bluuebunny/crossref_metadata_2025_split huggingface dataset:
A functional TGFB1 polymorphism in the donor associates with long-term graft survival after kidney transplantation
Authors: Poppelaars Felix , da Costa Mariana Gaya , Faria Bernardo , Eskandari Siawosh K. , Damman Jeffrey , Seelen Marc A. 
Published: July 2021

AbstractIntroductionImprovement of long-term outcomes in kidney transplantation remains one of the most pressing challenges, yet drug development is stagnating. Human genetics offers an opportunity for much-needed target validation in transplantation. Conflicting data exist about the effect of transforming growth factor-beta 1 (TGF-β1) on kidney transplant survival since TGF-β1 has pro-fibrotic and protective effects. We investigated the impact of a recently discovered functional TGBF1 polymorphism on kidney graft survival.MethodsWe performed an observational cohort study analyzing recipient and donor DNA in 1,271 kidney transplant-pairs from the University Medical Center Groningen in The Netherlands and associated a low-producing TGBF1 polymorphism (rs1800472-C>T) with 5, 10, and 15-year death-censored kidney graft survival.ResultsDonor genotype frequencies of rs1800472 in TGBF1 differed significantly between patients with and without graft loss (P=0.014). Additionally, the low-producing TGBF1 polymorphism in the donor was associated with an increased risk of graft loss following kidney transplantation (HR 2.12 for the T-allele; 95%-CI 1.18–3.79; P=0.012). The incidence of graft loss within 15 years of follow-up was 16.4% in the CC-genotype group and 31.6% in the CT-genotype group. After adjustment for transplant-related covariates, the association between the TGBF1 polymorphism in the donor and graft loss remained significant. In contrast, there was no association between the TGBF1 polymorphism in the recipient and graft loss.ConclusionKidney allografts possessing a low-producing TGBF1 polymorphism have a higher risk of late graft loss. Our study adds to a growing body of evidence that TGF-β1 is beneficial, rather than harmful, for kidney transplant survival.
Vaccination and COVID-19 dynamics in hemodialysis patients: a population-based study in France
Authors: Karoui Khalil El , Hourmant Maryvonne , Ayav Carole , Glowacki François , Couchoud Cécile , Lapidus Nathanaël 
Published: July 2021

AbstractImportanceMaintenance hemodialysis (MHD) patients have a high mortality risk after COVID-19 and an altered humoral response to vaccines, but vaccine clinical efficacy remains unknown in this population.ObjectiveTo estimate the association between vaccination and COVID-19 hospitalization rate in MHD patientsDesignUsing Bayesian multivariable spatiotemporal models, we estimated the expected number of SARS-CoV-2 severe infections (infections with hospital admission) in MHD patients from simultaneous cases in the general population.SettingFrench population-based retrospective analysis in MHD and non-dialysis patients.ParticipantsModels were fitted from 3620 hospitalizations of MHD patients and 457,160 hospitalizations in the general population.ExposureSevere SARS-CoV-2 infections in the general population and vaccine exposure.Main Outcome and MeasureWeekly incidence of severe infections in MHD patients.ResultsDuring the first epidemic wave, incidence of severe infections in MHD patients was approximately proportional to incidence in the general population. However, our model overestimated incidence during the second wave, suggesting an effect of prevention measures during the 2nd wave. A second model (based on data up to the end of the 2nd wave) estimated that the risk in MHD patients decreased between waves 1 and 2, with incidence rate ratio (IRR) = 0.70 (95% CI: 0.64, 0.76). Moreover, while this model correctly estimated the reported MHD cases up to the end of the 2nd wave, predictions overestimated the expected number of cases from the beginning of the vaccination campaign. Using vaccination coverages as additional predictors permitted to correctly fit the weekly reported number of cases, with IRR in MHD patients of 0.41 (95% CI: 0.28, 0.58) for vaccine exposure in MHD patients and 0.50 (95% CI: 0.40, 0.61) per 10% increase in vaccination coverage in the same-age general population.Conclusions and RelevanceOur findings suggest that both individual and herd immunity due to vaccination may yield a protective effect against severe forms of COVID-19 in MHD patients.QuestionWhether vaccination against SARS-CoV-2 limits hospitalization rates in hemodialysis patients is still unknown.FindingsBy modeling the dynamics of 3620 hospital admissions for SARS-CoV-2 infections among hemodialysis patients, as a proportion of 457,160 cases reported in the French general population from March 2020 to April 2021, we identified vaccination coverage in both hemodialysis patients and the general population as independently associated with protection of hemodialysis patients against severe infection.MeaningVaccination against SARS-CoV-2 is associated with reduced hospitalization rate in hemodialysis patients.
A Design Thinking Approach to Enhance Interprofessional Education Between Technology and Medicine for Innovative Elder Pain Care
Authors: Gomutbutra Patama , Choosri Noppon , Lerttrakarnnon Peerasak 
Published: July 2021

AbstractBackgroundDesign thinking (DT) describes three stages in the design thinking cycle: 1) inspiration, which embodies the initial problem or opportunity; 2) ideation, which encompasses the development and refinement of ideas; and 3) implementation, which involves the introduction and application of the derived solution.MethodThe prospective educational program evaluation July 2020 – December 2020. A 150 min interactive workshop regarding developing innovative elder pain care. Medical students will be grouping into four medical students: 1 technological student. Then they will be assigned to match with a technology student. The interprofessional education design thinking activity consists of three parts; a brief introduction, the brainstorming process to identified pain points by persona and user journey to generate the idea, and the prototype presentation.ResultsForty sixth-year medical students and twelve technological students participated. 58% of medical students and 95% of technological students perceived DT as very helpful for their careers. However, only 30% of medical students and 60% of technological students were inspired to develop actual prototypes after the course. Nearly all of the students responded they comfortable with this interdisciplinary project-based style. Still, the time of the workshop is too limited, and among those responding with no interest pursue the project gave a reason that they lack time after rotating to other courses.ConclusionMost medical students and technological students perceived DT as beneficial for their career and displayed satisfy in this co-project style. However, finding matched schedule of two disciplines made long-term interpersonal education challenging.
Applying Topical Anesthetic on Pediatric Lacerations in the Emergency Department: A Quality Improvement Project
Authors: Faris Nagham , Mesto Mohamad , Mrad Sandra , Kebbi Ola El , Asi Noor , Sawaya Rasha D. 
Published: July 2021

AbstractBackgroundCaring for pediatric lacerations in the Emergency Department (ED) is typically painful because of irrigation and suturing. To improve this painful experience, we aimed to increase the use of a topical anesthetic, Eutectic Mixture of Local Anesthetics (EMLA) on eligible pediatric lacerations with an attainable, sustainable, and measurable goal of 60%.Local ProblemThe baseline rate of applying topical anesthetic to eligible lacerations was 23% in our ED. We aimed to increase the use of topical anesthetics on eligible pediatric lacerations to a measurable goal of 60% within 3 months of implementing our intervention.MethodsWe conducted a prospective, single center, interrupted time series, ED quality improvement project from November 2019 to July 2020. A multidisciplinary team of physicians and nurses performed a cause-and-effect analysis identifying two key drivers: early placement of EMLA and physician buy-in on which we built our Plan, Do, Study, and Act (PDSA) cycles. We collected data on number of eligible patients receiving EMLA, as well as patient and physician feedback via phone calls within 2 days post encounter. Balancing measures included ED length of stay (LOS), patient and physician satisfaction with EMLA, and side effects of EMLA.ResultsWe needed 3 PDSA cycles to reach our goal of 60% in 3 months, which was also maintained for 5 months. PDSA cycles used educational interventions, direct provider feedback about non-compliance and patient satisfaction results obtained via phone calls. Balancing measures were minimally impacted: 75% good patient satisfaction, No adverse events but an increase in LOS of patients who received EMLA compared to those who did not (1.79 ± 0.66 VS 1.41 ± 0.83 hours, p<0.001). The main reasons for dissatisfaction for physicians were the increased LOS and the preference for procedural sedation or intranasal medications.ConclusionWith a few simple interventions, our aim of applying EMLA to 60% of eligible pediatric lacerations was attained and maintained.
Prevalence of SARS-CoV-2 Antibodies from a one-year National Serosurveillance of Kenyan Blood Transfusion Donors
Authors: Uyoga Sophie , Adetifa Ifedayo M.O. , Otiende Mark , Gitonga John N. , Mugo Daisy , Nyagwange James , Karanja Henry K. , Tuju James , Makale Johnstone , Aman Rashid , Mwangangi Mercy , Amoth Patrick , Kasera Kadondi , Ng’ang’a Wangari , Kilonzo Nduku , Chege Evelynn , Yegon Christine , Odhiambo Elizabeth , Rotich Thomas , Orgut Irene , Kihara Sammy , Bottomley Christian , Kagucia Eunice W. , Gallagher Katherine E. , Etyang Anthony , Voller Shirine , Lambe Teresa , Wright Daniel , Barasa Edwine , Tsofa Benjamin , Mwangangi Joseph , Bejon Philip , Ochola-Oyier Lynette I. , Warimwe George M. , Agweyu Ambrose , Scott J. Anthony G. 
Published: July 2021

AbstractIn tropical Africa, SARS-CoV-2 epidemiology is poorly described because of lack of access to testing and weak surveillance systems. Since April 2020, we followed SARS-CoV-2 seroprevalence in plasma samples across the Kenya National Blood Transfusion Service. We developed an IgG ELISA against full length spike protein. Validated in locally-observed, PCR-positive COVID-19 cases and in pre-pandemic sera, sensitivity was 92.7% and specificity was 99.0%. Using sera from 9,922 donors, we estimated national seroprevalence of SARS-CoV-2 antibodies at 4.3% in April-June 2020 and 9.1% in August-September 2020. Kenya’s second COVID-19 wave peaked in November 2020. Here we estimate national seroprevalence in early 2021.Between January 3 and March 15, 2021, we collected 3,062 samples from donors aged 16-64 years. Among 3,018 samples that met our study criteria, 1,333 were seropositive (crude seroprevalence 44.2%, 95% CI 42.4-46.0%). After Bayesian test-performance adjustment and population weighting to represent the national population distribution, the national estimate of seroprevalence was 48.5% (95% CI 45.2-52.1%). Seroprevalence varied little by age or sex but was higher in Nairobi (61.8%), the capital city, and lower in two rural regions.Almost half of Kenya’s adult donors had evidence of past SARS-CoV-2 infection by March 2021. Although high, the estimate is corroborated by other population-specific estimates in country. Between March and June, 2% of the population were vaccinated against COVID-19 and the country experienced a third epidemic wave. Natural infection is outpacing vaccine delivery substantially in Africa, and this reality needs to be considered as objectives of the vaccine programme are set.
Critical timing for triggering public health interventions to prevent COVID-19 resurgence: a mathematical modelling study
Authors: Zou Zhuoru , Fairley Christopher K , Shen Mingwang , Scott Nick , Xu Xianglong , Li Zengbing , Li Rui , Zhuang Guihua , Zhang Lei 
Published: July 2021

SummaryTo prevent the catastrophic health and economic consequences from COVID-19 epidemics, some nations have aimed for no community transmission outside of quarantine. To achieve this, governments have had to respond rapidly to outbreaks with public health interventions. But the exact characteristics of an outbreak that trigger these measures differ and are poorly defined. We used existing data from epidemics in Australia to establish a practical model to assist stakeholders in making decisions about the optimal timing and extent of interventions. We found that the number of reported cases on the day that interventions commenced strongly predicted the size of the outbreaks. We quantified how effective interventions were at containing outbreaks in relation to the number of cases at the time the interventions commenced. We also found that containing epidemics from novel variants that had higher transmissibility would require more stringent interventions that commenced earlier. In contrast, increasing vaccination coverage would enable more relaxed interventions. Our model highlights the importance of early and decisive action in the early phase of an outbreak if governments aimed for zero community transmission, although new variants and vaccination coverage may change this.
Initial SARS-CoV-2 vaccination response can predict booster response for BNT162b2 but not for AZD1222
Authors: Perkmann Thomas , Perkmann-Nagele Nicole , Mucher Patrick , Radakovics Astrid , Repl Manuela , Koller Thomas , Jordakieva Galateja , Wagner Oswald F , Binder Christoph J , Haslacher Helmuth 
Published: July 2021

AbstractObjectivesOur objective was to determine whether SARS-CoV-2 antibody levels after the first dose can predict the final antibody response and whether this is dependent on the vaccine type.Methods69 BNT162b2 (Pfizer/BioNTech) and 55 AZD1222 (AstraZeneca) vaccinees without previous infection or immunosuppressive medication were included. Anti-body levels were quantified 3 weeks after dose 1, in case of AZD1222 directly before boostering (11 weeks after dose 1) and 3 weeks after dose 2, with the Roche SARS-CoV-2 S total antibody assay.ResultsPre-booster (BNT162b2: 80.6 [25.5-167.0] BAU/mL, AZD1222: 56.4 [36.4-104.8] BAU/mL, not significant) and post-booster levels (BNT162b2: 2,092.0 [1,216.3-4,431.8] BAU/mL, AZD1222: 957.0 [684.5-1,684.8] BAU/mL, p<0.0001) correlated well in BNT162b2 (ρ=0.53) but not in AZD1222 recipients. Moreover, antibody levels after the first dose of BNT162b2 correlated inversely with age (ρ=-0.33, P=0.013), whereas a positive correlation with age was observed after the second dose in AZD1222 recipients (ρ=0.26, P=0.030).ConclusionsIn conclusion, our data suggest that antibody levels quantified by the Roche Elecsys SARS-CoV-2 S assay before the booster shot could infer post-booster responses to BNT162b2, but not to AZ1222. In addition, we found a vaccine-dependent effect on antibody responses, suggesting a possible link between vaccine response and vector immunity.
A general model for the demographic signatures of the transition from pandemic emergence to endemicity
Authors: Li Ruiyun , Metcalf C. Jessica E. , Stenseth Nils Chr. , Bjørnstad Ottar N. 
Published: July 2021

AbstractAnticipating the medium- and long-term trajectory of pathogen emergence has acquired new urgency given the ongoing COVID-19 pandemic. For many human pathogens the burden of disease depends on age and prior exposure. Understanding the intersection between human population demography and transmission dynamics is therefore critical. Here, we develop a realistic age-structured (RAS) mathematical model that integrates demography, social mixing and immunity to establish the suite of possible scenarios of future age-incidence and burden of mortality. With respect to COVID-19, we identify a plausible transition in the age-structure of risks once the disease reaches seasonal endemism, whether assuming long-lasting or brief protective immunity, and across a range of assumptions of relative severity of primary versus subsequent reinfections. We train the model using diverse real-world demographies and age-structured social mixing patterns to bound expectations for changing age-incidence and disease burden. The mathematical framework is flexible and can help tailoring mitigation strategies countries worldwide with varying demographies and social mixing patterns.One Sentence SummaryA shift of COVID-19 risks to younger age-classes in future endemic circulation.
On the effectiveness of COVID-19 restrictions and lockdowns: Pan metron ariston
Authors: Spiliopoulos Leonidas 
Published: July 2021

AbstractI examine the dynamics of confirmed case (and death) growth rates conditional on different levels of severity in implemented NPIs, the mobility of citizens and other non restrictive policies. To account for the endogeneity of many of these variables, and the possibility of correlated latent (unobservable) country characteristics, I estimate a four structural model of the evolution of case growth rates, death growth rates, average changes in mobility and the determination of the severity of NPIs. There are strongly decreasing returns to the stringency of NPIs, especially for extreme lockdowns, as no significant improvement in the main outcome measures is found beyond NPIs corresponding to a Stringency Index range of 51–60 for cases and 41–50 for deaths. A non-restrictive policy of extensive and open testing has half of the impact on pandemic dynamics as the optimal NPIs, with none of the associated social and economic costs resulting from the latter. Decreases in mobility were found to increase, rather than decrease case growth rates, consistent with arguments that within-household transmission–resulting from spending more time at residences due to mobility restrictions–may outweigh the benefits of reduced community transmission. Vaccinations led to a fall in case and death growth rates, however the effect size must be re-evaluated when more data becomes available. Governments conditioned policy choice on recent pandemic dynamics, and were found to de-escalate the associated stringency of implemented NPIs more cautiously than in their escalation, i.e., policy mixes exhibited significant hysteresis. Finally, at least 90% of the maximum effectiveness of NPIs can be achieved by policies with an average Stringency index of 31–40, without restricting internal movement or imposing stay at home measures, and only recommending (not enforcing) closures on workplaces and schools, accompanied by public informational campaigns. Consequently, the positive effects on case and death growth rates of voluntary behavioral changes in response to beliefs about the severity of the pandemic, generally trumped those arising from mandatory behavioral restrictions. The exception being more stringent mandatory restrictions on gatherings and international movement, which were found to be effective. The findings suggest that further work should be directed at re-evaluating the effectiveness of NPIs, particularly towards empirically determining the optimal policy mix and associated stringency of individual NPIs.
Impact of Fkbp5 × Early Life Adversity × Sex in Humanized Mice on Multidimensional Stress Responses and Circadian Rhythmicity
Authors: Nold Verena , Portenhauser Michelle , Del Prete Dolores , Blasius Andrea , Harris Isabella , Koros Eliza , Peleh Tatiana , Hengerer Bastian , Kolassa Iris-Tatjana , Slezak Michal , Allers Kelly Ann 
Published: July 2021

AbstractThe cumulative load of genetic predisposition, early life adversity (ELA) and lifestyle shapes the prevalence of psychiatric disorders. Single nucleotide polymorphisms (SNPs) in the human FKBP5 gene were shown to modulate disease risk. To enable investigation of disease-related SNPs in behaviorally relevant context, we generated humanized mouse lines carrying either the risk (AT) or the resiliency (CG) allele of the rs1360780 locus and exposed litters of these mice to maternal separation. Behavioral and physiological aspects of their adult stress responsiveness displayed interactions of genotype, early life condition and sex. In humanized females carrying the CG-but not the AT-allele, ELA led to altered HPA-axis functioning, exploratory behavior and sociability. These changes correlated with differential expression of genes in the hypothalamus, where synaptic transmission, metabolism, and circadian entrainment pathways were deregulated. Our data suggest an integrative role of FKBP5 in shaping the sex-specific outcome of ELA in adulthood.
Spatial heterogeneity in forest carbon storage affects priorities for reforestation
Authors: Chaplin-Kramer Rebecca , Johnson Justin Andrew , Sharp Richard P. , Chatterton Julia , Weil Charlotte , Baccini Alessandro , Sim Sarah 
Published: July 2021

AbstractReforestation is an important strategy for nature-based climate solutions and identifying carbon storage potential of different locations is critical to its success. Applying average carbon values from forest inventories ignores the spatial heterogeneity in forest carbon and the effects of forest edges on carbon storage degradation. Here we show how spatially-explicit, predictive carbon modeling, that leverages satellite, social and biogeophysical datasets, can be used to identify more efficient restoration opportunities for climate mitigation than area-based carbon stock averages. Accounting for regeneration of forest edges, in addition to reforestation, boosts estimates of potential carbon gains by more than 20%. The total potential carbon gain that could be achieved through reforestation at the level indicated by the Bonn Challenge (350Mha) is 51 Gt CO2-eq, but the “missing carbon” in our current forests accounts for 64.6 Gt CO2-eq globally; the greatest potential carbon gains are found in areas of high fragmentation.
Genome-Wide Disease Screening in Early Human Embryos with Primary Template-Directed Amplification
Authors: Xia Yuntao , Gonzales-Pena Veronica , Klein David J , Luquette Joe J , Puzon Liezl , Siddiqui Noor , Reddy Vikrant , Park Peter , Behr Barry R , Gawad Charles 
Published: July 2021

AbstractCurrent preimplantation genetic testing (PGT) enables the selection of embryos based on fetal aneuploidy or the presence a small number of preselected disease-associated variants. Here we present a new approach that takes advantage of the improved genome coverage and uniformity of primary template-directed amplification (PTA) to call most early embryo genetic variants accurately and reproducibly from a preimplantation biopsy. With this approach, we identified clonal and mosaic chromosomal aneuploidy, de novo mitochondrial variants, and variants predicted to cause mendelian and non-mendelian diseases. In addition, we utilized the genome-wide information to compute polygenic risk scores for common diseases. Although numerous computational, interpretive, and ethical challenges remain, this approach establishes the technical feasibility of screening for and preventing numerous debilitating inherited diseases.