bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation hotspots, geographical and temporal distribution of SARS-CoV-2 lineages in Brazil, February 2020-2021: insights and limitations from uneven sequencing efforts
Authors: Franceschi Vinícius Bonetti , Ferrareze Patrícia Aline Gröhs , Zimerman Ricardo Ariel , Cybis Gabriela Bettella , Thompson Claudia Elizabeth 
Published: March 2021

AbstractThe COVID-19 pandemic has already reached approximately 110 million people and it is associated with 2.5 million deaths worldwide. Brazil is the third worst-hit country, with approximately 10.2 million cases and 250 thousand deaths. International efforts have been established to share information about SARS-CoV-2 epidemiology and evolution. However, sequencing facilities and research investments are very heterogeneous across different regions and countries. The understanding of the SARS-CoV-2 evolution plays a significant role in the development of effective strategies for public health and disease management. We aimed to analyze the available and high-quality genome sequences from Brazil between February 2020 and February 2021 to identify mutation hotspots, geographical and temporal distribution of SARS-CoV-2 lineages by using phylogenetics and phylodynamics analyses. We describe heterogeneous and episodic sequencing efforts, the progression of the different lineages along time, evaluating mutational spectra and frequency oscillations derived from the prevalence of novel and specific lineages across different Brazilian regions. We found at least seven major (1-7) and two minor clades (4.2 and 5.3) related to the six most prevalent lineages in the country and described its spatial distribution and dynamics. The emergence and recent frequency shift of lineages (P.1 and P.2) containing mutations of concern in the spike protein (e. g., E484K, N501Y) draws attention due to their association with immune evasion and enhanced receptor binding affinity. Improvements in genomic surveillance are of paramount importance and should be extended in Brazil to better inform policy makers and enable evidence-based decisions to fight the COVID-19 pandemic.
Early-life enteric infection and enteropathy markers are associated with changes in adipokine, apolipoprotein and cytokine profiles later in childhood consistent with those of an adverse cardiometabolic disease risk profile in a Peruvian birth cohort
Authors: Colston Josh M. , Chen Yen Ting , Hinson Patrick , Nguyen Nhat-Lan H. , Peñataro Yori Pablo , Olortegui Maribel Paredes , Trigoso Dixner Rengifo , Salas Mery Siguas , Guerrant Richard L. , François Ruthly , Kosek Margaret N. 
Published: March 2021

AbstractBackgroundMetabolic syndrome is a cluster of risk factors for cardiovascular disease thought to afflict over a billion people worldwide and is increasingly being identified in younger age groups and socio-economically disadvantaged settings in the global south. Enteropathogen exposure and environmental enteropathy in infancy may lead to metabolic syndrome by disrupting the metabolic profile in a way that is detectable in cardiometabolic markers later in childhood.Methods217 subjects previously enrolled in a birth cohort in Amazonian Peru were followed up annually from ages 2 to 5 years. Blood samples collected in later childhood were analyzed for a panel of 37 cardiometabolic biomarkers, including adipokines, apolipoproteins, cytokines, and other analytes. These were matched to extant early-life markers of enteropathy ascertained between birth and 2 years of age. Multivariate and multivariable regression models were fitted to test for associations adjusting for confounders.ResultsFecal and urinary markers of intestinal permeability and inflammation (myeloperoxidase, lactulose and mannitol) measured from birth to 2 years of age were independently associated with later serum concentrations of soluble CD40-ligand, a proinflammatory cytokine correlated with adverse metabolic outcomes. Fecal myeloperoxidase was also strongly, directly associated with later levels of the anti-inflammatory adipocytokine omentin-1. Cumulative enteric protozoa exposure before 2 years of age showed stronger associations with later cardiometabolic markers than enteric viruses and bacteria and overall diarrheal episodes.ConclusionEarly-life markers of enteric infection and enteropathy were associated with numerous changes in adipokine, apolipoprotein and cytokine profiles later in childhood consistent with those of an adverse cardiometabolic disease risk profile in this Peruvian birth cohort. Markers of intestinal permeability and inflammation measured in urine (lactulose, mannitol) and stool (myeloperoxidase, protozoal infections) during infancy, may predict disruptions to cytokine and adipocytokine production in later childhood that are precursors to metabolic syndrome in adulthood. Chronic enteric infections, such as by protozoan pathogens, may be more important drivers of these changes than symptomatic diarrhea or growth faltering.FundingBill & Melinda Gates Foundation OPP1066146 and OPP1152146.
Remote recruitment for Essential Coaching for Every Mother during COVID-19
Authors: Dol Justine , Murphy Gail Tomblin , McMillan Douglas , Aston Megan , Campbell-Yeo Marsha 
Published: March 2021

AbstractBackgroundWith a decrease in in-person support and increase in perinatal mental health concerns during the coronavirus pandemic, innovative strategies, such as mHealth, are more important than ever. However, due to physical distancing recommendations, recruitments for perinatal research needs to shift. The objective of this study is to desire the process evaluation of recruitment and retention of women for an mHealth pre-post intervention study for Essential Coaching for Every Mother.MethodsThree methods were used for recruitment: social media, posters in hospital, and media outreach. First time mothers were eligible for enrollment antenatally (37+ weeks) and postnatally (<3 weeks). Eligibility screening occurred remotely via text message. Outcomes were days to recruit 75 participants, eligibility vs. ineligibility rates, dropout and exclusion reasons, survey completion rates, perinatal timing of enrollment, and recruitment sources.ResultsRecruitment ran July 15th-September 19th (67 days) with 200 screened and 88 enrolled, 70% antenatally. It took 50 days to enroll 75 participants. Mothers recruited antenatally (n=53) were more likely to receive all intervention message (68% vs. 19%). Mothers recruited postnatally (n=35) missed more messages on average (13.8 vs. 6.4). Participants heard about the study through family/friends (31%), news (20%), Facebook groups (16%), Facebook ads (14%), posters (12%), or other ways (7%).ConclusionAntenatal recruitment resulted in participants enrolling earlier and receiving more of the study messages. Word of mouth and media outreach were successful, followed by advertisement on Facebook. Remote recruitment was a feasible way to recruit for Essential Coaching for Every Mother.
COVID-19: Optimal Allocation of Ventilator Supply under Uncertainty and Risk
Authors: Yin Xuecheng , Büyüktahtakın İ. Esra , Patel Bhumi P. 
Published: March 2021

AbstractThis study presents a new risk-averse multi-stage stochastic epidemics-ventilator-logistics compartmental model to address the resource allocation challenges of mitigating COVID-19. This epidemiological logistics model involves the uncertainty of untested asymptomatic infections and incorporates short-term human migration. Disease transmission is also forecasted through a new formulation of transmission rates that evolve over space and time with respect to various non-pharmaceutical interventions, such as wearing masks, social distancing, and lockdown. The proposed multi-stage stochastic model overviews different scenarios on the number of asymptomatic individuals while optimizing the distribution of resources, such as ventilators, to minimize the total expected number of newly infected and deceased people. The Conditional Value at Risk (CVaR) is also incorporated into the multi-stage mean-risk model to allow for a trade-off between the weighted expected loss due to the outbreak and the expected risks associated with experiencing disastrous pandemic scenarios. We apply our multi-stage mean-risk epidemics-ventilator-logistics model to the case of controlling the COVID-19 in highly-impacted counties of New York and New Jersey. We calibrate, validate, and test our model using actual infection, population, and migration data. The results indicate that short-term migration influences the transmission of the disease significantly. The optimal number of ventilators allocated to each region depends on various factors, including the number of initial infections, disease transmission rates, initial ICU capacity, the population of a geographical location, and the availability of ventilator supply. Our data-driven modeling framework can be adapted to study the disease transmission dynamics and logistics of other similar epidemics and pandemics.
Case-control, diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood
Authors: Hiza Hellen , Hella Jerry , Arbués Ainhoa , Magani Beatrice , Sasamalo Mohamed , Gagneux Sebastien , Reither Klaus , Portevin Damien 
Published: March 2021

ABSTRACTBackgroundCD4 T cell phenotyping-based blood assays have the potential to meet WHO target product profiles (TPP) of non-sputum-biomarker-based tests to diagnose tuberculosis (TB). Yet, substantial refinements are required to allow their implementation in clinical settings. This study assessed the real time performance of a simplified T cell activation marker (TAM)-TB assay to detect TB in adults from one millilitre of blood with a 24h turnaround time.MethodsWe recruited 479 GeneXpert®positive cases and 108 symptomatic but GeneXpert®negative controls from presumptive adult TB patients in the Temeke District of Dar-es-Salaam, Tanzania. TAM-TB assay accuracy was assessed by comparison with a composite reference standard comprising GeneXpert®and solid culture. A single millilitre of fresh blood was processed to measure expression of CD38 or CD27 by CD4 T cells producing INF-γ and/or TNF-α in response to a synthetic peptide pool covering the sequences ofMycobacterium tuberculosis(Mtb) ESAT-6, CFP-10 and TB10.4 antigens on a 4-color FACSCalibur apparatus.ResultsSignificantly superior to CD27 in accurately diagnosing TB, the CD38-based TAM-TB assay specificity reached 93.4% for a sensitivity of 82.2% with an area under the receiver operating characteristics curve of 0.87 (95% CI 0.84-0.91). The assay performance was not significantly affected by HIV status.ConclusionsWe successfully implemented TAM-TB immunoassay routine testing with a 24h turnaround time at district level in a resource limited setting. Starting from one millilitre of fresh blood and being not influenced by HIV status, TAM-TB assay format and performance appears closely compatible with the optimal TPP accuracy criteria defined by WHO for a non-sputum confirmatory TB test.
Characterizing the COVID-19 illness experience to inform the study of post-acute sequelae and recovery: a qualitative study
Authors: Santiago-Rodriguez Edda I. , Maiorana Andres , Peluso Michael J. , Hoh Rebecca , Tai Viva , Fehrman Emily A. , Hernandez Yanel , Torres Leonel , Spinelli Matthew A. , Gandhi Monica , Kelly J. Daniel , Martin Jeffrey N. , Henrich Timothy J. , Deeks Steven G. , Sauceda John A. 
Published: March 2021

AbstractWe aimed to characterize the variability in the illness experience and recovery process from COVID-19. We conducted in-depth individual interviews with participants enrolled in the Long-term Immunological Impact of Novel Coronavirus (LIINC) cohort study in San Francisco, California from June through October of 2020. Participants were adults who had a previously confirmed positive SARV-CoV-2 nucleic acid amplification test result, had recovered or were recovering from acute infection, and underwent serial evaluations at our clinical research center. We purposefully sampled 24 English- and Spanish-speaking adults with asymptomatic, mild and severe symptomatic infection, including those who were hospitalized, and those with HIV co-infection. Half of our sample (50.0%) identified as Latinx/Hispanic and most of the participants were men (62.5%). We used thematic analysis to characterize the illness experience, recovery process, and mental health impact of experiencing COVID-19 and present clinical data for each participant. Emergent themes were: (1) across symptom profiles and severity, experiencing COVID-19 was associated with psychological distress, (2) among participants with symptomatic infection, the illness experience was characterized by uncertainty in terms of managing symptoms and recovery, and (3) despite wide-ranging illness experiences, participants shared many common characteristics, including health information-seeking behavior facilitated by access to medical care, and uncertainty regarding the course of their illness and recovery. COVID-19 was associated with elevated levels of psychological distress, regardless of symptoms.
Integrin α6 upregulation in nucleus pulposus cell under high oxygen tension attenuates intervertebral disc degeneration
Authors: Xu Zeng , Zheng Jiancheng , Zhang Ying , Wu Huiqiao , Sun Bin , Zhang Ke , Wang Jianxi , Zang Fazhi , Zhang Xingkai , Guo Lei , Wu Xiaodong 
Published: March 2021

AbstractThe destruction of low oxygen microenvironment played critical roles in the pathogenesis of intervertebral disk degeneration (IVDD). In this study, high oxygen tension (HOT) treatment upregulated integrin α6(ITG α6) expression, which could be alleviated by blocking PI3K/AKT signaling pathway. And the levels of ITG α6 expression were increased in the NP tissue from IVDD patients and IVDD rat model with mild degeneration, which were reduced as degeneration degree increases. Further studies found that ITG α6 could protect NP cells against HOT-induced apoptosis and oxidative stress, and protect NP cells from HOT-inhibited ECM proteins synthesis. ITG α6 upregulation by HOT contributed to maintain a NP tissue homeostasis through the interaction with hypoxia inducible factor-1α (HIF-1α). Furthermore, silencing of ITG α6 in vivo could obviously accelerate puncture-induced IVDD. Taken together, ITG α6 upregulation by HOT in NP cells might be a protective factor in IVDD as well as restore NP cell function.
Efficacy and safety of Ayurveda interventions for Sinusitis: A systematic review and meta-analysis
Authors: Ahmad Azeem , S. Gundeti Manohar , P. Dave Parth , Jameela Sophia , Khanduri Shruti , Rao B.C.S. , Srikanth N. 
Published: March 2021

ABSTRACTObjectivesTo provide a broad evaluation of the efficacy and safety of Ayurveda interventions (procedural and non-procedural) for the management of sinusitis, and also of the relative efficacy and safety of different Ayurveda therapies for Sinusitis.MethodsFive electronic databases for published research articles, three databases for the unpublished doctoral thesis, clinical trial registries, and hand searches were done till August 2020. All comparative clinical trials recruiting sinusitis patients of any age group, receiving Ayurveda intervention, regardless of forms, dosages, and ingredients, for not less than one week were included. The data extraction and the risk of bias(RoB) assessment were done by two reviewers independently.ResultsA total of 2824 records were identified, of which 09 randomized parallel arms trials met inclusion criteria. No studies were found comparing Ayurveda versus placebo or non-Ayurveda interventions. Combined Ayurveda therapy (CT) was statistically more beneficial compared with either procedural or non-procedural Ayurveda therapy alone in reducing symptoms nasal discharge (standardized MD −0.71, 95% CI −1.16 to −0.26, I258%, 210 participants) and headache (standardized MD −0.44, 95% CI −0.86 to −0.02, I256%, 218 participants), however, no significant difference was found in reducing symptoms nasal obstruction and loss of smell. No numerical data related to the safety of Ayurveda intervention was found in included trials. Because, included trials(09) were having ‘high’ to ‘unclear’ overall bias, sub-standard methodology, and heterogeneity in results, the overall findings need to be interpreted cautiously.ConclusionsAlthough individual studies appeared to produce positive results, very low certainty of total effect(downgraded twice for RoB, once for inconsistency, indirectness, and imprecision each) hindered to arrive at any conclusion regarding efficacy or safety of Ayurveda interventions for sinusitis. There is a need for well-designed-executed-reported clinical studies on clinically relevant outcomes.PROSPERO registration numberRD42018103995ARTICLE SUMMARYStrength and limitations of this studyThis is the first systematic review to provide the status of available evidence on the efficacy and safety of Ayurveda interventions for sinusitis.The search strategy was comprehensive, all the relevant sources were searched for published as well as unpublished research works.This systematic review has a broad review question, which compromises its eternal validity.The certainty of the overall effect is ‘very low’ due to ‘unclear’ to ‘high’ overall risk of bias, lack of validated outcome measures, inconsistency in results with wide CIs, small sample sizes, incomplete reporting, etc.
Effect of intravesical chemotherapy on the survival of patients with non-muscle-invasive bladder cancer undergoing transurethral resection: a retrospective cohort study among older adults
Authors: Das Ashis Kumar , Mishra Devi Kalyan , Gopalan Saji Saraswathy 
Published: March 2021

AbstractBackgroundThe average age of diagnosis for bladder cancer is 73 and about 75 percent of all bladder cancers are non-muscle invasive at initial diagnosis. It is recommended that non-muscle invasive bladder cancers (NMIBC) should be treated with transurethral resection of the bladder tumor (TURBT) followed by chemotherapy. However, there is no large-scale study from real-world databases to show the effectiveness of chemotherapy on the survival of older adults with NMIBC that have undergone TURBT. This study aimed to investigate the effects of chemotherapy on survival among older NMIBC patients with TURBT.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015), we performed analyses of cancer-specific mortality and overall mortality comparing chemotherapy versus no chemotherapy after TURBT. Coarsened exact matching was performed to balance the baseline patient characteristics. Cox proportional hazards and Kaplan-Meir analyses were used to evaluate survival outcomes.ResultsA total of 3,222 matched patients with 1,611 in each arm (chemotherapy and no chemotherapy) were included in our study. After adjusting for covariates, multivariable Cox regression analyses show chemotherapy was associated with lower cancer-specific mortality (HR 0.63; 95% CI 0.42-0.94; p value 0.024). However, chemotherapy did not have any effect on overall mortality (HR 0.84; 95% CI 0.65-1.07; p value 0.159). The Kaplan-Meier curves show the protective effects of chemotherapy on cancer specific survival (p=0.032), but not on overall survival (p=0.34).ConclusionChemotherapy improved cancer specific survival among older patients with non-muscle invasive bladder cancer undergoing TURBT surgery, but it had no effect on overall survival. There is a need for more granular level real-world data on chemotherapy regimens and dosage to effectively investigate the effects of chemotherapy on survival of older patients with NMIBC that have undergone TURBT.
The role of connectivity on COVID-19 preventive approaches
Authors: Pina V. Miró , Nava-Trejo J. , Tóbiás A. , Nzabarushimana E. , González-Casanova A. , González-Casanova I. 
Published: March 2021

AbstractPreventive and modelling approaches to address the COVID-19 pandemic have been primarily based on the age or occupation, and often disregard the importance of heterogeneity in population contact structure and individual connectivity. To address this gap, we developed models based on Erdős-Rényi and a power law degree distribution that first incorporate the role of heterogeneity and connectivity and then can be expanded to make assumptions about demographic characteristics. Results demonstrate that variations in the number of connections of individuals within a population modify the impact of public health interventions such as lockdown or vaccination approaches. We conclude that the most effective strategy will vary depending on the underlying contact structure of individuals within a population and on timing of the interventions.Author summaryThe best strategy for public health interventions, such as lockdown or vaccination, depends on the contact structure of the population and the timing of the intervention. In general, for heterogeneous contact structures that mimic the COVID-19 spread, which is characterized by the presence of super spreaders, vaccinating the most connected individuals first was the most effective strategy to prevent infections and deaths, especially when coupled to serological tests. Models considering heterogeneity in human interactions need be used to identify the best potential vaccine prioritization strategies.
Using translational in vitro-in vivo modeling to improve drug repurposing outcomes for inhaled COVID-19 therapeutics
Authors: Stoddard Madison , Yuan Lin , Chakravarty Arijit 
Published: March 2021

AbstractThe ongoing COVID-19 pandemic has created an urgent need for antiviral treatments that can be deployed rapidly. Drug repurposing represents a promising means of achieving this objective, but repurposing efforts are often unsuccessful. A common hurdle to effective drug repurposing is a failure to achieve a sufficient therapeutic window in the new indication. A clear example is the use of ivermectin in COVID-19, where the approved dose (administered orally) fails to achieve therapeutic concentrations in the lungs. Our proposed solution to the problem of ineffective drug repurposing for COVID-19 antivirals is two-fold: to broaden the therapeutic window by reformulating therapeutics for the pulmonary route, and to select drug repurposing candidates based on their model-predicted therapeutic index for inhalation. In this article, we propose a two-stage model-driven screening and validation process for selecting inhaled antiviral drug repurposing candidates. While we have applied this approach in the specific context of COVID-19, this in vitro-in vivo translational methodology is also broadly applicable to repurposing drugs for diseases of the lower respiratory tract.
Transmembrane Kinases are essential for plant development
Authors: Li Qiang , Yang Jie , Zhang Yi , Wang Fen , Chang Mingzeng , Xu Tongda , Wang Shui , He Jun 
Published: March 2021

SUMMARYTransmembrane kinase family proteins (TMKs) have been implicated in regulating both auxin signaling and plant development. To obtain insights of the potential TMKs’ function in plant development, we regenerated new full sets oftmkmutants, and discovered many new phenotypes, such as defective organogenesis, smaller rosette leaves, fertility defects and selfing population defects in different combination oftmkmutants. Taken together, our results demonstrated that TMKs participated in multiple aspects of plant development, which provided a great reference for any future research.One-sentence summaryMultipletmkmutants analysis illustrated the key roles of TMKs in plant development.