bluuebunny/crossref_metadata_2025_split huggingface dataset:
Both social environment and chronological age shape the physiology of ant workers
Authors: Quque Martin , Brun Charlotte , Villette Claire , Sueur Cédric , Criscuolo François , Heintz Dimitri , Bertile Fabrice 
Published: June 2022

AbstractPosition within the social group has consequences on individual lifespans in diverse taxa. This is especially obvious in eusocial insects, where workers differ in both the tasks they perform and their aging rates. However, in eusocial wasps, bees and ants, the performed task usually depends strongly on age. As such, untangling the effects of social role and age on worker physiology is a key step towards understanding the coevolution of sociality and aging. We performed an experimental protocol that allowed a separate analysis of these two factors using four groups of black garden ant (Lasius niger) workers: young foragers, old foragers, young nest workers, and old nest workers. We highlighted age-related differences in the proteome and metabolome of workers that were primarily related to worker subcaste and only secondarily to age. The relative abundance of proteins and metabolites suggests an improved xenobiotic detoxification, and a fuel metabolism based more on lipid use than carbohydrate use in young ants, regardless of their social role. Regardless of age, proteins related to the digestive function were more abundant in nest workers than in foragers. Old foragers were mostly characterized by weak abundances of molecules with an antibiotic activity or involved in chemical communication. Finally, our results suggest that even in tiny species, extended lifespan may require to mitigate cancer risks. This is consistent with results found in eusocial rodents and thus opens up the discussion of shared mechanisms among distant taxa and the influence of sociality on life history traits such as longevity.
Stagnation in quality of next-generation sequencing assays for the diagnosis of hereditary hematopoietic malignancies
Authors: Roloff Gregory W. , Shaw Reid , O’Connor Timothy E. , Drazer Michael W. 
Published: June 2022

AbstractImportanceHereditary hematopoietic malignancies (HHMs) are hereditary cancer syndromes that constitute at least 14% of all myeloid malignancies, but genetic assays used to diagnose HHMs have historically been of variable quality. Here, we demonstrate that HHM assays continue to have persistent shortcomings. These diagnostic gaps place patients with HHMs at high risk for missed diagnoses, missed opportunities for cancer screening, and donor-derived leukemias following stem cell transplant.ObjectiveTo determine if the quality of HHM diagnostic assays has improved since 2020, when our group first demonstrated that most HHM diagnostic tests were insufficient for the accurate diagnosis of these syndromes. We hypothesized that the number of genes tested on each HHM assay increased from 2020 to 2022, in keeping with a more comprehensive sequencing approach.Design, Setting, and ParticipantsWe analyzed assays from eight commercial laboratories to determine which HHM-related genes were sequenced by these assays. We compared these assays to panels from 2020 to determine trends in sequencing quality.ResultsThe majority of HHM diagnostic assays did not change over time and are insensitive for the detection of the full spectrum of HHM-related mutations. The majority (75%) of HHM assays do not sequence CHEK2, the gene most frequently mutated in HHMs, and 25% of HHM assays do not sequence DDX41, the second most frequently mutated HHM gene.ConclusionsThe quality of HHM diagnostic assays has stagnated despite the discovery of novel HHM-related genes as well as prior work demonstrating heterogeneity in quality of HHM testing. The majority of commercially available HHM tests remain insufficient for the diagnosis of the full spectrum of HHM-related germline mutations.Key PointsQuestionHow have diagnostic assays for hereditary hematopoietic malignancies (HHMs) changed since 2020, when most HHM diagnostic assays were inadequate for the accurate diagnosis of HHMs?FindingsMost HHM assays have significant deficiencies in quality and do not sequence the most relevant HHM-related genes. No meaningful improvements in the quality of HHM diagnostic testing have occurred since 2020.MeaningThe quality of HHM diagnostic testing must be improved to universally include the most common HHM-related germline mutations. This will reduce the risk for false negatives, donor derived leukemias, improve genetic counseling, and improve screening for other HHM-related malignancies.
Use of systemic hormonal contraception and risk of attempted suicide
Authors: Toffol Elena , Heikinheimo Oskari , Partonen Timo , But Anna , Latvala Antti , Haukka Jari 
Published: June 2022

AbstractBackgroundEvidence regarding the role of hormonal contraception (HC) as a risk factor for attempted suicide (AS) is inconclusive. The aim was to assess the associations of use of different types of systemic hormonal contraceptives with the risk of AS in women aged 15–49 years.MethodsData were retrieved from national registers in Finland. The AS incidence in 2018-2019 was assessed in a population-based cohort of women (n=587,823) according to their HC use in 2017. To examine the risk of AS related to HC use in the six months preceding the suicide attempt (i.e. current use), we used a nested case-control design with 1:4 ratio (n=4090), and applied multivariable conditional logistic regression models.ResultsDuring the follow-up 1.174,346 million person-years were cumulated and 818 AS cases observed (incidence rate=0.70, 95% CI=0.63–0.83 per 1000 person-years). The incidence rate ratio of HC (n=344 cases) vs. no-HC (n=474 cases) was 0.73 (95% CI=0.63–0.83). Use of HC, and specifically of combined hormonal contraceptives was associated with a lower AS risk compared to non-use when controlling for marital status, socioeconomic status, education, chronic diseases and recent delivery (OR=0.55, 95% CI=0.42–0.73), but not when further adjusting for recent psychiatric hospitalizations and current use of psychotropic medications (OR=0.68, 95% CI=0.45–1.02). Current use of progestogen-only preparations was not associated with AS.ConclusionsHC use appeared not associated with an increased AS risk in fertile-aged women. The choice of the best and safest contraceptive option should take individual mental health status, including assessment of suicidal risk, into account.
The prevalence and topography of spinal cord demyelination in multiple sclerosis: a retrospective study
Authors: Waldman Alex D. , Catania Cecilia , Pisa Marco , Jenkinson Mark , Lenardo Michael J. , DeLuca Gabriele C. 
Published: June 2022

AbstractSpinal cord pathology is a major determinant of irreversible disability in progressive multiple sclerosis. The demyelinated lesion is a cardinal feature. The well-characterised anatomy of the spinal cord and new analytic approaches allows the systematic study of lesion topography and its extent of inflammatory activity unveiling new insights into disease pathogenesis. We studied cervical, thoracic, and lumbar spinal cord tissue from 119 pathologically confirmed multiple sclerosis cases. Immunohistochemistry was used to detect demyelination (PLP) and classify lesional inflammatory activity (CD68). Prevalence and distribution of demyelination, staged by lesion activity, was determined and topographical maps were created to identify patterns of lesion prevalence and distrtibution using mixed models and permutation-based voxelwise analysis. 460 lesions were observed throughout the spinal cord with 76.5% of cases demonstrating at least 1 lesion. The cervical level was preferentially affected by lesions. 58.3% of lesions were inflammatory with 87.9% of cases harbouring at least 1 inflammatory lesion. Topographically, lesions consistently affected the dorsal and lateral columns with relative sparing of subpial areas in a distribution mirroring the vascular network. The presence of spinal cord lesions and the proportion of active lesions related strongly with clinical disease milestones, including time from onset to wheelchair and onset to death. We demonstrate that spinal cord demyelination is common, highly inflammatory, has a predilection for the cervical level, and relates to clinical disability. The topography of lesions in the dorsal and lateral columns and relative sparing of subpial areas points to a role of the vasculature in lesion pathogenesis, suggesting short-range cell infiltration from the blood and signaling molecules circulating in the perivascular space incite lesion development. These findings challenge the notion that end-stage progressive multiple sclerosis is ‘burnt out’ and an outside-in lesional gradient predominates in the spinal cord. Taken together, this study provides support for long-term targeting of inflammatory demyelination in the spinal cord and nominates vascular dysfunction as a potential target for new therapeutic approaches to limit irreversible disability.
Protective efficacy of COVAXIN® against Delta and Omicron variants in hamster model
Authors: Yadav Pragya D , Mohandas Sreelekshmy , Shete Anita , Sapkal Gajanan , Deshpande Gururaj , Kumar Abhimanyu , Wakchaure Kundan , Dighe Hitesh , Jain Rajlaxmi , Ganneru Brunda , Yemul Jyoti , Gawande Pranita , Mohan Krishna , Abraham Priya 
Published: June 2022

AbstractThe immunity acquired after natural infection or vaccinations against SARS-CoV-2 tend to wane with time. Vaccine effectiveness also varies with the variant of infection. Here, we compared the protective efficacy of COVAXIN® following 2 and 3 dose immunizations against the Delta variant and also studied the efficacy of COVAXIN® against Omicron variants in a Syrian hamster model. The antibody response, clinical observations, viral load reduction and lung disease severity after virus challenge were studied. Protective response in terms of the reduction in lung viral load and lung lesions were observed in both the 2 dose as well as 3 doses COVAXIN® immunized group when compared to placebo group following the Delta variant challenge. In spite of the comparable neutralizing antibody response against the homologous vaccine strain in both the 2 dose and 3 dose immunized groups, considerable reduction in the lung disease severity was observed in the 3 dose immunized group post Delta variant challenge indicating the involvement of cell mediated immune response also in protection. In the vaccine efficacy study against the Omicron variants i.e., BA.1 and BA.2, lesser virus shedding, lung viral load and lung disease severity were observed in the immunized groups in comparison to the placebo groups. The present study shows that administration of COVAXIN® booster dose will enhance the vaccine effectiveness against the Delta variant infection and give protection against the Omicron variants BA.1.1 and BA.2.
Aspects determining adherence to wrist-hand orthoses in patients with peripheral neuropathies
Authors: Bula-Oyola Ena , Belda-Lois Juan-Manuel , Porcar-Seder Rosa , Page Alvaro 
Published: June 2022

AbstractBACKGROUNDPeople with peripheral neuropathies may experience significant sensorimotor impairment. Prescribed treatment includes wearing an orthosis. However, a common barrier to treatment effectiveness is patient adherence. Given the limited information available, it is essential to gather evidence on treatment adherence challenges.OBJECTIVEThis study aims to identify aspects that influence adherence to orthotic treatment in patients with peripheral neuropathies.METHODSWe applied a survey that included evaluation items from the Quest 2.0 to assess importance and satisfaction and self-developed questions. We conducted the assessment following the principles of Kano’s model to understand the nature of the aspects influencing adherence and prioritize opportunities for product improvement.RESULTSSatisfaction with ease of adjustment, weight, ease of use, effectiveness, and dimensions, as well as perceived interference with daily activities, influences adherence to treatment. We found no correlation between orthosis appearance and adherence. However, it is a basic quality attribute and should be considered a relevant design requirement to avoid product rejection.CONCLUSIONSWe found differences between the estimate of importance obtained by explicit and inexplicit queries. Thus, cross-checking information from different query methods could minimize potential biases and accurately assess users’ perceptions of rehabilitation products.
COVID-19 Vaccine Hesitancy and Confidence in the Philippines and Malaysia: A Cross-sectional Study of Sociodemographic Factors and Information-Seeking
Authors: Brackstone K , Marzo RR , Bahari R , Head MG , Patalinghug ME , Su TT 
Published: June 2022

AbstractWith the emergence of the highly transmissible Omicron variant, large-scale vaccination coverage is crucial to the national and global pandemic response, especially in populous Southeast Asian countries such as the Philippines and Malaysia. Little is known, however, about predictors of COVID-19 vaccine hesitancy and vaccine confidence among unvaccinated individuals in these regions. An internet-based cross-sectional survey was conducted from May 2021 to September 2021. Data from a total of 2558 participants from the Philippines (N = 1002) and Malaysia (N = 1556) were analysed. Results showed that Filipino (vs. Malaysian) participants indicated higher prevalence of COVID-19 vaccine hesitancy (56.6 vs. 22.9%, p = 0.001). However, there were no significant differences in ratings of vaccine confidence between Filipino (45.9%) and Malaysian (49.2%) participants (p = 0.105). Predictors associated with greater vaccine hesitancy included females (p = 0.029) and rural dwellers (p = 0.015) among Filipino participants, whereas females (p = 0.004), 25-34 year olds (p = 0.027), Christians (p < 0.001), and social media use (p < 0.001) were associated with hesitancy among Malaysian participants. Predictors associated with lower confidence included females (p = 0.026) and information seeking (p < 0.001) among Filipino participants, whereas predictors associated with lower confidence among Malaysian participants included residing in a rural community (p = 0.004), Christians (p < 0.001), online information seeking (p < 0.001), and determining relevance of online information (p = 0.013). Efforts to improve uptake of COVID-19 vaccination must be centred upon targeting specific communities using local authorities and for the masses through social media. Efforts should focus on determining effective interventions to decrease vaccination hesitancy and increase the uptake of COVID-19 vaccination, particularly in light of the Dengvaxia crisis in the Philippines.
Ultra-low coverage genome-wide association study – insights into gestational age using 17,844 embryo samples with preimplantation genetic testing
Authors: Li Shumin , Yan Bin , Li Thomas K.T. , Lu Jianliang , Gu Yifan , Tan Yueqiu , Gong Fei , Lam Tak-Wah , Xie Pingyuan , Wang Yuexuan , Lin Ge , Luo Ruibang 
Published: June 2022

AbstractBackgroundVery low coverage (0.1 to 1x) whole genome sequencing (WGS) has become a promising and affordable approach to discover genomic variants of human populations for Genome-Wide Association Study (GWAS). To support genetic screening using Preimplantation Genetic Testing (PGT) in a large population, the sequencing coverage goes below 0.1x to an ultra-low level. However, its feasibility and effectiveness for GWAS remains undetermined.MethodsWe devised a pipeline to process ultra-low coverage WGS data and benchmarked the accuracy of genotype imputation at the combination of different coverages below 0.1x and sample sizes from 2,000 to 16,000, using 17,844 embryo PGT with approximately 0.04x average coverage and the standard Chinese sample HG005 with known genotypes. We then applied the imputed genotypes of 1,744 transferred embryos who have gestational ages and complete follow-up records to GWAS.ResultsThe accuracy of genotype imputation under ultra-low coverage can be improved by increasing the sample size and applying a set of filters. From 1,744 born embryos, we identified 11 genomic risk loci associated with gestational ages and 166 genes mapped to these loci according to positional, expression quantitative trait locus and chromatin interaction strategies. Among these mapped genes,CRHBP, ICAM1andOXTRwere more frequently reported as preterm birth related. By joint analysis of gene expression data from previous studies, we constructed interrelationships of mainlyCRHBP, ICAM1, PLAGL1, DNMT1, CNTLN, DKK1andEGR2with preterm birth, infant disease and breast cancer.ConclusionsThis study not only demonstrates that ultra-low coverage WGS could achieve relatively high accuracy of adequate genotype imputation and is capable of GWAS, but also provides insights into uncovering genetic associations of gestational age trait existed in the fetal embryo samples from Chinese or Eastern Asian populations.
The membrane activity of the amphibian Temporin B peptide analog TB_KKG6K sheds light on the mechanism that kills Candida albicans
Authors: Kakar Anant , Sastré-Velásquez Luis Enrique , Hess Michael , Galgóczy László , Papp Csaba , Holzknecht Jeanett , Romanelli Alessandra , Váradi Györgyi , Malanovic Nermina , Marx Florentine 
Published: June 2022

AbstractTemporin B (TB) is a 13 amino acid long, cationic peptide secreted by the granular glands of the European frog Rana temporaria. We could recently show that the modified TB peptide analog TB_KKG6K rapidly killed planktonic and sessile Candida albicans at low µM concentrations and was neither hemolytic nor cytotoxic to mammalian cells in vitro. The present study aimed to shed light into its mechanism of action, with a focus on its fungal cell membrane activity. We utilized different fluorescent dyes to prove that it rapidly induces membrane depolarization and permeabilization. Studies on model membrane systems revealed that the TB analog undergoes hydrophobic and electrostatic membrane interactions showing a preference for anionic lipids and identified phosphatidylinositol and cardiolipin as possible peptide targets. Fluorescence microscopy using FITC-labelled TB_KKG6K in the presence of the lipophilic dye FM4-64 indicated that the peptide compromises membrane integrity and rapidly enters C. albicans cells in an energy independent manner. Peptide treated cells analyzed by cryo-based electron microscopy exhibited no signs of cell lysis; however, subcellular structures were disintegrated, suggesting that intracellular activity may form part of the killing mechanism of the peptide. Taken together, this study proved that the TB_KKG6K compromises C. albicans membrane function, which explains the previously observed rapid, fungicidal mode of action and promises its great potential as a future anti-Candida therapeutic.ImportanceFungal infections with the opportunistic human pathogen C. albicans are associated with high moratility rates in immunocompromised patients. This is partly due to the yeast’s ability to rapidly develop resistance towards currently available antifungals. Small, cationic, membrane-active peptides are promising compounds to fight against resistance development as many of them effectuate rapid fungal cell death. This fast killing is believed to hamper the development of resistance, as the fungi do not have sufficient time to adapt to the antifungal compound. We prevously reported that the synthetic variant of the amphibian Temporin B peptide, TB_KKG6K, rapidly kills C. albicans. In the current study, the mechanism of action of the TB analog was investigated. We show that this TB analog is membrane-active and impairs cell membrane function, highlighting its potential to be developed as an attractive alternative anti-C. albicans therapeutic, which may hinder the development of resistance.
Generation and characterization of conditional yeast mutants affecting each of the two essential functions of the scaffolding proteins Boi1/2 and Bem1
Authors: Sulpizio Abigail , Herpin Lancelot , Gingras Robert , Liu Wenyu , Bretscher Anthony 
Published: June 2022

AbstractBoi1 and Boi2 are closely related yeast scaffolding proteins, either of which can perform an essential function. Previous studies have suggested a role in cell polarity, interacting with lipids, components of the late secretory pathway, and actin nucleators. We report detailed studies of their localization, dynamics, and the generation and characterization of conditional mutants. Boi1/2 are present on the plasma membrane in dynamic patches, then at the bud neck during cytokinesis. These distributions are unaffected by perturbation of the actin cytoskeleton or the secretory pathway. We identify two critical aromatic residues, present in both Boi1 and Boi2, in the essential C-terminal PH domain, that cause temperature sensitive growth resulting in defects in polarized growth leading to cell lysis. The scaffolding protein, Bem1, colocalizes with Boi1 in patches at the growing bud, and at the bud neck, the latter requiring the N-terminal SH3 domain of Boi1p. Loss of function of Boi1-SH3 domain renders Bem1 essential which can be fully replaced by a fusion of the SH3b and PB1 domains of Bem1. Thus, the two essential functions of the Boi1/2/Bem1 proteins can be satisfied by Bem1-SH3b-PB1 and Boi1-PH. Generation and characterization of conditional mutations in the essential function of Bem1 reveal a slow onset of defects in polarized growth, which is difficult to define a specific initial defect. This study provides more details into the functions of Boi1/2 and their relationship with Bem1, and presents the generation of conditional mutants that will be useful for future genetic analysis.
Molecular Transport of the Zika Virus by the Human Cytoplasmic Dynein-1
Authors: Zavala Vargas Dan Israel , Carbajal Giovani Visoso , Barrón Leticia Cedillo , Filisola Villaseñor Jessica Georgina , Ramirez Romel Rosales , Ludert Juan E. , Morales-Ríos Edgar 
Published: June 2022

AbstractZika virus (ZIKV) infection is a major public health threat, making the study of its biology a matter of great importance. By analyzing the viral-host protein interactions and proposing them as new drug targets, we would diminish the emergence of new resistant strains. In this work, we have shown that human cytoplasmic dynein-1 (Dyn) interacts with the ZIKV. We additionally demonstrate that the envelope protein of the ZIKV and the dimerization domain of the heavy chain of Dyn binds directly without dynactin or cargo adaptor. In addition, we have analyzed this interaction in Vero cells, where we are proposing that the interaction ZIKV-Dyn is finely tuned within the replication cycle. Altogether, our data suggest a new step in the previously described replication cycle of the ZIKV, introducing a suitable molecular target to modulate infection by ZIKV.