bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological and Immunomicroenvironment Characteristics of Epstein–Barr Virus-Associated Gastric Cancer in a Chinese Population
Authors: Jia Xiaoxia , Guo Ting , Li Zhemin , Zhang Meng , Feng Yi , Dong Bin , Li Zhongwu , Hu Ying , Li Ziyu , Xing Xiaofang , Jia Shuqin , Ji Jiafu 
Published: January 2021

BackgroundEpstein–Barr virus-associated gastric cancer(EBVaGC)has a unique tumor immune microenvironment. We performed a comprehensive analysis of the tumor-infiltrating immune cells in a cohort of EBVaGC in a Chinese population.MethodsEpstein–Barr encoding region (EBER) in situ hybridization was performed in 1,328 consecutive cases of surgically resected GC. Densities of immune cells, including T cells, B cells, natural killer cells, and macrophages from the patients were calculated after immunohistochemical staining with CD3, CD20, CD57, and CD68 antibodies in tissue microarrays, respectively.ResultsEBVaGC patients accounted for 4.1% (55 of 1,328) cases in the overall population. The average age of patients with EBVaGC was lower than that of non-EBVaGC patients. Histologically, EBVaGC patients exhibited poorly differentiated adenocarcinoma (P = 0.004) and lower frequency of vascular invasion (P = 0.034). The density of CD3+ T lymphocytes (CD3, 23.84 ± 14.49 vs. 12.76 ± 8.93, P &lt; 0.001) and CD68+ macrophages (CD68, 9.73 ± 5.25 vs. 5.44 ± 4.18, P &lt; 0.001) was significantly higher in EBVaGC patients. CD3+ T cell density predicted better 5-year overall survival of EBVaGC patients (P = 0.022).ConclusionsEBVaGC patients were younger with low-differentiated adenocarcinoma and less vascular invasion. Increased infiltration of multiple immune cells affected the prognosis of patients, especially EBVaGC patients with more CD3+ T lymphocytes, who survived longer.
Prognostic Value of PLXND1 and TGF-β1 Coexpression and Its Correlation With Immune Infiltrates in Hepatocellular Carcinoma
Authors: Li Juanni , Hu Kuan , He Dongren , Zhou Lei , Wang Zhiming , Tao Yiming 
Published: January 2021

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with no curative treatments. Plexin D1 (PLXND1) is a cellular receptor whose functions have been explored in several human cancers; however, the critical roles of PLXND1 in HCC have rarely been probed. Therefore, the present study attempted to elucidate the expression pattern, prognostic significance, and potential roles of PLXND1 in HCC. We found that PLXND1 expression in HCC tissues was significantly higher compared with normal liver tissue from Gene Expression Profiling Interactive Analysis (GEPIA) and Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB) databases. This result was further validated by immunohistochemistry staining (IHC) using tissue microarrays, which contained 216 HCC cases collected from our hospital. Additionally, PLXND1 expression showed a significant correlation with several clinical characteristics, including tumor grade and tumor hemorrhage (TH). Moreover, TISIDB and GEPIA databases were used to investigate the roles of PLXND1 in tumor-immune system interactions in HCC. As an immunoinhibitor, transforming growth factor-beta (TGF-β1) displayed the greatest correlations with PLXND1 in HCC. Finally, Kaplan-Meier curves and Cox analysis were conducted to further examine the potential clinical value of PLXND1 in HCC. We described a subclassification of HCC based on PLXND1 and TGF-β1 expression, which could be used to predict clinical outcomes and patient prognosis. Taken together, the results of this study indicate that PLXND1 might be a promising prognostic biomarker and potential therapeutic target in HCC.
GFI1-Mediated Upregulation of LINC00675 as a ceRNA Restrains Hepatocellular Carcinoma Metastasis by Sponging miR-942-5p
Authors: Lu Libai , Li Shubo , Zhang Ying , Luo Zongjiang , Chen Yichen , Ma Jiasheng , Chen Pengyu , Wang Wei , Pu Jian , Wang Jianchu 
Published: January 2021

Hepatocellular carcinoma (HCC) is a common malignant liver tumor worldwide. Tumor recurrence and metastasis contribute to the bad clinical outcome of HCC patients. Substantial studies have displayed lncRNAs modulate various tumorigenic processes of many cancers. Our current work was aimed to investigate the function of LINC00675 in HCC and to recognize the potential interactions between lncRNAs and microRNAs. GFI1 can exhibit a significant role in the progression of human malignant tumors. Firstly, GFI1 was identified using real-time PCR in HCC tissues and cells. In this work, we indicated GFI1 was remarkably reduced in HCC tissues and cells. Meanwhile, GFI1 specifically interacted with the promoter of LINC00675. Up-regulation of LINC00675 obviously repressed the migration and invasion capacity of SMCC-7721 and QGY-7703 cells in vitro. Moreover, decrease of LINC00675 competitively bound to miR-942-5p that contributed to the miRNA-mediated degradation of GFI1, thus facilitated HCC metastasis. The ceRNA function of LINC00675 in HCC cells was assessed and confirmed using RNA immunoprecipitation assay and RNA pull-down assays in our work. Additionally, we proved overexpression of miR-942-5p promoted HCC progression, which was reversed by the up-regulation of GFI1. In summary, LINC00675 might act as a prognostic marker for HCC, which can inhibit HCC development via regulating miR-942-5p and GFI1.
Whole-Lesion Histogram Analysis of the Apparent Diffusion Coefficient as a Quantitative Imaging Biomarker for Assessing the Level of Tumor-Infiltrating Lymphocytes: Value in Molecular Subtypes of Breast Cancer
Authors: Tang Wen-jie , Jin Zhe , Zhang Yan-ling , Liang Yun-shi , Cheng Zi-xuan , Chen Lei-xin , Liang Ying-ying , Wei Xin-hua , Kong Qing-cong , Guo Yuan , Jiang Xin-qing 
Published: January 2021

PurposeTo assess whether apparent diffusion coefficient (ADC) metrics can be used to assess tumor-infiltrating lymphocyte (TIL) levels in breast cancer, particularly in the molecular subtypes of breast cancer.MethodsIn total, 114 patients with breast cancer met the inclusion criteria (mean age: 52 years; range: 29–85 years) and underwent multi-parametric breast magnetic resonance imaging (MRI). The patients were imaged by diffusion-weighted (DW)-MRI (1.5 T) using a single-shot spin-echo echo-planar imaging sequence. Two readers independently drew a region of interest (ROI) on the ADC maps of the whole tumor. The mean ADC and histogram parameters (10th, 25th, 50th, 75th, and 90th percentiles of ADC, skewness, entropy, and kurtosis) were used as features to analyze associations with the TIL levels in breast cancer. Additionally, the correlation between the ADC values and Ki-67 expression were analyzed. Continuous variables were compared with Student’s t-test or Mann-Whitney U test if the variables were not normally distributed. Categorical variables were compared using Pearson’s chi-square test or Fisher’s exact test. Associations between TIL levels and imaging features were evaluated by the Mann-Whitney U and Kruskal-Wallis tests.ResultsA statistically significant difference existed in the 10th and 25th percentile ADC values between the low and high TIL groups in breast cancer (P=0.012 and 0.027). For the luminal subtype of breast cancer, the 10th percentile ADC value was significantly lower in the low TIL group (P=0.041); for the non-luminal subtype of breast cancer, the kurtosis was significantly lower in the low TIL group (P=0.023). The Ki-67 index showed statistical significance for evaluating the TIL levels in breast cancer (P=0.007). Additionally, the skewness was significantly higher for samples with high Ki-67 levels in breast cancer (P=0.029).ConclusionsOur findings suggest that whole-lesion ADC histogram parameters can be used as surrogate biomarkers to evaluate TIL levels in molecular subtypes of breast cancer.
A Prediction Model for Optimal Primary Debulking Surgery Based on Preoperative Computed Tomography Scans and Clinical Factors in Patients With Advanced Ovarian Cancer: A Multicenter Retrospective Cohort Study
Authors: Gu Yu , Qin Meng , Jin Ying , Zuo Jing , Li Ning , Bian Ce , Zhang Yu , Li Rong , Wu Yu-mei , Wang Chun-yan , Zhang Ke-qiang , Yue Ying , Wu Ling-ying , Pan Ling-ya 
Published: January 2021

ObjectiveThis study assessed the predictive value of preoperative computed tomography (CT) scans and clinical factors for optimal debulking surgery (ODS) in patients with advanced ovarian cancer (AOC).MethodsPatients with AOC in International Federation of Gynecology and Obstetrics (FIGO) stage III-IV who underwent primary debulking surgery (PDS) between 2016 and 2019 from nine tertiary Chinese hospitals were included. Large-volume ascites, diffuse peritoneal thickening, omental cake, retroperitoneal lymph node enlargement (RLNE) below and above the inferior mesenteric artery (IMA), and suspected pelvic bowel, abdominal bowel, liver surface, liver parenchyma and portal, spleen, diaphragm and pleural lesions were evaluated on CT. Preoperative factors included age, platelet count, and albumin and CA125 levels.ResultsOverall, 296 patients were included, and 250 (84.5%) underwent ODS. The prediction model included age &gt;60 years (P=0.016; prediction index value, PIV=1), a CA125 level &gt;800 U/ml (P=0.033, PIV=1), abdominal bowel metastasis (P=0.034, PIV=1), spleen metastasis (P&lt;0.001, PIV=2), diaphragmatic metastasis (P=0.014, PIV=2), and an RLNE above the IMA (P&lt;0.001, PIV=2). This model had superior discrimination (AUC=0.788&gt;0.750), and the Hosmer-Lemeshow test indicated its stable calibration (P=0.600&gt;0.050). With the aim of maximizing the accuracy of prediction and minimizing the rate of inappropriate explorations, a total PIV ≥5 achieved the highest accuracy of 85.47% and identified patients who underwent suboptimal PDS with a specificity of 100%.ConclusionsWe developed a prediction model based on two preoperative clinical factors and four radiological criteria to predict unsatisfactory debulking surgery in patients with AOC. The accuracy of this prediction model needs to be validated and adjusted in further multicenter prospective studies.
A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective
Authors: Chassagne François , Samarakoon Tharanga , Porras Gina , Lyles James T. , Dettweiler Micah , Marquez Lewis , Salam Akram M. , Shabih Sarah , Farrokhi Darya Raschid , Quave Cassandra L. 
Published: January 2021

Background:Antimicrobial resistance represents a serious threat to human health across the globe. The cost of bringing a new antibiotic from discovery to market is high and return on investment is low. Furthermore, the development of new antibiotics has slowed dramatically since the 1950s’ golden age of discovery. Plants produce a variety of bioactive secondary metabolites that could be used to fuel the future discovery pipeline. While many studies have focused on specific aspects of plants and plant natural products with antibacterial properties, a comprehensive review of the antibacterial potential of plants has never before been attempted.Objectives:This systematic review aims to evaluate reports on plants with significant antibacterial activities.Methods:Following the PRISMA model, we searched three electronic databases: Web of Science, PubMed and SciFinder by using specific keywords: “plant,” “antibacterial,” “inhibitory concentration.”Results:We identified a total of 6,083 articles published between 1946 and 2019 and then reviewed 66% of these (4,024) focusing on articles published between 2012 and 2019. A rigorous selection process was implemented using clear inclusion and exclusion criteria, yielding data on 958 plant species derived from 483 scientific articles. Antibacterial activity is found in 51 of 79 vascular plant orders throughout the phylogenetic tree. Most are reported within eudicots, with the bulk of species being asterids. Antibacterial activity is not prominent in monocotyledons. Phylogenetic distribution strongly supports the concept of chemical evolution across plant clades, especially in more derived eudicot families. The Lamiaceae, Fabaceae and Asteraceae were the most represented plant families, whileCinnamomum verum,Rosmarinus vulgarisandThymus vulgariswere the most studied species. South Africa was the most represented site of plant collection. Crude extraction in methanol was the most represented type of extraction and leaves were the main plant tissue investigated. Finally,Staphylococcus aureuswas the most targeted pathogenic bacteria in these studies. We closely examine 70 prominent medicinal plant species from the 15 families most studied in the literature.Conclusion:This review depicts the current state of knowledge regarding antibacterials from plants and provides powerful recommendations for future research directions.
PK/PD Study of Mycophenolate Mofetil in Children With Systemic Lupus Erythematosus to Inform Model-Based Precision Dosing
Authors: Chen Yewei , Sun Li , Xu Hong , Dong Min , Mizuno Tomoyuki , Vinks Alexander A. , Brunner Hermine I. , Li Yifan , Li Zhiping 
Published: January 2021

Objectives: To evaluate the mycophenolic acid [MPA, the active form of mycophenolate mofetil (MMF)] pharmacokinetic parameters in relation to clinical response to identify target exposure ranges in pediatric patients with systemic lupus erythematosus (SLE).Methods: This was a retrospective study using pharmacokinetic data collected in 67 pediatric patients aged 4–18 years with SLE. Target MPA exposures for effective inhibition of SLE activity (as measured by SLE disease Activity Index (SLEDAI), active SLE was defined as a SLEDAI score of ≥6, and a controlled disease was defined as a SLEDAI score of ≤4) were assessed by receiver operating characteristic (ROC) curve and logistic regression. Exposure-response models were developed to quantitatively describe the relationship between SLEDAI score and AUC0–12 or Ctrough, respectively.Results: The MPA AUC0-12 in patients with active SLE was significantly lower than that in patients with inactive SLE. ROC analysis revealed that an AUC0–12 threshold of 39 μg h/ml or a Ctrough of 1.01 μg/ml was associated with the lowest risk of active SLE. Logistic regression analysis revealed that an AUC0–12 of less than 34 μg h/ml or a Ctrough of less than 1.2 μg/ml probably is associated with active SLE. The results of the exposure-response modeling also indicated that an AUC0-12 less than 32 μg h/ml or a Ctrough less than 1.1 μg/ml was associated with suboptimal clinical outcome. An AUC0-12 above 50 μg h/ml or a Ctrough above 1.7 ug/ml was associated with disease control.Conclusion: Both AUC0–12 and Ctrough of MPA are predictive of the likelihood of active SLE in pediatric patients receiving MMF. An individualized dosing regimen of MMF, with a target AUC0–12 or Ctrough, should be considered for SLE patients.
Health-Related Fitness in Adults From Eight European Countries—An Analysis Based on Data From the European Fitness Badge
Authors: Klemm Katja , Krell-Roesch Janina , De Clerck Ine Lucia , Brehm Walter , Boes Klaus 
Published: January 2021

BackgroundThere are conflicting reports about the fitness status of European adults, partly due to the lack of a standardized fitness test battery used across Europe. The European Fitness Badge (EFB) was developed in 2017 as an online-based tool to assess the health-related fitness of persons aged ≥ 18 years residing in European countries. We examined the demographic characteristics and fitness status of persons who completed the EFB between June 2017 and May 2019.MethodsWe conducted a multinational study in eight European countries. Participants completed the EFB which includes 11 validated motor tests to measure endurance, strength, coordination, and flexibility performance, under the supervision of an EFB instructor in different settings (e.g., sports club sessions, public events). Two different test batteries [test profiles (TPs)] are available to distinguish between less active (TP1) and active individuals (TP2). We calculated descriptive statistics and conducted analyses of variance to examine sample characteristics and a potential impact of sex, age, body mass index (BMI), physical activity, and posture on fitness as assessed by the EFB.ResultsThe sample included 6,019 adults (68.7% females; mean age 52.7 years; age range 18–89 years). Participants who completed TP1 were older (TP1: 61.4 years; TP2: 44.2 years; p = 0.00), reported a lower level of physical activity (TP1: 3.8; TP2: 4.0; p = 0.00), had a higher BMI (TP1: 25.7; TP2: 24.3; p = 0.00) and a higher frequency of postural abnormalities (TP1: 43%; TP2: 33%; p = 0.00) than TP2 participants. Among 3,034 participants who completed TP2, males had higher performance in endurance, strength, and overall fitness, whereas females performed better in coordination and flexibility tests. In addition, younger age, lower BMI, and higher level of physical activity engagement were associated with better EFB test performance.ConclusionThe EFB can be used to assess the health-related fitness status of individuals aged ≥ 18 years. Our results show that TP1 and TP2 were completed by persons from the respective target groups (i.e., less active vs. active), and also confirm findings from previous studies on potential determinants of fitness such as sex or age.
Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder
Authors: Alvarez-Mon Miguel Angel , Gomez-Lahoz Ana Maria , Orozco Arantxa , Lahera Guillermo , Sosa-Reina M. Dolores , Diaz David , Albillos Agustin , Quintero Javier , Molero Patricio , Monserrat Jorge , Alvarez-Mon Melchor 
Published: January 2021

Background: Major Depressive Disorder (MDD) is associated with both proinflammatory and adaptive immune response abnormalities. Regulatory T lymphocytes (Tregs), a subtype of CD4+ T cells, are relevant for maintaining immune-inflammatory system homeostasis and control of inflammation such as the kind potentially induced by the interactions between the intestinal microbiome and gut mucosa. We investigated the Treg population and its distribution along their stages of differentiation/activation, as well as its function in MDD patients without concomitant diseases. We also studied the potential association between Treg alterations, intestinal barrier damage, and bacterial translocation.Methods: 30 MDD patients and 20 healthy controls were studied. The levels of circulating CD25FoxP3+ Tregs and their distribution on the naïve (TN), effector (TE), central (TCM), and effector memory(TEM) differentiation/activation stages were analyzed using polychromatic flow cytometry. Chemokine receptors (CCR) 2, 5, and 6, and the intracytoplasmic IL-10 expression by the Tregs were also analyzed. The serum IL-10 was measured using Luminex. The serum levels of zonulin and the intestinal fatty acid-binding protein (I-FABP), both markers of gut barrier function, and the LPS-binding protein (LBP), a marker of bacterial translocation, were measured using an enzyme-linked immunosorbent assay.Results: MDD patients had increased number of circulating Tregs cells with enhanced number of Tregs at the TN, TE, TCM, and TEM stages. The percentage of Tregs cells at TN stage was significantly higher in MDD patients. The percentage of Tregs that expressed CCR2 and CCR6 was increased as well as those expressing IL-10. MDD patients had significantly increased levels of circulating I-FABP and LBP. MDD patients with high LBP levels had a significant reduction in the number of circulating Tregs compared to normal-LBP MDD patients.Conclusions: MDD patients showed an expansion of circulating Tregs and their CD25highFoxP3+ and CD25lowFoxP3+ subsets throughout the different stages of CD4+ T lymphocyte differentiation/activation. Tregs also showed an increased frequency of cells expressing CCR6 and CCR2. IL-10 Treg production was also enhanced in MDD patients that concurrently had increased serum IL-10 levels. However, this Treg expansion was blunted in MDD patients with gut barrier damage and increased bacterial translocation.
“The Graying Minority”: Lived Experiences and Psychosocial Challenges of Older Transgender Adults During the COVID-19 Pandemic in India, A Qualitative Exploration
Authors: Banerjee Debanjan , Rao T. S. Sathyanarayana 
Published: January 2021

Background: The Coronavirus disease 2019 (COVID-19) has emerged as a global health threat. Certain factors like age, an immunocompromised state, and social impoverishment, etc. can add to health vulnerabilities during this pandemic. One such group is older transgender adults, who often bear a combination of these risks. As the world is aging fast, their numbers have also been increasing. With this in mind, this study explores the lived experiences and psychosocial challenges of older transgender adults during the COVID-19 pandemic in India.Methods: A qualitative approach was used. Ten individuals with “transgender” identity above the age of 60 were recruited with consent through purposive sampling. In-depth interviews were conducted on the telephone using a pre-designed interview schedule. They were recorded, translated, and transcribed verbatim. Hasse's adaptation of Colaizzi's phenomenological method was used for analysis. Independent coding and respondent validation were used to ensure the rigor of data.Results: The super-arching categories (with themes) were marginalization (“second” priority, stigma, social disconnection), the dual burden of “age” and “gender” (ageism, othering, and psychosexual difficulties), and multi-faceted survival threats (physical, emotional, financial) during the pandemic. Social rituals, spirituality, hope, and acceptance of “gender dissonance” emerged as the main coping factors, whereas their unmet needs were social inclusion, awareness related to COVID-19, mental health care, and audience to their distress.Conclusion: The elderly gender minorities are at increased emotional and social risks during the ongoing pandemic, and their voices are mostly unheard. The need for policy implementation and community awareness about their social welfare is vital to improving their health and well-being.
Death Associated With Coronavirus (COVID-19) Infection in Individuals With Severe Mental Disorders in Sweden During the Early Months of the Outbreak—An Exploratory Cross-Sectional Analysis of a Population-Based Register Study
Authors: Maripuu Martin , Bendix Marie , Öhlund Louise , Widerström Micael , Werneke Ursula 
Published: January 2021

Background: Individuals with severe mental disorder (SMD) have a higher risk of somatic comorbidity and mortality than the rest of the population. We set up a population-based study to assess whether individuals with SMD had a higher risk of death associated with a COVID-19 infection (COVID-19 associated death) than individuals without SMD.Methods: Exploratory analysis with a cross-sectional design in the framework of a population-based register study covering the entire Swedish population. The Swedish Board for Health and Welfare (Socialstyrelsen) provided anonymized tabulated summary data for further analysis. We compared numbers of COVID-19 associated death in individuals with SMD (cases) and without SMD (controls). We calculated the odds ratio (OR) for the whole sample and by age group and four comorbidities, namely diabetes, cardiovascular disease, hypertension, chronic lung disease.Results: The sample comprised of 7,923,859 individuals, 103,999 with SMD and 7,819,860 controls. There were 130 (0.1%) COVID-19 associated deaths in the SMD group and 4,945 (0.06%) in the control group, corresponding to an OR of 1.98 (CI 1.66-2.35; p &lt; 0.001). The odds were 4-fold for the age groups between 60 and 79 years and 1.5-fold for cardiovascular diseases. Individuals with SMD without any of the risk factors under study had 3-fold odds of COVID-19 associated death.Conclusion: Our preliminary results identify individuals with SMD as a further group at increased risk of COVID-19 associated death. In regard to comorbidities, future studies should explore the potential confounding or mediation role in the relationship between SMD and COVID-19 associated deaths.