bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic Review of Knowledge, Attitudes, and Practices of Dairy Farmers and Consumers Towards Bovine Tuberculosis in Low- and Middle-Income Countries
Authors: Van Der Zwan Abigail , Campbell Patricia T. , Shi Nancy , Bortoli Nikita De , Villanueva-Cabezas Juan Pablo 
Published: April 2024

AbstractBackgroundBovine Tuberculosis (bTB), caused byMycobacterium bovis, is a neglected zoonotic disease primarily associated with cattle. The incidence of bTB is highest in low-income settings with high cattle density and unpasteurised dairy consumption. Smallholder dairy farming has been steadily growing in low- and middle-income countries (LMICs) with limited professional support for adequate bTB surveillance and risk mitigation. Several studies have explored the knowledge, attitudes, and practices (KAP) of milk value chain’s stakeholders towards bTB in LMICs, but this evidence has not been collated and synthesised.MethodologyWe conducted a systematic review to determine what is known, believed, and done in relation to bTB among dairy producers and consumers in LMICs. We performed a systematic search of studies in OVID Medline, Scopus and CABI on 11 September 2023. KAP data were summarised using narrative synthesis and forest plots.ResultsWe retrieved 2763 articles, retaining 51 for the review. Only studies from Africa (n=38) and Asia (n=13) met the eligibility criteria. Most populations reported awareness of human tuberculosis and knew it could be treated, but there was limited awareness of bTB and its zoonotic potential. Knowledge of bTB transmission routes and bTB mitigation varied and risky practices were also variable across populations. Inconsistencies in study design and survey tools suggest some results may have mid- to high risk of bias.ConclusionsAwareness of bTB is surprisingly low among African and Asian populations with high bTB exposure risk, possibly due to the long-standing divide between animal and human health messages that has obscured the One Health implications of bTB. Addressing bTB in LMICs requires a structural One Health approach and standard KAP survey tools to adequately explore the socio-cultural, political, and economic processes and drivers favouring bTB spread and persistence.
Immunogenicity and safety of an Omicron XBB.1.16 adapted vaccine for COVID-19: Interim results from a randomized, controlled, non-inferiority clinical trial
Authors: López Fernandez María Jesús , Narejos Silvia , Castro Antoni , Echave-Sustaeta José María , Forner María José , Arana-Arri Eunate , Molto Josep , Bernad Laia , Pérez-Caballero Raúl , Prado Julia G , Raïch-Regué Dàlia , Boreika Rytis , Izquierdo-Useros Nuria , Blanco Julià , Puig-Barberà Joan , Natalini Martínez Silvina 
Published: April 2024

AbstractBackgroundGlobal COVID-19 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB adapted PHH-1V81 vaccine compared to a XBB adapted mRNA vaccine against XBB and JN.1 SARS-CoV-2 strains.MethodsIn a Phase IIb/III pivotal trial, adults previously vaccinated with a primary scheme and at least one booster dose of an EU-approved mRNA vaccine randomly received either PHH-1V81 or BNT162b2 XBB.1.5 vaccine booster as a single dose. The primary efficacy endpoint assessed neutralisation titers against the Omicron XBB.1.16 variant at day 14. Secondary endpoints evaluated neutralization titers and cellular immunity against different variants. Safety endpoints comprised solicited reactions up to day 7 post-vaccination and serious adverse events until the cut-off date of the interim analysis. Changes in humoral responses were reported as GMT and GMFR assessed by PBNA or VNA.ResultsAt the cut-off date, immunogenicity assessments included 599 participants. Both boosters elicited neutralizing antibodies against XBB.1.5, XBB.1.16 and JN.1 with PHH-1V81 inducing a higher response for all variants. PHH-1V8 booster triggers a superior neutralizing antibodies response against XBBs variants compared to the mRNA vaccine. Subgroup analysis consistently revealed higher neutralizing antibody responses with PHH-1V81 across age groups, number of prior vaccination shots, and SARS-CoV-2 infection history. Safety analysis involved 607 participants at the day 14 visit, revealing favourable safety profiles without any serious vaccine-related adverse events at cut-off date of the interim analysis (12thDecember 2023).ConclusionsPHH-1V81 demonstrates superiority on humoral immunogenicity compared to mRNA vaccine agains XBB variants and non-inferiority against JN.1 with favourable safety profile and lower reactogenicity, confirming its potential as vaccine candidate.
Ochratoxin A status at birth is associated with reduced birthweight and ponderal index in rural Burkina Faso
Authors: Bastos-Moreira Yuri , Argaw Alemayehu , Di Palma Giulianmichela , Dailey-Chwalibóg Trenton , El-Hafi Jasmin , Ouédraogo Lionel Olivier , Toe Laeticia Celine , De Saeger Sarah , Lachat Carl , De Boevre Marthe 
Published: April 2024

AbstractBackgroundMycotoxin exposure during pregnancy has been associated with adverse birth outcomes and poor infant growth. We assessed multiple biomarkers and metabolites of exposure to mycotoxins at birth and their associations with birth outcomes and infant growth in 274 newborns in rural Burkina Faso.Methods and findingsWhole blood microsamples were analyzed for mycotoxin concentrations in newborns in the Biospecimen sub-study nested in MISAME-III trial using ultra performance liquid chromatography coupled to tandem mass spectrometry. Unadjusted and adjusted associations between mycotoxin exposure, and birth outcomes and infant growth at 6 months were estimated using linear regression models for continuous outcomes and linear probability models with robust variance estimation for binary outcomes. Infant growth trajectories from birth to 6 months were compared by exposure status using mixed-effects models with random intercept for the individual infant and random slope for the infant’s age. Ochratoxin A (OTA) exposure was detected in 38.3% of newborns, with other mycotoxins being detected in the range of 0.36% and 4.01%. OTA exposure was significantly associated with adverse birth outcomes, such as lower birthweight (β (95% CI): −0.11 kg (−0.21, 0.00);p= 0.042) and ponderal index (β (95% CI): −0.62 gm/cm3(−1.19, −0.05);p= 0.034), and a marginally significant lower height growth trajectories during the first 6 months (β (95% CI): −0.08 cm/mo (−0.15, 0.0);p= 0.057).ConclusionsOTA exposure was prevalent among newborns and also associated with lower growth at birth and during the first 6 months. The results emphasize the importance of nutrition-sensitive strategies to mitigate dietary OTA, as well as adopting food safety measures in Burkina Faso during the fetal period of development.
Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer’s disease (BenfoTeam)
Authors: Feldman Howard H. , Luchsinger José A. , Léger Gabriel C. , Taylor Curtis , Jacobs Diane M. , Salmon David P. , Edland Steven D. , Messer Karen , Revta Carolyn , Flowers Sarah A. , Jones Kerry S. , Koulman Albert , Yarasheski Kevin E. , Verghese Philip B. , Venkatesh Venky , Zetterberg Henrik , Durant January , Lupo Jody-Lynn , Gibson Gary E. ,   the ADCS BenfoTeam Study Group
Published: April 2024

AbstractBackgroundBenfotiamine provides an important novel therapeutic direction in Alzheimer’s disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches.ObjectiveTo conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD.MethodsThis is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA.ConclusionThe BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose.Trial RegistrationClinicalTrials.gov identifier:NCT06223360, registered on January 25, 2024.
Health Perceptions of Adverse Weather in Older Adults in England: Analysis of 2019/20 Survey Data
Authors: Turner Grace , Moreira de Sousa Agostinho , O’Connell Emer , Kovats Sari , Brooks Katya , Landeg Owen , Ismail Sharif , Rajamani Anusha , Hajat Shakoor 
Published: April 2024

AbstractIntroductionHealth risks to vulnerable groups associated with hot and cold weather are well-documented. Older adults, aged 65 and above, are particularly vulnerable to higher and lower temperatures.AimTo explore older adult perception of health risks from high and low temperatures, what health-protective measures they have undertaken, and the factors associated with risks and responses.MethodsIpsos MORI conducted face-to-face surveys for the UK Health Security Agency with 461 participants in the cold weather survey and 452 in the hot weather survey. Participants reported temperature-related symptoms, risk perceptions for different groups, and behaviours during hot and cold weather. Data analysis involved using binomial logistic regression models to assess potential factors (demographics, vulnerability, behaviours, and responses) associated with older adults’ health risk perception in hot and cold weather.ResultsLess than half of older adults in both surveys agreed that hot or cold weather posed a risk to their health. Older adults with higher education, household income >£25,000 annually or home ownership were less likely to perceive their health at risk during cold weather. In both surveys, older adults who perceived people of the same age or people living alone as at an increased risk were more likely to perceive their own health as at risk. Furthermore, during cold weather, older adults were more likely to self-identify their health at risk when reporting other adults aged 65yrs+ to be at an increased risk, but not during hot weather. Various temperature-related protective behaviours were associated with older adults’ risk perception in hot and cold weather.ConclusionThese findings highlight the need for effective risk communication strategies and targeted health messaging for older adults to support self-identification of risk. Future research should focus on barriers to risk perception and promoting health-protective behaviours in this population.
Atomic insights into the signaling landscape ofE. coliPhoQ Histidine Kinase from Molecular Dynamics simulations
Authors: Lazaridi Symela , Yuan Jing , Lemmin Thomas 
Published: April 2024

AbstractBacteria rely on two-component systems to sense environmental cues and regulate gene expression for adaptation. The PhoQ/PhoP system exemplifies this crucial role, playing a key part in sensing magnesium (Mg2+) levels, antimicrobial peptides, mild acidic pH, osmotic upshift, and long-chain unsaturated fatty acids, promoting virulence in certain bacterial species. However, the precise details of PhoQ activation remain elusive. To elucidate PhoQ’s signaling mechanism at atomic resolution, we combined AlphaFold2 predictions with molecular modeling and carried out extensive Molecular Dynamics (MD) simulations. Our MD simulations revealed three distinct PhoQ conformations that were validated by experimental data. Notably, one conformation was characterized by Mg2+bridging the acidic patch in the sensor domain to the membrane, potentially representing a repressed state. Furthermore, the high hydration observed in a putative intermediate state lends support to the hypothesis of water-mediated conformational changes during PhoQ signaling. Our findings not only revealed specific conformations within the PhoQ signaling pathway, but also hold significant promise for understanding the broader histidine kinase family due to their shared structural features. Our approach paves the way for a more comprehensive understanding of histidine kinase signaling mechanisms across various bacterial species and opens the door for developing novel therapeutics that target PhoQ modulation.
Enabling preprint discovery, evaluation, and analysis with Europe PMC
Authors: Levchenko Mariia , Parkin Michael , McEntyre Johanna , Harrison Melissa 
Published: April 2024

AbstractPreprints provide an indispensable tool for rapid and open communication of early research findings. Preprints can also be revised and improved based on scientific commentary uncoupled from journal-organised peer review. The uptake of preprints in the life sciences has increased significantly in recent years, especially during the COVID-19 pandemic, when immediate access to research findings became crucial to address the global health emergency.With ongoing expansion of new preprint servers, improving discoverability of preprints is a necessary step to facilitate wider sharing of the science reported in preprints. To address the challenges of preprint visibility and reuse, Europe PMC, an open database of life science literature, began indexing preprint abstracts and metadata from several platforms in July 2018. Since then, Europe PMC has continued to increase coverage through addition of new servers, and expanded its preprint initiative to include the full text of preprints related to COVID-19 in July 2020 and then the full text of preprints supported by the Europe PMC funder consortium in April 2022. The preprint collection can be searched via the website and programmatically, with abstracts and the open access full text of COVID-19 and Europe PMC funder preprint subsets available for bulk download in a standard machine-readable JATS XML format. This enables automated information extraction for large-scale analyses of the preprint corpus, accelerating scientific research of the preprint literature itself.This publication describes steps taken to build trust, improve discoverability, and support reuse of life science preprints in Europe PMC. Here we discuss the benefits of indexing preprints alongside peer-reviewed publications, and challenges associated with this process.
Flumequine, a fluoroquinolone in disguise
Authors: Swinkels Aram F. , Fischer Egil A.J. , korving Lisa , Christodoulou Rafaella , Wagenaar Jaap A. , Zomer Aldert L. 
Published: April 2024

AbstractFluoroquinolone resistance inE. coliisolates from livestock in Europe remains high even though the EMA restricted fluoroquinolone use in animals. However, flumequine, a quinolone similar to fluoroquinolones, is still used in livestock in the Netherland, Belgium, Greece or France. Therefore, we investigated whether flumequine selects for the same resistance mechanisms inE. coli.To accomplish this, we investigated and enumerated resistant and non-resistantE. coliisolates obtained from caecal fermentation assays and from broilers exposed to different concentrations of flumequine and enrofloxacin.Flumequine usage leads to approximately 3-fold increase of resistantE. coliin the caecal fermentation, comparable with enrofloxacin. Afterin vitroexposure to flumequine and enrofloxacin we detected the same SNPs (S83L, D87G) ingyrA. Furthermore, the same resistance-causing SNPs were found in phenotypic resistantE. coliisolates from broilers treated with enrofloxacin and flumequine.Flumequine induces similar resistance mechanisms as enrofloxacin and restriction for use should be the same.
Ubiquitylation of nucleic acids by DELTEX ubiquitin E3 ligase DTX3L
Authors: Zhu Kang , Chatrin Chatrin , Suskiewicz Marcin J , Aucagne Vincent , Ahel Dragana , Ahel Ivan 
Published: April 2024

AbstractRecent discoveries expanding the spectrum of ubiquitylation substrates to include non-proteinaceous molecules have broadened our understanding of this modification beyond conventional protein targets. However, the existence of additional types of substrates remains elusive. Here, we present evidence that nucleic acids can also be directly ubiquitylated. DTX3L, a member of the DELTEX family E3 ubiquitin ligases, ubiquitylates DNA and RNAin vitroand that this activity is not shared with another DELTEX family member DTX2. DTX3L shows preference for the 3’-terminal adenosine over other nucleotides. In addition, we demonstrate that ubiquitylation of nucleic acids is reversible by DUBs such as USP2 and SARS-CoV-2 PLpro. Overall, our study provides evidence for reversible ubiquitylation of nucleic acidsin vitroand discusses its potential functional implications.
Phase separation of a microtubule plus-end tracking protein into a fluid fractal network
Authors: Czub Mateusz P. , Uliana Federico , Grubić Tarik , Padeste Celestino , Rosowski Kathryn A. , Dufresne Eric R. , Menzel Andreas , Vakonakis Ioannis , Gasser Urs , Steinmetz Michel O. 
Published: April 2024

AbstractMicrotubule plus-end tracking proteins (+TIPs) are involved in virtually all microtubule-based cellular processes, and it has been recently proposed that they function as liquid condensates. However, the formation process and internal organization of +TIP condensates are poorly understood. Here, we have investigated the phase separation of the CLIP-170 family member Bik1, a key +TIP implicated in budding yeast cell division. We found that Bik1 is a rod-shaped dimer whose conformation is dominated by its central coiled-coil domain. Liquid condensation is accompanied by Bik1 conformational rearrangements, leading to a 2-3-fold rise in interactions between the protein’s folded and disordered domains. In contrast to classical liquids, the supramolecular structure of the Bik1 condensate is heterogeneous, with a fractal structure of protein-rich and protein-free domains. This observation provides structural evidence in support of recent models of biomolecular condensates based on percolation. More broadly, our results provide insights into the structure, dynamic rearrangement, and organization of a complex, multidomain protein in its dilute and condensed phases. Our experimental framework can be extended to other biomolecular condensates, including more intricate +TIP networks.
Dramatic reduction in trypanosome motility occurs without large-scale changes to paraflagellar rod ultrastructure
Authors: Gabriel Heloisa B , Kelly Ruby , Moreira-Leite Flavia , Sunter Jack D 
Published: April 2024

AbstractEukaryotic flagella - widely conserved structures involved in signalling, metabolism and motility – have a core microtubular axoneme that, in many organisms, is accompanied by prominent extra-axonemal structures. In kinetoplastids, including human parasites such as trypanosomes andLeishmania, a dense filamentous lattice called the paraflagellar rod (PFR) accompanies the axoneme for most of its length. While functional studies showed that the presence of the core PFR structure is required for normal motility, the evaluation of more subtle roles for the PFR in motility has been hampered by limited functional and localisation data, particularly on components not essential to form the ‘core’ PFR, such as signalling and metabolism proteins. Here, we addressed these issues by using the genome-wide protein localisation database TrypTag to define a PFR proteome, which was used as a base for a subtler analysis of PFR structure and function. We combined the localisation of fluorescently tagged PFR proteins relative to other cellular components with electron microscopy data on the PFR ultrastructure to localise 81 proteins to specific subdomains of the PFR. Functional analysis of a subset of PFR proteins by gene deletion and RNAi demonstrated that a novel PFR component (PFC21) is required for correct assembly of the outer PFR domain. Importantly, in some single deletion mutants, cell motility was impaired without gross disruption to the core PFR ultrastructure. Thus, our study shows that the PFR has subtle, likely regulatory roles in motility unrelated to any physical constraints that the ‘bulky’ PFR structure may impose on flagella function.
PAbFold: Linear Antibody Epitope Prediction using AlphaFold2
Authors: DeRoo Jacob , Terry James S. , Zhao Ning , Stasevich Timothy J. , Snow Christopher D. , Geiss Brian J. 
Published: April 2024

AbstractDefining the binding epitopes of antibodies is essential for understanding how they bind to their antigens and perform their molecular functions. However, while determining linear epitopes of monoclonal antibodies can be accomplished utilizing well-established empirical procedures, these approaches are generally labor- and time-intensive and costly. To take advantage of the recent advances in protein structure prediction algorithms available to the scientific community, we developed a calculation pipeline based on the localColabFold implementation of AlphaFold2 that can predict linear antibody epitopes by predicting the structure of the complex between antibody heavy and light chains and target peptide sequences derived from antigens. We found that this AlphaFold2 pipeline, which we call PAbFold, was able to accurately flag known epitope sequences for several well-known antibody targets (HA / Myc) when the target sequence was broken into small overlapping linear peptides and antibody complementarity determining regions (CDRs) were grafted onto several different antibody framework regions in the single-chain antibody fragment (scFv) format. To determine if this pipeline was able to identify the epitope of a novel antibody with no structural information publicly available, we determined the epitope of a novel anti-SARS-CoV-2 nucleocapsid targeted antibody using our method and then experimentally validated our computational results using peptide competition ELISA assays. These results indicate that the AlphaFold2-based PAbFold pipeline we developed is capable of accurately identifying linear antibody epitopes in a short time using just antibody and target protein sequences. This emergent capability of the method is sensitive to methodological details such as peptide length, AlphaFold2 neural network versions, and multiple-sequence alignment database. PAbFold is available athttps://github.com/jbderoo/PAbFold.