two survivors. Conclusions: Salmonella meningitis was rare, but the clinical conditions were serious. Carbapenems might be the first choice for treating Salmonella meningitis.
Food Environmental Interventions Protocol Using Social Marketing or Incentive-Based Strategies for Improving Dietary Behaviours and Health Outcomes - Systematic Review and Meta-Analysis
Authors: Sawada Kimi , Yamamoto Yoshiko , Lopes Katharina da Silva , Watanabe Norio 
Published: September 2020

Abstract
Background: In recent years, behavioural science theories such as social marketing or incentive-based food price strategies have been proposed to promote healthy and desirable eating habits potentially staving off a global increase in certain non-communicable disease (NCDs) such as obesity.This paper describes a systematic review protocol that validates the effectiveness of social marketing including financial incentive interventions in preventing unhealthy eating behaviour and diet-related NCDs.Methods: We will search online databases for interventions using randomized controlled trials (RCTs) and cluster RCTs. We will assess social marketing included financial incentive interventions in setting such as supermarkets, places of work, or school cafeterias and vending machines for all people. Two authors will read the papers independently, discuss the content, and come to a consensus on the judgment. If two authors cannot reach an agreement, they will consult with the other authors to reach a resolution. For the qualitative assessment, methodology relying on the Cochrane Collaboration Risk of Bias Tool 2 will be used to confirm the risk of bias for the included trials. Discussion: This is a protocol for a systematic review, and the main purpose of the review is to identify the effectiveness of social marketing and incentive-based approaches to increase desirable eating and consumption behaviours to prevent NCDs in communities, workplaces, and schools. Trial registration: This review protocol is registered with PROSPERO(CRD××) on〇, 〇, 2020.
Analysis of the Gap in PCR Monitoring Availability for Patients with Chronic Myeloid Leukemia in 60 Low- and Middle-Income Countries
Authors: Rowley Seth , Garcia-Gonzalez Patricia , Radich Jerald P , Usherenko Irina , Babigumira Joseph B 
Published: September 2020

Abstract
Purpose: To estimate the resource gap in the polymerase chain reaction (PCR) monitoring for patients with chronic myeloid leukemia (CML) in low- and middle-income countries (LMICs). Methods: We developed a model of demand and supply of PCR monitoring of CML patients in 60 LMICs. PCR testing was assumed to use Cepheid’s GeneXpert® IV system. We included costs of GeneXpert® instruments, uninterrupted power supplies, warranties, calibration kits, test cartridges, and shipping. We calculated the country-specific monetary gap in PCR monitoring, stratified by country priority defined as the availability of tyrosine kinase inhibitors (TKIs) through The Max Foundation initiatives. Results: The five-year gap in PCR monitoring was $29.1 million across all countries, 22% ($6.4 million) in countries with all five TKIs available, 20% ($5.7 million) in countries with four TKIs available, 50% ($14.5 million) in countries with three TKIs available, 8% ($2.2 million) in countries with two TKIs available, and 1% ($0.3 million) in countries with one TKI available. The gap was highest in South Asia (52%; $15.1 million) and lowest in Latin America (6%; $1.9 million). Excluding labor costs, the bulk of the resource needs (86%; $25.2 million) were for procurement of BCR-ABL cartridges. Conclusion: Removing the five-year gap in PCR monitoring capacity for CML in LMICs will require the mobilization of significant resources and will likely lead to better treatment outcomes and reduced treatment costs through optimization of treatment, discontinuation of therapy in appropriate patients, and facilitation of clinical research. Development of streamlined monitoring guidelines for resource-limited countries should be considered.
miR-17-5p Promotes the Invasion and Migration of Colorectal Cancer by Regulating HSPB2
Authors: Yu Wei fang , Wang Jia , Li Chao , Xuan Mingda , Han Shuangshuang , Zhang Yingfu , Liu Pengfei , Zhao Zengren 
Published: September 2020

Abstract
Background: MicroRNA (miRNA) can affect tumor progression by regulating cell proliferation, apoptosis and metastasis. After miRNA microarray chip analysis of colorectal cancer (CRC) tissues and adjacent normal tissues, a significant upregulation of miR-17-5p expression was found in CRC tissues. However, the underlying mechanism of miR-17-5p in CRC is still unclear.Methods: The levels of miR-17-5p in 47 paired CRC and adjacent normal tissue samples were determined by quantitative real-time PCR (qRT-PCR). CCK-8, colony formation, flow cytometry and transwell assays were used to explore the biological effects of miR-17-5p on CRC cells. In addition, the transcriptome sequencing and miRNA target prediction software were employed to identify targets of miR-17-5p. Luciferase reporter detection was used to demonstrate the direct binding of target genes by miR-17-5p. The rescue experiment was conducted to investigate the biological function of target genes and regulatory mechanism of miR-17-5p on target genes.Results: The expression of miR-17-5p was significantly higher in CRC tissues than in adjacent normal tissues. In CRC group, the expression of miR-17-5p in cancer tissues with lymph node metastasis was higher compared with those without lymph node metastasis. Overexpression of miR-17-5p inhibited CRC cell apoptosis, as well as promoting proliferation, migration and invasion. We hypothesized that HSPB2 might be a target gene of miR-17-5p and validated for the first time that miR-17-5p binds directly to the 3’-UTR of HSPB2. In the rescue experiment, the tumor suppressive effect of HSPB2 was detected and miR-17-5p could promote cell proliferation, migration and invasion by targeting HSPB2.Conclusion: MiR-17-5p promotes invasion and migration by inhibiting HSPB2 in CRC, thereby implicating its potential as a novel diagnostic biomarker and therapeutic target for CRC.
UXT, a novel DNMT3b-binding protein, promotes breast cancer progression via negatively modulating lncRNA MEG3/p53 axis
Authors: Huang Zhong-Feng , Tang Yu-Ling , Shen Zhao-Long , Yang Kai-Yan , Gao Kai 
Published: September 2020

Abstract
Background
UXT is highly expressed in tumor tissues, which function as a vital role in tumor progression. However, the exact role and potential mechanism of UXT in the tumorigenesis of breast cancer remains largely unknown.
Methods
Expression patterns of UXT and MEG3 were examined using qRT-PCR and western blot, respectively. The capacity of cell proliferation, apoptosis, migration and invasion was assessed using CCK-8, flow cytometry and transwell assays. The methylation of MEG3 promoter was determined using methylation specific PCR. Co-immunoprecipitation was performed to measure the UXT/DNMT3b interaction. RNA-immunoprecipitation was subjected to evaluate the regulation of MEG3 on p53 activity. The xenograft tumor experiment was further conducted to certify the molecular mechanism.
Results
UXT was up-regulated while MEG3 was down-regulated in breast cancer tissues and cell lines. UXT knockdown or MEG3 overexpression significantly inhibited the proliferation, promoted the apoptosis, and weakened the migration and invasion of MCF7 and ZR75 cells. The hypermethylation of MEG3 promoter was found in breast cancer cells, which was modulated by highly expressed DNMT3b. UXT inhibited the level of MEG3 via recruiting DNMT3b to its promoter. Mechanistically, MEG3 positively regulated the transcriptional activity of p53 via binding with it, thus regulating cell apoptosis, migration and invasion. The xenograft tumor experiment indicated that UXT negatively regulated the MEG3/p53 axis in a DNMT3b-dependent manner to promote the tumor growth.
Conclusions
UXT, a novel DNMT3b-binding protein, aggravates the progression of breast cancer through MEG3/p53 axis, which may provide a new insight involving in the treatment of breast cancer.
CAZyome and Sugar Transportome Unveil Singular Aspects of the Lignocellulolytic Enzyme System of Penicillium echinulatum 2HH
Authors: Lenz Alexandre Rafael , Balbinot Eduardo , Oliveira Nikael Souza de , Abreu Fernanda Pessi de , Silva Scheila de Avila e , Camassola Marli , Dillon Aldo José Pinheiro , Perez-Rueda Ernesto 
Published: September 2020

Abstract
Background: The production of bioethanol using lignocellulosic feedstocks has proved to be a cutting-edge technology. However, this technology faces limitations such as cost and yield of enzymatic systems, required to degrade efficiently the polysaccharides of plant cell walls. Penicillium echinulatum 2HH is a widely studied ascomycete, known by its efficient cellulolytic cocktails. One strategy to improve the saccharification yields for commercial exploitation is the design of hypersecreting strains. However, molecular knowledge about the lignocellulolytic system of this specific fungus is scarce. Understanding both lignocellulolytic and sugar uptake systems is essential to obtain industrial strains with adequate efficiency for bioethanol production. Results: We report a comprehensive in silico characterization of CAZymes and sugar transporters of P. echinulatum 2HH. The CAZyome reveals an outstanding repertoire of enzymes involved in plant biomass degradation. Among them, we highlight the cellulolytic enzyme system whose genes are predominantly orthologous to P. oxalicum 114-2, demonstrating the high similarity of these phylogenetically related enzyme producers. We also report a LPMO-type enzyme of the AA16 family described for the first time in these fungi. In addition to the well-known high activity of ß-glucosidases, we found that coding genes for the AA16, GH5-4 and GH45 families comprehend the main differences in the cellulolytic complexes of P. echinulatum 2HH and P. oxalicum 114-2, when both are compared to commercial producers. Our phylogenetic analysis of the sugar transportome suggests that P. echinulatum 2HH diversity and specificity of STs include eight major families with specificity to different groups of sugars. Finally, our phylogenetic analyses enabled the identification of several iBGLs and STs potentially involved in the accumulation of intracellular cellodextrins.Conclusions: Overall, both CAZyome and sugar transportome of P. echinulatum revealed new insights into the mechanisms underlying a flexible and highly functional metabolism to degrade plant biomass. Peculiarities found in our study help to highlight the cellulolytic complex of P. echinulatum 2HH, contributing to the commercial ascendance of Penicillium spp. as cellulolytic enzyme producers. Furthermore, the first phylogenetic classification of STs and iBGLs shed new light into the role of these genes regarding the preferred carbon source during fungal growth. Along these lines, these iBGLs and STs comprise valuable gene targets to understand the regulatory mechanisms underlying cellulolytic enzymes and to design hypersecreting strains with adequate efficiency for bioethanol production in large-scale.
Systematic Analysis of Direct Antiglobulin Test Results in Post-artesunate Delayed Hemolysis
Authors: Bartoli Tommaso Ascoli , Lepore Luciana , D'Abramo Alessandra , Adamo Giovanna , Corpolongo Angela , Scorzolini Laura , Giancola Maria Letizia , Bevilacqua Nazario , Palazzolo Claudia , Mariano Andrea , Ippolito Giuseppe , Buffet Pierre , Nicastri Emanuele 
Published: September 2020

Abstract
Background: “Post-Artesunate Delayed Hemolysis” (PADH) is common after severe malaria episodes. PADH is related to the “pitting” phenomenon and the synchronous delayed clearance of once-infected erythrocytes, initially spared during treatment. However, direct antiglobulin test (DAT) positivity has been reported in several PADH cases, suggesting a contribution of immune-mediated erythrocyte clearance. The aim of the present study was to compare clinical features of cases presenting a positive or negative DAT.Method: Articles reporting clinical data of patients diagnosed with PADH, for whom DAT had been performed, were collected from PubMed database. Data retrieved from single patients were extracted and univariate analysis was performed in order to identify features potentially related to DAT results and steroids use.Results: Twenty-two studies reporting 39 PADH cases were included: median baseline parasitemia was 20.8% (IQR: 11.2-30) and DAT was positive in 17 cases (45.5%). Compared to DAT-negative individuals, DAT-positive patients were older (49.5 vs 31; p=0.01), had a higher baseline parasitemia (27% vs 17%; p=0.03) and were more commonly treated with systemic steroids (11 vs 3 patients, p=0.002). Depth and kinetics of delayed anemia were not associated with DAT positivity.Conclusions: In this case series, almost half of the patients affected by PADH had a positive DAT. An obvious difference between the clinical courses of patients presenting with a positive or negative DAT was lacking. This observation strongly suggests that DAT result is not indicative of a pathogenic role of anti-erythrocytes antibodies in patients affected by PADH, but is rather a marker of immune activation.