bluuebunny/crossref_metadata_2025_split huggingface dataset:
A community-based mentoring scheme for pregnant and parenting adolescents in Sierra Leone: protocol for a hybrid pilot cluster randomised controlled trial
Authors: Fernandez Turienzo C , Kamara M , November L , Kamara P , Kingsford AM , Ridout A , Thomas S , Seed PT , Shennan AH , Sandall J , Williams PT 
Published: November 2023

AbstractBackgroundSierra Leone has a very high maternal mortality rate, and this burden falls heavily on adolescents, a particularly vulnerable group; this is usually driven by poverty, lack of education and employment opportunities. In 2017, a local grassroots organisation, Lifeline Nehemiah Projects, developed a community-based mentoring intervention ‘2YoungLives’ (2YLs) for adolescent girls in Eastern Freetown. We aim to formally assess the feasibility and implementation of the 2YL mentorship scheme in new communities in Sierra Leone.MethodsA hybrid type 2 pilot cluster randomised controlled trial of the 2YL mentoring scheme in urban and rural communities living around twelve peripheral health units (PHU) across five districts in Sierra Leone. Clusters will be matched into pairs and randomisation will be determined by computer-generated random numbers via a secure web-based system hosted by MedSciNet. All under-eighteen adolescents identified as pregnant in the community and/or the PHU are included. Feasibility (recruitment, retention, and attrition rates; data collection and completeness; sample calculation) and primary clinical outcome data (composite of maternal deaths, stillbirths, neonatal deaths) will be collected. A mixed-methods process evaluation will explore implementation outcomes, mechanisms of change, contextual factors, experiences of care, and health and wellbeing. A concurrent cost-consequence analysis will be undertaken. Main trial analysis will be pragmatic, by intention to treat, and a complementary per protocol analysis will also be included.DiscussionImproving health and wellbeing for adolescent girls (including sexual and reproductive health) remains a top priority in Sierra Leone indicated by several government policies targeted to this group, in which maternal and infant mortality are still persistently high. Supporting these girls and facilitating their wellbeing is imperative, along with sensitisation of communities, strengthening of youth friendly services and collaboration with stakeholders at all levels (government, regional, community, family). We believe 2YL supports the global holistic agenda to integrate and implement interventions across health, education, and social systems in order to protect, nurture, and support the health and development potential of every adolescent girl, and thus become a model of good practice for adolescent pregnancy, to be adopted more widely in Sierra Leone and elsewhere.Trial registrationISRCTN registryISRCTN32414369. Prospectively registered on 14/03/2022.
Associations of Objective and Self-Reported Physical Activity and Sedentary Behavior with Skeletal Muscle Energetics: The Study of Muscle, Mobility and Aging (SOMMA)
Authors: Qiao Yujia (Susanna) , Blackwell Terri L. , Cawthon Peggy M. , Coen Paul M. , Cummings Steven R. , Distefano Giovanna , Farsijani Samaneh , Forman Daniel E. , Goodpaster Bret H. , Kritchevsky Stephen B. , Mau Theresa , Toledo Frederico G.S. , Newman Anne B. , Glynn Nancy W. 
Published: November 2023

ABSTRACTBackgroundSkeletal muscle energetics decline with age, and physical activity (PA) has been shown to counteract these declines in older adults. Yet, many studies were based on self-reported PA or structured exercise interventions. We examined the associations of objective daily PA and sedentary behavior (SB) with skeletal muscle energetics and also compared with self-reported PA and SB. We also explored the extent to which PA would attenuate the associations of age with muscle energetics.MethodsAmong the Study of Muscle, Mobility and Aging (SOMMA) enrolled older adults, 810 (mean age=76±5, 58% women) had maximal muscle oxidative capacity measuredex vivovia high-resolution respirometry of permeabilized myofibers (maxOXPHOS) andin vivoby31Phosphorus magnetic resonance spectroscopy (ATPmax). Objective PA was measured using the wrist-worn ActiGraph GT9X over 7-days to capture sedentary behavior (SB), light, and moderate-to-vigorous PA (MVPA). Self-reported SB, MVPA, and all exercise-related PA were assessed with The Community Healthy Activities Model Program for Seniors questionnaire. Linear regression models with progressive covariate adjustments evaluated the associations between SB, PA and muscle energetics, and the attenuation of the age / muscle energetic association by PA.ResultsEvery 30 minutes more objective MVPA was associated with 0.65 pmol/s*mg higher maxOXPHOS and 0.012 mM/sec higher ATPmax, after adjustment for age, site/technician and sex. More time spent in objective light+MVPA was significantly associated with higher ATPmax, but not maxOXPHOS. In contrast, every 30 minutes spent in objective SB was associated with 0.43 pmol/s*mg lower maxOXPHOS and 0.004 mM/sec lower ATPmax. Only associations with ATPmaxheld after further adjusting for socioeconomic status, body mass index, lifestyle factors and multimorbidities. Self-reported MVPA and all exercise-related activities, but not SB, yielded similar associations with maxOXPHOS and ATPmax. Lastly, age was only significantly associated with muscle energetics in men. Adjusting for objective time spent in MVPA attenuated the age association with ATPmaxby nearly 60% in men.ConclusionMore time spent in daily PA, especially MVPA, were associated with higher muscle energetics. Interventions that increase higher intensity activity might offer potential therapeutic interventions to slow the age-related decline in muscle energetics. Our work also emphasizes the importance of taking PA into consideration when evaluating associations related to skeletal muscle energetics.
Modeling the START transition in the budding yeast cell cycle
Authors: Ravi Janani , Samart Kewalin , Zwolak Jason 
Published: November 2023

AbstractBudding yeast,Saccharomyces cerevisiae, is widely used as a model organism to study the genetics underlying eukaryotic cellular processes and growth critical to cancer development, such as cell division and cell cycle progression. The budding yeast cell cycle is also one of the best-studied dynamical systems owing to its thoroughly resolved genetics. However, the dynamics underlying the crucial cell cycle decision point called the START transition, at which the cell commits to a new round of DNA replication and cell division, are under-studied. The START machinery involves a central cyclin-dependent kinase; cyclins responsible for starting the transition, bud formation, and initiating DNA synthesis; and their transcriptional regulators. However, evidence has shown that the mechanism is more complicated than a simple irreversible transition switch. Activating a key transcription regulator SBF requires the phosphorylation of its inhibitor, Whi5, or an SBF/MBF monomeric component, Swi6, but not necessarily both. Also, the timing and mechanism of the inhibitor Whi5’s nuclear export, while important, are not critical for the timing and execution of START. Therefore, there is a need for a consolidated model for the budding yeast START transition, reconciling all known regulatory and spatial dynamics. We built a detailed mathematical model (START-BYCC) for the START transition in the budding yeast cell cycle based on all established molecular interactions and experimental phenotypes. START-BYCC recapitulates the underlying dynamics and correctly emulates key phenotypic traits of ∼150 known START mutants, including regulation of size control, localization of inhibitor/transcription factor complexes, and the nutritional effects on size control. Such a detailed mechanistic understanding of the underlying dynamics gets us closer towards deconvoluting the aberrant cellular development in cancer. All wildtype and mutant simulations of our START-BYCC model are available atsbmlsimulator.org/simulator/by-start, and the supporting data is available on GitHub:github.com/jravilab/start-bycc.
Polycomb Repressive Complex 2 is critical for mouse cortical glutamatergic neuron development
Authors: Currey Laura , Mitchell Benjamin , Al-Kahlily Majd , McElnea Sarah-Jayne , Harkins Danyon , Pelenyi Alexandra , Kurniawan Nyoman D. , Burne Thomas H. , Harris Lachlan , Thor Stefan , Piper Michael 
Published: November 2023

SummaryThe Polycomb Repressive Complex 2 (PRC2) regulates corticogenesis, yet the consequences of mutations to this epigenetic modifier in the mature brain are poorly defined. Importantly, PRC2 core genes are haploinsufficient and causative for several human neurodevelopmental disorders. To address the role of PRC2 in mature cortical structure and function, we conditionally mutated the PRC2 geneEedin the developing mouse telencephalon. Adult homozygotes displayed smaller forebrain structures. Single-nucleus transcriptomics revealed glutamatergic neurons were particularly affected, exhibiting dysregulation of cortical layer-specific profiles, accompanied by aberrations in neuronal morphology and connectivity. Incredibly, homozygous mice performed well on challenging cognitive tasks. In contrast, heterozygous mice did not exhibit anatomical or behavioral phenotypes but displayed dysregulation of neuronal genes and altered neuronal morphology that was strikingly different from homozygous phenotypes. Collectively, we demonstrate how alterations to PRC2 function shape the mature brain and reveal a dose-specific role for PRC2 in determining glutamatergic neuron identity.
The Host-specific Microbiota is Required for Diet-Specific Metabolic Homeostasis
Authors: Fei Na , Xie Bingqing , Long Tyler J. , StGeorge Marissa , Tan Alan , Manzoor Sumeed , Sidebottom Ashley M. , Spedale Melanie , Theriault Betty R , Sulakhe Dinanath , Chang Eugene B. 
Published: November 2023

AbstractIn complex mammals, the importance and host-specificity of microbial communities have been demonstrated through their positive effects on host immune fitness or performance. However, whether host metabolic physiology homeostasis depends on a specific bacterial community exclusive to the host remains unclear. Here, we show that the coevolved host-specific microbiota is required to maintain diet-specific flexible and sufficient metabolic homeostasis through a high colonization rate, modulating gut metabolites, and related targets. Using germ-free (GF) mice, we tested whether the fitness benefiting the host metabolic phenotype of microbiota was host-specific. We demonstrated that GF mice associated with exogenous microbiota (human microbiota (HM)), which exhibited different and reduced gut microbial species diversity, significantly elevated metabolic rate, and exhibited metabolic insufficiency, all characteristics of GF mice. Strikingly, the absence of the host-specific microbiome attenuated high-fat diet-specific metabolism features. Different diets caused different metabolic changes in only host-specific microbiota-associated mice, not the host-microbiota mismatched mice. While RNA sequencing revealed subtle changes in the expression of genes in the liver, GF mice and HM mice showed considerably altered expression of genes associated with metabolic physiology compared to GF mice associated with host-specific microbiota. The effect of diet outweighed microbiota in the liver transcriptome. These changes occurred in the setting of decreased luminal short-chain fatty acids (SCFAs) and the secondary bile acid (BAs) pool and downstream gut signaling targets in HM and GF mice, which affects whole-body metabolism. These data indicate that a foreign microbial community provides little metabolic benefit to the host when compared to a host-specific microbiome, due to the colonization selection pressure and microbiota-derived metabolites dysfunction. Overall, microbiome fitness effects on the host metabolic phenotype were host-specific. Understanding the impact of the host-specificity of the microbiome on metabolic homeostasis may provide important insights for building a better probiotic.HighlightsMicrobiome fitness effects on the host metabolic phenotype were host-specific in mammals.Human microbiota-associated mice exhibited lower host metabolic fitness or performance, and similar functional costs in GF mice.Different diets cause different metabolic changes only in host-specific microbiota-associated mice, not the host-microbiota mismatched mice.The defective gut microbiota in host-specific microbiota, microbial metabolites and related targets likely drive the metabolic homeostasis.Graphical Abstract
The Arabidopsiskatamari2Mutant Exhibits a Hypersensitive Seedling Arrest Response at the Phase Transition from Heterotrophic to Autotrophic Growth
Authors: Hosokawa Chika , Yagi Hiroki , Segami Shoji , Nagano Atsushi J. , Koumoto Yasuko , Tamura Kentaro , Oka Yoshito , Matsushita Tomonao , Shimada Tomoo 
Published: November 2023

AbstractYoung seedlings use nutrients stored in the seeds to grow and acquire photosynthetic potential. This process, called seedling establishment, involves a developmental phase transition from heterotrophic to autotrophic growth. Some membrane-trafficking mutants ofArabidopsis thaliana(Arabidopsis), such as thekatamari2(kam2) mutant, exhibit growth arrest during seedling development, with a portion of individuals failing to develop true leaves on sucrose-free solid medium. However, the reason for this seedling arrest is unclear. In this study, we show that seedling arrest is a temporal growth arrest response that occurs not only inkam2but also in wild-type Arabidopsis; however, the threshold for this response is lower inkam2than in the wild type. A subset of the arrestedkam2seedlings resumed growth after transfer to fresh sucrose-free medium. Growth arrest inkam2on sucrose-free medium was restored by increasing the gel concentration of the medium or covering the surface of the medium with a perforated plastic sheet. Wild-type Arabidopsis seedlings were also arrested when the gel concentration of sucrose-free medium was reduced. RNA sequencing revealed that transcriptomic changes associated with the rate of seedling establishment were observed as early as 4 days after sowing. Our results suggest that the growth arrest of bothkam2and wild-type seedlings is an adaptive stress response and is not simply caused by the lack of a carbon source in the medium. This study provides a new perspective on an environmental stress response under unfavorable conditions during the phase transition from heterotrophic to autotrophic growth in Arabidopsis.
Bioenergetic mapping of ‘healthy microbiomes’ via compound processing potential imprinted in gut and soil metagenomes
Authors: Liddicoat Craig , Edwards Robert A. , Roach Michael , Robinson Jake M. , Wallace Kiri Joy , Barnes Andrew D. , Brame Joel , Heintz-Buschart Anna , Cavagnaro Timothy R. , Dinsdale Elizabeth A. , Doane Michael P. , Eisenhauer Nico , Mitchell Grace , Rai Bibishan , Ramesh Sunita , Breed Martin F. 
Published: November 2023

ABSTRACTDespite mounting evidence of their importance in human health and ecosystem functioning, the definition and measurement of ‘healthy microbiomes’ remain unclear. More advanced knowledge exists on health associations for compounds used or produced by microbes. Environmental microbiome exposures (especially via soils) also help shape, and may supplement, the functional capacity of human microbiomes. Given the synchronous interaction between microbes, their feedstocks, and micro-environments, with functional genes facilitating chemical transformations, there exists an intriguing opportunity to examine microbiomes in terms of their capacity to process compounds relevant to human health. Here we integrate functional genomics and biochemistry frameworks to derive new quantitative measures of the potential for human gut and environmental soil metagenomes to process major compound classes (e.g., lipids, carbohydrates) and selected biomolecules (e.g., vitamins, short-chain fatty acids) linked to human health. Metagenome functional potential profile data were translated into a universal compound mapping ‘landscape’ based on bioenergetic van Krevelen mapping of function-level meta-compounds and corresponding functional relative abundances, reflecting imprinted genetic capacity of microbiomes to metabolize an array of different compounds. We show that measures of ‘compound processing potential’ associated with human health and disease (examining atherosclerotic cardiovascular disease, colorectal cancer, type 2 diabetes and anxious-depressive behavior case studies), and displayed seemingly predictable shifts along gradients of ecological disturbance in plant-soil ecosystems (three case studies). Ecosystem quality explained 60–92% of variation in soil metagenome compound processing potential measures in a post-mining restoration case study dataset. With growing knowledge of the varying proficiency of environmental microbiota to process human health associated compounds, we might design environmental interventions or nature prescriptions to modulate our exposures, thereby advancing microbiota-oriented approaches to human health. Compound processing potential offers a simplified, integrative approach for applying metagenomics in ongoing efforts to understand and quantify the role and linkages of microbiota in environmental- and human-health.
Multi-night EEG reveals positive association between sleep efficiency and hippocampal subfield volumes in healthy aging
Authors: Keresztes Attila , Bankó Éva , Báthori Noémi , Tomacsek Vivien , Varga Virág Anna , Nárai Ádám , Nemecz Zsuzsanna , Dénes Ádám , Gál Viktor , Hermann Petra , Simor Péter , Vidnyánszky Zoltán 
Published: November 2023

abstractAge-related atrophy of the human hippocampus and the enthorinal cortex starts accelerating at around age 60. Due to the contributions of these regions to many cognitive functions seamlessly used in everyday life, this can heavily impact the lives of elderly people. The hippocampus is not a unitary structure and mechanisms of its age-related decline appear to differentially affect its subfields. Human and animal studies have suggested that altered sleep is associated with hippocampal atrophy. Yet, we know little about subfield specific effects of altered sleep in healthy aging and their effect on cognition. Here, in a sample of 118 older adults (Mage= 63.25 years), we examined the association between highly reliable hippocampal subfield volumetry, sleep measures derived from multi-night recordings of portable electroencephalography and episodic memory. Objective sleep efficiency – but not self-report measures of sleep – was associated with entorhinal cortex volume when controlling for age. Age-related differences in subfield volumes were associated with objective sleep efficiency, but not with self-report measures of sleep. Moreover, older adults characterized by a common multivariate pattern of subfield volumes that contributed to positive sleep– subfield volume associations, showed lower rates of forgetting. Our results showcase the benefit of objective sleep measures in identifying potential contributors of age-related differences in brain-behavior couplings.
Exploring the perceptions and experiences of community rehabilitation for Long COVID from the perspectives of Scottish General Practitioners’ and people living with Long COVID: a qualitative study
Authors: Cooper Kay , Duncan Edward , Hart-Winks Erin , Cowie Julie , Shim Joanna , Stage Emma , Tooman Tricia , Alexander Lyndsay , Love Alison , Morris Jacqui , Ormerod Jane , Preston Jenny , Swinton Paul Alan 
Published: November 2023

ABSTRACTObjectivesTo explore the experience of accessing Long COVID community rehabilitation from the perspectives of people with Long COVID and General Practitioners (GPs).DesignQualitative descriptive study employing one-to-one semi-structured virtual interviews analysed using the framework method.SettingFour NHS Scotland territorial health boards.ParticipantsEleven people with Long COVID (1 male, 10 female; aged 40-65 [mean 53], and 13 GPs (5 male, 8 female).ResultsFour key themes were identified: i) The lived experience of Long COVID; ii) The challenges of an emergent and complex chronic condition; iii) Systemic challenges for Long COVID service delivery, and iv) Perceptions and experiences of Long COVID and its management, including rehabilitation.ConclusionsThere are several patient, GP, and service-level barriers to accessing community rehabilitation for Long COVID. There is a need for greater understanding by the public, GPs, and other potential referrers of the role of community rehabilitation professionals in the management of Long COVID. There is also a need for community rehabilitation services to be well promoted and accessible to the people with Long COVID for whom they may be appropriate. Service providers need to consider availability and accessibility of Long COVID rehabilitation and ensure adequate interprofessional communication and collaboration to enhance the experience for people with Long COVID.Strengths and limitations of this studyThis is the first study to explore the issue of accessing Long COVID community rehabilitation from the perspectives of potential service users and referrers in the Scottish context.One researcher conducted all interviews, ensuring consistency in their conductData were analysed and interpreted by multiple researchers, including people with Long COVIDThe small sample size, largely drawn from health boards with a similar approach to Long COVID rehabilitation, limits generalisability
Effectiveness and safety of drugs in pregnancy: evidence from drug target Mendelian randomization
Authors: Barry Ciarrah-Jane S , Walker Venexia M , Burden Christy , Havdahl Alexandra , Davies Neil M 
Published: November 2023

AbstractLimited information exists regarding the impact of pharmacotherapy in pregnancy due to ethical concerns of unintended foetal harm. We investigate genetically proxied intrauterine antihypertensive exposure on offspring outcomes, including gestational age and birthweight, using two-sample multivariable Mendelian randomization. Higher levels of maternal protein targets for calcium channel blockers increased gestational age by 3.99 days (95%CI: 0.02, 7.96) per 10mmHg decrease in SBP. Genetically proxied maternal protein targets for beta-adrenoceptor blocking drugs, vasodilator antihypertensive drugs on the KNCJ11 gene, potassium-sparing diuretics and aldosterone antagonists demonstrated little evidence of increased risk to offspring. Both parental genetic protein targets for vasodilator antihypertensive drugs demonstrated similar effects on birthweight, suggesting detrimental offspring effects due to genetic perturbation of these pathways is unlikely. Little evidence for increased risk of adverse offspring outcomes due to maternal antihypertensive drug target perturbation was found. Triangulation of these findings with existing evidence may guide physicians and mothers during pregnancy.