bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct Multivariate Structural Brain Profiles Are Related to Variations in Short- and Long-Delay Memory Consolidation Across Children and Young Adults
Authors: Schommartz Iryna , Lembcke Philip F. , Pupillo Francesco , Schuetz Henriette , de Chamorro Nina Wald , Bauer Martin , Kaindl Angela M. , Buss Claudia , Shing Yee Lee 
Published: August 2021

AbstractFrom early to middle childhood, brain regions that underlie memory consolidation undergo profound maturational changes. However, there is little empirical investigation that directly relates age-related differences in brain structural measures to the memory consolidation processes. The present study examined system-level memory consolidations of intentionally studied object-location associations after one night of sleep (short delay) and after two weeks (long delay) in normally developing 5-to-7-year-old children (n = 50) and young adults (n = 39). Behavioural differences in memory consolidation were related to structural brain measures. Our results showed that children, in comparison to young adults, consolidate correctly learnt object-location associations less robustly over short and long delay. Moreover, using partial least squares correlation method, a unique multivariate profile comprised of specific neocortical (prefrontal, parietal, and occipital), cerebellar, and hippocampal subfield structures was found to be associated with variation in short-delay memory consolidation. A different multivariate profile comprised of a reduced set of brain structures, mainly consisting of neocortical (prefrontal, parietal, and occipital), and selective hippocampal subfield structures (CA1-2 and subiculum) was associated with variation in long-delay memory consolidation. Taken together, the results suggest that multivariate structural pattern of unique sets of brain regions are related to variations in short- and long-delay memory consolidation across children and young adults.RESEARCH HIGHLIGHTSShort- and long-delay memory consolidation is less robust in children than in young adultsShort-delay brain profile comprised of hippocampal, cerebellar, and neocortical brain regionsLong-delay brain profile comprised of neocortical and selected hippocampal brain regions.Brain profiles differ between children and young adults.
Utilizing Pine Needles to Temporally and Spatially Profile Per- and Polyfluoroalkyl Substances
Authors: Kirkwood Kaylie I. , Fleming Jonathon , Nguyen Helen , Reif David M. , Baker Erin S. , Belcher Scott M. 
Published: August 2021

AbstractAs concerns continue to mount over exposure to per- and polyfluoroalkyl substances (PFAS), novel methods of profiling their presence and modifications are greatly needed as some have known toxic and bioaccumulative characteristics while others have unknown effects. This task however is not simple as over 5000 PFAS of interest have been named by the Environmental Protection Agency and this list continues to grow daily. In this work, we utilized widely available archived and field-sampled pine needles and a novel non-targeted analytical method to evaluate the temporal and spatial presence of numerous PFAS. Over 70 PFAS were detected in the pine needles from this study, providing information from the last six decades related to PFAS exposure, contamination, and reduction.
Effective Ensemble of Deep Neural Networks Predicts Neural Responses to Naturalistic Videos
Authors: Yang Huzheng , Zhang Shanghang , Wu Yifan , Li Yuanning , Gu Shi 
Published: August 2021

AbstractThis report provides a review of our submissions to the Algonauts Challenge 2021. In this challenge, neural responses in the visual cortex were recorded using functional neuroimaging when participants were watching naturalistic videos. The goal of the challenge is to develop voxel-wise encoding models which predict such neural signals based on the input videos. Here we built an ensemble of models that extract representations based on the input videos from 4 perspectives: image streams, motion, edges, and audio. We showed that adding new modules into the ensemble consistently improved our prediction performance. Our methods achieved state-of-the-art performance on both the mini track and the full track tasks.
Waning of BNT162b2 vaccine protection against SARS-CoV-2 infection in Qatar
Authors: Chemaitelly Hiam , Tang Patrick , Hasan Mohammad R. , AlMukdad Sawsan , Yassine Hadi M. , Benslimane Fatiha M. , Al Khatib Hebah A. , Coyle Peter , Ayoub Houssein H. , Kanaani Zaina Al , Kuwari Einas Al , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul Rahim Hanan F. , Nasrallah Gheyath K. , Al Kuwari Mohamed Ghaith , Al Romaihi Hamad Eid , Butt Adeel A. , Al-Thani Mohamed H. , Khal Abdullatif Al , Bertollini Roberto , Abu-Raddad Laith J. 
Published: August 2021

ABSTRACTBACKGROUNDWaning of vaccine protection against SARS-CoV-2 infection or COVID-19 disease is a concern. This study investigated persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the Beta and Delta variants have dominated incidence and PCR testing is done at a mass scale.METHODSA matched test-negative, case-control study design was used to estimate vaccine effectiveness against SARS-CoV-2 infection and against any severe, critical, or fatal COVID-19 disease, between January 1, 2021 to August 15, 2021.RESULTSEstimated BNT162b2 effectiveness against any infection, asymptomatic or symptomatic, was negligible for the first two weeks after the first dose, increased to 36.5% (95% CI: 33.1-39.8) in the third week after the first dose, and reached its peak at 72.1% (95% CI: 70.9-73.2) in the first five weeks after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating ≥15 weeks after the second dose, reaching diminished levels of protection by the 20thweek. Effectiveness against symptomatic infection was higher than against asymptomatic infection, but still waned in the same fashion. Effectiveness against any severe, critical, or fatal disease increased rapidly to 67.7% (95% CI: 59.1-74.7) by the third week after the first dose, and reached 95.4% (95% CI: 93.4-96.9) in the first five weeks after the second dose, where it persisted at about this level for six months.CONCLUSIONSBNT162b2-induced protection against infection appears to wane rapidly after its peak right after the second dose, but it persists at a robust level against hospitalization and death for at least six months following the second dose.
Using telehealth consultations for healthcare provision to patients from racial/ethnic minorities: A systematic review
Authors: Truong Mandy , Yeganeh Ladan , Cook Olivia , Crawford Kimberley , Wong Pauline , Allen Jacqueline 
Published: August 2021

ABSTRACTObjectiveThe COVID-19 pandemic has seen a rapid adoption of telehealth consultations, potentially creating new barriers to healthcare access for racial/ethnic minorities. This systematic review explored the use of telehealth consultations for people from racial/ethnic minority populations in relation to health outcomes, access to care, implementation facilitators and barriers, and satisfaction with care.Materials and MethodsThis review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and the JBI Manual for Evidence Synthesis. Five major databases were searched to identify relevant studies. Screening, full-text review, quality appraisal and data extraction were all completed independently and in duplicate. A convergent integrated approach to data synthesis was applied with findings reported narratively.ResultsA total of 28 studies met the inclusion criteria. Telehealth-delivered interventions were mostly effective for the treatment/management of physical and mental health conditions including depression, diabetes and hypertension. In several studies, telehealth improved access to care by providing financial and time benefits to patients. Technological difficulties were the main barriers to effective telehealth consultation, although overall satisfaction with telehealth-delivered care was high.DiscussionTelehealth-delivered care for racial/ethnic minorities offers promise across a range of conditions and outcomes, particularly when delivered in the patient’s preferred language. However, telehealth may be problematic for some due to cost and limited digital and health literacy.ConclusionThe development and implementation of guidelines, policies and practices in relation to telehealth consultations for racial/ethnic minorities should consider the barriers and facilitators identified in this review to ensure existing health disparities are not exacerbated.
Facility-based HIV self-testing strategies may substantially increase number of men and youth tested for HIV in Malawi: results from a data-driven individual-based model
Authors: Nichols Brooke E , de Nooy Alexandra , Benade Mariet , Balakasi Kelvin , Mphande Misheck , Rao Gabriella , Claassen Cassidy W , Khan Shaukat , Stillson Christian , Doi Naoko , Dovel Kathryn 
Published: August 2021

AbstractBackgroundMalawi is rapidly closing the gap in achieving the UNAIDS 95-95-95 targets, with 90% of people living with HIV in Malawi aware of their status. As we approach epidemic control, interventions to improve coverage will become more costly. There is therefore an urgent need to identify innovative and low-cost strategies to maintain and increase testing coverage without diverting resources from other HIV services.MethodsA data-driven individual-based model was parameterized with data from a community-representative survey (sociodemographic, health service utilization, HIV testing history) of men and youth in Malawi (data collected 08/2019). 79 different strategies for the implementation of HIV self-testing (HIVST) and provider-initiated-testing-and-counselling at the outpatient department (OPD) were evaluated. Outcomes included percent of men/youth tested for HIV in a 12-month period, cost-effectiveness, and human resource requirements. Testing yield was assumed to be constant across the scenarios.FindingsFacility-based HIVST offered year-round resulted in the greatest increase in proportion of men and youth tested in the OPD (from 45% to 72%-83%), was considered cost-saving for HIVST kit priced at $1.00, and generally reduced required personnel as compared to the status quo. At higher HIVST kit prices, and more relaxed eligibility criteria, all scenarios that considered year-round HIVST in the OPD remained on the cost-effectiveness frontier.InterpretationFacility-based HIVST is a cost-effective strategy to increase the proportion of men/youth tested for HIV and decreases the human resource requirements for HIV testing in the OPD-providing additional health care worker time for other priority health care activities.FundingFCDO; USAID
Differentials and predictors of hospitalization among the elderly people in India: Evidence from 75thround of National Sample Survey (2017-18)
Authors: Akhtar Saddaf Naaz , Saikia Nandita 
Published: August 2021

AbstractIntroductionThere are limited evidences on the determinants of hospitalization and its causes in India. We examined the differential in the hospitalization rates and its socio-economic determinants. We also examined the causes of diseases in hospitalization among the elderly (≥60 years) in India.MethodsWe used data from 75thround of the National Sample Survey Organizations (NSSO), collected from July 2017 to June 2018. The elderly samples in this survey are 42759, where 11070 were hospitalized, and 31,689 were not hospitalized in the last year or 365 days. We estimated hospitalization rates and carried out binary logistic regression analysis to examine the associations of hospitalization with the background variables. The cause of diseases in hospitalizations were also calculated.ResultsHospitalization rate was lower among female elderly compared to male elderly. Elderly who belongs to middle-old aged groups, non-married, North-Eastern region, Southern region, general caste, health insurance, partially & fully economically dependent elderly have a higher chance of being hospitalized. About 38% elderly were hospitalized due to communicable diseases (CDs), 52% due to non-communicable diseases (NCDs) and 10% due to Injuries & others. Nearly 40% elderly were hospitalized in public hospitals due to CDs, while 52% were hospitalized in private hospitals due to NCDs and 11% due to Injuries & others.ConclusionsRaising awareness, promoting a healthy lifestyle, and improving the quality of good healthcare provisions at the primary level is necessary. Early screening and early treatment for NCDs are needed, which is non-existent in almost all parts of India.
Transient DUX4 expression induces blastomere-like expression program that is marked by SLC34A2
Authors: Yoshihara Masahito , Kirjanov Ida , Nykänen Sonja , Sokka Joonas , Weltner Jere , Lundin Karolina , Gawriyski Lisa , Jouhilahti Eeva-Mari , Varjosalo Markku , Tervaniemi Mari H. , Otonkoski Timo , Trokovic Ras , Katayama Shintaro , Vuoristo Sanna , Kere Juha 
Published: August 2021

AbstractDUX4 has recently been recognized as a key regulator in human embryonic genome activation (EGA). The exact role of DUX4 in human embryo is still elusive, partly due to the cytotoxicity of persistent DUX4 expression in cellular models. We report here that a transient DUX4 expression in human embryonic stem cells (hESCs) retains cell viability while inducing an EGA-like expression program in a subpopulation of the cells. These cells showed resemblance to 8-cell stage blastomeres and were thus named induced blastomere-like (iBM) cells. Trajectory inference from the single-cell RNA-seq data suggested that the expression profile of these cells progressed in a manner similar to the morula to blastocyst transition in human embryo. Finally, viable iBM cells could be enriched using an antibody against NaPi2b (SLC34A2), paving the way for further experimental approaches. The iBM cells can become a powerful tool to model transcriptional dynamics and regulation during early human embryogenesis.
Diterpenoid Vinigrol activates ATF4/DDIT3-mediated PERK/eIF2α arm of unfolded protein response to drive breast cancer cell death
Authors: Wei Wencheng , Li Yunfei , Wang Chuanxi , Gao Sanxing , Wang Hao , Zhao Yan , Gao Ziying , Jiang Yanxiang , Gao Hao , Yao Xinsheng , Hu Yuhui 
Published: August 2021

AbstractVinigrol is a natural diterpenoid with unprecedented chemical structure, driving great efforts into its total synthesis and the chemical analogs in the past decades. Despite its pharmacological efficacies reported on anti-hypertension and anti-clot, comprehensive functional investigations on Vinigrol and the underlying molecular mechanisms are entirely missing. In this study, we carried out a complete functional prediction of Vinigrol using a transcriptome-based strategy, Connectivity Map, and identified “anti-cancer” as the most prominent biofunction ahead of anti-hypertension and anti-depression/psychosis. A broad cytotoxicity was subsequently confirmed on multiple cancer types. Further mechanistic investigation on MCF7 cells revealed that its anti-cancer effect is mainly through activating PERK/eIF2α arm of unfolded protein response (UPR) and subsequent upregulation of p53/p21 to halt the cell cycle. The other two branches of UPR, IRE1α and ATF6, are functionally irrelevant to Vinigrol-induced cell death. CRISPR/Cas9-based gene activation, repression, and knockout systems identified essential contribution of ATF4/DDIT3 not ATF6 to the death process. This study unraveled a broad anti-cancer function of Vinigrol and its underlying targets and regulatory mechanisms, and also paved the way for further inspection on the structure-efficacy relationship of the whole compound family, making them a novel cluster of chemical hits for cancer therapy.
Does genetic differentiation underlie behavioral divergence in response to migration barriers in sticklebacks? A common garden experiment
Authors: Ramesh A. , Domingues M. M. , Stamhuis E.J. , Groothuis A.G.G. , Weissing F.J. , Nicolaus M. 
Published: August 2021

AbstractWater management measures in the 1970s in the Netherlands have produced a large number of ‘resident’ populations of three-spined sticklebacks that are no longer able to migrate to the sea. This may be viewed as a replicated field experiment, allowing us to study how the resident populations are coping with human-induced barriers to migration. We have previously shown that residents are smaller, bolder, more exploratory, more active, more aggressive, exhibited lower shoaling and lower migratory tendencies compared to their ancestral ‘migrant’ counterparts. However, it is not clear if these differences in wild-caught residents and migrants reflect genetic differentiation, rather than different developmental conditions. To investigate this, we raised offspring of four crosses (migrant ♂ x migrant ♀, resident ♂ x resident ♀, migrant ♂ x resident ♀, resident ♂ x migrant ♀) under similar controlled conditions and tested for differences in morphology and behavior as adults. We found that lab-raised resident sticklebacks exhibited lower shoaling and migratory tendencies as compared to lab-raised migrants, retaining the differences in their wild-caught parents. This indicates genetic differentiation of these traits. For all other traits, the lab-raised sticklebacks of the various crosses did not differ significantly, suggesting that the earlier-found contrast between wild-caught fish reflect differences in their environment. Our study shows that barriers to migration can lead to rapid differentiation in behavioral tendencies over contemporary timescales (∼50 generations), and that part of these differences reflects genetic differentiation.Significance statementMany organisms face changes to their habitats due to human activities. Much research is therefore dedicated to the question whether and how organisms are able to adapt to novel conditions. We address this question in three-spined sticklebacks, where water management measures cut off some populations, prohibiting their seasonal migration to the North Sea. In a previous study, we showed that wild-caught ‘resident’ fish exhibited markedly different behavior than migrants. To disentangle whether these differences reflect genetic differentiation or differences in the conditions under which the wild-caught fish grew up, we conducted crosses, raising the F1 offspring under identical conditions. As their wild-caught parents, the F1 of resident x resident crosses exhibited lower migratory and shoaling tendencies than the F1 of migrant x migrant crosses, while the F1 of hybrid crosses were intermediate. This suggests that ∼50 years of isolation are sufficient to induce behaviorally relevant genetic differentiation.
Developmental Venous Anomalies are a Genetic Primer for Cerebral Cavernous Malformations
Authors: Snellings Daniel A. , Girard Romuald , Lightle Rhonda , Srinath Abhinav , Romanos Sharbel , Li Ying , Chen Chang , Ren Aileen A. , Kahn Mark L. , Awad Issam A. , Marchuk Douglas A. 
Published: August 2021

AbstractCerebral cavernous malformations (CCM) are a neurovascular anomaly that may occur sporadically in otherwise healthy individuals, or be inherited by autosomal dominant mutations in the genes that encode the proteins of the CCM signaling complex (KRIT1, CCM2, or PDCD10)1–4. CCMs have long been known to follow a genetic two-hit model where lesion formation is initiated by somatic mutations resulting in biallelic loss of a CCM complex gene5–8. Recent studies have shown that somatic mutations in MAP3K3 and PIK3CA also contribute to CCM pathogenesis9–11; however, it remains unclear how these mutations contribute to sporadic versus familial cases. Here we show that somatic mutations in MAP3K3 are mutually exclusive with mutations in CCM complex genes and that mutations in MAP3K3 contribute to sporadic, but not familial CCM. Using single-nucleus DNA sequencing, we show that co-occurring MAP3K3 and PIK3CA mutations are present within the same clonal population of cells. Furthermore, we identify PIK3CA mutations in CCM-associated developmental venous anomalies (DVA). It has long been known that sporadic CCM often develop in the vicinity of a DVA. However, the underlying cause of this association is unknown12–14. In this first report of the molecular pathology of CCM-associated DVA, we find that the identical PIKC3A mutation is found in both the DVA and its associated CCM, but that an activating MAP3K3 mutation appears only in the CCM. These results support a mechanism where DVA develop as the result of a PIK3CA mutation, creating a region of the brain vasculature that functions as a genetic primer for CCM development following acquisition of an additional somatic mutation.
A hierarchical GBP network promotes cytosolic LPS recognition and sepsis
Authors: Park Eui-Soon , Kim Bae-Hoon , Kumar Pradeep , Tretina Kyle , Maminska Agnieszka , Philbrick William M. , Flavell Richard A. , MacMicking John D. 
Published: August 2021

AbstractBacterial lipopolysaccharide (LPS) is one of the most bioactive substances known. Trace amounts trigger robust immunity to infection but also life-threatening sepsis causing millions of deaths each year. LPS contamination of the cytosol elicits a caspase-dependent inflammasome pathway promoting cytokine release and host cell death. Here, we report an immune GTPase network controls multiple steps in this pathway by genome-engineering mice to lack 7 different guanylate-binding proteins (GBPs). Gbp2-/- and Gbp3-/- mice had severe caspase-11-driven defects that protected them from septic shock. Gbp2 recruited caspase-11 for LPS recognition whereas Gbp3 assembled and trafficked the pyroptotic pore-forming protein, gasdermin D, after caspase-11 cleavage. Together, our results identify a new functional hierarchy wherein different GBPs choreograph sequential steps in the non-canonical inflammasome pathway to control Gram-negative sepsis.One-Sentence SummaryImmune GTPase network orchestrates hierarchical immunity to bacterial products in vivo
Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains
Authors: Ying Baoling , Whitener Bradley , VanBlargan Laura A. , Hassan Ahmed O. , Shrihari Swathi , Liang Chieh-Yu , Karl Courtney E. , Mackin Samantha , Chen Rita E. , Kafai Natasha M. , Wilks Samuel H. , Smith Derek J. , Carreño Juan Manuel , Singh Gagandeep , Krammer Florian , Carfi Andrea , Elbashir Sayda , Edwards Darin K. , Thackray Larissa B. , Diamond Michael S. 
Published: August 2021

SUMMARYAlthough mRNA vaccines prevent COVID-19, variants jeopardize their efficacy as immunity wanes. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike) or modified (mRNA-1273.351, designed for B.1.351 spike) preclinical Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Immunization with high or low dose formulations of mRNA vaccines induced neutralizing antibodies in serum against ancestral SARS-CoV-2 and several variants, although levels were lower particularly against the B.1.617.2 (Delta) virus. Protection against weight loss and lung pathology was observed with all high-dose vaccines against all viruses. Nonetheless, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, and serve as a possible model for waning immunity, showed breakthrough lung infection and pneumonia with B.1.617.2. Thus, as levels of immunity induced by mRNA vaccines decline, breakthrough infection and disease likely will occur with some SARS-CoV-2 variants, suggesting a need for additional booster regimens.