bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of Cx-43 Hemichannels Induces the Generation of Ca2+-Oscillations in White Adipocytes and Stimulates Lipolysis.
Authors: Turovskaya Maria , Turovsky Egor 
Published: March 2021

Abstract
With fluorescence microscopy, it was revealed that a decrease in the concentration of extracellular calcium ([Ca2+]ex) results in two types of Ca2+-responses in white adipocytes: Ca2+-oscillations and transient Ca2+-signals. Activation of connexin hemichannels is involved in the mechanism of generation of Ca2+-oscillations, since the blockers of connexin hemichannels - carbenoxolone, octanol and proadifen, as well as Cx43 gene knock-down lead to complete suppression of these signals. TIRF microscopy confirmed activation of Cx-43 in response to the reduction of [Ca2+]ex. In response to the activation of Cx-43, the secretion of ATP-containing vesicles from adipocytes occurs. And this ATP release is suppressed in adipocytes along with the Cx43 gene knock-down and is inhibited by Bafilomycin A1, a vacuolar ATPase inhibitor. At the level of intracellular signaling, the generation of Ca2+-oscillations in white adipocytes in response to a decrease in [Ca2+]ex takes place due to the mobilization of Ca2 + ions from the thapsigargin-sensitive Ca2+-pool in the endoplasmic reticulum via IP3R as a result of the activation of P2Y1 purinergic receptors and the phosphoinositide signaling pathway. Such paracrine activation of white adipose tissue in response to the opening of Cx43 hemichannels leads to local signal propagation and regulation of gene expression. At 24 hours after activation of Cx-43 and generation of Ca2+-oscillations in white adipocytes, there is a change in the expression of key genes involved in the regulation of lipolysis, which is accompanied by a decrease in the number of adipocytes that contained lipid droplets. Meanwhile, inhibition or knock-down of Cx-43 leads to inhibition of lipolysis and accumulation of lipid droplets. In this study, we elucidate and research the mechanism of generation of Ca2+-oscillations in white adipocytes in response to decreased concentration of Ca2 + ions in the external environment and show the correlation between periodic Ca2+-modes and lipolysis/lipogenesis balance regulation.
Insulin Resistance and Muscle Weakness Are Synergistic Risk Factors for Silent Lacunar Infarcts: the Bunkyo Health Study: a Cross Sectional Study
Authors: someya Yuki , Tamura Yoshifumi , Kaga Hideyoshi , Sugimoto Daisuke , kadowaki Satoshi , Suzuki Ruriko , Aoki Shigeki , Hattori Nobutaka , Motoi Yumiko , Shimada Kazunori , Daida Hiroyuki , Ishijima Muneaki , Kaneko Kazuo , Nojiri Shuko , Kawamori Ryuzo , Watada Hirotaka 
Published: March 2021

Abstract
Background: Previous studies showed that insulin resistance and reduced muscle strength are risk factors for silent lacunar infarcts, but it is unclear whether they are still independent risk factors when adjusted for each other. In addition, the effect of their combination on silent lacunar infarcts is completely unknown.Methods: We evaluated silent lacunar infarcts, insulin sensitivity, and knee extensor muscle strength by magnetic resonance imaging, PREDIM (an index for insulin sensitivity), and dynamometer, respectively, in 1531 elderly people aged 65–84 years living in an urban area of Tokyo. Results: Among the study subjects, 251 (16.4%) had silent lacunar infarcts. Impaired insulin sensitivity (High; 1.00 [reference], Medium; 1.53 [95% confidence interval (CI): 0.94-2.48], Low; 1.86 [95%CI: 1.02-3.39], p for trend 0.047) and reduced muscle strength (High; 1.00 [reference], Medium; 1.40 [95%CI: 0.98-2.02], Low; 1.49 [95%CI: 1.04-2.15], p for trend 0.037) were independently associated with increased risk for silent lacunar infarcts in the fully adjusted model. In terms of combined, subjects classified as having the lowest insulin sensitivity and lowest strength were 4.33 times (95%CI: 1.64-11.45) more likely to have a silent lacunar infarct than those classified as having the highest insulin sensitivity and highest strength.Conclusions: Impaired insulin sensitivity and reduced muscle strength were independently associated with higher risk of silent lacunar infarcts in elderly subjects, and their combination synergistically increased this risk.
A First-in-human Phase I Study of TAS0728, an Oral Covalent Binding Inhibitor of HER2, in Patients With Advanced Solid Tumors With HER2 or HER3 Aberrations.
Authors: Piha-Paul Sarina A , Azaro Analía , Arkenau Hendrik Tobias , Oh Do-Youn , Galsky Matthew D , Pal Sumanta Kumar , Hamada Kensuke , He Yaohua , Yamamiya Ikuo , Benhadji Karim , Hollebecque Antoine 
Published: March 2021

Abstract
TAS0728 is an oral covalent binding inhibitor of human epidermal growth factor receptor 2 (HER2). A first-in-human open-label, dose-escalation, phase I study (NCT03410927) was initiated to investigate the safety and dose-limiting toxicity (DLT) and to determine the maximum tolerated dose (MTD) and/or recommended phase II dose of TAS0728 in adults with advanced solid tumors with HER2 or HER3 overexpression, amplification or mutation. In total, 19 patients received TAS0728 at escalating doses from 50 to 200 mg BID for 21-day cycles. Following escalation of the dose to 200 mg BID, a total of two DLTs were observed, both cases of Grade 3 diarrhea (lasting >48 hours and not responsive to aggressive antidiarrheal treatment). Following de-escalation of the dose to 150 mg BID, another DLT of Grade 3 diarrhea was observed in one patient. Additionally, at 150 mg BID, one patient had a fatal cardiac arrest after receiving 1 cycle (21 days) of TAS0728. The etiology of the cardiac arrest event was not clear, however causal relationship to TAS0728 could not be excluded due to the temporal association observed. Partial responses were observed in 2 of 14 patients evaluable for TAS0728 treatment response. The study was stopped due to unacceptable toxicity during the dose-escalation as the overall risk-benefit ratio no longer favored the dose level being tested, therefore the MTD was not determined. ClinicalTrials.gov registration number: NCT03410927; registered on January 25, 2018.
Underestimation of Luminal Eosinophilia by Quantitative Sputum Cytometry
Authors: Kjarsgaard Melanie , Adatia Adil , Bhalla Anurag , LaVigne Nicola , Radford Katherine , Huang Chynna , Mukherjee Manali , Nair Parameswaran 
Published: March 2021

Abstract
Rationale: On Wright-stained sputum cytospins, eosinophil differential of >1.2% is considered abnormal and ≥3% clinically relevant. We hypothesized that failure to consider free eosinophil granules (FEG), and the re-emergence of eosinophilia (at ≥1.2 and ≥2.3%) underestimate the prevalence of the eosinophilic phenotype.Methods: This is a retrospective analysis of our Institutional Review Board-approved clinical sputum database. Of the 24,176 examinations, 17,693 had viable cell counts from 9570 patients (6604 on one occasion, 2967 with two or more) with various airway diseases. In all samples, FEGs were semi-quantified to estimate the prevalence of eosinophilia at <1.2 and <2.3%. In those patients with sputum examined on more than one occasion, subsequent results identified re-emergence of eosinophilia at ³1.2 and ³2.3%.Results: Of those with intact cell counts (n=15,278), 8562 (56.0%) and 9690 (63.4%) would have been classified as clinically non-relevant eosinophilia of <1.2% and <2.3% respectively. Among those with two or more intact cell counts, 1142 (38.5%) and 1083 (36.5%) of samples had re-emergence of eosinophilia (at 1.2 and 2.3%), either when a previous neutrophilia resolved (n= 218/19.1%, n=312/28.8%) or due to a reduction in the dose of corticosteroids (n=634/21.4%, n=666/22.4%) with no significant differences between groups (p=0.018). There was a significant difference between the proportions of eosinophilic versus non-eosinophilic at 1.2 and 2.3%, using the presence of FEG and the non-intact cell count (p<0.001).Conclusions: A total of 3180 (32.8%) samples identified as non-eosinophilic, had clinically relevant airway eosinophilia that would not have been identified if the phenotypic classification was limited to ≥2.3% intact eosinophils on one occasion. This underestimation is likely to be significantly more if other means of airway eosinophilic activity were included and if mast cell activity and lymphocyte numbers, (not routinely quantified by sputum cytometry), could be contributing to the under-appreciation of airway T2 inflammatory processes.
An investigation on discharge servo parameters and machining servo mode optimization of MS-WEDM
Authors: Ma Huliang , Wang Yanqing , Lv Ming , Yang Shengqiang 
Published: March 2021

Abstract
Increasing the machining efficiency of middle speed wire electrical discharge machining (MS-WEDM) is usually through optimizing process parameters, but the discharge servo parameters of the servo controller can also be optimized to achieve the same purpose. This paper develops a multi-mode servo controller for MS-WEDM to investigate discharge servo parameters. Firstly, the structure and control principle of the servo controller are introduced, and the core functions are described in detail. Secondly, it introduces the discharge servo parameters that can be optimized: gap state threshold and feedback period. At the same time, the platform specifications and parameters for optimization experiments are introduced. Thirdly, the experimental scheme and result analysis of parameter optimization are described, and the optimized parameters are obtained. Finally, different machining experiments are carried out for the multi-mode of the servo controller to investigate the effectiveness and practicability of the different machining servo modes. In the parameter optimization and machining experiments, the recording function of the servo controller was used to draw the speed curve, and the servo response effects of different servo modes was obtained.
Influence of Mercury Exposure During Pregnancy to Neurodevelopmental Disorder: A Systematic Review Protocol
Authors: Nasruddin Nhelvy Kumala , Amqam Hasnawati , Wirayuda Agus Bintara Wirayuda , Natsir Muh. Fajaruddin , Syamsuar Syamsuar 
Published: March 2021

Abstract
Background: The general population might expose to Hg through various pathways. Prenatal or postnatal exposure to mercury might affect the fetus's neurodevelopment and then further affect the growth and development of the children. There are many reports on mercury exposure, but systematic reviews to conclude the result are still limited, particularly concerning pregnancy. Previous studies focus on one exposure path to Hg and biomarker. The objective is to systematically summarize the relevant records from systematic studies on the relationship between the exposure pattern during pregnancy to pregnant women's Hg concentration and neurodevelopmental disorder that occurred in the children.Method: We will search online databases (Google Schoolar, PUBMED, Sciencedirect, Proquest, Web of Science, Springerlink, DOAJ (Directory of Open Access Journals) and EBSCO MEDLINE) and reference lists of included articles. Two reviewers will independently screen the titles and abstracts and select the research involving pregnant women with mercury exposure and neurodevelopmental disorder fetus or children. These reviewers will also independently extract and manage the obtained data using a data extraction form that will cover information on characteristic, exposure, and outcomes. Meta-analysis will also be applied when homogeneous group of studies found.Discussion: This study will describe the available epidemiological evidence and summarise prevalence and incidence rates of mercury exposure and neurodevelopmental disorder. Mean difference of mercury level will be also presented. A better understanding of the relationship between mercury exposure and any neurodevelopmental disorder form will be helpful in the development of guidelines for mercury exposure management.Systematic review registration: It has been submitted to PROSPERO on February, 10th 2021.
Prevalence of intestinal parasitic infection and its associated factors among children in Puducherry, South India: A community-based study
Authors: Jeyaram Suganya , Saya Ganesh Kumar , Rajkumari Nonika , Ulaganeethi Revathi , Roy Pritam Kumar , Mathavaswamy Vijayageetha 
Published: March 2021

Abstract
There is paucity of studies at community level on prevalence of intestinal parasitic infection among under eighteen years age group. This cross-sectional community-based research aimed to determine the prevalence of intestinal worm infections and its associated risk factors among 1 to 18 years age group in Puducherry, India. Sociodemographic, behavioral and other associated factors were collected using a structured questionnaire. One stool sample was collected from each participant and examined using direct (saline/iodine wet mount) and concentration (floatation/sedimentation) microscopic techniques. Log binomial regression analysis was used to find the factors independently associated with intestinal parasitic infection. Of 187 participants who provided the stool sample, 25 (13.4%) had at least one of the parasitic infections and among them 12 (6.4%) had Soil Transmitted Helminth infection (STH) and 13 (6.9%) had intestinal protozoan parasites. Parasitic infection is marginally higher among 1 to 7 years age group (14.4%) compared to 8 to 18 years age group (12.1%). After adjusting for confounding, urban residence (APR = 3.3, 95% CI: 1.4-8.0) and open-air defecation (APR = 3.3, 95 % CI 1.4–7.5) were significantly associated with intestinal parasitic infections. One out of eight children had any of the parasitic infection and nearly 50% of parasitic infections were caused by STH. Those children residing in urban areas and practice of open-air defecation had higher prevalence of parasitic infection.
Effect of Prophylactic Ligation of the Thoracic Duct on Long-Term Survival in Patients Undergoing Esophagectomy: A Meta-Analysis
Authors: kun Mei , Chao Ce , Xuanren Long , Chao Ma , Rui Zhou , Bin Wang , Dongmei DI 
Published: March 2021

Abstract
Objective: To evaluate the existing literature by comparing long-term survival between patients who underwent prophylactic thoracic duct ligation (PLG) and non-prophylactic thoracic duct ligation (NPLG) during esophagectomy for esophageal cancer, a meta-analysis of relevant studies was conducted.Background: The effect of PLG and NPLG on the long-term survival in patients undergoing esophagectomy for treatment of esophageal cancer has not been established.Methods: All articles searches were performed in PubMed, Cochrane, Embase, and Web of Science, and the deadline is August 31, 2020. The search terms included esophagectomy AND thoracic duct. The selected articles compared the long-term survival of patients undergoing esophagectomy to treat esophageal cancer with prophylactic thoracic duct ligation (PLG) and non-prophylactic thoracic duct ligation (NPLG). The I2 test and X2 test were used to determine statistical heterogeneity. Publication bias was assessed using the Egger test. The results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs). All data analysis was performed using Stata12.0 software.Result: A total of 4418 patients from eight studies were included in this meta-analysis. Pooled analysis revealed that a high overall survival (OS) was significantly associated with NPLG (HR=0.81, 95% CI: 0.74-0.88, P<.001), while the recurrence- free survival (RFS) and disease-free survival (DFS) were not significantly different (HR=1.02, 95% CI: 0.71-1.45, P<.001). There was no statistical difference in long-term survival among patients with different stages of esophageal cancer, while patients who underwent esophagectomy after 2019 had a better long-term prognosis (HR=0.57, 95% CI: 0.57-0.79). In addition, there was no significant difference in prognosis and survival between patients in Japan and China based on regional analysis.Conclusions: Our meta-analysis showed that NPLG was associated with better long-term survival. Thus, we should preserve the thoracic duct during esophageal cancer surgery.
IDH1R132H Mutation Inhibits the Proliferation and Glycolysis of Glioma Cells by Regulating the HIF-1α/LDHA Pathway
Authors: Li Hailong , Wang Shuwei , Wang Yonggang 
Published: March 2021

Abstract
Background: This study aims to explore the role and underlying mechanism of the IDH1R132H in the growth, migration, and glycolysis of glioma cells.Methods: The alternation of IDH1, HIF-1α, and LDHA genes in 283 LGG sample (TCGA LGG database) was analyzed on cBioportal. The expression of these three genes in glioma tissues with IDH1R132H mutation or IDH1 wild type (IDH1-WT) and normal brain tissues was also assessed using immunohistochemistry assay. In addition, U521 glioma cells were transfected with IDH1-WT or IDH1R132H to explore the role of IDH1 in the proliferation and migration of glioma cells in vitro. Cell growth curve, Transwell mitigation assay, and assessment of glucose consumption and lactate production were conducted to evaluate the proliferation, migration, and glycolysis of glioma cells.Results: The expression of HIF-1α and LDHA in IDH1R132H mutant was significantly lower than that in glioma cells with wild type IDH1 (P<0.05). IDH1R132H inhibited the proliferation and glycolysis of U521 glioma cells.Conclusion: The IDH1 mutation IDH1R132H plays an important role in the occurrence and development of glioma through inhibiting the expression of HIF-1α and glycolysis.
A Preliminary Study of Constructing Tissue Engineered Oral Mucosa
Authors: Zhang Qin , Tian Yu-Jing , Ding Tao , Femg De-Hong 
Published: March 2021

Abstract
Background: Adipose derived stem cells (ADSCs) have a great potential for tissue-engineering purposes, and they may be introduced in oral mucosa tissue engineering for urethroplasty. This study was aim to develop a tissue-engineered oral mucosa through seeding oral keratinocytes (OKs) and adipose derived stem cells (ADSCs) on small intestine submucosa (SIS). Methods: SIS was obtained from porcine small intestine, and OKs and ADSCs were obtained from canine sources and were cultured and expanded in vitro. The two cell lines were seeded on the two surfaces of the SIS, and the cell-scaffold compound graft was cultured in an air fluid level for 1 week.Results: The SIS exhibited a porous membrane, and no cells were found through HE staining. The model cultured with OK-SIS only formed a thin and loose epithelium. Whereas the model cultured with OK-SIS-ADSC was much thicker and denser. Conclusion: The co-cultured of ADSC and OK grew well on the SIS in which the OKs formed a multilayer of epithelium. So it is feasible to construct a tissue-engineered oral mucosa graft with ADSCs, OKs and SIS. The ADSCs contribute to a thicker epithelium formation.
Treatment of Posterolateral Tibial Plateau Fractures With a Rotational Support Plate and Special Pressurizer: a Technical Note and 12 Cases&nbsp;
Authors: Chen Yu-Feng , Ren Dong , Geng Lin-Dan , Yao Shuang-Quan , Song Zhao-Hui , Guang Liang , Wang Tian-Ci , Wang Peng-Cheng 
Published: March 2021

Abstract
Background: Posterolateral tibial plateau fractures are uncommon fractures and challenging to treat. Although there are many surgical approaches and fixation methods for the treatment of these fractures, all of these methods have limitations. We designed a new rotational support plate (RSP) and a special pressurizer that can fix the fracture directly via the anterolateral approach. This method is advantageous because it leads to little trauma, involves a simple operation and has a reliable fixation effect. This study details the technique of treating these fractures with the RSP and special pressurizer and provides the outcomes.Methods: From May 2016 to January 2019, the data of 12 patients with posterolateral tibial plateau fractures treated with the RSP and special pressurizer in our hospital were retrospectively analysed. Postoperative rehabilitation was advised, knee X-rays were taken at follow-ups, and fracture healing, complications, and knee range of motion were assessed. The Hospital for Special Surgery (HSS) knee score was used to evaluate knee function at the last follow-up.Results: The average follow-up time of all patients was 16.5 months (range, 12-25 months). The average bony union time was 3.2 months (range, 3-4.5 months). At the last follow-up, the average knee range of motion was 138° (range, 107°-145°). The average HSS score was 91 (range, 64-98). Skin necrosis, incision infections, and fixation failure did not occur during the follow-up period.Conclusions: With our newly designed RSP and special pressurizer, posterolateral tibial plateau fractures can be easily and effectively reduced and fixed through the anterolateral approach, which serves as a novel treatment for posterolateral tibial plateau fractures.
iPSC-Induced Neurons with the V337M MAPT Mutation are Selectively Vulnerable to Caspase-Mediated Cleavage of Tau and Apoptotic Cell Death
Authors: Theofilas Panos , Wang Chao , Butler David , Morales Dulce O. , Petersen Cathrine , Ambrose Andrew J. , Chin Brian , Yang Teddy , Khan Shireen , Ng Raymond , Kayed Rakez , Karch Celeste M. , Miller Bruce L. , Gestwicki Jason E. , Gan Li , Temple Sally , Arkin Michelle R. , Grinberg Lea T. 
Published: March 2021

Abstract

Background: Tau post-translational modifications (PTMs) are associated with progressive tau accumulation and neuronal loss in tauopathies, including forms of frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). Tau proteolysis by caspases, including caspase-6, represents an understudied PTM that may increase neurotoxicity and tau self-aggregation. Methods: To elucidate the presence and temporal course of caspase activation, tau cleavage, and neuronal death, we generated two novel epitope (neoepitope) monoclonal antibodies (mAbs) against caspase-6 tau proteolytic sites. We evaluated tau cleavage and response to apoptotic stress in cortical neurons derived from induced pluripotent stem cells (iPSCs) with frontotemporal dementia (FTD)-causing V337M MAPT mutation. We tested the neuroprotective effect of caspase inhibitors in the induced neurons. We also demonstrated the presence of the tau neoepitopes in postmortem brains from an individual with FTD (V337M MAPT) and an individual with AD, compared to a healthy control. Results: FTLD V337M MAPT and AD postmortem brains showed positivity for both cleaved tau mAbs and active caspase-6. Relative to isogenic wild-type MAPT controls, V337M MAPT neurons cultured for 3 months showed a time-dependent increase in pathogenic tau in the form of caspase-cleaved tau and phosphorylated (p)-tau, and higher levels of tau oligomers. Accumulation of toxic tau species in V337M MAPT neurons was correlated with increased vulnerability to pro-apoptotic stress. Notably, this mutation-associated cell death was pharmacologically rescued by inhibition of effector caspases.Conclusions: Culturing iPSC-derived neurons for three months exposes age-related tau pathologies, including caspase-mediated cleavage, that are also observed in human postmortem brains with abnormal tau deposition. Neoepitope antibodies to caspase-cleaved tau may serve as biomarkers of tau pathology. Furthermore, caspases could be viable therapeutic targets for tau pathogenesis in FTLD and other tauopathies.