bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta-analysis of the association between Apolipoprotein E polymorphism and risks of myocardial infarction
Authors: Shao Aiyu , Shi Jikang , Liang Zhuoshuai , Pan Lingfeng , Zhu Wenfei , Liu Sainan , Xu Jiayi , Guo Yanbo , Cheng Yi , Qiao Yichun 
Published: March 2022

Abstract
Background
Myocardial infarction (MI) remains the leading cause of death and disability among cardiovascular diseases worldwide. Studies show that elevated low-density lipid protein cholesterol (LDL-C) levels confer the highest absolute risk of MI, and Apolipoprotein E (ApoE) is implicated in regulating levels of triglycerides (TGs), cholesterol, and LDL-C. Our study aimed to evaluate the association between APOE polymorphism and MI, and to provide evidence for the etiology of MI.

Methods
Case–control studies on the association between APOE polymorphisms and the risk of myocardial infarction were included by searching PubMed, Web of Science, and CNKI, and this meta-analysis was written in accordance with PRISMA guideline statement. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using either random-effects or fixed-effects models by R software.

Results
A total of 33 eligible articles involving 13,706 cases and 14,817 controls were finally selected. The pooled analysis based on the total eligible articles showed that the risk of MI was associated with ApoE epsilon 2 and epsilon 4 alleles. The results showed that patients with MI had a low frequency of the ε2 allele (OR 0.74, 95% CI 0.64–0.86) and a high frequency of the ε4 allele (OR 1.24, 95% CI 1.09–1.42).

Conclusions
APOE ε2-involved genotypes may be protective factors for MI; in contrast, ε4-involved genotypes (ε4/ε3 vs. ε3/ε3, and ε4/ε4 vs. ε3/ε3) may be risk factors for MI.
Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy—effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker
Authors: Xiong Yingquan , Delic Denis , Zeng Shufei , Chen Xin , Chu Chang , Hasan Ahmed A. , Krämer Bernhard K. , Klein Thomas , Yin Lianghong , Hocher Berthold 
Published: March 2022

AbstractBackgroundHost factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2.MethodsWe investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression ofAce2,Tmprss2,Ren,Agtr2andAgtwas assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin.ResultsIn the kidney, the expression ofAce2was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin.ConclusionsOur study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials.
Comparing different montages of transcranial direct current stimulation on dual-task walking and cortical activity in chronic stroke: double-blinded randomized controlled trial
Authors: Wong Pei-Ling , Yang Yea-Ru , Tang Shun-Chang , Huang Shih-Fong , Wang Ray-Yau 
Published: March 2022

Abstract
Background
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation to modulate cortical activity for improving motor function. However, the different tDCS applications for modulating cortical activity and dual task gait performance in chronic stroke have not yet been investigated. This study investigated the effects of different tDCS applications on dual task gait performance and contralesional M1 activation in chronic stroke.

Methods
Forty-eight participants were randomized to anodal, bilateral, cathodal, and sham tDCS groups. Each group received 20 min of tDCS stimulation, except the sham group. Gait performance was measured by GaitRite system during cognitive dual task (CDT) walking, motor dual task (MDT) walking, and single walking (SW). Contralesional M1 activity of unaffected tibialis anterior (TA) was measured using transcranial magnetic stimulation (TMS). Intragroup difference was analyzed by Wilconxon sign ranks test with Bonferroni correction, and Kruskal–Wallis one-way analysis of variance by ranks was used for intergroup comparisons, followed by post-hoc Mann–Whitney U tests with Bonferroni correction.

Results
The bilateral tDCS (p = 0.017) and cathodal tDCS (p = 0.010) improved the CDT walking speed more than sham group. The bilateral tDCS (p = 0.048) and cathodal tDCS (p = 0.048) also improved the MDT walking speed more than sham group. Furthermore, bilateral tDCS (p = 0.012) and cathodal tDCS (p = 0.040) increased the silent period (SP) more than the anodal and sham group. Thus, one-session of bilateral and cathodal tDCS improved dual task walking performance paralleled with increasing contralesional corticomotor inhibition in chronic stroke.

Conclusions
Our results indicate that one-session of bilateral and cathodal tDCS increased contralesional corticomotor inhibition and improved dual task gait performance in chronic stroke.

Trial registration
Thai Clinical Trials Registry (TCTR20180116001). Registered prospectively on 16th Jan, 2018 at http://www.thaiclinicaltrials.org.
Cumulative exposure to maternal psychological distress in the prenatal and postnatal periods and atopic dermatitis in children: findings from the TMM BirThree Cohort Study
Authors: Kawaguchi Chikana , Murakami Keiko , Ishikuro Mami , Ueno Fumihiko , Noda Aoi , Onuma Tomomi , Matsuzaki Fumiko , Metoki Hirohito , Kuriyama Shinichi , Obara Taku 
Published: March 2022

Abstract
Background
Maternal mental health problems in each of the prenatal period and postnatal period have been demonstrated as possible risk factors for atopic dermatitis (AD) in children. However, the cumulative impacts of maternal psychological distress in the prenatal and postnatal periods on AD in children remain unclear. This study examined the association between cumulative exposure to maternal psychological distress in the prenatal and postnatal periods and the development of AD in children.

Methods
Data were derived from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan. In total, 8377 mother-child pairs in which the child had no AD at the age of 1 year were analyzed. Maternal psychological distress in early pregnancy and 1 year after delivery was defined as a K6 score ≥ 5, and the participants were categorized into four groups: no psychological distress in both the prenatal and postnatal periods; only the prenatal period; only the postnatal period; and both periods. The development of AD was defined as the presence of AD in a 2-year-old child without AD reported at the age of 1 year using the International Study of Asthma and Allergies in Childhood questionnaire. Generalized linear model analyses were conducted to examine the association between maternal psychological distress and the development of AD in children adjusted for age at delivery, educational attainment, smoking status in pregnancy, maternal history of AD, paternal history of AD, parity, maternal body mass index, and child sex.

Results
Between the ages of 1 and 2 years, 14.0% of children developed AD. Maternal psychological distress in both prenatal and postnatal periods was associated with an increased risk of AD in children compared to no psychological distress in both periods (relative risk (RR), 95% confidence interval (CI): 1.34, 1.20–1.47). Maternal psychological distress in only the postnatal period was associated with an increased risk of AD in children (RR, 95% CI: 1.23, 1.07–1.39), but not in only the prenatal period (RR, 95% CI: 1.14, 0.98–1.30).

Conclusions
Cumulative exposure to maternal psychological distress in the prenatal and postnatal periods was associated with the development of AD in children.
Context dependent isoform specific PI3K inhibition confers drug resistance in hepatocellular carcinoma cells
Authors: Narci Kubra , Kahraman Deniz Cansen , Koyas Altay , Ersahin Tulin , Tuncbag Nurcan , Atalay Rengul Cetin 
Published: March 2022

Abstract
Background
Targeted therapies for Primary liver cancer (HCC) is limited to the multi-kinase inhibitors, and not fully effective due to the resistance to these agents because of the heterogeneous molecular nature of HCC developed during chronic liver disease stages and cirrhosis. Although combinatorial therapy can increase the efficiency of targeted therapies through synergistic activities, isoform specific effects of the inhibitors are usually ignored. This study concentrated on PI3K/Akt/mTOR pathway and the differential combinatory bioactivities of isoform specific PI3K-α inhibitor (PIK-75) or PI3K-β inhibitor (TGX-221) with Sorafenib dependent on PTEN context.

Methods
The bioactivities of inhibitors on PTEN adequate Huh7 and deficient Mahlavu cells were investigated with real time cell growth, cell cycle and cell migration assays. Differentially expressed genes from RNA-Seq were identified by edgeR tool. Systems level network analysis of treatment specific pathways were performed with Prize Collecting Steiner Tree (PCST) on human interactome and enriched networks were visualized with Cytoscape platform.

Results
Our data from combinatory treatment of Sorafenib and PIK-75 and TGX-221 showed opposite effects; while PIK-75 displays synergistic effects on Huh7 cells leading to apoptotic cell death, Sorafenib with TGX-221 display antagonistic effects and significantly promotes cell growth in PTEN deficient Mahlavu cells. Signaling pathways were reconstructed and analyzed in-depth from RNA-Seq data to understand mechanism of differential synergistic or antagonistic effects of PI3K-α (PIK-75) and PI3K-β (TGX-221) inhibitors with Sorafenib. PCST allowed as to identify AOX1 and AGER as targets in PI3K/Akt/mTOR pathway for this combinatory effect. The siRNA knockdown of AOX1 and AGER significantly reduced cell proliferation in HCC cells.

Conclusions
Simultaneously constructed and analyzed differentially expressed cellular networks presented in this study, revealed distinct consequences of isoform specific PI3K inhibition in PTEN adequate and deficient liver cancer cells. We demonstrated the importance of context dependent and isoform specific PI3K/Akt/mTOR signaling inhibition in drug resistance during combination therapies. (https://github.com/cansyl/Isoform-spesific-PI3K-inhibitor-analysis).
Comparison of survival outcomes between squamous cell carcinoma and adenocarcinoma/adenosquamous carcinoma of the cervix after radical radiotherapy and chemotherapy
Authors: Liu Ping , Ji Mei , Kong Yanxiang , Huo Zhifeng , Lv Qiubo , Xie Qinghuang , Wang Danbo , Chen Biliang , Wang Hailin , Cui Zhumei , Wang Qianqing , Bin Xiaonong , Lang Jinghe , Chen Chunlin 
Published: March 2022

Abstract
Background
This study aimed to compare the survival outcomes between squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix after radical radiotherapy and chemotherapy.

Methods
Propensity score matching (1:4) was used to compare overall survival (OS) and disease-free survival (DFS) in cervical cancer patients with SCC and AC/ASC in China.

Results
Five thousand four hundred sixty-six patients were enrolled according to the criteria. The 5-year OS and DFS in the SCC group (n = 5251) were higher than those in the AC/ASC group (n = 215). After PSM (1:4), the 5-year OS and DFS in the SCC group were higher than those in the AC/ASC group (72.2% vs 56.9%, p < 0.001, HR = 1.895; 67.6% vs 47.8%, p < 0.001, HR = 2.056). In stage I-IIA2 patients, after PSM (1:4), there was no significant difference in 5-year OS between the SCC group (n = 143) and the AC/ASC group (n = 34) (68.5% vs 67.8%, P = 0.175). However, the 5-year DFS in the SCC group was higher than that in the AC/ASC group (71.0% vs 55.7%, P = 0.045; HR = 2.037, P = 0.033). In stage IIB-IV patients, after PSM (1:4), the 5-year OS and DFS in the SCC group (n = 690) were higher than those in the AC/ASC group (n = 173) (70.7% vs 54.3% P < 0.001 vs 1.940%, P < 0.001 vs 45.8%, p < 0.001).

Conclusions
For stage I-IIA2, there was no significant difference in 5-year survival time, but patients with AC/ASC were more likely to relapse. In the more advanced IIB-IV stage, the oncological outcome of radical radiotherapy and chemotherapy of cervical AC/ASC was worse than that of SCC.
Oral erythema multiforme after Pfizer-BioNTech COVID-19 vaccination: a report of four cases
Authors: Petruzzi Massimo , Galleggiante Sara , Messina Sabrina , della Vella Fedora 
Published: March 2022

Abstract
Background
The 2019 Coronavirus disease (Covid-19) has affected thousands of people worldwide. To date, vaccines appear to be the only method to prevent and reduce mortality. Four vaccinations have been outwardly approved by European Medicine Agency (EMA) in Europe: BNT162b2 (Comirnaty-BioNTech/Pfizer), mRNA-1273 (Spikevax-Moderna), ChAdOx1 (VaxzevriaAstrazeneca), and Ad26.COV2-S (Janssen-Johnson&Johnson). After vaccination, local and systemic adverse effects can occur. Cutaneous reactions like urticaria, local injection site pain, morbilliform rash have been documented after vaccination.

Cases presentation
We report four cases of oral erythema multiforme flare arising after BNT162b2 vaccination administration. All the patients denied previous erythema-like and herpetic manifestations history. Two of the reported cases (number 1 and 2) presented with both oral and cutaneous lesions, while cases 3 and 4 showed only oral manifestations. Three of the cases presented the erythema after the first vaccination dosage administration, only one case reported lesions after the second vaccination dosage administration. All the cases were treated with prednisone via oral administration and topical 0.05% clobetasol ointment.

Conclusions
The present reports represent some of the few cases of erythema multiforme occurring as a side effect of the BNT162b2 COVID-19 vaccination. The causal role of the vaccine for the erythema multiforme has not been proven yet; nevertheless, it is not uncommon for medications to trigger this disease. The vaccine could surface a silent herpes virus infection, which would induce the erythema multiforme instead.
Interpreter-mediated interactions between people using a signed respective spoken language across distances in real time: a scoping review
Authors: Warnicke Camilla , Granberg Sarah 
Published: March 2022

Abstract
Background
Communication between people who are deaf and sign and people who use a spoken language is possible by means of an interpreter. Interpreting in real time can be performed at a distance, which differs from interpreting face-to-face. Due to COVID-19, interpretation at a distance has increased.

Objective
The objective of this study was to map the existing literature to identify key characteristics by addressing the following question: What is known about interpreted mediated interactions between people using a signed respective spoken language across distances in real time?

Design
Eight online databases, complemented by a search in one nonindexed journal of relevance to the review, were used to identify original studies published in 2010–2020, and 17 publications met the inclusion criteria. Charting of the data revealed insight from 17 original studies that were extracted, summarized, and reported.

Results
Four key characteristics were identified: (1) advantages and challenges in remote interpreting; (2) the need for training in remote interpreting and video relay service (VRS); (3) regulations and organizational structures of VRS; and (4) the interpreter as an active party in VRS.

Conclusion
Remote interpreting has several challenges but also advantages. Knowledge of these kinds of interactions is limited, and further research must be initiated and realized, not least due to technological developments and the increased number of interpreting events.
Reprogramming of arachidonate metabolism confers temozolomide resistance to glioblastoma through enhancing mitochondrial activity in fatty acid oxidation
Authors: Tsai Yu-Ting , Lo Wei-Lun , Chen Pin-Yuan , Ko Chiung-Yuan , Chuang Jian-Ying , Kao Tzu-Jen , Yang Wen-Bing , Chang Kwang-Yu , Hung Chia-Yang , Kikkawa Ushio , Chang Wen-Chang , Hsu Tsung-I. 
Published: March 2022

Abstract
Background
Sp1 is involved in the recurrence of glioblastoma (GBM) due to the acquirement of resistance to temozolomide (TMZ). Particularly, the role of Sp1 in metabolic reprogramming for drug resistance remains unknown.

Methods
RNA-Seq and mass spectrometry were used to analyze gene expression and metabolites amounts in paired GBM specimens (primary vs. recurrent) and in paired GBM cells (sensitive vs. resistant). ω-3/6 fatty acid and arachidonic acid (AA) metabolism in GBM patients were analyzed by targeted metabolome. Mitochondrial functions were determined by Seahorse XF Mito Stress Test, RNA-Seq, metabolome and substrate utilization for producing ATP. Therapeutic options targeting prostaglandin (PG) E2 in TMZ-resistant GBM were validated in vitro and in vivo.

Results
Among the metabolic pathways, Sp1 increased the prostaglandin-endoperoxide synthase 2 expression and PGE2 production in TMZ-resistant GBM. Mitochondrial genes and metabolites were obviously increased by PGE2, and these characteristics were required for developing resistance in GBM cells. For inducing TMZ resistance, PGE2 activated mitochondrial functions, including fatty acid β-oxidation (FAO) and tricarboxylic acid (TCA) cycle progression, through PGE2 receptors, E-type prostanoid (EP)1 and EP3. Additionally, EP1 antagonist ONO-8713 inhibited the survival of TMZ-resistant GBM synergistically with TMZ.

Conclusion
Sp1-regulated PGE2 production activates FAO and TCA cycle in mitochondria, through EP1 and EP3 receptors, resulting in TMZ resistance in GBM. These results will provide us a new strategy to attenuate drug resistance or to re-sensitize recurred GBM.
Perplexity: evaluating transcript abundance estimation in the absence of ground truth
Authors: Fan Jason , Chan Skylar , Patro Rob 
Published: March 2022

Abstract
Background
There has been rapid development of probabilistic models and inference methods for transcript abundance estimation from RNA-seq data. These models aim to accurately estimate transcript-level abundances, to account for different biases in the measurement process, and even to assess uncertainty in resulting estimates that can be propagated to subsequent analyses. The assumed accuracy of the estimates inferred by such methods underpin gene expression based analysis routinely carried out in the lab. Although hyperparameter selection is known to affect the distributions of inferred abundances (e.g. producing smooth versus sparse estimates), strategies for performing model selection in experimental data have been addressed informally at best.

Results
We derive perplexity for evaluating abundance estimates on fragment sets directly. We adapt perplexity from the analogous metric used to evaluate language and topic models and extend the metric to carefully account for corner cases unique to RNA-seq. In experimental data, estimates with the best perplexity also best correlate with qPCR measurements. In simulated data, perplexity is well behaved and concordant with genome-wide measurements against ground truth and differential expression analysis. Furthermore, we demonstrate theoretically and experimentally that perplexity can be computed for arbitrary transcript abundance estimation models.

Conclusions
Alongside the derivation and implementation of perplexity for transcript abundance estimation, our study is the first to make possible model selection for transcript abundance estimation on experimental data in the absence of ground truth.
Epigenetic remodelling in human hepatocellular carcinoma
Authors: Braghini Maria Rita , Lo Re Oriana , Romito Ilaria , Fernandez-Barrena Maite G. , Barbaro Barbara , Pomella Silvia , Rota Rossella , Vinciguerra Manlio , Avila Matias A. , Alisi Anna 
Published: March 2022

AbstractHepatocellular carcinoma (HCC) is the most frequent primary liver cancer, being the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related death. As other heterogeneous solid tumours, HCC results from a unique synergistic combination of genetic alterations mixed with epigenetic modifications.In HCC the patterns and frequencies of somatic variations change depending on the nearby chromatin. On the other hand, epigenetic alterations often induce genomic instability prone to mutations. Epigenetics refers to heritable states of gene expression without alteration to the DNA sequence itself and, unlike genetic changes, the epigenetic modifications are reversible and affect gene expression more extensively than genetic changes. Thus, studies of epigenetic regulation and the involved molecular machinery are greatly contributing to the understanding of the mechanisms that underline HCC onset and heterogeneity. Moreover, this knowledge may help to identify biomarkers for HCC diagnosis and prognosis, as well as future new targets for more efficacious therapeutic approaches.In this comprehensive review we will discuss the state-of-the-art knowledge about the epigenetic landscape in hepatocarcinogenesis, including evidence on the diagnostic and prognostic role of non-coding RNAs, modifications occurring at the chromatin level, and their role in the era of precision medicine.Apart from other better-known risk factors that predispose to the development of HCC, characterization of the epigenetic remodelling that occurs during hepatocarcinogenesis could open the way to the identification of personalized biomarkers. It may also enable a more accurate diagnosis and stratification of patients, and the discovery of new targets for more efficient therapeutic approaches.