bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal High-fat Diet During Pregnancy Programs Platelet Hyperactivation in Male Mouse Offspring
Authors: Gaspar Renato Simões , Unsworth Amanda J , Bye Alex , Sage Tanya , Stewart Michelle , Wells Sara , Cox Roger D , Gibbins Jonathan M , Sellayah Dyan , Hughes Craig 
Published: July 2020

Abstract
Background: Maternal over-nutrition increases the risk of diabetes and cardiovascular events in offspring. While prominent effects on cardiovascular health are observed, the impact of this on platelet physiology has not been studied. Here, we sought to determine whether maternal high-fat diet (HF) ingestion can affect the platelet function in offspring.Methods: C57BL6/N mice dams were given a HF or control (C) diet for 8 weeks prior to and during pregnancy. Male offspring also received either C or HF diets for 26 weeks. Experimental groups were: C/C, dam and offspring fed chow; C/HF dam fed chow and offspring fed high-fat diet; HF/C and HF/HF. Various phenotypic (including body weight and % of body fat) and metabolic (glycaemia, triglyceridemia) tests were performed and blood collected for platelet studies. Results: Compared to C/C, HF/HF animals were obese, with fat accumulation, hyperglycaemia, insulin resistance and low respiratory exchange rate. HF/HF, but not C/HF mice also showed hypertriglyceredaemia and higher mean platelet volume. These platelets were hyperreactive, displaying higher fibrinogen binding after stimulation with different agonists. They also showed increased platelet adhesion and spreading on collagen. Maternal obesity led to an overall effect of increased platelet reactivity in offspring. Both maternal and offspring HF groups presented decreased levels of collagen receptor GPVI with increased oxidative stress. Western blotting experiments in stimulated platelets showed increased phosphorylation of PKC substrates, total tyrosine and AKT at Ser473, whilst response to nitric oxide donor PAPA-NONOate was unchanged compared to C/C.Conclusions: Maternal HF diet ingestion programmes platelet hyperactivation in male mouse offspring, whilst HF in both dams and offspring resulted in a 'double-hit' effect of increased serum triglyceride levels, large platelets and increased reactivity. This involved enhanced Tyr phosphorylation, ROS production and decreased GPVI expression. Since platelet function can be programmed by early developmental periods, it is possible to use this window of intervention to reduce the risk of thrombotic events.
Discriminant Models for the Prediction of Viral Shedding Time and Disease Progression in COVID-19
Authors: Li Wen Yang , Guo Yuhao , Zheng Xiaowei , Zhao Hongwen , Kang Jian , Wang Daqing , Wang Wei 
Published: July 2020

Abstract
Background

COVID-19 infection can cause life-threatening respiratory disease. This study aimed to fully characterize the clinical features associated with postponed viral shedding and disease progression, then develop and validate two prognostic discriminant models.
Methods

This study included 125 hospitalized patients with COVID-19. 44 parameters were recorded, including age, gender, underlying comorbidities, epidemic features, laboratory indexes, imaging characteristics and therapeutic regimen, et al. F-test and χ2 test were used for feature selection. All models were developed with 4-fold cross-validation, and the final performances of each model were compared by the Area Under Receiving Operating Curve (AUROC). After optimizing the parameters via L2 regularization, prognostic discriminant models were built to predict postponed viral shedding and disease progression of COVID-19 infection. The test set was then used to detect the predictive values via assessing models sensitivity and specificity.
Results

69 patients had a postponed viral shedding time (> 14 days), and 28 of 125 patients progressed into severe cases. Eleven and six demographic, clinical features and therapeutic regimen were significantly associated with postponed viral shedding and disease progressing, respectively (p < 0.05). The optimal discriminant models are: y1 (postponed viral shedding) = -0.244 + 0.2829x1 (the interval from the onset of symptoms to antiviral treatment) + 0.2306x4 (age) + 0.234x28 (Urea) − 0.2847x34 (Dual-antiviral therapy) + 0.3084x38 (Treatment with antibiotics) + 0.3025x21 (Treatment with Methylprednisolone); y2 (disease progression) = -0.348–0.099x2 (interval from Jan 1st, 2020 to individualized onset of symptoms) + 0.0945x4 (age) + 0.1176x5 (imaging characteristics) + 0.0398x8 (short- term exposure to Wuhan) − 0.1646x19 (lymphocyte counts) + 0.0914x20 (neutrophil counts) + 0.1254x21 (neutrphil/lymphocyte ratio) + 0.1397x22 (C-Reactive Protein) + 0.0814x23 (Procalcitonin) + 0.1294x24 (Lactic dehydrogenase) + 0.1099x29 (Creatine kinase). The output ≥ 0 predicted postponed viral shedding or disease progressing to severe/critical state. These two models yielded the maximum AUROC, and faired best in terms of prognostic performance (sensitivity of 73.3%, 75%, and specificity of 78.6%, 75% for prediction of postponed viral shedding and disease severity, respectively).
Conclusion

The two discriminant models could effectively predict the postponed viral shedding and disease severity, and be used as early-warning tools for COVID-19.
Characteristics of Klebsiella Pneumoniae ST4 Coharboring qnrB1, aac-Ib-cr, CTX-M-15 and SHV 11 in a Tunisian Hospital
Authors: Yaiche MARIEM Nasri , Rafraf Ikbel Denden , guo qinglan , Mastouri Maha , Aouni Mahjoub , Wang Minggui 
Published: July 2020

Abstract
Background: Multiresistant Klebsiella pneumoniae are predominant cause of hospital acquired infection. This work describes the molecular epidemiology of these isolates in Tunisian Hospital.Methods: Between October 2010 and June 2013, 50 non-duplicated clinical K.pneumoniae were selected on the basis of nalidixic acid (NA) resistance and were characterized. Isolates were identified using APi 20E system. Susceptibility testing was determined using the disc diffusion method and the microdilution technique to determine the MIC of ciprofloxacin.PMQR and ESBL genes were detected by PCR and positive results were confirmed by direct sequencing of PCR products. Multilocus sequence typing (MLST) was performed to determine the genetic relationship among isolates. Conjugation and transformation were done to know if PMQR and ESBL were carried with one or two plasmids.Results: A total of 20 PMQR harboring K.pneumoniae representing 40% of all NA resistant isolates were characterized. Among PMQR positive K.pneumoniae 13 were resistant to amoxicilline, amoxicilline/clavulanic acid, ticarcilline, piperacilline, cefaloridine, cefotaxime (CTX) and ceftazidime. The rate of resistance to gentamicine, tobramicine and amikacine were 85%, 95% and 25% respectively.Out of 20 K.pneumoniae (60%) were qnr positive (1 qnrA6 and 11 qnrB1) and (60%) were aac-Ib-cr positive. 33.3% coharbored the aac-Ib-cr and qnrB1 determinants. Out of all PMQR positive strains, 65% harbored ctx-M-15 gene. It was associated to shv11 in three cases and tem1 in two cases. The predominant types were ST4 (35%) and ST15 (20%). ST 101(15%) and ST 147 (10%) come in second order. one case of each ST14,ST86,ST336 and ST307 were also observed. qnrB1, aac-Ib-cr, Ctx-m-15 can be carried with more than one plasmid in the same bacteria.Conclusion: The co-existing of different genes conferring resistance among the same and different family of antibiotics is a big threat to patient because it limits the therapeutic process. This phenomonen is a problem of concern that needs to improve the resistance surveillance of multi gene carrying K pneumoniae.
A phase II study of amrubicin as palliative chemotherapy for previously treated malignant pleural mesothelioma
Authors: Watanabe Kageaki , Okuma Yusuke , Kawai Shoko , Nagamata Makoto , Hosomi Yukio 
Published: July 2020

Abstract
Background Treatment options for malignant pleural mesothelioma (MPM) are limited. Anthracyclines are considered key drugs for treating MPM. However, their use is limited by severe cardiac toxicities. Amrubicin (AMR) is a next-generation anthracycline that is commonly used to treat lung cancer. We conducted a phase II trial of this drug in patients with previously treated MPM.Methods Eligible patients with MPM having adequate organ function and a performance status of 0–2 were enrolled after disease progression following pemetrexed/platinum therapy. Patients received 35 mg/m2 AMR on days 1–3 every 3 weeks until tumor progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate (ORR). Median progression-free survival (PFS), overall survival (OS), number of treatment cycles, and adverse events (AEs) were evaluated as secondary endpoints.Results This trial was discontinued because of low accrual. From September 2013 to July 2018, five patients with MPM were enrolled. Stable disease (SD) was observed in three patients (60%), and progressive disease was noted in two patients (40%). The median PFS was 2.4 (range, 1.2–11.2) months, and the median OS was 9.1 (range, 6.2–22.0) months. The median number of treatment cycles was three (range, 2–11). Grade 1/2 toxicities were observed in all patients. Grade 3/4 neutropenia was observed in four patients (80%), but there were no cases of febrile neutropenia.Conclusion Despite the absence of the responders, the observation of SD in three patients suggests that AMR could have potential for treating MPM.Trial registration number and date of registrationUMIN000010739, May 16, 2013, retrospectively registered
Efficacy and safety of novel treatments in chemotherapy-naïve castration-resistant prostate cancer
Authors: Min ZhiChao 
Published: July 2020

Abstract
Background

Currently, novel treatment methods for chemotherapy-naïve castration-resistant prostate cancer (CRPC) patients have been applied in clinical practice. Since the optimum regimen remains inconclusive, this study compares the efficacy and safety of these treatments by network meta-analysis.

Methods

The PubMed and ClinicalTrials.gov database and review articles before January 30, 2020 were searched and date were extracted. A total of 29908 patients with CRPC from 23 randomized controlled trials were included. Relative hazard ratios (HR) had been used to assess the effects on overall survival (OS), progression-free survival (PFS) or radiographic PFS (rPFS), and adverse events (AEs). We then pooled the data and used Bayesian and frequentist random-effects model to identify the best treatment strategy.

Results

Compared with the placebo, both Bayesian and frequentist random-effects network meta-analyses found that only enzalutamide and abiraterone had a significant effect in OS. Similar results were observed in PFS/rPFS. Bicalutamide, tasquinimod and orteronel could also improve rPFS. Enzalutamide only could improve rPFS more effectively than abiraterone with no significant differences in OS/PFS/AEs. In any subgroups of patients with age <75, ≥75 or ECOG score = 0,1 or Gleason score ≤7, ≥8, enzalutamide could improve the OS significantly. Nevertheless, the significant benefit of abiraterone was only found in patients with age <75 and ECOG score = 0.

Conclusions

Our network analysis suggested that both enzalutamide and abiraterone are optimal treatment for chemotherapy-naïve CRPC patients with age <75 and ECOG score = 0 for great improvement on OS and PFS. In addition, enzalutamide is also an optimum therapy for chemotherapy-naïve CRPC patients with age ≥75 and ECOG score = 1.
SARS-CoV-2 Viral Load is Associated with Increased Disease Severity and Mortality
Authors: Fajnzylber Jesse , Regan James , Coxen Kendyll , Corry Heather , Wong Colline , Rosenthal Alexandra , Worrall Daniel , Giguel Francoise , Piechocka-Trocha Alicja , Atyeo Caroline , Fischinger Stephanie , Chan Andrew , Flaherty Keith , Hall Kathryn , Dougan Michael , Ryan Edward , Gillespie Elizabeth , Chishti Rida , Li Yijia , Jilg Nikolaus , Hanidziar Dusan , Baron Rebecca , Baden Lindsey , Tsibris Athe , Armstrong Katrina , Alter Galit , Kuritzkes Daniel , Walker Bruce , Yu Xu , Li Jonathan 
Published: July 2020

Abstract
The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). We quantified SARS-CoV-2 viral load from participants with a diverse range of COVID-19 severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. SARS-CoV-2 plasma RNA was detected in 27% of hospitalized participants and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, higher prevalence of detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, were associated with increased risk of mortality. SARS-CoV-2 viral load may aid in the risk stratification of patients with COVID-19 and its role in disease pathogenesis should be further explored.
Kaempferide Improves Glycolipid Metabolism Disorder by Activating PPARγ in High-Fat-Diet-Fed Mice
Authors: Zeng Qingfu , Tang Heng , Tang Ting , Pu Peng 
Published: July 2020

Abstract
Background: Kaempferide (Ka, 3,5,7-trihydroxy-4′-methoxyflavone), an active ingredient of Tagetes erecta L has been demonstrated to possess many pharmacological effects, including antioxidant, anti-inflammation, anticancer and antihypertension in previous study. However, there is no evidence of Ka on metabolic disorder in former studies. This study investigated the effects of Ka on glycolipid metabolism and explored the underlying mechanisms of action in vivo and vitro. Methods: High-fat diet (HFD) was used to induce the model of glycolipid metabolism disorder in mice.The hypolipidemic and hypoglycemic effect was detected by several indicators, like blood sample analysis blood glucose, serum insulin, HOMA index and intraperitoneal glucose tolerance tests (IPGTT). The signaling pathways of lipid metabolism (PPARγ/LXRα/ABCA1) and glucose metabolism (PPARγ/PI3K/AKT) were evaluated using Real-Time PCR and Western blot. The primary culture of hepatocytes was prepared to confirm the target of Ka by co-culturing with PPARγ agonist or inhibitor.Results: Administration of Ka at a dose of 10mg/kg for 16 weeks effectively attenuated obesity, hyperlipidemia, hyperglycemia and insulin resistance in HFD mice. Further studies revealed the hypolipidemic and hypoglycemic effects of Ka depended on the activation of PPARγ/LXRα/ABCA1 pathway and PPARγ/PI3K/AKT pathway, respectively. The primary hepatocyte test, co-cultured with PPARγ agonists or inhibitors, further confirmed the above signaling pathway and key protein. Conclusion: Ka played an important role in improving glycolipid metabolism disorder, which were causally associated with weight loss. The underlying mechanisms might are associated with the activation of PPARγ and its downstream signaling pathway. Our study helped to understand the pharmacological actions of Ka, and provides theoretical basis for Ka in the effective treatment of obesity, diabetes and other metabolic diseases.
High prevalence of pre-existing HBV polymerase mutations in pregnant women do not limit the telbivudine treatment efficacy
Authors: Wang Jing , Liu Jinfeng , Yu Qiang , Jin Li , Yao Naijuan , Yang Yuan , Yan Taotao , Hu Chunhua , He Yingli , Zhao Yingren , Chen Tianyan , Zheng Jie 
Published: July 2020

Abstract
Background: HBV resistant mutants in treatment-naïve patients may lead to antiviral treatment failure. It’s not clear if HBV resistant mutants present in the pregnant women before the antiviral treatment and the influence of the pre-existing resistant mutants on the short-term Telbivudine (TBV) therapy during the late pregnancy.Method: We enrolled 73 pregnant women with high HBV DNA load and TBV treatment during the pregnancy from 2012 to 2015 in this retrospective study. All subjects were followed at least 52 weeks postpartum. The UDPS was used to detect the HBV mutations before and after the TBV treatment.Results: Before TBV treatment, the complexity of HBV quasispecies of all subjects was 0.40± 0.09. At primary drug resistance mutation sites, 41.1% (30/73) and 53.4% (39/73) subjects had rtM204I/V and rtN236T/A detected, respectively; 9.6% (7/73) patients had more than 20% frequency mutation of rtM204I/V, which was also similar with high frequency of rtN236T/A mutation (41.1% vs. 53.4%, P = 0.136; frequencies > 20%: 9.6% vs. 5.5%, P = 0.347). After TBV treatment, 71.2% (52/73) subjects still had HBV DNA load ≥ 103IU/mL at delivery. Among them, 75.0% patietns with rtM204I positive had HBV DNA load ≥ 103IU/mL at delivery, which was comparable with the subjects without rtM204I (75.0% vs. 70.8%, P = 0.710). No changes were found in the frequencies and the complexity of HBV quasispecies of rtM204I mutation after the TVB treatment.Conclusion: The prevalence of pre-existing drug resistant mutations among the pregnant women was high using UPDS. However, the pre-existing HBV mutation had limited influence on the efficacy of short-term TBV treatment, and TBV treatment during late pregnancy seemed not to increase the risk of emerging HBV resistant mutants.
Prognostic risk model for advanced renal cell carcinoma (RCC) with immune-related genes
Authors: Cao Peng , Zhang Jian-Dong , Sun Ze-Jia , Zheng Xiang , Yu Bao-Zhong , Cao Hao-Yuan , Zhang Fei-Long , Gao Zi-Hao , Wang Wei 
Published: July 2020

Abstract
Background Renal cell carcinoma (RCC) is a common tumor of the urinary system. Nowadays, Immunotherapy is a hot topic in the treatment of solid tumors, especially for those tumors with pre-activated immune state. Methods In this study, we downloaded genomic and clinical data of RCC samples from The Cancer Genome Atlas (TCGA) database. Four immune-related genetic signatures were used to predict the prognosis of RCC by Cox regression analysis. We selected the most relevant genes from each signature to construct a prognostic risk model to predict prognosis via Kaplan-Meier (KM) survival analysis. And subgroups of the TCGA samples and external data from International Cancer Genome Consortium (ICGC) database were used to verify predictive stability of the model. We performed landscape analysis to assess the difference of gene mutant based on the data from TCGA. Finally, we explored the correlation between the selected genes and the level of tumor immune infiltration via Tumor Immune Estimation Resource (TIMER) platform. Results We found that the four prognostic risk models constructed by the signatures all could divide the RCC samples into high- and low-risk groups with significantly different prognosis, especially in advanced RCC. And the prognostic risk model was constructed by 8 candidate genes (HLA-B, HLA-A, HLA-DRA, IDO1, TAGAP, CIITA, PRF1 and CD8B) which divided the advanced RCC samples from TCGA database into high-risk and low-risk groups. And there was a significant difference in overall survival (OS) between the two groups. The validity of the model was verified by independent data from ICGC database. And the classification efficiency of the model was stable for the samples from different subgroups. landscape analysis showed that mutation ratios of some genes were different between two risk groups. In addition, the expression levels of the selected genes were significantly correlated with the infiltration degree of immune cells in the advanced RCC. Conclusions Sum up, eight immune-related genes were screened in our study to construct prognostic risk model with great predictive value for the prognosis of advanced RCC, and the genes were associated with infiltrating immune cells in tumors which have potential to conduct personalized treatment for advanced RCC.
Sole Adjuvant Intraoperative Breast Radiotherapy in Taiwan: A Single-Center Experience
Authors: Yang Hsin-Yi , Tu Chi-Wen , Hsu Yu-Chen 
Published: July 2020

Abstract
Introduction: Intraoperative radiotherapy (IORT) is more convenient than standard whole-breast external beam radiotherapy (EBRT) as a sole adjuvant radiotherapy for breast cancer. The impact of age on breast cancer course and treatment strategy is still under investigation, and the peak age for breast cancer in Taiwan is much younger than that in Western countries. We aimed to review the oncological outcomes of sole IORT compared with standard EBRT in a country with younger breast cancer patients.Patients and methods: We reviewed patients with invasive breast cancer who received breast-conserving surgery (BCS) from September 2014 to December 2016. The clinicopathologic characteristics and oncological outcomes of eligible patients who received EBRT or IORT as sole adjuvant radiotherapy after BCS were collected and reviewed.Results: A total of 170 patients were enrolled with a mean follow-up time of 3.53 ± 0.82 years. The risk of locoregional recurrence was 2.44% for EBRT versus 10.64% for IORT (p = 0.024). IORT was a significant risk factor of locoregional recurrence (p = 0.005). The hazard ratios (HRs) for locoregional recurrence in the IORT group compared with the EBRT group were significantly higher in non-suitable risk group patients (HR = 7.02, p = 0.009) and in patients under 50 years old (HR = 10.42, p = 0.011).Conclusions: Locoregional recurrence was significantly higher in patients who received IORT than in those who underwent EBRT. IORT should not be used alone in patients under 50 years old who do not belong to a suitable group.
Maternal Health Among Venezuelan Women Migrants at the Border of Brazil.
Authors: Bahamondes Luis Guillermo , Laporte Montas , Margatho Deborah , de Amorin Helder , Brasil Cinthia , Charles Charles Mpoca , Becerra Alejandra , Hidalgo Maria Margarethe 
Published: July 2020

Abstract
Background: Meeting the Sexual and reproductive health and rights (SRHR) for populations living in fragile and humanitarian settings is critical, essential as well as a basic human right. Compounded with the inherent vulnerabilities of women in crises, there are substantial complications that directly associated with increasing the risks of poor SRHR outcomes for displaced populations. The current forced displacement of the Venezuelans migrants is one of the largest in the Latin America’s history. Our research aimed to assess sexual and reproductive health and rights (SRHR) situation among Venezuelan women in Roraima State, Brazil. Methods: A study with face-to-face interviews was conducted. Data collection covered various issues pertaining to SRHR services, access and use among Venezuelan migrant’s women aged 18-49 years old. We used to data collection the Minimum Initial Service Package readiness assessment tools from the Inter-Agency Working Group on Reproductive Health. Results: We present results of interviews with 405 women were conducted between 24 and 30 November 2019. The most common observed findings in our research as reported by women were unmet family planning needs. A significant proportion of women who needed family planning reported that they were unable to access family planning. This was attributed to either inability to access them and unavailability at the health care centres. Further, 25.0% of pregnant women or postpartum women did not receive antenatal or postnatal care. Conclusion: Meeting the essential SRHR needs among Venezuelan’s migrant women in Roraima, State, Brazil appears to be limited and challenging. Given the high and growing numbers of this migrant population in Brazil, the Brazilian health system must be adaptable to meet the needs of this population. Efforts among not only health governmental sectors, but also academic, non-governmental and international organisations need to be encouraged as well as coordinated for a comprehensive SRHR response. Given the current high risks associated with the Covid-19 pandemic. Meeting the SRH needs migrant populations has become more critical than ever given the current COVID-19 pandemic.