bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the health impact, health-system costs and cost-effectiveness of using TrueNat on stool samples compared to usual care for the diagnosis of paediatric tuberculosis in primary care settings: a modelling analysis
Authors: Mafirakureva Nyashadzaishe , Daniel Olugbenga Kayode , Olayinka Jamiu Olabamiji , Ochei Kingsley Chinedum , Klinkenberg Eveline , Ihesie Austin , Nongo Debby , Eneogu Rupert Amanze , Mwansasu Andwele , Elom Emeka Uga , Aderonke Agbaje Vivian , Dakum Patrick Patrick Sunday , Mensah Charles Olalekan , Odola Oluwafemi Christopher , Olayemi Abiola Oladotun , Faleye Emily Yemisi , Makinde Adekunle Omotoso , Dodd Peter J. 
Published: November 2024

AbstractThe World Health Organisation (WHO) recommends rapid molecular diagnostics to improve bacteriological confirmation of tuberculosis in children. TrueNat MTB, MTB Plus and MTB-RIF Dx assays (Molbio Diagnostics, India), recommended by WHO, hold potential as point-of-care tests in resource-limited settings. Using stool samples with these assays could enhance testing access, improve linkage to care, reduce costs, and increase cost-effectiveness over traditional methods. However, evidence on their costs and cost-effectiveness is limited and needed for informed policy decisions on adoption and scale up. We used a decision-tree analytic modelling approach, time-and-motion study, and routine data to estimate the potential impact of implementing stool-based TrueNat testing for the diagnosis of pulmonary tuberculosis in children within Nigerian primary healthcare settings on healthcare outcomes, resource use, health system costs, and cost-effectiveness relative to the standard of care (SoC). The cost per test was $13.06 (standard deviation; $0.77) for TrueNat and $16.25 (standard deviation; $1.34) for Xpert. For every 100 children with presumptive tuberculosis, the stool-based TrueNat testing intervention was projected to increase case detection rate by 29% (95% uncertainty interval [UI 9-48]) and bacteriological confirmation by 6% (95% UI 3-8). Diagnoses at primary health centres (PHC) would increase by 34% (95% UI 20-46), averting 7 (95% UI 2-12) deaths and 182 (95% UI 59-311) discounted DALYs. Although resource use and health system costs increased by $6,172 (95% UI -2,427-10,455) per 100 children, the incremental cost-effectiveness ratio of $34 per DALY averted suggests cost-effectiveness at thresholds of 0.5×GDP per capita. Implementing stool-based TrueNat testing has potential to increase access and reduce direct health system costs associated with the diagnosis of pulmonary tuberculosis in children in routine health care settings. Such an approach is likely to represent a good value for money compared to SoC.FundingUSAID
Global Lipidomic and Metabolomic Uncovers Blood Signatures of Left Ventricular Assist Devices for Heart Failure
Authors: Zhang Na , Chen Hao , Li Heping , Xu XiaoYu , Zhang Xuman , Hou Haitao , Han Zhifu , He Guowei , Zhang Yu 
Published: November 2024

AbstractBackgroundThe left ventricular assist device (LVAD) significantly improves the health of patients with chronic advanced heart failure (HF); however, its underlying molecular mechanisms remain unclear. This study aimed to develop an integrated plasma pseudo-targeted lipidomic and untargeted metabolomic strategy to provide insight into the early postoperative changes that occur in the global blood metabolome profile and determine whether these changes can be used to screen patients for LVAD installation.MethodsData was collected from 20 pairs of patients with HF before and after LVAD surgery and compared with 36 healthy subjects. Plasma metabolomic and lipidomic profiles were established by liquid chromatography-mass spectrometry and analyzed by multivariate statistics.ResultsA total of 49 lipids showed significant recovery after LVAD pump loading compared with before pump loading. Moreover, 144 differential metabolites and 21 pathways were identified from healthy control and patients with HF. Among which, 33 metabolites were differentially regulated between pre and post-LVAD samples (p < 0.05, FC > 2). Further analysis revealed differential regulation in two key pathways: fatty acid metabolism and methionine metabolism. Simultaneously, we identified S-adenosylmethionine, L-methionine, FFA (14:1), and FFA (16:1) as potential diagnostic markers for the prediction of LVAD efficacy in HF. In three postLVAD patients who died within one year, we observed a decrease in SM (24:0) and SM (22:0) immediately before LVAD implantation, indicating that these metabolites may predict a poor outcome. Furthermore, we demonstrated that PS (18:1/20:4) and canavaninosuccinate were significantly attenuated in postLVAD patients.ConclusionsOur findings provide preliminary evidence that LVAD therapy is associated with changes in the metabolomic and lipidomic profiles of patients with HF. It highlights the potential use of metabolomics as a tool to stratify LVAD patients based on the risk of adverse events. These findings may help to guide patient selection for advanced HF therapies and identify new HF therapeutic targets.Graphical Abstract
Supervised and self-directed technology-based dual-task exercise training programme for older adults at risk of falling – Protocol for a feasibility study
Authors: Mathur Prerna , Thomas Helen , Cooper Angela , Chechlacz Magdalena , Stathi Afroditi , Goodyear Victoria , Miller Caroline , Krauss Taylor , Ives Natalie , Magill Laura , Kinghorn Philip , Wilson Daisy , Chiou Shin-Yi 
Published: November 2024

AbstractFalls among older adults pose a significant public health challenge, as they lead to severe outcomes such as fractures and loss of independence. Research has shown that training cognitive function and balance simultaneously, termed Dual-Task (DT) training, improves mobility and reduces fall risks in older adults. This study aims to evaluate the feasibility and acceptability of a blended supervised and self-directed technology-based DT training programme for older adults who have high risk of falling. This is a single-arm, non-randomised feasibility study employing quantitative and qualitative methods. Fifty healthy adults aged 65 years or above will be recruited from the NHS primary and secondary care pathways and from the community. Participants will undergo supervised cognitive and balance DT training for 12 weeks, followed by self-directed DT training for an additional 12 weeks. The cognitive training will be delivered using a commercial mobile application (app) available from the AppStore or Google Play. The balance training will involve static (Marching on the spot, Tandem Stand, Hip Abduction & Extension, Squats, Tiptoe Stand, and Pendulum/Sideways Sway) and dynamic (Figure of Eight Walk, Walking Forwards and Backwards, Lunges, Functional Reach, Toe Tapping, Upper Limb Strength Exercises, and Side-Steps/Simple Grapevine) exercises focused on improving balance, postural stability and strength. Feasibility outcomes will be recruitment, adherence, usage of the app, and attrition. Outcomes measure data, that will be collected at baseline and at 24 weeks, includes the Timed-Up and Go (TUG) test (likely primary outcome in any future trial), along with self-reported questionnaires assessing cognition, fear of falling, quality of life, healthcare service usage, and the self-reported number of falls. Focus group interviews will be conducted with thirty participants and thirty healthcare professionals for in-depth exploration of the feasibility and acceptability of the DT training programme.Trial registration numberISRCTN15123197
Polygyny among men in Ghana: a population based cross-sectional study
Authors: Quartey Gladys , Padi Abigail , Dadzie Louis Kobina , Dzirasah King David , Aboagye Richard Gyan , Ahinkorah Bright Opoku , Seidu Abdul-Aziz 
Published: November 2024

AbstractBackgroundPolygyny has been practiced in many cultures around the world over the past couple of decades. Available evidence indicates that polygyny is practiced in more than 83% of the 849 cultures globally. Therefore, this study seeks to assess the prevalence and determinants of polygyny among men in Ghana.MethodsThis research is based on 1,892 married men using the 2014 Ghana Demographic and Health Survey (GDHS) data. Polygyny was the outcome variable. Multilevel mixed-effects logistic regression models were fitted to examine the factors associated with polygyny. The results were presented as adjusted odds ratio with 95% confidence interval.ResultsThe prevalence of polygyny was 8.8[7.5%-10.5%]. Men aged 45-59[aOR=7.01; 95%CI= [2.87,17.15] and 30-44 [aOR=4.36; 95%CI= [1.81,10.53] were more likely to engage in polygyny compared to those aged 15-29. Men in communities with high wealth status had higher odds of polygyny compared to those in communities with low wealth status [aOR=2.49; 95%CI= [1.22,5.09]. On the other hand, men with a secondary level of education [aOR=0.53;95%CI= [0.29,0.95] and those with comprehensive knowledge of HIV and AIDS [aOR=0.59;95%CI= [0.37,0.94] were less likely to engage in polygyny compared to those with no formal education and those without comprehensive HIV and AIDS knowledge.ConclusionThe study has contributed to knowledge on the prevalence and determinants of polygyny among men in Ghana. In Ghana, age, education, community wealth status, and knowledge of comprehensive HIV/AIDS are determinants of polygyny among men. Interventions to improve universal access to education and social protection policies are critical to reshaping socio-cultural practices and views that engender polygyny among men in Ghana. In addition, strengthening existing laws and policies is important in addressing the social challenges caused by polygamous unions. Furthermore, explorative studies must be conducted to identify the possible impact of polygamy on those who practice it.
Post-Critical Period Transcriptional and Physiological Adaptations of Thalamocortical Connections after Sensory Loss
Authors: Iyer Laxmi , Johnson Kory , Collier Sean , Koretsky Alan P. , Petrus Emily 
Published: November 2024

SummaryAbstract FigureGraphical AbstractUnilateral whisker denervation activates plasticity mechanisms and circuit adaptations in adults. Single nucleus RNA sequencing and multiplex fluorescence in situ hybridization revealed differentially expressed genes related to altered glutamate receptor distributions and synaptogenesis in thalamocortical (TC) recipient layer 4 (L4) neurons of the sensory cortex, specifically those receiving input from the intact whiskers after whisker denervation.Electrophysiology detected increased spontaneous excitatory events at L4 neurons, confirming an increase in synaptic connections. Elevated expression levels of Gria2 mRNA and functional GluA2 subunit of AMPA receptors at the TC synapse indicate the presence of stabilized and potentiated TC synapses to L4 excitatory neurons along the intact pathway after unilateral whisker denervation. These adaptations likely underlie the increased cortical activity observed in rodents during intact whisker sensation after unilateral whisker denervation. Our findings provide new insights into the mechanisms by which the adult brain supports recovery after unilateral sensory loss.
Viral susceptibility and innate immune competency ofCarollia perspicillatabat cells produced for virological studies
Authors: Gonzalez Victoria , Word Cierra , Guerra-Pilaquinga Nahomi , Mazinani Mitra , Fawcett Stephen , Portfors Christine , Falzarano Darryl , Kell Alison M. , Jangra Rohit K. , Banerjee Arinjay , Seifert Stephanie N. , Letko Michael 
Published: November 2024

ABSTRACTMultiple viruses that are highly pathogenic in humans are known to have evolved in bats. How bats tolerate infection with these viruses, however, is poorly understood. As viruses engage in a wide range of interactions with their hosts, it is essential to study bat viruses in a system that resembles their natural environment like bat-derivedin vitrocellular models. However, stable and accessible bat cell lines are not widely available for the broader scientific community. Here, we generatedin vitroreagents for the Seba’s short-tailed bat (Carollia perspicillata), tested multiple methods of immortalization, and characterized their susceptibility to virus infection and response to immune stimulation. Using a pseudotyped virus library and authentic virus infections, we show that theseC. perspicillatacell lines derived from a diverse array of tissues are susceptible to viruses bearing the glycoprotein of numerous orthohantaviruses, including Andes and Hantaan virus and are also susceptible to live hantavirus infection. Furthermore, stimulation with synthetic double-stranded RNA prior to infection with VSV and MERS-CoV induced a protective antiviral response, demonstrating the suitability of our cell lines to study the bat antiviral immune response. Taken together, the approaches outlined here will inform future efforts to developin vitrotools for virology from non-model organisms and theseC. perspicillatacell lines will enable studies on virus-host interactions in bats.
Early-Life Systemic Inflammation Modulate Microglia Phenotype to Slow Down Aβ Pathology in the 5xFAD Mouse Model of Alzheimer’s Disease
Authors: Yang Yiyi , García-Cruzado Marta , Zeng Hairuo , Wang Xinrui , Bachiller Sara , Camprubí-Ferrer Lluís , Bahatyrevich-Kharitonik Bazhena , Fernández-Calle Rosalía , Deierborg Tomas 
Published: November 2024

SummaryEarly infection in life has been implicated in increasing the risk for neurological disorders. Here we performed single-cell sequencing of microglia and monocytes from 6-month-old WT and 5xFAD mice subjected to one dose of LPS (1mg/kg) at postnatal day 9. We successfully mapped disease-associated microglia (DAM) and perivascular macrophages in our data and demonstrated a subpopulation of microglia that adopted a monocyte-like profile, marked by Lyz2, Tmsb10, Lgals1and Lgals3. This unique subset appeared in response to early systemic LPS challenge and AD pathology but diminished in the presence of double stimulus. Different cytokines were altered in the brain and periphery as seen using mesoscale plates. GM-CSF and MIP-1α levels were altered in an amyloid-β(Aβ)-dependent manner in hippocampus. MIP-1β and IFN-γ were altered upon early LPS stimulation. In the periphery, we found MMP-9 was significantly increased in serum samples from 5xFAD mice. Interestingly, early LPS stimulation significantly elevated TNF-α in serum from WT and 5xFAD mice, but was reduced in the hippocampus due to Aβ pathology. The LPS treatment in 5xFAD mice had a tendency to improve the short-term memory deficit. Taken together, we observed long-lasting effects from early life stress, including activation of inflammation in the periphery and brain through modulation of different signaling cascades.
Scents Modulate Anxiety Levels, but Electroencephalographic and Electrocardiographic Assessments Could Diverge from Subjective Reports
Authors: Morozova Marina , Gabrielyan Irina , Kleeva Daria , Efimova Victoria , Lebedev Mikhail 
Published: November 2024

AbstractScents could modulate anxiety levels, such as anxiety in a medical office. Here we investigated the impact of two scents on the subjective and physiological anxiety markers in the dental office environment, utilizing self-reported anxiety assessments alongside physiological assessment with electroencephalographic (EEG) and electrocardiographic (ECG) measurements. Lavender was the first tested scent with the previously reported calming effect. African stone was the second stimulus with a musky scent. Twenty healthy participants took part in scent exposure sessions. Anxiety levels were assessed using the State-Trait Anxiety Inventory (STAI), EEG-based theta, alpha, and beta power ratios, and heart rate variability (HRV) indices derived from ECG data. Lavender exposure significantly decreased self-reported anxiety whereas African stone reduced physiological indicators of anxiety. Namely, African stone exposure led to decreased theta and increased alpha power in the parietal-occipital EEG signals. Additionally, decreases were observed in low-frequency (LF) HRV power and total HRV power, reflecting lowered autonomic arousal. These findings support the potential effectiveness for olfactory interventions to aid in anxiety management within clinical environments, but draw attention to the issue of proper evaluation of anxiety. In particular, the difference between the subjective reports and traditional EEG and HRV markers indicates that anxiety involves a complexity of factors, which makes its treatment by scents challenging.
Iso-orientation bias of layer 2/3 connections: the unifying mechanism of spontaneous, visually and optogenetically driven V1 dynamics
Authors: Rózsa Tibor , Cagnol Remy , Antolík Ján 
Published: November 2024

AbstractFunctionally specific long-range lateral connectivity in layer 2/3 of the primary visual cortex (V1) supports the integration of visual information across visual space and shapes spontaneous, visual and optogenetically driven V1 activity. However, a comprehensive understanding of how these diverse cortical regimes emerge from this underlying cortical circuitry remains elusive. Here we address this gap by showing how the same model assuming moderately iso-orientation biassed long-range cortical connectivity architecture explains diverse phenomena, including (i) range of visually driven phenomena, (ii) modular spontaneous activity, (iii) the propagation of spontaneous cortical waves, and (iv) neural responses to patterned optogenetic stimulation. The model offers testable predictions, including presence of slower and iso-tropic spontaneous wave propagation in layer 4 and non-monotonicity of optogenetically driven cortical response to increasingly larger disk of illumination. We thus offer a holistic framework for studying how cortical circuitry governs information integration across multiple operating regimes.
Anatomical characterisation of somatostatin-expressing neurons belonging to the anterolateral system
Authors: Ma Wenhui , Polgár Erika , Dickie Allen C. , Hajer Mai Abu , Quillet Raphaëlle , Gutierrez-Mecinas Maria , Yadav Mansi , Hachisuka Junichi , Todd Andrew J , Bell Andrew M. 
Published: November 2024

ABSTRACTAnterolateral system (ALS) spinal projection neurons are essential for pain perception. However, these cells are heterogeneous, and there has been extensive debate about the roles of ALS populations in the different pain dimensions. We recently performed single-nucleus RNA sequencing on a developmentally-defined subset of ALS neurons, and identified 5 transcriptomic populations. One of these, ALS4, consists of cells that expressSst, the gene coding for somatostatin, and we reported that these were located in the lateral part of lamina V. Here we use a SstCremouse line to characterise these cells and define their axonal projections. We find that their axons ascend mainly on the ipsilateral side, giving off collaterals throughout their course in the spinal cord. They target various brainstem nuclei, including the parabrachial internal lateral nucleus, and the posterior triangular and medial dorsal thalamic nuclei. We also show that in the L4 segmentSstis expressed by ∼75% of ALS neurons in lateral lamina V and that there are around 120Sst-positive lateral lamina V cells on each side. Our findings indicate that this is a relatively large population, and based on projection targets we conclude that they are likely to contribute to the affective-motivational dimension of pain.
An antibiotic-free antimicrobial combination of bacteriocins and a peptidoglycan hydrolase:in vitroandin vivoassessment of its efficacy
Authors: Kranjec Christian , Oftedal Thomas F. , Ovchinnikov Kirill V. , da Silva Duarte Vinicius , Hermansen Simen , Kaus-Drobek Magdalena , Sabała Izabela , Porcellato Davide , Carlsen Harald , Kjos Morten 
Published: November 2024

AbstractMastitis is an inflammatory disease of the mammary gland commonly brought about by bac-terial pathogens that gain physical access to the glandular epithelium through the teat canal. In bovines, common mastitis-causing agents are environmental or pathogenic bacterial spe-cies, including staphylococci, streptococci, enterococci, and Gram-negative bacteria such asEscherichia coli. Current therapeutic strategies for bovine mastitis typically involve the ad-ministration of antibiotic formulations within the infected udder, possibly resulting in in-creased selection of antibiotic resistance and the accumulation of antibiotic residues within the milk. In this study, we sought to design an antibiotic-free antimicrobial formulation to treat bovine mastitis based on bacterial antimicrobial peptides (bacteriocins) and proteins (pepti-doglycan hydrolases). Using a combination ofin vitroassays with a range of bacteriocins, we show that the combination of the thiopeptide micrococcin P1 (MP1) and the lantibiotic nisin A (NisA) is a robust antimicrobial formulation that effectively inhibits the growth of bo-vine mastitis-derived bacteria, both in planktonic and biofilm-associated growth modes. The addition of AuresinePlus (Aur, a staphylococcus-specific PGH) further increased the antimi-crobial potency againstS. aureus. Furthermore, using two mouse models, a skin infection model and a mastitis model, we show that the combination MP1-NisA-Aur effectively inhibits methicillin-resistantS. aureus(MRSA)in vivo. We discuss the potential and challenges of using antibiotic-free antimicrobial combinations in the treatment of bacterial infections.
Body Size Variation and Sexual Dimorphism in Eleven Species of Venezuelan Anurans
Authors: Cañizales Israel 
Published: November 2024

ABSTRACTThis study investigates intra- and interspecific variation in snout–vent length (SVL) and abdominal width (AW) across 11 anuran species in Venezuela, revealing significant patterns of sexual size dimorphism (SSD) in seven species. Females exhibited larger SVL than males in most species (e.g.,Atelopus cruciger,Leptodactylus fuscus, and Phyllomedusa trinitatis), with mean SVL differences ranging from 4 to 15 mm (p< 0.05). This study provides the first reference AW values for these species, contributing novel data for morphometric studies. Four species (Boana punctata,Leptodactylus fuscus,Rhinella marina, andScinax rostratus) showed no significant differences in SVL or AW (p> 0.05), indicating limited SSD or monomorphism. Statistical analyses highlighted geographic variation in SVL, with female-biased SSD more pronounced in arboreal species and male-biased SSD associated with territorial, burrow-digging behaviors in terrestrial species (p< 0.05). These findings support Rensch’s rule, where SSD scales with body size: SSD decreases with increasing female size and increases with male-biased size. InL. fuscus, for instance, SVL values (males: 54.5 mm; females: 61.56 mm) exceeded reported ranges but lacked statistical significance (p= 0.595), highlighting substantial geographic and ecological influences. Directional asymmetry was evident in arboreal species, linked to their ecological adaptations for locomotion. Conversely, terrestrial species displayed larger size variation associated with competition and reproductive strategies. Statistical tests demonstrated the role of ecological traits, activity patterns, and reproductive pressures in shaping SSD (e.g.,p< 0.01 for differences in tree vs. ground-dwelling species). This study underscores the complexity of SSD, influenced by ecological, behavioral, and geographic factors. Morphometric indices validated here offer practical tools for future studies, requiring careful application across species, populations, and developmental stages. The results emphasize the ecological and evolutionary importance of body size variation and provide critical data for conservation efforts in Venezuelan anurans.