bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Clinical Nomogram for Prediction of Response to Neoadjuvant Chemotherapy in Patients with Advanced Gastric Cancer
Authors: Liang Xianwen , Liao Xu-Liang , Pang Hua-Yang , Pan Tao , Song Xiao-Hai , Zhang Wei-Han , Liu Kai , Chen Xiao-Long , Chen Xin-Zu , Yang Kun , Hu Jian-Kun
Published: August 2021

Objective:The efficacy of neoadjuvant chemotherapy (NAC) among advanced gastric cancer (GC) is still a controversial issue. Our aim is to find the factors associated with chemosensitivity of NAC, and provide optimal therapeutic strategy for GC patients who received NAC.Methods: Clinical information was collected from 230 gastric cancer patients who received NAC in West China Hospital from January 2016 to December 2020. LASSO logistic regression analysis was performed to find the possible predictors which a nomogram model for prediction of response to NAC was based on.Results: A total of 230 patients were finally included in this study, including 154 males (67.0%) and 76 females (33.0%). And mean age was (59.37±10.60) years, ranging from 24 to 80 years. Based on the TRG standard, there were 95 cases in the obvious response group (grade 0 or grade 1) and 135 cases in the non-obvious response group (grade 2 or grade 3), and the obvious response rate was 41.3%. LASSO analysis showed that four risk factors that were significantly related to the efficacy of NAC, which included tumor location (P<0.001) , histological differentiation (P=0.001), clinical T stage (P=0.008) , CA724 (P=0.008) . The C-index for prediction nomogram was 0.806, and the calibration curve revealed the predicted value exhibited good agreement with the actual value, decision curve analysis showed that the nomogram had a good value in clinical application.Conclusions: The nomogram which combined tumor location, histological differentiation，clinical T stage and CA724 showed satisfactory predictive power to response of NAC, and could be used by gastrointestinal surgeons to identify optimal treatment strategy for advanced gastric cancer patients.
BRAF V600E-Mutant Colorectal Cancers with Liver-Only Metastases: A Retrospective Study.
Authors: Javed Sahir , Benoist Stéphane , Devos Patrick , Truant Stéphanie , Guimbaud Rosine , Lièvre Astrid , Sefrioui David , Cohen Romain , Artru Pascal , Dupré Aurélien , Bachet Jean-Baptiste , Fourchardière Christelle de la , Ploquin Anne , Turpin Anthony
Published: August 2021

BACKGROUND BRAF V600E-mutant colorectal cancers (CRCs) are associated with shorter survival than BRAF wild-type tumors. Therapeutic decision-making for colorectal liver metastases (CRLM) harboring this mutation remains difficult due to the scarce literature. Our aim was to study a large cohort of BRAF V600E-mutant CRLM patients in order to identify prognostic factors associated with overall survival. METHODS We retrospectively identified BRAF V600E-mutant CRCs diagnosed with liver-only metastases, resected or not, between April 2008 and December 2017, in 25 French centers. Clinical, molecular, pathological characteristics and treatment features were collected. Overall survival (OS) was defined as the time from CRLM diagnosis to death from any cause. Cox proportional hazard models were used for statistical analysis. RESULTSAmong the 105 patients included, 79 (75%) received chemotherapy, 18 (17%) underwent upfront CRLM surgery, and 8 (8%) received exclusive best supportive care. CRLM surgery was performed in 49 (46.7%) patients. CRLM were mainly synchronous (90%) with bilobar presentation (61%). The median OS was 34 months (range, 28.9–67.3 months) for resected patients and 10.6 (6.7–12.5) months for unresected patients (P < 0.0001). Most patients received doublet chemotherapy (72%), and 34% received a combination with bevacizumab as a first-line treatment. In multivariate analysis, primary tumor surgery (hazard ratio (HR) = 0.349; 95% confidence interval (CI) 0.164–0.744, P = 0.0064) and CRLM resection (HR = 0.169; 95% CI 0.082–0.348, P < 0.0001) were associated with significantly better OS. CONCLUSIONSIn the era of systemic cytotoxic chemotherapies, liver surgery seems to extend OS. Therefore, CRLM resectability should be assessed, regardless of mutational status.
Comprehensive Analysis of the Prognosis for Chemokine-Like Factor MARVEL Transmembrane Domain-Containing Family in Hepatocellular Carcinoma
Authors: Li Dan , Huang Shenglan , Sun Liying , Wu Jianbing
Published: August 2021

Background and Purpose: Chemokine-like factor (CKLF) MARVEL transmembrane domain-containing family (CMTMs), including chemokine-like factor (CKLF) and CMTM1 to CMTM8. All of these genes participate in tumor development and metastasis of hepatocellular carcinoma (HCC). However, prognosis values and the distinct roles of different CMTMs in HCC are still un-clarified.Materials and Methods: To address this issue, the study explored the function of CMTM family members in the prognosis of HCC by TCGA dataset, UALCAN, Kaplan-Meier Plotter, MethSurv, TIMER2.0 databases.Results: The CKLF and CMTM1/3/4/7/8 mRNA expression was obviously elevated in HCC tissues, while CMTM2/5/6 was lowly expressed. Besides, the mRNA level of CMTMs was closely linked to cancer stage, node metastasis status and tumor grades in HCC patients. What’s more, the expression of CMTM2/5 was correlated with favorable overall survival (OS), while high expressions CKLF and CMTM1/7 were associated with poor OS. Simultaneously, low CKLF and CMTM1/4/7 expressions were significantly relevant to better progression-free survival (PFS), while low CMTM5 expression was apparently concerned with worse PFS. In DNA methylation level, 47 CpGs of CMTMs displayed markedly prognostic values. Multivariate cox analysis also revealed that affecting shorter OS outcomes prognostic factors of CKLF and CMTM7 were independent. GSEA results suggested that CKLF and CMTM7 participated in the development and progression of HCC accompanied with multiple biological processes. Furthermore, CMTMs were dramatically associated with tumor immune infiltrating cells (TIICs) (e.g., neutrophils cells), but CMTM8 expression level was no significant correlations with TIICs.Conclusion: This study renders new insight into the prognostic values of CMTM family members in HCC. Overall, our results indicated that CKLF and CMTM7 could be the prognostic biomarkers in HCC patients.
The Assessment of Potential Observability for Joint Chemical States and Emissions in Atmospheric Modelings
Authors: Wu Xueran , Elbern Hendrik , Jacob Birgit
Published: August 2021

In predictive geophysical model systems, uncertain initial values and model parameters jointly influence the temporal evolution of the system. As for chemistry-transport models, emission rates are at least as important as initial values for model evolution controls. This renders initial-value-only optimization by traditional data assimilation methods as insufficient. However, blindly extending the optimization parameter set jeopardizes the validity of the resulting analysis since the ill-posedness of the inversion task is increased. Hence, it becomes important to assess the potential observability of measurement networks for model state and parameters in atmospheric modelings in advance of the optimization. In this paper, we introduce an approach to quantify the impact of observation networks jointly for initial trace gas state and emission rates for transport-diffusion models extended by emissions. Applying a Kalman smoother as underlying assimilation technique, we develop a quantitative assessment method to evaluate the potential observability and the sensitivity of observation networks to initial values and emission rates. For practical applications, we derive an ensemble based version of the approach and give several elementary experiments for illustration.
Sociodemographic Disparities in the Establishment of Health Records Among 0.5 Million Migrants From 2014 to 2017 in China: a Nationwide Cross-sectional Study
Authors: Wang Jun , Zhu Jingmin , Wang Xueyao , Che Yue , Bai Yang , Liu Jue
Published: August 2021

Background: Migrants account for a large part of China’s population. Many policies and inventions have been taken to improve access to public health services and the health of migrants. China’s Basic Public Health Services（BPHS) are a series of public health services in this policy domain, which aims at promoting the access of public health sevices and improve health equity of residents.The establishment of health records is the fundamental service of BPHS. However，there is little known about the establishment of health records among migrants in China, which hinders the more efficient provision of health services for migrants, and health equity is difficult to achieve. Based on the research gap, this study aims at showing the sociodemographic disparities in the establishment rate of health records, and identifying priorities and recommendations for promoting health equity of migrants in China.Methods: This study used national data from China Migrants Dynamic Survey(CMDS) from 2014 to 2017 to evaluate the sociodemographic disparities in the establishment rate of health records and utilization of relevant public health services.The study included 539926 respondents. Following the descriptive statistics of migrants, we showed the establishment rate of health records by sociodemographic characteristics and migrating related characteristics. Multivariate analysis was conducted to explore the associations between sociodemographic charicteristics, migrating related charicteristics and the establishment of health records.Results: The establishment rate of health records among migrants in the sampled years were 22.99%, 38.44%, 27.29% respectively, and 29.18% in general, and there existed heterogeneity in the establishment rate of health records by sociodemographic charicteristics and migrating related charicteristics. Female migrants who were older, from middle age, married or living with partner, with higher educational attainment, with urban household registration, migrated for longer time, migrated for the reason of studying or family issues, migrated in province were more likely to establish health records.Conclusion: There existed sociodemographic disparities in the establishment rate of health records and inequalities in the utilization of health records services among migrants in China. Migrating related characteristics also had impact on the establishment status. Policies should take both supply side and demand side of health services to improve the health equity of migrants, which means that relative departments should continue to invest in primary healthcare centers to improve their ability to provide services as well as migrants’ health literacy.
The Effectiveness of Non-pharmacological Treatments for Vestibular and Oculomotor Deficits in Post-concussive Syndrome: a Protocol for a Systematic Review and Meta-analysis
Authors: Sheeba Stella R , Cavaleri Rocco , Summers Simon J , Browne Cherylea J
Published: August 2021

Background: Concussion is a form of mild traumatic brain injury (mTBI) that disrupts brain function. Although symptoms are mostly transient, recovery can be delayed and result in post-concussive syndrome (PCS). Vestibular and oculomotor deficits are among the most debilitating impairments associated with PCS. Non-pharmacological interventions provide treatment with limited side effects in comparison to pharmacological interventions. The aim of this review is to synthesise and evaluate the effectiveness of non-pharmacological interventions that have been used to target vestibular and oculomotor deficits in PCS.Methods: Advanced searches will be conducted in electronic databases to identify articles eligible for inclusion. Studies employing non-pharmacological treatments for vestibular and/or oculomotor dysfunction in PCS will be included if they meet the eligibility criteria. Outcomes will be those pertaining to measures of oculomotor and vestibular function, in addition to adverse events. Meta-analysis will be undertaken using a random effects model followed by an assessment of clinical significance for each outcome as published in literature. Discussion: While non-pharmacological interventions are used commonly to treat vestibular and oculomotor deficits in PCS, the effectiveness of these treatments is yet to be completely elucidated. The present review will explore the effectiveness of non-pharmacological treatments for vestibular and oculomotor deficits in PCS to inform practice and future research.Systematic review registration: PROSPERO CRD42021254720
Thermoplasmonic Effect Onto Toad Physiology Signals by Plasmonic Microchip Structure
Authors: Akbari S. , Hamidi S. M. , Eftekhari H. , Soheilian A.
Published: August 2021

Cardiovascular diseases are considered as the leading cause of death and almost 80% of deaths from this disease are developed in poor and less developed countries where early detection facilities are less available, along with overlooking the importance of screening. In other words, real-time monitoring of the physiological signals using flexible and wearable biosensors plays an important role in human life style. Thus, the present study aims to propose two dimensional flexible and wearable gold covered plasmonic samples as a physiological signal recorder, in which chips with nano array of resonant nanowire patterns performing in an integrated platform of plasmonic devices. The produced surface plasmon waves in our main chip were paired with an electric wave from the heart pulse and it use for recording and detecting the heartbeat of a toad with high accuracy. This measurement was performed in normal state and under external laser heating process to check the ability of signal recording and also thermoplasmonic effect onto the toad's heart signal. Our results show that our sensor was enough sensitive for detection while raising the body temperature of the toad and changing its heart rate as flatting T and P waves by thermoplasmonic effect.
Global CO2 Fertilization of Sphagnum Peat Mosses via Suppression of Photorespiration During the 20th Century
Authors: Serk Henrik , Nilsson Mats , Bohlin Elisabet , Ehlers Ina , Wieloch Thomas , Olid Carolina , Grover Samantha , Kalbitz Karsten , Limpens Juul , Moore Tim , Münchberger Wiebke , Talbot Julie , Wang Xianwei , Knorr Klaus-Holger , Pancotto Verónica , Schleucher Jürgen
Published: August 2021

Natural peatlands contribute significantly to global carbon sequestration and storage of biomass, most of which derives from Sphagnum peat mosses. Atmospheric CO2 levels have increased dramatically during the 20th century, from 280 to > 400 ppm, which has affected plant carbon dynamics. Net carbon assimilation is strongly reduced by photorespiration, a process that depends on the CO2 to O2 ratio. Here we investigate the response of the photorespiration to photosynthesis ratio in Sphagnum mosses to recent CO2 increases by comparing deuterium isotopomers of historical and contemporary Sphagnum tissues collected from 36 peat cores from five continents. Rising CO2 levels generally suppressed photorespiration relative to photosynthesis but the magnitude of suppression depended on the current water table depth. By estimating the changes in water table depth, temperature, and precipitation during the 20th century, we excluded potential effects of these climate parameters on the observed isotopomer responses. Further, we showed that the photorespiration to photosynthesis ratio varied between Sphagnum subgenera, indicating differences in their photosynthetic capacity. The global suppression of photorespiration in Sphagnum suggests an increased net primary production potential in response to the ongoing rise in atmospheric CO2, in particular for mire structures with intermediate water table depths.
Eribulin activity in soft tissue sarcoma monolayer and three-dimensional cell line models: Could the combination with other drugs improve its antitumoral effect?
Authors: Escudero Javier , Heredia-Soto Victoria , Wang Yiyin , Ruiz Patricia , Gallego Alejandro , Pozo-Kreilinger Jose Juan , Martinez-Marin Virginia , Berjon Alberto , Ortiz-Cruz Eduardo , Bernabeu Daniel , Feliu Jaime , Tang Jing , Redondo Andres , Mendiola Marta
Published: August 2021

Background
Eribulin has shown antitumour activity in some soft tissue sarcomas (STSs), but it has only been approved for advanced liposarcoma (LPS).
Methods
In this study, we evaluated the effect of eribulin on proliferation, migration and invasion capabilities in LPS, leiomyosarcoma (LMS) and fibrosarcoma (FS) models, using both monolayer (2D) and three-dimensional (3D spheroid) cell cultures. Additionally, we explored combinations of eribulin with other drugs commonly used in the treatment of STS with the aim of increasing its antitumour activity.
Results
Eribulin showed activity inhibiting proliferation, 2D and 3D migration and invasion in most of the cell line models. Furthermore, we provide data that suggest for the first time a synergistic effect with ifosfamide in all models and with pazopanib in LMS as well as in myxoid and pleomorphic LPS.
Conclusions
Our results support the effect of eribulin on LPS, LMS and FS cell line models. The combination of eribulin with ifosfamide or pazopanib has shown in vitro synergy, which warrants further clinical research.
Development of a Human Umbilical Cord-derived Mesenchymal Stromal Cells-based Advanced Therapy Medicinal Product to treat immune and/or inflammatory diseases
Authors: MEBARKI Miryam , Iglicki Nathan , Marigny Céline , Abadie Camille , Nicolet Claire , Churlaud Guillaume , Maheux Camille , Boucher Hélène , Monsel Antoine , Menasché Philipe , Larghero Jérôme , Faivre Lionel , Cras Audrey
Published: August 2021

Background
Umbilical Cord-derived Mesenchymal Stromal Cells (UC-MSCs) revealed their key role in immune regulation, offering promising therapeutic perspectives for immune and inflammatory diseases. We aimed to develop a production process of an UC-MSCs-based product, then to characterize UC-MSCs properties and immunomodulatory activities in vitro, related to their clinical use and finally, to transfer this technology to a good manufacturing practice (GMP) compliant facility, to manufacture an Advanced Therapy Medicinal Product (ATMP).
Methods
Fifteen human umbilical cords (UCs) were collected to develop the production process. Three batches of UC-MSCs from a single donor were characterized at basal state and after in vitro pro-inflammatory stimulation by interferon-γ (IFNγ) and Tumor Necrosis Factor-α (TNFα). Proliferation, immunophenotype, activation markers expression and the inhibition of T-cells proliferation were assessed. Finally, this technology was transferred to a GMP-compliant facility to manufacture an UC-MSCs-based ATMP, from a single donor, using the explant method followed by the establishment of master and work cell stocks.
Results
Twelve UCs were processed successfully allowing to isolate UC-MSCs with doubling time and population doubling remaining stable until passage 4. CD90, CD105, CD73, CD44, CD29, CD166 expression was positive; CD14, CD45, CD31, HLA-DR, CD40, CD80 and CD86 negative, while CD146 and HLA-ABC expression was heterogeneous. Cell morphology, proliferation and immunophenotype were not modified by inflammatory treatment. Indoleamine 2,3-dioxygenase (IDO) expression was significantly induced by IFNγ and IFNγ + TNFα versus non-treated cells. Inter Cellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule 1 (VCAM-1) expression was induced significantly after priming. T-cells proliferation was significantly decreased in the presence of UC-MSCs in a dose-dependent manner. This inhibitory effect was improved by IFNγ or IFNγ + TNFα, at UC-MSCs:PBMC ratio 1:10 and 1:30, whereas only IFNγ allowed to decrease significantly T-cells proliferation at ratio 1:100. The manufacturing process of the UC-MSCs-based ATMP was qualified and authorized by the French regulatory agency for clinical use (NCT04333368).
Conclusion
This work allowed to develop an investigational UC-MSCs-based ATMP authorized for clinical use. Our results showed that an inflammatory environment preserves the biological properties of UC-MSCs with an improvement of their immunomodulatory functions.
Archaeometric studies on a Pompeian blue glass fragment from Regio I, Insula 14 for the characterization of glassmaking technology
Authors: Gelzo Monica , Corso Gaetano , Vergara Alessandro , Rossi Manuela , Miedico Oto , Arcari Ottavia , Chiaravalle Antonio Eugenio , Piccioli Ciro , Arcari Paolo
Published: August 2021

A Pompeian glass sample found in Reg. I, Insula 14, during the 1950’s Pompeii excavation was examined by Raman and Fourier transformed infrared spectroscopy, scanning electron microscopy, and inductively coupled plasma mass spectrometry. The analyzed specimen was selected based on its intense blue color and its well-preserved aspect. The purpose of the work was the chemical characterization of Pompeii’s glass in correlation to the actual knowledge of Roman glassmaking technology from the Mediterranean area. The results suggested that the Pompeii’s glass was a soda-lime-silica glass, but with a higher calcium content that, given the low content of lead, was used to stabilize the glass. The sample was in origin produced most likely as non-decolorized primary raw materials from eastern Mediterranean sites. Moreover, the intense blue color was related to the use mainly of cobalt, present in a weighty amount, and likely used as important coloring agents in the ancient secondary glass-making workshop.
Revisiting Szent-Györgyi's Cancer Hypothesis
Authors: Johnson Morris Alfred , Smits Michael
Published: August 2021

Rationale for this communication • -The promine/retine hypothesis on the control of cancer never reached a definite conclusion.• -The chemical natures of promine and retine remain unsettled though usually assumed to be glyoxalases and methylglyoxal.• -Many years ago we published some data that indicated the hypothesis may be operating in plants in which glyoxalase I may exist in normal cells in an inhibited state rather than compartmentalized as in early versions of the hypothesis.• -Manju Ray in India has published many papers claiming that methylglyoxal can be used to successfully treat cancer in humans.• -We present here previously unpublished data that shows depriving glyoxalase I of GSH allows methylglyoxal to kill mouse lymphoma cells. During treatment of two human cancer cell lines, killing of one line was enhanced by blocking thioredoxin as well as GSH.It is hoped that what is conveyed here may reignite interest in the near term. Nuclear methodology and statistics can be found in Figure 1. The data show a strong interaction between the hypothesis and thiols. It is concluded that the hypothesis has yet to be thoroughly investigated.
Association Between Schizoid and Aggressive Behaviors in Chinese Adolescents and the Mediating Influences of Childhood Trauma and Adverse Life Events
Authors: Yang Tingyu , He Yuqiong , Wu Shuxian , Luo Xuerong , Liu Jianbo
Published: August 2021

Background: This study investigated an association between schizoid and aggressive behaviors in Chinese adolescents, and the influences of childhood trauma and adverse life events on this association.Methods: The cross-sectional data of 3094 adolescents aged 12 to 16 years was collected from an epidemiological survey of child and adolescent mental disorders in Hunan Province, China. All these subjects completed the Achenbach’s Child Behavior Checklist, the Childhood Trauma Questionnaire-Short Form, and the Adolescent Self-rating Life Event Checklist. Use independent-sample t-test, Pearson’s correlation analysis, linear regression, mediation analysis and moderation analysis for data analysis.Results: The regression analysis showed that schizoid (βmale = 0.618, βfemale = 0.637, both P < 0.001) and adverse life events (βmale = 0.113, βfemale = 0.057, all P < 0.01) predicted aggressive behaviors. In addition, childhood trauma predicted aggressive behaviors (female: emotional abuse and sexual abuse (β = 0.118 and –0.062, both P < 0.01). Adverse Life events mediated the association between schizoid and aggressive behaviors in male and female adolescents. Emotional neglect in boys, and emotional abuse and sexual abuse in girls mediated the association. Only in female adolescents, the interaction between childhood trauma and life events affected the association between schizoid and aggressive behaviors (P = 0.023).Conclusions: Schizoid are associated with aggressive behaviors in Chinese adolescents. Life events and childhood trauma mediated the association between schizoid and aggressive behaviors, and the interaction between childhood trauma and life events affected girls’ aggressive behaviors. Hence, reducing childhood trauma and adverse life events can reduce the risk of aggressive behaviors in adolescents.
Study Of The Association Of Tumor Deposits With Tumour-infiltrating Lymphocytes And Prognosis In Gastric Cancer Patients
Authors: Li Xinyue , Yang Jing
Published: August 2021

Background: To investigate the relationship between tumour deposits(TDs) with the clinicopathological characteristics,prognosis of gastric cancer and tumour-infiltrating lymphocytes( TILs）.Methods: The pathological findings of 369 patients with gastric cancer were retrospectively analysed to observe the expression of TDs, and the levels of stromal TILs . The relationships between TDs status, clinicopathological characteristics, and TILs infiltration level were compared using the chi-square test, and rank data were tested using the rank sum test. Kaplan-Meier was used for survival analysis, and the log-rank test was used to determine the differences in survival curves between groups. The prognostic value of TDs was assessed using multivariate Cox proportional hazards regression analysis.Results: TDs were significantly associated with sex, Lymphovascular invasion, Perineural invasion, pathological TNM stage, and clinical stage (all P<0.05). TILs levels were lower in TDs(+) group and higher in TDs(-) group. TDs(+) group had poor Disease-free survival, cancer-specific survival , and overall survival as compared with TDs(-) groups.Conclusions: TDs is negatively correlated with TILs , and TDs+ was an Independent predictors of the prognosis of gastric cancer.
Cardiac-Specific Gene TNNI3 as a Potential Oncogene for Kidney Cancer and Its Involvement in Wnt Signaling Pathway
Authors: Zhao Weian , Yang Lu , Chen Xiaoxiang , Huang Wenqi
Published: August 2021

BackgroundCardiac troponin I (cTnI), encoded by TNNI3, is an inhibitory subunit of troponin complex expressed in cardiac muscle and is well known for its central role in the regulation of cardiac contraction. Although its aberrant expression has been reported in non-small cell lung cancer tissues and human carcinoma cells, its roles in cancers are still largely unknown. MethodsIn this work, the mRNA expression profiles of 289 Kidney renal papillary cell carcinoma (KIRP) samples were obtained from The Cancer Genome Atlas (TCGA) database. The tumor samples were classified into TNNI3-low and TNNI3-high groups. A total of 361 differentially expressed genes (DEgenes) were found correlated with TNNI3 expression. Univariate Cox analysis, log-rank test and the least absolute shrinkage and selection operator analysis were used to identify the candidate prognostic genes. The regulatory role of TNNI3 on Wnt signaling pathway was detected by western blot, wound healing assay and cell counting kit-8 assay.ResultsMultivariable Cox regression analysis was performed to establish a prognostic risk formula including genes PTPRH, LGR5 and DMRT3. The low-risk group had a better overall survival than the high-risk group (p < 0.0001), and the areas under the receiver operating characteristic curve for 3- and 5-year overall survival were 0.75 and 0.74, respectively. We thereafter constructed an target gene network to explore the potential functions of the three genes. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis identified their involvement with canonical Wnt signaling and several cancer-related pathways. In wound healing assay, the wound was closed obviously faster in the TNNI3 over-expression group as compared to control and blank groups. Significant increase in cell proliferation was seen at 72 h after transfection with TNNI3 as compared to the control and blank groups.The expressions of LGR5 and β-catenin increased in the TNNI3 over-expression group as compared to control and blank groups.ConclusionCollectively, our data provide evidence that TNNI3 could enhance cell migration and proliferation in 786-O cells and the three-gene signature related to TNNI3 could serve as an independent prognostic biomarker for KIRP. Insights are indeed provided into the potential oncogenic functions of TNNI3 in cancer research.
Citric Acid-Based Bicarbonate Dialysate Attenuates Aortic Arch Calcification in Maintenance Haemodialysis Patients: An Observational Study
Authors: Akiyama Ken-ichi , Hanafusa Norio , Miura Yutaka , Seki Momoko , Miyabe Yoei , Iwabuchi Yuko , Karasawa Kazunori , Sugiura Hidekazu , Uchida Keiko , Kawaguchi Hiroshi , Tsuchiya Ken , Kuro-o Makoto , Nitta Kosaku , Moriyama Takahito
Published: August 2021

Introduction: The progression of aortic calcification is associated with mortality in haemodialysis patients. Blood calciprotein particle (CPP) levels are associated with coronary artery calcification, and was reported to be inhibited when using citric acid-based bicarbonate dialysate (CD). Therefore, we examined the effect of CD on the progression of the aortic arch calcification score (AoACS) and blood CPP levels in haemodialysis patients.Methods: A 12-month retrospective observational study of 262 haemodialysis patients who met the eligibility criteria was conducted at Joban Hospital. Patients taking warfarin or bisphosphonates and those with baseline AoACS of 100% were excluded. Progression, defined as ΔAoACS (12 months – baseline) > 0%, was compared between the CD and acetic acid-based bicarbonate dialysate (AD) groups.Results: The CD group had significantly lower AoACS progression than the AD group (P = 0.037). ΔCPP and ΔAoACS were not correlated in the AD group (R2 = 0.030, P = 0.098), but were negatively correlated in the CD group (R2 = 0.065, P = 0.022). Multivariate logistic analysis showed that the CD (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.27‒0.97, P = 0.042) was significantly associated with the AoACS progression.Conclusion: CD may suppress the progression of vascular calcification in haemodialysis patients.
A Novel Rhizospheric Bacterium, Bacillus Velezensis NKMV-3 as a Biocontrol Agent against Alternaria Leaf Blight in Tomato
Authors: Murthy Vignesh , BodethalaNarayanan VedhaHari , Davoodbasha MubarakAli , ShankarRamakrishanan MadhanShankar
Published: August 2021

A novel strain of Bacillus isolated from rhizosphere has shown to be excellent biocontrol agents against various plant pathogens. In this study, a first report of a Bacillus strain NKMV-3 which effectively controlling Alternaria solani, which cause the Early Blight disease in tomato. Based on the cultural and molecular sequencing of 16S rRNA gene sequence, the identity of the strain was confirmed as Bacillus velezensis NKMV-3. The presence of the lipopeptide which are antibiotic synthesis genes namely Iturin C, Surfactin A, Fengycin B and D were confirmed through gene amplification. In addition, lipopetides was also confirmed through liquid chromatography. The extract showed inhibitory effect against A.solani in-vitro and detached tomato leaf assays. Bacillus velezensis strain NKMV-3 based formulations may provide an effective solution in controlling early blight disease in tomato and other crops.
Analysis of Prognostic and Therapeutic Values of Drug Resistance-Related Genes in the Lung Cancer Microenvironment
Authors: Zhu Liang , Chen Peixin , Wang Hao , Zhao Lishu , Guo Haoyue , Jiang Minlin , Zhao Sha , Li Wei , Zhu Jun , Yu Jia , Dai Jiawei , He Yayi
Published: August 2021

Background: The interaction between cancer cells and stromal cells has a significant contribution in tumorigenesis and tumor development, and plays an anti-tumor immune effect under the regulation of drug resistance related genes, which affects the outcome of patients. CCDC73, DLGAP1, DSEL, ESR1, and SEC14L5 were identified as drug resistance-related genes in lung cancer. However, these genes have no clear value in lung cancer in terms of expression and prognosis.Results: The transcriptional expression level of DLGAP1 was remarkably increased in lung cancer tissues, while the transcriptional level of SEC14L5 was significantly decreased. The pathological stage of lung adenocarcinoma (LUAD) was tightly correlated with the expression of SEC14L5. The lung cancer patients with high transcription level of CCDC73 gene tended to have a good prognosis. The function of drug resistance-related genes is mainly related to RNA polymerization. Our results showed that infiltration of six types of immune cells (dendritic cells, macrophages, neutrophils, B cells, CD4+T cells, and CD8+ T cells) significantly correlated with the expression of these drug resistance-related genes.Conclusions: Novel screening for immunotherapy targets and prognostic biomarkers in lung cancer may draw inspiration from our results.
Mean Corpuscular Hemoglobin Predicts Length of Hospital Stay Independent of Severity Classification in Acute Pancreatitis Patients: a Retrospective Study
Authors: Lin Hao , Yu Ting , Xu Rong , Li Xing
Published: August 2021

Background/Objectives: The aim of this study is to explore the relationship between length of hospital stay and mean corpuscular hemoglobin (MCH) in acute pancreatitis (AP) patients.Methods: The study included 273 AP patients without coronary heart disease, diabetes, hypertension, tumor, psychosis and anemia. The clinical data was collected from electronic medical records.Results: We separated all data into three groups according to length of hospital stay. We observed that gender (P=0.017) and severity classification (P=0.000) were significantly correlated with length of hospital stay among three groups. Notably, MCH level was significant increased among three groups (30.02±1.91, 30.21±1.81, 30.92±2.47 pg, P=0.009). Thus, we separated all data into two groups according to MCH level, and observed significant increases of length of hospital stay between two groups (11.95±7.03, 13.96±8.18 days, P=0.030). A positive correlation between length of hospital stay and MCH was observed in these individuals (r=0.172, P=0.004). Multiple linear regression analysis showed that MCH was independent correlated with length of hospital stay, no matter whether severity classification of AP was included (beta=0.248, P=0.000; beta=0.212, P=0.000).Conclusions: We concluded that length of hospital stay is correlated with MCH level in AP patients, and the MCH level may predict length of hospital stay independent of severity classification in this disease. Our results may provide a potential evaluation basis for the management of patients with AP.
Loss of RPS27a expression regulates cell cycle, apoptosis, and proliferation via the RPS27a-RPL11-MDM2-p53 pathway in lung adenocarcinoma cells
Authors: Li Hongyan , Zhang Hong , Huang Guomin , Bing Zhitong , Luo Hongtao , Xu Duling , Liu Jiadi , An Xiaoli
Published: August 2021

Background
Some ribosomal proteins (RPs) might regulate the MDM2–p53 loop by binding to RPL5 or RPL11. This study aimed to explore whether ribosomal protein S27a (RPS27a) interacted with the ribosomal protein L11 (RPL11) to regulate p53 in lung adenocarcinoma (LUAD) cells.
Methods
RPL11-interacting proteins were identified using a proteomics approach. Co-immunoprecipitation (co-IP), docking analysis, GST-fusion and in vitro ubiquitination assay were used to analyze the interaction of RPS27a and RPL11. Cell cycle, apoptosis, cell invasion, cell viability and colony-formation assay were analyzed by knocking down RPS27a. The RPS27a mRNA expression in LUAD was analyzed based on the TCGA dataset and the RPS27a expression was detected by immunohistochemistry in LUAD samples. At last, the RPS27a and p53 expression were analyzed by immunohistochemistry in xenograft tumors by blocking RPS27a.
Results
The ablation of RPS27a inhibits murine double minute 2 (MDM2)-mediated p53 ubiquitination, induced G1/S cell cycle arrest and apoptosis, and inhibited the proliferation of LUAD cells. Also, it induced p53-dependent cell cycle arrest and RPL11-dependent p53 activation. The protein–protein docking results revealed that RPS27a and RPL11 formed a stable complex structure. The GST-fusion protein–protein association assay demonstrated that RPS27a bound to RPL11. The overexpressed RPS27a in LUAD was found to be correlated with a poorer prognosis based on the TCGA dataset. RPS27a expression was high in patients with LUAD. Blocking RPS27a increased p53, thus, suppressing cell proliferation and A549 xenograft growth in nude mice.
Conclusions
This study was novel in reporting that RPs bound to RPL11 to regulate the MDM2-p53 feedback loop, revealing that RPS27a plays an important function in LUAD growth. Hence, RPS27a might provide a diagnostic marker or therapeutic target for patients with LUAD.
­­­­Optimal Glucose and Stress-hyperglycaemia Ratio Cut-off Values for Predicting 1-year Mortality in Diabetic and Non-diabetic Acute Myocardial Infarction Patients
Authors: Sia Ching-Hui , Chan Mervyn Huan-Hao , Zheng Huili , Ko Junsuk , Ho Andrew Fu-Wah , Chong Jun Hua , Foo David , Foo Ling-Li , Lim Patrick Zhan-Yun , Liew Boon Wah , Chai Ping , Yeo Tiong-Cheng , Tan Huay-Cheem , Chua Terrance , Chan Mark Yan-Yee , Tan Jack Wei Chieh , Bulluck Heerajnarain , Hausenloy Derek J
Published: August 2021

Background

Stress-induced hyperglycaemia at time of hospital admission has been linked to worse prognosis following acute myocardial infarction (AMI). The stress-hyperglycaemia ratio (SHR) index normalises the acute increase in blood glucose values to background glycaemic status. However, the optimal cut-off blood glucose and SHR values for predicting adverse outcomes post-AMI are unknown. As such, we determined the optimal blood glucose and SHR cut-offs for predicting 1-year all cause mortality in diabetic and non-diabetic non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI) patients.
Methods

We undertook a national, registry-based study of patients with AMI from January 2008 to December 2015. We determined the optimal blood glucose and SHR cut-off values using the Youden’s formula for 1-year all-cause mortality. We subsequently analyzed the sensitivity, specificity, positive and negative predictive values of the cut-offs in the diabetic and non-diabetic subgroups, stratified by the type of AMI.
Results

There were 5,841 STEMI and 4,105 NSTEMI in the study. In STEMI patients, both glucose and SHR were independent predictors of 1-year all-cause mortality [Glucose: OR 2.19 (95% CI 1.74–2.75); SHR: 2.19 (95% CI 1.73–2.78)]. However, in NSTEMI patients, glucose and SHR were not independently associated with 1-year all-cause mortality [Glucose: OR 1.37 (95% CI 1.00-1.89); SHR: 1.27 (95% CI 0.91–1.78)]. In STEMI patients, ROC analysis showed that SHR performed better than glucose (AUC for glucose 0.633 versus AUC for SHR 0.692, P < 0.001) in diabetic patients, whereas in non-diabetic patients, SHR and glucose performed equally well (AUC for glucose 0.720 versus AUC for SHR 0.717, P < 0.664). The optimal glucose cut-off values were 15.0mmol/L for diabetic STEMI patients and 11mmol/L for non-diabetic STEMI patients and the corresponding optimal cut-off values for SHR were 1.7 and 1.5, respectively.
Conclusions

Glucose on admission and SHR were independent predictors of 1-year all-cause mortality in STEMI, whereas this was not the case in NSTEMI patients. In STEMI setting, SHR performed better than admission glucose to predict 1-year all-cause mortality in diabetic patients, whereas in non-diabetic patients both SHR and glucose performed equally well.
Mitochondrial Fission Regulator 2 (MTFR2) Confers anti-ER Endocrine Therapy Resistance to Breast Cancer Cells by Modulating Mitochondrial Autophagy through Direct Phosphorylation of FUNDC1
Authors: Zhang Zhanqiang , Lu Guanming , Lin Bo , Li Yanghong , Li Fuju , Wen Zipeng , Lv Weiming , Lai Yuanhui , li jie
Published: August 2021

Background: Mitochondrial fission regulator 2 (MTFR2) belongs to the MTFR1/ family with sequence similarity 54 (FAM54) family. Recently, it was reported that MTFR2 promotes the proliferation and invasion of breast cancers (BCs). However, the relationship between MTFR2 and endocrine crine therapy resistance is still unknown.Materials and methods: We collected 36 ER+ BC tissues and adjacent normal tissues and 10 samples from patients who received endocrine therapy. We detected the expression pattern of MTFR2 and the fold change in MTFR2 in cells treated with tamoxifen and letrozole. The autophagy status was also determined.Results: MTFR2 expression was upregulated in ER+ BC tissues and was strongly upregulated in the samples that were treated with endocrine therapy. Knocking out MTFR2 increased BC cell sensitivity to endocrine therapy. In addition, MTFR2 directly bound to FUNDC1 and promoted FUNDC1 phosphorylation, thus inhibiting autophagy.Conclusion: Taken together, our results indicate that increased expression of MTFR2 is associated with endocrine therapy resistance in BC cells. Our findings indicate that MTFR2 could serve as a novel therapeutic target for ER+ BC patients who suffer from endocrine therapy resistance.
Cost-Effectiveness of Remdesivir Plus Supportive Care for Patients with COVID-19 in Iran
Authors: Gholamhoseini Mohammad Tasavon , Goudarzi Reza , Yazdi-Feyzabadi Vahid , Mehrolhassani Mohammad Hossein , Yousefi Meysam
Published: August 2021

Background: Remdesivir is a medication used for moderate to severe Coronavirus disease 2019 (COVID-19) patients with favorable effects. However, it is an expensive medication. Therefore, the present study aimed to assess the cost-effectiveness of remdesivir plus supportive care (SC) for COVID-19 patients in Iran.Methods: Markov model was used to compare costs and quality-adjusted life-days (QALDs) of remdesivir+SC and SC for patients with COVID-19. The model simulated a cycle length of one day and a 30-day time horizonin TreeAge 2020 software. The costs from the healthcare system perspective were obtained from Afzalipour hospital as a referral hospital for the hospitalization of COVID-19 patients in Kerman, Iran. All the costs were converted to 2018 purchasing power parity (PPP) US dollars. Utility values were derived from published sources. The results were presented as an incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of three times the Gross Domestic Product per capita of Iran. Both deterministic and probabilistic sensitivity analyses were performed.Results: The base-case results showed that the treatment of COVID-19 patients with remdesivir+SC had a cost of 8795 PPP US dollars for 21.13 QALD gained. The SC alone cost 8637 PPP US dollars with a gain of 20.20 QALD. Our findings demonstrated that at a WTP threshold of 159 PPP US dollars per QALD, remdesivir+SC was not cost-effective with an ICER of 168 PPP US dollars per QALD. Deterministic sensitivity analysis indicated ICER to be sensitive to the transition probabilities and costs. Probabilistic sensitivity analysis revealed that remdesivir+SC was cost-effective at a WTP of 159 PPP US dollars per QALD in 47% of iterations.Conclusions: Our findings demonstrated thatremdesivir+SC is not cost-effective, compared to SC alone. Considering the lack of studies on the effectiveness of remdesivir, the findings should be interpreted with caution. Further evaluations are recommended to determine the efficacy and effectiveness of remdesivir in COVID-19 patients.
Changes of Gait Characteristics in Stroke Patient with Foot Drop After Treating by Foot Drop Stimulator Combined with Moving Treadmill Training
Authors: CHEN Peishun , ZHOU Haiwang , LI Taotao , GUANG Hongli , MIN Yu , ZHANG Wanrong
Published: August 2021

Background and PurposeTo analyze the changes of gait characteristics in stroke patient with foot drop after treating by foot drop stimulator combined with moving treadmill, and provide a basis for the improvement of foot drop gait after stroke.Methods Sixty patients with stroke and hemiplegia with foot drop were randomly divided into the experimental group and the control group. Both groups received basic rehabilitation training. On this basis, the experimental group received foot drop stimulator combined with moving treadmil. The control group received foot drop stimulator training. The treatment time of the two groups was 30 minutes/time, 5 times a week, for 3 consecutive weeks. Gait Watch three-dimensional gait analysis system was used to record the angle of hip flexion, knee flexion and ankle flexion before and after treatment. Results After treatment, the angles of hip flexion, knee flexion, and ankle flexion of the two groups of patients changed, but the above changes in the experimental group were better than those in the control group, The difference is statistically significant (p<0.05). ConclusionsThe foot drop stimulator combined with moving treadmill can significantly improve the foot gait after stroke, and promote the normalization of hip flexion and knee flexion.
Antitumor Effects of Cadmium Against Diethylnitrosamine-induced Liver Tumors in Mice
Authors: Nie Yu , Huang Bo , Hu An-Ling , Xu Yun-Yan , Zou Yan , Liu Yun , Liu Jie
Published: August 2021

Background: Cadmium (Cd) is reported to have antitumor effects against chemical-induced liver tumors. Antitumor effects of Cd are not completely understood, but may be related to metallothionein-deficiency in tumors, which makes tumor vulnerable to necrotic effects of Cd. Methods: Eight-week old male C57BL/6 mice were given injections of diethylnitrosamine (DEN, 90 mg/kg, and 50 mg/kg two weeks later), followed by promotion with CCl4. CdCl2 was administered in the drinking water (500 ppm) from 21-40 weeks after DEN initiation. Body weights were recorded and liver tumor formation was monitored via ultrasound. At the end of experiments, livers were removed, weighed, and the tumor incidence, tumor numbers and tumor size scores were recorded. Liver histology and metallothionein immunostaining were performed. Results: After DEN injection, animal body weight decreased, and slowly recovered afterwards. Cd treatment did not affect animal body weight gain. Ultrasounds detected liver tumors 35 weeks after DEN injection. Animals were necropsied at 40 weeks. Liver/body weight ratios increased in DEN and DEN+Cd groups. Cd treatment decreased tumor incidence (71% vs 17%), tumor numbers (15 vs 2), and tumor scores (22 vs 3). Histopathology showed hepatocyte degeneration in all groups, and immunohistochemistry showed metallothionein-deficiency in liver tumors, while metallothionein stain was intensified in tumor surrounding tissues. RT-qPCR showed increases of alpha-fetoprotein in DEN-treated livers, and increases of metallionein-2 and TNFα in Cd-treated livers. Conclusion: Cd is effective in suppression of DEN-induced liver tumors, and the mechanisms may be related to metallothionein-deficiency in tumors and induction of TNFα to kill tumor cells.