bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring predictive frameworks for malaria in Burundi
Authors: Mfisimana Lionel Divin , Nibayisabe Emile , Badu Kingsley , Niyukuri David 
Published: July 2021

AbstractMalaria is a major public health concern in Burundi. The infection has been increasing in the last decade despite efforts to increase access to health services, and the deployment of several intervention programs. The use of different data sources can help to build predictive models of malaria cases in different sub-populations. We built predictive frameworks using generalized linear model (GLM), and artificial neural network to predict malaria cases in four sub-populations (pregnant women and children under 5 years, pregnant women, children between 0 and 11 months, children between 12 and 59 months), and the overall general population. The results showed that almost half malaria infections are observed in pregnant women and children under 5 years, but children between 12 and 59 months carry the highest burden. Neural network model performed better in predicting total cases compared to GLM. But the latter provided information on the effect of predictors, which is an important source of information to mainstream target interventions. Early prediction of cases can provide timely information needed to be proactive for intervention strategies, and it can help to mitigate the epidemics and reduce its impact on populations and the economy.
Time trends, factors associated with, and reasons for COVID-19 vaccine hesitancy in a massive online survey of US adults: January-May 2021
Authors: King Wendy C , Rubinstein Max , Reinhart Alex , Mejia Robin 
Published: July 2021

AbstractImportanceCOVID-19 vaccine hesitancy has become a leading barrier to increasing the US vaccination rate.ObjectiveTo evaluate time trends in COVID-19 vaccine intent during the US vaccine rollout, and identify key factors related to and self-reported reasons for COVID-19 vaccine hesitancy in May 2021.Design, participants and settingA COVID-19 survey was offered to US adult Facebook users in several languages yielding 5,088,772 qualifying responses from January 6 to May 31, 2021. Data was aggregated by month. Survey weights matched the sample to the age, gender, and state profile of the US population.ExposureDemographics, geographic factors, political/COVID-19 environment, health status, beliefs, and behaviors.Main outcome measures“If a vaccine to prevent COVID-19 were offered to you today, would you choose to get vaccinated.” Hesitant was defined as responding probably or definitely would not choose to get vaccinated (versus probably or definitely would, or already vaccinated).ResultsCOVID-19 vaccine hesitancy decreased by one-third from 25.4% (95%CI, 25.3, 25.5) in January to 16.6% (95% CI, 16.4, 16.7) in May, with relatively large decreases among participants with Black, Pacific Islander or Hispanic race/ethnicity and ≤high school education. Independent risk factors for vaccine hesitancy in May (N=525,644) included younger age, non-Asian race, < 4 year college degree, living in a more rural county, living in a county with higher Trump vote share in the 2020 election, lack of worry about COVID-19, working outside the home, never intentionally avoiding contact with others, and no past-year flu vaccine. Differences in hesitancy by race/ethnicity varied by age (e.g., Black adults more hesitant than White adults <35 years old, but less hesitant among adults ≥45 years old). Differences in hesitancy by age varied by race/ethnicity. Almost half of vaccine hesitant respondents reported fear of side effects (49.2% [95%CI, 48.7, 49.7]) and not trusting the COVID-19 vaccine (48.4% [95%CI, 48.0, 48.9]); over one-third reported not trusting the government, not needing the vaccine, and waiting to see if safe. Reasons differed by degree of vaccine intent and by race/ethnicity.ConclusionCOVID-19 vaccine hesitancy varied by demographics, geography, beliefs, and behaviors, indicating a need for a range of messaging and policy options to target high-hesitancy groups.
Apathy: an underestimated feature in GBA and LRRK2 non-manifesting mutation carriers
Authors: Pachi Ioanna , Koros Christos , Simitsi Athina M , Papadimitriou Dimitra , Bougea Anastasia , Prentakis Andreas , Papagiannakis Nikolaos , Bozi Maria , Antonelou Roubina , Angelopoulou Efthalia , Beratis Ion , Stamelou Maria , Trapali Xenia Geronicola , Papageorgiou Sokratis G. , Stefanis Leonidas 
Published: July 2021

AbstractBackgroundHigher prevalence of motor and non-motor features has been observed in non-manifesting mutation carriers of Parkinson’s Disease (PD) compared to Healthy Controls (HC).ObjectivesThe aim was to detect the differences between GBA and LRRK2 mutation carriers without PD and HC on neuropsychiatric symptoms.MethodsThis is a cross-sectional retrospective study of non-manifesting GBA and LRRK2 mutation carriers and HC enrolled into Parkinson’s Progression Markers Initiative (PPMI). Data extracted from the PPMI database contained: demographics and performance in MoCA scale and MDS-UPDRS scale part 1A (neuropsychiatric symptoms). All six features were treated as both continuous (MDS-UPDRS individual scores) and categorical variables (MDS-UPDRS individual score>0 and MDS-UPDRS individual score=0). Logistic regression analyses were applied to evaluate the association between mutation carrying status and neuropsychiatric symptoms.ResultsWe found that non-manifesting mutation carriers as a whole (total N=654, GBA: n=285, LRRK2: n=369) were 2.3 times more likely to present apathy compared to HC, even after adjustment for covariates (adjusted OR=2.3, 95% CI=1.1-5.0, p-value=0.027). The effect was mainly driven by GBA mutation carriers (adjusted OR= 2.6, 95% CI=1.1-6.3, p=0.031), while the higher percentage of apathy for LRRK2 carriers compared to HC was marginally non-significant. Other neuropsychiatric symptoms, such as psychotic or depressive manifestations, did not differ between groups.ConclusionsSymptoms of apathy could be present in the premotor period of LRRK2 and, especially, GBA mutation carriers. Longitudinal data, including detailed neuropsychiatric evaluation and neuroimaging, would be essential to further investigate the pathophysiological basis of this finding.
BNT162b2 Vaccination efficacy is marginally affected by the SARS-CoV-2 B.1.351 variant in fully vaccinated individuals
Authors: Mor Orna , Zuckerman Neta S. , Hazan Itay , Fluss Ronen , Ash Nachman , Ginish Netanel , Mendelson Ella , Alroy-Preis Sharon , Freedman Laurence , Huppert Amit 
Published: July 2021

ABSTRACTBackgroundIsraeli has vaccinated over 80% of its adult population, with two doses of the Pfizer BNT162b2 vaccine. This intervention has been highly successful in curtailing the coronavirus 2 outbreak. One major concern is the ability of the virus to mutate which potentially can cause SARS-CoV-2 to partially escape from the immune system. Here we evaluate the efficacy of the Pfizer vaccine against the B.1.351 variant.MethodsThe Ministry of Health, initiated sequencing of selected positive swab samples identified as being of interest. We used logistic regression, with variant type as the dependent variable, vaccination status as the main explanatory variable, controlling for age, sex, subpopulation, place of residence and time of sample, to estimate the odds ratio for a vaccinated case to have the B. 1.351 versus the B.1.1.7 variant, within vaccinated and unvaccinated persons who tested positive.FindingsThere were 19 cases of B.1.351 variant (3.2%) among those vaccinated more than 14 days before the positive sample and 88 (3.5%) among the unvaccinated. The estimated odds ratio was 1.29 [95% CI: 0.66-2.50]. From this result, assuming the efficacy against the B.1.1.7 variant to be 95%, the estimated efficacy against the B.1.351 variant was 94% [95% CI: 87-97%].InterpretationDespite the concerns caused by the B.1.351 variant, the BNT162b2 vaccine seems to provide substantial immunity against both that variant and the B.1.1.7. Our results suggest that from 14 days following the second vaccine dose the efficacy of BNT162b2 vaccine is at most marginally affected by the B.1.351 variant.FundingNo funding
Parsing Genetically Influenced Risk Pathways: Genetic Loci Impact Problematic Alcohol Use Via Externalizing and Specific Risk
Authors: Barr Peter B. , Mallard Travis T. , Sanchez-Roige Sandra , Poore Holly E. , Linnér Richard Karlsson ,   COGA Collaborators, Waldman Irwin D. , Palmer Abraham A. , Harden K. Paige , Dick Danielle M. 
Published: July 2021

AbstractImportanceCharacterizing whether genetic variants for psychiatric outcomes operate via specific versus general pathways provides more informative measures of genetic risk, and, potentially, allows us to design more targeted prevention and interventions.ObjectiveEmploy multivariate methods to tease apart variants associated with problematic alcohol use through either general or specific pathways and compare results to standard univariate genetic analysis of problematic alcohol use.DesignWe compared results from a univariate genome wide association study (GWAS) of problematic alcohol use to those from a previous multivariate GWAS of externalizing phenotypes. We identified genetic variants associated with problematic alcohol use through a broad liability to externalizing, and those that remain after removing shared variance with externalizing. We compared these results across SNP overlap, bioannotations, genetic correlations, and polygenic scores.SettingWe included GWAS summary statistics from existing GWAS, and two US based hold out samples: The National Longitudinal Study of Adolescent to Adult Health (Add Health) and the Collaborative Study on the Genetics of Alcoholism (COGA).ParticipantsPublicly available GWAS of externalizing behaviors and participants in Add Health (N=5,107) and COGA (N=7,483), limited to individuals of European ancestries.Exposure(s)N/AMain Outcome(s) and Measure(s)Outcomes included problematic alcohol use (ALCP-O), shared risk for externalizing (EXT), and problematic alcohol use-specific risk (ALCP-S) for the GWASs; a preregistered list of 99 available phenotypes for genetic correlations; and substance use, substance use disorder criteria, and alcohol misuse in the polygenic score analyses.ResultsThe analysis differentiated SNPs operating through common versus specific risk pathways. While ALCP-O was associated with multiple phenotypes, ALCP-S was predominantly associated with alcohol use and other forms of psychopathology. Polygenic scores for ALCP-O were associated with a variety of other forms of substance use and substance use disorders, polygenic scores for ALCP-S were only associated with alcohol phenotypes. Polygenic scores for both ALCP-S and EXT show differential patterns of associations with alcohol misuse across development.Conclusions and RelevanceFocusing on the differential impacts of shared and specific risk can better characterize pathways of risk for alcohol use disorders. Multivariate methods can be a useful tool for studying many psychiatric conditions. Parsing risk pathways will become increasingly relevant as genetic information is incorporated into clinical practice for psychiatric outcomes.
NO INCREASE IN RELATIVE MORTALITY RATES FOR THOSE WITHOUT A COLLEGE DEGREE DURING COVID-19: AN ANOMALY
Authors: Case Anne , Deaton Angus 
Published: July 2021

ABSTRACTAmerican mortality rates have diverged in recent years between those with and without a four-year college degree, and there are many reasons to expect the education-mortality gradient to have steepened during the pandemic. Those without a BA are more likely to work in frontline occupations, to rely on public transportation, and to live in crowded quarters, all of which are associated with an increase in infection risk, a risk that was zero prior to the pandemic. We use publicly available data from the National Center for Health Statistics on deaths by age, sex, education and race/ethnicity to assess the protective effect of a BA in 2020 compared to 2019. While the BA was strongly protective during 2020, the ratio of mortality rates between those with and without a degree was little changed relative to pre-pandemic years. Among 60 groups (gender by race/ethnicity by age) that are available in the data, the relative risk reduction associated with a BA fell for more than half the groups between 2019 and 2020, and increased by more than 5 percentage points for only five groups. Our main finding is not that the BA was protective against death in 2020, which has long been the case, but that the protective effect was little different than in 2019 and earlier years, in spite of the change in the pattern of risk by occupation and income. The virus maintained the mortality-education gradient that existed pre-pandemic, at least through the end of 2020. Our results suggest that changes in the risk of infection were less important in structuring mortality than changes in the risk of death conditional on infection.
Associations between forensic loci and neighboring gene expression levels may compromise medical privacy
Authors: Bañuelos Mayra M. , Zavaleta Jhony A. , Roldan Alennie , Reyes Rochelle-Jan , Guardado Miguel , Rojas Berenice Chavez , Nyein Thet , Vega Ana Rodriguez , Santos Maribel , Sanchez Emilia Huerta , Rohlfs Rori 
Published: July 2021

ABSTRACTA set of 20 short tandem repeats (STRs) is used by the United States criminal justice system to identify suspects, and to maintain a database of genetic profiles for individuals who have been previously convicted or arrested. Some of these STRs were identified in the 1990s, with a preference for markers in putative gene deserts to avoid forensic profiles revealing protected medical information. We revisit that assumption, investigating whether forensic genetic profiles reveal information about gene expression variation, or potential medical information. We find six significant correlations (FDR = 0.23) between the forensic STRs and the expression levels of neighboring genes in lymphoblastoid cell lines. We explore possible mechanisms for these associations, with evidence compatible with forensic STRs causing expression variation, or being in LD with a causal locus in three cases, and weaker or potentially spurious associations in the other three cases. Together, these results suggest that forensic genetic loci may reveal expression level and, perhaps, medical information.
Sex-specific effects of aging on the humoral immune response to repeat vaccination with the high-dose seasonal influenza vaccine in older adults
Authors: Shapiro Janna R. , Li Huifen , Morgan Rosemary , Chen Yiyin , Kuo Helen , Ning Xiaoxuan , Shea Patrick , Wu Cunjin , Merport Katherine , Saldanha Rayna , Liu Suifeng , Abrams Engle , Chen Yan , Kelly Denise C. , Sheridan-Malone Eileen , Wang Lan , Zeger Scott L. , Klein Sabra L. , Leng Sean X. 
Published: July 2021

AbstractOlder adults (≥65 years of age) bear a significant burden of severe disease and mortality associated with influenza, despite relatively high annual vaccination coverage and substantial pre-existing immunity to influenza. To test the hypothesis that host factors, including age and sex, play a role in determining the effect of repeat vaccination and levels of pre-existing humoral immunity to influenza, we evaluated pre- and post-vaccination strain-specific hemagglutination inhibition (HAI) titers in adults over 75 years of age who received a high-dose influenza vaccine in at least four out of six influenza seasons (NCT02200276). Neither age, sex, body mass index, frailty, nor repeat vaccination were significantly associated with post-vaccination HAI titer outcomes. Pre-vaccination titers, however, were significantly predictive of post-vaccination outcomes. Pre-vaccination titers to H1N1 remained constant with age, while those to H3N2 and influenza B decreased substantially with age in males but not in females. Our findings highlight the importance of pre-existing immunity in this highly vaccinated older adult population and suggest that older males are particularly vulnerable to reduced pre-existing humoral immunity to influenza from previous annual vaccination.
Cell-Mediated and Humoral Immune Response to 2-Dose SARS-CoV2 mRNA vaccination in Immunocompromised patient population
Authors: Ramanathan Muthukumar , Murugesan Kanagavel , Yang Lu M. , Costales Cristina , Bulterys Philip L. , Schroers-Martin Joseph , Alizadeh Ash A. , Boyd Scott D. , Brown Janice M. , Nadeau Kari C. , Nadimpalli Sruti S. , Wang Aileen X. , Busque Stephan , Pinsky Benjamin A. , Banaei Niaz 
Published: July 2021

AbstractCharacterization of cell-mediated and humoral immune responses to SARS-CoV2 mRNA vaccine has implications for protective immunity in immunocompromised patients. However, studies have demonstrated poor humoral response to SARS-CoV2 mRNA vaccine in immunocompromised patients and data on cellular immune response are currently lacking. Here we compared immune response after 2-dose vaccination in 100 immunocompromised patients (solid organ transplant recipients, hematologic malignancy, autoimmune condition, and primary immunodeficiency) and 16 immunocompetent healthy healthcare workers. We find that 100% (CI=80.6-100%) of immunocompetent individuals show positive cell-mediated and humoral immune response post vaccination while only 50% (CI=40.4-59.6%) of immunocompromised patients show humoral immune response and 69% (CI=59.4-77.2%) have a positive cell-mediated immune response. 21% of immunocompromised patients have no humoral immune response or cell-mediated immune response and thus are likely vulnerable to SARS-CoV2 infection. Monitoring of immune response in immunocompromised populations, particularly in high-risk immunocompromised patients (solid organ transplant recipients, patients with severe autoimmunity, and those ≥50 years), with clinical IGRA and serological assay after vaccination may identify patients who may benefit from revaccination or prophylactic monoclonal antibody therapy to prevent COVID-19 in this patient population
Phase 1 Safety and Pharmacokinetics Studies of BRII-196 and BRII-198, SARS-CoV-2 Spike-Targeting Monoclonal Antibodies
Authors: Zhang Yao , Hao Xiaohua , Ma Ji , Wang Mingming , Li Yanyan , Liu Yang , Zhao Dong , Zhang Wen , Li Chunming , Yan Li , Zhu Qing , Zhang Fujie 
Published: July 2021

AbstractBackgroundBRII-196 and BRII-198 are two anti-SARS-CoV-2 monoclonal neutralizing antibodies with modified Fc region that extends half-life and are being developed as cocktail therapy for the treatment of COVID-19. Safety, tolerability, pharmacokinetics, and immunogenicity of BRII-196 and BRII-198 were investigated in healthy adults.MethodsSingle ascending doses of BRII-196 and BRII-198 were evaluated in parallel in the first-in-human, placebo-controlled phase 1 studies. A total of 32 healthy adults were randomized and received a single intravenous infusion of 750, 1500, and 3000 mg of BRII-196 (n=12), BRII-198 (n=12), or placebo (n=8) and were followed for 180 days.ResultsAll infusions were well tolerated at infusion rates between 0.5 mL/min to 4 mL/min with no dose-limiting adverse events, deaths, serious adverse events, or any systemic or local infusion reactions. Most treatment-emergent adverse events were isolated asymptomatic laboratory abnormalities of Grade 1-2 in severity. Each mAb displayed pharmacokinetics expected of Fc-engineered human IgG1 with mean terminal half-lives of approximately 46 days and 76 days, respectively, with no evidence of significant anti-drug antibody development.ConclusionsBRII-196 and BRII-198 were well-tolerated. Clinical results support further development as therapeutic or prophylactic options for SARS-CoV-2 infection.
Trait Mindful Nonreactivity and Nonjudgment Prospectively Predict of COVID-19 Health Protective Behaviors Across a Two-Month Interval in a USA Sample
Authors: O’Brien William H. , Wang Shan , Varga Aniko Viktoria , Lim Chung Xiann , Xu Huanzhen , Jarukasemthawee Somboon , Pisitsungkagarn Kullaya , Suvanbenjakule Piraorn , Braden Abby 
Published: July 2021

AbstractThe COVID-19 pandemic has prompted a growing recommendation for social distancing and using personal protective equipment (PPE) to help mitigate the virus transmission. Previous studies have shown promising relationships between perceived susceptibility to COVID-19, mindfulness-related variables, and COVID-19 health protective behaviors (social distancing and PPE use). In this longitudinal study, the variables were measured across a two-month interval during the earlier phase of the pandemic in June (Time 1) and August (Time 2), 2020. The results from 151 matched USA MTurk participants indicated that the perceived susceptibility to COVID-19 did not significantly predict the health protective behaviors. For mindfulness, nonreactivity was positively related to PPE use while nonjudgement was negatively related to PPE use. Accordingly, mindfulness promotion messages could be a way to increase the likelihood of people performing health protective behaviors to better constrain the COVID-19 outbreak.
Kinome state is predictive of cell viability in pancreatic cancer tumor and stroma cell lines
Authors: Berginski Matthew E. , Jenner Madison R. , Joisa Chinmaya U. , Herrera Loeza Silvia G. , Golitz Brian T. , Lipner Matthew B. , Leary John R. , Rashid Naim U. , Johnson Gary L. , Yeh Jen Jen , Gomez Shawn M. 
Published: July 2021

ABSTRACTNumerous aspects of cellular signaling are regulated by the kinome – the network of over 500 protein kinases that guides and modulates information transfer throughout the cell. The key role played by both individual kinases and assemblies of kinases organized into functional subnetworks leads to kinome dysregulation being a key driver of many diseases, particularly cancer. In the case of pancreatic ductal adenocarcinoma (PDAC), a variety of kinases and associated signaling pathways have been identified for their key role in the establishment of disease as well as its progression. However, the identification of additional relevant therapeutic targets has been slow and is further confounded by interactions between the tumor and the surrounding tumor microenvironment. Fundamentally, it is an open question as to the degree to which knowledge of the state of the kinome at the protein level is able to provide insight into the downstream phenotype of the cell.In this work, we attempt to link the state of the kinome, or kinotype, with cell viability in representative PDAC tumor and stroma cell lines. Through the application of both regression and classification models to independent kinome perturbation and kinase inhibitor cell screen data, we find that the inferred kinotype of a cell has a significant and predictive relationship with cell viability. While regression models perform poorly, we find that classification approaches are able to predict drug viability effects. We further find that models are able to identify a set of kinases whose behavior in response to perturbation drive the majority of viability responses in these cell lines. Using the models to predict new compounds with cell viability effects and not in the initial data set, we conducted a validation screen that confirmed the accuracy of the models. These results suggest that characterizing the state of the protein kinome provides significant opportunity for better understanding signaling behavior and downstream cell phenotypes, as well as providing insight into the broader design of potential therapy design for PDAC.