bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burden and Economic Impact of Respiratory Viral Infections in Adults Aged 60 and Older: A Focus on RSV
Authors: Peláez A. , Jimeno S. , Villarreal M. , Gil M. , Gutiérrez I. , Sanz M. , Natalini S. 
Published: January 2025

Background/ObjectivesRespiratory syncytial virus (RSV) represents a significant cause of acute respiratory infections (ARI) in adults aged 60 years and older, often leading to severe clinical out-comes and high healthcare costs. This study aimed to evaluate the clinical and economic burden of RSV compared to other ARI, focusing on specific age groups, comorbidities, and demographic factors.MethodsA retrospective observational study was conducted using electronic medical records of adults aged ≥60 years hospitalized for ARI, including RSV, in Spain. Direct costs related to hospitalizations, intensive care unit (ICU) admissions, and treatments were analyzed. The study also assessed demographic, clinical, and comorbidity-related factors influencing the economic burden.ResultsRSV infections resulted in significantly higher direct costs compared to other ARI, particularly in patients aged 70–80 years. Comorbidities such as asthma and smoking history were associated with increased costs in RSV cases. Although ICU costs were comparable between groups, hospitalizations for RSV required longer stays and more intensive treatments, amplifying the overall economic burden. Differences in costs by age and sex highlighted the need for tailored clinical management strategies.ConclusionsRSV poses a substantial economic and clinical burden on adults aged 60 years and older, particularly in those with comorbidities. Preventive measures, such as vaccination, could reduce healthcare costs and improve outcomes in this vulnerable population. These findings support the inclusion of RSV vaccines in immunization programs, especially in aging populations like Spain, to alleviate healthcare pressures during peak respiratory disease seasons.
Prognostic value of compact myocardial thinning in patients with left ventricular non-compaction
Authors: Gegenava Tea , Tukker Martijn , Caliskan Kadir , Hirsch Alexander , Manohar Ashish , Lee Seung-Pyo , Owens Anjali , Kwon Deborah H. , Ramchand Jay , Wheeler Matthew T. , Tang W. H. Wilson , Nieman Koen 
Published: January 2025

AbstractIntroductionLeft ventricular non-compaction (LVNC) can be associated with a wide spectrum of clinical presentations, ranging from asymptomatic to ventricular tachyarrhythmia (VT), heart failure (HF), and cerebrovascular accidents (CVA). In this multicenter study, we explored the associations between clinical and imaging characteristics and outcomes of patients with LVNC, and externally validated the predictive value of myocardial thinning identified on cardiac magnetic resonance imaging (CMR) as previously described.Methods214 adult patients (54% male, mean age 41±16 years) meeting the imaging criteria for LVNC were identified. Baseline clinical data, echocardiographic findings, and CMR characteristics were analyzed. Long-axis balanced steady-state free precession CMR sequences were used to assess myocardial thickness. Myocardial thinning was defined as a 50% or greater diameter reduction of the compacted myocardium compared to a contiguous segment. The primary endpoint was a composite of all-cause mortality, HF hospitalization, need of left ventricular assist device (LVAD) or heart transplant, cardiac resynchronization therapy (CRT), CVA/transient ischemic attacks (TIA), and VT and appropriate implantable cardioverter defibrillator (ICD) therapy.ResultsFocal myocardial thinning was observed in 42 patients (20%). Over a median follow-up period of 7 years (IQR, 4–10 years), 54 patients (24%) experienced a primary outcome (including all-cause mortality n=15 (7%), HF hospitalization/CRT n=33 (15%), CVA/TIA n=10 (5%), VT and appropriate ICD therapy n=14 (7%), LVAD/heart transplant n=3 (1.4%). Patients with myocardial thinning had more cumulative adverse events compared to those without myocardial thinning (chi-square = 29.516, log-rank < 0.001), even after matching for medical risk score. In a multivariate Cox regression model, myocardial thinning remained associated with outcomes: HR 3.052(95% CI: 1.569-5.937, p=0.001). When evaluating the incremental prognostic value of myocardial thinning over clinical and imaging characteristics, we observed that adding myocardial thinning added value to prediction models that included clinical and imaging features.ConclusionsThe presence of myocardial thinning is associated with adverse cardiovascular events in adult LVNC patients. Along with the medical risk score and other imaging variables, this feature enhances the risk stratification of individuals with LVNC. Incorporating myocardial thinning into medical risk assessments can improve the prediction and management of adverse outcomes in these patients.
Intussusceptive angiogenesis-on-a-chip: Evidence for transluminal vascular bridging by endothelial delamination
Authors: Staples Sabrina C.R. , Yin Hao , Sutherland Frances S.K. , Prescott Emma , Tinney Dylan , Hamilton Douglas W. , Goldman Daniel , Poepping Tamie L. , Ellis Christopher G. , Pickering J. Geoffrey 
Published: January 2025

AbstractIntussusceptive angiogenesis is an increasingly recognized vessel duplication process that generates and reshapes microvascular beds. However, the mechanism by which a vessel splits into two is poorly understood. Particularly vexing is formation of the hallmark transluminal endothelial cell bridge. How an endothelial cell comes to cross a flowing lumen rather than line it is enigmatic. To elucidate this, we used a microvessel-on-a-chip strategy, creating a micro-conduit coherently lined with flow-sensitive endothelial cells but in which transluminal bridges also formed. Bridge morphologies ranged from filamentous strand to multicellular columns with a central core. These bridge architectures were found to recapitulate those in microvessels in embryos, tumours, diseased organs, and the dermis of patients with limb-threatening ischemia. Time-lapse, multi-plane, 3D microscopy of the micro-physiologic conduit revealed that bridges arose from endothelial cells oriented orthogonal to flow that partially released from the wall while retaining attachments at the ends. This delamination process was blocked by hyperactivation of Rho and augmented by interventions that weaken cell-substrate interactions, including inhibiting non-muscle myosin II and blocking α5ß1 integrin but, interestingly, not αvß3 integrin. Thus, endothelial cells can leave their monolayer and transect a flowing lumen through controlled delamination. This previously unrecognized lumen entry program could explain the launch of intussusceptive angiogenesis and opens a framework for intervening.Significance StatementRapid generation of small blood vessels is vital for embryonic development and many diseases. An efficient means of creating a new microvessel is for an existing vessel to split into two, a process recognized for over 35 years. However, the cellular events underlying vessel splitting remain largely a mystery. The challenge is how to look inside a microvessel and capture transient events. We address this challenge using a microvessel-on-a-chip strategy. We discovered that select endothelial cells lining the wall can partially lift to transect the lumen. This resolves the paradox of an adhesion-dependent cell reaching across a pressurized lumen. It also reframes microvascular therapy considerations, including for diabetics with leg ulcers, a condition we show has hallmarks of microvessel splitting.
Thermodynamic Stability Modulates Chaperone-Mediated Disaggregation of α-Synuclein Fibrils
Authors: Fricke Celia , Kunka Antonin , Norrild Rasmus K. , Wang Shuang-Yan , Dang Thi Lieu , Wentink Anne S. , Bukau Bernd , Buell Alexander K. 
Published: January 2025

AbstractThe aggregation of the intrinsically disordered protein alpha-synuclein into amyloid fibrils and their subsequent intracellular accumulation are characteristic features of several neurodegenerative disorders, such as Parkinson’s disease. Currently, there are no curative treatment options available. In this study, we demonstrate that the thermodynamic stability of alpha-synuclein fibrils is a crucial factor influencing the efficiency with which they are disaggregated by the human chaperone system comprising HSP70, DNAJB1, and Apg2. We quantify the increasing stability of alpha-synuclein fibrils formed under four different solution conditions over a three-month incubation period. The chaperone system effectively disaggregates three out of the four fibril types, with varying efficiencies that correlate with their thermodynamic stability. The fibrils exhibit differential sensitivities to chaperone-mediated depolymerization, suggesting that both structural features and thermodynamic stability contribute to the susceptibility of alpha-synuclein fibrils to chaperone disaggregation. Our findings thus reveal a connection between the thermodynamic stability of fibrils and their susceptibility to chaperone-mediated disaggregation.
Endocrine modulation of cortical and retinal blood flow across the menstrual cycle
Authors: Wright Melissa E. , Crofts Andrew , Davies Saajan , Chandler Hannah L. , Driver Ian , Germuska Michael , Giarratano Ylenia , Rashid Darwin , Bernabeu Miguel O. , Terry Louise , Steventon Jessica J. , Murphy Kevin 
Published: January 2025

AbstractThe ovarian hormones, oestrogen and progesterone, have vaso- and neuroprotective effects, likely due to interactions with the cerebrovascular system. This study investigates their neuroendocrine influence on a range of cerebral and retinal vascular functions across a healthy menstrual cycle.Twenty-six healthy, menstruating females completed imaging sessions and assessment of circulating hormone levels during their early follicular, late follicular, and mid-luteal phase (1-4, 10-12 and 20-22 days after menses onset). Cerebral blood flow (CBF), arterial arrival time (AAT), global oxygen extraction fraction (OEF), cerebrovascular metabolic rate of oxygen (CMRO2), carotid artery radius and carotid pulsatility index (PI) were measured using 3T MRI. Retinal vessel density and blood flow resistance were assessed with optical coherence tomography angiography (OCT-A).Assessed with linear models, increased oestradiol was related to increased global CBF (χ2(1)=35.05; p=3.2×10-9) and increased AAT (χ2(1)=5.87; p=0.015). Increased progesterone was associated with increased global CBF (χ2(1)=13.00; p=0.0003). In the retina, a relationship was found between oestradiol and decreased retinal blood flow resistance (χ2(1)=5.28; p=0.0215), which was primarily driven by centrally localised vessels.This study finds that circulating oestrogen increases blood flow in the eye and brain, while progesterone significantly impacts the brain alone. These effects suggest a potential pathway for neuroprotective mechanisms.
Voice identity invariance by anterior temporal lobe neurons
Authors: Giamundo M. , Trapeau R. , Thoret E. , Renaud L. , Brochier T. G. , Belin P. 
Published: January 2025

AbstractThe ability to recognize speakers by their voice despite acoustical variation plays a significant role in primate social interactions. While neurons in the macaque anterior temporal lobe (ATL) show invariance to face viewpoint, whether they also encode abstract representations of caller identity is not known. Here we show that neurons in the voice-selective ATL of two macaques show invariance to voice identity via dynamic representations that minimize within-caller neuronal distances while maintaining distinct neural trajectories for different individuals. A small proportion of highly identity-selective neurons plays a central role although less selective neurons are also informative. Our findings provide a neural basis for voice identity recognition in primates and highlight the ATL as a key hub for integrating perceptual voice features into higher-level identity representations.
EngineeringSaccharomyces cerevisiaefor growth on xylose using an oxidative pathway
Authors: Tanaka Kenya , Yukawa Takahiro , Bamba Takahiro , Wakiya Miho , Kumokita Ryota , Jin Yong-Su , Kondo Akihiko , Hasunuma Tomohisa 
Published: January 2025

AbstractThe fermentative production of valuable chemicals from lignocellulosic feedstocks has attracted considerable attention. AlthoughSaccharomyces cerevisiaeis a promising microbial host, it lacks the ability to efficiently metabolize xylose, a major component of lignocellulosic feedstocks. The xylose oxidative pathway offers advantages such as simplified metabolic regulation and fewer enzymatic steps. Specifically, the pathway involves the conversion of xylose into 2-keto-3-deoxy-xylonate, which can be channeled into two distinct pathways, the Dahms pathway and the Weimberg pathway. However, the growth of yeast on xylose as the sole carbon source through the xylose oxidative pathway has not been achieved, limiting its utilization. We successfully engineeredS. cerevisiaeto metabolize xylose as its sole carbon source via the xylose oxidative pathways, achieved by enhancing enzyme activities through iron metabolism engineering and rational enzyme selection. We found that increasing the supply of the iron-sulfur cluster to activate the bottleneck enzyme XylD byBOL2disruption andtTYW1overexpression facilitated the growth on xylose and the production of ethylene glycol at 1.5 g/L via the Dahms pathway. Furthermore, phylogenetic analysis of xylonate dehydratases led to the identification of a highly active homologous enzyme. A strain possessing the Dahms pathway with this highly active enzyme exhibited reduced xylonate accumulation. Furthermore, the introduction of enzymes based on phylogenetic tree analysis allowed for the utilization of xylose as the sole carbon source through the Weimberg pathway. This study highlights the potential of iron metabolism engineering and phylogenetic enzyme selection for the development of non-native metabolic pathways in yeast.Key points1.5 g/L ethylene glycol was produced via Dahms pathway inS. cerevisiae.Enzyme activation enabled growth on xylose via both the Dahms and Weimberg pathways.Tested enzymes in this study may expand application of xylose oxidative pathway.
Multispecies relations shape bird-feeding practices
Authors: Aivelo Tuomas , Aulio Mikko , Enström Johanna , Deshpande Purabi , Haukka Anna , Lähdesmäki Heta , Rönkä Katja , Santangeli Andrea , Väkkärä Virpi , Lehikoinen Aleksi , Thorogood Rose , Kervinen Anttoni 
Published: January 2025

AbstractWhile humans often feed birds in their backyards, there is growing awareness that this has positive and negative effects on local biodiversity. Whether the observed species assemblage shapes human activities has, however, rarely been investigated. We analyzed 15,088 open-ended answers from 9,473 Finnish respondents about why they have increased or reduced feeding birds. They mentioned 58 avian and non-avian species linked to changed practices. The main reasons for change were 1) respondent’s relation to non-human species, 2) respondent’s relation to other humans and 3) relations between non-human species. Most taxa and reasons could lead to both increase or decrease in feeding, although the direction was context-dependent. We suggest that bird-feeding is an interactive process where the species community strongly affects feeding practices, which in turn can affect community composition. Recognising this process is crucial for understanding the effects of bird-feeding on both humans and nature and providing more nuanced guidance.
Cryo-EM Structure of the relaxosome, a complex essential for bacterial mating and the spread of antibiotic resistance genes
Authors: Williams Sunanda M. , Raffl Sandra , Kienesberger Sabine , Ilangovan Aravindan , Zechner Ellen L. , Waksman Gabriel 
Published: January 2025

AbstractBacterial mating, or conjugation was discovered nearly 80 years ago as a process transferring genes from one bacterial cell (the donor) to another (the recipient). It requires three key multiprotein complexes in the donor cell: a DNA-processing machinery called the relaxosome, a double-membrane spanning type 4 secretion system (T4SS), and an extracellular appendage termed pilus. While the near-atomic resolution structures of the T4SS and pilus are known, that of the relaxosome is not1–3. Here, we describe the cryo-EM structure of the fully assembled relaxosome encoded by the paradigm F plasmid in two different states corresponding to distinct functional steps along the DNA processing reaction. By varying the structures of model DNAs we delineate conformational changes required to initiate conjugation. Mutational studies of the various protein-protein and protein-DNA interaction hubs suggest a complex highly sensitive to trigger signals, that could arise from cell-to-cell contacts with recipient cells.
StreptoCAD: An open-source software toolbox automating genome engineering workflows in streptomycetes
Authors: Levassor Lucas , Whitford Christopher M. , Petersen Søren D. , Blin Kai , Weber Tilmann , Frandsen Rasmus J. N. 
Published: January 2025

AbstractStreptomycetes hold immense potential for discovering novel bioactive molecules for applications in medicine or sustainable agriculture. However, high-throughput exploration is hampered by the currentStreptomycesgenetic engineering methods that involve the manual design of complex experimental molecular biological engineering strategies for each targeted gene. Here, we introduceStreptoCAD, an open-source software toolbox that automates and streamlines the design of genome engineering strategies inStreptomyces,supporting various CRISPR-based and gene overexpression methods. Once initiated, StreptoCAD designs all necessary DNA primers and CRISPR guide sequences, simulates plasmid assemblies (cloning) and the resulting modification of the genomic target(s), and further summarizes the information needed for laboratory implementation and documentation. StreptoCAD currently offers six design workflows, including the construction of overexpression libraries, base-editing, including multiplexed CRISPR-BEST plasmid generation, and genome engineering using CRISPR-Cas9, CRISPR-Cas3, and CRISPRi systems. In addition to automating the design process, StreptoCAD further secures compliance with the FAIR principles, ensuring reproducibility and ease of data management via standardized output files. To experimentally demonstrate the design process and output of StreptoCAD, we designed and constructed a series of gene overexpression strains inStreptomyces Gö40/10, underscoring the tool’s efficiency and user-friendliness. This tool simplifies complex genetic engineering tasks and promotes collaboration through standardized workflows and design parameters. StreptoCAD is set to transform genome engineering inStreptomyces, making sophisticated genetic manipulations accessible for all and accelerating natural product discovery.Graphical abstract
Genome-wide association analyses in dairy heifers highlight genes overlapping with mouse and human fertility and human health traits
Authors: Marrella Mackenzie A. , Schettini Gustavo P. , Morozyuk Michael , Walsh Allison , Cockrum Rebecca , Biase Fernando H. 
Published: January 2025

AbstractHeifer Infertility and disease are important challenges in dairy cattle production. We investigated genetic differences between Holstein heifers with varying fertility potential and health. We carried out a genome-wide association analysis comparing heifers that conceived at first insemination against those requiring multiple attempts or failing to become pregnant, as well as heifers culled due to health issues. There were 12 significant SNPs (P<5x10-5) associated with fertility and 35 SNPs associated with health traits. There were 166 significant SNPs when infertile, sub-fertile and animals culled due to health issues were grouped. Two SNPs identified in the analysis of infertility were found nearNUFIP1and withinTENM4genes, both genes are linked to embryonic lethality in mouse knockouts. Follow-up CRISPR-Cas9 mediated disruption ofNUFIP1significantly (P<0.05) reducedin vitroblastocyst development in cattle embryos, whileTENM4editing did not alterin vitroblastocyst development. Additionally, SNPs overlapped with previously identified reproduction-related QTL (CNTN4,DLG2,PARP10,PRICKLE,TMEM150B) or health-related QTL (FAM162A,PARP10). We also identified genes within or near genes previously associated with age at menarche (CADM2, DLG2,FHIT,LSAMPandTENM4) or lung function or pulmonary diseases (ASCC2,BCAS3,BTBD9,CADM2,CNTN4,CPEB4,CTNNA2,DEUP1,DGKH,DLG2,ENOX1,EPHB1,ERC2,ERGIC1,EYA2,FAM162A,FGF18,FHIT,GRID1, KCNIP4,LINGO2,LRMDA,MALRD1,NEBL,PLA2G6,PLXDC2,PRPF18,SLC8A1,TEAD4,TSPAN9) in humans. These results further support genetic components of fertility and health in cattle. The findings also show overlapping genetic architecture between fertility and health traits, with a degree of conservation across mammals.Summary sentenceSeveral genetic variants that influence female fertility and health in cattle were identified, and many genes harboring or near significant polymorphisms are common to equivalent phenotypes in mice and humans.
Spatial Transcriptomics Reveals Expression Gradients in Developing Wheat Inflorescences at Cellular Resolution
Authors: Long Katie A. , Lister Ashleigh , Jones Maximillian R. W. , Adamski Nikolai M. , Ellis Rob E. , Chedid Carole , Carpenter Sophie J. , Liu Xuemei , Backhaus Anna E. , Goldson Andrew , Knitlhoffer Vanda , Pei Yuanrong , Vickers Martin , Steuernagel Burkhard , Kaithakottil Gemy G. , Xiao Jun , Haerty Wilfried , Macaulay Iain C. , Uauy Cristobal 
Published: January 2025

AbstractThe diversity of plant inflorescence architectures is specified by gene expression patterns. In wheat (Triticum aestivum), the lanceolate-shaped inflorescence (spike) is defined by rudimentary spikelets at the base which initiate first but subsequently lag in development compared with central spikelets. While previous studies identified gene expression differences between central and basal inflorescence sections, the spatio-temporal dynamics and gradients along the apical-basal axis remain poorly resolved due to bulk tissue-level techniques. Here, using spatial transcriptomics, we profiled 200 genes across four stages of wheat inflorescence development to cellular resolution. Cell segmentation and unsupervised clustering identified 18 expression domains and their enriched genes, revealing dynamic spatio-temporal organisation along the apical-basal axis of the inflorescence. Along this axis, we uncovered distinct and spatially coordinated gene expression gradients patterning meristems prior to the visible delay in basal spikelet development. This study demonstrates the potential for spatial transcriptomics time-series to advance plant developmental biology.