bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Midwifery-led units in Spain: lessons from the first 5 years
Authors: Palau-Costafreda Roser , Orus-Covisa Lluna , Vicente-Castellví Edgar , Espada-Trespalacios Xavier , Medina Català Albert , Alcover Carlota , Obregón Gutiérrez Noemí , Escuriet Ramon 
Published: July 2024

ABSTRACTIntroductionThe global rise in medical interventions during childbirth, such as caesarean sections, has raised concerns regarding their necessity and impact on maternal and neonatal outcomes. Midwifery-led units (MLUs) have demonstrated lower intervention rates and higher maternal satisfaction.This study evaluates the implementation and effects of the first MLU in the Spanish National Health System.MethodsA retrospective cross-sectional trend study and a cohort study were conducted to compare childbirth interventions and outcomes at XX with other hospitals of varying complexities.ResultsThe introduction of the MLU at XX resulted in a significant reduction in caesarean sections, decreasing from 23.5% to 13.5%, and an increase in spontaneous vaginal births, rising from 64.2% to 78.7%. These trends reversed following the MLU’s closure in 2022, with caesarean sections increasing to 22.9% and spontaneous births dropping to 69.0%. The MLU served 1286 women, with the majority classified as low-risk pregnancies. Obstetric emergencies in the MLU were low and comparable to those in countries with established MLUs.DiscussionThis study highlights the potential benefits of integrating MLUs into traditionally medicalized healthcare systems to promote physiological childbirth and reduce unnecessary interventions. The positive outcomes achieved at HM are comparable to those in countries with more established MLU practices, reflecting the unit’s commitment to evidence-based care. The increasing interest among women in midwifery-led care indicates a broader demand for supportive, less medicalized childbirth environments.ConclusionsMLU can lead to lower caesarean section rates and higher spontaneous vaginal birth rates, contributing to more positive maternal and neonatal outcomes. However, sustained support and investment in these units are crucial to maintain these benefits. Policymakers and healthcare providers should consider expanding the integration of MLUs within the Spanish National Health System to enhance maternal care quality and align with best practices.
The impact of genome-wide histocompatibility on liver transplantation outcomes
Authors: Semenova M , Liukkonen V , Markkinen S , Färkkilä M , Nordin A , Partanen J , Åberg F , Hyvärinen K 
Published: July 2024

ABSTRACTLiver transplantation (LT) is the standard treatment for end-stage liver diseases. However, the role of human leukocyte antigen (HLA)-matching in LT remains unclear. Immunological allograft injury and rejection are ongoing concerns, particularly when efforts are made to minimize immunosuppression. Although HLA matching currently has no established role in LT, interest in non-HLA compatibility in the field of transplantation is growing.We compared 666 LT recipient-donor pairs and identified amino acid-changing genetic mismatches outside the HLA gene segment in different protein groups, and mismatches in 40 common gene deletions.We evaluated the association between mismatches and LT outcomes by using adjusted Cox models for missense variant mismatches and deletion analyses. The primary endpoints were acute rejection, late rejection, graft loss, and overall survival. Statistical significance was set at a false discovery rate (FDR) <0.05.Mismatches in missense variants coding for all proteins were associated with late rejection, with an adjusted hazard ratio (aHR) of 0.998 (95% confidence interval [CI]: 0.996–0.999;P= 0.011, FDR <0.05). Deletion mismatches tagged with rs11985201, rs2342606, rs2174926, and rs1944862 were identified as risk factors for LT outcomes. The sum of mismatches in deletion variants rs11985201, rs2342606, and rs1944862 was associated with time to acute rejection, with an aHR of 1.377 (95% CI: 1.139– 1.664,P= 0.001, FDR <0.05).Genome-wide mismatches outside of the HLA region contribute to the risk of LT complications. Robust, large-scale studies are required to validate these results.
The Healthy Life in an Urban Setting (HELIUS) study in Amsterdam, The Netherlands: cohort update 2024 and key findings
Authors: Galenkamp Henrike , Koopman Anitra D.M. , Esi van der Zwan J. , van den Born Bert-Jan H. , Lok Anja , Moll van Charante Eric P. , Prins Maria , Verhoeff Arnoud P. , Zwinderman Aeilko H. , Stronks Karien 
Published: July 2024

AbstractThe Healthy Life in an Urban Setting (HELIUS) study is an ongoing prospective multi-ethnic cohort study, in Amsterdam, The Netherlands that started in 2011. The principle aim of the HELIUS study is to investigate the causes of (the unequal burden of) diseases across ethnic groups, with emphasis on mental disorders, cardiovascular disease and infectious disease, and their interrelationships. Stratified sampling by ethnic group was used to allow for an equal representation of the largest ethnic groups resulting in similar-sized samples of individuals of Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Turkish and Moroccan origin. A total of 24,780 individuals participated in the baseline examination that consisted of a questionnaire, physical examination and collection of biological material. Follow-up data have been collected through linkage with health care registries and a first follow-up data collection that took part between 2019 and 2022 and included 11,035 participants with an average follow-up time of 6.4 years. The data collection included information on demographics, medical history (including medication use and mental health status), anthropometrics, and fasting blood, urine and stool samples. Here we give an update on the HELIUS study and its methods regarding the first follow-up data collection, data linkage, and additional analyses using stored biomaterials. In addition, we provide a summary of key findings.
Growing up in poverty, growing old with multimorbidity in America, Britain, China, Europe and Indonesia: a retrospective and prospective study in 31 countries
Authors: Tampubolon Gindo 
Published: July 2024

AbstractThe childhood poor in rich countries have reported worse cognitive, muscle and mental functions in old age. But it is uncertain whether the childhood poor around the world are at higher risks of multimorbidity because childhood recollections are often erroneous.METHODSSome 81,804 older adults over 50 years in 31 countries recalled their childhood conditions at ten to fourteen and prospectively reported their chronic conditions. Childhood conditions in Britain and Europe include numbers of books, rooms and people, presence of running hot water and central heating. Across in America, these are mostly replaced with financial hardship or family indebtedness, in China starvation to death due to government edict while in Indonesia presence of running cold water. Per prior practice childhood poverty is a latent construct of these error-laced recollections while multimorbidity is defined as at least two from a set of chronic conditions. Associations with multimorbidity are obtained with fixed effects probit model, controlling for age, education, wealth, marital status and youth illness. Extensive sensitivity analyses assessed robustness.RESULTSChildhood poverty associates with higher probabilities of multimorbidity (0.088, [95% confidence interval 0.057 – 0.118]) in 31 rich and developing countries. And women reported lower probabilities of multimorbidity (−0.071, [-0.096 – -0.047]). Frequencies of multimorbidity vary across countries, and likewise age profiles of multimorbidity in later life.DISCUSSIONEvidence is accumulating that childhood lasts a life time in rich and developing nations. The various childhood recollections indicating poverty show that the childhood poor grow old with more chronic conditions. Because population ageing is posing a momentous challenge across the world, more research is needed on the life course shaping of healthy ageing. But this strong evidence calls for urgent actions to eliminate child poverty on account of its lifelong rewards. [287 + 4233 words]
Proteomic analysis identifies dysregulated proteins in albuminuria: a South African pilot study
Authors: Khoza Siyabonga , George Jaya A. , Naicker Previn , Stoychev Stoyan H. , Fabian June , Govender Ireshyn S. 
Published: July 2024

AbstractAlbuminuria may precede decreases in glomerular filtration rate (GFR) and both tests are insensitive predictors of early stages of kidney disease. Our aim was to characterise the urinary proteome in black African individuals with albuminuria and well-preserved GFR from South Africa. A case-controlled study that compared urinary proteomes of 52 normoalbuminuric (urine albumin: creatinine ratio (uACR) <3 mg/mmol) and 56 albuminuric (uACR ≥ 3 mg/mmol) adults of Black African ethnicity. Urine proteins were precipitated, reduced, alkylated, digested, and analysed using an Evosep One LC coupled to a Sciex 5600 Triple-TOF in data-independent acquisition mode. Data were searched on SpectronautTM15. Differentially abundant proteins (DAPs) were filtered ≥ 2.25-fold change and false discovery rate ≤ 1%. Receiver operating characteristic curves were used to assess the discriminating ability of proteins of interest. Pathway analysis was performed using Enrichr software. The albuminuric group had a higher uACR (7.9 vs 0.55 mg/mmol,p<0.001). The median eGFR (mL/min/1.73m2) showed no difference between the groups (111 vs 114,p=0.707). We identified 80 DAPs in the albuminuria group compared to normoalbuminuria, of which 59 proteins increased while 21 proteins decreased in abundance. We found 12 urinary proteins with AUC > 0.8, andp-value <0.001 in the multivariate analysis. Furthermore, an 80-protein model was developed that showed a high AUC >0.907 and a predictive accuracy of 91.3% between the two groups. Pathway analysis associated with DAPs were involved in insulin growth factor (IGF) functions, innate immunity, platelet degranulation, and extracellular matrix organization. In albuminuric individuals with well-preserved eGFR, pathways involved in preventing the release and uptake of IGF by insulin growth factor binding protein were significantly enriched. These proteins are indicative of a homeostatic imbalance in a variety of cellular processes underlying renal dysfunction and are implicated in chronic kidney disease.
Functional genomics of chitin degradation byVibrio parahaemolyticusreveals finely integrated metabolic contributions to support environmental fitness
Authors: Getz Landon P. , Robinson Oriana , Thomas Nikhil A. 
Published: July 2024

AbstractVibriospecies are marine prokaryotes that inhabit diverse ecological niches, colonizing abiotic and biotic surfaces. These bacteria are vital players in the global carbon cycle, assimilating billions of tonnes of chitin for carbon (and nitrogen) metabolites. Many bacterial proteins involved in the process-including chitinases, sugar transporters, and modifying enzymes-have been well studied. However, the genetic functional interplay and key drivers ofVibriocompetitive survival in the presence of chitin as the dominant carbon source is not understood. To address this question, we carried out transposon sequencing (Tn-seq) to determine the genetic fitness ofVibrio parahaemolyticusmutants grown on chitin as a sole carbon source. Along with validating knownVibriogenes associated with chitin metabolism, our data newly identified vital roles for an unclassified OprD-like import porin and a HexR family transcriptional regulator. Furthermore, we functionally implicated HexR in regulating multiple physiological processes involved inV. parahaemolyticusenvironmental survival including carbon assimilation and cell growth, biofilm formation, and cell motility. Notably, our data revealed a strict requirement for HexR in filamentous cell morphology, a critical trait forV. parahaemolyticusenvironmental fitness. Therefore, a vital import porin and genomic regulation mediated by HexR supports multiple physiological processes forVibriochitinolytic growth and environmental fitness.
The SARS-CoV-2 nucleocapsid protein inhibits the cellular Nonsense-Mediated mRNA Decay (NMD) pathway preventing the full enzymatic activation of UPF1
Authors: Nuccetelli Veronica , Mghezzi-Habellah Makram , Deymier Séverine , Roisin Armelle , Gerard-Baraggia Francine , Rocchi Cecilia , Coureux Pierre-Damien , Gouet Patrice , Cimarelli Andrea , Mocquet Vincent , Fiorini Francesca 
Published: July 2024

The Nonsense-mediated mRNA decay (NMD) pathway triggers the degradation of defective mRNAs and governs the expression of mRNAs with specific characteristics. Current understanding indicates that NMD is often significantly suppressed during viral infections to protect the viral genome. In numerous viruses, this inhibition is achieved through direct or indirect interference with the RNA helicase UPF1, thereby promoting viral replication and enhancing pathogenesis.In this study, we employed biochemical, biophysical assays, and cellular investigations to explore the interplay between UPF1 and the Nucleocapsid (Np) protein of SARS-CoV-2. We evaluated their direct interaction and its impact on inhibiting cellular NMD. Furthermore, we characterized how this interaction affects UPF1’s enzymatic function. Our findings demonstrate that Np inhibits the unwinding activity of UPF1 by physically obstructing its access to structured nucleic acid substrates. Additionally, we showed that Np binds directly to UPF2, disrupting the formation of the UPF1/UPF2 complex essential for NMD progression. Intriguingly, our research also uncovered a surprising pro-viral role of UPF1 and an antiviral function of UPF2.These results unveil a novel, multi-faceted mechanism by which SARS-CoV-2 evades the host’s defenses and manipulates cellular components. This underscores the potential therapeutic strategy of targeting Np-UPF1/UPF2 interactions to treat COVID-19.
Cryo-EM Structures ofSaccharolobus solfataricusInitiation Complexes with Leaderless mRNAs Highlight Archaeal Features and Eukaryotic Proximity
Authors: Bourgeois Gabrielle , Coureux Pierre-Damien , Lazennec-Schurdevin Christine , Madru Clément , Gaillard Thomas , Duchateau Magalie , Chamot-Rooke Julia , Bourcier Sophie , Mechulam Yves , Schmitt Emmanuelle 
Published: July 2024

ABSTRACTThe archaeal ribosome is of the eukaryotic type. Genomic and phylogenetic studies have indicated that TACK and Asgard, the closest relatives of eukaryotes, have ribosomes containing eukaryotic ribosomal proteins not found in other archaeal branches, eS25, eS26 and eS30. In our study, we investigated the case ofSaccharolobus solfataricus, a crenarchaeon belonging to the TACK branch, which mainly uses leaderless mRNAs. We characterized the small ribosomal subunit ofS. solfataricusbound to SD-leadered or leaderless mRNAs (lmRNAs). Cryo-EM structures show for the first time archaeal versions of eS25, eS26 and eS30 proteins bound to the small subunit. In addition, we identify two novel ribosomal proteins named aS33 and aS34 as well as a domain of eS6, that highlight the diversity of archaeal ribosomes. Leaderless mRNAs are bound to the small ribosomal subunit, and the 5’-triphosphate group contributes to their binding. Archaeal eS26 is in the mRNA exit channel wrapped around the 3’ end of ribosomal RNA, as it is in eukaryotes. Its position is not compatible with an SD:antiSD duplex in the mRNA exit channel. Overall, our results suggest a role of eS26 in translation regulation and possible evolutionary routes from archaeal to eukaryotic translation.
MELATONIN INDUCES CHANGES ON THE CIRCADIAN RHYTHMS OF REPRODUCTIVE HORMONES DURING SPERMATOGENESIS IN PUBERTAL MALE SEA BASS,Dicentrarchus labrax
Authors: Alvarado M.Victoria , Espigares Felipe , Carrillo Manuel , Felip Alicia 
Published: July 2024

ABSTRACTReproduction is a highly demanding biological process that occurs at the optimal time of the year and day to ensure the success of spawn and offspring. Melatonin is a hormone that, secreted mainly by the pineal gland, plays a critical role in the integration of the photoneuroendocrine information from environment (annual and daily variations) to modulate reproductive activity and gonadal development in fish. In this study we assessed the effect of exogenous melatonin on the circadian levels of sex steroids and gonadotropins in pubertal 2 yr-old male sea bass during their reproductive cycle including, pre-spermatogenesis (Pspg), spermiation (Spm) and post-spermiation (PSpm) stages. Our results demonstrated that all reproductive hormones displayed circadian variations along the entire reproductive cycle in pubertal fish. Circulating levels of the luteinizing hormone (Lh) were affected by both melatonin injection and the daily timing of administration during the Spm and PSpm stages, thus evoking variations of Lh levels at night. Melatonin also significantly affected circadian rhythms of Fsh during the Spm stage. Overall, both 11-Kt and T plasma levels displayed circadian variations during the reproductive cycle in the sea bass which were not prevented by melatonin. However, melatonin showed a significant decrease of plasma levels of 11-Kt 1h after dusk during the Pspg stage, while it increased those levels of T 5 h after dusk during the PSpm stage. These findings provide new insights into the role of melatonin in fish reproduction as a key factor in regulation of daily variation of key hormones involved in gonadal development. This circumstance may have implications in the control of gametogenesis and management of fish in aquaculture.HighlightsPlasma levels of Fsh, Lh, T and 11-Kt show daily rhythms in pubertal male sea bass.Melatonin evokes changes in daily rhythms of Lh during the reproductive cycle.Melatonin yields Fsh plasma level differences during spermiation stage.Melatonin elicits T and 11-Kt plasma level differences depending on reproductive stage and time.
In vitroevolution of ciprofloxacin resistance inNeisseriacommensals and derived mutation population dynamics in naturalNeisseriapopulations
Authors: Robinson Leah R. , McDevitt Caroline J. , Regan Molly R. , Quail Sophie L. , Wadsworth Crista B. 
Published: July 2024

AbstractCommensalNeisseriaare members of a healthy human oropharyngeal microbiome; however, they also serve as a reservoir of antimicrobial resistance for their pathogenic relatives. Despite their known importance as sources of novel genetic variation for pathogens, we still do not understand the full suite of resistance mutations commensal species can harbor. Here, we usein vitroselection to assess the mutations that emerge in response to ciprofloxacin selection in commensalNeisseriaby passaging 4 replicates of 4 different species in the presence of a selective antibiotic gradient for 20 days; then categorized derived mutations with whole genome sequencing. 10/16 selected cells lines across the 4 species evolved ciprofloxacin resistance (≥ 1 ug/ml); with resistance-contributing mutations primarily emerging inDNA gyrase subunit AandB(gyrAandgyrB),topoisomerase IV subunits CandE(parCandparE), and themultiple transferable efflux pump repressor(mtrR). Of note, these derived mutations appeared in the same loci responsible for ciprofloxacin reduced susceptibility in the pathogenicNeisseria, suggesting conserved mechanisms of resistance across the genus. Additionally, we tested for zoliflodacin cross-resistance in evolved strain lines and found 6 lineages with elevated zoliflodacin minimum inhibitory concentrations. Finally, to interrogate the likelihood of experimentally derived mutations emerging and contributing to resistance in naturalNeisseria, we used a population-based approach and identified GyrA 91I as a substitution circulating within commensalNeisseriapopulations and ParC 85C in a single gonococcal isolate. Small clusters of gonococcal isolates had commensal-like alleles atparCandparE, indicating recent cross-species recombination events.
Diffusing protein binders to intrinsically disordered proteins
Authors: Liu Caixuan , Wu Kejia , Choi Hojun , Han Hannah , Zhang Xulie , Watson Joseph L. , Shijo Sara , Bera Asim K. , Kang Alex , Brackenbrough Evans , Coventry Brian , Hick Derrick R. , Hoofnagle Andrew N. , Zhu Ping , Li Xingting , Decarreau Justin , Gerben Stacey R. , Yang Wei , Wang Xinru , Lamp Mila , Murray Analisa , Bauer Magnus , Baker David 
Published: July 2024

AbstractProteins which bind intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) with high affinity and specificity could have considerable utility for therapeutic and diagnostic applications. However, a general methodology for targeting IDPs/IDRs has yet to be developed. Here, we show that starting only from the target sequence of the input, and freely sampling both target and binding protein conformation, RFdiffusion can generate binders to IDPs and IDRs in a wide range of conformations. We use this approach to generate binders to the IDPs Amylin, C-peptide and VP48 in a range of conformations with Kds in the 3 -100nM range. The Amylin binder inhibits amyloid fibril formation and dissociates existing fibers, and enables enrichment of amylin for mass spectrometry-based detection. For the IDRs G3bp1, common gamma chain (IL2RG) and prion, we diffused binders to beta strand conformations of the targets, obtaining 10 to 100 nM affinity. The IL2RG binder colocalizes with the receptor in cells, enabling new approaches to modulating IL2 signaling. Our approach should be widely useful for creating binders to flexible IDPs/IDRs spanning a wide range of intrinsic conformational preferences.
Robust Effective Ground State in a Nonintegrable Floquet Quantum Circuit
Authors: Ikeda Tatsuhiko N. , Sugiura Sho , Polkovnikov Anatoli 
Published: July 2024

An external periodic (Floquet) drive is believed to bring any initial state to the featureless infinite temperature state in generic nonintegrable isolated quantum many-body systems in the thermodynamic limit, irrespective of the driving frequency Ω. However, numerical or analytical evidence either proving or disproving this hypothesis is very limited and the issue has remained unsettled. Here, we study the initial state dependence of Floquet heating in a nonintegrable kicked Ising chain of length up to L=30 with an efficient quantum circuit simulator, showing a possible counterexample: the ground state of the effective Floquet Hamiltonian is exceptionally robust against heating, and could stay at finite energy density even after infinitely many Floquet cycles, if the driving period is shorter than a threshold value. This sharp energy localization transition or crossover does not happen for generic excited states. The exceptional robustness of the ground state is interpreted by (i) its isolation in the energy spectrum and (ii) the fact that those states with L-independent ℏΩ energy above the ground state energy of any generic local Hamiltonian, like the approximate Floquet Hamiltonian, are atypical and viewed as a collection of noninteracting quasiparticles. Our finding paves the way for engineering Floquet protocols with finite driving periods realizing long-lived, or possibly even perpetual, Floquet phases by initial state design.

Published by the American Physical Society
2024