bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical, Environmental, and Genetic Risk Factors for Substance Use Disorders: Characterizing Combined Effects across Multiple Cohorts
Authors: Barr Peter B. , Driver Morgan N. , Kuo Sally I-Chun , Stephenson Mallory , Aliev Fazil , Karlsson Linnér Richard , Marks Jesse , Anokhin Andrey P. , Bucholz Kathleen , Chan Grace , Edenberg Howard J. , Edwards Alexis C. , Francis Meredith W. , Hancock Dana B. , Harden K. Paige , Kamarajan Chella , Kaprio Jaakko , Kinreich Sivan , Kramer John , Kuperman Samuel , Latvala Antti , Meyers Jacquelyn L. , Palmer Abraham A. , Plawecki Martin H. , Porjesz Bernice , Rose Richard J. , Schuckit Marc A. , Salvatore Jessica E. , Dick Danielle M. 
Published: January 2022

ABSTRACTSubstance use disorders (SUDs) incur serious social and personal costs. Risk for SUDs is complex, ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (NEUR = 12,659) and African (NAFR = 2,475) ancestries. SUD outcomes included: 1) alcohol dependence, 2) nicotine dependence; 3) drug dependence, and 4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 1.37 – 1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11 – 1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09 – 1.18). The full model explained 6% - 13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86 - 8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.
Mortality and predictors of Chronic Kidney Diseases (CKD) in selected dialysis centers in Addis Ababa, Ethiopia
Authors: Desta Beza Zewdu , Derseh Behailu Tariku , Dadi Abel Fekadu 
Published: January 2022

AbstractBackgroundChronic Kidney Disease (CKD) affects 10-15% of the population worldwide. The number of dialysis patients is steadily rising in Ethiopia. Chronic hemodialysis patients experience high rates of mortality; however, data is lacking in Ethiopia. We explored the mortality and its driving factors in selected dialysis center in Addis AbabaMethodwe retrospectively followed a group of End-Stage Renal Disease patients on hemodialysis from 2016 to2020 in St. Paul Millennium Medical College (SPMMC), Zewditu Memorial Hospital (ZMH), and Menellik II Hospital. We fitted Kaplan Meier analysis to estimate the one and five year’s survival probability of these patients and Cox Proportional regression analysis to model the predictors of mortality at p value ≤0.05.ResultWe analyzed a data of (139) patients under follow up. The mean age (± SD) of the patients was 36.8 (±11.95) years. Twenty-four (17%) of the patients died at the end of follow-up. The median survival time was 46.2 months (95% CI: 41.8, 50.5). The one and five-year’s survival probability of these patients was 64.8% and 18.7%, respectively. Our analysis showed that patients with hypertension (AHR = 4.33; 95% CI: 1.02, 34.56), cardiac complication (AHR = 4.69; 95% CI: 1.32, 16.8), and infection during dialysis (AHR = 3.89; 95% CI: 1.96, 13.8) were more likely to die.ConclusionThe survival status of hemodialysis patients in three was low. Preventing and treating comorbidities and complication during dialysis would reduce mortality of CKD patients.
Screening for SARS-CoV-2 in close contacts of individuals with confirmed infection: performance and operational considerations
Authors: Zobrist Stephanie , Oliveira-Silva Michelle , Vieira Alexia Martines , Bansil Pooja , Gerth-Guyette Emily , Leader Brandon T. , Golden Allison , Slater Hannah , de Lucena Cruz Catherine Duran , Garbin Eduardo , Sagalovsky Mariana , Pal Sampa , Gupta Vin , Wolansky Leo , Vieira Dall’Acqua Deusilene Souza , Naveca Felipe Gomes , do Nascimento Valdinete Alves , Villalobos Salcedo Juan Miguel , Drain Paul K. , Tavares Costa Alexandre Dias , Domingo Gonzalo J , Pereira Dhélio 
Published: January 2022

AbstractBackgroundPoint-of-care and decentralized testing for SARS-CoV-2 is critical to inform public health responses. Performance evaluations in priority use cases such as contact tracing can highlight trade-offs in test selection and testing strategies.MethodsA prospective diagnostic accuracy study was conducted among close contacts of COVID-19 cases in Brazil. Two anterior nares swabs (ANS), a nasopharyngeal swab (NPS), and saliva were collected at all visits. Vaccination history and symptoms were assessed. Household contacts were followed longitudinally. Three rapid antigen tests and one molecular method were evaluated for usability and performance against reference RT-PCR on NPS.ResultsFifty index cases and 214 contacts (64 household) were enrolled. Sixty-five contacts were RT-PCR positive during at least one visit. Vaccination did not influence viral load. Gamma variants were most prevalent; Delta emerged increasingly during implementation. Overall sensitivity of evaluated tests ranged from 33%–76%. Performance was higher among symptomatic cases and cases with Ct<34 and lower among oligo/asymptomatic cases. Assuming a 24-hour time-to-result for RT-PCR, the cumulative sensitivity of an ANS rapid antigen test was >70% and almost 90% after four days.ConclusionsThe near immediate time-to-result for antigen tests significantly offsets lower analytical sensitivity in settings where RT-PCR results are delayed or unavailable.
Persistently reduced humoral and cellular immune response following third SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients
Authors: Bajwa Hamza Mahmood , Novak Frederik , Nilsson Anna Christine , Nielsen Christian , Holm Dorte K. , Østergaard Kamilla , Witt Agnes Hauschultz , Byg Keld-Erik , Johansen Isik S. , Mittl Kristen , Rowles William , Zamvil Scott S. , Bove Riley , Sabatino Joseph J. , Sejbaek Tobias 
Published: January 2022

AbstractObjectiveTo examine humoral and cellular response in multiple sclerosis patients on anti-CD20 therapy after third BNT162b2 mRNA SARS-CoV-2 vaccination.MethodsA prospective longitudinal study design from first throughout third vaccination in Danish and American MS centers. All participants were treated with ocrelizumab. Antibody (Ab) levels were assessed before and after third vaccination using SARS-CoV-2 IgG II Quant assay (Abbott Laboratories). B- and T-lymphocytes enumeration was done with BD Multitest™6-color TBNK reagent. Spike-specific T-cell responses were measured through PBMC stimulation with spike peptide pools (JPT Peptide Technologies).ResultsWe found that 14.0%, 37.7%, and 33.3% were seropositive after first, second and third vaccination. The median Ab-levels were 74.2 BAU/mL (range: 8.5-2427), 43.7 BAU/ml (range: 7.8-366.1) and 31.3 BAU/mL (range: 7.9-507.0) after first, second and third vaccination, respectively. No difference was found in levels after second and third vaccination (p=0.1475). Seropositivity dropped to 25.0% of participants before the third vaccination, a relative reduction of 33.3% (p=0.0020). No difference was found between frequencies of spike reactive CD4+ and CD8+ T-cells after second (0.65 ± 0.08% and 0.95 ± 0.20%, respectively) and third vaccination (0.99 ± 0.22% and 1.3 ± 0.34%), respectively.ConclusionIn this longitudinal cohort we found no significant increased humoral or cellular response with administration of a third SARS-CoV-2 mRNA vaccination. These findings suggest the need for clinical strategies to include allowance of B cell reconstitution before repeat vaccination and/or provision of pre-exposure prophylactic monoclonal antibodies.Key PointsWhat is already known on this topicStudies have described decreased humoral response and sustained T-cell reactivity after standard two-dose SARS-CoV-2 mRNA vaccination during anti-CD20 therapy in multiple sclerosis participants.What this study addsPersistently decreased humoral, but stable cellular reactivity following a third SARS-CoV-2 mRNA vaccination.How this study might affect research, practice or policyThe findings suggest the need for clinical strategies to include allowance of B cell reconstitution before repeat vaccination and/or provision of pre-exposure prophylactic monoclonal antibodies.
Identifying the regional substrates predictive of Alzheimer’s disease progression through a convolutional neural network model and occlusion
Authors: Kwak Kichang , Stanford William , Dayan Eran ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2022

AbstractProgressive brain atrophy is a key neuropathological hallmark of Alzheimer’s disease (AD). However, atrophy patterns along the progression of AD are diffuse and variable. Consequently, identifying the major regional atrophy patterns underlying AD progression is challenging. In the current study, we propose a method that evaluates the degree to which specific regional atrophy are predictive of AD progression, while holding all other atrophy changes constant. We first trained a dense convolutional neural network model to differentiate individuals with mild cognitive impairment (MCI) who progress to AD vs. those with a stable MCI diagnosis. Then, we retested the model multiple times, each time occluding major regions from the model’s testing set’s input. This revealed that the hippocampus, fusiform, and inferior temporal gyri, were the strongest predictors of AD progression, in agreement with established staging models. These results shed light on the major regional patterns of atrophy predictive of AD progression.
Evaluation of the CD4+ T cell response to SARS-CoV-2 infection and cross reactivity to beta variant in children of all ages
Authors: Paul Kevin , Sibbertsen Freya , Weiskopf Daniela , Lütgehetmann Marc , Barroso Madalena , Danecka Marta K. , Glau Laura , Hecher Laura , Hermann Katharina , Kohl Aloisa , Oh Jun , zur Wiesch Julian Schulze , Sette Alessandro , Tolosa Eva , Vettorazzi Eik , Woidy Mathias , Zapf Antonia , Zazara Dimitra E. , Mir Thomas S. , Muntau Ania C. , Gersting Søren W. , Dunay Gábor A. 
Published: January 2022

AbstractSARS-CoV-2 is still a major burden for global health despite effective vaccines. With the reduction of social distancing measures, infection rates are increasing in children, while data on the pediatric immune response to SARS-CoV-2 infection is still lacking. Although the typical disease course in children has been mild, emerging variants may present new challenges in this age group.Peripheral blood mononuclear cells (PBMC) from 51 convalescent children, 24 seronegative siblings from early 2020, and 51 unexposed controls were stimulated with SARS-CoV-2-derived peptide MegaPools from the ancestral and beta variants. Flow cytometric determination of activation-induced markers and secreted cytokines were used to quantify the CD4+ T cell response.The average time after infection was over 80 days. CD4+ T cell responses were detected in 61% of convalescent children and were markedly reduced in preschool children. Cross-reactive T cells for the SARS-CoV-2 beta variant were identified in 45% of cases after infection with an ancestral SARS-CoV-2 variant. The CD4+ T cell response was accompanied most predominantly by IFN-γ and Granzyme B secretion.An antiviral CD4+ T cell response was present in children after ancestral SARS-CoV-2 infection, which was reduced in the youngest age group. We detected significant cross-reactivity of CD4+ T cell responses to the more recently evolved immune-escaping beta variant. Our findings have epidemiologic relevance for children regarding novel viral variants of concern and vaccination efforts.
Psychological Outcomes of Surgery Trainees in the Era of COVID-19 at a Tertiary Care Hospital of Karachi, Pakistan: A Cross-Sectional Study
Authors: Lakhani Gulzar , Bajwa Mohammad Hamza , Zahid Nida , Enam Syed Ather 
Published: January 2022

AbstractObjectivesThe COVID-19 pandemic has resulted in interruptions in training for surgical residents in particular. This has been compounded by burnout and mental health concerns among surgical trainees across the world. We aim to determine the impact of the COVID-19 pandemic on psychological outcomes of surgical trainees in a tertiary-care hospital in Pakistan.SettingA cross-sectional, online survey-based study was conducted at a private tertiary care hospital of Karachi, Pakistan.ParticipantsAll the surgery trainees including; residents, fellows and instructors acquiring training at a private tertiary care hospital of Karachi, Pakistan were included in the study.Outcome measuresThe participants were assessed for their perceptions, and concerns regarding the COVID-19 pandemic, impact on their quality of life and generalized anxiety disorder (GAD).ResultsA majority (85%) of surgical trainees were concerned regarding contracting COVID-19 infections. Residents were more concerned with fellow residents developing burnout and anxiety as compared to their own psychological concerns. A strong, significant positive correlation (r=0.66, p <0.001) was noted between negative impact on QoL scores and developing GAD in surgical residents. On multivariable analysis, significant associations with GAD remained for family system, and negative impact of COVID-19 on QoL. The increased working hours for junior trainees showed more likelihood of developing GAD as compared to senior trainees.ConclusionOur investigation on QoL and psychological outcomes of surgical residents showed significant rates of burnout and GAD, which were attributed to concerns with the COVID-19 pandemic. We showed the impact this had on surgical trainees’ perception regarding their training and concerns with infecting others. This calls for structural interventions to address mental health concerns and provide psychological and educational support to surgical residents.Strengths and Limitations of the studyValidated measures were used for evaluating the outcomesThe study results can be generalized to all the surgery resident trainees working at private tertiary care hospitals.The response rate of trainees was 50%, the authors attempted to mitigate this through regular follow-up emails and reminders for responses.
Neuroprotective effects of Canagliflozin: lessons from aged genetically diverse UM-HET3 mice
Authors: Jayarathne Hashan S. M. , Debarba Lucas K. , Jaboro Jacob J. , Miller Richard A. , Sadagurski Marianna 
Published: January 2022

AbstractThe aging brain is characterized by a progressive increase in neuroinflammation and central insulin resistance, which contribute to neurodegenerative diseases and cognitive impairment. Recently, the Interventions Testing Program (ITP) demonstrated that the anti-diabetes drug, Canagliflozin (Cana), a sodium-glucose transporter 2 inhibitor (SGLT2i), led to lower fasting glucose and improved glucose tolerance in both sexes, but extended median lifespan by 14% only in male mice. Here we show that Cana treatment significantly improved central insulin sensitivity in the hypothalamus and the hippocampus of 30-month-old male mice. Remarkably, Cana-treated mice showed significant reductions in age-associated hypothalamic gliosis with a decrease in inflammatory cytokine production by microglia in both sexes. In the hippocampus, Cana reduced microgliosis and astrogliosis in males, but not in female mice. The decrease in microgliosis was partially dependent on mTOR signaling, as evidenced by reduced phosphorylation of S6 kinase in microglia of Cana-treated aged male, but not female mice. Remarkably, Cana treatment improved exploratory and locomotor activity of 30-month-old male but not female mice. Taken together, our findings demonstrate sex-specific neuroprotective effects of Cana treatment, suggesting its application for the potential treatment of neurodegenerative diseases.
COVID-19 self-testing in Nigeria: Stakeholders’ opinions and perspective on its value for case detection
Authors: Undelikwo Veronica A. , Shilton Sonjelle , Folayan Morenike Oluwatoyin , Alaba Oluwatoyin , Reipold Elena Ivanova , Martínez-Pérez Guillermo Z. 
Published: January 2022

AbstractBackgroundCOVID-19 testing coverage is limited in Nigeria. Access to SARS-CoV-2 self-testing kits may help improve the detection of asymptomatic and mildly symptomatic cases and increase the currently low rate of COVID-19 testing in the country. Before implementing SARS-CoV-2 self-testing in Nigeria, it is imperative to assess the populations’ perceptions regarding this innovation. We therefore conducted a qualitative study to investigate people’s values and preferences for SARS-CoV-2 self-testing in Nigeria.MethodsWe used semi-structured interviews and focus group discussions among healthcare workers, community representatives, and public health implementors to explore values and perceptions around various aspects of COVID-19 testing, including conventional COVID-19 testing, SARS-CoV-2 self-testing, the safe and effective use of SARS-CoV-2 self-testing, actions upon receiving a positive SARS-CoV-2 self-test result, and future prospects for SARS-CoV-2 self-testing.ResultsRespondents reported that there is limited availability of conventional SARS-CoV-2 testing in Nigeria. While just a few respondents were familiar with SARS-CoV-2 testing, respondents generally supported the use of SARS-CoV-2 self-testing as they felt it could assist with early case detection and improve access to testing. Concerns relating to the use of SARS-CoV-2 self-testing were majorly about the ability among low literacy populations to use and interpret the test, the affordability of tests, equity of access, and the availability of healthcare system support for those who test positive.ConclusionThough the public perceive multiple benefits associated with access to SARS-CoV-2 self-testing, the efficiency of the national health service delivery system may limit access of the users of the kits to psychosocial and clinical support. In Nigeria, where COVID-19 vaccine coverage is low and the risk of further waves of COVID-19 is high, self-testing may assist in the prompt detection of cases and contribute to halting the spread of the virus.
Wastewater surveillance for COVID-19 response at multiple geographic scales: Aligning wastewater and clinical results at the census-block level and addressing pervasiveness of qPCR non-detects
Authors: Safford Hannah , Zuniga-Montanez Rogelio E. , Kim Minji , Wu Xiaoliu , Wei Lifeng , Sharpnack James , Shapiro Karen , Bischel Heather 
Published: January 2022

Abstract
Wastewater surveillance is a useful complement to clinical testing for managing COVID-19. While good agreement has been found between community-scale wastewater and clinical data, little is known about sub-community relationships between the two data types. Moreover, effects of non-detects in qPCR wastewater data have been largely overlooked. We used data collected from September 2020–June 2021 in Davis, California (USA) to address these gaps. By applying a predictive probability model to spatially disaggregate clinical results, we compared wastewater and clinical data at the community scale, in 16 sampling zones isolating city sub-regions, and in seven zones isolating high-priority building complexes or neighborhoods. We found reasonable agreement between wastewater and clinical data at all scales. Greater activity (i.e., more frequent detections) in clinical data tended to be mirrored in wastewater data. Small, isolated clinical-data spikes were often matched as well. We also developed a method for handling such non-detects using multiple imputation and compared results to (i) single imputation using half the qPCR limit of detection, (ii) single imputation using maximum qPCR cycle number, and (iii) non-detect censoring. Apparent wastewater trends were significantly influenced by non-detect handling. Multiple imputation improved correlation relative to single imputation, though not necessarily relative to censoring.
Neutralizing Activities against the Omicron Variant after a Heterologous Booster in Healthy Adults Receiving Two Doses of CoronaVac Vaccination
Authors: Assawakosri Suvichada , Kanokudom Sitthichai , Suntronwong Nungruthai , Auphimai Chompoonut , Nilyanimit Pornjarim , Vichaiwattana Preeyaporn , Thongmee Thanunrat , Duangchinda Thaneeya , Chantima Warangkana , Pakchotanon Pattarakul , Srimuan Donchida , Thatsanatorn Thaksaporn , Klinfueng Sirapa , Yorsang Ritthideach , Sudhinaraset Natthinee , Wanlapakorn Nasamon , Mongkolsapaya Juthathip , Honsawek Sittisak , Poovorawan Yong 
Published: January 2022

AbstractBackgroundThe use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) against SARS-CoV-2 is implemented worldwide. However, waning immunity and breakthrough infections have been observed. Therefore, we hypothesized that the heterologous booster might improve the protection against the delta and omicron variants.MethodsA total of 224 individuals who completed the two-dose CoronaVac for six months were included. We studied reactogenicity and immunogenicity following a heterologous booster with the inactivated vaccine (BBIBP), the viral vector vaccine (AZD1222), and the mRNA vaccine (both BNT162B2 and mRNA-1273). We also determined immunogenicity at 3- and 6-months boosting intervals.ResultsThe solicited adverse events (AEs) were mild to moderate and well-tolerated. Total RBD immunoglobulin (Ig), anti-RBD IgG, focus reduction neutralization test (FRNT50) against delta and omicron variants, and T cell response were highest in the mRNA-1273 group followed by the BNT162b2, AZD1222 and BBIBP groups, respectively. We also witnessed a higher total Ig anti-RBD in the long-interval than in the short-interval groups.ConclusionsAll four booster vaccines significantly increased binding and NAbs in individuals immunized with two doses of CoronaVac. The present evidence may benefit vaccine strategies development to thwart variants of concern, including the omicron variant.