bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-omic analysis reveals the esophageal dysbiosis as the predominant trait of eosinophilic esophagitis
Authors: Massimino Luca , Barchi Alberto , Mandarino Francesco Vito , Spanò Salvatore , Lamparelli Luigi Antonio , Vespa Edoardo , Passaretti Sandro , Peyrin-Biroulet Laurent , Savarino Edoardo Vincenzo , Jairath Vipul , Ungaro Federica , Danese Silvio 
Published: January 2023

Abstract
Background
Eosinophilic esophagitis (EoE) is a chronic immune-mediated rare disease, characterized by esophageal dysfunctions. It is likely to be primarily activated by food antigens and is classified as a chronic disease for most patients. Therefore, a deeper understanding of the pathogenetic mechanisms underlying EoE is needed to implement and improve therapeutic lines of intervention and ameliorate overall patient wellness.

Methods
RNA-seq data of 18 different studies on EoE, downloaded from NCBI GEO with faster-qdump (https://github.com/ncbi/sra-tools), were batch-corrected and analyzed for transcriptomics and metatranscriptomics profiling as well as biological process functional enrichment. The EoE TaMMA web app was designed with plotly and dash. Tabula Sapiens raw data were downloaded from the UCSC Cell Browser. Esophageal single-cell raw data analysis was performed within the Automated Single-cell Analysis Pipeline. Single-cell data-driven bulk RNA-seq data deconvolution was performed with MuSiC and CIBERSORTx. Multi-omics integration was performed with MOFA.

Results
The EoE TaMMA framework pointed out disease-specific molecular signatures, confirming its reliability in reanalyzing transcriptomic data, and providing new EoE-specific molecular markers including CXCL14, distinguishing EoE from gastroesophageal reflux disorder. EoE TaMMA also revealed microbiota dysbiosis as a predominant characteristic of EoE pathogenesis. Finally, the multi-omics analysis highlighted the presence of defined classes of microbial entities in subsets of patients that may participate in inducing the antigen-mediated response typical of EoE pathogenesis.

Conclusions
Our study showed that the complex EoE molecular network may be unraveled through advanced bioinformatics, integrating different components of the disease process into an omics-based network approach. This may implement EoE management and treatment in the coming years.
Lipolysis and gestational diabetes mellitus onset: a case-cohort genome-wide association study in Chinese
Authors: Zhang Miao , Li Qing , Wang Kai-Lin , Dong Yao , Mu Yu-Tong , Cao Yan-Min , Liu Jin , Li Zi-Heng , Cui Hui-Lu , Liu Hai-Yan , Hu An-Qun , Zheng Ying-Jie 
Published: January 2023

AbstractBackgroundGenetic knowledge of gestational diabetes mellitus (GDM) in Chinese women is quite limited. This study aimed to identify the risk factors and mechanism of GDM at the genetic level in a Chinese population.MethodsWe conducted a genome-wide association study (GWAS) based on single nucleotide polymorphism (SNP) array genotyping (ASA-CHIA Bead chip, Illumina) and a case-cohort study design. Variants including SNPs, copy number variants (CNVs), and insertions-deletions (InDels) were called from genotyping data. A total of 2232 pregnant women were enrolled in their first/second trimester between February 2018 and December 2020 from Anqing Municipal Hospital in Anhui Province, China. The GWAS included 193 GDM patients and 819 subjects without a diabetes diagnosis, and risk ratios (RRs) and their 95% confidence intervals (CIs) were estimated by a regression-based method conditional on the population structure. The calling and quality control of genotyping data were performed following published guidelines. CNVs were merged into CNV regions (CNVR) to simplify analyses. To interpret the GWAS results, gene mapping and overexpression analyses (ORAs) were further performed to prioritize the candidate genes and related biological mechanisms.ResultsWe identified 14 CNVRs (false discovery rate corrected P values < 0.05) and two suggestively significant SNPs (P value < 0.00001) associated with GDM, and a total of 19 candidate genes were mapped. Ten genes were significantly enriched in gene sets related to lipase (triglyceride lipase and lipoprotein lipase) activity (LIPF, LIPK, LIPN, and LIPJ genes), oxidoreductase activity (TPH1 and TPH2 genes), and cellular components beta-catenin destruction complex (APC and GSK3B genes), Wnt signalosome (APC and GSK3B genes), and lateral element in the Gene Ontology resource (BRCA1 and SYCP2 genes) by two ORA methods (adjusted P values < 0.05).ConclusionsGenes related to lipolysis, redox reaction, and proliferation of islet β-cells are associated with GDM in Chinese women. Energy metabolism, particularly lipolysis, may play an important role in GDM aetiology and pathology, which needs further molecular studies to verify.
Home-based brain–computer interface attention training program for attention deficit hyperactivity disorder: a feasibility trial
Authors: Lim Choon Guan , Soh Chui Pin , Lim Shernice Shi Yun , Fung Daniel Shuen Sheng , Guan Cuntai , Lee Tih-Shih 
Published: January 2023

Abstract
Background
Attention deficit hyperactivity disorder (ADHD) is a prevalent child neurodevelopmental disorder that is treated in clinics and in schools. Previous trials suggested that our brain–computer interface (BCI)-based attention training program could improve ADHD symptoms. We have since developed a tablet version of the training program which can be paired with wireless EEG headsets. In this trial, we investigated the feasibility of delivering this tablet-based BCI intervention at home.

Methods
Twenty children diagnosed with ADHD, who did not receive any medication for the preceding month, were randomised to receive the 8-week tablet-based BCI intervention either in the clinic or at home. Those in the home intervention group received instructions before commencing the program and got reminders if they were lagging on the training sessions. The ADHD Rating Scale was completed by a blinded clinician at baseline and at week 8. Adverse events were monitored during any contact with the child throughout the trial and at week 8.

Results
Children in both groups could complete the tablet-based intervention easily on their own with minimal support from the clinic therapist or their parents (at home). The intervention was safe with few reported adverse effects. Clinician-rated inattentive symptoms on the ADHD-Rating Scale reduced by 3.2 (SD 6.20) and 3.9 (SD 5.08) for the home-based and clinic-based groups respectively, suggesting that home-based intervention was comparable to clinic-based intervention.

Conclusions
This trial demonstrated that the tablet version of our BCI-based attention training program can be safely delivered to children in the comfort of their own home.
Trial registration This trial is registered at clinicaltrials.gov as NCT01344044
Transient inhibition of microsomal prostaglandin E synthase-1 after status epilepticus blunts brain inflammation and is neuroprotective
Authors: Yasmen Nelufar , Sluter Madison N. , Li Lexiao , Yu Ying , Jiang Jianxiong 
Published: January 2023

AbstractStatus epilepticus (SE) in humans is characterized by prolonged convulsive seizures that are generalized and often difficult to control. The current antiseizure drugs (ASDs) aim to stop seizures quickly enough to prevent the SE-induced brain inflammation, injury, and long-term sequelae. However, sole reliance on acute therapies is imprudent because prompt treatment may not always be possible under certain circumstances. The pathophysiological mechanisms underlying the devastating consequences of SE are presumably associated with neuroinflammatory reactions, where prostaglandin E2 (PGE2) plays a pivotal role. As the terminal synthase for pathogenic PGE2, the microsomal prostaglandin E synthase-1 (mPGES-1) is rapidly and robustly induced by prolonged seizures. Congenital deletion of mPGES-1 in mice is neuroprotective and blunts gliosis following chemoconvulsant seizures, suggesting the feasibility of mPGES-1 as a potential antiepileptic target. Herein, we investigated the effects of a dual species mPGES-1 inhibitor in a mouse pilocarpine model of SE. Treatment with the mPGES-1 inhibitor in mice after SE that was terminated by diazepam, a fast-acting benzodiazepine, time-dependently abolished the SE-induced PGE2 within the brain. Its negligible effects on cyclooxygenases, the enzymes responsible for the initial step of PGE2 biosynthesis, validated its specificity to mPGES-1. Post-SE inhibition of mPGES-1 also blunted proinflammatory cytokines and reactive gliosis in the hippocampus and broadly prevented neuronal damage in a number of brain areas. Thus, pharmacological inhibition of mPGES-1 by small-molecule inhibitors might provide an adjunctive strategy that can be implemented hours after SE, together with first-line ASDs, to reduce SE-provoked brain inflammation and injury.
TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability
Authors: Chen Xintian , Yong Hongmei , Chen Miaolei , Deng Chuyin , Wang Pengfei , Chu Sufang , Li Minle , Hou Pingfu , Zheng Junnian , Li Zhongwei , Bai Jin 
Published: January 2023

Abstract
Background
Metabolic reprogramming is a hallmark of various cancers. Targeting metabolic processes is a very attractive treatment for cancer. Renal cell carcinoma (RCC) is a type of metabolic disease, and the lipidomic profile of RCC is significantly altered compared with that of healthy tissue. However, the molecular mechanism underlying lipid metabolism regulation in RCC is not clear.

Methods
The XF long-chain fatty acid oxidative stress test kits were used to assess the dependence on long-chain fatty acids and mitochondrial function after knockdown TRIM21 in RCC cells. The effect of TRIM21 on the lipid content in RCC cells was determined by metabolomics analysis, Oil Red O staining, and cellular Nile red staining. qRT-PCR and western blot were used to explore the relationship between TRIM21 and lipogenesis, and then the key molecule sterol regulatory element binding transcription factor 1 (SREBF1) was identified to interact with TRIM21 by immunoprecipitation, which was also identified in an orthotopic model. Subsequently, the relevance and clinical significance of TRIM21 and SREBF1 were analyzed by The Cancer Genome Atlas (TCGA) database, and 239 tissues were collected from RCC patients.

Results
TRIM21 silencing attenuated the dependence of RCC cells on fatty acids, and enhanced lipid accumulation in RCC cells. TRIM21 overexpression significantly decreased lipid contents by decreasing the expression of lipogenic enzymes via ubiquitination-mediated degradation of SREBF1. SREBF1 is critical for TRIM21-mediated lipogenesis inhibition in vitro and in vivo. Moreover, TRIM21 expression is negatively correlated with SREBF1 expression, and TRIM21-SREBF1 is a reliable combinational biomarker for RCC prognosis.

Conclusion
The findings from this study reveal a novel pathway through which TRIM21 inhibits the lipid metabolism process of RCC and shed light on the development of targeted metabolic treatment and prognosis diagnosis of RCC.
Studies on the mechanism of Toxoplasma gondii Chinese 1 genotype Wh6 strain causing mice abnormal cognitive behavior
Authors: Tao Qing , Yang Di , Qin Kunpeng , Liu Lei , Jin Mengmeng , Zhang Famin , Zhu Jinjin , Wang Jie , Luo Qingli , Du Jian , Yu Li , Shen Jilong , Chu Deyong 
Published: January 2023

Abstract
Background
Alzheimer's disease presents an abnormal cognitive behavior. TgCtwh6 is one of the predominant T. gondii strains prevalent in China. Although T. gondii type II strain infection can cause host cognitive behavioral abnormalities, we do not know whether TgCtwh6 could also cause host cognitive behavioral changes. So, in this study, we will focus on the effect of TgCtwh6 on mouse cognitive behavior and try in vivo and in vitro to explore the underlying mechanism by which TgCtwh6 give rise to mice cognitive behavior changes at the cellular and molecular level.

Methods
C57BL/6 mice were infected orally with TgCtwh6 cysts. From day 90 post-infection on, all mice were conducted through the open field test and then Morris water maze test to evaluate cognitive behavior. The morphology and number of cells in hippocampus were examined with hematoxylin-eosin (H&E) and Nissl staining; moreover, Aβ protein in hippocampus was determined with immunohistochemistry and thioflavin S plaque staining. Synaptotagmin 1, apoptosis-related proteins, BACE1 and APP proteins and genes from hippocampus were assessed by western blotting or qRT-PCR. Hippocampal neuronal cell line or mouse microglial cell line was challenged with TgCtwh6 tachyzoites and then separately cultured in a well or co-cultured in a transwell device. The target proteins and genes were analyzed by immunofluorescence staining, western blotting and qRT-PCR. In addition, mouse microglial cell line polarization state and hippocampal neuronal cell line apoptosis were estimated using flow cytometry assay.

Results
The OFT and MWMT indicated that infected mice had cognitive behavioral impairments. The hippocampal tissue assay showed abnormal neuron morphology and a decreased number in infected mice. Moreover, pro-apoptotic proteins, as well as BACE1, APP and Aβ proteins, increased in the infected mouse hippocampus. The experiments in vitro showed that pro-apoptotic proteins and p-NF-κBp65, NF-κBp65, BACE1, APP and Aβ proteins or genes were significantly increased in the infected HT22. In addition, CD80, pro-inflammatory factors, notch, hes1 proteins and genes were enhanced in the infected BV2. Interestingly, not only the APP and pro-apoptotic proteins in HT22, but also the apoptosis rate of HT22 increased after the infected BV2 were co-cultured with the HT22 in a transwell device.

Conclusions
Neuron apoptosis, Aβ deposition and neuroinflammatory response involved with microglia polarization are the molecular and cellular mechanisms by which TgCtwh6 causes mouse cognitive behavioral abnormalities.

Graphical Abstract
TRPA1 as a potential factor and drug target in scleroderma: dermal fibrosis and alternative macrophage activation are attenuated in TRPA1-deficient mice in bleomycin-induced experimental model of scleroderma
Authors: Mäki-Opas Ilari , Hämäläinen Mari , Moilanen Eeva , Scotece Morena 
Published: January 2023

Abstract
Background
Systemic sclerosis is a rheumatoid disease best known for its fibrotic skin manifestations called scleroderma. Alternatively activated (M2-type) macrophages are normally involved in the resolution of inflammation and wound healing but also in fibrosing diseases such as scleroderma. TRPA1 is a non-selective cation channel, activation of which causes pain and neurogenic inflammation. In the present study, we investigated the role of TRPA1 in bleomycin-induced skin fibrosis mimicking scleroderma.

Methods
Wild type and TRPA1-deficient mice were challenged with intradermal bleomycin injections to induce a scleroderma-mimicking disease. Macrophages were investigated in vitro to evaluate the underlying mechanisms.

Results
Bleomycin induced dermal thickening and collagen accumulation in wild type mice and that was significantly attenuated in TRPA1-deficient animals. Accordingly, the expression of collagens 1A1, 1A2, and 3A1 as well as pro-fibrotic factors TGF-beta, CTGF, fibronectin-1 and YKL-40, and M2 macrophage markers Arg1 and MRC1 were lower in TRPA1-deficient than wild type mice. Furthermore, bleomycin was discovered to significantly enhance M2-marker expression particularly in the presence of IL-4 in wild type macrophages in vitro, but not in macrophages harvested from TRPA1-deficient mice. IL-4-induced PPARγ-expression in macrophages was increased by bleomycin, providing a possible mechanism behind the phenomenon.

Conclusions
In conclusion, the results indicate that interfering TRPA1 attenuates fibrotic and inflammatory responses in bleomycin-induced scleroderma. Therefore, TRPA1-blocking treatment could potentially alleviate M2 macrophage driven diseases like systemic sclerosis and scleroderma.
The beneficial effect on cognition of noninvasive brain stimulation intervention in patients with dementia: a network meta-analysis of randomized controlled trials
Authors: Tseng Ping-Tao , Chen Yen-Wen , Zeng Bing-Yan , Zeng Bing-Syuan , Hung Chao-Ming , Sun Cheuk-Kwan , Cheng Yu-Shian , Stubbs Brendon , Carvalho Andre F. , Brunoni Andre R. , Su Kuan-Pin , Tu Yu-Kang , Wu Yi-Cheng , Chen Tien-Yu , Lin Pao-Yen , Liang Chih-Sung , Hsu Chih-Wei , Chu Che-Sheng , Suen Mein-Woei , Li Cheng-Ta 
Published: January 2023

Abstract
Background
Dementia [i.e., Alzheimer disease (AD)], the most common neurodegenerative disease, causes profound negative impacts on executive function and quality of life. Available pharmacological treatments often fail to achieve satisfactory outcomes. Noninvasive brain stimulation (NIBS) techniques, which focally modify cortical function and enhance synaptic long-term potentiation, are potentially beneficial for the cognition in patients with AD. The aim of the current network meta-analysis (NMA) was to evaluate the efficacy and safety of different NIBS interventions in patients with AD through NMA.

Methods
Only randomized controlled trials (RCTs) examining NIBS interventions in patients with AD had been included. All NMA procedures were performed under the frequentist model. The primary and secondary outcomes were changes in cognitive function and quality of life, respectively.

Results
Nineteen RCTs (639 participants) were included. The mean treatment and follow-up durations were 5.7 and 10.5 weeks, respectively. The combination of cathodal tDCS of the left dorsolateral prefrontal cortex and anodal tDCS over the right supraorbital region (c-tDCS-F3 + a-tDCS-Fp2) was associated with a significant beneficial effect on cognition compared with sham controls (standardized mean difference=2.43, 95% confidence interval=0.61–4.26, n=12 and 11). It was also associated with the greatest beneficial effect on cognition among all the investigated NIBS approaches. All the methods were well tolerated with regard to the safety profile, as reflected in the rates of adverse events or local discomfort, as well as acceptability, as indicated by dropout rate.

Conclusions
The present findings provide evidence of the benefits of NIBS, especially tDCS, for beneficial effect on cognition in patients with AD. However, because of few studies included, this effect was not replicated yet in the other studies. Therefore, future larger-scale and longer follow-up duration RCTs should be warranted.

Trial registration
PROSPERO CRD42020209516. The current study had been approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB No. B-109-29).
Joint hybrid-precoding design for MU-MISO systems with a subconnected architecture
Authors: Bahingayi Eduard E. , Lee Kyungchun 
Published: January 2023

AbstractIn this study, we propose a joint hybrid-precoding algorithm for multiuser multiple-input single-output downlink systems. Specifically, we consider that the base station employs an energy-efficient hybrid-precoding subconnected (SC) architecture with fixed equal subarrays (FESA) (SC-FESA). Optimizing the analog precoding matrix in an SC-FESA architecture is challenging due to its unique constraint structure. In this study, to maximize system sum rate, we propose an efficient method to transform the system’s sum-rate optimization problem into a continuous and differentiable objective function wherein only the nonzero elements of the analog precoding matrix are optimized. For the formulated problem, we develop an alternating optimization (AO) approach to jointly optimize the digital and analog precoders in succession by maximizing the system’s sum rate. Specifically, in the proposed AO method, when the digital precoder is fixed, we employ the Riemannian conjugate gradient algorithm to generate the analog precoder. Furthermore, when the analog precoder is fixed, we use the minimum mean squared error method to obtain the digital precoder. Numerical simulation results show that the proposed AO algorithm improves the sum rate and energy efficiency of the SC-FESA architecture compared to existing algorithms.
Using computer-based habit versus chess-based cognitive remediation training as add-on therapy to modify the imbalance between habitual behavior and cognitive control in tobacco use disorder: protocol of a randomized controlled, fMRI study
Authors: Karl Damian , Wieland Alfred , Shevchenko Yury , Grundinger Nadja , Machunze Noah , Gerhardt Sarah , Flor Herta , Vollstädt-Klein Sabine 
Published: January 2023

AbstractBackgroundAlthough the vast majority of smokers are aware of the enormous preventable health hazards caused by smoking, only a small percentage of smokers manage to remain abstinent in the long term. One possible explanation for this discrepancy lies in the inflexibility of addictive behavior and associated disadvantageous decision‐making. According to a dual‐process theory of decision‐making, two distinct decision systems can be identified. One slow deliberate system based on desirable expectations of outcome value described as goal‐directed behavior and a fast reflexive system based on habitual instrumental behavior and driven by reinforcement experienced in the past. In the course of addiction development, an imbalance occurs between habitual behavior and goal-directed. The present study aims to investigate the modifiability of the balance between habitual and goal-directed behavior at the neurobiological and behavioral level in smokers using two different novel add-on therapies. We hypothesize that both interventions change the balance between goal-directed and habitual behavior, but by different mechanisms. Whereas a cognitive remediation treatment should directly improve cognitive control, in contrast an implicit priming task should affect the early processing and the emotional valence of smoking and smoking cues.MethodsWe will conduct a randomized controlled study in treatment-seeking individuals with tobacco use disorder applying either chess-based cognitive remediation training (N = 30) or implicit computer-based habit-modifying training (N = 30) as add on therapy compared to the standard smoking cessation group therapy (N = 30) only. We will address neurobiological and neuropsychological correlates associated with craving, reward devaluation, cue reactivity and attentional bias. In addition, various effects of treatment and prediction of treatment outcome will be examined using behavioral and neural measures.DiscussionThe present study will apply different examination methods such as functional magnetic resonance imaging, neuropsychological tests, and self-report before and after the interventions. This allows the identification of intervention-specific mechanisms and therefore potential neurobiology-based specific treatment targets for individuals with Tobacco Use Disorder.Trial registration: Registered at clinicaltrials.gov/ct2/show/NCT03764969 (05 December 2018).