bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measles and Rubella Serosusceptibity Among Population Vaccinated with Different Schedule of Vaccination: The Potential Impact on Measles Elimination in Iran.
Authors: Saffar Hana , Khalifeloo Maryam , Saffar Mohammed-Jafar , Abdollahi Ali-Reza , Parsaei Mohammad-Reza , Ghorbani Gholam-Reza , Salarvand Samaneh , Aarabi Mohsen 
Published: July 2020

Abstract
Background: In addition to schedule 2-doses monovalent measles vaccine (mMV) immunization of Iranian children since 1984, a nationwide campaign of measles-rubella (MR) immunization among 5- 25 years-old population in December 2003 was conducted. From 2004 mMV was replaced with measles- mumps-rubella (MMR) vaccine. Despite a high vaccination coverage, outbreaks of measles occurred in the country. Study was designed to investigate seroimmunity against measles and rubella among various age groups of population who were vaccinated with different schedule since 1984. Also, immunologic response to revaccination in seronegative subjects was evaluated. Methods: From 1 November 2017 to 30 June 2018 a cross- sectional study among 7- 33 year old healthy population with documented history of measles vaccination was conducted. Based on their age and history of vaccination categorized as GA: 20-23 years old; vaccinated with 1-2 dose of mMV, and also MR revaccinated. GB: 15-19 years, vaccinated only with 2- doses of mMV at the ages of 9 and 15 months. GC: 12-14 years and GD: 7-11 years; vaccinated with 2- dose of MMR vaccine at the ages 15 months - 6 years, and 12-18 month respectively. Collected sera were assessed to measure antimeasles and antirubella IgG antibodies concentration. Four to 6 weeks after revaccination of seronegative subjects, antimeasles-antirubella IgM and IgG antibodies were rechecked. Collected data were analyzed using descriptive statistical methods.Results: Totally 635 individuals, 312 female were included. Relative distribution of subjects in each group was as: GA: 98, GB: 295, GC: 139, and GD: 103 persons. Overall, 12.28% and 18.4% of population were soronegative, and varied greatly between groups: 2%-0/0%, 15.2%- 25.0%, 11.5%- 17.2%; and 14.6%-18.4% to measles and rubella, respectively. After revaccination, 92% and 94.9% showed 1gG response to measles and rubella vaccine respectively.Conclusion: Despite high coverage rate with measles containing vaccine, a significant numbers of vaccinated subjects lost their seroprotection, possibly because of secondary vaccine failure. This may affect measles-rubella elimination goal in the country. If these data were confirmed by further studies, more strengthen regional/ national supplementary immunization activity should be considered.
The clinical characteristics and outcome of cryptococcal meningitis with AIDS in a tertiary hospital in China: An observational cohort study
Authors: Wu Liang , Xiao Jiang , Song Yangzi , Gao Guiju , Zhao Hongxin 
Published: July 2020

Abstract
Background We collected the clinical data of hospitalized AIDS patients who complicated with cryptococcal meningitis (CM) in nearly 10 years, to analyze the influencing factors of prognosis and provide help for early identification of severe patients, timely rescue measures and improvement of prognosis. Methods The 128 subjects were divided into two groups according to the effective/ineffective clinical treatment. Analyzed and compared the data from various aspects. Results 119 cases (93.0%) had headache, 109 (85.2%) had fever, 95 (74.2%) had nausea and vomiting, 52 (40.6%) had consciousness disorder. 101 patients (78.9%) were effective in clinical treatment, while 27 (21.1%) were ineffective. Multivariate Logistic regression analysis showed that the occurrence of cerebral herniation increased the risk of poor prognosis by 405 times, and the occurrence of disturbance of consciousness increased the risk of poor prognosis by 4.4 times. However, each week of extension of the course of induction therapy reduced the risk of poor prognosis by 0.683 times, and increased the effective outcome of clinical treatment by 1.5 times. In addition, the prognosis of patients with ventriculoperitoneal shunt or lumbar cisterna shunt decompression was better than that of patients without shunt therapy. Conclusions Cerebral hernia and disturbance of consciousness are risk factors for prognosis of AIDS patients with CM, and duration of induction therapy is a protective factor for prognosis. Anticryptococcal therapy with high efficiency and sufficient treatment time during induction period is especially critical for improving prognosis. Shunt decompression therapy may improve the prognosis of patients with AIDS complicated with CM.
Early leucine programming on protein utilization and mTOR signaling by DNA methylation in zebrafish (Danio rerio)
Authors: Zhu Qiang-Sheng , Wang Jie , he shan , Liang Xu-Fang , Xie Shuang , Xiao Qian-Qian 
Published: July 2020

Abstract
Background
Early nutritional programming affects a series of metabolism, growth and development in mammals. Fish also exhibit the developmental plasticity by early nutritional programming. However, little is known about the effect of early amino acid programming on growth and metabolism.
Methods
In the present study, zebrafish (Danio rerio) was used as the experimental animal to study whether early leucine stimulation can programmatically affect the mechanistic target of rapamycin (mTOR) signaling pathway, growth and metabolism in the later life, and to undercover the mechanism of epigenetic regulation. Zebrafish larvas at 3 days post hatching (dph) were raised with 1.0% leucine from 3 to 13 dph during the critical developmental stage, then back to normal water for 70 days (83 dph).
Results
The growth performance and crude protein content of zebrafish in the early leucine programming group were increased, and consistent with the activation of the mTOR signaling pathway and the high expression of genes involved in the metabolism of amino acid and glycolipid. Furthermore, we compared the DNA methylation profiles between the control and leucine-stimulated zebrafish, and found that the methylation levels of CG-differentially methylated regions (DMGs) and CHH-DMGs of genes involved in mTOR signaling pathway were different between the two groups. With quantitative PCR analysis, the decreased methylation levels of CG type of Growth factor receptor-bound protein 10 (Grb10), eukaryotic translation initiation factor 4E (eIF4E) and mTOR genes of mTOR signaling pathway in the leucine programming group, might contribute to the enhanced gene expression.
Conclusions
The early leucine programming could improve the protein synthesis and growth, which might be attributed to the methylation of genes in mTOR pathway and the expression of genes involved in protein synthesis and glycolipid metabolism in zebrafish. These results could be beneficial for better understanding of the epigenetic regulatory mechanism of early nutritional programming.
Assessment of the Susceptibility Status of Aedes aegypti (Diptera: Culicidae) Populations to Pyriproxyfen and Malathion in a National Wide Monitoring of Insecticide Resistance in Brazil, 2017-2018.
Authors: Campos Kauara Brito , Martins Ademir Jesus , Rodovalho Cynara de Melo , Bellinato Diogo Fernandes , Dias Luciana dos Santos , Macoris Maria de Lourdes da Graça , Andrighetti Maria Teresa Macoris , Lima José Bento Pereira , Obara Marcos Takashi 
Published: July 2020

Abstract
Background: In Brazil chemical control has been used since 1985. For the effectiveness of chemical control, it is essential to monitor the vector susceptibility to insecticides. This study aimed to describe bioassays standardization and to determine the susceptibility profile of Ae. aegypti populations to the products in use malathion and pyriproxyfen on national scale between 2017 and 2018, and to discuss the observed results impact in arboviruses control.Methods: The diagnostic-doses (DD) of pyriproxyfen and malathion were determined as the double of the inhibition of adult emergence (EI) and lethal doses for 99% of the Rockefeller reference strain, respectively. For the monitoring of natural populations, collections were performed in 132 Brazilian cities, through egg traps. Colonies were raised in the laboratory for one or two generations (F1 or F2) and submitted to susceptibility tests with larvae exposed to DD of pyriproxyfen (0.03 µg/L) and adults with the malathion DD herein obtained (20 µg), in addition to the World Health Organization (WHO) indicated DD (50 µg) in bottle assay. Dose-response bioassays with pyriproxyfen were performed with populations which did not achieved 98% EI in the DD assays. Results: Alteration of susceptibility to pyriproxyfen was recorded in 6 (4.5%) Ae. aegypti populations, with Resistance Ratio RR95 from 1.51 to 3.58. These populations were concentrated in Bahia and Ceará states. For malathion, 73 (55,3%) populations distributed all over the country were resistant when exposed to the local DD 20µg/bottle. On the other hand, no one population was resistant, and only 10 (7,6%) populations were considered with decreased susceptibility (mortality ratio between 90 and 98%) when the WHO DD (50 µg/bottle was used). These populations are in the 8 from 27 states.Conclusions: We evidenced the feasibility of conducting an insecticide resistance monitoring action at a national wide scale, employing standardized and strongly coordinated sampling methods and laboratory bioassays. We for the first time identified Brazilian Ae. aegypti populations with decreased susceptibility to pyriproxyfen. Local DD for malathion was more sensitive than the WHO DD to early detect decrease in susceptibility.
Lung Microbiota is Associated with Bacterial Detection and with Clinical Improvements in Severe Community-Acquired Pneumonia Patients
Authors: Du Sisi , Li Binbin , Wang Yimin , Xia Yudi , Shang Lianhan , Yu Donghao , Liu Zhibo , Wang Chunlei , Liu Xinmeng , Xiong Zhujia , Zou Xiaohui , Lu Binghuai , Liu Yingmei , Cao Bin 
Published: July 2020

Abstract
Background: Few studies have described the key features of the lung microbiota in patients with severe community-acquired pneumonia (SCAP). We conducted the study to identify the association between the lung microbiota on admission and the clinical prognosis in SCAP patients. Methods: The consecutive SCAP patients admitted from intensive care unit (ICU) were enrolled prospectively. 16S rRNA gene sequencing was applied to bronchoalveolar lavage fluid (BALF) collected within 48 hours. The clinical information was recorded during the stay of hospitalization. The primary endpoint was the rate of clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy.Results: Sixty-seven patients were included. Multivariable Permutational multivariate analysis of variance (PERMANOVA) found that bacterial detection had the strongest independent relationship with the lung microbiota (R2=0.033; p=0.018), followed by acute kidney injury (AKI R2=0.032; p=0.011) and plasma MIP-1beta level (R2=0.027; p=0.044). Random forest identified that families Prevotellaceae, Moraxellaceae, Staphylococcaceae were the biomarkers related to bacterial detection. In the patients with positive bacteriology results, the mean relative abundance of families Prevotellaceae and Actinomycetaceae decreased while families Moraxellaceae, Staphylococcaceae and Streptococcaceae increased. Multivariable Cox regression showed that the increase in alpha-diversity and the abundance of families Prevotellaceae and Actinomycetaceae were associated with clinical improvements.Conclusions: The bacterial detection and patients’ intrinsic factors were associated with the lung microbiota. The increased alpha diversity and the enrichment of families Prevotellaceae and Actinomycetaceae in the lung microbiota were associated with clinical improvements.
Interaction Analysis of Statistically Enriched Mutations Identified in Cameroon Recombinant Subtype CRF02_AG that can Influence the Development of Dolutegravir Drug Resistance Mutations
Authors: Mikasi Sello Given , Isaacs Darren , Chotongo Rumbidzai , Ikomey George Mondinde , Cloete Ruben , Jacobs Graeme Brendon 
Published: July 2020

Abstract
Background The Integrase (IN) strand transfer inhibitor (INSTI), Dolutegravir (DTG), has been given the green light to form part of first-line combination antiretroviral therapy (cART) by the World Health Organization (WHO). DTG is clinically effective against all HIV-1 isolates previously showing resistance to INSTIs.Methods We evaluated the HIV-1 CRF02_AG IN gene sequences from Cameroon for the presence of resistance-associated mutations (RAMs) against INSTIs and naturally occurring polymorphisms (NOPs), using study sequences (n=20) and (n=278) sequences data derived from HIV Los Alamos National Library (LANL) database. The possible impact of NOPs on protein structure caused by HIV-1 CRF02_AG variations was addressed within the context of a 3D model of the HIV-1 IN complex. Results We observed 12.8% (37/287) sequences to contain RAMs, with only 1.0% (3/287) of the sequences having major INSTI RAMs: T66A, Q148H, R263K and N155H. Of these,11.8% (34/287) of the sequences contained five different IN accessory mutations; namely Q95K, T97A, G149A, E157Q and D232N. NOP rates equal or above 50% were found for 66% of central core domain (CCD) positions, 44% C-terminal domain (CTD) positions and 35% of the N-terminal domain (NTD) positions.Conclusions Our analysis indicated that all mutations that resulted in a change in the number of interactions encompassing residues were found within the stable alpha-helix secondary structure element and not in close proximity to the drug active site. Our findings highlight the structural basis for HIV-1 IN interactions and that INSTIs will remain effective against CRF02_AG.
The Beneficial Use of Melanin in Inhibiting and Treating HCC Through Preventing CBC, Liver Enzymes, Oxidative Stress, and Lipid Peroxidation Alterations
Authors: Abdelhalim Mohamed Anwar K , Al-Mohy Yanallah H , Al-Ayed Mohammed S 
Published: July 2020

Abstract
Hepatocellular carcinoma (HCC) accounts for more than 90% of primary liver cancers and is a major global health problem. The present application relates to normalizing abnormal levels of hematological blood parameters, oxidative stress indicators, and liver enzyme levels in the rats using melanin, and particularly, to treating their abnormal levels, in addition to evaluate the role of melanin during and after the progression of HCC, which will be supplemented histologically. Hematological blood parameters such as white blood cells (WBCs), red blood cells (RBCs), hemoglobin (HGB), hematocrit (HCT), and platelets (PLTs); liver enzymes such as alanine transaminase (ALT) and aspartate transaminase (AST); oxidative stress such as glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD); LP malondialdehyde (MDA) were evaluated in all groups of rats. Injection of Diethylnitrosamine (DEN) and 2-Acetyaminofluorine (2-AFF) induced HCC in the rats accompanied with a significant reduction in WBCs, RBCs, HGB, HCT, and PLTs, GSH-PX, and SOD; while a significant elevation was observed in ALT and AST, and MDA compared to the control. Melanin normalized all the above mentioned parameters during and after the progression of cancer towards their control values. These results demonstrate the beneficial use of melanin as a powerful antioxidant tool in inhibiting and treating HCC in the rats.
County-Level Longitudinal Clustering of COVID-19 Mortality to Incidence Ratio in the United States
Authors: Vahabi Nasim , Salehi Masoud , Duarte Julio , Mollalo Abolfazl , Michailidis George 
Published: July 2020

Abstract
Background: As of June 3, 2020, the mortality to incidence ratio (MIR) of COVID-19 was 5.8%. We utilized a longitudinal model-based clustering system based on the disease trajectories over time.Methods: County-level COVID-19 cases and deaths (March-June 2020), and a set of potential risk factors were collected for 3050 U.S. counties. We used growth mixture models to identify clusters of counties exhibiting similar COVID-19 MIR growth trajectories and risk-factors over time. Results: We identified clusters 1 (rural-areas of IA, NC, OK, VA, FL, GA, LA, OH states), and 7 (rural-areas of AR, CO, GA, KS, NE, TN, TX states) as the so-called “more vulnerable” clusters. Tuberculosis (OR=1.3), drug use disorder (OR=1.1), and particulate matter (OR=1.1) were significantly associated with increased odds of being in a more vulnerable cluster. Heart complications and cancer were the main risk factors increasing the COVID-19 MIR (range: 0.08%-0.72% MIR↑).Conclusion: We identified two county-clusters exhibiting the highest COVID-19 MIR trajectories, indicating that enhancing the capacity and access to healthcare resources would be key to successfully manage COVID-19 in these “vulnerable” clusters. These findings provide insights for public health policymakers on the groups of people and locations they need to pay particular attention while managing the COVID-19 epidemic.
An online tool for predicting the prognosis of cancer patients with SARS-CoV-2 infection: a multi-center study
Authors: Song Congkuan , Dong Zhe , Gong Hongyun , Liu Xiao-Ping , Dong Xiaorong , Wang Aifen , Chen Yuan , Song Qibin , Hu Weidong 
Published: July 2020

Abstract
Purpose: During the coronavirus disease 2019 (COVID-19) pandemic, oncologists face new challenges and they need to adjust their cancer management strategies as soon as possible to reduce the risk of SARS-CoV-2 infection and tumor recurrence. However, data on cancer patients with SARS-CoV-2 infection remains scarce. Methods: We performed a retrospective study of 223 cancer patients with SARS-CoV-2 from 26 hospitals in Hubei, China. An individualized nomogram was constructed based on multivariable Cox analysis. Considering the convenience of the nomogram application, an online tool was also created by shiny app. C-index, calibration curves and decision curve analysis (DCA) were performed to verify the prediction performance and clinical application of the nomogram.Results: Among cancer patients with SARS-CoV-2, there were significant differences in clinical characteristics between survivors and non-survivors, and lung cancer patients had similar short-time survival with other cancer patients. Male, dyspnea, elevated PCT, increased heart rate, elevated D-dimers, decreased platelets and so on were risk factors for these patients. Furthermore, good prediction performance of the online tool (dynamic nomogram: https://covid-19-prediction-tool.shinyapps.io/DynNomapp/). was also fully demonstrated with the C-index of 0.841 (95% CI: 0.782 - 0.900) in the development cohort and 0.780 (95% CI: 0.678-0.882) in the validation cohort. Conclusion: Overall, cancer patients with SARS-CoV-2 had unique clinical features, and the established online tool could guide clinicians to predict the prognosis of patients and to develop more rational treatment strategies for cancer patients during the COVID-19 epidemic.
Cytotoxic T-Lymphocyte Elicited Vaccine against SARS-CoV-2 employing Immunoinformatics Framework
Authors: Kumar Neeraj , Admane Nikita , Kumari Anchala , Sood Damini , Grover Sonam , Prajapati Vijay Kumar , Chandra Ramesh , Grover Abhinav 
Published: July 2020

Abstract
Development of effective counteragents against the novel coronavirus disease caused by SARS CoV-2 strains requires clear insights for understanding immune responses associated with it. The succumbing of available therapeutics utterly warrants the development of a potential vaccine to contest the deadly situation. Herein, we report Cytotoxic T-cell Lymphocytes immunomodulator by advanced immunoinformatics avenues for spike-glycoprotein of SARS CoV-2, which can generate robust immune response with convincing immunological parameters (Antigenicity, TAP affinity, MHC-binder) engendering an efficient viral vaccine. Strong binding of the CTL construct with MHC-1 and membrane-specific TLR2 was conferred through molecular docking and molecular dynamics simulation in an explicit system. Steep magnitude RMSD variation and compelling residual fluctuations existed in terminal residues and various loops of the β linker segments of TLR2-epitope (residues 105-156 and 239-254) to about 0.4nm. The reduced Rg value (3.3nm) and stagnant SASA analysis (275nm/S2/N after 8ns and 5ns) for protein surface and its orientation in exposed and buried regions suggests more compactness by strong binding of epitope. The CTL vaccine candidate establishes a high capability to elicit critical immune regulators, like T-cells and memory cells as proven by in silico immunization assays and can be further corroborated through in vitro and in vivo assays.
Prevalence and Susceptibility Patterns Associated with Staphylococcus Aureus Presence in Marketed Milk and Milk Products.
Authors: MACHARIA JOHN MACHARIA , Kaposztas Zsolt , Richard Cheruiyot , Andrew Nyerere K. , Muriithi Mathenge J. , Raposa Bence L. 
Published: July 2020

Abstract
The authors have requested that this preprint be removed from Research Square.
Recurrent Uterine Tumors Resembling Ovarian Sex-Cord Tumors with The Growth Regulation by Estrogen in Breast Cancer 1-Nuclear Receptor Coactivator 2 Fusion Gene: A Case Report and Literature Review
Authors: Chang Bin , Bai Qianming , Liang Lin , Ge Huijuan , Yao Qianlan 
Published: July 2020

Abstract
Background: Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are rare mesenchymal neoplasms predominantly arising in perimenopausal and postmenopausal women. UTROSCTs with growth regulation by estrogen in breast cancer 1 (GREB1)-rearrangement or GREB1-rearranged uterine tumors are exceptionally rare, with only 12 previously reported cases. Here, we report a case of UTROSCT with the GREB1-nuclear receptor coactivator 2 (NCOA2) fusion gene. Case Presentation: A 57-year-old woman presented with a 10.0-cm uterine mass. The tumor was composed of short spindle or epithelioid cells, arranged in diffused sheets, nested, and trabecular/cordlike. The tumor harbored the GREB1-NCOA2 fusion gene, as confirmed by RNA sequencing. The tumor recurred in the pelvis at 30 months after the initial diagnosis. We also compared the clinical and pathologic features of this case with those of the 12 previously published uterine GREB1-rearranged tumors. Of the combined 13 cases (present case and 12 previous cases), the mean age of patients was 64.8 years (range, 51‒74 years). Of the nine reported cases of GREB1-rearranged tumor with follow up, four cases recurred or metastasized (44.4%). Microscopically, most tumors (10/12, 83.3%) showed infiltrative growth, and two were well demarcated. Mitotic figures ranged from 0 to 14 per 10 high-power fields (2 mm2; mean: 3.6). Lymphovascular invasion and necrosis were each present in two cases (2/12, 16.7% and 2/7, 28.6%, respectively). Conclusions: This case provided further evidence that UTROSCTs with GREB1-rearrangement may have a high risk of recurrence. Further studies are necessary to clarify the clinical features of this type of tumor, particularly the prognosis, potential treatment, and range of possible molecular events.