bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional characterization of
Microplitis demolitor
bracovirus genes that encode nucleocapsid components
Authors: Lorenzi Ange , Arvin Michael J. , Burke Gaelen R. , Strand Michael R. 
Published: October 2023

ABSTRACT

Bracoviruses (BVs) are endogenized nudiviruses in parasitoid wasps of the microgastroid complex (order Hymenoptera: Family Braconidae). BVs produce replication-defective virions that adult female wasps use to transfer DNAs encoding virulence genes to parasitized hosts. Some BV genes are shared with nudiviruses and baculoviruses with studies of the latter providing insights on function, whereas other genes are only known from nudiviruses or other BVs which provide no functional insights. A proteomic analysis of
Microplitis demolitor
bracovirus (MdBV) virions recently identified 16 genes encoding nucleocapsid components. In this study, we further characterized most of these genes. Some nucleocapsid genes exhibited early or intermediate expression profiles, while others exhibited late expression profiles. RNA interference (RNAi) assays together with transmission electron microscopy indicated
vp39
,
HzNVorf9-like2
,
HzNVorf93-like
,
HzNVorf106-like
,
HzNVorf118-like
,
and 27b
are required to produce capsids with a normal barrel-shaped morphology. RNAi knockdown of
vlf-1a
,
vlf-1b-1
,
vlf-1b-2
,
int-1,
and
p6.9-1
did not alter the formation of barrel-shaped capsids but each reduced processing of amplified proviral segments and DNA packaging as evidenced by the formation of electron translucent capsids. All of the genes required for normal capsid assembly were also required for proviral segment processing and DNA packaging. Collectively, our results deorphanize several BV genes with previously unknown roles in virion morphogenesis.

IMPORTANCE

Understanding how bracoviruses (BVs) function in wasps is of broad interest in the study of virus evolution. This study characterizes most of the
Microplitis demolitor
bracovirus (MdBV) genes whose products are nucleocapsid components. Results indicate several genes unknown outside of nudiviruses and BVs are essential for normal capsid assembly. Results also indicate most MdBV tyrosine recombinase family members and the DNA binding protein
p6.9-1
are required for DNA processing and packaging into nucleocapsids.
HPV38 impairs UV-induced transcriptional activation of the IL-18 pro-inflammatory cytokine
Authors: Ceraolo Maria Grazia , Romero-Medina Maria Carmen , Gobbato Simone , Melita Giusi , Krynska Hanna , Sirand Cecilia , Gupta Purnima , Viarisio Daniele , Robitaille Alexis , Marvel Jacqueline , Tommasino Massimo , Venuti Assunta , Gheit Tarik 
Published: October 2023

ABSTRACT
Increasing evidence suggests that the beta genus of human papillomavirus (β-HPV) cooperates with ultraviolet B (UVB) radiation in inducing non-melanoma skin cancer (NMSC). For instance, expression of E6 and E7 oncoproteins from cutaneous human papillomavirus type 38 (HPV38) in a transgenic mouse model (Tg38) leads to the development of squamous cell carcinoma (SCC) after chronic UVB exposure. Transcriptomic analysis of the Tg38 SCC samples revealed a deregulation of inflammasome pathway-related genes such as IL-18, which is consistent with the well-known capability of several oncogenic viruses to modulate the immune response, in order to efficiently produce new progeny. However, the mechanism at the gene expression level by which UVB and HPV38 synergize and modulate the innate immune response has not been elucidated yet. Here, we propose a new molecular mechanism for the regulation of the IL-18 promoter that involves direct binding of p53 to specific response elements. This mechanism seems to be impaired in the presence of the β-HPV38 oncoproteins. Instead, a newly described inhibitory complex formed by DNA methyltransferase 1 (DNMT1)/PKR/ΔNp73α is recruited to the region formerly occupied by p53 in primary keratinocytes. Together, these results corroborate our hypothesis that β-HPV38 plays an important role in the inhibition of the ultraviolet-induced inflammasome response. This downregulation is likely to impair the ability of keratinocytes to recruit the immune cell population at the UVB-exposed area, causing a defect in the clearance of cells harboring DNA damage and promoting a favorable environment for the progression of NMSC.

IMPORTANCE
Here, we demonstrate that the direct binding of p53 on the IL-18 promoter region regulates its gene expression. However, the presence of E6 and E7 from human papillomavirus type 38 impairs this mechanism via a new inhibitory complex formed by DNA methyltransferase 1 (DNMT1)/PKR/ΔNp73α, which binds to the region formerly occupied by p53 in primary keratinocytes.
Parenting stress and health-related quality of life among parents of extremely preterm born early adolescents in England: a cross-sectional study
Authors: Suonpera Emmi , Lanceley Anne , Ni Yanyan , Marlow Neil 
Published: October 2023

ObjectiveTo determine whether extremely preterm (EP) birth exerts persisting effects on parents in early adolescence.DesignCross-sectional survey conducted between March 2017 and October 2018.SettingEvaluation of a longitudinal population-based birth cohort in England at 11 years of age (EPICure2@11 Study).ParticipantsParents of EP (<27 weeks of gestation) adolescents and control parents of term born (≥37 weeks of gestation) classmates of similar age and sex.Main outcome measuresThe Parenting Stress Index Short Form (PSI-4-SF) and the Short Form Health Survey (SF-12v1).ResultsThe 163 EP and 125 comparison respondents were most commonly mothers in their mid-40s. EP parents reported higher total parenting stress scores compared with controls, overall (adjusted difference in means: 14 (95% CI 9 to 20)) and after exclusion of moderate and severe child disability and multiples (9 (95% CI 3 to 15). Average physical and mental health-related quality of life scores were similar in the two groups (adjusted difference in means physical health: −2 (95% CI −4 to 1) and mental health: −1 (95% CI −4 to 1)). Among EP parents, 12% (20/164) reported the combination of high parenting stress and low mental health scores. With increasing child age, parenting stress scores for preterm parents were lower in contrast to controls who reported increasing parenting stress.ConclusionsIn early adolescence, compared with parents of term-born children, EP parents experience increased levels of parenting stress that are particularly high among a proportion of parents and associated with lower mental health-related quality of life. Practitioner awareness of this continuing risk throughout childhood is important to support parental abilities and well-being.
Diagnostic value of rapid test for malaria among febrile neonates in a tertiary hospital in North-East Nigeria: a prospective cross-sectional study
Authors: Adeniji Yasangra Rabo , Jalo Iliya , Okonkwo Ikechukwu , Poksireni Mercy Raymond , Manga Mohammed , Wariri Oghenebrume , Alhassan Halima Abdulkarim , Warnow Elon Isaac 
Published: October 2023

ObjectiveThe WHO recommends testing using microscopy or rapid diagnostic test (RDT) before treatment for malaria. However, the use of RDT to diagnose neonatal malaria has not been widely validated with most studies limited to the first week of life. Thus, we conducted this study to determine the utility of RDT in the diagnosis of congenital and acquired malaria in febrile neonates in Nigeria.DesignThis prospective cross-sectional descriptive study consecutively recruited 131 febrile neonates at the Special Care Baby Unit (SCBU) of the Federal Teaching Hospital Gombe, Nigeria. All study participants concurrently had RDT (HRP2, LDH) and malaria microscopy. The performance of both methods was then compared.ResultSeventy-eight of 131 neonates tested for malaria by blood smear microscopy demonstrated malaria parasites; a prevalence of 59.5%. Parasite count ranged from 16 to 520 /μL and the median parasite count was 81.0 /μL with IQR (40.0–134.5). The majority of patients (93.5%) had low-density parasitaemia (≤2+). All species identified werePlasmodium falciparum. None of the 131 neonates tested positive on RDT. The sensitivity and positive predictive value of RDT for neonatal malaria was zero. Congenital malaria was the most common form of neonatal malaria, accounting for 75.6%, while acquired and transfusion-related malaria were estimated at 12.8% and 11.6%, respectively.ConclusionThe RDT used in this study was not sensitive in the diagnosis of congenital or acquired neonatal malaria; therefore, microscopy remains the preferred method of diagnosis of neonatal malaria.
Device-measured physical activity, sedentary time, and risk of all-cause mortality: an individual participant data analysis of four prospective cohort studies
Authors: Sagelv Edvard H , Hopstock Laila Arnesdatter , Morseth Bente , Hansen Bjørge H , Steene-Johannessen Jostein , Johansson Jonas , Nordström Anna , Saint-Maurice Pedro F , Løvsletten Ola , Wilsgaard Tom , Ekelund Ulf , Tarp Jakob 
Published: October 2023

ObjectivesTo examine whether moderate-to-vigorous physical activity (MVPA) modifies the association between sedentary time and mortality and vice versa, and estimate the joint associations of MVPA and sedentary time on mortality risk.MethodsThis study involved individual participant data analysis of four prospective cohort studies (Norway, Sweden, USA, baseline: 2003–2016, 11 989 participants ≥50 years, 50.5% women) with hip-accelerometry-measured physical activity and sedentary time. Associations were examined using restricted cubic splines and fractional polynomials in Cox regressions adjusted for sex, education, body mass index, smoking, alcohol, study cohort, cardiovascular disease, cancer, and/or diabetes, accelerometry wear time and age.Results6.7% (n=805) died during follow-up (median 5.2 years, IQR 4.2 years). More than 12 daily sedentary hours (reference 8 hours) was associated with mortality risk only among those accumulating <22 min of MVPA per day (HR 1.38, 95% CI 1.10 to 1.74). Higher MVPA levels were associated with lower mortality risk irrespective of sedentary time, for example, HR for 10 versus 0 daily min of MVPA was 0.85 (95% CI 0.74 to 0.96) in those accumulating <10.5 daily sedentary hours and 0.65 (95% CI 0.53 to 0.79) in those accumulating ≥10.5 daily sedentary hours. Joint association analyses confirmed that higher MVPA was superior to lower sedentary time in lowering mortality risk, for example, 10 versus 0 daily min of MVPA was associated with 28–55% lower mortality risk across the sedentary time spectrum (lowest risk, 10 daily sedentary hours: HR 0.45, 95% CI 0.31 to 0.65).ConclusionsSedentary time was associated with higher mortality risk but only in individuals accumulating less than 22 min of MVPA per day. Higher MVPA levels were associated with lower mortality risk irrespective of the amount of sedentary time.
Filling the evidence void: exploration of coach and healthcare provider experiences working with pregnant and postpartum elite athletes – a qualitative study
Authors: Davenport Margie H , Ray Lauren , Nesdoly Autumn , Thornton Jane S , Khurana Rshmi , McHugh Tara-Leigh F 
Published: October 2023

ObjectiveRecent research grounded in the experiences of elite female athletes has shed light on the complex challenges of navigating sport environments that do not support or value pregnant or postpartum athletes. The purpose of this study was to explore the unique experiences of coaches and healthcare providers working with pregnant and postpartum elite athletes, and to identify actionable steps for research, policy and culture change to support them.MethodsSixteen participants (five coaches, three physicians and eight physiotherapists), who have worked with pregnant and/or postpartum elite athletes within the last 5 years, participated in this qualitative study. Thirteen participants self-identified as women, and three as men. Data were generated via semistructured one-on-one interviews that were audiorecorded, transcribed verbatim and analysed through a process of content analysis.ResultsThe findings of this research are represented by five main themes: (a) lack of female athlete reproductive research, (b) need for evidence-informed education and training, (c) need to develop evidence-based progression for sport participation in pregnancy and postpartum, (d) open communication to support athlete-centred care and (e) essential supports and changes required for pregnant/postpartum athletes.ConclusionFindings from this study, which are grounded in the unique perspectives of coaches and healthcare providers, outline specific recommendations to inform policy and practices that support athletes through the perinatal period, such as developing evidence-based return-to-sport protocols.
Predictors of transitioning to adult mental health services and associated costs: a cross-country comparison
Authors: Appleton Rebecca , Canaway Alastair , Tuomainen Helena , Dieleman Gwen , Gerritsen Suzanne , Overbeek Mathilde , Maras Athanasios , van Bodegom Larissa , Franić Tomislav , de Girolamo Giovanni , Madan Jason , McNicholas Fiona , Purper-Ouakil Diane , Schulze Ulrike M E , Tremmery Sabine , Singh Swaran P 
Published: October 2023

BackgroundYoung people are at risk of falling through the care gap after leaving child and adolescent mental health services (CAMHS) despite an ongoing need for mental health support. Currently, little is known about the predictors of transitioning to adult mental health services (AMHS), and associated healthcare and societal costs as young people cross the transition boundary.ObjectiveTo conduct a secondary data analysis exploring predictors of transitioning or falling through the gap and associated costs.MethodsData were used from a longitudinal study, which followed young people from seven European countries for 2 years after reaching their CAMHS boundary. Predictors of transitioning (including sociodemographic and clinical variables) and longitudinal resource use were compared for 488 young people who transitioned to AMHS versus those who fell through the gap.FindingsYoung people were more likely to transition to AMHS if they were severely ill. Those from Italy, the Netherlands and the UK were more likely to fall through the gap than transition to AMHS. Healthcare costs fell for all young people over the study, with a sharper decrease for those who fell through the gap.ConclusionsTotal healthcare costs fell for all participants, indicating that the intensity of mental health support reduces for all young people as they cross the CAMHS boundary, regardless of clinical need.Clinical implicationsIt is important that alternative forms of mental health support are available for young people who do not meet the AMHS care threshold but still have mental health needs after leaving CAMHS.
Proportion of medical admissions that may be hospitalised at home and their service utilisation patterns: a single-centre, descriptive retrospective cohort study in Singapore
Authors: Ko Stephanie Q , Wang Zhemin , Goh Samuel Li Earn , Soong John T Y 
Published: October 2023

ObjectivesFor eligible patient groups, hospital-at-home (HaH) programmes have been shown to deliver equivalent patient outcomes with cost reduction compared with standard care. This study aims to establish a benchmark of inpatient admissions that could potentially be substituted by HaH services.DesignDescriptive retrospective cohort study.SettingAcademic tertiary hospital in Singapore.Participants124 253 medical admissions over 20 months (January 2016 to August 2017).Primary and secondary outcome measuresThe primary measure was the proportion of hospitalised patients who may be eligible for HaH, based on eligibility criteria adapted for the Singapore context. The secondary measures were the utilisation patterns and outcomes of these patients.ResultsApplying generalised eligibility criteria to the retrospective dataset showed that 53.0% of 124 253 medical admissions fitted the eligibility criteria for HaH based on administrative data. 46.8% of such patients had a length of stay <48 hours (‘short-stay’) and 53.1% had a length of stay ≥48 hours (‘medium-stay’). The mortality rate and the 30-day readmission rate were lower in the ‘short-stay’ cohort (0.6%, 12.8%) compared with the ‘medium-stay’ cohort (0.7%, 20.3%). The key services used by both groups were: parenteral drug administration, blood investigations, imaging procedures and consultations with allied health professionals.ConclusionsUp to 53.0% of medical admissions receive care elements that HaH programmes could provide. Applying estimates of functional limitations and patient preferences, we propose a target of ~18% of inpatient medical admissions to be substituted by HaH services. The methodology adopted in this paper is a reproducible approach to characterise potential patients and service utilisation requirements when developing such programmes.
Study protocol of LANTana: a phase Ib study to investigate epigenetic modification of somatostatin receptor-2 with ASTX727 to improve therapeutic outcome with [177Lu]Lu-DOTA-TATE in patients with metastatic neuroendocrine tumours, UK
Authors: Murphy Ravindhi , Chander Gurvin , Martinez Maria , Ward Caroline , Khan Sairah R , Naik Mitesh , Barwick Tara , Aboagye Eric , Sharma Rohini 
Published: October 2023

IntroductionSuitability for peptide receptor radionuclide therapy (PRRT) for neuroendocrine neoplasia (NENs) depends on presence of somatostatin receptor-2 (SSTR2) determined by [68Ga]Ga-DOTA-peptide-positron emission tomography (PET). Some patients have low or no uptake on [68Ga]Ga-DOTA-peptide-PET, precluding PRRT. The upstream promoter region of SSRT2 is methylated, with percentage of methylation correlating with SSTR2 expression. Demethylating agents increase uptake on PET imaging in vivo such that tumours previously negative on PET become positive, correlating with a dose dependent increase in tumorous SSTR2 expression. LANTana will determine whether treatment with the demethylating agent, ASTX727, results in re-expression of SSTR2 using [68Ga]Ga-DOTA-peptide-PET to image epigenetic modification of the SSTR2 locus, allowing subsequent PRRT.Methods and analysis27 participants with a histological diagnosis of NEN (Ki67<55%) with no or low uptake on baseline [68Ga]Ga-DOTA-TATE-PET/CT will be recruited. Patients will receive 5 days of ASTX727 (fixed dose 35 mg decitabine+100 mg cedazuridine). [68Ga]Ga-DOTA-peptide-PET/CT will be repeated day 8±2; where there is significant uptake greater than liver in most lesions, PRRT will be administered. Primary objective is to determine re-expression of SSTR2 on PET imaging. Tolerability, progression-free survival, overall response and quality of life will be assessed. Methylation in peripheral blood mononuclear cells and tumorous methylation will be evaluated.Ethics and disseminationLANTana has ethical approval from Leeds West Research Ethics Committee (REC Reference: 21/YH/0247).Sponsored by Imperial College London and funded by Advanced Accelerator Applications pharmaceuticals. Results will be presented at conferences and submitted to peer-reviewed journals for publication and will be available on ClinicalTrials.gov.Trial registration numbersEUDRACT number: 2020-003800-15,NCT05178693.
Prognostic prediction models for clinical outcomes in patients diagnosed with visceral leishmaniasis: protocol for a systematic review
Authors: Wilson James , Chowdhury Forhad , Hassan Shermarke , Harriss Elinor K , Alves Fabiana , Dahal Prabin , Stepniewska Kasia , Guérin Philippe J 
Published: October 2023

IntroductionVisceral leishmaniasis (VL) is a neglected tropical disease responsible for many thousands of preventable deaths each year. Symptomatic patients often struggle to access effective treatment, without which death is the norm. Risk prediction tools support clinical teams and policymakers in identifying high-risk patients who could benefit from more intensive management pathways. Investigators interested in using their clinical data for prognostic research should first identify currently available models that are candidates for validation and possible updating. Addressing these needs, we aim to identify, summarise and appraise the available models predicting clinical outcomes in VL patients.Methods and analysisWe will include studies that have developed, validated or updated prognostic models predicting future clinical outcomes in patients diagnosed with VL. Systematic reviews and meta-analyses that include eligible studies are also considered for review. Conference abstracts and educational theses are excluded. Data extraction, appraisal and reporting will follow current methodological guidelines. Ovid Embase; Ovid MEDLINE; the Web of Science Core Collection, SciELO and LILACS are searched from database inception to 1 March 2023 using terms developed for the identification of prediction models, and with no language restriction. Screening, data extraction and risk of bias assessment will be performed in duplicate with discordance resolved by a third independent reviewer. Risk of bias will be assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Tables and figures will compare and contrast key model information, including source data, participants, model development and performance measures, and risk of bias. We will consider the strengths, limitations and clinical applicability of the identified models.Ethics and disseminationEthics approval is not required for this review. The systematic review and all accompanying data will be submitted to an open-access journal. Findings will also be disseminated through the research group’s website (www.iddo.org/research-themes/visceral-leishmaniasis) and social media channels.PROSPERO registration numberCRD42023417226.
Estimating the prevalence of diagnosed Alzheimer disease in England across deprivation groups using electronic health records: a clinical practice research datalink study
Authors: Leahy Thomas Patrick , Simpson Alex , Sammon Cormac , Ballard Clive , Gsteiger Sandro 
Published: October 2023

ObjectiveEstimate the prevalence of diagnosed Alzheimer’s disease (AD) and early Alzheimer’s disease (eAD) overall and stratified by age, sex and deprivation and combinations thereof in England on 1 January 2020.DesignCross-sectional.SettingPrimary care electronic health record data, the Clinical Practice Research database linked with secondary care data, Hospital Episode Statistics (HES) and patient-level deprivation data, Index of Multiple Deprivation (IMD).Outcome measuresThe prevalence per 100 000 of the population and corresponding 95% CIs for both diagnosed AD and eAD overall and stratified by covariates. Sensitivity analyses were conducted to assess the sensitivity of the population definition and look-back period.ResultsThere were 448 797 patients identified in the Clinical Practice Research Datalink that satisfied the study inclusion criteria and were eligible for HES and IMD linkage. For the main analysis of AD and eAD, 379 763 patients are eligible for inclusion in the denominator. This resulted in an estimated prevalence of diagnosed AD of 378.39 (95% CI, 359.36 to 398.44) per 100 000 and eAD of 292.81 (95% CI, 276.12 to 310.52) per 100 000. Prevalence estimates across main and sensitivity analyses for the entire AD study population were found to vary widely with estimates ranging from 137.48 (95% CI, 127.05 to 148.76) to 796.55 (95% CI, 768.77 to 825.33). There was significant variation in prevalence of diagnosed eAD when assessing the sensitivity with the look-back periods, as low as 120.54 (95% CI, 110.80 to 131.14) per 100 000, and as high as 519.01 (95% CI, 496.64 to 542.37) per 100 000.ConclusionsThe study found relatively consistent patterns of prevalence across both AD and eAD populations. Generally, the prevalence of diagnosed AD increased with age and increased with deprivation for each age category. Women had a higher prevalence than men. More granular levels of stratification reduced patient numbers and increased the uncertainty of point prevalence estimates. Despite this, the study found a relationship between deprivation and prevalence of AD.