bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell type-specific orientation and migration responses for a microgrooved surface with shallow grooves
Authors: Nagayama Kazuaki , Hanzawa Tatsuya 
Published: February 2022

BACKGROUND: Directional cell migration due to mechanosensing for in vivo microenvironment, such as microgrooved surfaces, is an essential process in tissue growth and repair in both normal and pathological states. Cell migration responses on the microgrooved surfaces might be reflected by the cell type difference, which is deeply involved in cellular physiological functions. Although the responses are implicated in focal adhesions (FAs) of cells, limited information is available about cell migration behavior on the microgrooved surfaces whose dimensions are comparable with the size of FAs. OBJECTIVE: In the present study, we investigated the cell orientation and migration behavior of normal vascular smooth muscle cells (VSMCs) and cervical cancer HeLa cells on the microgrooved surface. METHOD: The cells were cultured on the PDMS substrate comprising shallow grooves with 2-µm width and approximately 150-nm depth, which indicates the same order of magnitude as that of the horizontal and vertical size of FAs, respectively. The cell migration and intracellular structures were analyzed by live cell imaging and confocal fluorescence microscopy. The intracellular tension was also assessed using atomic force microscopy (AFM). RESULTS: VSMCs presenting well-aligned actin stress fibers with mature FAs revealed marked cell elongation and directional migration on the grooves; however, HeLa cells with nonoriented F-actin with smaller FAs did not. The internal force of the actin fibers was significantly higher in VSMCs than that in HeLa cells, and the increase or decrease in the cytoskeletal forces improved or diminished the sensing ability for shallow grooves, respectively. The results strongly indicated that directional cell migration should be modulated by cell type-specific cytoskeletal arrangements and intracellular traction forces. The differences in cell type-specific orientation and migration responses can be emphasized on the microgrooves as large as the horizontal and vertical size of FAs. CONCLUSION: The microgoove structure in the size range of the FA protein complex is a powerful tool to clarify subtle differences in the intracellular force-dependent substrate mechanosensing.
No Higher Risk-Seeking Tendencies or Altered Self-Estimation in a Social Decision-Making Task in Patients with Parkinson’s Disease
Authors: Zapf Alexandra C. , Folkerts Ann-Kristin , Kahler Larissa , Schnitzler Alfons , Reker Paul , Barbe Michael T. , Florin Esther , Kalbe Elke 
Published: February 2022

Background: Parkinson’s disease (PD) has been associated with a tendency towards more risky decisions. However, the commonly used paradigms typically neglect the social context. Objective: Here, we investigated social decision-making and self-estimation in a competitive experimental task. Methods: A computerized experimental setting was used in which 86 PD patients (age = 66.5 [50–79], 62.8% male, H&Y = 2 [1.5–3]) and 44 healthy controls (HC; age = 67 [54–79], 54.4% male) in groups of four performed mathematical addition tasks in which they were asked to calculate as many sums as possible in five minutes. Participants had to choose their preferred compensation scheme (“piece rate” versus “tournament”) and retrospectively rank their performance in comparison to the suspected performance of the others. A comprehensive neuropsychological test battery was also conducted. Results: No significant difference was found in overall social decision-making and self-estimation between PD patients and HC. However, for those individuals who made inadequate decisions, PD patients engaged in significantly more risk-averse and HC in more risky decisions. Concerning those inadequate decisions, the PD patients made more extreme decisions (severity of social decision-making) in both directions (risk-averse, risk-seeking). Conclusion: Our data indicate that social decision-making behavior and self-estimation are largely intact in PD patients with mild to moderate disease stages and intact global cognition, executive functions, and social cognition. Future studies with more heterogeneous PD samples regarding their neuropsychological profile will have to examine at which state social decision-making may be affected and by which factors this behavior might be influenced.
Caffeine citrate effects on gastrointestinal permeability, bacterial translocation and biochemical parameters in newborn rats after long-term oral administration
Authors: Bouabsa Foufa , Tir Touil Aicha , Al Zoubi Mazhar Salim , Chelli Nadia , Leke André , Meddah Boumediene 
Published: February 2022

BACKGROUND: Caffeine is a potent central and respiratory acting agent used in neonatology to treat apnea in premature newborns. OBJECTIVE: This study investigates the effects of caffeine orally administered to newborn rats on gastrointestinal permeability, bacterial translocation and different biochemical parameters. METHODS: Newborn rats were divided into different groups ( N = 06). The treated newborn rats were orally administered with standard caffeine doses (12 mg/kg per day), and the control groups received a placebo. The animals were weighed daily until sacrifice. Blood samples, mesenteric lymph nodes (MLN) and organs were aseptically collected. Furthermore, different biochemical (D-Lactate) and oxidative stress biomarkers (MDA, CAT, SOD and GSH) were examined. Microbiological analyses were performed to assess microbiota alterations and bacterial translocation. RESULTS: Preliminary results showed that caffeine administration decreased the level of bacterial translocation over time. The treatment reduced plasma D-lactate levels ( p < 0.05). Additionally, caffeine induced a disturbance in the concentrations of biochemical parameters and oxidative stress biomarkers. Indeed, liver enzymes (AST and ALT) were significantly ( p < 0.05) risen after caffeine treatment. Glutathione (GSH) levels were significantly higher in caffeine treated groups (75.12±0.32; 51.98±1.12 U/mg; p < 0.05) comparing to control ones (40.82±0.25; 42.91±0.27 U/mg; p < 0.05) in the ileum and the colon, respectively. CONCLUSIONS: Thus, besides improving gastrointestinal permeability, our data show that caffeine has beneficial effects on the intestinal antioxidant system.
Comparison of Five Different Criteria for Diagnosis of Subclinical Hypothyroidism in a Large-Scale Chinese Population
Authors: Zheng Yan-song , Dong Sheng-yong , Gong Yan , Wang Jia-hong , Wang Fei , Zeng Qiang 
Published: February 2022

BackgroundSeveral different criteria for subclinical hypothyroidism (SCH) have been used in the literature, but the performance of these criteria was unknown.ObjectiveThis retrospective study was to evaluate the diagnostic criteria for SCH.MethodsEligible participants were based on centration of thyroglobulin antibodies (TG-Ab), thyroid peroxidase antibodies (TPO-Ab), and five thyroid-related hormones including total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH). Euthyroid individuals were identified via specific criteria. Five different SCH diagnostic criteria were compared based on the distributions of those indicators. An appropriate TSH cut-off value was reconsidered.ResultsThe study included 145,015 participants. The number of SCH cases diagnosed using criterion 5 was significantly different compared to the cases diagnosed using criteria 1-4 (P&lt;0.05) and had the highest positive proportions of TG-Ab and TPO-Ab. Analysis of 60,515 subjects with normal other thyroid hormones revealed a median TSH concentration of 2.04 mIU/L, and the P2.5–P97.5 CI was 0.48-7.03 mIU/L. When the threshold for TSH elevation was elevated from ≥4.5 mIU/L to ≥6.50 mIU/L, the number of diagnosed SCH cases decreased from 7.30% to 2.09% and the proportions of positive TG-Ab and TPO-Ab increased from 23.69% and 24.07% to 33.75% and 35.06%, respectively (P&lt;0.01).ConclusionsCombination of an elevated TSH and normal TT3, TT4, FT3, and FT4 concentrations is a must for the diagnosis of SCH. A new TSH threshold should be identified for better patient monitoring and management, according to the real-world characteristics of TSH distribution in Chinese population.
Genetic Analysis of TB Susceptibility Variants in Ghana Reveals Candidate Protective Loci in SORBS2 and SCL11A1 Genes
Authors: Asante-Poku Adwoa , Morgan Portia , Osei-Wusu Stephen , Aboagye Samuel Yaw , Asare Prince , Otchere Isaac Darko , Adadey Samuel Mawuli , Mnika Khuthala , Esoh Kevin , Mawuta Kenneth Hayibor , Arthur Nelly , Forson Audrey , Mazandu Gaston Kuzamunu , Wonkam Ambroise , Yeboah-Manu Dorothy 
Published: February 2022

Despite advancements made toward diagnostics, tuberculosis caused by Mycobacterium africanum (Maf) and Mycobacterium tuberculosis sensu stricto (Mtbss) remains a major public health issue. Human host factors are key players in tuberculosis (TB) outcomes and treatment. Research is required to probe the interplay between host and bacterial genomes. Here, we explored the association between selected human/host genomic variants and TB disease in Ghana. Paired host genotype datum and infecting bacterial isolate information were analyzed for associations using a multinomial logistic regression. Mycobacterium tuberculosis complex (MTBC) isolates were obtained from 191 TB patients and genotyped into different phylogenetic lineages by standard methods. Two hundred and thirty-five (235) nondisease participants were used as healthy controls. A selection of 29 SNPs from TB disease-associated genes with high frequency among African populations was assayed using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Using 26 high-quality SNPs across 326 case-control samples in an association analysis, we found a protective variant, rs955263, in the SORBS2 gene against both Maf and Mtb infections (PBH = 0.05; OR = 0.33; 95% CI = 0.32–0.34). A relatively uncommon variant, rs17235409 in the SLC11A1 gene was observed with an even stronger protective effect against Mtb infection (MAF = 0.06; PBH = 0.04; OR = 0.05; 95% CI = 0.04–0.05). These findings suggest SLC11A1 and SORBS2 as a potential protective gene of substantial interest for TB, which is an important pathogen in West Africa, and highlight the need for in-depth host-pathogen studies in West Africa.
The Follow-Up of Chinese Patients in cblC Type Methylmalonic Acidemia Identified Through Expanded Newborn Screening
Authors: Ling Shiying , Wu Shengnan , Shuai Ruixue , Yu Yue , Qiu Wenjuan , Wei Haiyan , Yang Chiju , Xu Peng , Zou Hui , Feng Jizhen , Niu Tingting , Hu Haili , Zhang Huiwen , Liang Lili , Lu Deyun , Gong Zhuwen , Zhan Xia , Ji Wenjun , Gu Xuefan , Han Lianshu 
Published: February 2022

Objective: The cblC type of combined methylmalonic acidemia and homocystinuria, an inherited disorder with variable phenotypes, is included in newborn screening (NBS) programs at multiple newborn screening centers in China. The present study aimed to investigate the long-term clinical benefits of screening individual.Methods: A national, retrospective multi-center study of infants with confirmed cblC defect identified by NBS between 2004 and 2020 was conducted. We collected a large cohort of 538 patients and investigated their clinical data in detail, including disease onset, biochemical metabolites, and gene variation, and explored different factors on the prognosis.Results: The long-term outcomes of all patients were evaluated, representing 44.6% for poor outcomes. In our comparison of patients with already occurring clinical signs before treatment to asymptomatic ones, the incidence of intellectual impairment, movement disorders, ocular complications, hydrocephalus, and death were significantly different (p &lt; 0.01). The presence of disease onset [Odd ratio (OR) 12.39, 95% CI 5.15–29.81; p = 0.000], variants of c.609G&gt;A (OR 2.55, 95% CI 1.49–4.35; p = 0.001), and c.567dupT (OR 2.28, 95% CI 1.03–5.05; p = 0.042) were independently associated with poor outcomes, especially for neurodevelopmental deterioration.Conclusion: NBS, avoiding major disease-related events and allowing an earlier treatment initiation, appeared to have protective effects on the prognosis of infants with cblC defect.
Establishment and Validation of a Ferroptosis-Related Long Non-Coding RNA Signature for Predicting the Prognosis of Stomach Adenocarcinoma
Authors: Zhang Shuqiong , Zheng Naisheng , Chen Xiaocui , Du Kun , Yang Junyao , Shen Lisong 
Published: February 2022

Background: Ferroptosis is a form of regulated cell death that follows cell membrane damage and mostly depends on iron-mediated oxidative. Long non-coding RNAs (LncRNAs) are associated with the development of a variety of tumors. Till date, LncRNAs have been reported to intervene in ferroptosis. Therefore, we intended to provide a prognostic ferroptosis-related-lncRNA signature in stomach adenocarcinoma (STAD).Methods: We downloaded ferroptosis-related genes from the FerrDb database and RNA sequencing data and clinicopathological characteristics from The Cancer Genome Atlas. Gene differential expression analysis was performed using the “limma” package. We used Cox regression analysis to determine the ferroptosis-related lncRNAs signature with the lowest AIC value. The Kaplan–Meier curve, ROC curve, and nomogram were used to evaluate the prognostic value of the risk score. Gene set enrichment analysis (GSEA) was used to explore the biologic functions of the three ferroptosis-related lncRNAs. LINC01615 expression in gastric cancer cell lines and tissues was measured by real-time PCR. A nuclear-cytoplasmic fractionation assay was used to analyze the subcellular localization for LINC01615. Furthermore, we used bioinformatics to predict potential target microRNAs (miRNAs) of LINC01615 and their target ferroptosis-related mRNAs.Results: Three ferroptosis-related-lncRNA signatures (AP000695.2, AL365181.3, and LINC01615) were identified, and then Kaplan–Meier, Cox regression analyses, and ROC curve confirmed that the ferroptosis-related-lncRNA model could predict the prognosis of STAD. The GSEA indicated that the three ferroptosis-related lncRNAs might be related to the extracellular matrix and cellular activities. LINC01615 is highly expressed in gastric cancer cell lines and tissues. A nuclear-cytoplasmic fractionation assay confirmed that in gastric cancer cell lines, most LINC01615 was enriched in the cytoplasm. Bioinformatics further predicts four potential target miRNAs of LINC01615 and then figured out 26 target ferroptosis-related mRNAs.Conclusion: We established a three-ferroptosis-related-lncRNA model (AP000695.2, AL365181.3, and LINC01615) that can predict the prognosis of STAD patients. We also expected to provide a promising target for LINC01615 for research in the future, which was highly expressed in gastric cancer and cell lines and acted as a ceRNA to get involved in ferroptosis.
Chemokines in Type 1 Diabetes Mellitus
Authors: Pan Xiongfeng , Kaminga Atipatsa C. , Kinra Sanjay , Wen Shi Wu , Liu Hongying , Tan Xinrui , Liu Aizhong 
Published: February 2022

BackgroundPrevious studies suggested that chemokines may play an important role in the formation and mediation of immune microenvironments of patients affected by Type 1 Diabetes Mellitus (T1DM). The aim of this study was to summarise available evidence on the associations of different chemokines with T1DM.MethodsFollowing PRISMA guidelines, we systematically searched in PubMed, Web of Science, Embase and Cochrane Library databases for studies on the associations of different chemokines with T1DM. The effect size of the associations were the standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) of the chemokines concentrations, calculated as group differences between the T1DM patients and the controls. These were summarized using network meta-analysis, which was also used to rank the chemokines by surface under cumulative ranking curve (SUCRA) probabilities.ResultsA total of 32 original studies on the association of different chemokines with T1DM were identified. Fifteen different chemokine nodes were compared between 15,683 T1DM patients and 15,128 controls, and 6 different chemokine receptor nodes were compared between 463 T1DM patients and 460 controls. Circulating samples (blood, serum, and plasma) showed that concentrations of CCL5 and CXCL1 were significantly higher in the T1DM patients than in the controls (SMD of 3.13 and 1.50, respectively). On the other hand, no significant difference in chemokine receptors between T1DM and controls was observed. SUCRA probabilities showed that circulating CCL5 had the highest rank in T1DM among all the chemokines investigated.ConclusionThe results suggest that circulating CCL5 and CXCL1 may be promising novel biomarkers of T1DM. Future research should attempt to replicate these findings in longitudinal studies and explore potential mechanisms underlying this association.
Rhinovirus-Induced Cytokine Alterations With Potential Implications in Asthma Exacerbations: A Systematic Review and Meta-Analysis
Authors: Liew Kong Yen , Koh Sue Kie , Hooi Suet Li , Ng Matthew Kah Lup , Chee Hui-Yee , Harith Hanis Hazeera , Israf Daud Ahmad , Tham Chau Ling 
Published: February 2022

BackgroundRhinovirus (RV) infections are a major cause of asthma exacerbations. Unlike other respiratory viruses, RV causes minimal cytotoxic effects on airway epithelial cells and cytokines play a critical role in its pathogenesis. However, previous findings on RV-induced cytokine responses were largely inconsistent. Thus, this study sought to identify the cytokine/chemokine profiles induced by RV infection and their correlations with airway inflammatory responses and/or respiratory symptoms using systematic review, and to determine whether a quantitative difference exists in cytokine levels between asthmatic and healthy individuals via meta-analysis.MethodsRelevant articles were obtained from PubMed, Scopus, and ScienceDirect databases. Studies that compared RV-induced cytokine responses between asthmatic and healthy individuals were included in the systematic review, and their findings were categorized based on the study designs, which were ex vivo primary bronchial epithelial cells (PBECs), ex vivo peripheral blood mononuclear cells (PBMCs), and human experimental studies. Data on cytokine levels were also extracted and analyzed using Review Manager 5.4.ResultsThirty-four articles were included in the systematic review, with 18 of these further subjected to meta-analysis. Several studies reported the correlations between the levels of cytokines, such as IL-8, IL-4, IL-5, and IL-13, and respiratory symptoms. Evidence suggests that IL-25 and IL-33 may be the cytokines that promote type 2 inflammation in asthmatics after RV infection. Besides that, a meta-analysis revealed that PBECs from children with atopic asthma produced significantly lower levels of IFN-β [Effect size (ES): -0.84, p = 0.030] and IFN-λ (ES: -1.00, p = 0.002), and PBECs from adult atopic asthmatics produced significantly lower levels of IFN-β (ES: -0.68, p = 0.009), compared to healthy subjects after RV infection. A trend towards a deficient production of IFN-γ (ES: -0.56, p = 0.060) in PBMCs from adult atopic asthmatics was observed. In lower airways, asthmatics also had significantly lower baseline IL-15 (ES: -0.69, p = 0.020) levels.ConclusionOverall, RV-induced asthma exacerbations are potentially caused by an imbalance between Th1 and Th2 cytokines, which may be contributed by defective innate immune responses at cellular levels. Exogenous IFNs delivery may be beneficial as a prophylactic approach for RV-induced asthma exacerbations.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=184119, identifier CRD42020184119.
Cannabidiol and Terpene Formulation Reducing SARS-CoV-2 Infectivity Tackling a Therapeutic Strategy
Authors: Santos Susana , Barata Pedro , Charmier Adilia , Lehmann Inês , Rodrigues Suzilaine , Melosini Matteo M. , Pais Patrick J. , Sousa André P. , Teixeira Catarina , Santos Inês , Rocha Ana Catarina , Baylina Pilar , Fernandes Ruben 
Published: February 2022

In late 2019, COVID-19 emerged in Wuhan, China. Currently, it is an ongoing global health threat stressing the need for therapeutic compounds. Linking the virus life cycle and its interaction with cell receptors and internal cellular machinery is key to developing therapies based on the control of infectivity and inflammation. In this framework, we evaluate the combination of cannabidiol (CBD), as an anti-inflammatory molecule, and terpenes, by their anti-microbiological properties, in reducing SARS-CoV-2 infectivity. Our group settled six formulations combining CBD and terpenes purified from Cannabis sativa L, Origanum vulgare, and Thymus mastichina. The formulations were analyzed by HPLC and GC-MS and evaluated for virucide and antiviral potential by in vitro studies in alveolar basal epithelial, colon, kidney, and keratinocyte human cell lines.Conclusions and ImpactWe demonstrate the virucide effectiveness of CBD and terpene-based formulations. F2TC reduces the infectivity by 17%, 24%, and 99% for CaCo-2, HaCat, and A549, respectively, and F1TC by 43%, 37%, and 29% for Hek293T, HaCaT, and Caco-2, respectively. To the best of our knowledge, this is the first approach that tackles the combination of CBD with a specific group of terpenes against SARS-CoV-2 in different cell lines. The differential effectiveness of formulations according to the cell line can be relevant to understanding the pattern of virus infectivity and the host inflammation response, and lead to new therapeutic strategies.