bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linalool fumigation improves mating competitiveness of males for population suppression of the global fruit pestCydia pomonella
Authors: Huang Sheng-Wang , Wang Peng-Cheng , Wang Yan , Wang Jie-Qiong , Gao Ping , Ji Qing-E , Yang Xue-Qing 
Published: July 2024

AbstractBACKGROUNDThe implementation of sterile insect technique (SIT) has proven effective in the area-wide suppression of several significant agricultural and sanitary pests by employing traditional cobalt-60 (60Co-γ) as a radiation source. Recently, X-ray has been validated as a feasible alternative to60Co-γ radiation sources. Nonetheless, higher doses of X-ray irradiation lead to insect sterility but diminish mating competitiveness, thereby impacting the effectiveness of SIT applications. Thus, it is crucial to ascertain the optimal irradiation dose and develop strategies to enhance the mating competitiveness of sterile insects to enhance SIT efficacy.RESULTSIn this study, we determined the effect of various X-ray irradiation doses (ranging from 0 to 366 Gy) on the fecundity, fertility, and mating competitiveness ofCydia pomonella, a globally invasive fruit pest. Results demonstrated that the sterility rate of sterile males increased proportionally with irradiation dose up to 200 Gy, beyond which it plateaued. Notably, exposure to 200 Gy of irradiation notably decreased the mating competitiveness of male, as evidenced by a mating competitiveness index of 0.17 in laboratory and 0.096 in the orchard. This decline in mating competitiveness is likely linked to the down-regulation of genes associated with the recognition of sex pheromones, specificallyCpomOR3a,CpomOR3b, andCpomOR5, following X-ray irradiation. Fumigation of the plant volatile, linalool at varying concentrations (70, 83, and 96 μ L/m ³) resulted in differential enhancements in male mating competitiveness, with the moderate concentration significantly improving the competitiveness of sterilized males, possibly by restoring their ability to recognize sex pheromones. Implementation of repeated releases of sterilized males on a pilot scale led to a notable reduction in the population ofC. pomonellain the field.CONCLUSIONThese findings indicate that fumigation with plant volatiles has the potential to mitigate male sterility induced by X-ray irradiation, offering a promising approach to enhance the efficacy of SIT applications for the control ofC. pomonella.Graphic AbstractWe determined the optimal X-ray irradiation dose and developed a linalool fumigation approach to improve the mating competitiveness of sterilized insects, thereby bolstering the efficacy of againstCydia pomonella.
Evaluating Inadequate Therapy Response in Ulcerative Colitis Adult Patients: A Retrospective Analysis of German Health Claims Data on Advanced Therapy Initiation
Authors: Dignass Axel , Blumenstein Irina , Schwedhelm Carolina , Strassen Katrin , Berger Leonie , Marquardt Sophie , Seiffert Anna , Kulchytska Nataliia , Hänsel Ivonne , Benson Alexa , Kisser Agnes 
Published: July 2024

AbstractBackgroundThe treatment landscape for active ulcerative colitis (UC) is rapidly evolving and current real-world evidence on response to advanced therapy is limited. This study aimed to determine indicators of inadequate therapeutic response among patients with UC in Germany initiating advanced therapy.MethodsThis retrospective analysis used German claims data (2015-2022) from adult patients (≥18 years). Prevalence and incidence of UC (ICD-10-GM: K51.X) were estimated. Inadequate response to therapy was evaluated in patients initiating advanced therapy based on eight predefined indicators observed for 12 months following index treatment prescription.ResultsMean UC patient age in 2016-2022 ranged from 49.6 to 51.5 years, 47.6%-48.3% were female. Administrative prevalence ranged from 0.45% in 2016 to 0.53% in 2022. Number of patients initiating advanced treatment ranged from 157 to 347 across the study years (3.2%-4.9% of overall treated study population). On average from 2016-2021, 78.8% had inadequate response in the 12 months following index treatment. Common indicators included prolonged use of corticosteroids (46.2%) and augmentation with conventional therapies (43.9%).ConclusionsAdult UC patients showed a high prevalence of inadequate response to advanced therapies. Our findings reveal a need for improved UC advanced therapy options, providing insight into inadequate response patterns. This may help identify patients who could benefit from a change in therapy to improve long-term outcomes.
Isolation ofBorrelia puertoricensisfrom ticks collected in Merida, Yucatan, Mexico
Authors: Vázquez-Guerrero Edwin , Kneubehl Alexander R. , Reyes-Solís Guadalupe C. , Machain-Williams Carlos , Krishnavajhala Aparna , de los Santos Paulina Estrada , Lopez Job E. , Ibarra J. Antonio 
Published: July 2024

AbstractIsolation of tick-borne relapsing fever (TBRF) spirochetes has proven to be a useful tool to understand their distribution by geographic areas where the tick vectors inhabit. However, their isolation and culture are not easy and in general an animal model is needed to achieve this task. Here, argasid ticks were collected from a neighborhood in Ciudad Caucel, Merida, Mexico, andBorrelia puertoricensiswas isolated with an immunosuppressed mouse model. By using this model, a higher number of spirochetes were observed in blood samples, and these were successfully cultivated in Barbour-Stoenner-Kelly (BSK)-IIB media. Genomic analyses confirmed that the isolate to beB. puertoricensis. The present report shows that this spirochete is present in argasid ticks in Ciudad Caucel and presents a potential medical and veterinary health risk.Author SummaryRelapsing fever is a neglected disease caused by spirochetes bacteria of theBorreliaand genus that are different than those in the Lyme disease group. These bacteria are transmitted mostly byOrnithodoros(Alectorobious) soft ticks. In many countries, including Mexico,Ornithodorosspecies are understudied and often misidentified. In this report we obtained an isolate ofBorrelia puertoricensisfrom ticks captured in a small park in the city of Merida, Yucatan. These results emphasize the need for fine-scale vector surveillance in neighborhoods to determine the abundance ofBorreliaspecies, and to define their impact on humans and domestic and wild animals.
Operationalizing multimorbidity in relation to mortality and physical function: findings from a prospective longitudinal cohort study
Authors: Seo Han Sang , Davis Daniel , Khanolkar Amal R. , Hughes Alun , Patalay Praveetha 
Published: July 2024

AbstractBACKGROUND AND OBJECTIVESThere is little consensus on how multimorbidity should be operationalized in life course research. We set out to derive better empirical definitions for multimorbidity by examining its different operationalizations and their associations with mortality, functional independence and physical capability in a longitudinal population-representative cohort.RESEARCH DESIGN AND METHODSWe used data from 2653 (51.6% female) study members in the MRC National Survey of Health and Development (NSHD), a British cohort born in 1946. We examined predictive utility of five multimorbidity operationalizations by age 63 (binary multimorbidity, unweighted disease count, weighted disease count, clustered multimorbidity, cumulative multimorbidity) using 16 chronic disease, to predict 12-year mortality and age 69 functional independence and physical capability (grip strength, chair rise speed, balance).RESULTSThe multimorbidity operationalizations ofunweighted disease count(16.3%) andweighted disease count(16.7%) explained the highest variation for mortality compared with other operationalizations. Similarly, explained variation forunweighted disease count(17.0%) andweighted disease count(16.4%) showed the highest prediction for functional independence and physical capability at age 69 years, with minor variations in physical performance measures where clustered multimorbidity also explained high variance (e.g. 8.6% for changes in chair rise speed). Binary multimorbidity, although frequently used in research was the least predictive of all outcomes.DISCUSSION AND IMPLICATIONSThe associations between various multimorbidity measures and mortality and physical functioning lend support to important influence of multimorbidity on later-life health and functioning while highlighting the differences in variance prediction and point estimates when different approaches to operationalizing multimorbidity are used. An unweighted disease count approach might be suitable for many epidemiological research questions as it is simple to estimate while being as predictive as other more complex approaches such as weighted disease counts.Translational SignificanceMultimorbidity research urgently needs a standardized approach to its measurement and operationalization. This study simultaneously compares different strengths of association between multimorbidity definitions and mortality, functional independence and physical capability. This adds possibility by using the predictive utility for mortality, functional independence and physical capability as criteria for determining the usefulness of a given operationalization. Quantifying how these vary offers practical choices between methods of operationalizing multimorbidity for various purposes in research and clinical settings, for example, a targeted strategy aimed at understanding mortality, physical function and health care utilization.
Epigenetic Signatures of Asthma: A Comprehensive Study of DNA Methylation and Clinical Markers
Authors: Van Asselt Austin J. , Beck Jeffrey J. , Johnson Brandon N. , Finnicum Casey T. , Kallsen Noah , Viet Sarah , Huizenga Patricia , Ligthart Lannie , Hottenga Jouke-Jan , Pool René , Maitland-van der Zee A.H , Vijverberg S.J. , de Geus Eco , Boomsma Dorret I. , Ehli Erik A. , van Dongen Jenny 
Published: July 2024

AbstractBackgroundAsthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma. The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood samples from 319 participants. They were part of the Netherlands Twin Register from families with at least one member suffering from severe asthma. Repeat blood samples were taken after 10 years from 182 of these individuals. Principal component analysis (PCA) on the clinical markers yielded ten principal components (PCs) that explained 92.8% of the total variance. We performed epigenome-wide association studies (EWAS) for each of the ten PCs correcting for familial structure and other covariates.Results221 unique CpGs reached genome-wide significance at timepoint 1 (T1) after Bonferroni correction. PC7 accounted for the majority of associations (204), which correlated with loadings of eosinophil counts and immunoglobulin levels. Enrichment analysis via the EWAS Atlas identified 190 of these CpGs to be previously identified in EWASs of asthma and asthma-related traits. Proximity assessment to previously identified SNPs associated with asthma identified 17 unique SNPs within 1 MB of two of the 221 CpGs. EWAS in 182 individuals with epigenetic data at a second timepoint (T2) identified 49 significant CpGs. EWAS Atlas enrichment analysis indicated that 4 of the 49 were previously associated with asthma or asthma-related traits. Comparing the estimates of all the significant associations identified across the two time points (271 in total) yielded a correlation of 0.81.ConclusionWe identified 270 unique CpGs that were associated with PC scores generated from 35 clinical markers of asthma, either cross-sectionally or 10 years later. A strong correlation was present between effect sizes at the 2 timepoints. Most associations were identified for PC7, which captured blood eosinophil counts and immunoglobulin levels and many of these CpGs have previous associations in earlier studies of asthma and asthma-related traits. The results point to using this robust DNA methylation profile as a new, stable biomarker for asthma.
Surveillance for TB drug resistance using routine rapid diagnostic testing data: Methodological development and application in Brazil
Authors: Baum Sarah E. , Pelissari Daniele M. , Costa Fernanda Dockhorn , Harada Luiza O. , Sanchez Mauro , Bartholomay Patricia , Cohen Ted , Castro Marcia C. , Menzies Nicolas A. 
Published: July 2024

AbstractEffectively responding to drug-resistant tuberculosis (TB) requires accurate and timely information on resistance levels and trends. In contexts where use of drug susceptibility testing has not been universal, surveillance for rifampicin-resistance—one of the core drugs in the TB treatment regimen—has relied on resource-intensive and infrequent nationally-representative prevalence surveys. The expanded availability of rapid diagnostic tests (RDTs) over the past decade has increased testing coverage in many settings, however, RDT data collected in the course of routine (but not universal) use may provide biased estimates of resistance. Here, we developed a method that attempts to correct for non-random use of RDT testing in the context of routine TB diagnosis to recover unbiased estimates of resistance among new and previously treated TB cases. Specifically, we employed statistical corrections to model rifampicin resistance among TB notifications with observed Xpert MTB/RIF (a WHO-recommended RDT) results using a hierarchical generalized additive regression model, and then used model output to impute results for untested individuals. We applied this model to case-level data from Brazil. Modeled estimates of the prevalence of rifampicin resistance were substantially higher than naïve estimates, with estimated prevalence ranging between 28-44% higher for new cases and 2-17% higher for previously treated cases. Our estimates of RR-TB incidence were considerably more precise than WHO estimates for the same time period, and were robust to alternative model specifications. Our approach provides a generalizable method to leverage routine RDT data to derive timely estimates of RR-TB prevalence among notified TB cases in settings where testing for TB drug resistance is not universal.Author SummaryWhile data on drug-resistant tuberculosis (DR-TB) may be routinely collected by National TB Control Programs using rapid diagnostic tests (RDTs), these data streams may not be fully utilized for DR-TB surveillance where low testing coverage may bias inferences due to systematic differences in RDT access. Here, we develop a method to correct for potential biases in routine RDT data to estimate trends in the prevalence of TB drug resistance among notified TB cases. Applying this approach to Brazil, we find that modeled estimates were higher than naïve estimates, and were more precise compared to estimates produced by the World Health Organization. We highlight the value of this approach to settings where testing coverage is low or variable, as well as settings where coverage may surpass existing coverage thresholds, but that could nonetheless benefit from additional statistical correction.
Gene expression evolution during adaptation is predicted by stronger genetic selection at more pleiotropic genes inTribolium castaneum
Authors: Koch Eva L. , Rocabert Charles , Beeravolu Reddy Champak , Guillaume Frédéric 
Published: July 2024

AbstractChanges in gene expression play a fundamental role in the process of adaptation and can inform on the genetic basis of adaptation. We utilized transcriptome-wide variation in gene expression as a means to uncover genes under selection for expression changes during adaptation to heat and drought stress and to understand the nature of selection on gene expression traits of the red flour beetleTribolium castaneum. We showed that estimates of genetic selection on transcript abundance were predictive of evolutionary changes in gene expression after 20 generations of adaptation in seven independent experimental lines. Having measured the genetic covariance between gene expression and relative fitness and among expression traits, we showed that evolutionary changes were caused by indirect selection acting on genetically correlated partners rather than direct selection acting on isolated genes. Consequently, pleiotropic genes with central positions in gene co-expression networks experienced stronger selection and exhibited larger evolutionary changes in expression. Our genomic analysis revealed that selection on expression levels drives parallel allele frequency changes (AFC) in the respective genes. More pleiotropic genes and those carrying expression quantitative trait loci (eQTLs) showed a higher degree of parallel evolution. More generally, genes with more parallel AFCs were under stronger genetic selection. Contrary to previous evidence of constrained evolution at more connected genes, adaptation was driven by selection acting disproportionately on genes central to co-expression gene networks. We demonstrated that measures of selection at the transcriptome level can provide accurate evolutionary predictions and critical information on the molecular basis of rapid adaptation.
Promotion of RNF168-Mediated Nucleosomal H2A Ubiquitylation by Structurally-defined K63-Polyubiquitylated Linker Histone H1
Authors: Shi Qiang , Deng Zhiheng , Zhang Liying , Tong Zebin , Li Jia-Bin , Chu Guo-Chao , Ai Huasong , Liu Lei 
Published: July 2024

ABSTRACTThe chemical synthesis of histones with homogeneous modifications is a potent approach for quantitatively deciphering the functional crosstalk between different post-translational modifications (PTMs). Here, we developed an expedient site-specific (poly)ubiquitylation strategy (CAEPL, Cysteine-Aminoethylation coupled with Enzymatic Protein Ligation), which integrates the Cys-aminoethylation reaction with the process of ubiquitin-activating enzyme UBA1-assisted native chemical ligation. Using this strategy, we successfully prepared monoubiquitylated and K63-linked di- and tri-ubiquitylated linker histone H1.0 proteins, which were incorporated into individual chromatosomes. Quantitative biochemical analysis of different RNF168 constructs on ubiquitylated chromatosomes with different ubiquitin lengths demonstrated that K63-linked polyubiquitylated H1.0 could directly stimulate RNF168 ubiquitylation activity by enhancing the affinity between RNF168 and chromatosome. Subsequent cryo-EM structural analysis of the RNF168/UbcH5c–Ub/H1.0–K63-Ub3chromatosome complex revealed the potential recruitment orientation between RNF168 UDM1 domain and K63-linked ubiquitin chain on H1.0. Finally, we explored the impact of H1.0 ubiquitylation on RNF168 activity in the context of asymmetric H1.0–K63-Ub3di-nucleosome substrate, revealing a comparable stimulation effect of both the inter- and intra-nucleosomal crosstalk. Overall, our study highlights the significance of access to structurally-defined polyubiquitylated H1.0 by CAEPL strategy, enabling in-depth mechanistic investigations ofin-transPTM crosstalk between linker histone H1.0 and core histone H2A ubiquitylation.
Inhibition ofFusarium oxysporumgrowth in banana by silver nanoparticles:in vitroandin vivoassays
Authors: Mendoza Natalia , Yánez Paola , Magdama Freddy , Pacheco Ricardo , Vielma Joel , Vanegas María Eulalia , Bogdanchikova Nina , Pestryakov Alexey , Chong Pablo 
Published: July 2024

AbstractFusarium wilt is a devastating disease that affects banana crops worldwide. In Ecuador, bananas are one of the most important commodities and staple food. Nanoparticles are emerging as innovative solutions to control fungal diseases in plant protection. In this study,in vitroandin vivoassays were carried out to validateFusarium oxysporumgrowth and disease inhibition. 96-well plates experiments were used to calculate the IC50of three different silver nanoparticle formulations (Argovit-1220, Argovit-1221, and Argovit-C) against four EcuadorianFusariumstrains (EC15-E-GM1, EC19-LR-GM3, EC35-G-GM6, EC40-M-GM2). More than 95% inhibition rate was obtained at 25 mg L-1concentration. Fusarium wiltin vivoassay was carried out with Gros Michel plants, where better control was obtained by applying silver nanoparticles to the roots, reducing disease development by an average of 68%. This study shows that silver nanoparticles have a high antifungal potential for controlling the Fusarium wilt of bananas. To the best of our knowledge, this is the first study to test the potential of silver nanoparticles againstFusarium oxysporumin planta under greenhouse conditions.
Functional gene embeddings improve rare variant polygenic risk scores
Authors: Londhe Shubhankar , Lindner Jonas , Chen Zhifen , Holtkamp Eva , Hölzlwimmer Florian R. , Casale Francesco Paolo , Brechtmann Felix , Gagneur Julien 
Published: July 2024

AbstractRare variant association testing is a powerful strategy for identifying effector genes underlying common traits. However, its effectiveness is limited by the scarcity of high-impact rare allele carriers, posing challenges for sensitivity and robustness. Here, we introduce FuncRVP, a rare variant association framework addressing this issue by leveraging functional information across genes. FuncRVP models the effects of rare variants as a weighted sum of gene impairment scores, with weights regularized through a prior based on functional gene embeddings. Modeling 41 quantitative traits from unrelated UK Biobank participants showed that FuncRVP consistently outperformed linear regressions on significantly associated genes and did so more effectively for traits with higher burden heritability. The framework demonstrated versatility, yielding consistent improvements across diverse gene embeddings. Moreover, FuncRVP generated more robust gene effect estimates and yielded more gene discoveries, especially among genetically constrained genes. These findings demonstrate the value of integrating functional information in rare variant association studies and showcase FuncRVP as a promising tool for enhancing phenotype prediction and gene discovery.