bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma
Authors: Feng Zitong , Qu Jingge , Liu Xiao , Liang Jinghui , Li Yongmeng , Jiang Jin , Zhang Huiying , Tian Hui 
Published: August 2021

AbstractEsophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. The role of molecular alterations and the immune microenvironment in ESCC development has not been fully elucidated. The present study aimed to elucidate key candidate genes and immune cell infiltration characteristics in ESCC by integrated bioinformatics analysis. Nine gene expression datasets from the Gene Expression Omnibus (GEO) database were analysed to identify robust differentially expressed genes (DEGs) using the robust rank aggregation (RRA) algorithm. Functional enrichment analyses showed that the 152 robust DEGs are involved in multiple processes in the tumor microenvironment (TME). Immune cell infiltration analysis based on the 9 normalized GEO microarray datasets was conducted with the CIBERSORT algorithm. The changes in macrophages between ESCC and normal tissues were particularly obvious. In ESCC tissues, M0 and M1 macrophages were increased dramatically, while M2 macrophages were decreased. A robust DEG-based protein–protein interaction (PPI) network was used for hub gene selection with the CytoHubba plugin in Cytoscape. Nine hub genes (CDA, CXCL1, IGFBP3, MMP3, MMP11, PLAU, SERPINE1, SPP1 and VCAN) had high diagnostic efficiency for ESCC according to receiver operating characteristic (ROC) curve analysis. The expression of all hub genes except MMP3 and PLAU was significantly related to macrophage infiltration. Univariate and multivariate regression analyses showed that a 7-gene signature constructed from the robust DEGs was useful for predicting ESCC prognosis. Our results might facilitate the exploration of potential targeted TME therapies and prognostic evaluation in ESCC.
Isoforms of soluble vascular endothelial growth factor in stress-related mental disorders: a cross-sectional study
Authors: Wallensten Johanna , Mobarrez Fariborz , Åsberg Marie , Borg Kristian , Beser Aniella , Wilczek Alexander , Nager Anna 
Published: August 2021

AbstractVascular endothelial growth factor (VEGF) has been implicated in the pathophysiology of stress-related mental disorders. However, VEGF levels have seldom been compared across mental disorders and never by isoforms. Pathophysiological processes involving leakage of astrocyte-derived extracellular vesicles (EVs) across the blood–brain barrier could be associated with VEGF levels in patients with stress-related mental disorders. This cross-sectional study compared plasma levels of VEGF121, VEGF165, and VEGF121 + VEGF165 (VEGFtotal) in patients with stress-induced exhaustion disorder (SED) (n = 31), patients with major depressive disorder (MDD) (n = 31), and healthy controls (n = 61). It also analyzed the correlation between VEGF and astrocyte-derived EVs in plasma. An enzyme-linked immunosorbent assay (ELISA) was used to measure VEGF121 and VEGF165 in citrate plasma, and flow cytometry was used to measure astrocyte-derived EVs in plasma. The mean concentration of soluble VEGF121 (sVEGF121) was significantly higher in patients with SED than healthy controls (P = 0.043). Mean sVEGF165 was significantly lower in patients with MDD than patients with SED (P = 0.004) or healthy controls (P = 0.037). Mean sVEGFtotal was significantly higher in patients with SED than in patients with MDD (P = 0.021) and also higher in patients with SED than healthy controls (P = 0.040). Levels of sVEGF121 were positively correlated with levels of astrocyte-derived EVs only in patients with SED (P = 0.0128). The same was true of levels of sVEGFtotal and astrocyte-derived EVs (P = 0.0046). Differing levels of VEGF isoforms may reflect different pathophysiological mechanisms in SED and MDD. Further research is needed to better understand the potential roles of VEGF isoforms and astrocyte-derived EVs in mental disorders.
Characterization of an in vitro 3D intestinal organoid model by using massive RNAseq-based transcriptome profiling
Authors: Lu Jing , Krepelova Anna , Rasa Seyed Mohammad Mahdi , Annunziata Francesco , Husak Olena , Adam Lisa , Nunna Suneetha , Neri Francesco 
Published: August 2021

AbstractOrganoids culture provides unique opportunities to study human diseases and to complement animal models. Several organs and tissues can be in vitro cultured in 3D structures resembling in vivo tissue organization. Organoids culture contains most of the cell types of the original tissue and are maintained by growth factors mimicking the in vivo state. However, the system is yet not fully understood, and specific in vivo features especially those driven by cell-extrinsic factors may be lost in culture. Here we show a comprehensive transcriptome-wide characterization of mouse gut organoids derived from different intestinal compartments and from mice of different gender and age. RNA-seq analysis showed that the in vitro culture strongly influences the global transcriptome of the intestinal epithelial cells (~ 60% of the total variance). Several compartment-, age- and gender-related transcriptome features are lost after culturing indicating that they are driven by niche or systemic factors. However, certain intrinsic transcriptional programs, for example, some compartment-related features and a minority of gender- and aging- related features are maintained in vitro which suggested possibilities for these features to be studied in this system. Moreover, our study provides knowledge about the cell-extrinsic or cell-intrinsic origin of intestinal epithelial transcriptional programs. We anticipated that our characterization of this in vitro system is an important reference for scientists and clinicians using intestinal organoids as a research model.
Plasticity of intrinsic excitability across the estrous cycle in hypothalamic CRH neurons
Authors: Power Emmet M. , Iremonger Karl J. 
Published: August 2021

AbstractStress responses are highly plastic and vary across physiological states. The female estrous cycle is associated with a number of physiological changes including changes in stress responses, however, the mechanisms driving these changes are poorly understood. Corticotropin-releasing hormone (CRH) neurons are the primary neural population controlling the hypothalamic–pituitary–adrenal (HPA) axis and stress-evoked corticosterone secretion. Here we show that CRH neuron intrinsic excitability is regulated over the estrous cycle with a peak in proestrus and a nadir in estrus. Fast inactivating voltage-gated potassium channel (IA) currents showed the opposite relationship, with current density being lowest in proestrus compared to other cycle stages. Blocking IA currents equalized excitability across cycle stages revealing a role for IA in mediating plasticity in stress circuit function over the female estrous cycle.
GCH1-regulated miRNAs are potential targets for microglial activation in neuropathic pain
Authors: Jia Shu , Chen Guowu , Liang Yanhu , Liang Xiao , Meng Chunyang 
Published: August 2021

Abstract
Neuropathic pain (NP) is a chronic pain directly caused by injury or disease of the somatosensory nervous system. Previous studies suggest that GTP cyclohydrolase I (GCH1) may play a pivotal role in microglial activation, which has been shown to be essential for NP. However, its underlying mechanisms in microglial activation remain unclear. A wide range of microRNAs (miRNAs) have been found to be involved in microglial activation-induced NP. To identify the miRNAs regulated by GCH1 and predict their functions in the progression of microglial activation, we analyzed the miRNA expression profiles of GCH1-knockdown (KD) BV2 microglial cells. Small RNA-sequencing analysis revealed 13 differentially expressed (DE) miRNAs in GCH1-KD cells. The target genes of DE miRNAs mainly participate in PI3K-Akt signaling pathway, peroxisome and ferroptosis. The miRNA–mRNA regulatory network analysis showed that GCH1, MAP4K5 and YWHAB acted as hub genes. qRT-PCR results further verified the expression levels of mmu-miR-1a-3p, mmu-miR-133a-3p, mmu-miR-7a-5p and mmu-miR-10a-5p in GCH1-KD cells, which were consistent with the sequencing data. In addition, our data indicated that overexpression of mmu-miR-133a-3p alleviated the pro-inflammatory cytokines IL-1β and IL-6 production induced by lipopolysaccharide (LPS), indicating that mmu-miR-133a-3p has a negative effect on microglial activation. Taken together, our findings suggest that many miRNAs regulated by GCH1 may be involved in microglial activation, which may provide new potential targets for GCH1 in the pathogenesis of NP.
Metabolic profiling of maternal serum of women at high-risk of spontaneous preterm birth using NMR and MGWAS approach
Authors: Gupta Juhi K. , Care Angharad , Goodfellow Laura , Alfirevic Zarko , Lian Lu-Yun , Müller-Myhsok Bertram , Alfirevic Ana , Phelan Marie M. 
Published: August 2021

Abstract
Preterm birth (PTB) is a leading global cause of infant mortality. Risk factors include genetics, lifestyle choices and infection. Understanding the mechanism of PTB could aid the development of novel approaches to prevent PTB. This study aimed to investigate the metabolic biomarkers of PTB in early pregnancy and the association of significant metabolites with participant genotypes. Maternal sera collected at 16 and 20 weeks of gestation, from women who previously experienced PTB (high-risk) and women who did not (low-risk controls), were analysed using 1H nuclear magnetic resonance (NMR) metabolomics and genome-wide screening microarray. ANOVA and probabilistic neural network (PNN) modelling were performed on the spectral bins. Metabolomics genome-wide association (MGWAS) of the spectral bins and genotype data from the same participants was applied to determine potential metabolite-gene pathways. Phenylalanine, acetate and lactate metabolite differences between PTB cases and controls were obtained by ANOVA and PNN showed strong prediction at week 20 (AUC = 0.89). MGWAS identified several metabolite bins with strong genetic associations. Cis-eQTL analysis highlighted TRAF1 (involved in the inflammatory pathway) local to a non-coding SNP associated with lactate at week 20 of gestation. MGWAS of a well-defined cohort of participants highlighted a lactate-TRAF1 relationship that could potentially contribute to PTB.
Detecting Hearing Loss in Infants With a Syndrome or Craniofacial Abnormalities Following the Newborn Hearing Screen
Authors: Horn Philippa , Driscoll Carlie , Fitzgibbons Jane , Beswick Rachael 
Published: August 2021

PurposeThe current Joint Committee on Infant Hearing guidelines recommend that infants with syndromes or craniofacial abnormalities (CFAs) who pass the universal newborn hearing screening (UNHS) undergo audiological assessment by 9 months of age. However, emerging research suggests that children with these risk factors are at increased risk of early hearing loss despite passing UNHS. To establish whether earlier diagnostic audiological assessment is warranted for all infants with a syndrome or CFA, regardless of screening outcome, this study compared audiological outcomes of those who passed UNHS and those who referred.MethodA retrospective analysis was performed on infants with a syndrome or CFA born between July 1, 2012, and June 30, 2017 who participated in Queensland, Australia's state-wide UNHS program.ResultsPermanent childhood hearing loss (PCHL) yield was higher among infants who referred on newborn hearing screening (51.20%) than in those who passed. Nonetheless, 27.47% of infants who passed were subsequently diagnosed with hearing loss (4.45% PCHL, 23.02% transient conductive), but PCHL was generally milder in this cohort. After microtia/atresia, the most common PCHL etiologies were Trisomy 21, other syndromes, and cleft palate. Of the other syndromes, Pierre Robin sequence featured prominently among infants who passed the hearing screen and were subsequently diagnosed with PCHL, whereas there was a broader mix of other syndromes that caused PCHL in infants who referred on screening.ConclusionChildren identified with a syndrome or CFA benefit from early diagnostic audiological assessment, regardless of their newborn hearing screening outcome.
Effects of Task Demands on Neural Correlates of Acoustic and Semantic Processing in Challenging Listening Conditions
Authors: Devaraju Dhatri S. , Kemp Amy , Eddins David A. , Shrivastav Rahul , Chandrasekaran Bharath , Hampton Wray Amanda 
Published: August 2021

Purpose
Listeners shift their listening strategies between lower level acoustic information and higher level semantic information to prioritize maximum speech intelligibility in challenging listening conditions. Although increasing task demands via acoustic degradation modulates lexical-semantic processing, the neural mechanisms underlying different listening strategies are unclear. The current study examined the extent to which encoding of lower level acoustic cues is modulated by task demand and associations with lexical-semantic processes.

Method
Electroencephalography was acquired while participants listened to sentences in the presence of four-talker babble that contained either higher or lower probability final words. Task difficulty was modulated by time available to process responses. Cortical tracking of speech—neural correlates of acoustic temporal envelope processing—were estimated using temporal response functions.

Results
Task difficulty did not affect cortical tracking of temporal envelope of speech under challenging listening conditions. Neural indices of lexical-semantic processing (N400 amplitudes) were larger with increased task difficulty. No correlations were observed between the cortical tracking of temporal envelope of speech and lexical-semantic processes, even after controlling for the effect of individualized signal-to-noise ratios.

Conclusions
Cortical tracking of the temporal envelope of speech and semantic processing are differentially influenced by task difficulty. While increased task demands modulated higher level semantic processing, cortical tracking of the temporal envelope of speech may be influenced by task difficulty primarily when the demand is manipulated in terms of acoustic properties of the stimulus, consistent with an emerging perspective in speech perception.
Speech-in-Speech Recognition and Spatially Selective Attention in Children and Adults
Authors: Kane Stacey G. , Dean Kelly M. , Buss Emily 
Published: August 2021

Purpose
Knowing target location can improve adults' speech-in-speech recognition in complex auditory environments, but it is unknown whether young children listen selectively in space. This study evaluated masked word recognition with and without a pretrial cue to location to characterize the influence of listener age and masker type on the benefit of spatial cues.

Method
Participants were children (5–13 years of age) and adults with normal hearing. Testing occurred in a 180° arc of 11 loudspeakers. Targets were spondees produced by a female talker and presented from a randomly selected loudspeaker; that location was either known, based on a pretrial cue, or unknown. Maskers were two sequences comprising spondees or speech-shaped noise bursts, each presented from a random loudspeaker. Speech maskers were produced by one male talker or by three talkers, two male and one female.

Results
Children and adults benefited from the pretrial cue to target location with the three-voice masker, and the magnitude of benefit increased with increasing child age. There was no benefit of location cues in the one-voice or noise-burst maskers. Incorrect responses in the three-voice masker tended to correspond to masker words produced by the female talker, and in the location-known condition, those masker intrusions were more likely near the cued loudspeaker for both age groups.

Conclusions
Increasing benefit of the location cue with increasing child age in the three-voice masker suggests maturation of spatially selective attention, but error patterns do not support this idea. Differences in performance in the location-unknown condition could play a role in the differential benefit of the location cue.
Train related injuries: A descriptive analysis highlighting orthopaedic injuries and management
Authors: Kontoghiorghe Christina Niovi , Graham Simon Matthew , Rodriguez Joel , Matzopoulos Richard , Maqungo Sithombo 
Published: August 2021

Introduction: Orthopaedic injuries constitute a major aspect of morbidity and mortality following train accidents. The pattern of orthopaedic/musculoskeletal injuries sustained following these accidents has not been fully characterised. The main aim of this study is to describe the range of orthopaedic injuries reported in a major trauma centre and evaluate their management, as well as reporting mortality and amputation rates. Further aims are to identify the social and demographic background of the patients to suggest treatment and prevention strategies. Methods: This study is a retrospective observation of all clinical files of patients presented to Level 1 Trauma Centre in Cape Town, South Africa, as “train casualty” from January 2013 to July 2019, which were reviewed and evaluated. A total of 174 patients were included, of which 92 were orthopaedic referrals. The average age was 29 years, and 87% were male. Results: Tibial fractures were most common (N = 19), 38% of patients sustained open fractures, and 68% of patients (in total) underwent surgery. Wound debridement was the most common operation, followed by open reduction internal fixation (ORIF). Twelve patients (13%) underwent amputation to 14 body parts. Eight patients (4.6%) (in total) died in the trauma unit. Discussion: This study provides insight into train accident victims and their orthopaedic injuries and management patterns. The victims are largely young males. The majority of orthopaedic injuries require surgical intervention, and those who make it to the hospital have a good chance of survival and limb salvage. It appears that in addition to early hospital access and specialised updated treatments, morbidity and mortality in train accidents could be reduced by improving safety measures and social awareness to reduce railway violence and accidents.
Dissociation of water on atomic oxygen-covered Rh nanoclusters supported on graphene/Ru(0001)
Authors: Huang Yi-Cheng , Yen Hung-Yu , Lan Liang-Wei , Dutta D. , Rahmah A. , Lai Yu-Ling , Hsu Yao-Jane , Kuo Chien-Cheng , Wang Jeng-Han , Luo Meng-Fan 
Published: August 2021

We studied the dissociation of water (H2O*, with * denoting adspecies) on atomic oxygen (O*)-covered Rh nanoclusters (RhO*) supported on a graphene film grown on a Ru(0001) surface [G/Ru(0001)] under ultrahigh-vacuum conditions and with varied surface-probe techniques and calculations based on density-functional theory. The graphene had a single rotational domain; its lattice expanded by about 5.7% to match the Ru substrate structurally better. The Rh clusters were grown by depositing Rh vapors onto G/Ru(0001); they had an fcc phase and grew in (111) orientation. Water adsorbed on the Rh clusters was dissociated exclusively in the presence of O*, like that on a Rh(111) single-crystal surface. Contrary to the case on Rh(111)O*, excess O* (even at a saturation level) on small RhO* clusters (diameter of 30–34 Å) continued to promote, instead of inhibiting, the dissociation of water; the produced hydroxyl (OH*) increased generally with the concentration of O* on the clusters. The difference results from more reactive O* on the RhO* clusters. O* on RhO* clusters activated the dissociation via both the formation of hydrogen bonds with H2O* and abstraction of H directly from H2O*, whereas O* on Rh(111)O* assisted the dissociation largely via the formation of hydrogen bonds, which was readily obstructed with an increased O* coverage. As the disproportionation (2 OH* → H2O* + O*) is endothermic on the RhO* clusters but exothermic on Rh(111)O*, OH* produced on RhO* clusters showed a thermal stability superior to that on the Rh(111)O* surface—thermally stable up to 400 K.
Silicon microchannel frames for high-energy physics experiments
Authors: Poonsawat W. , Supadech J. , Klunngien N. , Jeamsaksiri W. , Ritjoho N. , Laojamnongwong N. , Mapelli A. , Francescon A. , Alvarez Feito D. , Kobdaj C. 
Published: August 2021

Abstract
The design of detectors used for experiments in high-energy
physics requires a light, stiff, and efficient cooling system with a
low material budget. The use of silicon microchannel cooling plates
has gained considerable interest in the last decade. In this study,
we propose the development of silicon microchannel cooling frames
studied within the framework of the major upgrade of the Inner
Tracking System (ITS) of the ALICE experiment at CERN. The
preliminary results obtained with these frames demonstrate that they
can withstand the internal pressure arising from the flow of the
coolant with a limited mass penalty.
The Effect of Using an Active Earmuff on High Frequency Hearing in United States Marine Corps Weapons Instructors
Authors: Federman Jeremy , Karch Stephanie , Duhon Christon , Hughes Linda , Kulinski Devon 
Published: August 2021

Abstract

Objectives
To investigate the change in hearing and perceived comfort over 1 year related to using an active hearing protection device (HPD) among United States Marine Corps (USMC) personnel routinely exposed to hazardous noise.

Methods
USMC Weapons Instructors (n = 127) were issued an active earmuff that met military standards and was compatible with other protective equipment. These participants completed pre- and post-hearing tests and comfort surveys. A control cohort (n = 94) was also included to compare individual changes in high-frequency pure tone average (HF-PTA) over 1 year.

Results
The control group’s HF-PTA was 3 dB worse than the intervention group after only 1 year. Survey responses revealed perceived improvements in the ability to hear and understand, situational awareness, and safety.

Conclusions
Active HPDs can reduce hearing loss and improve hearing-related occupational tasks.
Risk and DoE-Based Analytical Failure Mode Effect Analysis (AFMEA) to Simultaneous Estimation of Montelukast Sodium and Bilastine by HPTLC Method Using Enhanced AQbD Approach
Authors: Prajapati Pintu , Tamboli Jayesh , Mishra Ashish 
Published: August 2021

Abstract
The fixed-dose combination (FDC) of montelukast sodium (MLS) and bilastine (BIL) is used for monotherapy in the patient with seasonal allergic rhinoconjuctivitis and asthma. According to the upcoming ICH (International Council for Harmonization) Q14 guideline, the development of the analytical method by the implementation of the Analytical Quality by Design (AQbD) approach based on principles of Quality Risk Management (QRM) and design of experiments (DoE) would be a regulatory requirement for the registration of new drug substance and product in ICH countries. Hence, a robust high-performance thin layer chromatography method has been developed, which was not previously reported for simultaneous estimation of MLS and BIL using risk and DoE-based enhanced AQbD approach. The analytical failure mode effect analysis (AFMEA) was started with the identification of potential analytical failure modes followed by their effect analysis by RPN ranking and filtering method. The DoE-based AFMEA was applied for optimization of high-risk analytical failure modes by central composite design using Design-Expert software. The method operable design ranges and control strategy was set for quality risk management throughout the lifecycle of the developed method. The developed method was validated as per ICH Q2 (R1) guideline. The method was applied for the assay of FDC, and results were found in compliance with the labeled claim.