bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small nucleolar RNAs in plasma and their discriminatory power as diagnostic biomarkers of Alzheimer’s disease
Authors: Fitz Nicholas F. , Nam Kyong Nyon , Wang Jiebiao , Kamboh M. Ilyas , Koldamova Radosveta , Lefterov Iliya 
Published: May 2021

AbstractThe clinical diagnosis of Alzheimer’s disease, at its early stage, remains a difficult task. Advanced imaging technologies and laboratory assays to detect Aβ peptides Aβ42 and Aβ40, total and phosphorylated tau in CSF provide a set of biomarkers of developing AD brain pathology and facilitate the diagnostic process. The search for biofluid biomarkers, other than in CSF, and the development of biomarker assays have accelerated significantly and now represent the fastest-growing field in AD research. The goal of this study was to determine the differential enrichment of noncoding RNAs (ncRNAs) in plasma-derived extracellular vesicles (EV) of AD patients and Cognitively Normal controls (NC). Using RNA-seq, we profiled four significant classes of ncRNAs: miRNAs, snoRNAs, tRNAs, and piRNAs. We report a significant enrichment of SNORDs – a group of snoRNAs, in AD samples compared to NC. To verify the differential enrichment of two clusters of SNORDs – SNORD115 and SNORD116, localized on human chromosome 15q11-q13, we used plasma samples of an independent group of AD patients and NC. We applied ddPCR technique and identified SNORD115 and SNORD116 with a high discriminatory power to differentiate AD samples from NC. The results of our study present evidence that AD is associated with changes in the enrichment of SNORDs, transcribed from imprinted genomic loci, in plasma EV and provide a rationale to further explore the validity of those SNORDs as plasma biomarkers of AD.
Prognostic value of the level of gut microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: a meta-analysis and systematic review
Authors: Li-na Miao , Jian-peng Du , Ming Guo , Zhu-hong Chen , Hua Qu , Da-zhuo Shi 
Published: May 2021

AbstractAimsIntestinal microbial metabolite trimethylamine N-oxide (TMAO) is considered to be a key mediator between intestinal microbiota changes and heart failure (HF). Clinical evidences showed that patients with HF had relatively high level of plasma TMAO than those without. However, the relationship between plasma TMAO and the prognostics of patients with HF has not been investigated. This study aims to evaluate the relationship between plasma TMAO and the outcomes of patients with HF.Methods and resultsPubMed, EMBASE, Cochrane Library databases were included for systematic literature search. The included studies were used for the extraction of overall hazard ratios of adverse events data (myocardial infarction, cardiovascular hospitalization, cardiovascular mortality, revascularization and stroke) as well as all‐cause mortality data. Cochran’s Q test and I2 statistical methods were applied to assess heterogeneity. Selection of random effects model or fixed effects model were according to heterogeneity. Sensitivity analysis and subgroup analysis were used to find the source of heterogeneity. Among the 7 included studies, all studies published all‐cause mortality data and 6 provided adverse events. And the results demonstrated that higher level of plasma TMAO (defined according to original studies)was an indicator of risk of all‐cause mortality (HR =0.26, 95% CI: 0.20-0.32, I2 = 96.1%,) and risk of adverse events (HR =1.79, 95% CI: 1.37-2.22, I2 = 78.6%). There was no significant publication bias among the included studies (Egger’s,P = 0.130;Begg’s tests P = 0.452). Further subgroup analysis did not show that study location, follow-up time, or year of publication had any effect on the results. The results of sensitivity analysis do not indicate that any of the included affected the robustness of the results.ConclusionHeart failure patients with higher baseline plasma TMAO is a risk factor for all-cause mortality and adverse events.
Effects of recreational sports and combined training on blood pressure and glycosylated hemoglobin in middle-aged and older adults: a systematic review and meta-analysis
Authors: Schneider Vinícius Mallmann , Frank Paula , Fuchs Sandra C. , Ferrari Rodrigo 
Published: May 2021

ABSTRACTBackgroundCombined resistance and aerobic training (CT) is the most suitable form of exercise training to simultaneously improve cardiometabolic profile and functional capacity in middle-aged and older adults. Recreational sports (RS) emerge as an alternative to traditional exercises to improve these outcomes that could be used as a retention and continuity strategy, promoting health benefits associated with pleasure and satisfaction during the physical activity.ObjectivesThe aim was to conduct a meta-analysis on the effects of RS and CT on systolic blood pressure (SBP), diastolic blood pressure (DBP) and glycosylated hemoglobin (HbA1c) in middle-aged and older adults and to compare these exercise interventions to a non-exercising control group (CON).Data SourcesA literature search was conducted using the databases at PubMed, COCHRANE and SciELO between July and August 2020.Study Eligibility CriteriaStudies that included men and women aged ≥45 years, healthy or with values of baseline for SBP ≥130mmHg or DBP ≥80 mmHg or with type II diabetes, in which the participants performed RS or CT versus CON, and evaluated SBP, DBP and HbA1c.Study Appraisal and Synthesis MethodsTwo independent reviewers screened search results, performed data extraction, and assessed of methodological quality of studies. Random effects modeling was used to compare pre-to post-intervention changes in BP and HbA1c from RS and CT versus CON, and the effect size were calculated through the weighted mean difference (MD) with a 95% confidence interval (CI).ResultsFrom 6017 records, 27 studies were included (9 RS and 18 CT interventions). The analysis included 1411 participants with 55 ± 8 years (range, 45–73 years). Overall, RS was associated reduction in SBP (MD: -7.20 mmHg; CI: -13.7 to -0.7) and DBP (MD: -3.6 mmHg; 95%CI: -6.6 to -0.5) versus CON. CT reduction SBP (MD: -3.6 mmHg; 95%CI: -5.2 to -2.0) and DBP (MD: -3.10 mmHg; 95%CI: -3.75 to -2.44) versus CON. RS not reduced HbA1c (MD: -0.24 %; CI: -0.53 to 0.06) versus CON. However, CT reduced HbA1c (MD: -0.47%; 95%CI: -0.67 to -0.27) versus CON.ConclusionsRS and CT are effective exercise interventions to improve blood pressure in middle-aged and older adults. Additionally, CT seems to be an excellent strategy to reduce HbA1c, and future studies are necessary to confirm the effectiveness of recreational sports to improve HbA1c.Systematic Review Registration NumberCRD42020207250Key PointsRecreational sports promote similar or even greater blood pressure reduction when compared to traditional exercises.Combined training promotes improvements in blood pressure and HbA1c in aging adults.As alternative to traditional exercises, recreational sports emerge as an effective strategy to improve the cardiometabolic profile in middle-aged and older adults.
Extracorporeal membrane oxygenation in COVID-19 patients and in-hospital mortality: results from the Brazilian Registry using a propensity score matched analysis
Authors: Ponce Daniela , Marcolino Milena Soriano , Pires Magda Carvalho , de Carvalho Rafael Lima Rodrigues , Vianna Heloisa Reniers , Alves Nogueira Matheus Carvalho , Botoni Fernando Antonio , Graça Aranha Fernando , de Moura Costa André Soares , Vietta Giovanna Grunewald , Martins Graça Aranha Felipe Ferraz , Barbosa Lima Maria Clara Pontello , da Silva Etges Ana Paula Beck , de Sá Antonio Tolentino Nogueira , Oliveira Luana Martins , Polanczyk Carisi Anne 
Published: May 2021

AbstractAround 5% of coronavirus disease 2019 (COVID-19) patients develop critical disease, with severe pneumonia and acute respiratory distress syndrome (ARDS). In these cases, extracorporeal membrane oxygenation (ECMO) may be considered when conventional therapy fails. This study aimed to assess the clinical characteristics and in-hospital outcomes of COVID-19 patients with ARDS refractory to standard lung-protective ventilation and pronation treated with ECMO support and to compare them to patients who did not receive ECMO. Patients were selected from the Brazilian COVID-19 Registry. At the moment of the analysis, 7,646 patients were introduced in the registry, eight of those received ECMO support (0.1%). The convenience sample of patients submitted to ECMO was compared to control patients selected by genetic matching for gender, age, comorbidities, pronation, ARDS and hospital, in a 5:1 ratio. From the 48 patients included in the study, eight received ECMO and 40 were matched controls. There were no significant differences in demographic, clinical and laboratory characteristics. Mortality was higher in the ECMO group (n = 7; 87.5%) when compared with controls (n = 17; 42.5%), (p=0.048). In conclusion, COVID 19 patients with ARDS refractory to conventional therapy who received ECMO support had worse outcomes to patients who did not receive ECMO. Our findings are not different from previous studies including a small number of patients, however there is a huge difference from Extracorporeal Life Support Organization results, which encourages us to keep looking for our best excellence.
Evaluation of the Weightage on Pain Management in Pharmacology Curricula of the Undergraduate Medical Program (MBBS) of Bangladesh
Authors: Ferdoush Jannatul , Johora Fatema , Jeenia Fatiha Tasmin , Momtaz Tashfia , Towfiq Hossain Sharif Mohammad , Sadia Halima , Abbasy Asma Akter , Rahman Md. Sayedur 
Published: May 2021

AbstractBackgroundPrioritizing problem-oriented undergraduate medical education is paramount to adequate management of pain in real life scenarios. The present research was conducted with an attempt to explore the important baseline information for pain medicine education and evaluation within undergraduate pharmacology curricula in Bangladesh.Materials and methodsThis descriptive cross-sectional study evaluates the curriculum (pharmacology portion of undergraduate medical curriculum), and written question (SAQ) of MBBS Examination of last ten years extending from January 2010 to November,2019 of all 7 universities offering MBBS degree. The evaluation was conducted through searching certain key phrases.ResultIn Pharmacology & Therapeutics portion of the curriculum, only 4 hours and 2 hours are allocated to discuss pain management in lecture and tutorial respectively. In the study period, average marks allocated in pharmacology written question papers was 4.4 (SD = 2.7) and the difference among studied universities was not significant (p value 0.7).ConclusionAllocated time in the curriculato teach pain management is very low and weightage received in assessment is also inadequate. Education on pain medication as well as management should receive more emphasis.
Unified real-time environmental-epidemiological data for multiscale modeling of the COVID-19 pandemic
Authors: Badr Hamada S. , Zaitchik Benjamin F. , Kerr Gaige H. , Nguyen Nhat-Lan H. , Chen Yen-Ting , Hinson Patrick , Colston Josh M. , Kosek Margaret N. , Dong Ensheng , Du Hongru , Marshall Maximilian , Nixon Kristen , Mohegh Arash , Goldberg Daniel L. , Anenberg Susan C. , Gardner Lauren M. 
Published: May 2021

AbstractAn impressive number of COVID-19 data catalogs exist. None, however, are optimized for data science applications, e.g., inconsistent naming and data conventions, uneven quality control, and lack of alignment between disease data and potential predictors pose barriers to robust modeling and analysis. To address this gap, we generated a unified dataset that integrates and implements quality checks of the data from numerous leading sources of COVID-19 epidemiological and environmental data. We use a globally consistent hierarchy of administrative units to facilitate analysis within and across countries. The dataset applies this unified hierarchy to align COVID-19 case data with a number of other data types relevant to understanding and predicting COVID-19 risk, including hydrometeorological data, air quality, information on COVID-19 control policies, and key demographic characteristics.
SARS CoV-2 variant B.1.617.1 is highly pathogenic in hamsters than B.1 variant
Authors: Yadav Pragya D. , Mohandas Sreelekshmy , Shete Anita M , Nyayanit Dimpal A , Gupta Nivedita , Patil Deepak Y. , Sapkal Gajanan N. , Potdar Varsha , Kadam Manoj , Kumar Abhimanyu , Kumar Sanjay , Suryavanshi Deepak , Mote Chandrashekhar S. , Abraham Priya , Panda Samiran , Bhargava Balram 
Published: May 2021

ABSTRACTBackgroundThe recent emergence of new SARS-CoV-2 lineage B.1.617 in India has been associated with a surge in the number of daily infections. This variant has combination of specific mutations L452R, E484Q and P681R reported to possibly enhance the transmissibility with likelihood of escaping the immunity. We investigated the viral load and pathogenic potential of B.1.617.1 in Syrian golden hamsters.MethodsTwo groups of Syrian golden hamsters (9 each) were inoculated intranasally with SARS CoV-2 isolates, B.1 (D614G) and B.1.617.1 respectively. The animals were monitored daily for the clinical signs and body weight. The necropsy of three hamsters each was performed on 3, 5- and 7-days post-infection (DPI). Throat swab (TS), nasal wash (NW) and organ samples (lungs, nasal turbinate, trachea) were collected and screened using SARS-CoV-2 specific Real-time RT-PCR.ResultsThe hamsters infected with B.1.617.1 demonstrated increased body weight loss compared to B.1 variant. The highest viral load was observed in nasal turbinate and lung specimens of animals infected with B.1.167.1 on 3 DPI. Neutralizing antibody (NAb) and IgG response in hamsters of both the groups were observed from 5 and 7 DPI respectively. However, higher neutralizing antibody titers were observed against B.1.167.1. Gross pathology showed pronounced lung lesions and hemorrhage with B.1.671 compared to B.1.ConclusionsB.1617.1 and B.1 variant varied greatly in their infectiousness, pathogenesis in hamster model. This study demonstrates higher pathogenicity in hamsters evident with reduced body weight, higher viral load in lungs and pronounced lung lesions as compared to B.1 variant.SummaryB.1.617.1 is the new SARS-CoV-2 lineage that emerged in India. Maximal body weight loss and higher viral load in hamsters infected with B.1.617.1. It caused pronounced lung lesions in hamsters compared to B.1 variant which demonstrates the pathogenic potential of B.1.617.1.
Manipulation of carotenoid metabolism stimulates biomass and stress tolerance in tomato
Authors: Vallarino Jose G. , Mi Jianing , Petřík Ivan , Novák Ondřej , Correa Sandra M. , Kosmacz Monika , Havaux Michel , Rodriguez-Concepcion Manuel , Al-Babili Salim , Fernie Alisdair R. , Skirycz Aleksandra , Moreno Juan C. 
Published: May 2021

ABSTRACTImproving yield, nutritional value and tolerance to abiotic stress are major targets of current breeding and biotechnological approaches that aim at increasing crop production and ensuring food security. Metabolic engineering of carotenoids, the precursor of Vitamin-A and plant hormones that regulate plant growth and response to adverse growth conditions, has been mainly focusing on provitamin A biofortification or the production of high-value carotenoids. Here, we show that the introduction of a single gene of the carotenoid biosynthetic pathway in different tomato cultivars simultaneously improved photosynthetic capacity and tolerance to various abiotic stresses (e.g., high light, salt, and drought), caused an up to 77% fruit yield increase and enhanced fruit’s provitamin A content and shelf life. Our findings pave the way for developing a new generation of crops that combine high productivity and increased nutritional value with the capability to cope with climate change-related environmental challenges.
Optimized Quantification of Intrahost Viral Diversity in SARS-CoV-2 and Influenza Virus Sequence Data
Authors: Roder AE , Johnson KEE , Knoll M , Khalfan M , Wang B , Schultz-Cherry S , Banakis S , Kreitman A , Mederos C , Youn J-H , Mercado R , Wang W , Ruchnewitz D , Samanovic MI , Mulligan MJ , Lassig M , Łuksza M , Das S , Gresham D , Ghedin E 
Published: May 2021

ABSTRACTHigh error rates of viral RNA-dependent RNA polymerases lead to diverse intra-host viral populations during infection. Errors made during replication that are not strongly deleterious to the virus can lead to the generation of minority variants. However, accurate detection of minority variants in viral sequence data is complicated by errors introduced during sample preparation and data analysis. We used synthetic RNA controls and simulated data to test seven variant calling tools across a range of allele frequencies and simulated coverages. We show that choice of variant caller, and use of replicate sequencing have the most significant impact on single nucleotide variant (SNV) discovery and demonstrate how both allele frequency and coverage thresholds impact both false discovery and false negative rates. We use these parameters to find minority variants in sequencing data from SARS-CoV-2 clinical specimens and provide guidance for studies of intrahost viral diversity using either single replicate data or data from technical replicates. Our study provides a framework for rigorous assessment of technical factors that impact SNV identification in viral samples and establishes heuristics that will inform and improve future studies of intrahost variation, viral diversity, and viral evolution.IMPORTANCEWhen viruses replicate inside a host, the virus replication machinery makes mistakes. Over time, these mistakes create mutations that result in a diverse population of viruses inside the host. Mutations that are neither lethal to the virus, nor strongly beneficial, can lead to minority variants that are minor members of the virus population. However, preparing samples for sequencing can also introduce errors that resemble minority variants, resulting in inclusion of false positive data if not filtered correctly. In this study, we aimed to determine the best methods for identification and quantification of these minority variants by testing the performance of seven commonly used variant calling tools. We used simulated and synthetic data to test their performance against a true set of variants, and then used these studies to inform variant identification in data from clinical SARS-CoV-2 clinical specimens. Together, analyses of our data provide extensive guidance for future studies of viral diversity and evolution.
The division defect of aBacillus subtilis minD nocdouble mutant can be suppressed by Spx-dependent and Spx-independent mechanisms
Authors: Yu Yuanchen , Dempwolff Felix , Oshiro Reid T. , Gueiros-Filho Frederico J. , Jacobson Stephen C. , Kearns Daniel B. 
Published: May 2021

ABSTRACTDuring growth, bacteria increase in size and divide. Division is initiated by the formation of the Z-ring, an intense ring-like cytoskeletal structure formed by treadmilling protofilaments of the tubulin homolog FtsZ. FtsZ localization is thought to be controlled by the Min and Noc systems, and here, we explore why cell division fails at high temperature when the Min and Noc systems are simultaneously mutated. Microfluidic analysis of aminD nocdouble mutant indicated that FtsZ formed proto-Z-rings at periodic inter-chromosome locations but that the rings failed to mature and become functional. Extragenic suppressor analysis indicated that a variety of mutations restored high temperature growth to theminD nocdouble mutant, and while many were likely pleiotropic, others implicated the proteolysis of the transcription factor Spx. Further analysis indicated that a Spx-dependent pathway activated the expression of ZapA, a protein that primarily compensates for the absence of Noc. Additionally, an Spx-independent pathway increased the activity of the divisome to reduce the length of the cytokinetic period. Finally, we provide evidence of an as-yet-unidentified protein that is activated by Spx and governs the frequency of polar division and minicell formation.IMPORTANCEBacteria must properly position the location of the cell division machinery in order to grow, divide, and ensure each daughter cell receives one copy of the chromosome. InB. subtilis, cell division site selection is thought to depend on two systems called Min and Noc, and while neither is individually essential, cells fail to grow at high temperature when both are mutated. Here, we show that cell division fails in the absence of Min and Noc, not due to a defect in FtsZ localization, but rather a failure in the maturation of the cell division machinery. To understand what happens when the division machinery fails to mature, suppressor mutations that bypass the need for Min, Noc, or both were selected. Some of the mutants activated the Spx stress response pathway while others appeared to directly enhance divisome activity.
Insights into the L3 to L4 developmental program through proteomics
Authors: Bennuru Sasisekhar , Meng Zhaojing , McKerrow James , Lustigman Sara , Nutman Thomas B 
Published: May 2021

AbstractThe establishment of infection with the lymphatic dwelling filarial parasites is dependent on the infectivity and subsequent development of the infective larvae (L3) within the human host to later stages (L4, adults) that require several developmental molts. The molecular mechanisms underlying the developmental processes in parasitic nematodes are not clearly defined. We report the proteomic profiles throughout the entire L3 to L4 molt using an establishedin vitromolting process for the human pathogenB. malayi. A total of 3466 proteins ofB. malayiand 54 fromWolbachiawere detected at one or more time points. Based on the proteomic profiling, the L3 to L4 molting proteome can be broadly divided into an early, middle and late phase. Enrichment of proteins, protein families and functional categories between each time point or between phases primarily relate to energy metabolism, immune evasion through secreted proteins, protein modification, and extracellular matrix-related processes involved in the development of new cuticle. Comparative analyses with somatic proteomes and transcriptomes highlighted the differential usage of cysteine proteinases (CPLs), BmCPL-1, -4 and -5 in the L3-L4 molt compared to the adults and microfilariae. Inhibition of the CPLs effectively blocked thein-vitroL3 to L4 molt. Overall, only 4Wolbachiaproteins (Wbm0495, Wbm0793, Wbm0635, and Wbm0786) were detected across all time points and suggest that they play an inconsequential role in the early developmental process.ImportanceThe neglected tropical diseases of lymphatic filariasis, onchocerciasis (or river blindness), and loiasis are the three major filarial infections of humans that cause long-term disability, impaired childhood growth, reduced reproductive capacity. Global efforts to control and/or eliminate these infections as a public health concern are based on strategies and tools to strengthen the diagnostics, therapeutic and prophylactic measures. A deeper understanding of the genes, proteins and pathways critical for the development of the parasite is needed to help further investigate the mechanisms of parasite establishment and disease progression, because not all the transmitted infective larvae get to develop successfully and establish infections. The significance of this study is in identifying the proteins and the pathways that are needed by the parasite for successful developmental molts, that in turn will allow for investigating targets of therapeutic and prophylactic potential.