bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracellular expression of arginine deimimase activates the mitochondrial apoptosis pathway through inhibiting cytosolic ferritin and inducing chromotin autophagy
Authors: Feng Qingyuan , Bian Xuzhao , Liu Xuan , Wang Ying , Zhou Huiting , Ma Xiaojing , Quan Chunju , Yao Yi , Zheng Zhongliang
Published: April 2020

Background Based on its low toxicity, arginine starvation therapy has the potential to treat those malignant tumors that can’t be treated by surgery. Arginine deiminase (ADI; EC 3.5.3.6) gene is indicated to be an ideal cancer-suppressor gene. ADI expressed in cytosol displayed higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000)[1]. However, it is still unknown whether cytosolic ADI has the same function mechanism as ADI-PEG20 or other underlying mechanisms in cells. Methods The interaction of ADI and other protein factors was screened by yeast hybrid, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting ferritin light-chain domain (FTL) on mitochondria damage was evaluated by site-directed mutation and flow cytometry. The apoptosis pathway of mitochondria control was analyzed by Western Blot and real-time PCR. The effect of p53 expression on cancer cell death was assessed by siTP53 transfection. The chromatin autophagy was explored by immunofluorescent staining and Western Blot. Results ADI expressed in cytosol inhibited the activity of cytosolic ferritin through interacting with FTL. The inactive mutant of ADI still aroused the apoptosis of some cells through mitochondria damage. Arginine deprivation also induced the expression increase of p53 and p53AIP1, which aggravated cellular mitochondria damage. Chromatin autophagy appeared at the later stage of arginine deprivation. DNA damage came along with the whole process of arginine starvation. Histone 3 (H3) was found in autophagosomes, which implied that cancer cells try to utilize the arginine in histones to survive during arginine starvation. Conclusions Mitochondria damage is the major mechanism for ADI expressed in cytosol to induce cancer cell death. Chromatophagy accumulation not only drives cancer cell to utilize histone arginine but also speeds up cancer cell death at the later time point of arginine deprivation.
Occurrence of anterior uveitis in patients with spondyloarthritis treated with tumor necrosis factor inhibitors: comparing the soluble receptor to monoclonal antibodies in a large observational cohort
Authors: khoury Gisèle , Morel Jacques , Combe Bernard , Lukas Cédric
Published: April 2020

Background: The objective of this study was to compare in real life the occurrence of anterior uveitis in patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA), treated with the soluble-receptor etanercept (ETA) or monoclonal antibodies (mAb). Methods: This was an observational, retrolective study. Patients with SpA who were prescribed anti-TNF agents between 2000 and 2014 were included. The risk of uveitis was interpreted qualitatively (number of subjects with at least one uveitis) and quantitatively (number of uveitis flares for each individual). Models were adjusted for propensity score of receiving preferentially mAbs or ETA.Results: 429 patients were included (302 with SpA and 127 with PsA); 203 received a mAb and 226 ETA as a first TNF-a inhibitor. Probability of uveitis occurring during the first year of treatment was lower with ETA than mAbs but not significantly (odds ratio 0.94 [95% confidence interval 0.35; 2.54], p=0.90, on qualitative analysis and relative risk 0.62 [0.26; 1.46], p=0.27, on quantitative analysis) after adjustment for the propensity score. The over-time risk of uveitis was numerically higher with ETA than mAbs, but the differences were not statistically significant. Conclusion: In this observational study, the risk of uveitis in patients with SpA does not appear to be greater with ETA than mAbs treatment. The occurrence of uveitis in patients receiving an anti-TNF-a agent seems linked more to history of uveitis than the prescribed molecule.
The genome-wide supported CACNA1C gene polymorphisms and the risk of schizophrenia: an updated meta-analysis
Authors: Liu Yongping , Wu Xue , Xia Xi , Yao Jun , Wang Bao-jie
Published: April 2020

Background: The CACNA1C gene was defined as a risk gene for schizophrenia in a large genome-wide association study of European ancestry performed by the Psychiatric Genomics Consortium. Previous meta-analyses focused on the association between the CACNA1C gene rs1006737 and schizophrenia. The present study focused on whether there was a racial difference in the effect of the CACNA1C gene rs1006737 on schizophrenia. rs2007044 and rs4765905 were analyzed for their effect on the risk of schizophrenia. Methods: Pooled, subgroup, sensitivity, and publication bias analysis were conducted.Results: A total of 18 studies met the inclusion criteria, including fourteen rs1006737 studies (15,213 cases, 19,412 controls), three rs2007044 studies (6,007 cases, 6,518 controls), and two rs4765905 studies (2,435 cases, 2,639 controls). An allele model study also related rs2007044 and rs4765905 to schizophrenia. The overall meta-analysis for rs1006737, which included the allele contrast, dominant, recessive, codominance, and complete overdominance models, showed significant differences between rs1006737 and schizophrenia. However, the race-based subgroup analysis for rs1006737 found that the genotypes GG and GG + GA were only protective factors for schizophrenia in European populations. In contrast, the rs1006737 GA genotype only reduced the risk of schizophrenia in Asian populations. Conclusions: Rs1006737, rs2007044, and rs4765905 of the CACNA1C gene were associated with susceptibility to schizophrenia. However, the influence model for rs1006737 on schizophrenia in Asian and European populations demonstrated both similarities and differences between the two populations.
Pretreatment Thrombocytosis as an Independent Predictive Factor for Chemoresistance and Poor Survival in Epithelial Ovarian Cancer
Authors: Nakao Sari , Minaguchi Takeo , Itagaki Hiroya , Hosokawa Yoshihiko , Shikama Ayumi , Tasaka Nobutaka , Akiyama Azusa , Ochi Hiroyuki , Matsumoto Koji , Satoh Toyomi
Published: April 2020

Background Thrombocytosis is related to tumor stage and survival in ovarian cancer in addition to the common complications of malignant diseases, such as anemia and inflammation. The aim of our study was to clarify the precise prognostic impact of pretreatment thrombocytosis in epithelial ovarian cancer. Methods We retrospectively analyzed 280 consecutive patients who were treated for epithelial ovarian cancer at our institution between 2001 and 2011. Results Pretreatment thrombocytosis was observed in 18.9% of all patients and was associated with advanced FIGO stage, primary treatment, operation achievement, histologic subtype, microcytic hypochromic anemia (MHA), and nonmalignant inflammatory condition ( P =0.0018, 0.0028, 0.00050, 0.034, 0.00090 and 0.0022). In the patients who relapsed after primary adjuvant chemotherapy (n=126), thrombocytosis was associated with a shorter treatment-free interval (TFI) ( P =0.0091). The univariate and multivariate analyses revealed that thrombocytosis was independently associated with TFI and MHA ( P =0.021 and 0.0091). Patients with thrombocytosis had worse progression-free survival (PFS) and overall survival (OS) than those without thrombocytosis ( P <0.0001 and <0.0001). The multivariate analyses for prognostic factors demonstrated that thrombocytosis was significant for poor PFS and OS ( P =0.0050 and 0.022) independent of stage, histology, primary treatment, operation achievement, nonmalignant inflammatory condition and MHA. Conclusions The current findings indicate that the detrimental survival impact of pretreatment thrombocytosis in epithelial ovarian cancer may be independent of tumor extent but rather attributed to chemoresistance, further supporting the therapeutic potential of targeting thrombopoietic cytokines in the disease.
Remotely monitoring ecosystem respiration from various grasslands along a large-scale east-west transect across Northern China
Authors: Tang Xuguang , Zhou Yanlian , Li Hengpeng , Yao Li , Ding Zhi , Ma Mingguo , Yu Pujia
Published: April 2020

Background: Grassland ecosystems play an important role in the terrestrial carbon cycles through carbon emission by ecosystem respiration (Re) and carbon uptake by plant photosynthesis (GPP). Surprisingly, given Re occupies a large component of annual carbon balance, rather less attention has been paid to developing the estimates of Re compared to GPP.Results: Based on 11 flux sites over the diverse grassland ecosystems in northern China, this study examined the amounts of carbon released by Re as well as the dominant environmental controls across temperate meadow steppe, typical steppe, desert steppe and alpine meadow, respectively. Multi-year mean Re revealed relatively less CO2 emitted by the desert steppe in comparison with other grassland ecosystems. Meanwhile, C emissions of all grasslands were mainly controlled by the growing period. Correlation analysis revealed that apart from air and soil temperature, soil water content exerted a strong effect on the variability in Re, which implied the great potential to derive Re using relevant remote sensing data. Then, these field-measured Re data were up-scaled to large areas using time-series MODIS information and remote sensing-based piecewise regression models. These semi-empirical models appeared to work well with a small margin of error (R2 and RMSE ranged from 0.45 to 0.88 and from 0.21 to 0.69 g C m-2 d-1, respectively). Conclusions: Generally, the piecewise models from the growth period and dormant season performed better than model developed directly from the entire year. Moreover, the biases between annual mean Re observations and the remotely-derived products were usually within 20%. Finally, the regional Re emissions across northern China's grasslands was approximately 100.66 Tg C in 2010, about 1/3 of carbon fixed from the MODIS GPP product. Specially, the desert steppe exhibited the highest ratio, followed by the temperate meadow steppe, typical steppe and alpine meadow. Therefore, this work provides a novel framework to accurately predict the spatio-temporal patterns of Re over large areas, which can greatly reduce the uncertainties in global carbon estimates and climate projections.
Improvement of a Delayed Swallowing Reflex with Treatment in Advanced Head and Neck Cancer Patients
Authors: Ohkoshi Akira , Kato Kengo , Ogawa Takenori , Nakanome Ayako , Ishii Ryo , Katori Yukio
Published: April 2020

Background: The latency of the swallowing reflex is an important factor causing dysphagia in head and neck cancer patients. Although there are many reports comparing voluntary swallowing function before and after treatment, few studies have focused on the latency of the swallowing reflex, which is a risk factor for pneumonia due to silent aspiration. The aim of this retrospective study was to clarify the changes in the latency of the swallowing reflex before and after treatment.Methods: The latency of the swallowing reflex was quantified using the time from the injection of 1 ml of distilled water into the pharynx through a nasal catheter to the onset of swallowing. Results: The latency time of the swallowing reflex was significantly decreased 3 months after treatment compared to before treatment. A significant reduction was also observed in patients with pharyngeal cancer who underwent chemoradiation therapy.Conclusions: This retrospective study showed that a delayed swallowing reflex improved with treatment in advanced head and neck cancer patients.Trial registration number: The Institutional Review Board of Tohoku University Hospital (Number 2014-1-274).
Early ghrelin intervention protects against the progressive dopaminergic neuron loss in Parkinson’s disease mice
Authors: Jiao Lingling , Jia Fengju , Du Xixun , Zhang Pei , Li Yong , Zhu Dexiao , Tang Tingting , Jiao Qian , Jiang Hong
Published: April 2020

BackgroundGhrelin has been identified as a multifunctional peptide that has many potential applications for the treatment of various diseases, including Parkinson’s disease (PD). However, little is known about the pathophysiological function and mechanism of ghrelin in PD. MethodELISA was used for detecting plasma total and active ghrelin levels, dopamine (DA) content was measured by HPLC-ECD, immunofluorescence staining and Western blot were used to detect protein expressions, and cytokine was tested by Bio-PlexPro™ assay.ResultsHere, we reported a PD model that overexpressing mutant human A53T α-syn mice exhibited a decreased levels of total and active ghrelin in plasma, fewer tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN), lower DA content in the striatum (Str), and less weight. These changes were rescued by the subcutaneous administration of low-dose ghrelin. Interestingly, ghrelin had no effect on weight gain in wild-type mice but improved weight loss in A53T mice. In addition, ghrelin administration also attenuated the decreased Bcl-2/Bax ratio and superoxide dismutase1 (SOD1) protein levels and inhibited the upregulation pro-inflammatory cytokine interleukin-6 (IL-6) and tumour necrosis factor a (TNFa) and the downregulation of anti-inflammatory cytokine IL-10. In addition, ghrelin inhibited the increase in Iba1-positive cells in mice with PD.ConclusionsHere we reported that ghrelin had a protective effect on dopaminergic neurons and against weight loss from PD via anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms, which suggested that ghrelin could be an endogenous protective factor that prevents the onset or the progression of PD.
Urinary exosomal CA9 as a liquid biopsy for diagnosis of bladder cancer
Authors: Wen Jin , Li HanZhong , Li Guo R
Published: April 2020

BackgroundThe purpose of this study was to assess the possibility of using urinary exosomal CA9 as a new liquid biopsy for the diagnosis of bladder cancer.Methods158 bladder cancer patients and 88 healthy subjects were included in the study. An in-house technique was developed to isolate urinary exosomes. The expression level of CA9 was detected by RT-qPCR. The diagnostic performance of urinary urinary exosomal CA9 was evaluated.ResultsThe level of urinary exosomal CA9 was significantly higher in bladder cancer group than in healthy control group (p < 0.001). The area under the ROC curve was 0.806 (95% CI: 0.753–0.858). With an optimal cutoff of 0.433, the sensitivity was 68.35% and the specificity was 85.23% for the diagnosis of bladder cancer.ConclusionsThe urinary exosomes were abundant in the urine of cancer patients. CA9 could be detectable in urinary exosomes. The urinary exosmal CA9 may present a new liquid biopsy for the diagnosis of bladder cancer.*Contributed equally to this work
The effect of maternal education on preventive behaviors of iron deficiency anemia in children: A randomized controlled trial
Authors: Larijani Nayereh Mohammadzadeh , khorsandi Mahboobeh , Shamsi Mohsen , Ranjbaran Mehdi
Published: April 2020

BackgroundIron deficiency anemia (IDA) is the most common hematological disease in infancy and childhood. Therefore, it is necessary to provide maternal education using models that identify factors affecting behavior. Hence, this study was conducted to evaluate the effect of maternal education based on the health belief model (HBM) on preventive behaviors of IDA in children aged 1–6 years in rural health centers of Babol, Mazandaran Province, Iran in 2015.MethodsIn this quasi-experimental study, 119 mothers were selected through multi-stage random sampling and divided into two groups of intervention and control. The data collection tool was a researcher-made questionnaire whose validity and reliability were studied and confirmed. A pretest was conducted in both groups. Need assessment was done according to the pretest results, and educational intervention was performed in four educational sessions in the intervention group. The same questionnaire was applied for posttest three months after the intervention. SPSS version 20 was used for data analysis.ResultsThere was no significant difference in the mean scores of awareness, HBM constructs, and performance of the mothers between the two groups before the intervention (P < 0.05) while the difference was significant after the intervention (P < 0.001). The mean score of performance, increased significantly from 80.84 to 88.68 in the intervention group after the intervention (P < 0.001).ConclusionEducational intervention, according to the HBM based on a primary needs assessment effectively improves maternal performance about IDA prevention in children. Therefore, it is suggested that these interventions replace conventional educational programs.Trial registration: This trial has been registered at IRCT, IRCT2014082118892N1. Registered on 2014-11-23, https://en.irct.ir/trial/17015
Characterization of Codon Usage Pattern in Novel Coronavirus SARS-CoV-2
Authors: Hou Wei
Published: April 2020

The outbreak of COVID-19 due to a novel coronavirus SARS-CoV-2 has posed significant threats to international health. In this study we perform bioinformatic analysis to take a snapshot of the codon usage pattern of SARS-CoV-2 and uncover that this novel coronavirus has a relatively low codon usage bias. The information from this research may not only be helpful to get new insights into the evolution of SARS-CoV-2, but also have potential value for developing coronavirus vaccines.
CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK and AP-1 pathway
Authors: Chen PoChun , Hou Sheng-Mou , Liu Ju-Fang
Published: April 2020

Background
Osteoarthritis (OA) and rheumatoid arthritis (RA) are common joint disorders that are considered to be different diseases due to their unique molecular mechanisms and pathogenesis. Chemokines and their corresponding receptors have been well-characterized in RA progression, but less so in OA pathogenesis.
Methods
The human primary synovial fibroblasts (SFs) were obtained from human OA and RA tissue samples. The Western blot and qPCR were performed to analyze expression levels of CXCL1, as well as CXCL-promoted IL-6 expression in both OASFs and RASFs. The signal cascades that mediate the CXCL1-promoted IL-6 expression were identified by using chemical inhibitors, siRNAs and shRNAs.
Results
Here, we found that both diseases feature elevated levels of CXCL1 and interleukin (IL)-6, an important proinflammatory cytokine that participates in OA and RA pathogenesis. In OASFs and RASFs, CXCL1 promoted IL-6 expression in a dose- and time-dependent manner. In OASFs and RASFs overexpressing CXCL1 or transduced with shRNA plasmid, IL-6 expression was markedly upregulated. CXCR2, c-Raf and MAPKs was found to regulate CXCL1-induced IL-6 expression in OASFs and RASFs. Finally, CXCL1 triggered the transcriptional activities of c-Jun (which regulates the expression of proinflammatory proteins) in OASFs and RASFs.
Conclusions
Our present work suggests that the CXCL1/CXCR2 axis helps to orchestrate inflammatory responses in OA and RA SFs.
Study on tsunami-resistance of a reinforced soil wall based on water tank experiment
Authors: Kuribayashi Kentaro , Hara Tadashi , Hazarika Hemanta , Tsuji Shinichiro , Kuroda Shuichi
Published: April 2020

Background：The 2011 off the pacific coast of Tohoku earthquake (Mw=9.0) caused great damage of geotechnical structures in the vicinity of the eastern coasts. In contrast, many of reinforced soil walls constructed along the coast were less damaged by the tsunami. In this study, a model test using water tank is conducted to evaluate the behavior of a reinforced soil wall under strong water flow and water pressure like tsunami as an experimental prototype. The scale of model is 1/40, the height of wall is 25cm and the water level is 20cm, supposing that a tsunami hit the wall whose height is 10m in a full-scale without overflowing. Water flow hit the wall keeping its velocity and level. When the water penetrates into the backfill soil until ground water level is same as the level of water flow, the water was stopped and drained out of the tank.In this study, 2 test cases were conducted. One is a sound wall, and the other is a wall with some opening of the front panels which simulates the gap of the wall due to residual settlement after an earthquake.Results：The sound wall has no deformation during and after the tsunami action. In the wall with some opening, around 30 minutes after the start of the tsunami action, the wall panel showed gradual deviations such as slippage. In all cases, the pore water pressure in the backfill soil rises with seepage of the water, but the soil was not completely saturated.Conclusions：It was found that a reinforced soil wall does not have large deformation unless there are some opening of the front panels and the backfill soil flow out of the wall. This result shows that reinforced soil wall does not collapse by seepage to the backfill soil or wave force of tsunami, but collapses by backfill soil flowing out from wall surface. Our results support that a reinforced soil wall has high tsunami-resistance. Given this information, it is necessary to prevent the wall from making some opening and prevent the backfill soil from flowing out.
Fast Fluorine-18 Labeling and Preclinical Evaluation of Novel Mucin1 and its Folate Hybrid Peptide conjugate for Targeting Breast Carcinoma.
Authors: aljammaz ibrahim , Al-Otaibi Basem , Al-Malki Yousif , Abousekhrah Abdel , Okarvi S. M.
Published: April 2020

Background: There is a need to develop new and more potent radiofluorinated peptide and their hybrid conjugates for multiple-receptors targeting properties that overexpress on many cancers. Methods: We have synthesized MUC1-[18F]SFB and MUC1-FA-[18F]SFB hybrid conjugates using a convenient and one-step nucleophilic displacement reactions. In vitro cell binding and in vivo evaluation in animals were performed to determine the potential of these radiolabeled compounds. Results: Radiochemical yields for MUC1-[18F]SFB and MUC1-FA-[18F]SFB conjugates were greater than 70% in less than 30 min synthesis time. Radiochemical purities were greater than 97% without HPLC purification, which make these approaches amenable for automation. In vitro studies on MCF7 breast cancer cells showed that the significant amounts of the radiofluorinated conjugates were associated with cell fractions and held good affinity and specificity for MCF7 cells. In vivo characterization in Balb/c mice revealed rapid blood clearance with excretion predominantly by urinary as well as hepatobiliary systems for MUC1-[18F]SFB and MUC1-FA-[18F]SFB, respectively. Biodistribution in SCID mice bearing MCF7 xenografts, demonstrated excellent tumor uptake (12% ID/g) and favorable kinetics for MUC1-FA-[18F]SFB over MUC1-[18F]SFB. The tumor uptake was blocked by the excess co-injection of cold peptides suggesting the receptor-mediated process. Conclusion: Initial PET/CT imaging of SCID mice with MCF7 xenografts, confirmed these observations. These results demonstrate that MUC1-FA-[18F]SFB may be useful PET imaging probe for breast cancer detection and monitoring tumor response to the treatment.
Cellphone laws and teens’ calling while driving: analysis of repeated cross-sectional surveys in 2013, 2015, and 2017
Authors: Li Li , Pope Caitlin N , Andridge Rebecca R , Bower Julie K , Hu Guoqing , Zhu Motao
Published: April 2020

Background
Distracted driving among teen is a public health and safety concern. Most states in the U.S. have sought to restrict cellphone use while driving by enacting laws. This study aims to examine the difference in prevalence of self-reported calling while driving (CWD) between states with different types of cellphone bans.
Methods
Demographics and CWD data were extracted from state Youth Risk Behavior Surveys (YRBS) from 14 states in 2013, 2015 and 2017. The state YRBS is conducted every two years with a representative sample of 9th through 12th grade students attending public school. States were grouped by type of enacted cellphone law(s): concurrent bans (concurrently enacted handheld calling ban and young driver ban); young driver ban (no handheld calling and enacted young driver ban only); and no ban (no handheld calling and no young driver ban). Poisson regression models with robust variance were used to estimate prevalence ratios comparing CWD prevalence across cellphone laws.
Results
In total, 109,069 high school students participated in the surveys, and 56, 492 (56%) participants reached the minimum learner’s permit age for their states and drove during the 30 days before the survey. Approximately 46% of participants reported CWD at least once during the previous 30 days and the percentages varied widely across states (range: 29%-62%). Compared to students from states with no ban enacted, those from states with concurrent bans were 14% less likely to engage in CWD (95% CI: 3%-23%). Students in states with concurrent bans were 15% less likely to engage in CWD compared to students in states with young driver bans (95% CI:7%-21%). Young driver bans were not associated with a decrease of CWD.
Conclusions
Engaging in CWD is common among teen drivers. The concurrent implementation of a handheld calling ban and a young driver ban was associated with a decrease of CWD. States without a handheld calling ban are encouraged to implement such law to reduce teen drivers engaging in cellular-based distraction behind the wheel.
MEK inhibitor augments antitumor activity of B7-H3-redirected bispecific antibody
Authors: Li Hongjian , Huang Cheng , Zhang Zongliang , Feng Yunyu , Wang Zeng , Tang Xin , Zhong Kunhong , Hu Yating , Guo Gang , Zhou Liangxue , Guo Wenhao , Xu Jianguo , Yang Hui , Tong Aiping
Published: April 2020

Background

Targeting cancer antigens by T cell-engaging bispecific antibody (BiAb) or chimeric antigen receptor T cell therapy has achieved successes in haematological cancers, but attempts to use them to fight solid cancers have been disappointing, in part due to antigen escape. MEK inhibitor had limited activity as a single agent, but enhanced antitumor activity when combined with other therapies, such as targeted drugs or immunotherapy agents. This study aimed to analyze the expression of B7-H3 in non-small-cell lung cancer (NSCLC) and bladder cancer (BC) and to evaluate the combinatorial antitumor effect of a B7-H3 × CD3 BiAb with MEK inhibitor trametinib.
Methods

We analyzed the mRNA expression of B7-H3 in NCSLC and BC using Oncomine database and validated its expression by immunohistochemistry staining of clinical samples. B7-H3 expression and the effects of trametinib on RAS-mutated NSCLC and BC cell lines were determined by flow cytometry. Antitumor efficacy of B7-H3 × CD3 BiAb alone and its combination with trametinib were evaluated both in vitro and in vivo.
Results

B7-H3 was highly expressed in NSCLC and BC compared with normal samples and its increased expression was associated with poor prognosis. Treatment with trametinib alone could induce apoptosis in tumor cell, while has no effect on T cell proliferation, and a noticeable elevation of B7-H3 expression in tumor cells was also observed following treatment. B7-H3 × CD3 BiAb specifically and efficiently redirected their cytotoxicity against B7-H3-overexpressing tumor cells both in vitro and in xenograft mouse models, which was synergized by trametinib. While trametinib treatment alone affected tumor growth, the combined therapy increased T cell infiltration and significantly suppressed tumor growth.
Conclusion

Together, these data suggest that combination therapy with B7-H3 × CD3 BiAb and MEK inhibitor may serve as a new therapeutic strategy in the future clinical practice for the treatment of NSCLC and BC.
TMEM88 inhibits TGF-β1-induced-extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) program in human pleural mesothelial cells through modulating TGF-β1/Smad pathway
Authors: Sun Zhongmin , Qian Ning , Li Hong , Hu Tinghua , Tang Ling , Wen Qing , liangrong_shen@126.com Liangrong Shen
Published: April 2020

Pleural fibrosis is an irreversible pathological process occurred in the development of several lung diseases. TMEM88 is a member of transmembrane (TMEM) family and has been found to be involved in the regulation of fibrogenesis. However, the role of TMEM88 in pleural fibrosis remains unknown. In this study, we aimed to explore the role of TMEM88 in pleural fibrosis in vitro using TGF-β1-induced human pleural mesothelial cell line MeT-5A cells. Our results showed that the expression levels of TMEM88 were downregulated in pleural fibrosis tissues and TGF-β1-treated Met-5A cells. Overexpression of TMEM88 inhibited the proliferation of Met-5A cells under TGF-β1 stimulation. In addition, TMEM88 overexpression prevented TGF-β1-induced extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) in Met-5A cells with decreased expression levels of Col I and fibronectin, increased levels of cytokeratin-8 and E-cadherin, as well as decreased levels of vimentin and α-SMA. Furthermore, overexpression of TMEM88 inhibited the expression of TGF-β receptor I (TβRI) and TβRII and suppressed the phosphorylation of Smad2 and Smad3 in Met-5A cells. In conclusion, these results indicated that TMEM88 exhibited an anti-fibrotic activity in pleural fibrosis via inhibiting the activation of TGF-β1/Smad signaling pathway.
Effect of mindfulness on physical activity in primary healthcare patients: a randomised controlled trial pilot study.
Authors: Nymberg Peter , Calling Susanna , Stenman Emelie , Palmér Karolina , Hansson Eva Ekvall , Sundquist Kristina , Sundquist Jan , Zöller Bengt
Published: April 2020

Increased physical activity can have health benefits among inactive individuals. In Sweden, the healthcare system uses Physical Activity on Prescription (PAP) to motivate patients to increase their physical activity level. Mindfulness may further heighten the internal motivation to engage in physical activity. However, previous research has not demonstrated clear evidence of such associations.Aim: Examine the feasibility of the study design as a preparation for a full-scale study, and examine the differences, between three interventions, in change over time in physical activity levels and in related variables.Method: Comparison between three different interventions in an ordinary primary health care setting: PAP, mindfulness, and a combination of PAP and mindfulness. Physical activity was measured with self-report and ACTi Graph GT1X activity monitor. Statistical analysis was performed with a mixed effect model to account for repeated observations and estimate differences both within groups and between groups at three and six months follow-up.Results: Between September 2016 and December 2018, a total of 88 participants were randomised into three groups. Eleven participants were excluded from analysis due to low activity monitor wear time. The total dropout rate was 20.4%, the attendance rate to the mindfulness courses (52% > 6 times) and the web-based mindfulness training (8% > 800 minutes) was low according to the stated feasibility criteria. Self-reported leisure time physical activity showed a significant difference in change between the groups (p= 0.04); the mindfulness group did not report the same increase as the other groups. The activity monitor data showed no significant differences between the groups. However, within the combination group, there was a significant increase of percentage time in light physical activity, which was not found in the other groups. Among the secondary aims, self-rated health showed a significant increase only within the combination group.Conclusion: The study design needs adjustment for the mindfulness intervention design before a fully scaled study can be conducted. A combination of PAP and mindfulness may increase physical activity and self-rated health more than PAP or mindfulness alone.Trial registration: ClinicalTrials.gov, registration number NCT02869854. Regional Ethical Review Board in Lund registration number 2016/404.
ATUAÇÃO ESTRATÉGICA DO ADVOGADO NAS EMPRESAS PRIVADAS
Authors: ANDRADE Priscilla
Published: April 2020

Essa pesquisa visa apresentar uma reflexão sobre a atuação do advogado dentro das empresas privadas buscando desenvolver estratégias de atuação que ultrapassem o domínio técnico-jurídico, ao estabelecer um comportamento associado a tecnologia jurídica. O tema da pesquisa foi delimitado pensando em um estudo de interdisciplinaridade entre os conhecimentos das áreas de administração de empresas e de Direito. A questão de pesquisa se limitou a responder se é possível o advogado atuar de maneira estratégica nas empresas privadas através de uma postura preventiva e proativa visando um alinhamento com o ordenamento jurídico, para evitar litígios e perdas diversas.Com isso, o advogado passaria de um agente operacional na empresa privada (que é chamado somente quando há uma demanda) para um agente estratégico (que contribui na obtenção de uma vantagem competitiva no dia a dia da empresa). Como os resultados dessa pesquisa constatou-se que os advogados em sua formação acadêmica no Brasil, em sua grande maioria são treinados para atuarem com uma visão processualista e reativa e não de maneira estratégica e preventiva. Isso demonstra também a dificuldade que as empresas têm de conseguir incorporar um advogado em sua estrutura organizacional, que possuem uma visão sistêmica do negócio e da legislação para construírem uma vantagem competitiva. Dessa maneira constata-se que há uma oportunidade de mercado para o advogado que quer atuar de maneira preventiva e proativa e que alguns escritórios de advocacia que realizam esse trabalho no Brasil atribuem essa atividade pouca explorada no Direito de tecnologia jurídica.
OS DIREITOS TRABALHISTAS DA PESSOA COM DEFICIÊNCIA COMO FORMA DE EFETIVAÇÃO DOS SEUS DIREITOS FUNDAMENTAIS
Authors: MOSCARDINI Maria Laura Bolonha
Published: April 2020

O objetivo geral do artigo, que apresenta os resultados de pesquisa de iniciação científica, é investigar a necessidade da concretização dos direitos trabalhistas da pessoa com deficiência e sua inserção no mercado de trabalho como forma de garantir a efetivação de seus direitos fundamentais e sua inclusão social. É realizado um estudo sócio jurídico sobre as raízes da exclusão das pessoas com deficiência, suas principais melhorias, suas motivações e seus resultados até os dias atuais, na busca por demonstrar a evolução no trato para com tal assunto, as mudanças positivas que aconteceram e também os pontos que necessitam de alterações para tornar as políticas públicas e ações afirmativas do Estado mais efetivas em cumprir com seus objetivos. Para tanto, buscou-se estudos referentes ao direito ao trabalho da pessoa com deficiência e sua efetivação, a partir dos quais foi possível entender as principais questões levantadas sobre o tema e também as sugestões que visam implementar as políticas públicas e garantir que, de fato, haja a inclusão da pessoa com deficiência no mercado de trabalho. Em suma, foi possível concluir a partir da análise realizada, que o direito ao trabalho não só está ligado à inclusão da pessoa com deficiência na sociedade, mas sua concretização é um dos pilares para a efetivação dos direitos fundamentais de qualquer ser humano, uma vez que é a partir do direito ao trabalho que se garantem os meios necessários para uma vida digna. Logo, concluiu-se que o maior investimento e preocupação com este direito social da pessoa com deficiência faz-se necessário para o processo de evolução e inclusão deste grupo em todas as esferas sociais, com o efetivo gozo de seus direitos fundamentais.
GÊNERO E DIREITO: Reflexões sobre o princípio da não discriminação na execução da igualdade da mulher no mercado de trabalho.
Authors: RODRIGUES Rafaela Amaral
Published: April 2020

O objetivo fundamental deste trabalho é realizar uma análise histórica da inserção da mulher na esfera trabalhista, demonstrando como o Direito foi se adaptando ao ingresso da mulher neste meio e, por fim, explora-se a finalidade principal desta pesquisa, de trazer dados atuais da realidade brasileira, que indicam que a discriminação de gênero ainda está presente, principalmente no que tange à diferença salarial e ocupação de cargos. O resultado foi a constatação de que o motivo para a discriminação da mulher ainda estar presente é o grande abarco cultural que o país carrega, predominantemente machista, que já atingiu uma importante evolução no sentido à igualdade, porém ainda não conquistada plenamente. Conclui-se que são necessárias políticas públicas para que haja a efetivação da proteção que está consolidada em dispositivos legais, além da caminhada para a quebra do paradigma de que a mulher é um ser frágil e destinado ao cuidado dos lares.
Linguistic Diversity in Kharkiv: Between “Pride” and “Profit,” Between the Local and the Global
Authors: Pletnyova Ganna (Anna)
Published: April 2020

This paper explores the linguistic diversity of the city of Kharkiv, focusing on the language ideologies and practices of Russian-speaking Kharkivites in the wake of the Russo-Ukrainian military conflict of 2014. This conflict polarized Ukrainian Russophones into competing ideological positions for or against Russia and gave fresh vigour to the long-existing linguistic debate in Ukraine, which was a result of the Russian government’s manipulations of the Ukrainian language situation. The political convictions of Russian-speaking Kharkivites affect their linguistic behaviour, motivating them to attempt to switch to Ukrainian, to advocate bi- or multilingualism, or to demonstratively use only Russian.

A field study that I carried out in Kharkiv in the summer of 2018 examined correlations and discrepancies between Kharkivites’ linguistic ideologies and their real-life language practices, focusing on the interaction between two factors: the discourse of “pride” in speaking a particular language, which is anchored in a speaker’s interpretations of the role of language in a nation, and the discourse of “profit,” which is based on a speaker’s expectation of economic benefits related to mastering a certain language.

The study results reveal the vacillations of this Russian-speaking community between support for the monolingual ideology of the nation-state and the globalizing concept of multilingualism, demonstrating an interplay between discourses of “pride” and “profit” and the influence of local and global forces.
Review of Michael S. Flier and Andrea Graziosi, editors. The Battle for Ukrainian: A Comparative Perspective.
Authors: Nedashkivska Alla
Published: April 2020

Review of Michael S. Flier and Andrea Graziosi, editors. The Battle for Ukrainian: A Comparative Perspective. Ukrainian Research Institute, Harvard University, 2017. Distributed by Harvard UP. Harvard Papers in Ukrainian Studies. x, 626 pp. Map. Tables. End-of-chapter notes. Index. $29.95, paper.
Review of Iryna Starovoyt. A Field of Foundlings: Selected Poems.
Authors: Powell Sara Jo
Published: April 2020

Review of Iryna Starovoyt. A Field of Foundlings: Selected Poems. Translated from the Ukrainian by Grace Mahoney, Lost Horse Press, 2017. Lost Horse Press Contemporary Ukrainian Poetry Series 1. 92 pp. Illustrations. $21.00, paper.
Influence of Rootstock Propagation Method on Traits of Grafted Sweet Orange Trees
Authors: Albrecht Ute , Bodaghi Shahrzad , Meyering Bo , Bowman Kim D.
Published: April 2020

The rootstock plays a large role in modern citrus production because of its influence on tolerance to adverse abiotic and biotic soil-borne stresses, and on the general horticultural characteristics of the grafted scion. In recent years, rootstock has received increased attention as a management strategy to alleviate the devastating effects of the bacterial disease huanglongbing (HLB), also known as “citrus greening.” In commercial citrus nursery production, rootstocks are typically propagated by seed. Because of the increased demand for HLB-tolerant rootstocks, seed supply is often inadequate for the most popular cultivars. Cuttings and tissue culture (TC) propagation are alternative methods to supply adequate quantities of genetically identical rootstocks to be used as liners for grafting. However, there are concerns among nursery owners and citrus growers regarding the possible inferiority of rootstocks that are not propagated by seed. This study investigates the influence of rootstock propagation method on traits of sweet orange trees grafted on four commercially important rootstock cultivars during the nursery stage and during the first year of growth in a commercial citrus orchard. Several of the measured traits during the nursery stage, including rootstock sprouting, grafted tree growth, and root mass distribution were significantly influenced by the rootstock propagation method, but traits were also influenced by the rootstock cultivar. Our results also suggest that for tissue culture-propagated plants, differences in the starting material and the culturing method can affect the grafted tree behavior. Except for canopy spread and scion to rootstock trunk diameter ratio, tree growth during the orchard stage was determined by the combination of propagation method and rootstock, rather than by propagation method alone.
Yield and Yield Component Performance of Chile Pepper in Myanmar and Vietnam
Authors: Barchenger Derek W. , Thandar Khin , Myint Thain Gi , Hung Tran Ngoc , Hung Nguyen Quoc , Lin Shih-wen , Wang Yen-wei , Lin Tsung-han
Published: April 2020

Chile pepper (Capsicum annuum) is an increasingly important crop worldwide, and Vietnam and Myanmar are major producing countries. The chile pepper markets in Myanmar and Vietnam are different, with production primarily for domestic consumption in Myanmar and for the export market in Vietnam. However, there is an overall lack of domestically developed cultivars in both countries. The objective of this study was to identify high-performing chile pepper entries, adapted to local conditions, for use in domestic breeding programs or direct release. Fruit length, width, weight, and yield were measured during two seasons (2016–17 and 2018–19), and the same entries were evaluated in Hanoi, Vietnam, and Nay Pyi Taw, Myanmar. However, different entries were tested in each season. During the 2016–17 season, AVPP1324 grown in Hanoi had the overall highest yield (15.3 t·ha–1), followed by AVPP1330 (15.0 t·ha–1 in Hanoi) and AVPP1111 (14.4 and 14.9 t·ha–1 in Hanoi and Nay Pyi Taw, respectively). AVPP0303 had the greatest fruit length, fruit width, and fruit weight in both Hanoi and Nay Pyi Taw during the 2016–17 season. During the 2018–19 season, AVPP1345 (24.8 t·ha–1) followed by AVPP9905 (22.5 t·ha–1) in Nay Pyi Taw, and AVPP1245 (17.4 t·ha–1) in Hanoi had the highest yield. AVPP9905 had the greatest fruit weight and width in both locations. AVPP1345 and AVPP9905 had the greatest fruit length during the 2018–19 season. There is an obvious need for domestically produced cultivars in Myanmar and Vietnam that meet local farmer and consumer preferences and that are adapted to the pests, diseases, and stress in each country. Several high-performing lines were identified that can be used as direct release or incorporated in local breeding programs for the development of inbred or F1 hybrid cultivars. This research also provides a basis for future studies on stability of yield and yield components in Southeast Asia.
POSSIBILITIES OF ADDITIVE TECHNOLOGIES IN THE MEAT INDUSTRY. A REVIEW
Authors: Gorbunova Nataliya A.
Published: April 2020

Three-dimensional printing (3D printing) is a rapidly developing market of digital technologies with a huge potential for food production, which gives an opportunity to create new food products with the improved nutritional value and sensory profile, and adapted for a particular consumer. The review presents historical aspects of the development of the additive technologies and their classification, examines advantages and drawbacks of the 3D food printing, discusses key aspects of safety of three-dimensional food printing and probable peculiarities of their labeling, analyzes potential possibilities of using the 3DP technology for meat processing and aspects influencing the possibility of printing and following processing of 3D printed meat products.
La crisis de la vivienda pública en el boom económico de la frontera norte: El caso de Tijuana
Authors: Negrete Mata José , Reyes Santos Marcos Sergio
Published: April 2020

El presente artículo tiene como objetivo contribuir a los estudios de desigualdad social y urbana en la frontera norte, para ello, se ha dividido en tres secciones: en la primera, se pretende mostrar que el crecimiento físico e histórico de la ciudad de Tijuana ha estado regido por una lucha permanente de la sociedad, no sólo por apropiarse de un espacio físico para vivir sino también por construir su ciudad, como un espacio social; en la segunda, se describen los resultados del análisis de los datos del XI Censo General de Población y Vivienda del Instituto Nacional de Estadística, Geografía e Informática (INEGI) para la ciudad de Tijuana, sobre las características y localización espacial de las viviendas en la ciudad de Tijuana, Baja California, de acuerdo con sus atributos de precariedad y de no precariedad; y en la tercera, se bosquejan algunas conclusiones acerca de la forma desigual del crecimiento físico y social y se hacen algunos señalamientos sobre política pública de desarrollo urbano para la ciudad de Tijuana, Baja California
Tiraderos o depósitos de desechos tóxicos y radioactivos en la frontera noreste: Cronología y notas de una experiencia reciente
Authors: Tamayo Jesús
Published: April 2020

En este trabajo se presenta una cronología de los acontecimientos relacionados con un proyecto estadounidense para construir tres confinamientos de desechos tóxicos y radioactivos en localidades cercanas a la frontera con México. Se reseña, además, la actuación de los diversos agentes involucrados en la cuestión ambiental, así como la participación de asociaciones civiles de ambos países
Enfoques lingüísticos sobre la prehistoria del sur de California
Authors: Laylander Don
Published: April 2020

El estudio de la evidencia sobre los idiomas indígenas yumanos, utoaztecanos y chumashanos del sur de California y de la parte norte de Baja California se plantea por el autor como una forma que puede ayudarnos a entender mejor el desarrollo prehistórico de la región. Para esto, se analizan en este documento diversos enfoques utilizados en los estudios lingüísticos de estas comunidades tempranas. El modelo genético de la descendencia lingüística sugiere que grupos de idiomas del periodo histórico tienen orígenes comunes, que son seguidos por una sucesión de separaciones que se pueden atribuir a diversos factores. La glotocronología ofrece estimaciones de los periodos de esas separaciones. La teoría de la migración evalúa la probabilidad relativa de que sean regiones particulares las patrias originales de las comunidades lingüísticas antes de que se dividieran. La difusión de lenguajes refleja las yuxtaposiciones geográficas e interacciones de comunidades de idiomas en el pasado. Por su parte la reconstrucción de la proto-cultura promete ayudar en la identificación de las patrias originales y de las sucesiones de innovaciones culturales
Nñait Jatñil, soy Caballo Negro
Authors: Zárate Loperena David Andrés
Published: April 2020

La historia de un personaje kumiai que sobresalió como líder de los indígenas de las regiones ocupadas al norte y sur de la actual frontera entre Estados Unidos y México es relatada en este artículo. De varias fuentes historiográficas y de descripciones que hace Ros Mishkwish, se reconstruye el escenario histórico-cultural de este líder kumiai que vivió a fines del siglo XVIII y principios de XIX, lapso durante el cual terminaba el dominio de los misioneros dominicos e iniciaba la etapa de México independiente. Jatñil fue un héroe para los kumiai.
Zou het kunnen dat al de toestellen die we hebben, onze smartphones, laptops, ... magische dingen zijn?
Authors: Van Baarle Kristof
Published: April 2020

Een gesprek met Kris Verdonck en een epiloog door Kristof van Baarle