bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variations inEIF2AK3are associated with neurocognitive impairment in people living with HIV
Authors: Akay-Espinoza Cagla , Bond Sarah , Dombroski Beth A. , Kallianpur Asha , Bharti Ajay , Franklin Donald R. , Schellenberg Gerard D. , Heaton Robert K. , Grant Igor , Ellis Ronald J. , Letendre Scott L. , Jordan-Sciutto Kelly L. 
Published: May 2022

AbstractCoding and noncoding single-nucleotide variants (SNVs) ofEIF2AK3, which encodes an integrated stress response (ISR) kinase, may play a role in neurodegenerative disorders. We used a candidate gene approach to determine the correlation ofEIF2AK3SNVs with neurocognitive (NC) impairment (NCI), which can persist with viral suppression from antiretroviral therapy (ART) in people with HIV (PWH). This retrospective study of prospectively collected data included participants of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort, after excluding participants with severe neuropsychiatric comorbidities. Genome-wide data previously obtained in the CHARTER cohort participants (n=1,047) were analyzed to interrogate the association of three noncodingEIF2AK3SNVs with the continuous global deficit score (GDS) and global NCI (GDS≥0.5). Targeted sequencing (TS) was performed in 992 participants with available genomic DNA to determine the association of three codingEIF2AK3SNVs with GDS and NCI. Analyses included univariable and multivariable methods such as analysis of variance and regression. Multivariable models covaried demographic, disease-associated, and treatment characteristics. The cohort characteristics were as follows: median age, 43.1 years; females, 22.8%; European ancestry, 41%; median CD4+ T cell counts, 175/µL (nadir) and 428/µL (current). At first assessment, 70.5% used ART and 68.3% of these had plasma HIV RNA ≤ 200 copies/mL. A minority of participants had at least one risk allele for rs6739095 (T,41.7%), rs1913671 (C,41.4%), and rs11684404 (C,39.4%). All three noncodingEIF2AK3SNVs were associated with significantly worse GDS and more NCI (allp<0.05). By TS, fewer participants had at least one risk allele for rs1805165 (G,30.9%), rs867529 (G,30.9%), and rs13045 (A,41.2%). Homozygosity for all three coding SNVs was associated with significantly worse GDS and more NCI (allp<0.001). By multivariable analysis, the rs13045 A risk allele, current ART use, and Beck Depression Inventory-II (BDI) > 13 were independently associated with GDS and NCI (p<0.001). The other two coding SNVs did not significantly correlate with GDS or NCI after including rs13045 in the model. The codingEIF2AK3SNVs were specifically associated with worse performance in executive functioning, motor functioning, learning, and verbal fluency. Coding and non-coding SNVs ofEIF2AK3were associated with global NC and domain-specific performance. The effects were small-to-medium in size but were present in multivariable analyses. Specific SNVs inEIF2AK3may be an important component of genetic vulnerability to NC complications in PWH. Identification of host factors that predict NCI could allow for earlier interventions, including those directly modulating the ISR, to improve NC outcomes.
Safety, tolerability and immunogenicity of Biological E’s CORBEVAX™ vaccine in children and adolescents: A Prospective, Randomised, Double-blind, Placebo controlled, Phase-2/3 Study
Authors: Thuluva Subhash , Paradkar Vikram , Gunneri SubbaReddy , Yerroju Vijay , Mogulla Rammohan , Suneetha Pothakamuri Venkata , Turaga Kishore , Kyasani Mahesh , Manoharan Senthil Kumar , Adabala Srikanth , Javvadi Aditya Sri , Medigeshi Guruprasad , Singh Janmejay , Shaman Heena , Binayke Akshay , Zaheer Aymaan , Awasthi Amit , Narang Manish , Nanjappa Pradeep , Mahantshetti Niranjana , Garg Bishan Swarup , Ravi Mandal Ravindra Nath 
Published: May 2022

ABSTRACTBackgroundAfter establishing safety and immunogenicity of Biological E’s CORBEVAX™ vaccine in adult population (18-80 years) in Phase 1-3 studies, vaccine is further tested in children and adolescents in this study.MethodsThis is a phase-2/3 prospective, randomised, double-blind, placebo controlled, study evaluating safety, reactogenicity, tolerability and immunogenicity of CORBEVAX™ vaccine in children and adolescents of either gender between <18 to ≥12 years of age in Phase-II and <18 to ≥5 years of age in Phase-III with placebo as a control. This study has two age sub groups; age subgroup-1 with subjects <18 to ≥12 years of age and age subgroup-2 with subjects <12 to ≥5 years of age. In both age sub groups eligible subjects (SARS-CoV-2 RT-PCR negative and seronegative at baseline) were randomized to receive either CORBEVAX™ vaccine or Placebo in 3: 1 ratio.FindingsThe safety profile of CORBEVAX™ vaccine in both pediatric cohorts was comparable to the placebo control group. Majority of reported adverse events (AEs) were mild in nature. No severe or serious AEs, medically attended AEs (MAAEs) or AEs of special interest (AESI) were reported during the study period and all the reported AEs resolved without any sequelae. In both pediatric age groups, CORBEVAX™ vaccinated subjects showed significant improvement in humoral immune-responses in terms of anti-RBD-IgG concentrations, anti-RBD-IgG1 titers, neutralizing antibody (nAb)-titers against Ancestral Wuhan and Delta strains. Significantly high interferon gamma immune response (cellular) was elicited by CORBEVAX™ vaccinated subjects with minimal effect on IL-4 cytokine secretion.InterpretationsThe safety profile of CORBEVAX™ vaccine in <18 to ≥5 years’ children and adolescents was found to be safe and tolerable. The adverse event profile was also found to be acceptable. Significant increase in anti-RBD IgG and nAb titers and IFN-gamma immune responses were observed post vaccination in both pediatric age sub groups. Both humoral and cellular immune responses were found to be non-inferior to the immune responses induced by CORBEVAX™ vaccine in adult population. This study shows that CORBEVAX™ vaccine is highly immunogenic and can be safely administered to pediatric population as young as 5 years old.The study was prospectively registered with clinical trial registry of India-CTRI/2021/10/037066
DBS for substance use disorders? An exploratory qualitative study of perspectives of people currently in treatment
Authors: Versalovic Erika , Klein Eran , Goering Sara , Ngo Quyen , Gliske Kate , Boulicault Marion , Sullivan Laura Specker , Thomas Mark J , Widge Alik S 
Published: May 2022

ABSTRACTObjectiveWhile previous studies have discussed the promise of deep brain stimulation (DBS) as a possible treatment for substance use disorders (SUDs) and collected researcher perspectives on possible ethical issues surrounding it, none have consulted those with SUDs themselves. We addressed this gap by interviewing those with SUDs.MethodsParticipants viewed a short video introducing DBS, followed by a 1.5 hour semi-structured interview on their experiences with SUDs and their perspective on DBS as a possible treatment option. Interviews were analyzed by multiple coders who iteratively identified salient themes.ResultsWe interviewed 20 people in 12-step based, inpatient treatment programs (10 [50%] white/Caucasian, 7 Black/African American [35%], 2 Asian [10%], 1 Hispanic/Latino [5%], and 1 [5%] Alaska Native/American Indian; 11 [45%] women). Interviewees described a variety of barriers they currently faced through the course of their disease that mirrored barriers often associated with DBS (stigma, invasiveness, maintenance burdens, privacy risks) and thus made them more open to the possibility of DBS as a future treatment option.ConclusionsIndividuals with SUDs gave relatively less weight to surgical risks and clinical burdens associated with DBS than previous surveys of provider attitudes anticipated. These differences derived largely from their experiences living with an often-fatal disease and encountering limitations of current treatment options. These findings support the study of DBS as a treatment option for SUDs, with extensive input from people with SUDs and advocates.
Seasonal patterns of SARS-CoV-2 transmission in secondary schools: a modelling study
Authors: Pham Thi Mui , Westerhof Ilse , Bootsma Martin C.J. , Kretzschmar Mirjam E. , Rozhnova Ganna , Bruijning-Verhagen Patricia 
Published: May 2022

AbstractBackgroundThe Omicron variant has caused a new wave of SARS-CoV-2 infections worldwide. We explore crucial epidemiological parameters driving seasonal patterns of SARS-CoV-2 transmission in secondary schools and assess various infection control interventions over a 2.5-year time frame.MethodsWe developed an agent-based model parameterised with data from secondary schools in the Netherlands. We modelled the circulation of Omicron assuming a stable introduction rate of infections and accounted for uncertainty in epidemiological parameters describing virus transmissibility, susceptibility to reinfection, vaccine immune escape, and waning of sterilising immunity. We quantified the SARS-CoV-2 health burden defined as number of symptomatic student days. We further evaluated the cost-benefit (number of prevented infected students per absent student) for reactive quarantine interventions, regular screening using antigen tests, and annual booster vaccinations.FindingsDurability of sterilising immunity is a key parameter that governs temporal SARS-CoV-2 transmission patterns in secondary schools. Our model predicts pronounced within-school seasonal patterns with dominant autumn outbreaks and smaller winter outbreaks and a maximum prevalence of 2.9% (95% CI: 0.7%-6.6%) symptomatic students during infection peaks. Regular screening and annual booster vaccination may reduce the health burden up to 15% (95% CI: 1.5%-27.8%) and have a higher cost-benefit ratio than reactive quarantine interventions (reduction: 4.3%; 95% CI: -10.1% to 17.6%).InterpretationImmunity waning will determine the intensity and pattern of SARS-CoV-2 transmission in secondary schools in the medium-term future. If mitigation strategies are needed, screening and annual booster vaccination have the highest cost-benefit by reducing viral transmission with little educational disruption.
Global burden of mental health problems among children and adolescents during COVID-19 pandemic: A systematic umbrella review
Authors: Hossain M. Mahbub , Nesa Fazilatun , Das Jyoti , Aggad Roaa , Tasnim Samia , Bairwa Mohan , Ma Ping , Ramirez Gilbert 
Published: May 2022

AbstractMental health problems among children and adolescents are increasingly reported amidst the coronavirus disease (COVID-19) pandemic. In this umbrella review, we aimed to synthesize global evidence on the epidemiologic burden and correlates of child and adolescent mental health (CAMH) problems during this pandemic from existing systematic reviews and meta-analyses. We evaluated 422 citations and identified 17 eligible reviews on the epidemiology of CAMH in the context of COVID-19. Most of the reviews reported a high prevalence of anxiety, depression, sleep disorders, suicidal behavior, stress-related disorders, attention-deficit/hyperactivity disorder, and other mental health problems. Also, factors associated with CAMH such as age, gender, place of residence, educational attainment, household income, sedentary lifestyle, social media and internet use, comorbidities, family relationships, parents’ psychosocial conditions, COVID-19 related experiences, closure of schools, online learning, and social support were reported across reviews. As most studies were cross-sectional and used nonrepresentative samples, future research on representative samples adopting longitudinal and intervention designs is needed. Lastly, multipronged psychosocial care services, policies, and programs are needed to alleviate the burden of CAMH problems during and after this pandemic.
Monitoring One Heart to Help Two: Heart Rate Variability and Resting Heart Rate using Wearable Technology in Active Women Across the Perinatal Period
Authors: Rowan Shon P. , Lilly Christa L. , Claydon Elizabeth A. , Wallace Jenna , Merryman Karen 
Published: May 2022

AbstractBACKGROUNDCharacterizing normal heart rate variability (HRV) and resting heart rate (RHR) in healthy women over the course of a pregnancy allows for further investigation into disease states, as pregnancy is the ideal time period for these explorations due to known decreases in cardiovascular health. To our knowledge, this is the first study to continuously monitor HRV and RHR using wearable technology in healthy pregnant women.METHODSA total of eighteen healthy women participated in a prospective cohort study of HRV and RHR while wearing a WHOOP® strap prior to conception, throughout pregnancy, and into postpartum. The study lasted from March 2019 to July 2021; data were analyzed using linear mixed models with splines for non-linear trends.RESULTSEighteen women were followed for an average of 405.8 days (SD=153). Minutes of logged daily activity decreased from 28 minutes pre-pregnancy to 14 minutes by third trimester. A steady decrease in daily HRV and increase in daily RHR were generally seen during pregnancy (HRV Est. = -0.10, P<0.0001; RHR Est. = 0.05, P<0.0001). The effect was moderated by activity minutes for both HRV and RHR. However, at 49 days prior to birth there was a reversal of these indices with a steady increase in daily HRV (Est.=0.38, P< 0.0001) and decrease in daily RHR (Est. = -0.23, P< 0.0001), regardless of activity level, that continued into the postpartum period.CONCLUSIONSIn healthy women, there were significant changes to HRV and RHR throughout pregnancy, including a rapid improvement in cardiovascular health prior to birth that was not otherwise known. Physical activity minutes of any type moderated the known negative consequences of pregnancy on cardiovascular health. By establishing normal changes using daily data, future research can now evaluate disease states as well as physical activity interventions during pregnancy and their impact on cardiovascular fitness.
Shared N417-dependent epitope on the SARS-CoV-2 Omicron, Beta and Delta-plus variants
Authors: Moyo-Gwete Thandeka , Madzivhandila Mashudu , Mkhize Nonhlanhla N , Kgagudi Prudence , Ayres Frances , Lambson Bronwen E , Manamela Nelia P , Richardson Simone I , Makhado Zanele , van der Mescht Mieke A , de Beer Zelda , de Villiers Talita Roma , Burgers Wendy A , Ntusi Ntobeko A B , Rossouw Theresa , Ueckermann Veronica , Boswell Michael T , Moore Penny L 
Published: May 2022

AbstractAs SARS-CoV-2 continues to evolve, several variants of concern (VOCs) have arisen which are defined by multiple mutations in their spike proteins. These VOCs have shown variable escape from antibody responses, and have been shown to trigger qualitatively different antibody responses during infection. By studying plasma from individuals infected with either the original D614G, Beta or Delta variants, we show that the Beta and Delta variants elicit antibody responses that are overall more cross-reactive than those triggered by D614G. Patterns of cross-reactivity varied, and the Beta and Delta variants did not elicit cross-reactive responses to each other. However, Beta-elicited plasma was highly cross-reactive against Delta plus (Delta+) which differs from Delta by a single K417N mutation in the receptor binding domain, suggesting the plasma response targets the N417 residue. To probe this further, we isolated monoclonal antibodies from a Beta-infected individual with plasma responses against Beta, Delta+ and Omicron, which all possess the N417 residue. We isolated a N417-dependent antibody, 084-7D, which showed similar neutralization breadth to the plasma. The 084-7D mAb utilized the IGHV3-23*01 germline gene and had similar somatic hypermutations compared to previously described public antibodies which target the 417 residue. Thus, we have identified a novel antibody which targets a shared epitope found on three distinct VOCs, enabling their cross-neutralization. Understanding antibodies targetting escape mutations such as K417N, which repeatedly emerge through convergent evolution in SARS-CoV-2 variants, may aid in the development of next-generation antibody therapeutics and vaccines.ImportanceThe evolution of SARS-CoV-2 has resulted in variants of concern (VOCs) with distinct spike mutations conferring varying immune escape profiles. These variable mutations also influence the cross-reactivity of the antibody response mounted by individuals infected with each of these variants. This study sought to understand the antibody responses elicited by different SARS-CoV-2 variants, and to define shared epitopes. We show that Beta and Delta infection resulted in antibody responses that were more cross-reactive compared to the original D614G variant, but each with differing patterns of cross-reactivity. We further isolated an antibody from Beta infection, which targeted the N417 site, enabling cross-neutralization of Beta, Delta+ and Omicron, all of which possess this residue. The discovery of antibodies which target escape mutations common to multiple variants highlights conserved epitopes to target in future vaccines and therapeutics.
Long-COVID post-viral chronic fatigue syndrome and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study
Authors: Al-Hakeim Hussein Kadhem , Al-Rubaye Haneen Tahseen , Al-Hadrawi Dhurgham Shihab , Almulla Abbas F. , Maes Michael 
Published: May 2022

AbstractThe immune-inflammatory response during the acute phase of COVID-19, as assessed using peak body temperature (PBT) and peripheral oxygen saturation (SpO2), predicts the severity of chronic fatigue, depression and anxiety (“physio-affective”) symptoms three to four months later. The present study was performed to characterize whether the effects of SpO2 and PBT on the physio-affective phenome of Long COVID are mediated by immune, oxidative and nitrosative stress (IO&NS) pathways. This study assayed SpO2 and PBT during acute COVID-19, and C-reactive protein (CRP), malondialdehyde (MDA), protein carbonyls (PCs), myeloperoxidase (MPO), nitric oxide (NO), zinc, and glutathione peroxidase (Gpx) in 120 Long COVID individuals and 36 controls. Cluster analysis showed that 31.7% of the Long COVID patients had severe abnormalities in SpO2, body temperature, increased oxidative toxicity (OSTOX) and lowered antioxidant defenses (ANTIOX), and increased total Hamilton Depression (HAMD) and Anxiety (HAMA) and Fibromylagia-Fatigue (FF) scores. Around 60% of the variance in the physio-affective phenome of Long COVID (a factor extracted from HAMD, HAMA and FF scores) was explained by OSTOX/ANTIOX ratio, PBT and SpO2. Increased PBT predicted increased CRP and lowered ANTIOX and zinc levels, while lowered SpO2 predicted lowered Gpx and increased NO production. Both PBT and SpO2 strongly predict OSTOX/ATIOX during Long COVID. In conclusion, the impact of acute COVID-19 on the physio-affective symptoms of Long COVID is partly mediated by OSTOX/ANTIOX, especially lowered Gpx and zinc, increased MPO and NO production and lipid peroxidation-associated aldehyde formation. Post-viral physio-affective symptoms have an inflammatory origin and are partly mediated by neuro-oxidative toxicity.
Supporting the revision of the health benefits package in Uganda: a constrained optimisation approach
Authors: Mohan Sakshi , Walker Simon , Sengooba Freddie , Kiracho Elizabeth Ekirapa , Mayora Chrispus , Ssennyonjo Aloysius , Aliti Candia Tom , Revill Paul 
Published: May 2022

ABSTRACTThis study demonstrates how the linear constrained optimization approach can be used to design a health benefits package (HBP) which maximises the net disability adjusted life years (DALYs) averted given the health system constraints faced by a country, and how the approach can help assess the marginal value of relaxing health system constraints. In the analysis performed for Uganda, 58 interventions were included in the HBP in the base scenario, resulting in a total of 49.9 million net DALYs averted. When task shifting of pharmacists’ and nutrition officers’ tasks to nurses is allowed, 68 interventions were included in the HBP resulting in a total of 53.8 million net DALYs averted (a 7.8% increase). Further, investing only $39 towards hiring additional nutrition officers’ time could avert one net DALY; this increased to $55, $56, and $123 for nurses, pharmacists and doctors respectively, and $971 for expanding the consumable budget.
Asymptomatic carriage ofPlasmodium falciparumin children living in a hyperendemic area occurs independently of IgG responses but is associated with a balanced inflammatory cytokine ratio
Authors: Fogang Balotin , Schoenhals Matthieu , Maloba Franklin M. , Biabi Marie Florence , Essangui Estelle , Donkeu Christiane , Cheteug Glwadys , Kapen Marie , Keumoe Rodrigue , Kemleu Sylvie , Nsango Sandrine , Cornwall Douglas H. , Eboumbou Carole , Perraut Ronald , Megnekou Rosette , Lamb Tracey J. , Ayong Lawrence S. 
Published: May 2022

AbstractBackgroundAsymptomatic carriage of infected red blood cells (iRBCs) can be prevalent in communities regardless of transmission patterns and can occur with infection of differentPlasmodiumspecies. Clinical immunity dampens the inflammatory responses leading to disease symptoms in malaria. The aim of this study was to define the immunological correlates of asymptomatic carriage ofP. falciparumin a highly exposed population.Methods142 asymptomaticPlasmodium-infected individuals greater than 2 years of age without fever (body temperature <37.5°C) were followed weekly for 10 weeks before being treated with artemisinin-based combination treatment (ACT). Plasma levels of 38 cytokines were measured at baseline by Luminex and the quantity and growth inhibitory activities of circulating parasite-reactive antibodies measured. ThePlasmodiumantigen tested includedP. falciparummerozoite extract (ME) and schizont extract (SE), and the recombinant proteins Erythrocyte binding antigen 175 (EBA-175) and merozoite surface protein 1 (MSP-119).ResultsMedian levels of IgG againstP. falciparumEBA-175 and MSP-119at baseline were significantly higher in those older than 20 years of age compared with the younger age group and appeared to correlate with better parasite control. Amongst all participants there were no discernible changes in IgG levels over time. Parasite density was higher in the younger age group and associated with IL-10, TNF-α and MCP-1 levels. A balanced IL-10:TNF-α ratio was associated with asymptomatic malaria regardless of age, and balanced ratios of IL-10/TNF-α and IL-10/IFN-γ were the only significant correlate of maintenance of asymptomatic malaria over the course of the study in individuals 20 years of age and younger.ConclusionThe above findings indicate that asymptomatic carriage ofP. falciparumin children living in a hyperendemic area occurs independently of IgG but is associated with a balanced inflammatory cytokine ratio.