bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the humoral response to the homologous Gam-COVID-Vac (Sputnik V) or heterologous Sputnik V/mRNA-1273 (Moderna) vaccination against SARS-CoV-2 in dialysis patients
Authors: Laham Gustavo , Martínez Alfredo P. , Gimenez Wanda Rojas , Amaya Lucas , Abib Anabel , Echegoyen Natalia , Díaz Carlos , Lucero Alicia , Martelli Antonella , Videla Cristina , Neukam Karin , Di Lello Federico A. 
Published: May 2022

ABSTRACTIntroductionThe humoral response to vaccines is the most used tool to evaluate the protection against SARS-CoV-2 infection. Dialysis patients are a high-risk population and have a reduced immune response to vaccination.ObjectiveTo assess the humoral response to homologous Gam-COVID-Vac (Sputnik V) and heterologous Sputnik V/mRNA-1273 (Moderna) vaccination in dialysis patients.MethodsSARS-CoV-2 anti-spike IgG (RBD) concentration was estimated 3-16 weeks after complete vaccination. Reactogenicity was evaluated until day 7 by patients’
s self-reported side events.Results107 participants were enrolled [n=84 homologous (SpV/SpV), n=23 heterologous (SpV/Mod)]. Median (IQR) age was 64 (50-75) years old and 79 (73.8%) were male. Additionally, 19 (22.6%) of the SpV/SpV and 4 (17.4%) of the SpV/Mod group had a prior confirmed SARS-CoV-2 infection (p=0.589). In the overall population, 103 patients reached seroconversion (96.3%). Anti-S-RBD IgG median titers (IQR) were higher in the heterologous [1222 (288-5680) BAU/mL] than in the homologous scheme [447 (100-1551) BAU/mL], p=0.022. In a linear model adjusted for age and gender, previous SARS-COV-2 infection (B: 1944.3; CI95: 1136.2-2753.4; p<0.001), and SpV/Mod vaccination scheme (B: 1241.5; CI95: 420.39-2062.6; p=0.003) were independently associated with anti-S-RBD levels. Finally, a higher frequency of adverse effects was associated with the heterologous scheme, although they were well tolerated by all individuals.ConclusionThe present study provides evidence that the homologous SpV/SpV and heterologous SpV/Mod schemes showed good efficacy and safety under dialysis conditions. These results could be useful for future vaccination strategies, especially aimed at this risk group.
Modelling Road Accident Fatalities with Underdispersion and Zero-inflated Counts
Authors: Simmachan Teerawat , Wongsai Noppachai , Wongsai Sangdao , Lerdsuwansri Rattana 
Published: May 2022

AbstractBackgroundThailand was rank second in the world in 2013 on the road accident fatality (RAF) rate, killing 36.2 of every 100,000 Thai peoples. In the past decade, during Songkran festival, the traditional Thai new year, the number of road traffic accidents (RTAs) was markedly higher than normal day life, but few studies have yet investigated this issue as the effect of festivity. The objective of this study was to investigate factors contributing to RAF using various count regression models.MethodsData of 20,229 accidents in 2015 were collected from the Department of Disaster Prevention and Mitigation, Thailand. Poisson, Conway–Maxwell–Poisson, and their Zero-Inflated versions were applied to analyze factors associated with the number of fatalities in an accident.ResultsThe RAFs in Thailand follow a count distribution with underdispersion and excessive zeros which is rare. The best fitting model, the ZICMP regression model returns significant predictors (road characteristics, weather conditions, environmental conditions, and month) on the number of fatalities in an accident. The model consists of the count part encapsulating both non-excess zeros and death counts and the zero-part representing the considerable number of zeros during the festival months. The estimated proportion of the zero-part is 0.275 accounting for 5,563 non-fatal accidents. More specifically, the excessive number of no deaths can be explained by the month factor. The mean number of fatalities was lower in the festive periods than other months, with the highest in November.ConclusionFor long, Thai authorities have put a lot of efforts and resources into improving road safety over the festival weeks, often they failed. This study indicates that people’s risk perception and public awareness of RAFs are mislead. Instead, nationwide road safety should have been announced by the authorities to raise the awareness of society towards everyday personal safety and the safety of others.
Food Security after Nuclear Winter: A Preliminary Agricultural Sector Analysis for Aotearoa New Zealand
Authors: Wilson Nick , Prickett Marnie , Boyd Matt 
Published: May 2022

AbstractAimWe aimed to estimate the current dietary energy content of food exports for Aotearoa New Zealand (NZ) and food security after “nuclear winter” scenarios following a nuclear war.MethodsFrom published sources we estimated dietary energy available from the major domains of food exports, with adjustments for wastage. The impacts on food production in NZ after three nuclear winter scenarios were based on those published inNature Foodin 2022 and from an earlier NZ Planning Council study.ResultsCurrent major food exports are equivalent to 3.9 times current dietary energy intakes for all NZ citizens ie, 34,100 kJ (8150 kcal) per person per day. Exported dairy products were estimated to be able to provide 338% of this energy intake, followed by exports of: meat (34%); fruit (8.6%), alcohol (4.8%), marine products (4.6%), and vegetables (2.7%). After the various nuclear winter scenarios considered (minimal to severe), food production available from diverted exported foods was estimated to still be 3.6 to 1.5 times current daily energy intakes.ConclusionsThis analysis suggests that NZ could have excess food production capacity, even after a severe nuclear winter scenario. But substantial further research is needed to clarify agricultural impacts and the role of nuclear war impacts on the interlinked domains of energy, transport, manufacturing, finance, industrial materials, trade and societal functioning.
Infectious viral shedding of SARS-CoV-2 Delta following vaccination: a longitudinal cohort study
Authors: Garcia-Knight Miguel , Anglin Khamal , Tassetto Michel , Lu Scott , Zhang Amethyst , Goldberg Sarah A. , Catching Adam , Davidson Michelle C. , Shak Joshua R. , Romero Mariela , Pineda-Ramirez Jesus , Sanchez Ruth Diaz , Rugart Paulina , Donohue Kevin , Massachi Jonathan , Sans Hannah M. , Djomaleu Manuella , Mathur Sujata , Servellita Venice , McIlwain David , Gaudiliere Brice , Chen Jessica , Martinez Enrique O. , Tavs Jacqueline M. , Bronstone Grace , Weiss Jacob , Watson John T. , Briggs-Hagen Melissa , Abedi Glen R. , Rutherford George W. , Deeks Steven G. , Chiu Charles , Saydah Sharon , Peluso Michael J. , Midgley Claire M. , Martin Jeffrey N. , Andino Raul , Kelly J. Daniel 
Published: May 2022

AbstractThe impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P=0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset.Significance statementWe present longitudinal data on the magnitude, duration and decay rate of viral RNA and the magnitude and duration of infectious virus in nasal specimens from vaccinated and unvaccinated participants. On average, vaccinated participants (infected with the highly transmissible Delta variant) showed a lower probability of having infectious virus after 5 days of symptoms compared to unvaccinated participants (infected with mostly pre-delta viral lineages), even though both groups had a similar magnitude of infectious virus at or near the peak. These data help improve our understanding of the duration of the infectious period when infection occurs following vaccination and serves as a reference for future studies of shedding dynamics following infections with novel variants of concern.
GRID1/GluD1 homozygous variants linked to intellectual disability and spastic paraplegia impair mGlu1/5 receptor signaling and excitatory synapses
Authors: Ung Dévina C. , Tricoire Ludovic , Pietrancosta Nicolas , Zlatanovic Andjela , Pode-Shakked Ben , Raas-Rothschild Annick , Elpeleg Orly , Abu-Libdeh Bassam , Hamed Nasrin , Papon Marie-Amélie , Marouillat Sylviane , Thépault Rose-Anne , Stevanin Giovanni , Lambolez Bertrand , Toutain Annick , Hepp Régine , Laumonnier Frédéric 
Published: May 2022

AbstractThe ionotropic glutamate delta receptor GluD1, encoded by theGRID1gene, is involved in synapse formation, function, and plasticity. GluD1 does not bind glutamate, but instead cerebellin and D-serine, which allow the formation of trans-synaptic bridges, and trigger transmembrane signaling. Despite wide expression in the nervous system, pathogenicGRID1variants have not been characterized in humans so far. We report homozygous missenseGRID1variants in five individuals from two unrelated consanguineous families presenting with intellectual disability and spastic paraplegia, without (p.Thr752Met) or with (p.Arg161His) diagnosis of glaucoma, a threefold phenotypic association whose genetic bases had not been elucidated previously. Molecular modeling indicated that Arg161His and Thr752Met mutations alter the hinge between GluD1 cerebellin and D-serine binding domains and the stiffness of this latter domain, respectively. Expression, trafficking, physical interaction with metabotropic glutamate receptor mGlu1, and cerebellin binding of GluD1 mutants were not conspicuously altered. Conversely, we found that both GluD1 mutants hampered signaling of metabotropic glutamate receptor mGlu1/5 via the ERK pathway in neurons of primary cortical culture. Moreover, both mutants impaired dendrite morphology and excitatory synapse density in neurons of primary hippocampal culture. These results show that the clinical phenotypes are distinct entities segregating in the families as an autosomal recessive trait, and caused by pathophysiological effects of GluD1 mutants involving metabotropic glutamate receptor signaling and neuronal connectivity. Our findings unravel the importance of the GluD1 receptor signaling in sensory, cognitive and motor functions of the human nervous system.
Somatic mutations reveal clonal cell populations in atherosclerotic plaques
Authors: Steffensen LB , Kavan S , Jensen PS , Møller-Larsen S , Larsen MK , Dembic M , Andersen LvB , Lindholt JS , Houlind KC , Thomassen M , Rasmussen LM 
Published: May 2022

ABSTRACTBackgroundIn recent years, the potential involvement of clonal cell populations in atherosclerosis has gained renewed interest. Evidence from independent research groups unambiguously showed that smooth muscle cells clonally expand in experimental atherosclerosis, and clonal hematopoiesis of indeterminate potential (CHIP) has been proposed as a novel risk factor for atherosclerotic cardiovascular disease in humans. However, direct evidence for the presence of clonal cell populations within human atherosclerotic tissue is lacking.Here, we investigated whether characterizing the mutational landscape of human atherosclerotic plaques could provide insights into the role of clonal cell populations in human atherosclerosis.Methods and ResultsWe conductedin-depthwhole-exome sequencing of 65 samples derived from 13 carotid plaques obtained from patients undergoing carotid endarterectomy. This approach unveiled a landscape of somatic mutations exclusively confined to plaque tissue (i.e., not detected in patient-matched buffy coats). Leveraging variant allele frequencies, we inferred that distinct locally expanded clones often accounted for over 10% of the cell population within the plaque samples, and certain clones extended across multiple segments within the same plaque, necessitating a physical clone size of at least 1 cm. Furthermore, clones carrying multiple mutations spanned diverse plaque regions, encompassing the media, sub-core intima, and necrotic core. We did not detect any mutational hotspots, however, 21 of the mutated genes appeared in the Integrative Onco Genomics database of 619 mutational cancer driver genes (χ2test:p= 0.015). Moreover, unbiased pathway enrichment analysis disclosed enrichment of terms linked to cell-cell adhesion and the contractile apparatus, and genes underlying these enrichments were primarily expressed by smooth muscle cells, endothelial cells, and fibroblasts, as corroborated by analysis of single-cell RNA sequencing data. Finally, six patients were CHIP carriers, and in several of these patients, hematopoietic clones constributed significantly to the cell population of plaque segments.ConclusionsIn summary, our study provides compelling evidence that somatic mutations are an intrinsic aspect of human plaques. Moreover, we substantiate that specific mutation-carrying cells within plaque tissue undergo expansion, giving rise to clones of substantial size. We propose that unraveling the fundamental underpinnings of clonal biology and the phenotypic traits of expanding clones may unveil novel mechanisms to impede lesion development or enhance plaque stability.
Feasibility of a Novel Ultra-Low-Cost Bubble CPAP (bCPAP) System for Neonatal Respiratory Support at Muhimbili National Hospital, Tanzania
Authors: Tayler Ashtyn , Ashworth Henry , Saba Ghassan Bou , Wadhwa Hena , Dundek Michelle , Ng Ellie , Opondo Kennedy , Mkony Martha , Moshiro Robert , Burke Thomas 
Published: May 2022

ABSTRACTObjectiveContinuous Positive Airway Pressure (CPAP) is recommended in the treatment of respiratory distress syndrome of premature newborns, however there are significant barriers to its implementation in low resource settings. The objective of this study was to evaluate the feasibility of use and integration of Vayu bCPAP Systems into the newborn unit at Muhimbili National Hospital in Tanzania.Study DesignA Mixed Methods study was conducted from April 6 to October 6 2021. Demographic and clinical characteristics of patients treated with Vayu bCPAP Systems were collected and analyzed. Healthcare workers were interviewed until thematic saturation. Interviews were transcribed, coded, and analyzed using a framework analysis.Results370 patients were treated with Vayu bCPAP Systems during the study period. Mean birth weight was 1522 g (500-3800), mean duration of bCPAP treatment was 7.2 days (<1-39 d), and survival to wean was 81.4%. Twenty-four healthcare workers were interviewed and perceived Vayu bCPAP Systems as having become essential for treating neonatal respiratory distress at MNH. Key reasons were that Vayu bCPAP Systems improve patient outcomes, are easy to use, and more patients are now able to receive quality care. Barriers to integration included durability of oxygen tubing material and training.ConclusionsIt was feasible to implement and integrate Vayu bCPAP Systems into the care of neonates at Muhimbili National Hospital.
Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the Omicron wave
Authors: Jurdi Ayman Al , Morena Leela , Cote Mariesa , Bethea Emily , Azzi Jamil , Riella Leonardo V. 
Published: May 2022

AbstractThe neutralizing monoclonal antibody combination of tixagevimab/cilgavimab has been shown to reduce the risk of SARS-CoV-2 infection in unvaccinated individuals during the Alpha (B.1.1.7) and Delta (B.1.617.2) waves. However, data on efficacy and safety of tixagevimab/cilgavimab in vaccinated solid organ transplant recipients during the Omicron wave is limited. To address this, we conducted a retrospective cohort study comparing 222 solid organ transplant recipients who received tixagevimab/cilgavimab for pre-exposure prophylaxis and 222 age-matched vaccinated solid organ transplant recipients who did not receive tixagevimab/cilgavimab. Subjects were followed for a mean of 67 ± 18 days. Kaplan-Meier estimates of the 60-day incidence of breakthrough infection were 1.8% in the tixagevimab/cilgavimab group and 4.7% in the control group (P = 0.045). Adverse events were uncommon, occurring in 4% of our cohort and most were mild. There was no significant change in serum creatinine or liver chemistries in kidney and liver transplant recipients respectively. In conclusion, we found that tixagevimab/cilgavimab use is safe and associated with a lower risk of breakthrough SARS-CoV-2 infection in vaccinated solid organ transplant recipients during the Omicron wave.
Safety of the BNT162b2 mRNA COVID-19 Vaccine in Children below 5 Years (CoVacU5) – an Investigator-Initiated Retrospective Cohort Study
Authors: Töpfner Nicole , von Meißner Wolfgang C G , Strumann Christoph , Drinka Denisa , Stuppe David , Jorczyk Maximilian , Moor Jeanne , Püschel Johannes , Liss Melanie , Poblotzki Emilie von , Berner Reinhard , Moor Matthias B. , Chao Cho-Ming 
Published: May 2022

AbstractBackgroundThe safety of SARS-CoV-2 vaccines is unknown in children aged <5 years. Here, we retrospectively evaluated the safety of BNT162b2 vaccine used off-label in children of this age group in Germany.MethodsAn investigator-initiated retrospective cohort study (CoVacU5) included parents or caregivers having children aged <5 years registered for SARS-CoV-2 vaccination in outpatient care facilities in Germany. Reported short-term safety data of 1-3 doses of 3-10µg BNT162b2 in children aged 0 to <60 months are presented. Co-primary outcomes were the frequencies of 11 categories of symptoms post-vaccination with bivariate analyses and regression models adjusting for age, sex, weight and height. On-label non-SARS-CoV-2 vaccines served as controls in an active-comparator design.ResultsThe study included 7806 of 19,000 registered children representing a 41% response rate. 338 children received the first dose of BNT162b2 at age 0-<12 months, n=1272 at age 12-24 months and n=5629 at age ≥24 to <60 months. A 10µg dosage was more frequently associated with injection-site symptoms compared to lower dosages. The probability of any symptoms (OR: 1.62 [95% confidence interval (CI): 1.36-1.94]), injection-site, musculoskeletal, dermatological or otolaryngological symptom categories were modestly elevated after BNT12b2 compared to non-SARS-CoV-2 vaccines, whereas the probabilities of general symptoms (OR: 0.74 [95% CI: 0.64-0.85]) and fever (OR: 0.43 [95% CI: 0.35-0.51]) were lower after BNT162b2. Symptoms requiring hospitalization (n=10) were reported only at BNT162b2 dosages higher than 3µg.ConclusionsThe symptoms reported after BNT162b2 administration were overall comparable to on-label non-SARS-CoV-2 vaccines in this cohort of children aged <5 years. (German Clinical Trials Register ID: DRKS00028759).
APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge
Authors: Lee Sangderk , Devanney Nicholas A. , Golden Lesley R. , Smith Cathryn T. , Schwarz James L. , Walsh Adeline E. , Clarke Harrison A. , Goulding Danielle S. , Allenger Elizabeth J. , Morillo-Segovia Gabriella , Friday Cassi M. , Gorman Amy A. , Hawkinson Tara R. , MacLean Steven M. , Williams Holden C. , Sun Ramon C. , Morganti Josh M. , Johnson Lance A. 
Published: May 2022

SummaryThe E4 allele of Apolipoprotein E (APOE) is associated with both metabolic dysfunction and a heightened pro-inflammatory response – two findings that may be intrinsically linked through the concept of immunometabolism. Here, we combined bulk, single-cell, and spatial transcriptomics with cell-specific and spatially resolved metabolic analyses to systematically address the role of APOE across age, neuroinflammation, and AD pathology. RNAseq highlighted immunometabolic changes across the APOE4 glial transcriptome, specifically in subsets of metabolically distinct microglia enriched in the E4 brain during aging or following an inflammatory challenge. E4 microglia display increased Hif1α expression, a disrupted TCA cycle, and are inherently pro-glycolytic, while spatial transcriptomics and MALDI mass spectrometry imaging highlight an E4-specific response to amyloid that is characterized by widespread alterations in lipid metabolism. Taken together, our findings emphasize a central role for APOE in regulating microglial immunometabolism.
SARM1 promotes axonal, synaptic, and mitochondrial pathologies in Charcot-Marie-Tooth disease type 2A
Authors: Sato-Yamada Yurie , Strickland Amy , Sasaki Yo , Bloom Joseph , DiAntonio Aaron , Milbrandt Jeffrey 
Published: May 2022

AbstractCharcot-Marie-Tooth disease (CMT) type 2A is an axonal neuropathy caused by mutations in the mitofusin 2 (MFN2) gene. MFN2 mutations result in profound mitochondrial abnormalities, but the mechanism underlying axonal pathology is unknown. SARM1, the central executioner of axon degeneration, can induce neuropathy and is activated by dysfunctional mitochondria. We tested the role of SARM1 in a rat model carrying a dominant CMT2A mutation (Mfn2H361Y) that exhibits progressive dying-back axonal degeneration, NMJ abnormalities, muscle atrophy, and mitochondrial abnormalities, all hallmarks of the human disease. We generated Sarm1 knockout and Mfn2H361Y, Sarm1 double mutant rats and find that deletion of SARM1 rescues axonal, synaptic, and muscle phenotypes, demonstrating that SARM1 induces much of the neuropathology in this model. Despite the presence of mutant Mfn2 protein in these double mutant rats, loss of SARM1 also dramatically suppressed many mitochondrial defects, including the number, size, and cristae density defects of synaptic mitochondria. This surprising finding indicates that dysfunctional mitochondria activate SARM1, and activated SARM1 feeds back on mitochondria to exacerbate mitochondrial pathology. As such, this work identifies SARM1 inhibition as an exciting therapeutic candidate for the treatment of CMT2A and other neurodegenerative diseases with prominent mitochondrial pathology.
Feasibility and Utility of a Structured Guide for Cannabis Tolerance Breaks in Young Adults
Authors: Fontana Thomas JK , Schulz Jonathan A. , Budney Alan J. , Villanti Andrea C. 
Published: May 2022

ABSTRACTObjectiveTo explore the feasibility and utility of a tolerance break (T-Break) guide on young adults’ cannabis use.ParticipantsYoung adults aged 18-29 (n=125) who were current cannabis users.MethodsParticipants recruited through posters and listservs at various universities were offered the T-Break Guide—daily activities, advice, and encouragement—to help complete a 21-day cannabis break. Bivariate analyses examined associations between Guide use and follow-up measures.ResultsCompared to non-Guide users, participants who used the Guide “a lot” were more likely to complete the 21-day abstinence break (84% vs. 57%), revise their personal definition of balance to mean less cannabis (84% vs. 62%), and plan a future break (32% vs. 11%).ConclusionUse of this self-directed Guide may help young adults take a break from cannabis use and reduce future use. Further research using more rigorous designs to test the Guide’s efficacy and assess longer-term maintenance of effects is needed.