bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-dimensional quantitative micro-elastography reveals alterations in spatial elasticity patterns of follicles and corpora lutea in murine ovaries during ageing
Authors: Jaeschke Anna , Hepburn Matt S. , Mowla Alireza , Kennedy Brendan F. , Chan Chii Jou 
Published: October 2024

SummaryFibrosis and tissue stiffening are hallmarks of ovarian ageing, linked to a decrease in fertility. However, the lack of three-dimensional (3D) characterization of ovary elasticity limits our understanding of localized elasticity patterns and their connection to the tissue composition. Here, we developed an integrated approach to link ovarian tissue elasticity, volume, and cell-matrix composition using quantitative micro-elastography (QME), a label-free, non-invasive approach to study the 3D microscale elasticity in conjunction with immunofluorescence microscopy. QME revealed distinct spatial elasticity patterns in ovarian compartments, namely follicles and corpora lutea (CLs), and local elasticity alterations in different age cohorts. For example, CL elasticity significantly increased during ovarian ageing while follicle elasticity changed minimally. CLs showed size-dependent elasticity changes, while follicles exhibited distinct spatial variations in elasticity correlated with the emergence of theca cell layers during follicle development. These findings have the potential to guide the development of novel diagnostic tools and identify therapeutic targets, improving women’s reproductive health and longevity.Graphical Abstract
Neuregulin-1 Attenuates Myocardial Ischemia/Reperfusion Injury by Activating the UCP2/PINK1/LC3B-mediated Mitophagy
Authors: Li Xin-Tao , Li Xin-Yue , Tian Tian , Yang Wen-He , Cheng Yi , Su Kai , Lu Xi-Hua , Jin Mu , Xue Fu-Shan 
Published: October 2024

AbstractBACKGROUNDIschemia/reperfusion (I/R) injury may significantly affect the treatment outcomes and prognosis of patients with acute myocardial infarction following coronary artery recanalization. Available evidence suggests that neuregulin-1 (NRG-1) can provide a protection against myocardial I/R injury and is involved in various cardioprotective interventions by potential regulation of mitophagy. However, the molecular mechanisms linking NRG-1 and mitophagy remain to be clarified. This experiment aimed to determine whether NRG-1 postconditioning attenuated myocardial I/R injury through the regulation of mitophagy and to explore the underlying mechanisms.METHODBoth anin vivomyocardial I/R injury model of rats and anin vitrohypoxia/reoxygenation (H/R) model of H9C2 cardiomyocytes were applied. NRG-1 treatment was conducted immediately after I/R or H/R intervention. In thein vivoexperiment, cardioprotective effects of NRG-1 were determined by infarct size, cardiac enzyme and histopathologic examinations. The potential downstream pathways and molecular targets of NRG-1 were screened by the RNA sequencing and the Protein-Protein Interaction Networks (PPI). The expression levels of mitochondrial uncoupling protein 2 (UCP2) and mitophagy-related protein in both the I/R myocardium and H/R cardiomyocytes were measured by immunofluorescence staining and Western blots. The activation of mitophagy was observed with the transmission electron microscopy (TEM) and JC-1 staining.RESULTSThe KEGG and GSEA analyses showed that the mitophagy-related pathways were enriched in the I/R myocardium treated with NRG-1, and UCP2 exhibited a significant correlation between mitophagy and interaction with PINK1. Meanwhile, the treatment with mitophagy inhibitor Mdivi-1 significant eliminated the cardioprotective effects of NRG-1 postconditioningin vivo, and the challenge with UCP2 inhibitor genipin could also attenuate the activating effect of NRG-1 postconditioning on mitophagy. Consistently, thein vitroexperiment using H9C2 cardiomyocytes showd that NRG-1 treatment significantly up-regulated the expression levels of UCP2 and mitophagy-related proteins, and activated the mitophagy, whereas the challenge with small interfering RNA (siRNA)-mediated UCP2 knockdown abolished the effects of NRG-1.CONCLUSIONSNRG-1 postconditioning can produce a protection against the myocardial I/R injury by activating mitophagy through the UCP2/PINK1/LC3B signaling pathway.
rbfox1loss in zebrafish drives HPI axis hyperactivation viabdnf/trkb2pathway and allostatic overload during later life
Authors: Leggieri Adele , García-González Judit , Hosseinian Saeedeh , Ashdown Peter , Anagianni Sofia , Wang Xian , Havelange William , Fernàndez-Castillo Noèlia , Cormand Bru , Brennan Caroline H. 
Published: October 2024

ABSTRACTMutations in theRBFOX1gene are associated with psychiatric disorders but how RBFOX1 influences psychiatric disorder vulnerability remains unclear. Recent studies showed that RBFOX proteins mediate the alternative splicing of PAC1, a critical HPA axis activator. Further, RBFOX1 dysfunction is linked to dysregulation of BDNF/TRKB, a pathway promoting neuroplasticity, neuronal survival, and stress resilience. Hence, RBFOX1 dysfunction may increase psychiatric disorder vulnerability via HPA axis dysregulation, leading to disrupted development and allostatic overload. To test this hypothesis, we generated a zebrafishrbfox1loss-of-function (LoF) line and examined behavioural and molecular effects during development. We found thatrbfox1LoF mutants exhibited hyperactivity, impulsivity and heightened arousal, alongside alterations in proliferation – traits associated with neurodevelopmental and stress-related disorders. In adults, loss ofrbfox1function led to decreased fertility and survival, consistent with allostatic overload. At the molecular level, at larval stagesrbfox1LoF disrupted the expression ofbdnf,trkb2, pac1a-hopand HPI axis genes. Pharmacological intervention targeting TRKB restored HPI axis andbdnf/trkb2gene expression. In adults, dysregulation ofbdnf/trkb2and HPI axis genes was only seen following acute stress exposure. Our findings revealed a fundamental role for RBFOX1 in integrating stress responses through its regulation of BDNF/TRKB and neuroendocrine signalling. By uncovering how RBFOX1 modulates stress adaptation from development to adulthood, our study provides novel insights into the molecular basis of stress resilience and psychiatric disease vulnerability, suggestingRBFOX1loss predisposes to psychiatric diseases through HPA axis hyperactivation during development, impairing adaptation and heightening vulnerability to allostatic overload in later life.
Anxious/depressed individuals exhibit disrupted frontotemporal synchrony during cognitive conflict encoding
Authors: Shekara Aniruddha , Ross Alexander , Soper Daniel J. , Paulk Angelique C. , Cash Sydney S. , Shear Paula K. , Sheehy John P. , Basu Ishita 
Published: October 2024

AbstractAnxiety and depressive disorders are associated with cognitive control deficits, yet their underlying neural mechanisms remain poorly understood. Here, we used high-resolution stereotactic EEG (sEEG) to determine how anxiety and/or depression modulates neural and behavioral responses when cognitive control is engaged in individuals with medically refractory epilepsy undergoing sEEG monitoring for surgical evaluation.We analyzed sEEG data recorded from frontotemporal regions of 29 participants (age range: 19-55, mean age: 35.5, female: 16/29) while they performed a Multi-Source Interference Task (MSIT) designed to elicit cognitive conflict. Neurobehavioral interviews, symptom rating scales, and clinical documentation were used to categorize participants as demonstrating anxiety and/or depression symptoms (A/D, n=13) or as epilepsy controls (EC, n=16). Generalized linear mixed-effects (GLME) models were used to analyze behavioral and neural data. Models of oscillatory power were used to identify brain regions within conflict-encoding networks in which coherence and phase locking values (PLV) were examined in A/D and EC.A/D participants demonstrated a greater conflict effect (response time slowing with higher cognitive load), without impairment in response time (RT) or accuracy compared to EC. A/D participants also showed significantly enhanced conflict-evoked theta (4-8Hz) and alpha (8-15Hz) power in the dorsolateral prefrontal cortex (dlPFC) and amygdala as well as widespread broadband activity in the lateral temporal lobe (LTL) compared to EC. Additionally, theta coherence and PLV between dlPFC-LTL and dlPFC-amygdala were reduced by conflict in A/D.Our findings suggest individuals with anxiety/depression symptoms exhibit heightened frontotemporal oscillatory activity and disrupted frontotemporal synchrony during cognitive conflict encoding, which may indicate a greater need for cognitive resources due to ineffective cognitive processing. These results highlight a potential role of frontotemporal circuits in conflict encoding that are altered in anxiety/depression, and may further inform future therapeutic interventions aimed at enhancing cognitive control in these populations.
Disease-Modifying, Neuroprotective Effect of N-acetyl-L-leucine in Adult and Pediatric Patients with Niemann–Pick disease type C
Authors: Patterson Marc , Ramaswami Uma , Donald Aimee , Foltan Tomas , Gautschi Matthias , Hahn Andreas , Jones Simon , Kolnikova Miriam , Arash-Kaps Laila , Park Julien , Reichmannová Stella , Walterfarng Mark , Wibawa Pierre , Rohrbach Marianne , Martakis Kyriakos , Bremova-Ertl Tatiana , Gissen P. 
Published: October 2024

AbstractBackgroundThe phase 3 randomized, placebo-controlled, crossover trial, IB1001-301, comparing N-acetyl-L-leucine (NALL) with placebo for the treatment of Niemann-Pick disease Type C (NPC) after 12 weeks met both its primary and secondary endpoints. In an open-label Extension Phase (EP) follow-up data have been obtained to evaluate the long-term effects of NALL for NPC. Here, we report on the safety and efficacy after 12 and 18 months of extended follow-up.MethodsIn the ongoing EP, pediatric and adult NPC patients received treatment with orally administered NALL 2-3 times per day in three tiers of weight-based dosing. The primary endpoint was the modified 5-domain Niemann-Pick disease type C Clinical Severity Scale (5-Domain NPC-CSS) (range 0-25 points; lower score representing better neurological status). Comparisons were made to the expected annual trajectory of decline (i.e. disease progression) on the 5-domain NPC-CSS established in published natural history studies. Analyses were also performed on exploratory endpoints including the 15-domain and 4-domain NPC-CSS and Scale for Assessment and Rating of Ataxia (SARA) scale.ResultsA total of 54 patients aged 5 to 67 years have been enrolled in the EP. After 12 months, the mean (SD) change from baseline on the 5-domain NPC-CSS was -0.32 (2.43) with NALL versus 1.5 (3.16) in the historical cohort (95% Confidence Interval, -3.11 to -0.53; p=0.007), corresponding to a 121% reduction in annual disease progression. After 18 months, the mean (SD) change was -0.067 (2.94) with NALL versus 2.25 (4.74) in the historical cohort (95% Confidence Interval, -4.17 to -0.46; p=0.017). The results of the 15-domain and 4-domain NPC-CSS were consistent with the primary analysis. The improvements in neurological signs and symptoms demonstrated in the Parent Study’s primary SARA endpoint were sustained over the long-term follow-up. NALL was well-tolerated, and no treatment-related serious AEs occurred.ConclusionIn patients with NPC, treatment with NALL after 12 and 18 months was associated with a significant reduction in disease progression, demonstrating a disease-modifying, neuroprotective effect.Trial Registration InformationThe trial is registered withClinicalTrials.gov(NCT05163288; registered 06-Dec-2021), EudraCT (2021-005356-10). The first patient was enrolled into the EP on 08-Mar-2023.
Exploring intersectional determinants of, and interventions for, low uptake of human papillomavirus vaccine in Sub-Saharan Africa: A scoping review protocol
Authors: Kailemia Peter N , Mukami Victoria N 
Published: October 2024

ABSTRACTIntroductionCervical cancer is the most diagnosed cancer and the leading cause of cancer death in 36 low and middle-income countries with the majority being located in sub-Saharan Africa (SSA), South America, and South Eastern Asia. The highest regional incidence and mortality occur in SSA. Despite the high efficacy and cost-effectiveness of the HPV vaccine in preventing cervical cancer, its uptake remains unacceptably low in SSA. This scoping review aims to integrate evidence from SSA on social determinants of HPV vaccine uptake with complementary evidence on interventions to promote its uptake.Methods and analysisThe proposed review will be conducted following the guidelines by the Joanna Briggs Institute Scoping Review Methodology Group. Additionally, sequential explanatory design will guide the integration ofdeterminants evidencewithinterventions evidence. This scoping review will be reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) checklist. Five databases, PubMed/MEDLINE, LIVIVO, Google Scholar, BASE (Grey Literature), Preprints databases (e.g. OSF and MedRxiv), and African Journals Online (AJOL) will be searched, with results limited to English language publications and those published from 2006 to 2024. Two forms will be used for data extraction from the determinants and interventions studies by two independent reviewers. A narrative summary of evidence from the both determinants and interventions studies will be conducted. Furthermore, a multi-level analysis will be conducted to explore the intersections of determinants across socioecological levels of health behaviour. A further integrative cross-study analysis of results from determinants and interventions studies will be conducted where the determinants evidence will be used to interrogate the intervention evidence. Data will be presented in tables and matrices.Ethics and disseminationNo ethical approval will be required for this study because it will be based on data collected from publicly available records. The review results will be disseminated widely through a peer-reviewed publication and other forums such as workshops, conferences, and meetings with local health administrators, policymakers and other wider stakeholder engagements.This protocol has been registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/5JKZ8)
Proportional recovery in mice with cortical stroke
Authors: Kalantari Aref , Hambrock Carolin , Grefkes Christian , Fink Gereon R. , Aswendt Markus 
Published: October 2024

AbstractThe proportional Recovery Rule (PRR) has been frequently used to predict recovery of lost motor function in acute stroke patients. However, it still needs to be explored whether the same concept applies to preclinical, i.e. animal models of stroke recovery. To address this question, we investigated behavioral data from 125 adult male C57Bl/6J mice with photothrombotic strokes in the sensorimotor cortex. Lesion size and location were determined in the first week using in vivo T2-weighted MRI. Motor recovery was evaluated repeatedly over four weeks using the cylinder, grid walk, and rotating beam test. Recovery trajectories were analyzed using a newly formulated Mouse Recovery Rule (MRR), comparing it against the traditional PRR. Initial findings indicated variable recovery patterns, which were separated using a stepwise linear regression approach resulting in two clusters: 47% PRR and 53% MRR. No significant correlation was found between recovery patterns and lesion size or location, suggesting that other biological factors drive individual differences in recovery. Of note, in the MRR cluster, animals recovered to 90% of their initial behavioral state within the first four weeks post-stroke, which is higher than the 70% recovery usually reported in human PRR studies. This study demonstrates the complexity of translating the PRR to stroke recovery models in mice and underscores the need for species-specific recovery models. Our findings have implications for designing and interpreting therapeutic strategies for stroke recovery in preclinical settings, with the potential to improve the predictive accuracy of stroke recovery assessments.
Identifying sexually dimorphic circulating microRNAs in gonochoristic and hermaphroditic marine fish species
Authors: Geffroy Benjamin , Houdelet Camille , Blondeau-Bidet Eva , Mialhe Xavier , Bajek Aline , Falguière Jean-Claude , Guiguen Yann , Bobe Julien 
Published: October 2024

AbstractIn many fish species, males and females are hard to distinguish at the juvenile stage and size differences appear during maturation, often favoring females. Molecular tools for sexing live fish would benefit aquaculture, fisheries, and conservation research. Here we aimed to explores to what extent circulating microRNAs (miRNAs) can decipher phenotypic males from phenotypic females in gonochoristic fish species (the European seabassDicentrarchus labrax, the TurbotScophthalmus maximus, the Red drumSciaenops ocellatus, and the Blue RunnerCaranx crysos) as well as sexual stages in a protandrous hermaphrodite species (the Gilthead seabreamSparus aurata). We collected and extracted total RNA from 258 plasma samples, of which 96 samples with satisfactory RNA quality were sequenced using small RNA-seq. Circulating miRNAs detected in the plasma allowed to easily discriminate species, but some miRNAs were significantly correlated to one sex, independently of the species. In immature fishes, 3 miRNAs: miR-21a-3p, miR-18a-3p, and miR-29-1a-5p were overexpressed in females compared to males, while in mature fish, miR-21a-3p exhibited an opposite pattern. In the Gilthead seabream, we detected that both the miR-21a-3p and the miR-125b-2/3-5p were likely involved in the sexual transition from male to female. A complementary analysis on the 3′UTR sequences of all fish species allowed to predict potential mRNA targets of those two miRNAs, some of them being particularly relevant regarding sexual development (i.e. wnt4, esrrb, esrrga and hsd17b1). The identification of miRNAs like miR-21a-3p and miR-125b-2/3-5p as potential sex markers could offer a new, poorly-invasive method to monitor sex and developmental stages in fishes.
Confronting decisions related to the termination or continuation of doctoral supervision: a supervisor perspective
Authors: Massyn Liezel , Wichmann-Hansen Gitte , Areskoug Josefsson Kristina 
Published: October 2024

Purpose
This paper explores theoretical perspectives on supervisors' pedagogical dilemmas when deciding whether to terminate or continue problematic supervision relationships. This paper aims to unravel the complexities and challenges inherent in such decision-making processes while also discussing potential support mechanisms for supervisors.

Design/methodology/approach
Adopting a reflective narrative approach, this paper presents a fictional narrative to illustrate the intricacies of doctoral supervision. The narrative is divided into three parts, each followed by an analysis rooted in theoretical perspectives.

Findings
This article offers guidelines across individual, departmental and organisational levels to address critical moments in doctoral supervision. By incorporating various strategies and perspectives, it helps to understand the dilemmas that supervisors may encounter. A decision-making support guide is also provided to suggest ways of handling these challenging situations.

Practical implications
Drawing from theoretical perspectives, this paper offers practical solutions. A supervision support guide is developed to help establish support mechanisms at different levels, assisting supervisors in managing critical moments in doctoral supervision.

Originality/value
Addressing a rarely discussed issue, this paper highlights the complexity of supervisors' decisions regarding the termination of PhD students. It not only sheds light on these difficult choices but also offers practical guidelines for supervisors navigating such scenarios.
Genetics, emotion and care: Navigating future reproductive decisions in families of children with rare genetic conditions
Authors: Coveney Catherine , Salem Basma 
Published: October 2024

AbstractLittle is known regarding the future reproductive decision‐making of parents of children with rare genetic conditions. Our research draws on data from an online survey and qualitative photo‐elicitation interviews with families living with Noonan Syndrome. We demonstrate how genetic knowledge and prenatal genetic testing become embedded in reproductive practices. Yet the idea of using selective genetic technologies to influence reproductive outcomes remains highly emotive. Our analysis reveals that for these parents, the rationalities of reproduction, although technologised and biomedicalised, remain centred on caring for their disabled child. Genetic subjectivities become entangled with responsibilities of care‐giving and emotion tied to the realities of living with disability. We argue that for these parents, reproductive decisions are relational and affective, situated within families and communities and shaped by access to emotional, financial, physical and temporal resources. Our findings provide new insights into the ontologies of selective genetic technologies and reproductive governance in families living with disability.
Modeling and chewing parameters calibration of Euryale ferox based on discrete element method
Authors: Ben Zongyou , He Jinwei , Shi Jiahui , Leng Hongni , Fu Zihao , Zheng Rongmin , Bai Yu 
Published: October 2024

AbstractEuryale ferox was chosen for this study to examine its mechanical properties during chewing. Experiments and the discrete element method were used to conduct the study. Initially, the intrinsic and contact parameters of E. ferox were established through physical tests. The maximum compressive force of breakage and chewing mechanical properties (hardness, springiness, and chewiness) were measured using a texture profile analyzer (TPA). A Hertz–Mindlin with bonding model of the E. ferox was constructed. Optimal values for significant factors, including the normal stiffness per unit area, shear stiffness per unit area, and bonding radius, were obtained through single‐factor, Plackett–Burman, steepest ascent, and Box–Behnken response surface tests, with the maximum compressive force as the index. Under optimal parameter combination conditions, the relative error between the simulated and experimental values of the maximum compressive force was 0.79%, and the relative errors between the simulated and TPA test values of all indicators were less than 5.65%. This study provides a valuable reference for simulating the textural characteristics of agricultural products.