bluuebunny/crossref_metadata_2025 huggingface dataset:
Human parainfluenza virus 3 field strains undergo extracellular fusion protein cleavage to activate entry
Authors: Stearns Kyle , Lampe George , Hanan Rachel , Marcink Tara , Niewiesk Stefan , Sternberg Samuel H. , Greninger Alexander L. , Porotto Matteo , Moscona Anne
Published: October 2024

Human parainfluenza virus 3 (HPIV3) infection is driven by the coordinated action of viral surface glycoproteins hemagglutinin-neuraminidase (HN) and fusion protein (F). Receptor-engaged HN activates F to insert into the target cell membrane and drive virion-cell membrane fusion. For F to mediate entry, its precursor (F0) must first be cleaved by host proteases. F0 cleavage has been thought to be executed during viral glycoprotein transit through the trans-Golgi network by the ubiquitously expressed furin because F0 proteins of laboratory-adapted viruses contain a furin recognition dibasic cleavage motif RXKR around residue 108. Here, we show that the F proteins of field strains have a different cleavage motif from laboratory-adapted strains and are cleaved by unidentified proteases expressed in only a narrow subset of cell types. We demonstrate that extracellular serine protease inhibitors block HPIV3 F0 cleavage for field strains, suggesting F0 cleavage occurs at the cell surface facilitated by transmembrane proteases. Candidate proteases that may process HPIV3 F
in vivo
were identified by a genome-wide CRISPRa screen in HEK293/dCas9-VP64 + MPH cells. The lung-expressed extracellular serine proteases TMPRSS2 and TMPRSS13 are both sufficient to cleave HPIV3 F and enable infectious virus release by otherwise non-permissive cells. Our findings support an alternative mechanism of F activation
in vivo
, reliant on extracellular membrane-bound serine proteases expressed in a narrow subset of cells. The proportion of HPIV3 F proteins cleaved and infectious virus release is determined by host cell expression of requisite proteases, allowing just-in-time activation of F and positioning F cleavage as another key regulator of HPIV3 spread.

IMPORTANCE

Enveloped viruses cause a wide range of diseases in humans. At the first step of infection, these viruses must fuse their envelope with a cell membrane to initiate infection. This fusion is mediated by viral proteins that require a critical activating cleavage event. It was previously thought that for parainfluenza virus 3, an important cause of respiratory disease and a representative of a group of important pathogens, this cleavage event was mediated by furin in the cell secretory pathways prior to formation of the virions. We show that this is only true for laboratory strain viruses, and that clinical viruses that infect humans utilize extracellular proteases that are only made by a small subset of cells. These results highlight the importance of studying authentic clinical viruses that infect human tissues for understanding natural infection.
Emergent ecology in a microscale model of the surface ocean
Authors: Eigemann Falk , Hoffmann Jutta , Schampera Charlotte , Liu Shuting , Bolaños Luis M. , Heemeyer Mats , Carlson Craig A. , Giovannoni Stephen , Hellweger Ferdi L.
Published: October 2024

Microbial processes operate at the microscale, which is not resolved by existing ecosystem models. Here, we present a novel model that simulates a 1 mL three-dimensional cube using a hybrid Lagrangian–Eulerian approach, at ecologically relevant timescales. The model simulates individual microbes, including three phytoplankton size classes with healthy, senescent, and dead lifecycle stages; copiotrophic and oligotrophic heterotrophic bacteria; and dissolved organic matter at 50 µm resolution. Diffusion, shear, sedimentation, chemotaxis, and attachment processes are explicitly resolved. The emerging quantitative representation of the ecosystem shows that (1) copiotrophs grow mostly attached to eukaryotic phytoplankters and get almost all of their carbon from them vs. oligotrophs that grow on exudates and lysates of cyanobacteria; (2) contrasting diel patterns in substrate appearance in the phycosphere vs. ambient water and growth of particle-associated copiotrophs vs. free-living oligotrophs; (3) attached bacteria reduce carbon flux from the phycosphere, lowering chemotactic efficiency toward eukaryotes below that toward cyanobacteria; (4) shear reduces chemotactic efficiency and fitness of the copiotroph; and (5) the main benefit of chemotaxis is to locate attachment partners. These patterns are consistent with available observations. Our study provides insights into the microscale ecology of marine bacteria, and the open-source code is a tool for further research in this area.

IMPORTANCE

A large amount of global CO
2
fixation is performed by marine phytoplankton, and a substantial fraction of that is released as dissolved organic carbon and further processed by heterotrophic bacteria. The interaction between phytoplankton and bacteria, i.e., the carbon flux between them, is therefore an important process in the global carbon and climate system. Some bacteria have developed specialized behavioral traits, like swimming and attachment, to increase their carbon acquisition. These interactions occur at the micrometer scale, for example, the immediate vicinity of phytoplankters (the phycosphere), but existing biogeochemical models typically only simulate down to the 1 meter vertical or ~100 kilometer horizontal scale. We present a new microscale model and use it to predict fluxes and other features in the surface ocean. The model makes important predictions about the fluxes between various types of phytoplankton and bacteria and the role of behavioral traits, and it provides a basis and tool for further research in this area.
Annotated genome sequences of
Salmonella
Haifa,
Salmonella
Bangkok, and
Salmonella
Reading, isolated from chicken meat in South Africa
Authors: Mathole Masenyabu , Carroll Laura , Khabo-Mmekoa Collette , Mabogoane Nomsa , Matle Itumeleng
Published: October 2024

This paper presents the annotated genomes of
Salmonella
Haifa,
Salmonella
Bangkok, and
Salmonella
Reading, which are uncommonly isolated from meat in South Africa. Despite their rarity in South Africa, these serotypes have been linked to several high-profile outbreaks in other parts of the world.
A fur plucking model to study herpes simplex virus reactivation and recurrent disease
Authors: Philip Drake T. , Goins Nigel M. , Lazear Helen M.
Published: October 2024

Herpes simplex viruses (HSV-1 and HSV-2) most commonly cause ulcerative epithelial lesions (cold sores and genital herpes). Importantly, HSV establishes life-long persistent (latent) infection in peripheral neurons. Reactivation from latency produces recurrent epithelial lesions, which constitute the greatest burden of HSV disease in people. The mechanisms that regulate latency and reactivation remain incompletely understood, in part due to limitations in the animal models available for studying HSV reactivation. We have developed a simple and tractable model to induce HSV-1 and HSV-2 reactivation from latency to cause recurrent skin disease. We infected C57BL/6 mice with HSV-1 (strains NS, F, SC16, 17syn+) or HSV-2 (strain 333) on flank skin depilated by manual plucking. After at least 35 days post-infection (dpi), we replucked the fur from the infected flank and observed recurrent lesions in the same dermatome as the primary infection. We detected HSV DNA in dermatome skin through 4 days post-replucking and observed viral antigen and reporter signal in skin lesions by histology, consistent with viral replication following reactivation. In addition to C57BL/6 mice, we were able to produce reactivation in Balb/c and SKH-1 mice. We found that shaving the ipsilateral flank or plucking the contralateral flank did not induce recurrent skin lesions, suggesting that fur plucking is a specific stimulus that induces HSV reactivation. Furthermore, we were able to induce multiple rounds of plucking-induced recurrent disease, providing a model to investigate the lifelong nature of HSV infection. This new model provides a tractable system for studying pathogenic mechanisms of and therapeutic interventions against HSV reactivation and recurrent disease.

IMPORTANCE

Herpes simplex viruses (HSV-1 and HSV-2) have infected over half of the US adult population to cause a lifelong, persistent infection; however, our understanding of the mechanisms that govern HSV reactivation and recurrent disease is incomplete. This is in part due to limitations in the animal models used to study recurrent disease, which are laborious and inefficient in mice. To address this technical gap, we developed a mouse model in which fur plucking after flank skin infection is sufficient to induce episodes of HSV reactivation and recurrent disease. Our work provides a model for the field to investigate the pathogenic mechanisms of HSV and immune responses during recurrent disease and provides an opportunity to investigate the neurobiology of HSV infection.
Black Dark Matter and Antimatter
Authors: Dolgov A. D.
Published: October 2024

It is shown that the dense population of the early universe with well developed galaxies and supermassive black holes (quasars), observed by HST and JWST, nicely fits the conjecture that the galaxies and quasars are seeded by primordial black holes (PBHs), proposed in our work more than 30 years ago. This idea of galaxy seeding by massive black holes is rediscovered in recent publications by several groups. The predicted log-normal mass spectrum of PBHs very well agrees with the observations. Our other prediction of noticeable amount of antimatter in the Galaxy is also confirmed by the data.
Effects of a sedentary behaviour intervention in emergency dispatch centre phone operators: a study protocol for the SECODIS randomised controlled cross-over trial
Authors: Clinchamps Maëlys , Bouillon-Minois Jean-Baptiste , Trousselard Marion , Schmidt Jeannot , Pic Daniel , Taillandier Thierry , Mermillod Martial , Pereira Bruno , Dutheil Frédéric
Published: October 2024

Introduction

Sedentary behaviour is a public health problem. We mainly have sedentary behaviour at work, transforming them into occupational risk. To our knowledge, there is no intervention study on the reduction of occupational sedentary behaviour in a real work situation and its impact on health and biomarkers of stress. The main objective is to study changes in sedentary behaviour following a behavioural intervention (sit-and-stand desk and cycle ergometer).

Methods and analysis

This is a randomised controlled trial in cross-over design conducted in a single centre. The study will be proposed to emergency medical dispatchers of Clermont-Ferrand. Each volunteer will be followed during three cycles of 1 week (3 weeks in total). Each 1-week cycle is made up of 12 hours of work (three conditions: a control and two interventions), 12 hours of successive rest and 6 days of follow-up. For each condition, the measurements will be identical: questionnaire, measure of heart rate variability, electrodermal activity and level of physical activity, saliva and blood sampling. The primary outcome is sedentary behaviour at work (ie, number of minutes per day standing/active). Data will be analysed with both intention-to-treat and per protocol analysis. A p<0.05 will be considered as indicating statistical significance.

Ethics and dissemination

The study protocol has been approved by the Ethics Committee Ouest IV, FRANCE. The study is registered in ClinicalTrials.gov. All patients will be informed about the details of the study and sign written informed consent before enrolment in the study. Results from this study will be published in a peer-reviewed journal. This study involves human participants and was approved by Comité de protection des personnes Ouest IVCPP reference: 23/132-2National number: 2022-A02730-43.

Trial registration number

NCT05931406.
Development and validation of predictive models for mortality of cases with COVID-19 (Omicron BA.5.2.48 and B.7.14): a retrospective study
Authors: Li Peifang , Yang Huiliang , Wu Jinyu , Ma Yanfei , Hou Ailin , Chen Jiali , Ning Ning
Published: October 2024

Objectives

With the emergence of new COVID-19 variants (Omicron BA.5.2.48 and B.7.14), predicting the mortality of infected patients has become increasingly challenging due to the continuous mutation of the virus. Existing models have shown poor performance and limited clinical utility. This study aims to identify the independent risk factors and develop practical predictive models for mortality among patients infected with new COVID-19 variants.

Design

A retrospective study.

Setting and participants

We extracted data from 1029 COVID-19 patients in the respiratory disease wards of a general hospital in China between 22 December 2022 and 15 February 2023.

Outcome measures

Mortality within 15 days after hospital discharge.

Results

A total of 987 cases with new COVID-19 variants (Omicron BA.5.2.48 and B.7.14) were eventually included, among them, 153 (15.5%) died. Non-invasive ventilation, intubation, myoglobin, international normalised ratio, age, number of diagnoses, respiratory rate, pulse, neutrophil count and albumin were the most important predictors of mortality among new COVID-19 variants. The area under the curve of logistic regression (LR), decision tree (DT) and Extreme Gradient Boosting (XGBoost) models were 0.959, 0.883 and 0.993, respectively. The diagnostic accuracy was 0.926 for LR, 0.918 for DT and 0.977 for XGBoost. XGBoost model had the highest sensitivity (0.908) and specificity (0.989).

Conclusion

Our study developed and validated three practical models for predicting mortality in patients with new COVID-19 variants. All models performed well, and XGBoost was the best-performing model.
Influence of temperament on early neurodevelopmental disorders: a systematic review protocol
Authors: Ponce Rodriguez Lucia , Fuentes Rueda Carmen M , Rojo Franconetti Maria , Esteban Laura , Ibáñez-Alfonso Joaquín A
Published: October 2024

Introduction

Several studies have highlighted the role of temperament as a relevant construct to understand the wide variability observed in neurodevelopmental disorders (NDDs) such as autism spectrum disorder and attention deficit hyperactivity disorder. Some studies have pointed to temperamental traits such as strained control as possible precursors to the development of these disorders. In addition, how temperament influences high-risk populations, as well as intervention programmes aimed at families, has been investigated.

Methods and analysis

This paper presents the protocol that will be followed to carry out a systematic review, the objective of which is to know how child temperament is related to the different domains of development in children with NDD or the risk of suffering from it. The search strategy will be implemented in Web of Science (WoS Core Collection), PubMed, ERIC, PsycINFO and Cochrane databases. The risk of bias will be measured by the Newcastle-Ottawa Scale to carry out the integration of the results obtained to synthesis without meta-analysis will be used. This systematic review aims to improve scientific evidence for institutions and professionals and enhance the effectiveness of early care programmes for children with NDD and their families.

Ethics and dissemination

No express approval has been sought from any ethics committee because there is no primary data involved and no access to confidential patient information.

PROSPERO registration number

CRD42023445173.
Oxford Vaccine Hesitancy Scale (OVHS): a UK-based and US-based online mixed-methods psychometric development and validation study of an instrument to assess vaccine hesitancy
Authors: Kantor Jonathan , Carlisle Robert C , Morrison Michael , Pollard Andrew J , Vanderslott Samantha
Published: October 2024

Objectives

To describe the development, validation and reliability of the Oxford Vaccine Hesitancy Scale (OVHS), a new instrument to assess vaccine hesitancy in the general population.

Design

Cross-sectional validation study.

Setting

Internet-based study with participants in the UK and USA.

Participants

Demographically representative (stratified by age, sex and race) samples from the UK and USA recruited through the Prolific Academic platform.

Main outcome measures

To demonstrate OVHS development, exploratory factor analysis with categorical variables and a polychoric correlation matrix followed by promax oblique rotation on the UK sample was performed. Confirmatory factor analysis with a Satorra-Bentler scaled test statistic evaluating goodness of fit statistics including the root mean squared error of approximation (RMSEA), standardised root mean squared residual (SRMR) and comparative fit index (CFI) was performed on the US sample. Reliability as internal consistency was assessed using McDonald’s omega. Evidence in support of the predictive, convergent and discriminant validity of the scale was assessed using logistic regression ORs of association (OR) or Pearson correlation coefficients.

Results

Data for factor analysis were obtained from 1004 respondents, 504 in the UK and 500 in the USA. A scree plot, minimum average partial correlation analysis and parallel analysis suggested a three-factor 13-item scale with domains of vaccine beliefs (seven items), pain (three items) and personal deliberation (three items). Responses were recorded on a Likert scale ranging from disagree completely to agree completely, with higher score reflecting greater hesitancy. Potential total scores ranged from 13 to 65. Goodness of fit was excellent, with RMSEA=0.044, SRMR=0.041 and CFI=0.977. Predictive validity for COVID-19 vaccination status was excellent, with logistic regression ORs of association (95% CI) of 0.07 (0.04, 0.13), p<0.0001 for the UK sample for each SD increase in OVHS score, suggesting a 93% decrease in the odds of being vaccinated against COVID-19 for each SD increase in OVHS score. Convergent validity between the OVHS score and the 5C short version scale demonstrated a correlation coefficient of 0.32 (p<0.0001). Discriminant validity with an unrelated desire to perform outdoor activities demonstrated an OR (95% CI) of 1.06 (0.88, 1.29), p=0.523 for the UK sample for each SD increase in OVHS score. McDonald’s omega was 0.86 and 0.87 in the UK and US samples, respectively.

Conclusions

The OVHS is a feasible, valid and reliable scale for assessing vaccine hesitancy; further testing is warranted.
Quality and completeness of, and spin in reporting of, pilot and feasibility studies in hip and knee arthroplasty: a protocol for a methodological survey
Authors: Chung Zinnia , Mbuagbaw Lawrence , Mokete Lipalo , Bhandari Mohit , Thabane Lehana
Published: October 2024

Introduction

Pilot or feasibility trials examine the feasibility, viability and recruitment potential of larger, main trials. Specifically, a pilot trial can be instrumental in identifying methodological issues essential to the development of an effective research protocol. However, numerous studies published as pilot or feasibility studies have demonstrated notable inconsistencies in the nature of information reported, resulting in poor-quality and incomplete reporting. It is unclear whether such low quality or incompleteness of reporting is also prevalent in arthroplasty pilot trials.

Methods and analysis

This protocol outlines a methodological survey examining the completeness of reporting among hip and knee arthroplasty pilot trials in accordance with the Consolidated Standards of Reporting Trials (CONSORT) 2010 extension to pilot trials. Secondary objectives include: (1) determining the prevalence of ‘spin’ practices, defined as: (a) placing a focus on statistical significance rather than feasibility, (b) presenting results that show the trial to be non-feasible as feasible or (c) emphasising the effectiveness or potential intervention benefits rather than feasibility; (2) determining factors associated with incomplete reporting, and ‘spin’. A search of PubMed will be conducted for pilot trials in hip or knee arthroplasty published between 01 January 2017 and 31 December 2023. Following screening, appropriate data will be extracted from eligible publications and reported as descriptive statistics, encompassing elements of the CONSORT checklist associated with completeness of reporting. Logistic regression analysis and Poisson regression will be used to analyse factors associated with completeness of reporting and spin.

Ethics and dissemination

This methodological review does not require formal ethical approval, as it will solely involve the use of published and publicly reported literature. The results of this study will be disseminated through submission to peer-reviewed journals and academic conference presentations. Study details will be sent to McMaster University’s media coordinators to be shared through the institution’s research-focused platforms.
Prevalence of and factors associated with pre-diabetes among adolescents in Eastern Sudan: a community-based cross-sectional study
Authors: Alsafi Walaa Mamoun , Al Eed Ashwaq , Hassan Ahmed Ali , Al-Nafeesah Abdullah , Alfaifi Jaber , Adam Ishag
Published: October 2024

Objectives

There is an increasing trend of pre-diabetes and diabetes mellitus (DM) among adolescents, and sub-Saharan Africa is no exception. However, few published data on pre-diabetes among adolescents in Sudan exist. We aimed to investigate the prevalence of and factors associated with pre-diabetes among adolescents in Eastern Sudan.

Design

A community-based cross-sectional study was conducted from August to October 2023.

Settings

This community-based study was conducted in Gadarif city, the capital of Gadarif state, Eastern Sudan.

Participants

Adolescents (within the ages of 10–19 years).

Main outcome measures

A questionnaire was used to collect socio-demographic information. Anthropometric and glycated haemoglobin (HbA1c) measurements were performed in accordance with standard procedures. Multivariate logistic regression analysis was performed.

Results

Of the 387 enrolled adolescents, 207 (53.5%) were female and 180 (46.5%) were male. The median (IQR) age was 14.0 (12.0–16.0) years. 39.5% of the participants’ fathers were employed. The median (IQR) HbA1c was 5.5% (5.2%–5.8%). One-third (32.6%) of the adolescents had pre-diabetes or DM. Of the participants, 67.4%, 30.0% and 2.6% had no DM, pre-diabetes or type 2 DM, respectively. In the univariate analysis, the father’s employment (OR=1.60, 95% CI=1.03 to 2.50) was associated with increased odds of pre-diabetes; age, sex, parents’ education, the mother’s occupation, body mass index z-score, cigarette smoking and a family history of DM were not associated with pre-diabetes. In the multivariate analysis, the father’s employment (adjusted OR=1.70, 95% CI=1.03 to 2.50) was associated with increased odds of pre-diabetes.

Conclusion

Pre-diabetes is a significant public health problem among adolescents in Eastern Sudan. The introduction of early screening programmes for pre-diabetes at the community level is recommended to halt the progression of pre-diabetes to DM and to deal with existing DM among adolescents.
Cohort profile: a nationwide study in DutchCHEK2c.1100delC families using the infrastructure of the HEreditary Breast and Ovarian cancer study Netherlands – Hebon-CHEK2
Authors: Schreurs Maartje A.C. , Adank Muriel A , Hollestelle Antoinette , de Groot Rosa , Stommel-Jenner Denise J , Van Asperen Christi J. , Ausems Margreet G.E.M. , Berger Lieke P V , Blok Marinus J , van Engelen Klaartje , Hogervorst Frans B L , Geurts-Giele Willemina , Gille Johan J P , Wevers Marijke R , Schmidt Marjanka K , Hooning Maartje J.
Published: October 2024

Purpose

CHEK2c.1100delC is associated with an increased breast cancer risk in women. While this variant is prevalent in the Netherlands (1% in the general population), knowledge of aetiology and prognosis of breast cancer and other tumours inCHEK2c.1100delC carriers is lacking. The nationwide HEreditary Breast and Ovarian cancer study the Netherlands (Hebon) cohort aims to answer study questions in families with an increased risk of breast cancer and ovarian cancer. While initially focusing onBRCA1/2-variant families, Hebon gradually expanded to include pathogenic variants in other genes associated with breast and/or ovarian cancer over time. This provides an excellent setting to establish a cohort to ultimately study the impact ofCHEK2c.1100delC on cancer risk prediction and surveillance, breast cancer treatment and prognosis.

Participants

We invited all heterozygous and homozygousCHEK2c.1100delC indexes and tested female relatives. 1802 women were included, of whom 1374 were heterozygotes and 938 were breast cancer cases. Pedigrees were collected from all clinical genetic departments. Furthermore, participants completed a detailed questionnaire on hormonal and lifestyle factors, family history, cancer diagnosis and treatment.

Findings to date

Mean age at study inclusion was 53 years. Linkage with the Netherlands Cancer Registry showed a younger age at diagnosis in homozygotes (mean age 41.7 years) and heterozygotes (47.9 years) than non-carriers (51.2 years). Furthermore, carriers were more often diagnosed with grade 2, oestrogen receptor-positive breast cancer and more often developed contralateral breast cancer than non-carriers. Most women consumed alcohol regularly and about half never smoked.

Future plans

Further data linkages with the Netherlands Cancer Registry will allow prospective follow-up and breast cancer risk assessment in unaffected women at the time of genetic testing, risk of contralateral breast cancer and survival in patients with breast cancer. Also, linkage with the nationwide network and registry of histopathology and cytopathology in The Netherlands (PALGA) allows us to retrieve tumour samples to study tumourigenesis.
Decline in and recovery of fertility rates after COVID-19-related state of emergency in Japan
Authors: Mitoma Tomohiro , Maki Jota , Ooba Hikaru , Masuyama Hisashi
Published: October 2024

Introduction

The COVID-19 pandemic led to a decline in fertility rates worldwide. Although many regions have experienced a temporary drop in fertility rates with the spread of the infection, subsequent recovery has varied across countries. This study aimed to evaluate the impact of COVID-19 infection rates and regional sociodemographic factors on the recovery of fertility rates in Japan following the state of emergency.

Methods

This study examined prefectural fertility data from before the COVID-19 pandemic to forecast fertility rates up to 2022 using a seasonal autoregressive integrated moving average model. A regression analysis was conducted on fertility rates during the first state of emergency and the subsequent recovery rate with respect to the number of new COVID-19 cases and sociodemographic factors specific to each prefecture.

Results

During the first state of emergency, the monthly fertility rate decreased by an average of −13.8% (SD: 6.26, min: −28.78, max: 0.15) compared with the previous year. Over the following 22 months, the average fertility recovery rate was +2.31% (SD: 3.57; min: −8.55, max: 19.54). Multivariate analysis of the impact of the pandemic on fertility changes during the first emergency indicated a negative correlation between new COVID-19 cases per capita and the proportion of nuclear households. No significant correlation was found between fertility recovery rate and new COVID-19 cases or emergency duration. When classifying fertility rate fluctuation patterns before and after the emergency into four clusters, variations were noted in the proportion of the elderly population, marriage divorce rate and the number of internet searches related to pregnancy intentions across the clusters.

Conclusions

No association was found between pregnancy intentions related to the spread of infection, such as the number of new cases and the fertility recovery rate following the first state of emergency. Differences in the patterns of decline and recovery during the pandemic were observed based on population composition and internet searches for infection and pregnancy across different prefectures.
Objectively measured daily steps and health outcomes: an umbrella review of the systematic review and meta-analysis of observational studies
Authors: Xu Chunlan , Jia Jinli , Zhao Binbin , Yuan Man , Luo Nan , Zhang Fan , Wang Hui
Published: October 2024

Objectives

The purpose of this review is to summarise the evidence from a systematic review and meta-analysis of observational studies that objectively measure daily steps and health outcomes.

Design

This is an umbrella review.

Data sources

PubMed, Embase, Scopus, the Cochrane Library and Web of Science databases were searched through 31 January 2024.

Eligibility

We included systematic reviews of observational studies (with or without meta-analysis) that assessed the association of objectively measured daily steps with human health-related outcomes. Methodological quality was assessed using ‘A MeaSurement Tool to Assess systematic Reviews 2’.

Results

A total of 10 systematic reviews and 6 health outcomes were included after excluding irrelevant and duplicate studies. Higher daily steps were associated with more benefits than harms for a range of health-related outcomes, including all-cause mortality, cardiovascular event, skeletal muscle lesions, metabolic diseases and respiratory disease. A dose-response analysis showed that an increase of 500–1000 steps per day was associated with lower all-cause mortality and cardiovascular events. Beneficial associations were also found in patients with asthma and acutely hospitalised older adults. Conversely, one study within a systematic review suggested that higher daily steps (≥10 000) might be associated with an increased 52% risk of meniscal pathologies in individuals without knee osteoarthritis. However, one study within a systematic review suggested a potential increased risk of meniscal pathologies in individuals without knee osteoarthritis. Specifically, those exceeding 10 000 steps per day showed a 52% increase in risk.

Conclusion

The results of this study suggest that daily steps are associated with a lower risk of all-cause mortality and cardiovascular events. Future research could focus on identifying specific populations that may benefit most from increased daily steps and exploring potential mechanisms to enhance our understanding of how daily steps contribute to improved health outcomes.

PROSPERO registration number

CRD42022347055.
Semaglutide treatment for PRevention Of Toxicity in high-dosE Chemotherapy with autologous haematopoietic stem-cell Transplantation (PROTECT): study protocol for a randomised, double-blind, placebo-controlled, investigator-initiated study
Authors: Sørum Maria Ebbesen , Gang Anne Ortved , Tholstrup Dorte Maegaard , Gudbrandsdottir Sif , Kissow Hannelouise , Kornblit Brian , Müller Klaus , Knop Filip K
Published: October 2024

Introduction

Cancer treatment with high-dose chemotherapy damages the mucosal barrier of the gastrointestinal (GI) tract and is associated with severe toxicity involving mucositis, severe inflammation and organ dysfunction. Currently, there is no effective prophylaxis against this. Glucagon-like peptide 1 (GLP-1), a well-known regulator of blood glucose, has been suggested in mouse studies to possess trophic effects on gut epithelial cells as well as anti-inflammatory properties. In line with this, endogenous GLP-1 levels have been shown to be inversely correlated with toxicities after haematopoietic stem cell transplantation (HSCT) and treatment with a GLP-1 receptor agonist (GLP-1RA) was shown to limit chemotherapy-induced mucositis in rodents. This present study investigates the effects of the GLP-1RA semaglutide on GI mucositis severity score in patients with lymphoma undergoing high-dose chemotherapy followed by autologous (auto) HSCT.

Methods and analysis

This is a randomised, double-blind, placebo-controlled, two-centre investigator-initiated clinical study. Forty adult patients with malignant lymphoma referred for auto-HSCT will be randomised in a 1:1 manner to receive either semaglutide or placebo once-weekly for 8 weeks. This includes a run-in period of 3–4 weeks with semaglutide 0.25 mg prior to high-dose chemotherapy treatment followed by a period of 4–5 weeks with semaglutide 0.5 mg including the 1 week of high-dose chemotherapy treatment. Clinical assessment of endpoint measurements and safety will be performed weekly during treatment and in a follow-up period of 10 weeks. The primary endpoint is GI mucositis severity (mean severity grade (0–II) during week 1–4 after auto-HSCT). Secondary endpoints include C-reactive protein increment, quality of life and safety. Fever, bacteraemia, antibiotic use, weight loss, morphine consumption, duration of hospitalisation, use of parenteral nutrition, change in muscle mass and clinical and laboratory evidence of organ toxicities will also be assessed.

Ethics and dissemination

The study complies with Danish and European Union legislation and is approved by the Danish Medicines Agency, the Danish National Medical Research Ethics Committee (EU CT #2022-502139-20-00) and the Danish Data Protection Agency. The study is monitored by the Capital Region of Denmark’s good clinical practice unit. All results, positive, negative and inconclusive, will be disseminated at national and international scientific meetings and in peer-reviewed scientific journals.

Trial registration number

NCT06449625
Exploring the early experiences of assisted dying in Aotearoa New Zealand: a qualitative study protocol
Authors: Young Jessica , Dehkhoda Aida , Ahuriri-Driscoll Annabel , Cheung Gary , Diesfeld Kate , Egan Richard , Karaka-Clarke Te Hurinui , Moeke-Maxwell Tess , Reid Kate , Robinson Jackie , Snelling Jeanne , White Ben , Winters Janine
Published: October 2024

Introduction

Increasing numbers of jurisdictions are legalising assisted dying (AD). Developing research protocols to study the experiences and outcomes of legislation is imperative. AD is a topic that, by nature of its complexity and inherent ethical issues, lends itself to qualitative research. Using the objectives of the statutory framework, this qualitative study aims to provide a robust review of the newly formed AD service in New Zealand and the extent to which it is safe, people-centred, dignity-enhancing, accessible and available equitably to all eligible people.

Methods and analysis

The research uses an appreciative inquiry design to focus on what is working well, what could be improved, what constitutes the ‘ideal’ and how to enable people to achieve that ideal. We are using online semi-structured interviews and face-to-face focus groups to explore the experiences of key stakeholders: eligible/ineligible service users; eligible/ineligible service users with impairments; families of service users; AD providers; non-providers (providers who object to AD and others who are not directly involved in providing AD but are not opposed in principle); health service leaders; and Māori community members. An estimated 110 participants will be interviewed. We will conduct thematic and regulatory analyses of data.

Ethics and dissemination

The ethical aspects of this study have been approved by the Northern A Health and Disability Ethics Committee through the full review pathway (2023 EXP 18493). To disseminate the findings, we will draft resources to support interviewee groups, to be developed with feedback from stakeholder meetings. We will submit evidence-based recommendations to inform the government review of the End of Life Choice Act 2019. Findings will be disseminated in peer-reviewed publications, conferences, webinars, media, stakeholder feedback sessions and accessible research briefings.
Control of myopia using diffusion optics spectacle lenses: 4-year results of a multicentre randomised controlled, efficacy and safety study (CYPRESS)
Authors: Laughton Deborah , Hill Jennifer S , McParland Marcella , Tasso Vanessa , Woods Jill , Zhu Xiaoying , Young Graeme , Craven Ruth , Hunt Chris , Neitz Jay , Neitz Maureen , Chalberg Thomas W , Jones Deborah , Wolffsohn James S
Published: October 2024

Aims

To evaluate the myopia control efficacy of Diffusion Optics Technology (DOT) spectacle lenses in children over a 4-year treatment period.

Methods

CYPRESS Part 1 (NCT03623074) was a 3-year multicentre, randomised, controlled, double-masked trial comparing two investigational spectacle lens DOT designs (Test 1, Test 2) and standard single vision Control lenses in 256 North American children aged 6–10 years. Children completing Part 1 (n=200) were invited to enrol in CYPRESS Part 2 (NCT04947735) for an additional 1-year period. In Part 2, Test 1 (n=35) and Control groups (n=42) continued with their original lens assignment and the Test 2 group (n=21) were crossed over to Test 1 (DOT 0.2) lenses. The co-primary endpoints were change from baseline in axial length (AL) and cycloplegic spherical equivalent refraction (cSER).

Results

Test 1 spectacle lenses demonstrated superiority to the Control in both co-primary endpoints: with a difference between means (Test 1−Control) of −0.13 mm for AL (p=0.018) and 0.33 D for cSER (p=0.008) in Part 1 and −0.05 mm for AL (p=0.038) and 0.13 D for cSER (p=0.043) in Part 2. Comparing treatment effects in Part 1 and 2 suggests that COVID-19 public health restrictions negatively impacted treatment efficacy in study years 2 and 3.

Conclusion

DOT 0.2 spectacle lenses are safe and effective at reducing myopia progression, with additional benefit evident in year 4 of wear. These results support the hypothesis that a mild reduction in retinal contrast can slow myopia progression in young children. The unprecedented disruption in participant schooling and lifestyle during the COVID-19 pandemic may have depressed treatment efficacy in Part 1.
Impact of the asylum determination process on mental health in the UK and EU+: a systematic review and thematic synthesis
Authors: Mulcaire Jessie , Smetham Dom , Holt Leah , Zard Sana , Brady Francesca , O'Driscoll Ciarán
Published: October 2024

Introduction

People seeking asylum are at increased risk of mental health difficulties due to premigration and postmigration experiences. The objective of this review was to understand how asylum determination process in the EU+ and UK influences the mental health of asylum seekers.

Methods

Web of Science, MEDLINE, PsycINFO, PsychArticles and Scopus were searched, with no start date specified, up to 24 August 2023. Peer-reviewed studies were eligible if they provided a qualitative analysis of primary data from adult asylum seekers and refugees regarding lived experience of asylum determination procedures in the UK and EU+, and contextual factors associated with the mental health and well-being. The protocol was not preregistered. From a total of 4902 articles, duplicates were removed, 3235 abstracts were assessed and of the remaining 113 identified for full-screen articles, 39 relevant qualitative studies were retrieved. Six further studies were identified through citation searches.

Results

45 studies were included in the qualitative thematic synthesis, representing the perspectives of 1158 asylum seekers and refugees. Themes demonstrate high levels of psychological distress during and after the asylum process. This was associated with the hostile environments created by policies and procedures. Participants’ mental health was affected by being caught in a stalemate while awaiting the outcome of their claim. The procedures exacerbated previous mental health difficulties. External and internal protective factors were identified, such as non-governmental organisations, religion and cognitive strategies.

Conclusions

The accumulation of each step of the asylum process contributes to psychological distress and exacerbates mental health difficulties, leading to longer-term consequences for asylum seekers and refugees. Preventive strategies and policy changes are recommended. To minimise the impact of asylum procedures, clinicians should consider peer-led groups, interventions that cultivate a sense of autonomy and meaning and reduce a sense of alienation and isolation.
County-level racial bias is associated with worse care for white and especially black older US adults: a cross-sectional observational study
Authors: Mizel Matthew L , Haas Ann , Adams John L , Martino Steven C , Haviland Amelia M , Ghosh-Dastidar Bonnie , Dembosky Jacob W , Williams Malcolm , Abel Gary , Maksut Jessica , Gildner Jennifer , Elliott Marc N
Published: October 2024

Objective

To assess the association of county-level bias about black and white people with patient experience, influenza immunisation, and quality of clinical care for black and white older US adults (age 65+ years).

Design

Linear multivariable regression measured the cross-sectional association of county-level estimates of implicit and explicit bias about black and white people with patient experiences, influenza immunisation, and clinical quality-of-care for black and white older US adults.

Participants

We used data from 1.9 million white adults who completed implicit and explicit bias measures during 2003–2018, patient experience and influenza immunisation data from respondents to the 2009–2017 Medicare Consumer Assessment of Healthcare Providers and Systems (MCAHPS) Surveys, and clinical quality-of-care data from patients whose records were included in 2009–2017 Healthcare Effectiveness Data and Information Set (HEDIS) submissions (n=0.8–2.9 million per measure).

Main outcome measures

Three patient experience measures and patient-reported influenza immunisation from the MCAHPS Survey; five HEDIS measures.

Results

In county-level models, higher pro-white implicit bias was associated with lower immunisation rates and worse scores for some patient experience measures for black and white adults as well as larger-magnitude black-white disparities. Higher pro-white implicit bias was associated with worse scores for some HEDIS measures for black and white adults but not with black-white disparities in clinical quality of care. Most significant associations were small in magnitude (effect sizes of 0.2–0.3 or less).

Conclusions

To the extent that county-level pro-white implicit bias is indicative of bias among healthcare providers, there may be a need for interventions designed to prevent such bias from adversely affecting the experiences and preventive care of black patients and the clinical quality of care for all patients.
Systemic concentration of apelin, but not resistin or chemerin, is altered in patients with schizophrenia
Authors: Kozłowska Elżbieta , Brzezińska-Błaszczyk Ewa , Wysokiński Adam , Żelechowska Paulina
Published: October 2024

It has been suggested that immune-inflammatory processes might be involved in the etiopathogenesis of schizophrenia. Since growing evidence indicates that adipokines strongly modulate the course of immune response and inflammatory processes, it is currently suggested the contribution of those factors in the etiology of schizophrenia as well. The aim of this study was to determine the serum levels of 4 adipokines—apelin, resistin, chemerin, and omentin—in patients with schizophrenia as compared with healthy subjects. Fifty-seven adult patients with schizophrenia and 31 healthy volunteers were included in this prospective study. ELISA was used to measure the serum concentration of resistin, apelin, omentin-1, and chemerin. No difference in the mean concentration of resistin (p=0.20) and chemerin (p=0.30) between patients with schizophrenia and the healthy group was observed. Apelin concentration was significantly (p=0.004) lower in patients with schizophrenia as compared with controls. A significant difference in apelin level between men with schizophrenia and control group (p=0.04) was reported. Apelin concentration was significantly correlated with waist-to-hip ratio, whereas chemerin concentration was significantly correlated with the Positive and Negative Syndrome Scale G score. There exists evidence that apelin might be involved in the pathogenesis of schizophrenia.
Factors associated with failure of intraosseous access in prehospital trauma treatment by military medical personnel
Authors: Rittblat Mor , Kotovich D , Tsur N , Beer Z , Radomislensky I , Gendler S , Almog O , Tsur A M , Avital G , Talmy T
Published: October 2024

Introduction

Intraosseous devices have become an alternative to peripheral intravenous (PIV) access. Despite the established success of intraosseous devices in laboratory and simulator studies, there is a lack of data regarding their real-world utilisation in prehospital settings. Therefore, this study aims to evaluate the success rates of intraosseous access in a prehospital military context and identify factors associated with failure.

Methods

Using the Israel Defense Forces (IDF) Trauma Registry, we retrospectively collected data from 2010 to 2023. The primary outcome was the first pass success rate of intraosseous access, and logistic regression models were applied to identify variables associated with first pass failure.

Results

The study included 172 trauma patients who underwent attempted intraosseous access with 46.5% cases which were classified as military events. The median age was 22 years, and 17.3% were paediatric patients. First pass success was achieved in 67.4% of cases, with a cumulative success rate of 80.8% after multiple attempts. Moreover, significant differences were noted when examining the success rate of the three intraosseous devices used by the IDF teams, with the highest success rate being documented for the NIO Adult versus the EZ-IO or the BIG (81.4%; 76.7%; 62.4%). However, logistic regression analysis revealed that the number of PIV access attempts was the only variable significantly associated with decreased odds of achieving first pass intraosseous access.

Conclusion

These findings suggest that intraosseous devices are a viable alternative for establishing vascular access in prehospital military settings. However, success rates were slightly lower than previous reports, potentially due to the severity of injuries in the study cohort. Our analyses revealed a higher number of PIV access attempts correlated with reduced first pass intraosseous success, possibly stemming from caregiver proficiency in obtaining vascular access. Further research is needed to explore additional factors affecting intraosseous access success rates.
Cardiovascular risk according to genetic predisposition to gout, lifestyle and metabolic health across prospective European and Korean cohorts
Authors: Moon Ki Won , Jung Sang‑Hyuk , Do Hyunsue , Son Chang-Nam , Kim Jaeyoung , Nam Yonghyun , Yun Jae-Seung , Park Woong-Yang , Won Hong-Hee , Kim Dokyoon
Published: October 2024

Objective

Recent studies have reported that gout is associated with a risk of cardiovascular disease (CVD) later in life. However, the predictive value of genetic predisposition to gout combined with lifestyle habits for CVD risk remains unclear. This study aimed to examine the association between genetic predisposition to gout and lifestyle habits and the risk of developing CVD in two diverse prospective cohorts from different ancestries.

Methods

A total of 224 689 participants of European descent from the UK Biobank and 50 364 participants of East Asian descent from the Korean Genome and Epidemiology Study were included. The genetic risk for gout was assessed using a polygenic risk score (PRS) derived from a meta-genome-wide association study (n=444 533). The incident CVD risk was evaluated according to genetic risk, lifestyle and metabolic syndrome (MetS).

Results

Individuals at high genetic risk for gout had a higher risk of incident CVD than those with low genetic risk across ancestry. Notably, a reduction in CVD risk by up to 62% (HR 0.38; 95% CI 0.31 to 0.46; p <0.001) was observed in individuals at both low and high genetic risk for gout when they maintained ideal MetS and favourable lifestyle habits.

Conclusions

Our findings indicate that a higher genetic risk of gout is significantly associated with an increased risk of CVD. Moreover, adherence to a favourable lifestyle can significantly reduce CVD risk, particularly in individuals with high genetic risk. These results underscore the potential of PRS-based risk assessment to improve clinical outcomes through tailored preventative strategies.