bluuebunny/crossref_metadata_2025 huggingface dataset:
Pilot study protocol evaluating the impact of telerobotics interactions with autistic children during a Denver intervention on communication skills using single-case experimental design
Authors: Fournier Carole , Michelon Cécile , Granit Véronique , Audoyer Paul , Bernardot Arielle , Picot Marie-Christine , Kheddar Abderrahmane , Baghdadli Amaria
Published: November 2024

Introduction

For several years, studies have been conducted on the contribution of social robots as an intervention tool for children with autism spectrum disorder (ASD). One of the early intervention models recommended by the French National Authority for Health is the Early Start Denver Model, an individualised, intensive programme based on play activities chosen by the child. While studies published in recent years suggest that robots provide benefits for autistic children in learning social interactions within a clinical setting, there is no scientific consensus on the widespread contribution and maintenance of their effects over time. On the other hand, a robotic solution controlled directly by a practitioner (ie, on-site telepresence system) enables greater adaptability to children’s responses and choices during interventions. We believe that such a solution would enable better assessment of progress in the fundamental skills of expressive communication and imitation as well as greater engagement during interventions.

Methods and analysis

This is a prospective, monocentric, descriptive and evaluative pilot study based on single-case experimental design (SCED) methodology. The study will recruit eight children diagnosed with ASD aged between 2 and 5 years. The intervention will take place 15 min after the usual weekly care. The SCED methodology is constructed in three stages: (A) 4 weekly sessions at baseline without the robot, (B) 9 weekly sessions with intervention modification using a social robot as cotherapist and (C) 4 weekly sessions without the robot for follow-up.

Ethics and dissemination

Ethical approval was obtained from the South East IV Ethics Committee (CPP Sud-Est IV) (number: 2023-A00895-40) in France. Explicit consent is required from all legal representatives (parents) of children participating in this study. We aim to disseminate the results of this study through national and international conferences, international peer-reviewed journals and social media.

Trial registration number

NCT05991791.
Combination of body mass index and body fat percentage in middle and late pregnancy to predict pregnancy outcomes in patients with gestational diabetes in Wenzhou, China: a single-centre retrospective cohort study
Authors: Chen Bingru , Chen Lanxi , Zhao Xiner , You Tao , Zheng Zhi , Chen Yilin , Zhu Shuoru
Published: November 2024

Objectives

The present study aimed to evaluate whether body mass index (BMI) and body fat percentage (BFP) could be used to predict pregnancy outcomes in patients with gestational diabetes mellitus (GDM).

Design

Retrospective cohort study.

Setting

Wenzhou Medical University Affiliated Second Hospital (Zhejiang Province, China). Clinical data were collected from electronic medical records.

Participants

Data from 683 patients with GDM admitted to the Wenzhou Medical University Affiliated Second Hospital between January 2019 and December 2021 were retrospectively analysed.

Outcome measures

Pregnancy outcomes.

Results

The results showed that pregnant women with BFP ≥33% were more prone to abnormal amniotic fluid volume, abnormal blood pressure and anaemia (p<0.05). Additionally, these patients were more likely to experience postpartum haemorrhage and macrosomia, as well as risk factors associated with caesarean section at labour (p<0.05). BMI exhibited a strong predictive value for abnormal blood pressure (OR 1.170; 95% CI 1.090 to 1.275), anaemia (OR 1.073; 95% CI 1.016 to 1.134), caesarean section (OR 1.150; 95% CI 1.096 to 1.208) and macrosomia (OR 1.169; 95% CI 1.063 to 1.285). Additionally, classified BFP had a predictive value for abnormal amniotic fluid volume (OR 3.196; 95% CI 1.294 to 7.894), abnormal blood pressure (OR 2.321; 95% CI 1.186 to 4.545), anaemia (OR 1.817; 95% CI 1.216 to 2.714), and caesarean section (OR 1.734; 95% CI 1.270 to 2.367).

Conclusions

The results suggest that patients with GDM with BFP ≥33% were more likely to experience unfavourable pregnancy outcomes, undergo caesarean section and develop macrosomia. The combination of BMI with classified BFP could better predict abnormal blood pressure and caesarean section in patients with GDM during the middle and late stages of pregnancy.
Persuasive design principle of social support in digital interventions targeting mental health symptoms: a systematic review and meta-analysis
Authors: Mutter Agnes , Bücheler Mara , Idrees Abdul Rahman , Domhardt Matthias , Baumeister Harald
Published: November 2024

Objective

This systematic review and meta-analysis evaluates the available evidence on efficacy of social support strategies, as defined by the persuasive system design framework, in internet-based and mobile-based interventions (IMI) targeting mental health.

Design

Systematic review and meta-analysis.

Data sources

PubMed, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials.

Eligibility criteria for selecting studies

Randomised controlled trials comparing IMI implementing a social support strategy for mental health symptoms to various control conditions. Publications up to June 2023 (date of search 6 June 2023) were considered.

Data extraction and synthesis

Two independent reviewers screened and extracted data in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed with the Risk of Bias Tool V.2.0. Data were pooled based on a random-effects model.

Results

After screening 6484 records, a total of 45 studies met our inclusion criteria. At 96%, social support was predominantly implemented through the strategy of social facilitation, by which users recognising others using the intervention (eg, discussion forum). IMI implementing social support strategies showed moderate effect sizes of Hedges’g=−0.34 (95% CI −0.47 to −0.21, p<0.001) in comparison to different control conditions. Heterogeneity was considerable (I2=73.6%; 95% CI 64.8 to 80.3). Subgroup analyses revealed a significant influence of targeted psychological condition (p<0.001), type of social support (p<0.001) and control condition (p<0.001). Ink=11 component studies (ie, comparison to a disentangled version of the same intervention), IMI with social support strategies were not significantly more effective in comparison to the same IMI without social support (Hedges’g=−0.08 (95% CI −0.22 to 0.05, p=0.19, I2=0%). 64% (k=7) of component studies reported higher adherence rates in IMI with social support.

Conclusions

Based on a small number of component studies, implementing social support strategies in IMI that target mental health symptoms has no significant incremental benefit on effectiveness. To draw more robust conclusions, the potential of other social support strategies besides social facilitation should be exploited in future component studies.

PROSPERO registration number

CRD42020222810.
Mothers’ health-seeking practices and associated factors towards neonatal danger signs in Ethiopia: a systematic review and meta-analysis
Authors: Ferede Wassie Yazie , Yimer Tigist Seid , Gelaw Tiruset , Mekie Maru , Zewude Shimeles Biru , Mekete Getachew , Alemayehu Habtam Desse , Sisay Fillorenes Ayalew , Ayalew Abeba Belay , Mitiku Assefa Kebie , Yehuala Enyew Dagnew , Erega Besfat Berihun
Published: November 2024

Background

A decrease in obtaining quality healthcare is a major cause of maternal and newborn deaths in low-income and middle-income countries. Ethiopia has one of the highest neonatal mortality rates. Increasing mothers’ health-seeking practices related to neonatal danger signs is an essential strategy for reducing the death rate of newborns. However, the pooled prevalence of mothers’ health-seeking practices related to neonatal danger signs is not well known in Ethiopia.

Objective

The main aim of this systematic review and meta-analysis is to assess the mothers’ health-seeking practices and associated factors towards neonatal danger signs in Ethiopia.

Design

Systematic review and meta-analysis.

Primary and secondary outcomes

The primary outcome was to assess the mothers’ health-seeking practices towards neonatal danger signs and the secondary outcome was to identify factors associated with health-seeking practices.

Methods

In total, comprehensive literature was searched in the PubMed, Google Scholar, HINARI, Embase and CINAHL databases published up to 30 December 2023. A random effect model was used to estimate the pooled prevalence and adjusted OR (AOR). Stata (V.17.0) was used to analyse the data. I2statistics were computed to assess heterogeneity among studies. To minimise the underlying heterogeneity, a subgroup analysis was conducted based on the study region and year of publication. To assess publication bias, Egger’s test and funnel plots were used.

Results

Overall, 1011 articles were retrieved, and 11 cross-sectional studies, with a total of 5066 study participants, were included in this systematic review. The overall pooled prevalence of mothers’ health-seeking practices for neonatal danger signs in Ethiopia was 52.15%. Postnatal care follow-up (AOR 2.72; 95% CI 1.62 to 4.56), good maternal knowledge (AOR 3.20, 95% CI 2.24 to 4.56), educational status of secondary school and above (AOR 4.17, 95% CI 2.04 to 8.55), women’s decision-making autonomy (AOR 3.59, 95% CI 1.60 to 8.06) and place of delivery (AOR 2.71, 95% CI 1.21 to 6.04) were significantly associated with mothers’ health-seeking practices for neonatal danger signs.

Conclusion

The maternal health-seeking practices of women towards neonatal danger signs were found to be low in Ethiopia. When barriers to seeking care for newborn danger signs are successfully removed, women’s practices for seeking care for neonatal danger signs could decrease perinatal mortality.
Weight control efforts and practices and health professional advice: a cross-sectional national survey in England
Authors: Jackson Sarah E , Warr William , Brown Jamie , Hartmann-Boyce Jamie , Jebb Susan A , Tudor Kate , Shahab Lion , Aveyard Paul
Published: November 2024

Objectives

There is evidence that general practitioners (GPs) can increase the uptake of weight management programmes that enhance weight loss compared with self-directed efforts, but the rate at which they do so is unclear. This study examined the prevalence of weight control efforts and practices, the reported frequency and impact of receipt of GP advice on weight loss attempts and perceptions of the appropriateness of health professionals delivering weight loss advice.

Design

A nationally representative cross-sectional survey.

Setting

England.

Participants

1722 adults (≥16 years) surveyed in October 2018 (mean (SD) age=47.4 (19.2), 51.1% women).

Main outcome measures

Weight control efforts and practices, whether a GP gave advice or a specific referral/prescription medication, perception of the appropriateness of GP weight loss advice.

Results

Two-thirds (64.7% (95% CI 58.1% to 71.3%)) of people with obesity reported trying to lose weight. Of people with obesity who visited their GP in the past year, 40% (95% CI 32.2% to 47.7%) recalled receiving any advice on weight loss: 30.8% (95% CI 23.5% to 38.2%) general advice and 9.2% (95% CI 4.6% to 13.7%) a referral to a weight loss service or prescription medication for weight loss. Having received weight loss advice from a GP was strongly associated with a greater likelihood of trying to lose weight (general advice: ORadj=4.49, 95% CI 2.52 to 8.00; referral/medication: ORadj=9.25, 95% CI 2.65 to 32.3). Views on whether health professionals should deliver weight loss advice were mixed, with a substantial minority (19.4% (95% CI 17.5% to 21.4%)) finding it unacceptable. People with a BMI outside of the healthy weight range (underweight/overweight/obesity), women and those from more disadvantaged social grades were less likely to find it acceptable.

Conclusions

Most people with obesity reported trying to lose weight but less than half recalled receiving advice on weight loss from their GP in the past year and few were referred to community weight-loss programmes. Those who recalled receiving GP advice on weight loss were substantially more likely to report taking action to lose weight. One in five people thought GP advice on weight loss was inappropriate.
High-flow weaning strategies for infants with bronchiolitis: protocol for a pilot randomised controlled trial in the UK
Authors: Towriss Christopher , Dafydd Carwyn , Edwards Martin
Published: November 2024

Introduction

Ward-based high-flow nasal cannula (HFNC) is an effective therapy for children with bronchiolitis who have failed standard oxygen therapy. However, HFNC can increase hospital length of stay perhaps because there is a lack of evidence to guide weaning strategies.

We aim to conduct a pilot study to identify the most effective weaning strategy for infants, up to 12 months, supported on HFNC for bronchiolitis. This may lead to reduced time on respiratory support and shorter length of stay. If this pilot study is deemed feasible, it will inform a larger multicentre trial.

Methods and analysis

This open label, non-blinded, randomised controlled trial will be conducted over 24 months at the Noah’s Ark Children’s Hospital for Wales, Cardiff, and will aim to recruit 20 patients. It will compare high-flow only weaning (high-flow discontinued at FiO2of 21%) to HFNC and low-flow weaning (HFNC discontinued at 30% and replaced by low-flow up to 2 L/min). HFNC therapy will be delivered at 2 L/kg/min (maximum 20 L/min). The primary outcome is to examine the feasibility of different weaning strategies for infants with bronchiolitis requiring HFNC. Secondary outcomes include the time from decision to wean HFNC to the patient no longer requiring respiratory support and a safety assessment of the weaning strategies.

Ethics and dissemination

Health Research Authority and Health and Care Research Wales approval was granted on 8 September 2020 following review by the NHS research ethics committee.The sponsor is Cardiff and Vale University Health Board. We will publish the results in a peer-reviewed medical journal, via websites and newsletters.

Trial registration number

NCT04287959.
Exploring how to widen the acceptability of public health interventions: a systematic review protocol
Authors: Conway-Moore Kaitlin , Graham Fiona , McKinlay Alison R , Birch Jack , Oliver Emily , Bambra Clare , Kelly Michael P , Bonell Chris
Published: November 2024

Introduction

Health interventions that require significant change to individual lifestyles or social norms can pose a challenge for widespread public acceptability and uptake. At the same time, over the last two decades, there has been increasing attention paid to the rise of populist movements globally, defined by ‘the people’ pushing against ‘an elite’ viewed as depriving the people of their sovereignty. To understand potential overlap in these two areas, this study aims to synthesise existing international evidence on linkages between populist attitudes and reduced uptake, acceptability, adherence and/or effectiveness of public health interventions. The goal of this work is to create a conceptual framework that can be used to inform policy strategies aimed at widening the impact of public health interventions.

Methods and analysis

A systematic review will be performed via searches across databases and websites relevant to public health and social science research, informed by preliminary searches on the topic. There will be no language restrictions, but included studies will be limited to those produced since 2008, the year of the global financial crisis, from which most current literature on populism dates. Risk of bias will be assessed using validated tools according to study design. Due to expected heterogeneity across included studies, this will be a systematic review without meta-analysis. Findings will be synthesised narratively, and the strength of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The review will be reported according to the Systematic Reviews without Meta-Analysis reporting guidelines.

Ethics and dissemination

Ethical review is not required for this study. Public dissemination will be informed via consultation with our Patient and Public Involvement and Engagement Strategy Group, along with reporting via peer-reviewed publication, relevant international conferences, a policy brief and a workshop with public health and communications experts.

PROSPERO registration number

CRD42024513124.
A service evaluation of the uptake and effectiveness of a digital delivery of the NHS health check service
Authors: Salway Ruth , Sillero-Rejon Carlos , Forte Chloe , Grey Elisabeth , Jessiman Patricia , McLeod Hugh , Harkes Rebecca , Stokes Paul , De Vocht Frank , Campbell Rona , Jago Russell
Published: November 2024

Objectives

To compare the uptake, effectiveness and costs of a digital version of the National Health Service (NHS) Health Check (DHC) to the standard face-to-face NHS Health Check (F2F).

Participants and setting

A random sample of 9000 patients aged 40–74 eligible for an NHS Health Check in Southwark, England, between January and April 2023.

Intervention and design

The DHC was an online tool with a health assessment section, an advice and support section, and a section on how to obtain and update follow-up physical measures (blood pressure, cholesterol, glycated haemoglobin (HbA1c)). 6000 patients from GP records were randomly allocated to receive a DHC invitation and 3000 to receive an F2F invitation. Those invited to DHC were able to choose F2F if they preferred.

Outcomes

The primary outcome was the uptake of any type of health check, either a completed F2F appointment or completion of the DHC health assessment section, along with demographics and data on appointments, medications and referrals within the study period. QRISK3 and QDiabetes risk scores were calculated. Management and operation costs were estimated for F2F and DHC pathways.

Results

Excluding participants who moved away or died, the DHC uptake to the health assessment section was 21% (1189/5705), with a further 3% (198/5705) choosing F2F, compared with 11% (305/2900) for F2F completion (p<0.001). The DHC uptake was lower among those from Black (14%) and Mixed (13%) compared with White (29%) ethnicities (p<0.001), and there was no evidence of higher DHC uptake among groups less likely to engage in NHS Health Checks. Of those who completed the health assessment, 60% (714) completed the support section, and 7% (84) completed the provision and updating of physical measures. Appointments, medications and referrals were lower among DHC service users than among F2F users (p<0.001). The estimated total management and operation costs for F2F were £154.80 per user, compared with total management and operation costs for DHC of £68.48 per user for health assessment only, £134.46 including the support section and £1479.01 per user with completed physical measures.

Conclusions

The study suggests that a choice of Health Check pathways may potentially reduce pressures on the NHS. Cholesterol and HbA1c were not generally known, and the options to obtain and update these measures require further development for the DHC to be considered a viable comparable alternative to the F2F service for estimating cardiovascular disease and diabetes risk. Strategies are still needed to reach those groups not currently engaging with NHS Health Checks.

Registration

This study was registered on the Open Science Framework:https://osf.io/y87zt.
Perinatal health in a cohort of children conceived after assisted reproduction in the UK: a population-based record-linkage study
Authors: Purkayastha Mitana , Sutcliffe Alastair , Brison Daniel R , Nelson Scott M , Lawlor Deborah , Roberts Stephen A
Published: November 2024

Objective

To compare the risk of hospitalisation for conditions originating in the perinatal period between children conceived via assisted reproductive technology and those that are naturally conceived, differentiating by treatment type.

Study design, setting and participants

Population-based record-linkage study of children born after assisted reproduction in the UK between 2002 and 2009 (n=44 618), their naturally conceived siblings (n=8462) and matched naturally conceived population (n=89 072) controls linked to their hospital inpatient records up to 31 March 2016.

Primary and secondary outcome measures

Robust estimates of the overall and cause-specific risk of hospital admission for adverse perinatal events and the comparison of outcomes by type of treatment.

Results

Over the study period, 17 132 (38.40%) children conceived via assisted reproduction and 30 306 (34.02%) and 1738 (20.54%) naturally conceived population and sibling controls, respectively, were admitted to the hospital for severe perinatal events. Compared with the population controls, singletons (Risk ratio (95% CI 1.30 (1.26, 1.34))) and twins (1.01 (0.99, 1.03)) conceived via assisted reproduction exhibited a higher risk of hospitalisation for any adverse perinatal event. However, no such increase was observed in the within-sibling analysis (0.97 (0.84, 1.12)). Similar patterns were seen for diagnoses related to length of gestation and fetal growth (vs population controls: 1.37 (1.29, 1.46); vs siblings: 1.17 (0.86, 1.60)); birth trauma (vs population controls: 1.23 (1.04, 1.44); vs siblings: 0.78 (0.47, 1.30)); respiratory and cardiovascular disorders (vs population controls: 1.28 (1.20, 1.38); vs siblings: 0.72 (0.53, 0.98)); infections (vs population controls: 1.30 (1.06, 1.59); vs siblings: 0,68 (0.24, 1.90)) and several other conditions. Associations were similar when comparing in vitro fertilisation to intracytoplasmic sperm injection and were higher when comparing fresh to frozen embryo transfers.

Conclusion

Children conceived via assisted reproduction showed modest increases in the risk of hospitalisations for severe perinatal events when compared with population controls, although these findings were attenuated in the sibling analyses. The imprecision of within-sibling analyses highlights the need for larger studies to explore potential causal effects.
Insights on health policies from a political philosophy perspective
Authors: Abiétar Daniel G , Martí-González Mariacarla , Aguiló Elena , Sánchez-Valdivia Nacho
Published: November 2024

Health policies play a crucial role in shaping people’s well-being. While public health often relies on evidence-based policy to improve health outcomes, many non-scientific factors determine the health policy-making process. This article explores how public health advocacy can be strengthened by examining the relationship between political philosophy and the scientistic aspirations of public health.

We begin by critically assessing the deliberative decision-making model, offering insights on policy processes that could inspire new directions in health policy research. To enhance these efforts, we delve into the philosophical critique of scientism, aiming to liberate public health from its technocratic inclinations. Our analysis draws on political philosophy from two angles: first, we revisit Renaissance utopias to highlight the risks of a science-driven society devoid of ethics; second, we introduce modern perspectives on democratic justice, advocating for health policies that resist domination.

Ultimately, we argue for a new model of health policy science that positions public health as a key political actor. By focusing on the everyday realities of policy-making, public health can tackle two fundamental questions: How are citizens’ interests considered in health policy? And how do we deliberate the goals and means of health policy? By addressing these questions, our proposals aim to enhance public health advocacy, promoting research and actions that lead to more just and inclusive health policies, ensuring the protection of everyone’s health.
Within-person relationship between employment insecurity and mental health: a longitudinal analysis of the Understanding America Study
Authors: Jin Haomiao , Lee Woo Jung , Maupin Daniel , Lee Jungeun Olivia
Published: November 2024

Background

Employment insecurity is a socioeconomic factor influencing mental health, yet the empirical evidence supporting this claim has important limitations. The fluctuations in employment insecurity throughout the COVID-19 pandemic offered a distinctive opportunity to delve deeper into this issue. By viewing employment as a dynamic process, this study explores the within-person relationship between shifts in employment status and corresponding changes in mental health.

Methods

24 waves of data between April 2020 and March 2021 from the Understanding America Study (N=3824) were analysed using a within-person multilevel model. Employment security was modelled as a dynamic process involving transitions between secure employment, underemployment and unemployment with or without benefits. Mental health was measured by questionnaires on core symptoms of depression and anxiety.

Results

Downward transitions in employment security, from secure employment to underemployment or unemployment without benefits, were associated with worse mental health. Persisting in unemployment without benefits was also associated with poorer mental health, and regaining job security did not immediately improve it. Timely provision of unemployment benefits mitigated the adverse mental health impacts. Significant cross-level moderation effects were observed for prepandemic mental health status, Hispanic ethnicity and education level.

Conclusion

Downward transitions in employment security compromise mental health, and certain segments of the population experience worse consequences. Regaining job security is not associated with immediate improvement in mental health. Timely provision of unemployment benefits, providing support for both unemployment and underemployment and targeting vulnerable groups are vital for alleviating adverse mental health impacts from losing job security.
High long-term mortality in ischaemic heart disease accentuated among ethnic minorities in Eastern Europe: findings from a prospective all-comers percutaneous coronary intervention registry in Romania
Authors: Călburean Paul-Adrian , Grebenișan Paul , Nistor Ioana-Andreea , Șulea Ioana Paula , Scurtu Anda-Cristina , Brinzaniuc Klara , Suciu Horatiu , Harpa Marius , Dobreanu Dan , Hadadi Laszlo
Published: November 2024

Background

Long-term outcomes in cardiovascular diseases are historically under-reported in Eastern Europe. Our aim was to report long-term survival and to identify survival predictors in a prospective Romanian percutaneous coronary intervention (PCI) registry, with an emphasis on important under-resourced minorities, such as Hungarian and Roma ethnicities.

Methods

An all-comers patient population treated by PCI in a tertiary cardiovascular centre that has been included prospectively in the local registry since January 2016 was analysed. Cardiovascular cause and all-cause mortality data were available as of December 2023.

Results

A total of 6867 patients with 8442 PCI procedures were included. Romanian group consisted of 5095 (74.2%) patients, the Hungarian group consisted of 1417 (20.6%) patients and the Roma group consisted of 355 (5.1%) patients. During a median follow-up of 3.60 (1.35–5.75) years, a total of 1064 cardiovascular-cause and 1374 all-cause events occurred. Romanian, Hungarian and Roma patients suffered 5.12, 5.89 and 7.71 all-cause deaths per 100 patient-years, respectively. Romanian, Hungarian and Roma patients suffered 3.94, 4.63 and 6.22 cardiovascular-cause deaths per 100 patient-years, respectively. Both Hungarian and Roma patients presented significantly higher all-cause mortality than Romanian patients (adjusted HR (aHR)=1.20 (1.05–1.36), p=0.005 and aHR=1.51 (1.21–1.88), p=0.0001). Similarly, Hungarian and Roma patients presented significantly higher cardiovascular cause mortality than Romanian patients (aHR=1.22 (1.05–1.41), p=0.006 and aHR=1.51 (1.18–1.92), p=0.0008).

Conclusions

High long-term cardiovascular and all-cause mortality was observed for the entire included population. Long-term survival was significantly lower in ethnic minorities, such as the Hungarian and Roma minority than in the Romanian population.
ICOS-expressing CAR-T cells mediate durable eradication of triple-negative breast cancer and metastasis
Authors: Cao Lixue , Peng Haojie , Chen Yanzhen , Xia Baijin , Zeng Tao , Guo Jialing , Yu Fei , Ye Haiyan , Zhang Hui , Chen Xinxin
Published: November 2024

Background

The failure of conventional therapies and the propensity for recurrence and metastasis make triple-negative breast cancer (TNBC) a formidable challenge with grim prognoses and diminished survival rates. Immunotherapy, including immune checkpoint blockade and chimeric antigen receptor (CAR)-T cell therapy, presents innovative and potentially more effective strategies for addressing TNBC. Within this context, the inducible costimulator (ICOS), a member of the CTLA4/CD28 family, plays a crucial role in regulating immune responses and T-cell differentiation by binding to its ligand ICOSL. However, the impact of the ICOS/ICOSL axis on cancer varies.

Methods

In this study, immunohistochemistry was conducted to examine the expression level of ICOSL in TNBC tumor tissues. We developed ICOS-enhanced B7H3-CAR-T cells (ICOS-B7H3-CAR) using the third-generation CAR-T cell technology, which featured magnified ICOS expression and targeted the B7H3 antigen. Xenograft and metastasis models of TNBC were conducted to examine the cytotoxicity and durability of CAR-T cells in tumors. Overexpression and CRISPR/Cas9-mediated knockout (KO) techniques were employed to regulate the expression of ICOSL on TNBC cell lines.

Results

Notably, we observed elevated ICOSL expression in TNBC tumor tissues, which correlated with poor survival prognosis in patients with TNBC. Compared with conventional B7H3-CAR-T cells, ICOS-B7H3-CAR-T cells significantly inhibited the tumor growth of TNBC cells both in vitro and in vivo, accompanied by increased secretion of cytokines such as interferon gamma and tumor necrosis factor alpha. Furthermore, the in vivo experiments illustrated that ICOS-B7H3-CAR-T cells exhibited prolonged antitumor activity and could effectively eradicate metastases in a TNBC metastasis model, consequently extending survival. Importantly, manipulating the expression of ICOSL on TNBC cells through overexpression or KO significantly influenced the function of ICOS-B7H3-CAR-T cells. This suggests that the level of ICOSL expression on TNBC cells is critical for enhancing the potent antitumor effects of ICOS-B7H3-CAR-T cells.

Conclusion

Overall, our study highlights the potential clinical application of ICOS as a promising strategy for combating TNBC recurrence and metastasis.
Making my voice and owning its future
Authors: Preece Jamie , Sullivan Emma , Tams-Gray Fin , Pullin Graham
Published: November 2024

This article explores disabled experience and the future of technologies relating to augmentative and alternative communication (AAC). This field includes people’s use of AAC devices, typically in combination with other modes of communication, including vocalising, revoicing and body language. Such devices have speech technology and digital voices built into them and we will consider who could be said to have ownership of these technologies. We will also explore the role that people who use AAC have in making their AAC—and how this also contributes to shaping its future. The meanings of ‘voice’, ‘making’ and ‘ownership’ in the context of AAC are many. Yet too often the relationship between these is presented as if it is singular and straightforward. This paper will start by considering the most prevalent, obvious interpretations and build alternative and more complex directions from there. One of the authors uses AAC and is constantly personalising his software, editing and remaking it to reflect his needs and current thinking, representing his voice in ways that he feels ownership of; another is a life partner and can also be thought of as being part of his AAC. Two authors are researchers in an art school, where the act of making things in studios and workshops is inseparable from creative authorship and ownership. Together, all four authors are exploring the meaning and making of speech technology, experimenting with and appropriating it in ways not anticipated by its developers. This paper is a hybrid of voices: disabled and non-disabled; academic and non-academic coresearchers; designers and codesigners. Its unconventional format is intended to reflect the unconventional relationship between the researchers and to represent the conversation between these different voices.
Using disease-modifying treatments in multiple sclerosis: Association of British Neurologists (ABN) 2024 guidance
Authors: Rashid Waqar , Ciccarelli Olga , Leary Siobhan M , Arun Tarunya , Doshi Anisha , Evangelou Nikos , Ford Helen L , Hobart Jeremy , Jacob Saiju , Muraro Paolo Antonio , Murray Katy , Palace Jacqueline , Dobson Ruth
Published: November 2024

The Association of British Neurologists last published guidelines on disease-modifying treatment (DMT) in multiple sclerosis (MS) in 2015. Since then, additional DMTs have been licensed and approved for prescribing within the National Health Service for relapsing-remitting MS, early primary progressive MS and active secondary progressive MS. This updated guidance provides a consensus-based approach to using DMTs. We provide recommendations for eligibility, starting, monitoring, switching and stopping of DMTs; pregnancy; equitable access to DMT; autologous haemopoietic stem-cell transplantation; and use of generics. We highlight best practice where it exists and discuss future priorities.
Cognitive screening instruments: time for retirement
Authors: Larner Andrew J
Published: November 2024

Cognitive screening instruments are used daily in clinics devoted to the assessment of cognitive disorders and also in general neurology clinics where patients with complaints of memory disorder may be encountered. However, these instruments have significant theoretical and practical shortcomings that are generally overlooked or ignored. In pursuit of biological rather than nosological diagnosis, and in light of these shortcomings, I recommend that cognitive screening instruments should now be abandoned.
Exploring small retailers’ perspectives on selling tobacco after the tripling of Tasmania’s tobacco licence fee
Authors: Smith Abby L , Mihrshahi Seema , Freeman Becky
Published: November 2024

Background

Licensing of tobacco retailers, including high retail licence fees, is one tobacco control measure that may reduce tobacco retail availability. Between 2015 and 2018, the tobacco licence fee in Tasmania, Australia, tripled to $A1132/year. We sought to explore small retailer perspectives on selling tobacco following the tripling of the licence fee.

Methods

In-depth semistructured telephone interviews (n=21) were conducted with business owners and managers between March and July 2020. Participants were asked broad questions about their business, attitudes and intentions towards selling tobacco and the perceived importance of tobacco to their business.

Results

Participants’ perspectives and decision-making about selling tobacco were influenced by an interplay of factors, including tobacco’s perceived core business value and its waning importance in small retail due to declining demand. Although participants frequently reported tobacco as unprofitable, with many describing it as their least profitable product, most continued selling it. The high tobacco licence fee created a tipping point that challenged the cost-benefit balance previously weighted towards selling tobacco. While the fee, alongside the increasing cost of tobacco itself, pushed some retailers towards a critical decision point to stop selling tobacco, others continued to sell tobacco but appear to be headed in the same direction.

Conclusion

A high annual tobacco licence fee serves as a potential mechanism for phasing out the sale of commercial tobacco in small retailers in a jurisdiction with other strong tobacco control measures.
Hierarchical modelling of epibenthic communities on the Scotian Shelf and Gulf of Maine (Atlantic Canada) in support of conservation planning
Authors: Murillo Francisco Javier , Weigel Benjamin , Clark Donald , Kenchington Ellen
Published: November 2024

Identification of ecologically significant units at different spatial scales is essential for management of biodiversity attributes. This case study illustrates a coupled methodological approach to delineate benthic habitats and associated assemblages at different spatial scales. Two complementary analyses were employed based on the occurrences of 99 epibenthic invertebrate species in Atlantic Canada, sampled during depth-stratified random trawl sets. To identify epibenthic assemblage types, isometric feature mapping and partitioning around medoids (ISOPAM) was used in combination with a joint species distribution model (JSDM), which also produced continuous distribution surfaces across the spatial domain. ISOPAM identified nine significantly spatially coherent assemblages (biotopes) at spatial scales of hundreds of meters to hundreds of kilometers, with associated diagnostic species. Those assemblages were closely matched by eight regions of common profile using the JSDM, indicating strong environmental influences on their distributions. These smaller-scale assemblages were grouped into three biophysical units. The results from the JSDM were validated with independent data showing good congruence. This indicates that the spatial units ascribed to identified assemblages are robust and suitable for marine spatial planning and monitoring.
Delineating early life stages of Belone belone: analysis of external morphology and postcranial skeletal development of the garfish
Authors: Fischbach Vivian , Thieme Philipp , Polte Patrick , Moritz Timo
Published: November 2024

During fish larvae development functional, morphological, and physiological adaptations are key in larval survival strategies and can determine mortality bottlenecks. For many fish groups such as needlefish, which play crucial roles in marine food webs, studies on early life stages are almost lacking. Herein, the development, with focus on the postcranial skeleton, of the garfish Belone belone (Linnaeus, 1761) is described and a staging system is introduced. Ten larval and juvenile life stages are proposed in three main phases: yolk sac, larval, and juvenile development. During the yolk sac phase the garfish deplete their yolk reservoirs and finish the development of their unpaired fins. During the larval period the lower jaw elongates and the needlenose stage is reached. In the juvenile phase, the upper jaw elongates until both jaws are almost equally long. Since B. belone larvae develop much of their postcranial skeleton in the late embryonic and yolk sac phases they might not experience a severe bottleneck in this early stage such as many other marine fish species. Therefore, young garfish could be more resilient to environmental changes.
Representations of the su(1,1) current algebra and probabilistic perspectives
Authors: Floreani Simone , Jansen Sabine , Wagner Stefan
Published: November 2024

We construct three representations of the [Formula: see text] current algebra: in extended Fock space, with Gamma random measures, and with negative binomial (Pascal) point processes. For the second and third representations, the lowering and neutral operators are generators of measure-valued branching processes (Dawson–Watanabe superprocesses) and spatial birth–death processes. The vacuum is the constant function [Formula: see text] and iterated application of raising operators yields Laguerre and Meixner polynomials. In addition, we prove a Baker–Campbell–Hausdorff formula and give an explicit formula for the action of unitaries [Formula: see text] on exponential vectors. We explain how the representations fit in with a general scheme proposed by Araki and with representations of the [Formula: see text] current group with Vershik, Gelfand and Graev’s multiplicative measure.
ENHANCEMENT OF ALUMINUM ALLOY (AL7075) COMPOSITE BY THE ADDITION OF CRS PARTICLE VIA STIR CASTING TECHNIQUE
Authors: Arunkumar S. , Ashok Kumar R. , Bibin Chidambaranathan , Soundararajan Gopinath
Published: November 2024

In this research, we added crushed rock sand (CRS) particles to an Al7075 matrix material, and composites were fabricated through a stir-casting approach. The reinforcement percentage varies from 0% to 12% by weight in discrete increments of 3%. Physical and mechanical parameters such as hardness, ultimate tensile strength, and impact toughness and corrosion performance by the gravimetric method, as well as tribological properties such as specific wear rate and coefficient of friction (COF), were tested at both ambient temperature ([Formula: see text]C) and elevated temperature ([Formula: see text]C). The density of the developed composite samples has been substantially lowered with an intensification in wt.% of CRS particles. The mechanical parameters of the developed composite samples have been considerably enhanced with an intensification in wt.% of CRS particles. The 9[Formula: see text]wt.% CRS-reinforced samples have an outstanding incrementation percentage of 52.44% hardness, 24.85% tensile strength, and 19.90% impact toughness. Better corrosion resistance is observed for the 9[Formula: see text]wt.% sample. Similarly, the same sample shows a 28.06% increase in specific wear rate at [Formula: see text]C and a 43.35% increase at [Formula: see text]C.
ANALYSIS OF PARAMETRIC INFLUENCES AND MACHINING BEHAVIOR IN EDM OF Al 6061–B4C–Fe2O3 BY TAGUCHI APPROACH
Authors: RAJAN A. FRANCIS XAVIER , KUMAR L. RAMESH , SURESH R.
Published: November 2024

Wire Electrical Discharge Machining (WEDM) to achieve high-quality finishes by minimizing the experimental errors in the application of Metal Matrix Composites, which are often necessary with various manufacturing industries. The Al 6061 composites have been made by the fabrication the alloy through stir casting process. In this work, metallurgical and the effect of machining characteristics of Al alloy, Al 6061, through reinforcing with B4C and Fe2O3 investigated. This work an effort has been made on applying Taguchi and ANOVA methods in order to optimize the outcomes L[Formula: see text] orthogonal array was utilized in this investigation. The third dimension perspective to this composite has been acquired for the input settings, comprising higher composites (wt.%) and current, lower pulse on time ([Formula: see text]) and pulse off time ([Formula: see text]), and the output variables, which include material removal rate (MRR), electrode wear rate (EWR), and depth, with the aid of the Signal to Noise (S/N) and the small is preferable. The analysis of these trial results via S/N ratios makes it clear that the minimized pulse on and off and more current found in machining, and lower pulse on and off, optimal results parameters were also reached.
Is It Possible to Truly Understand Performance in LLMs?
Authors: Greengard Samuel
Published: November 2024

Seeking to understand when, and how, emergence takes place.
PEak: A Single Source of Truth for Hardware Design and Verification
Authors: Donovick Caleb , Melchert Jackson , Daly Ross , Truong Lenny , Raina Priyanka , Hanrahan Pat , Barrett Clark
Published: November 2024

Domain-specific languages for hardware can significantly enhance designer productivity, but sometimes at the cost of ease of verification. On the other hand, ISA specification languages are too static to be used during early stage design space exploration. We present PEak, an open-source hardware design and specification language, which aims to improve both design productivity and verification capability. PEak does this by providing a single source of truth for functional models, formal specifications, and RTL. PEak has been used in several academic projects, and PEak-generated RTL has been included in three fabricated hardware accelerators. In these projects, the formal capabilities of PEak were crucial for enabling both novel design space exploration techniques and automated compiler synthesis.
MagNet: Multilevel Dynamic Wavelet Graph Neural Network for Multivariate Time Series Classification
Authors: Hong Xiaobin , Hu Jiangyi , Xu Taishan , Ren Xiancheng , Wu Feng , Ma Xiangkai , Li Wenzhong
Published: November 2024

Multivariate Time Series Classification (MTSC)
is a fundamental data mining task, which is widely applied in the fields like health care and energy management. However, the existing MTSC methods are mostly adapted from univariate versions and model the static patterns among series in the time domain. We argue they fail to capture the inter-dependencies across variables and rarely consider the unique dynamic features in multilevel frequencies, which are susceptible to signal noise and lack sufficient feature extraction capability to achieve satisfactory classification accuracy. To address these issues, we propose a novel framework called
Multilevel Dynamic Wavelet Graph Neural Network (MagNet)
, which effectively captures inherent temporal-frequency dependencies in multivariate time series data in a global view, facilitating the information flow among inter-related variables and leveraging learnable
Graph Neural Networks (GNNs)
to uncover dynamic frequency dependencies. We propose an orthogonal temporal convolution layer that utilizes soft orthogonal losses to constrain features learned at different frequency components to reduce feature redundancy. Additionally, we introduce a hierarchical graph coarsening operator to address the flat learning challenges in traditional GNNs. Our dynamic wavelet GNN and hierarchical coarsening enable deep model stacking and end-to-end learning. Extensive experiments on 30 UEA benchmarks demonstrate that our method outperforms the state-of-the-art baselines in the MTSC tasks.
A Saturation-Based Unification Algorithm for Higher-Order Rational Patterns
Authors: Chen Zhibo , Pfenning Frank
Published: November 2024

Higher-order unification has been shown to be undecidable. Miller discovered the pattern fragment and subsequently showed that higher-order pattern unification is decidable and has most general unifiers. We extend the algorithm to higher-order rational terms (a.k.a. regular Böhm trees, a form of cyclic

\(\lambda\)

-terms) and show that pattern unification on higher-order rational terms is decidable and has most general unifiers. We prove the soundness and completeness of the algorithm.