bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimised proteomic analysis of insulin granules from MIN6 β-cells identifies Scamp3, a novel regulator of insulin secretion and content
Authors: Norris Nicholas , Yau Belinda , Famularo Carlo , Thomas Helen E. , Larance Mark , Senior Alistair M. , Kebede Melkam A. 
Published: April 2024

AbstractPancreatic β-cells in the islets of Langerhans are key to maintaining glucose homeostasis, by secreting the peptide hormone insulin. Insulin is packaged within vesicles named insulin secretory granules (ISGs), that have recently been considered to have intrinsic structures and proteins that regulate insulin granule maturation, trafficking, and secretion. Previously, studies have identified a handful of novel ISG-associated proteins using different separation techniques. Here, this study combines an optimized ISG isolation technique and mass spectrometry-based proteomics, with an unbiased protein correlation profiling and targeted machine learning approach to uncover 211 ISG-associated proteins. Five of these proteins: Syntaxin-7, Synaptophysin, Synaptotagmin-13, Zinc transporter ZIP8 and SCAMP3 have not been previously ISG-associated. Through colocalization analysis of confocal imaging we validate the association of these proteins to the ISG in MIN6 and human β-cells. We further validate the role for one (SCAMP3) in regulating insulin storage and secretion from β-cells for the first time. SCAMP3 knock-down INS-1 cells show a reduction in insulin content and dysfunctional insulin secretion. These data provide the basis for future investigation into β-cell biology and the regulation of insulin secretion.Article HighlightsWhy did we undertake this study?We undertook this study to optimize insulin granule isolation techniques alongside enhanced proteomics analyses to establish the first published murine insulin granule proteome.What is the specific question(s) we wanted to answer?We aimed to specifically answer and investigate what proteins are present on insulin granules from MIN6 cells to further our understanding of insulin granule biogenesis, trafficking, and secretion.What did we find?We find and validate the presence of 5 novel insulin granule-associated proteins.What are the implications of our findings?An extensive proteomics analysis of MIN6 insulin granules and implicate Scamp3 as a novel protein that regulates insulin content and secretion in beta-cells.
Beyond the Smoke: A Phenomenological Study of Health and Social Implications of Kush Use Among Sierra Leonean Youths
Authors: Bangura Ronald Abu , Mayei Alhassan , Fatoma Patrick , Bunting-Graden Joseph Anderson , Kaisam John Paul , Ansumana Rashid 
Published: April 2024

ABSTRACTBackgroundThe rising use of “Kush” among Sierra Leone’s youth is a public health concern. Kush, a concoction of Cannabis indica and synthetic substances, symbolizes the broader issue of drug misuse in low-income settings. This study explored the intricacies of Kush use among young Sierra Leoneans, highlighting the gravity of the crisis.MethodsThe research employed a phenomenological method, gathering insights through Focus Group Discussions (FGDs), Key Informant Interviews (KIIs), and In-Depth Interviews (IDIs) to understand the motivations and repercussions of Kush consumption. Selecting participants from diverse socio-demographic groups, the study included habitual users and those in vulnerable situations. Ten interviews were analyzed thematically, facilitated by NVivo software and Concept maps, to distill information.ResultsFindings identified numerous reasons for Kush use, from managing stress and trauma to seeking social belonging and economic necessity. Users experienced severe health issues, economic instability, and productivity loss. The effects varied by Kush strain, underscoring its heterogeneous nature. Despite a strong will to quit, influenced by health, family, and aspirations, youths faced hurdles like withdrawal symptoms, peer pressure, and scarce support systems.ConclusionKush consumption in Sierra Leonean youths is entwined with socioeconomic and post-conflict factors, leading to significant adverse effects. Effective intervention requires a multifaceted strategy, focusing on underlying drug abuse causes and providing robust support systems. This study calls for tailored measures and policies that acknowledge the complex motivations behind Kush use and its impacts, aiming to foster an environment conducive to youth empowerment and health.
Evaluating the impact of the Mellow Babies group-based parenting programme for supporting at-risk mothers in Tajikistan
Authors: Duncan Natalie , Jones Ailsa , Tainsh Rachel , Muhamedjonova Nazira , Ibrahim Raquib , MacBeth Angus 
Published: April 2024

AbstractParental mental health has a long-lasting impact on developmental outcomes for infants and children through its impact on the family environment. Targeted parenting interventions should address both parental health and parenting skills. However, data is limited on how interventions perform in Central Asian populations.Using routine evaluation data from n=194 participants, we modelled the effectiveness of the Mellow Babies (MB) programmes, delivered to mothers from Tajikistan and their children as part of a community support approach. Pre-post intervention changes were measured on depression, anxiety, parenting stress, quality of life, and child behaviour outcomes. Demographics were modelled as covariates.Participation in MB was associated with improvements in maternal mental health, parenting stress, quality of life and child behaviour. Demographic factors moderated interactions between pre and post intervention outcomes, including urban/rural differences, parental employment, marital status and child disability status. Our findings suggest that MB is acceptable, effective and potentially scalable as a parenting intervention in Tajikistan. Future replication using implementation designs and replication of MB in other global settings is merited.
Primary health facility readiness to care for infants under six months at risk of poor growth and development: A HHFA-based survey
Authors: van Immerzeel Tabitha D. , Ba Abou , Diagne Maty , Deme-Ly Indou , Murungi Amanda E. , Penzias Rebecca , Seck Daouda , Diallo Abdallah , Grijalva-Eternod Carlos S. , Kerac Marko , Day Louise T. 
Published: April 2024

AbstractMalnutrition in infants under six months of age (u6m) is poorly identified and managed in many countries, increasing these children’s risk of poor growth and development and preventable mortality and morbidity. New 2023 WHO malnutrition guidelines recommend assessment, classification and treatment at primary health care level. This study aimed to assess primary health facility availability and readiness for WHO-recommended nutritional care in infants u6m.We adapted the WHO Harmonized Health Facility Assessment (HHFA) with additional items forManagement of small and nutritionallyAt-risk Infants u6m and theirMothers (MAMI): the HHFA-MAMI tool. Methods included survey of health care providers, direct observation and data extraction from routine registers to calculate mean percentages of a set of items for different readiness areas. We assessed 15 primary health facilities in Senegal, focusing on the five contact points for infants u6m: delivery and postnatal care, immunization programmes, sick child clinics and community health care.The HHFA-MAMI mean scores (n=15) were: general service availability 51%, general service readiness 69%, management & finance 50%, clinical quality of care 47%. MAMI availability scored 48% and readiness 35%, MAMI infrastructure scored 72%, health workforce 61%, assess MAMI 54%, classify MAMI 15% and treat MAMI 38%, equipment 33% and guidelines & training 22%. Service utilization was highest in postnatal care and immunization contact points, MAMI availability & readiness was highest in delivery and postnatal care.We conclude that primary health facilities in Senegal have potential to care for infants u6m at risk of poor growth and development with high general PHC readiness and frequent use of care contact points for infants u6m. MAMI availability and readiness require improvements to provide WHO-recommended care.
Assessment of Donated Medications and their Use in Tikur Anbessa Specialized Hospital: Promoting Green Health and Circular Economy
Authors: Alemaw Elbethel Getinet , Demisse Bezawit Negash 
Published: April 2024

AbstractIntroductionDespite the increased access to medicine, developing countries receive large amounts of medicines from donations. Donated medication could save lives and alleviate suffering but they could also cause deleterious effects on recipients. These effects can lead to the disposal of harmful drugs, affecting health infrastructure and causing negative. Organizations donate drugs for various reasons, including charitable, publicity, or humanitarian reasons. Despite the need for donated drugs, drug dumping remains a prevalent issue in Sub-Saharan Africa.The volume of pharmaceutical waste that accumulates worldwide is now a major concern. The idea of a sustainable, circular bioeconomy on a global scale is appealing. It prioritizes environmental sustainability and human well-being atop economic recovery.The primary objective of this study was to evaluate the status of donated medicines in Tikur Anbessa Specialized Hospital (TASH) and develop suggestions. Medicines donated from April 2022 up to May 2022 were included in this studyMaterials and MethodsA cross-sectional survey conducted at an institutional level employed both quantitative and qualitative research methodologies. The study was conducted from April 2022 to May 2022, focusing on pharmaceuticals donated to Tikur Anbessa Specialized Hospital (TASH) between November 2021 and March 2022. For the qualitative part, employees of Tikur Anbessa Specialized Hospital (TASH) working at different dispensary units, and pharmaceutical stores constituted the source population.Results and recommendationsA total of six donors contributed a combined value of 11,715,389 Ethiopian birr worth of medicines, supplies, and equipment. The donated items comprised 45 product categories and a total of 160 individual products. Among these, the most prevalent product categories included Opioids (27.48%), ASRVI (10.22%), PDE-5 Inhibitors (7.70%), Antihemophilic agents (7.34%), Antibiotics (7.02%), Anticonvulsants (5.67%), and Antifungals (3.36%). Management of medicines, supplies, and equipment at Tikur Anbessa Specialized Hospital (TASH) is facilitated through the Pharmaceutical Management Information System (PMIS), similar to other medication management processes. The acquisition of donated medications primarily occurs through both recipient requests and donor initiatives. Delivery of drugs near expiry, too small amount, discontinuation, disposal cost and push pull scenario were among the problems. Simple effective communication among donors and the hospital can uplift these problems and enhance the positive impacts of donations. Furthermore, the hospital needs to update its policy on donation and schedule donations to optimize the effects of donations; as a result promoting sustainability.
The impact of COVID vaccination on incidence of long COVID and healthcare resource utilisation in a primary care cohort in England, 2021-2022
Authors: Yang Jingyan , Rai Kiran K. , Alfred Tamuno , Massey Lucy , Massey Olivia , McGrath Leah , Andersen Kathleen M. , Tritton Theo , Tsang Carmen , Butfield Rebecca , Reynard Charlie , Mendes Diana , Nguyen Jennifer L 
Published: April 2024

ABSTRACTBackgroundLong COVID, a diverse set of symptoms that persist after a minimum of 4 weeks from the initial SARS-CoV-2 infection, has posed substantial burden to healthcare systems. There is some evidence that COVID-19 vaccination may be associated with lower risk of long COVID. However, little is known about the association between vaccination status and long COVID-associated healthcare resource utilisation (HCRU) and costs.MethodsWe conducted a cohort study using primary care electronic health record data in England from the Clinical Practice Research Datalink (CPRD) Aurum dataset linked to Hospital Episode Statistics where applicable. Adult (≥18 years) patients were indexed on a COVID-19 diagnosis between 1stMarch 2021 and 1stDecember 2021. Vaccination status was assessed at index: unvaccinated or completed primary series (two doses for immunocompetent and three doses for immunocompromised patients). Covariate balance was conducted using entropy balancing. Weighted multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) for incident long COVID, and separately long COVID primary care resource use, by vaccination status. Patients were followed up to a maximum of 9-months post index.ResultsA total of 35,713 patients who had completed primary series vaccination, and 75,522 unvaccinated patients were included. The weighted and adjusted IRR for long COVID among patients vaccinated with the primary series compared to being unvaccinated was 0.81 (95% CI: 0.77-0.86) in the overall cohort, 0.83 (95% CI: 0.78-0.88) in the immunocompetent cohort and 0.28 (95% CI: 0.13-0.58) in the immunocompromised cohort. Among those with long COVID, there was no association between the rate of primary care consultations and vaccination status in the overall and immunocompetent cohorts. Cost of primary care consultations was greater in the unvaccinated group than for those who completed primary series.ConclusionVaccination against COVID-19 may reduce the risk of long COVID in both immunocompetent and immunocompromised patients. However, no association was found between frequency of primary care visits and vaccination among patients diagnosed in 2021. Future studies with larger sample size, higher vaccine uptake, and longer study periods during the pandemic are needed to further quantify the impact of vaccination on long COVID.
Initial treatment choices for long term remission of insomnia disorder in adults: a systematic review and network meta-analysis
Authors: Furukawa Yuki , Sakata Masatsugu , Furukawa Toshi A. , Efthimiou Orestis , Perlis Michael 
Published: April 2024

ABSTRACTBackgroundCognitive behavioral therapy for insomnia (CBT-I), pharmacotherapy and their combination are effective for insomnia. However, it remains unclear which treatment is more likely to lead to favorable long-term outcomes when used as the initial treatment. We aimed to evaluate the comparative efficacy and acceptability of CBT-I, pharmacotherapy, and their combination in the long- and short-terms among adults with insomnia disorder.MethodsWe searched PubMed, CENTRAL, PsycINFO and WHO ICTRP from database inception to Dec 27, 2023, to identify published and unpublished randomized controlled trials. We included trials in hypnotic-free adults with insomnia disorder comparing at least two of the following: CBT-I with at least one effective component (sleep restriction, stimulus control, cognitive restructuring, and third wave components), pharmacotherapy, or their combination. We assessed the confidence in evidence using CINeMA. The primary outcome was long-term remission (longest follow-up between 3 to 12 months). Secondary outcomes included all-cause dropout and self-reported sleep continuity measures at long-term follow-up, and the same outcomes at the end of the acute treatment phase. We performed frequentist random-effects network meta-analyses. We used odds ratio (OR) for dichotomous outcomes and mean difference for continuous outcomes, expressed in minutes and percent. This study is registered in PROSPERO (CRD42024505519).FindingsWe identified 13 trials, including 823 randomized participants (mean age, 47.8 years, 60% women). Results suggested that CBT-I was more beneficial than pharmacotherapy in the long-term (remission OR 1.82 [95% Confidence Interval (CI), 1.15 to 2.87; certainty of evidence: high]), while there was weaker evidence of benefit of combination against pharmacotherapy (OR 1.71 [95%CI, 0.88 to 3.30: moderate]) and no clear evidence of difference of CBT-I against combination (OR 1.07 [95%CI, 0.63 to 1.80: moderate]). CBT-I was associated with less dropouts than pharmacotherapy in the long-term. Short-term outcomes also favored CBT-I over pharmacotherapy except total sleep time. Given the average long-term remission rate in the pharmacotherapy-initiating arms of 28%, CBT-I resulted in a long-term remission rate of 41% (95% CI: 31% to 53%) and combination 40% (95% CI: 25% to 56%).InterpretationThis study found that starting with CBT-I for the treatment of adults with chronic insomnia leads to better outcomes than starting with pharmacotherapy. Combination therapy may be better than pharmacotherapy alone, but unlikely to be worth the additional burden over CBT-I alone.FundingNone.
The hippocampus pre-orders movements for skilled action sequences
Authors: Yewbrey Rhys , Kornysheva Katja 
Published: April 2024

AbstractPlasticity in the subcortical motor basal ganglia-thalamo-cerebellar network plays a key role in the acquisition and control of long-term memory for new procedural skills, from the formation of population trajectories controlling trained motor skills in the striatum to the adaptation of sensorimotor maps in the cerebellum. However, recent findings demonstrate the involvement of a wider cortical and subcortical brain network in the consolidation and control of well-trained actions, including an area traditionally associated with declarative memory – the hippocampus. Here, we probe which role these subcortical areas play in skilled motor sequence control, from sequence feature selection during planning to their integration during sequence execution. An fMRI dataset collected after participants learnt to produce four finger sequences entirely from memory with high accuracy over several days was examined for both changes in BOLD activity and their informational content in subcortical regions of interest. Although there was a widespread activity increase in effector-related striatal, thalamic and cerebellar regions, the associated activity did not contain information on the motor sequence identity. In contrast, hippocampal activity increased during planning and predicted the order of the upcoming sequence of movements. Our findings show that the hippocampus pre-orders movements for skilled action sequences, thus contributing to the higher-order control of skilled movements. These findings challenge the traditional taxonomy of episodic and procedural memory and carry implications for the rehabilitation of individuals with neurodegenerative disorders.
Insulin signaling accelerates the anterograde movement of Rab4 vesicles in axons through Klp98A/KIF16B recruitment via Vps34-PI3Kinase
Authors: Singh Kamaldeep , Das Semanti , Sutradhar Sabyasachi , Howard Jonathon , Ray Krishanu 
Published: April 2024

AbstractRab4 GTPase organizes endosomal sorting essential for maintaining the balance between recycling and degradative pathways. Rab4 localizes to many cargos whose transport in neurons is critical for regulating neurotransmission and neuronal health. Furthermore, elevated Rab4 levels in the CNS are associated with synaptic atrophy and neurodegeneration inDrosophilaand humans, respectively. However, how the transport of Rab4-associated vesicles is regulated in neurons remains unknown. Usingin vivotime-lapse imaging ofDrosophilalarvae, we show that activation of insulin signaling via Dilp2 and dInR increases the anterograde velocity, run length, and flux of Rab4 vesicles in the axons. Molecularly, we show that activation of neuronal insulin signaling further activates Vps34, elevates the levels of PI(3)P on Rab4-associated vesicles, recruits Klp98A (a PI(3)P-binding kinesin-3 motor) and activates their anterograde transport. Together, these observations delineate the role of insulin signaling in regulating axonal transport and synaptic homeostasis.HighlightsDilp2-mediated insulin signaling activates anterograde transport of Rab4 vesiclesVps34 regulates anterograde velocity, run length and flux of Rab4 vesiclesLocal PI(3)P signaling on Rab4 vesicles regulates their motility in the axonsPI(3)P production upon acute insulin stimulation recruits Klp98A on Rab4 vesicles
95 GeV Higgs boson in the Georgi-Machacek model
Authors: Chen Ting-Kuo , Chiang Cheng-Wei , Heinemeyer Sven , Weiglein Georg 
Published: April 2024

CMS and ATLAS have reported small excesses in the search for low-mass Higgs bosons in the diphoton decay channel at exactly the same mass, 95.4 GeV. These searches rely on improved analysis techniques, enhancing in particular the discrimination against the Z→e+e− background. In models beyond the Standard Model (SM) that extend the Higgs sector with triplets, doubly charged Higgs bosons are predicted which can contribute substantially to the diphoton decay rate of a light Higgs boson. The Georgi-Machacek (GM) Model is of particular interest in this context, since despite containing Higgs triplets it preserves the electroweak ρ-parameter to be 1 at the tree level. We show that within the GM model, a Higgs boson with a mass of ∼95  GeV with a diphoton decay rate as observed by CMS and ATLAS can be well-described. We discuss the diphoton excess in conjunction with an excess in the bb¯ final state observed at LEP and an excess observed by CMS in the ditau final state, which have been found at comparable masses with local significances of about 2σ and 3σ, respectively. The presence of a Higgs boson at about 95 GeV within the GM model would imply good prospects of the searches for additional light Higgs bosons. In particular, the observed excess in the diphoton channel would be expected to be correlated in the GM model with a light doubly charged Higgs boson in the mass range between 100 and 200 GeV, which motivates dedicated searches in upcoming LHC Runs.

Published by the American Physical Society
2024
Factors influencing entrepreneurial intentions among Chilean secondary vocational students
Authors: Torres-Ortega Jorge , Loyola-Campos Javier , Ibarra-Pérez Davor , Hernández-Muñoz Valentina 
Published: April 2024

PurposeThis paper aims to determine the effect of a set of factors (attitude toward entrepreneurship, perceived behavioral control or entrepreneurial self-efficacy, previous experience, internal locus of control and entrepreneurial alertness) on the entrepreneurial intentions of Chilean secondary vocational school students.Design/methodology/approachAn online survey was sent to all secondary-level students from four Chilean vocational schools (3,052 students). A total of 1,644 valid questionnaires were received. The data were analyzed using partial least squares structural equation modeling (PLS-SEM).FindingsThe results show that attitude toward entrepreneurship and perceived behavioral control positively and significantly impact the students’ entrepreneurial intentions, but not the previous experience.Research limitations/implicationsSince this research was carried out in a specific reality, the results may lack generalizability. Also, the proposed model requires further development through the incorporation of other factors. It is then suggested to replicate this study in other countries as well as to incorporate new variables and test new relationships.Practical implicationsEntrepreneurship education programs at the secondary level should emphasize changing/stimulating adolescents’ attitudes toward entrepreneurship as well as improving their confidence in their entrepreneurial abilities.Originality/valueThis is one of the few studies that provide empirical evidence about the determinants of entrepreneurial intentions in adolescents, particularly in Latin America, and with a large sample.