bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cenobamate for treatment-resistant focal seizures: current evidence and place in therapy
Authors: Singh Alok 
Published: March 2022

Background Cenobamate is newly approved for partial-onset seizures in adults, albeit the mechanism of its action remain poorly understood. Methods This article aims to review the efficacy, safety, and tolerability of cenobamate in treating partial-onset seizures. Data Collection: The English language articles were searched in the National Institute of Health clinical trials registry, PubMed, and the Cochrane library between 2010 and June 2021 using the keywords cenobamate, YKP 3089, and seizure, and filter “trial” was applied. Results: A total of 31 articles were retrieved. Eventually, two randomized, double-blind, multicenter clinical trials involving 659 patients were analyzed. Cenobamate has shown significant reduction in seizure frequency compared to placebo. In cenobamate group, a greater number of participants showed ≥50% reduction in seizure frequency, adverse effects, and drug discontinuation compared to placebo. Multiple drug-drug interactions with other anti-seizure drugs were also observed. Conclusions Based on the findings of these trials, cenobamate seems to be an attractive option for treatment-resistant partial-onset seizures; however, multiple treatment-related adverse effects and drug-drug interactions are the areas of concern.
Female sexual dysfunction after bariatric surgery in women with obesity: A systematic review and meta-analysis
Authors: Loh Huai H. , Shahar Mohammad A. , Loh Huai S. , Yee Anne 
Published: March 2022

Background and objective: Obesity is prevalent and has a negative impact on women’s health, including sexual dysfunction. Recent review articles suggest improvement in Female Sexual Function Index (FSFI) and proportion of female sexual dysfunction (FSD) among women with obesity after bariatric surgery. Methods: We pooled data from 16 observational studies involving 953 women. The study outcomes were mean FSFI scores and proportion of FSD before and after bariatric surgery. We also sub-analyzed whether age and duration of follow-up affected these outcomes. Results: The mean age of the subjects was 39.4 ± 4.2 years. Body mass index (BMI) showed significant reduction postoperatively ( p < 0.0001). Bariatric surgery led to significant improvement in total FSFI score ( p = 0.0005), and all sexual domains except pain. Bariatric surgery reduced the odds of having FSD by 76% compared with those who did not undergo operation (OR 0.24, 95% CI = 0.17, 0.33, p < 0.0001). Our sub-analysis demonstrated a significant reduction in the proportion of FSD for patients <40 years of age. The improvement of total FSFI scores and reduction in proportion of FSD remained significant within the first 12 months after surgery. Univariate meta-regression showed that BMI was not a significant covariate for improvement of FSFI scores ( β = 0.395, p = 0.1, 95% CI = 0.884, 0.095). Conclusions: Bariatric surgery is shown to improve sexual function scores and prevalence of FSD. This is especially significant among women <40 years of age. This benefit remained significant within the first year after surgery. This appears to be an additional benefit for these patients.
Functionally graded cellular cores of sandwich panels fabricated by additive manufacturing
Authors: Garrido Silva B , Alves F , Sardinha M , Reis L , Leite M , Deus A M , Vaz M Fatima 
Published: March 2022

Functionally graded cellular materials, which combine cellular materials with a gradient of properties, have been recently investigated as cores of sandwich panels. The present work aims to evaluate the flexural properties of functionally graded cellular structures with a gradient of cell thickness on configurations recently proposed. The structures hexagonal honeycomb (Hr), lotus (Lt), and hexagonal honeycomb with Plateau borders (Pt) were designed with three different gradients of cell thickness. The parts were manufactured by material extrusion using FFF (Fused Filament Fabrication). To evaluate the mechanical properties, three-point bending tests were conducted, both experimentally and by numerical modelling, by means of the finite element method. The materials used were polylactic acid (PLA) and aluminum. Although experimental and numerical results exhibited some deviations, they revealed the same trends. The results showed that the stiffness and the absorbed energy of the graded Hr, Lt and Pt structures, made of PLA, are higher than such values for the regular hexagonal honeycombs. For the same gradient of cell thickness, the lotus structure tends to exhibit the highest stiffness and absorbed energy, while the hexagonal honeycomb arrangement achieves the largest value of strength. Graded aluminum specimens also attain higher values of stiffness, strength and absorbed energy in comparison with non-graded hexagonal honeycomb configurations. Thus, the use of gradients of cell thickness can promote structures with higher stiffness and absorbed energy, which may compete with the conventional structures of sandwich panel cores.
Mortality, seasonal variation, and susceptibility to acute exacerbation of COPD in the pandemic year: a nationwide population study
Authors: Sarc Irena , Lotric Dolinar Alesa , Morgan Tina , Sambt Joze , Ziherl Kristina , Gavric Dalibor , Selb Julij , Rozman Ales , Dosenovic Bonca Petra 
Published: March 2022

Background: Previous studies have suggested that the coronavirus disease 2019 (COVID-19) pandemic was associated with a decreased rate of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Data on how the COVID-19 pandemic has influenced mortality, seasonality of, and susceptibility to AECOPD in the chronic obstructive pulmonary disease (COPD) population is scarce. Methods: We conducted a national population-based retrospective study using data from the Health Insurance Institute of Slovenia from 2015 to February 2021, with 2015–2019 as the reference. We extracted patient and healthcare data for AECOPD, dividing AECOPD into severe, resulting in hospitalisation, and moderate, requiring outpatient care. The national COPD population was generated based on dispensed prescriptions of inhalation therapies, and moderate AECOPD events were analysed based on dispensed AECOPD medications. We extracted data on all-cause and non-COVID mortality. Results: The numbers of severe and moderate AECOPD were reduced by 48% and 34%, respectively, in 2020. In the pandemic year, the seasonality of AECOPD was reversed, with a 1.5-fold higher number of severe AECOPD in summer compared to winter. The proportion of frequent exacerbators (⩾2 AECOPD hospitalisations per year) was reduced by 9% in 2020, with a 30% reduction in repeated severe AECOPD in frequent exacerbators and a 34% reduction in persistent frequent exacerbators (⩾2 AECOPD hospitalisations per year for 2 consecutive years) from 2019. The risk of two or more moderate AECOPD decreased by 43% in 2020. In the multivariate model, pandemic year follow-up was the only independent factor associated with a decreased risk for severe AECOPD (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.61–0.84; p < 0.0001). In 2020, non-COVID mortality decreased (−15%) and no excessive mortality was observed in the COPD population. Conclusion: In the pandemic year, we found decreased susceptibility to AECOPD across severity spectrum of COPD, reversed seasonal distribution of severe AECOPD and decreased non-COVID mortality in the COPD population.
Finding my Way into Resistance
Authors: Pelias Ronald J. 
Published: March 2022

The essay presents satiric accounts of the author’s encounters with Trump signage. It shows how political T-shirts, yard signs, and hats can become emotional triggers, often resulting problematic discourse. As a corrective, it calls upon several scholars who offer more productive ways of conversing with those who hold oppositional views. The essay then raises the question of whether the recommended strategies are effective with those who do not act in good faith. The essay ends with a postscript written 2 weeks after the 2020 election.
Phenobarbital-induced autoimmune haemolytic anaemia, thrombocytopenia and peripheral lymphadenomegaly due to reactive lymphoid hyperplasia in a cat
Authors: Walton-Clark Michelle , Travail Victoria , Best Matthew 
Published: March 2022

Case summary A female neutered domestic longhair cat, aged 1 year and 5 months, presented with lymphadenomegaly and anaemia following therapy with phenobarbital for idiopathic epilepsy. Physical examination revealed pale pink mucous membranes and peripheral lymphadenomegaly. Haematology showed a regenerative anaemia (haematocrit 19.3%, reticulocyte count 118.08 ×109/l), and saline agglutination was positive. Infectious disease screening was negative and lymph node cytology was consistent with reactive lymphoid hyperplasia. A diagnosis of phenobarbital-induced reactive lymphoid hyperplasia and immune-mediated anaemia was suspected. Complete resolution of the lymphadenomegaly and anaemia was documented within 4 weeks of phenobarbital discontinuation. Relevance and novel information There are limited case reports of phenobarbital-induced haematological changes and lymphadenomegaly; however, the combination has not previously been reported in cats and is similar to the rare but significant syndrome in humans known as ‘anticonvulsant hypersensitivity syndrome’. Anticonvulsant hypersensitivities should be considered as a potentially serious, yet reversible, sequela to phenobarbital treatment that may be mistaken for more severe illness such as neoplasia.
CNN-DDI: a learning-based method for predicting drug–drug interactions using convolution neural networks
Authors: Zhang Chengcheng , Lu Yao , Zang Tianyi 
Published: March 2022

Abstract
Background
Drug–drug interactions (DDIs) are the reactions between drugs. They are compartmentalized into three types: synergistic, antagonistic and no reaction. As a rapidly developing technology, predicting DDIs-associated events is getting more and more attention and application in drug development and disease diagnosis fields. In this work, we study not only whether the two drugs interact, but also specific interaction types. And we propose a learning-based method using convolution neural networks to learn feature representations and predict DDIs.

Results
In this paper, we proposed a novel algorithm using a CNN architecture, named CNN-DDI, to predict drug–drug interactions. First, we extract feature interactions from drug categories, targets, pathways and enzymes as feature vectors and employ the Jaccard similarity as the measurement of drugs similarity. Then, based on the representation of features, we build a new convolution neural network as the DDIs’ predictor.

Conclusion
The experimental results indicate that drug categories is effective as a new feature type applied to CNN-DDI method. And using multiple features is more informative and more effective than single feature. It can be concluded that CNN-DDI has more superiority than other existing algorithms on task of predicting DDIs.
A multi-network integration approach for measuring disease similarity based on ncRNA regulation and heterogeneous information
Authors: Zhang Ningyi , Zang Tianyi 
Published: March 2022

AbstractBackgroundMeasuring similarity between complex diseases has significant implications for revealing the pathogenesis of diseases and development in the domain of biomedicine. It has been consentaneous that functional associations between disease-related genes and semantic associations can be applied to calculate disease similarity. Currently, more and more studies have demonstrated the profound involvement of non-coding RNA in the regulation of genome organization and gene expression. Thus, taking ncRNA into account can be useful in measuring disease similarities. However, existing methods ignore the regulation functions of ncRNA in biological process. In this study, we proposed a novel deep-learning method to deduce disease similarity.ResultsIn this article, we proposed a novel method, ImpAESim, a framework integrating multiple networks embedding to learn compact feature representations and disease similarity calculation. We first utilize three different disease-related information networks to build up a heterogeneous network, after a network diffusion process, RWR, a compact feature learning model composed of classic Auto Encoder (AE) and improved AE model is proposed to extract constraints and low-dimensional feature representations. We finally obtain an accurate and low-dimensional feature representation of diseases, then we employed the cosine distance as the measurement of disease similarity.ConclusionImpAESim focuses on extracting a low-dimensional vector representation of features based on ncRNA regulation, and gene–gene interaction network. Our method can significantly reduce the calculation bias resulted from the sparse disease associations which are derived from semantic associations.
Transcriptomic characterization of the molecular mechanisms induced by RGMa during skeletal muscle nuclei accretion and hypertrophy
Authors: Copola Aline Gonçalves Lio , dos Santos Íria Gabriela Dias , Coutinho Luiz Lehmann , Del-Bem Luiz Eduardo Vieira , de Almeida Campos-Junior Paulo Henrique , da Conceição Izabela Mamede Costa Andrade , Nogueira Júlia Meireles , do Carmo Costa Alinne , Silva Gerluza Aparecida Borges , Jorge Erika Cristina 
Published: March 2022

Abstract
Background
The repulsive guidance molecule a (RGMa) is a GPI-anchor axon guidance molecule first found to play important roles during neuronal development. RGMa expression patterns and signaling pathways via Neogenin and/or as BMP coreceptors indicated that this axon guidance molecule could also be working in other processes and diseases, including during myogenesis. Previous works from our research group have consistently shown that RGMa is expressed in skeletal muscle cells and that its overexpression induces both nuclei accretion and hypertrophy in muscle cell lineages. However, the cellular components and molecular mechanisms induced by RGMa during the differentiation of skeletal muscle cells are poorly understood. In this work, the global transcription expression profile of RGMa-treated C2C12 myoblasts during the differentiation stage, obtained by RNA-seq, were reported.

Results
RGMa treatment could modulate the expression pattern of 2,195 transcripts in C2C12 skeletal muscle, with 943 upregulated and 1,252 downregulated. Among them, RGMa interfered with the expression of several RNA types, including categories related to the regulation of RNA splicing and degradation. The data also suggested that nuclei accretion induced by RGMa could be due to their capacity to induce the expression of transcripts related to ‘adherens junsctions’ and ‘extracellular-cell adhesion’, while RGMa effects on muscle hypertrophy might be due to (i) the activation of the mTOR-Akt independent axis and (ii) the regulation of the expression of transcripts related to atrophy. Finally, RGMa induced the expression of transcripts that encode skeletal muscle structural proteins, especially from sarcolemma and also those associated with striated muscle cell differentiation.

Conclusions
These results provide comprehensive knowledge of skeletal muscle transcript changes and pathways in response to RGMa.
RNA-Seq reveals miRNA role in thermogenic regulation in brown adipose tissues of goats
Authors: Liu Xin , Zhu Yuehua , Zhan Siyuan , Zhong Tao , Guo Jiazhong , Cao Jiaxue , Li Li , Zhang Hongping , Wang Linjie 
Published: March 2022

Abstract
Background
MicroRNAs (miRNAs) are a family of short non-coding RNA molecules and play important roles in various biological processes. However, knowledge of the expression profiles and function of miRNAs on the regulation of brown adipose tissue (BAT) thermogenesis remains largely unknown.

Results
In this study, we found that brown adipose tissue (BAT) existed within the perirenal fat at 1 day after birth (D1) and transferred into white adipose tissue (WAT) at 30 days after birth (D30) by UCP1 protein expression and immunohistochemistry analysis. After that, we performed RNA sequencing on six libraries of goat BAT and WAT. A total of 238 known miRNAs and 1834 goat novel miRNAs were identified. Moreover, 395 differentially expressed miRNAs including 167 up-regulated and 228 down-regulated miRNAs were obtained in BAT. For the known BAT enriched miRNA, 30 miRNAs were enriched in goat BAT but not in mouse BAT. In addition, miR-433 was enriched in goat BAT but not in mouse BAT. Gain- and loss-of-function experiments reveal that miR-433 reduced the lipid accumulation of brown adipocytes and decreased the expression of BAT marker and mitochondrial related genes. However, miR-433 had no effect on lipid accumulation and thermogenesis in white adipocytes. In addition, miR-433 inhibited the expression of MAPK8 by targeting to the 3’UTR of MAPK8 gene. These data demonstrate that miR-433 acts as a negative regulator in controlling brown adipocytes differentiation and thermogenesis.

Conclusion
The present study provides a detailed miRNAs expression landscape in BAT and WAT. Furthermore, we found that miR-433, which was highly expressed on BAT had a negative regulatory function on the thermogenesis and adipogenesis in goat brown adipocytes. This study provides evidence for understanding the role of miRNAs in regulating BAT thermogenesis and energy expenditure in goats.
The effect of daily consumption of probiotic yogurt on liver enzymes, steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD): study protocol for a randomized clinical trial
Authors: Ebrahimi-Mousavi Sara , Alavian Seyed Moayed , Sohrabpour Amir Ali , Dashti Fatemeh , Djafarian Kurosh , Esmaillzadeh Ahmad 
Published: March 2022

Abstract
Background
Given the increasing prevalence of non-alcoholic fatty liver disease, it is necessary to find an easy and cost-effective method in its management and treatment. Probiotics are a group of living microorganisms that might affect NAFLD through the intestinal-liver axis. The present clinical trial aims to examine the effect of probiotic yogurt consumption on liver enzymes, steatosis and liver fibrosis in patients with NAFLD.

Methods
Sixty-eight patients with NAFLD will be recruited in this study. After block matching for sex, BMI and age, patients will be randomly assigned to receive 300 g/d probiotic yogurt containing 106 cfu/g of Lactobacillus acidophilus and Bifidobacterium lactis strains or 300 g/d plain yogurt daily for 12 weeks and those in the control group would receive similar amounts of plain yogurts. Weight, height, and waist circumference will be measured at study baseline and after the intervention. Biochemical indicators including plasma glucose, serum insulin, lipid profile, liver markers (ALT, AST and GGT) will be examined at study baseline and at the end of the trial. Insulin resistance and insulin sensitivity will be determined using the HOMA-IR and QUICKI equation. The degree of steatosis and hepatic fibrosis will also be assessed at the beginning and end of the intervention by the same gastroenterologist using elastography with fibroscan.

Discussion
Probiotics have been suggested as a new strategy in the management of NAFLD. Their effects might be mediated through intestinal microbiota modification and production of short-chain fatty acids. Consumption of probiotic-enriched foods, rather than their supplements, might be a cost-effective method for long-term use in these patients. In case of finding the beneficial effects of probiotic yogurt consumption in the current clinical trial, its inclusion in the dietary plan of NAFLD patients can be recommended.
Trial registration This clinical trial was registered in Iranian Registry of Clinical Trials (www.irct.ir) at 2021-04-19 with code number of IRCT20210201050210N1.
Thrombospondin-2 holds prognostic value and is associated with metastasis and the mismatch repair process in gastric cancer
Authors: Chu Xiao-dong , Lin Zheng-bin , Huang Ting , Ding Hui , Zhang Yi-ran , Zhao Zhan , Huangfu Shu-chen , Qiu Sheng-hui , Guo Yan-guan , Chu Xiao-li , Pan Jing-hua , Pan Yun-long 
Published: March 2022

Abstract
Background
This study aims to investigate thrombospondin 2 (TSP2) expression levels in gastric cancer (GC) and determine the relationship between TSP2 and clinical characteristics and prognosis.

Methods
The online database Gene Expression Profile Interactive Analysis (GEPIA) was used to analyse TSP2 mRNA expression levels in GC. The Kaplan–Meier plotter prognostic analysis tool was used to evaluate the influence of TSP2 expression on clinical prognosis in GC patients. TSP2 expression levels were analysed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. The relationship between the clinicopathological characteristics and prognosis of GC patients was assessed. Transwell experiments were used to evaluate the effect of TSP2 on HGC27 and AGS cell invasion and migration. The EdU experiment was used to detect the effect of transfection of TSP2 on cell proliferation, and the flow cytometry experiment was used to detect the effect of TSP2 on cell apoptosis and the cell growth cycle. Western blotting (Wb) technology was used to detect MMP, E-cadherin, N-cadherin, Vimentin, Snail, AKT, PI3K, and VEGF protein expression in HGC27 cells.

Results
Compared with normal tissues, TSP2 mRNA expression in GC was significantly upregulated and was closely related to the clinical stage of GC. High TSP2 expression significantly affected the OS, FP and PPS of patients with GC. Among these patients, TSP2 expression levels did not affect the prognosis of patients with GC in the N0 subgroup but significantly affected the prognosis of patients with GC in the N (1 + 2 + 3) subgroup. TSP2 protein expression levels were significantly higher in GC tissue compared with normal tissues (P < 0.01). The overall survival (OS) and relapse-free survival (RFS) of patients with high TSP2 expression were lower than those of patients with low TSP2 expression. Cells transfected with the TSP2-silencing sequence exhibited increased apoptosis and inhibition of proliferation, migration and invasion. AKT and PI3K expression in cells was significantly downregulated (P < 0.01). AKT, PI3K and VEGF expression in cells transfected with the TSP2 silencing sequence was significantly reduced. Proliferation, migration, invasion ability, and TSP2 expression levels significantly correlated with mismatch repair genes, such as PMS2, MSH6, MSH2, and MLH1 (P < 0.05).

Conclusion
TSP2 expression is significantly increased in GC. TSP2 expression is closely related to metastasis and the mismatch repair process in GC patients and affects GC patient prognosis. The mechanism may involve regulating gastric cancer cell proliferation and migration by modulating the VEGF/PI3K/AKT signalling pathway. TSP2 is a potential marker and therapeutic target for the prognosis of GC patients.