bluuebunny/crossref_metadata_2025 huggingface dataset:
Generative artificial intelligence in ophthalmology: current innovations, future applications and challenges
Authors: Sonmez Sadi Can , Sevgi Mertcan , Antaki Fares , Huemer Josef , Keane Pearse A
Published: June 2024

The rapid advancements in generative artificial intelligence are set to significantly influence the medical sector, particularly ophthalmology. Generative adversarial networks and diffusion models enable the creation of synthetic images, aiding the development of deep learning models tailored for specific imaging tasks. Additionally, the advent of multimodal foundational models, capable of generating images, text and videos, presents a broad spectrum of applications within ophthalmology. These range from enhancing diagnostic accuracy to improving patient education and training healthcare professionals. Despite the promising potential, this area of technology is still in its infancy, and there are several challenges to be addressed, including data bias, safety concerns and the practical implementation of these technologies in clinical settings.
Modelling years of life lost due to acute type A aortic dissection in the German healthcare setting: a predictive study
Authors: Schiele Philipp , König Adriana N , Meyer Alexander , Falk Volkmar , Nienaber Christoph A , Kurz Stephan D
Published: June 2024

Objectives

This study aimed to develop a patient-centred approach to the burden of acute type A aortic dissection (ATAAD) through modelling. The main objective was to identify potential improvements in managing this life-threatening cardiovascular condition and to provide evidence-based recommendations to optimise outcomes.

Design

We developed a predictive model along patient pathways to estimate the burden of ATAAD through the years of life lost (YLLs) metric. The model was created based on a systematic review of the literature and was parameterised using demographic data from the German healthcare environment. The model was designed to allow interactive simulation of different scenarios resulting from changes in key impact factors.

Setting

The study was conducted using data from the German healthcare environment and results from the literature review.

Participants

The study included a comprehensive modelling of ATAAD cases in Germany but did not directly involve participants.

Interventions

There were no specific interventions applied in this study based on the modelling design.

Primary and secondary outcome measures

The single outcome measure was the estimation of YLL due to ATAAD in Germany.

Results

Our model estimated 102 791 YLL per year for ATAAD in Germany, with 62 432 and 40 359 YLL for men and women, respectively. Modelling an improved care setting yielded 93 191 YLL or 9.3% less YLL compared with the current standard while a worst-case scenario resulted in 113 023 or 10.0% more YLL. The model is accessible athttps://acuteaorticdissection.com/to estimate custom scenarios.

Conclusions

Our study provides an evidence-based approach to estimating the burden of ATAAD and identifying potential improvements in the management of pathways. This approach can be used by healthcare decision-makers to inform policy changes aimed at optimising patient outcomes. By considering patient-centred approaches in any healthcare environment, the model has the potential to improve efficient care for patients suffering from ATAAD.
Comparing the effectiveness and cost-effectiveness of text-message reminders and telephone patient navigation to improve the uptake of faecal immunochemical test screening among non-responders in London: a randomised controlled trial protocol
Authors: Duffy Thomas , Gil Natalie , Siddique Benzeer , Duffy Stephen , Prentice Andrew , Marshall Sarah , Djedovic Natasha K , Lewis Michael , Ruwende Josephine , von Wagner Christian , Kerrison Robert
Published: June 2024

Introduction

Participation in bowel cancer screening is lower in regions where there is high ethnic diversity and/or socioeconomic deprivation. Interventions, such as text message reminders and patient navigation (PN), have the potential to increase participation in these areas. As such, there is interest in the comparative effectiveness of these interventions to increase bowel cancer screening participation, as well as their relative cost-effectiveness.

Methods and analysis

This study will use a three-arm randomised controlled trial design to compare the effectiveness and cost-effectiveness of text message reminders and PN to increase the uptake of bowel cancer screening in London. Participants will be individuals who have not returned a completed faecal immunochemical test kit within 13 weeks of receiving a routine invitation from the London bowel cancer screening hub. Participants will be randomised (in a 1:1:1 ratio) to receive either (1) usual care (ie, ‘no intervention’), (2) a text message reminder at 13 weeks, followed by repeated text message reminders at 15, 17 and 19 weeks (in the event of non-response) or (3) a text message reminder at 13 weeks, followed by PN telephone calls at 15, 17 and 19 weeks in the event of non-response. The primary endpoint will be participation in bowel cancer screening, defined as ‘the return of a completed kit by week 24’. Statistical analysis will use multivariate logistic regression and will incorporate pairwise comparisons of all three groups, adjusted for multiple testing.

Ethics and dissemination

Approvals to conduct the research have been obtained from University College London’s Joint Research Office (Ref: 150666), the Screening Research, Innovation and Development Advisory Committee (‘RIDAC’, Ref: 2223 014 BCSP Kerrison), the Health Research Authority (Ref: 22/WM/0212) and the Confidentiality Advisory Group (Ref: 22/CAG/0140). Results will be conveyed to stakeholders, notably those managing the screening programme and published in peer-reviewed journals/presented at academic conferences.

Trial registration number

ISRCTN17245519
Promotive and protective effects of community-related positive childhood experiences on adult health outcomes in the context of adverse childhood experiences: a nationwide cross-sectional survey in Japan
Authors: Mitani Haruyo , Kondo Naoki , Amemiya Airi , Tabuchi Takahiro
Published: June 2024

Objective

Although adverse childhood experiences (ACEs) are associated with poor health in adulthood, positive childhood experiences (PCEs) can reduce the risk of negative health outcomes. This study aimed to investigate whether PCEs in the community (CPCEs, ie, trusted adults other than parents, supportive friends, belongingness to school, or community traditions) would have an independent effect on better health outcomes and moderate the association between ACEs and adult illnesses.

Design

Cross-sectional survey.

Setting

Data were gathered from a nationwide, cross-sectional internet survey conducted in Japan in 2022.

Participants

This study included 28 617 Japanese adults aged 18–82 years (51.1% female; mean age=48.1 years).

Primary and secondary outcome measures

The associations among self-reported ACEs, CPCEs before the age of 18 years and current chronic diseases (eg, cancer and depression) were investigated using multivariable logistic regression models.

Results

CPCEs were associated with lower odds of adult diseases (such as stroke, chronic obstructive pulmonary disease (COPD), chronic pain, depression, suicidal ideation and severe psychological distress) after adjusting for ACEs. More CPCEs weakened the association between ACEs and adult diseases. Specifically, among those with ACEs, ≥3 CPCEs (vs 0–2 CPCEs) lowered the adjusted prevalence by ≥50% for stroke (2.4% to 1.2%), COPD (2.2% to 0.7%) and severe psychological distress (16.4% to 7.4%).

Conclusion

CPCEs could reduce ACE-related risk of poor physical and mental health in later life. Early-life interventions that enhance PCEs in schools and/or neighbourhoods are recommended.
Improving diagnostic of cervical dysplasia among postmenopausal women aged ≥50 years using local vaginal oestrogen treatment prior to colposcopy: study protocol for a multicentre randomised controlled trial (the IDEAL study)
Authors: Bertelsen Vibe Munk , Tranberg Mette , Petersen Lone Kjeld , Booth Berit , Bor Pinar
Published: June 2024

Introduction

Colposcopy is the most important diagnostic tool to detect cervical precancerous lesions and thereby prevention of cervical cancer. Due to age-dependent changes of the cervix, colposcopy is challenging in postmenopausal women, as the majority will have a non-visible transformation zone, resulting in increased risk of missing disease, a diagnostic cone biopsy and prolonged follow-up with repeated colposcopies. This study will be among the first to investigate, if treatment with vaginal oestrogen prior to colposcopy will improve the colposcopy performance, to ensure accurate and timely diagnosis of precancerous cervical lesions among postmenopausal women.

Methods and analysis

A randomised blinded controlled multicentre study. Enrolment will be performed at gynaecology departments in Central Denmark Region and Region of Southern Denmark. A total of 150 postmenopausal women aged ≥50 years referred for colposcopy due to abnormal cervical screening results will be randomised 1:1 to either pretreatment with vaginal application of Vagifem 30 µg or placebo once a day for 14 days prior to colposcopy. The primary outcome will be to compare the percentage of women in the two groups with a visible transformation zone at colposcopy, and biopsies representative of the transformation zone. Secondary outcomes will be the proportion of detected cervical intraepithelial neoplasia grade 2 or higher in the cervical biopsies; the proportion of diagnostics cone biopsies; the patients’ report on possible side effects and compliance to the pretreatment.

Ethics and dissemination

The study has been approved by the Central Denmark Region Committee on Biomedical Research Ethics (1-10-72-34-22), the Central Denmark Regions’ Research Unit (1-16-02-72-22) and The Danish Health Authority (Danish Medicine Agency; 2022015030). The study’s EudraCT number is (1-23-456; 2022-000269-42) and it is registered onwww.clinicaltrials.gov. The local Good Clinical Practice (GCP) unit will supervise and monitor the study closely before, during and after the study period. Findings will be disseminated in peer-reviewed scientific journals and presented in relevant conferences.

Trial registration number

NCT05283421.
Feasibility and acceptability of general practitioners using sit–stand desks: a feasibility trial
Authors: Biddle Gregory James Hamilton , Thomas Nicholas , Edwardson Charlotte L , Clemes Stacy A , Daley Amanda J
Published: June 2024

Objectives

The primary aim of this study was to investigate the feasibility and acceptability of general practitioners (GPs) using sit–stand desks to facilitate standing during consultations. A further aim was to examine the views of patients about GPs standing for their consultations.

Design

A pre–post single-group experimental trial design.

Setting

General practices in England, UK.

Participants

42 GPs (working a minimum of five clinical sessions per week) and 301 patients (aged ≥18 years).

Interventions

The intervention consisted of each GP having a sit–stand desk (Opløft Sit-Stand Platform) installed in their consultation room for 4 working weeks. Sit–stand desks allow users to switch, in a few seconds, between a sitting and standing position and vice versa, by adjusting the height of the desk.

Main outcome measures

To test feasibility and acceptability, GPs reported their views about using sit–stand desks at work at baseline and follow-up. Sitting time and physical activity were also measured via accelerometer at baseline and follow-up. Patients who attended a consultation where their GP was standing were asked to complete an exit questionnaire about the perceived impact on the consultation.

Results

Most GPs reported using their sit–stand desk daily (n=28, 75.7%). 16 GPs (44.4%) used their sit–stand desk during face-to-face consultations every day. Most GPs and patients did not view that GPs standing during face-to-face consultations impacted the doctor–patient relationship (GPs; 73.5%, patients; 83.7%). GPs’ sitting time during work was 121 min per day lower (95% CI: −165 to −77.58) at follow-up compared with baseline.

Conclusions

Use of sit–stand desks is acceptable within general practice and may reduce sitting time in GPs. This may benefit GPs and help reduce sitting time in patients.

Trial registration number

ISRCTN76982860.
PERI-operative biologic DMARD management: Stoppage or COntinuation during orthoPaEdic operations (the PERISCOPE trial) – a study protocol for a pragmatic, UK multicentre, superiority randomised controlled trial with an internal pilot, economic evaluation and nested qualitative study
Authors: Brady Samantha , Mott Andrew , Carlisle Katie , Abhishek Abhishek , Adamson Joy , Coates Laura , van Duren Bernard , Emery Paul , Goodman Susan Marion , Hewitt Catherine , Li Jinshuo , Mandefield Laura , Parkinson Gillian , Marzo-Ortega Helena , Maxwell James , Nanchahal Jagdeep , Rangan Amar , Richards Duncan , Ronaldson Sarah , Shepherd Susan , Taylor Johanna , Wilkinson Jeremy Mark , Pandit Hemant , Mankia Kulveer Singh
Published: June 2024

Introduction

Biological disease-modifying antirheumatic drugs (bDMARDs) have revolutionised the treatment of inflammatory arthritis (IA). However, many people with IA still require planned orthopaedic surgery to reduce pain and improve function. Currently, bDMARDs are withheld during the perioperative period due to potential infection risk. However, this predisposes patients to IA flares and loss of disease control. The question of whether to stop or continue bDMARDs in the perioperative period has not been adequately addressed in a randomised controlled trial (RCT).

Methods and analysis

PERISCOPE is a multicentre, superiority, pragmatic RCT investigating the stoppage or continuation of bDMARDs. Participants will be assigned 1:1 to either stop or continue their bDMARDs during the perioperative period. We aim to recruit 394 adult participants with IA. Potential participants will be identified in secondary care hospitals in the UK, screened by a delegated clinician. If eligible and consenting, baseline data will be collected and randomisation completed. The primary outcome will be the self-reported PROMIS-29 (Patient Reported Outcome Measurement Information System) over the first 12 weeks postsurgery. Secondary outcome measures are as follows: PROMIS - Health Assessment Questionnaire (PROMIS-HAQ), EQ-5D-5L, Disease activity: generic global Numeric Rating Scale (patient and clinician), Self-Administered Patient Satisfaction scale, Health care resource use and costs, Medication use, Surgical site infection, delayed wound healing, Adverse events (including systemic infections) and disease-specific outcomes (according to IA diagnosis). The costs associated with stopping and continuing bDMARDs will be assessed. A qualitative study will explore the patients’ and clinicians’ acceptability and experience of continuation/stoppage of bDMARDs in the perioperative period and the impact postoperatively.

Ethics and dissemination

Ethical approval for this study was received from the West of Scotland Research Ethics Committee on 25 April 2023 (REC Ref: 23/WS/0049). The findings from PERISCOPE will be submitted to peer-reviewed journals and feed directly into practice guidelines for the use of bDMARDs in the perioperative period.

Trial registration number

ISRCTN17691638.
Sexual health services for adolescents on Reunion Island: results from a descriptive interview-based study
Authors: Reynaud Danielle , Laboureur Estelle , Marimoutou Catherine , Cartron Emmanuelle
Published: June 2024

Objectives

To describe the experiences of sexual health services available for adolescents aged 15–19 years on Reunion Island.

Design

A qualitative descriptive study was conducted from 3 December 2022 to 24 October 2023. Data were analysed using the phenomenological interpretative method.

Setting

Centre Hospitalier Universitaire of Reunion Island.

Participants

15 participants were recruited through convenience sampling, but 3 of them did not attend the interviews.

Interventions

Face-to-face or videoconferencing open-ended individual interviews.

Primary and secondary outcome measures

Barriers and facilitators to access sexual health services, relationship between adolescents and healthcare professionals when using these services and suggestions made by adolescents for improving access to care and quality of care.

Results

In total, 12 adolescents were included with most being female (11 with a mean age of 18 years). Most interviewees were in a relationship, lived in urban areas and had sexual intercourse (nine, respectively). Participants attended high school, university and preparatory college (four, respectively). Most interviews were face to face (11). The mean duration of the interviews was 32 min. Two themes revealing the experiences of sexual health services emerged. Participants described maintaining sexual health as a difficult journey in their quest for information about sexual health and the available services provided. Participants demonstrated that they had the ability to cope with the consequences of unprotected sex.

Conclusions

To date, sexual health services available on Reunion Island may not meet the needs of adolescents. Implementation of a strategy aimed at providing young people with skills, addressing their needs and working with them in a collaborative manner may be necessary. Appropriate teaching methods and the training of healthcare professionals should also be considered.
When medical assistance in dying is not a last resort option: survey of the Canadian public
Authors: Choi William J W , Astrachan Isabel Marie , Sinaii Ninet , Kim Scott Yung Ho
Published: June 2024

Objectives

What are the Canadian public’s understanding of and views toward medical assistance in dying (MAID) in persons refusing recommended treatment or lacking access to standard treatment or resources?

Design/setting

An online survey assessed knowledge of and support for Canadian MAID law, and views about four specific scenarios in a two (medical or psychiatric) by two (treatment refusal or lack of access) design.

Participants

A quota sample (N=2140) matched to the 2021 Canadian census by age, gender, income, education and province.

Main outcomes

Participants’ level of support for MAID in general and in the four specific scenarios.

Results

Only 12.1% correctly answered ≥4 of 5 knowledge questions about the MAID law; only 19.2% knew terminal illness is not required and 20.2% knew treatment refusal is compatible with eligibility. 73.3% of participants expressed support for the MAID law in general, matching a nationally representative poll that used the same question. 40.4% of respondents supported MAID for mental illnesses. Support for MAID in the scenarios depicting refusal or lack of access to treatment ranged from 23.2% (lack of access in medical condition) to 32.0% (treatment refusal in medical illness). Older age, more education, higher income, lower religious attendance or being white was associated with greater support for MAID in general but was either negatively associated or not associated with support for MAID in the four refusal or lack of access scenarios.

Conclusions

Most Canadians support the current MAID law but appear unaware that MAID cases they do not support are compatible with that law. The lower support for MAID in the four scenarios cuts across sociodemographics. The gap between current policy and public opinion warrants further study. For jurisdictions debating MAID, opinion surveys may need to go beyond assessing general attitudes, and target knowledge and views regarding implications of legalisation.
Epidemiology and morbidity of spina bifida in Hispanic Americans: a systematic review
Authors: Abdelmageed Sunny , Votoupal Megan , Lam Sandi K , Garcia Roxanna M
Published: June 2024

Objective

To comprehensively describe the epidemiology and morbidity of spina bifida in Hispanic Americans and identify risk factors associated with the increased prevalence of spina bifida.

Design

A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources

Three databases (MEDLINE, Embase and Scopus) were searched between inception of the database and June 2023. Study designs included case–control, descriptive, cross-sectional and databases.

Eligibility criteria

Observational and experimental analytical studies reporting epidemiology or morbidity of spina bifida in Hispanic Americans or Latinx individuals were eligible.

Data extraction and synthesis

Data were extracted independently by authors. Descriptive analysis was used to summarise findings.

Results

Of 392 publications, 32 studies met inclusion criteria. Study periods ranged from 1955 to 2020. A total of 50 382 patients with spina bifida were included and 13 209 identified as Hispanic American (26.2%). Five studies report higher prevalence of spina bifida at birth per 10 000 births in Hispanic Americans compared with non-Hispanic white individuals, while one reported no significant difference (2.11 vs 2.24). Risk factors associated with spina bifida included prenatal exposures, sociodemographic factors and maternal clinical characteristics. Lower levels of maternal education, age and income were associated with an increased risk of spina bifida. Eleven papers found spina bifida had high morbidity among Hispanic Americans resulting in high financial, physical and socioeconomic impacts. There was high study heterogeneity that can be explained by the varying time periods and geographical distribution.

Conclusion

Increased prevalence and morbidity of spina bifida in Hispanic Americans are due to a variety of inter-related factors relating to existing health disparities. High heterogeneity across the studies suggests a need for future studies and increased standardisation of reporting guidelines.
Effects of dry needling on spasticity and motor function in paralympic athletes: a study protocol for a randomised controlled trial
Authors: Aliasgharpour Fatemeh , Honarpishe Roshanak , Hosseini-Asl Seyed Hossein , Khonji Mohammad Saeid , Abbaschian Faezeh , Nakhostin Ansari Noureddin , Naghdi Soofia , Gallego Pablo Herrero , Nakhostin-Ansari Amin
Published: June 2024

No study has evaluated the effects of dry needling on Paralympic athletes. Therefore, in this study, we will evaluate the effect of dry needling on lower limb spasticity and motor performance, as well as the range of motion of Paralympic athletes. The study will be a triple-blinded, randomised controlled trial. Twenty-four athletes aged 18–45 in T35–T38 groups of the International Paralympic Committee classification will be included in the study. Twelve participants will receive dry needling of the quadriceps and gastrocnemius muscles, and 12 will receive placebo treatment with sham needles at similar points. We will assess the spasticity of the quadriceps and gastrocnemius muscles using the Modified Ashworth Scale, evaluate motor function using the Selective Control Assessment of the Lower Extremity Scale and measure ankle range of motion (ROM) with a goniometer. Considering our hypothesis, the athletes who will undergo the dry needling are supposed to achieve better improvements in spasticity, ROM and motor performance. This study can provide useful information to help better decide on managing complications in Paralympics and its long-term outcomes, to cover the current lack in the literature.
Gut microbiota signatures of vulnerability to food addiction in mice and humans
Authors: Samulėnaitė Solveiga , García-Blanco Alejandra , Mayneris-Perxachs Jordi , Domingo-Rodríguez Laura , Cabana-Domínguez Judit , Fernàndez-Castillo Noèlia , Gago-García Edurne , Pineda-Cirera Laura , Burokas Aurelijus , Espinosa-Carrasco Jose , Arboleya Silvia , Latorre Jessica , Stanton Catherine , Hosomi Koji , Kunisawa Jun , Cormand Bru , Fernández-Real Jose Manuel , Maldonado Rafael , Martín-García Elena
Published: June 2024

Objective

Food addiction is a multifactorial disorder characterised by a loss of control over food intake that may promote obesity and alter gut microbiota composition. We have investigated the potential involvement of the gut microbiota in the mechanisms underlying food addiction.

Design

We used the Yale Food Addiction Scale (YFAS) 2.0 criteria to classify extreme food addiction in mouse and human subpopulations to identify gut microbiota signatures associated with vulnerability to this disorder.

Results

Both animal and human cohorts showed important similarities in the gut microbiota signatures linked to food addiction. The signatures suggested possible non-beneficial effects of bacteria belonging to the Proteobacteria phylum and potential protective effects of Actinobacteria against the development of food addiction in both cohorts of humans and mice. A decreased relative abundance of the species
Blautia wexlerae
was observed in addicted humans and of
Blautia
genus in addicted mice. Administration of the non-digestible carbohydrates, lactulose and rhamnose, known to favour
Blautia
growth, led to increased relative abundance of
Blautia
in mice faeces in parallel with dramatic improvements in food addiction. A similar improvement was revealed after oral administration of
Blautia wexlerae
as a beneficial microbe.

Conclusion

By understanding the crosstalk between this behavioural alteration and gut microbiota, these findings constitute a step forward to future treatments for food addiction and related eating disorders.
APOLLO: neo-adjuvant pembrolizumab for primary vulvar squamous cell carcinoma—a multicenter, single-arm, phase II, clinical proof-of-concept study
Authors: van Poelgeest M I E , Kortekaas Kim E , van Doorn Helena C , Oonk Maaike , Nijman Hans W , Boere Ingrid , Eerkens Anneke L , Reyners Anna K L , Ewing-Graham Patricia C , Bart Joost , Bosse Tjalling , Welters Marij J P , Kroep Judith R , van der Burg Sjoerd H
Published: June 2024

Background

Vulvar squamous cell carcinoma (VSCC) is a rare cancer for which the cornerstone of treatment is surgery with high complication rates. The unmet need is a less radical and more effective treatment for VSCC.

Primary Objectives

To investigate the impact of mono-immunotherapy pembrolizumab as neoadjuvant treatment for primary resectable VSCC patients.

Study Hypothesis

Some primary VSCC patients display a specific immune profile which is associated with better survival. In other tumors, this profile is associated with a better response to programmed cell death protein 1 (PD-1) checkpoint blockade which may reinvigorate tumor-specific T cells. This potentially results in a reduced tumor load and less radical surgery and/or adjuvant treatment in patients with this immune profile.

Trial Design

This is an investigator-initiated, prospective, single arm, multicenter, phase II clinical trial.

Inclusion Criteria

Patients with VSCC clinical stage International Federation of Gynecology and Obstetrics (FIGO) I-III (2021) eligible for primary surgery, with at least one measurable lesion of at least one dimension ≥10 mm in the largest diameter, are included in this study.

Main Exclusion Criteria

Patients not suitable for surgery and/or previously treated with immunomodulatory agents, and/or who suffer from comorbidities that may interfere with PD-1 blockade, are excluded from the study.

Endpoints

The clinical efficacy of neoadjuvant pembrolizumab in VSCC is measured by an objective change in tumor size according to the Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) and documented by calipers using standardized digital photography with a reference ruler. In addition, the activation, proliferation, and migration of T cells in the tumor will be studied. The secondary endpoints are pathological complete responses at the time of surgery, feasibility, and safety.

Sample Size

40 patients with FIGO I-III (2021) primary VSCC will be enrolled.

Estimated Dates for Completing Accrual and Presenting Results

The intervention phase started in July 2023 and will continue until July 2025. The expected completion of the entire study is July 2026.

Trial Registration Number

NCT05761132
Expression of VISTA regulated via IFN-γ governs endogenous T-cell function and exhibits correlation with the efficacy of CD19 CAR-T cell treated B-malignant mice
Authors: Tang Donghai , Zhao Li , Yan Fen , Ren Chunxiao , Xu Kailin , Zhao Kai
Published: June 2024

Background

Despite continuous improvements in the new target and construction of chimeric antigen receptor (CAR)-T, relapse remains a significant challenge following CAR-T therapy. Tumor microenvironment (TME) strongly correlates with the efficacy of CAR-T therapy. V-domain Ig suppressor of T-cell activation (VISTA), which exerts a multifaceted and controversial role in regulating the TME, acts not only as a ligand on antigen-presenting cells but also functions as a receptor on T cells. However, the characteristics and underlying mechanisms governing endogenous T-cell activation by VISTA, which are pivotal for reshaping the TME, remain incompletely elucidated.

Methods

The immunocompetent B acute lymphoblastic leukemia (B-ALL), lymphoma, and melanoma murine models were employed to investigate the characteristics of endogenous T cells within the TME following CD19 and hCAIX CAR-T cell therapy, respectively. Furthermore, we examined the role of VISTA controlled by interferon (IFN)-γ signaling in regulating endogenous T-cell activation and functionality in B-ALL mice.

Results

We demonstrated that the administration of CD19 CAR-T or hCAIX CAR-T cell therapy elicited augmented immune responses of endogenous T cells within the TME of B-ALL, lymphoma, and melanoma mice, thereby substantiating the efficacy of CAR-T cell efficacy. However, in the TME lacking IFN-γ signaling, VISTA levels remained elevated, resulting in attenuated cytotoxicity of endogenous T cells and reduced B-ALL recipient survival. Mice treated with CD19 CAR-T cells exhibited increased proportions of endogenous memory T cells during prolonged remission, which possessed the tumor-responsive capabilities to protect against B-ALL re-challenge. Compared with wild-type (WT) CAR-T treated mice, the administration of IFN-γ−/−CAR-T to both WT and IFN-γ−/−recipients resulted in a reduction in the numbers of endogenous CD4+and CD8+effectors, while exhibiting increased populations of naïve-like CD4+T and memory CD8+T cells. VISTA expression consistently remained elevated in resting or memory CD4+T cells, with distinct localization from programmed cell death protein-1 (PD-1) expressing T subsets. Blocking the VISTA signal enhanced dendritic cell-induced proliferation and cytokine production by syngeneic T cells.

Conclusion

Our findings confirm that endogenous T-cell activation and functionality are regulated by VISTA, which is associated with the therapeutic efficiency of CAR-T and provides a promising therapeutic strategy for relapse cases in CAR-T therapy.
Fc–Fc interactions and immune inhibitory effects of IgG4: implications for anti-PD-1 immunotherapies
Authors: Zhang Weifeng , Chen Xueling , Chen Xingxing , Li Jirui , Wang Hui , Yan Xiaomiao , Zha Han , Ma Xiaonan , Zhao Chanyuan , Su Meng , Hong Liangli , Li Penghao , Ling Yanyu , Zhao Wenhui , Xia Yu , Li Baiyong , Zheng Tianjing , Gu Jiang
Published: June 2024

Background

The majority of anti-programmed cell-death 1 (PD-1) monoclonal antibodies (mAbs) use S228P mutation IgG4 as the structural basis to avoid the activation of immune cells or complement. However, little attention has been paid to the Fc–Fc interactions between IgG4 and other IgG Fc fragments that could result in adverse effects. Fc-null IgG1 framework is a potential safer alternative to avoid the undesirable Fc–Fc interactions and Fc receptor binding derived effects observed with IgG4. This study provides a comprehensive evaluation of anti-PD-1 mAbs of these two frameworks.

Methods

Trastuzumab and rituximab (both IgG1), wildtype IgG1 and IgG4 were immobilized on nitrocellulose membranes, coated to microplates and biosensor chips, and bound to tumor cells as targets for Fc–Fc interactions. Wildtype IgG1 and IgG4, anti-PD-1 mAb nivolumab (IgG4 S228P), penpulimab (Fc-null IgG1), and tislelizumab (Fc-null IgG4 S228P-R409K) were assessed for their binding reactions to the immobilized IgG proteins and quantitative kinetic data were obtained. To evaluate the effects of the two anti-PD-1 mAbs on immune responses mediated by trastuzumab and rituximab in the context of combination therapy, we employed classic immune models for antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement dependent cytotoxicity. Tumor-bearing mouse models, both wildtype and humanized, were used for in vivo investigation. Furthermore, we also examined the effects of IgG1 and IgG4 on diverse immune cell populations

Results

Experiments demonstrated that wildtype IgG4 and nivolumab bound to immobilized IgG through Fc–Fc interactions, diminishing antibody-dependent cell-mediated cytotoxicity and phagocytosis reactions. Quantitative analysis of kinetic parameters suggests that nivolumab and wildtype IgG4 exhibit comparable binding affinities to immobilized IgG1 in both non-denatured and denatured states. IgG4 exerted inhibitory effects on various immune cell types. Wildtype IgG4 and nivolumab both promoted tumor growth in wildtype mouse models. Conversely, wildtype IgG1, penpulimab, and tislelizumab did not show similar adverse effects.

Conclusions

Fc-null IgG1 represents a safer choice for anti-PD-1 immunotherapies by avoiding both the adverse Fc–Fc interactions and Fc-related immune inhibitory effects of IgG4. Fc-null IgG4 S228P-R409K and Fc-null IgG1 displayed similar structural properties and benefits. This study contributes to the understanding of immunotherapy resistance and the advancement of safer immune therapies for cancer.
Electromyography and range-of-motion measurements in German soldiers wearing different types of body armour while marching
Authors: Lang Patricia , Amann M , Riesner H-J , Friemert B , Siebers H , Betsch M , Palm H-G
Published: June 2024

Introduction

In this study, we used surface electromyography (EMG) electrodes in order to measure and compare activity in the neck, back and thigh muscles of soldiers wearing two different types of body armour. A secondary objective was to analyse shoulder and hip ranges of motion using inertial motion sensors.

Methods

Fourteen male soldiers were instructed to march 6 km on a treadmill while wearing different types of body armour. All participants wore shorts and a T-shirt and the same size vest regardless of their body size. We measured back and thigh muscle activity as well as shoulder and hip ranges of motion at regular intervals during the march.

Results

Over the course of a 6 km march, muscle activity was already increased to 1.3 to 2.0 times after putting on the vest and increased by up to 13 times during the march with equipment. The new vest with hip belt required higher levels of muscle activity.

Conclusions

Body armour with hip belt placed higher levels of stress on back and neck muscles during a 6 km march than without. There was no major difference between the two types of body armour in terms of thigh muscle activity.

Trial registration number

DRKS00016005.
Use of regional anesthesia within a pediatric interventional radiology suite reduced periprocedural opioid use without delaying the overall workflow: a retrospective study
Authors: Gaelen Jordan I , Wu Chunyi , Yang Amy , Rajeswaran Shankar , Lazar Alina , Cheon Eric C , Vargas Angelica A
Published: June 2024

Background

Nerve block utility has been extensively described in the operating room, however, there is a paucity of evidence regarding blocks in the interventional radiology (IR) suite, with no studies examining its safety and efficacy in children.

Methods

A retrospective study was conducted at a single tertiary-care children’s hospital to evaluate the analgesic utility of nerve blocks during IR-performed sclerotherapy for bone cysts, venous malformations, and lymphatic malformations. Lymphatic and venous malformations were combined for final analysis. Patients between January 2016 and September 2022 had their medical records reviewed for procedural data, postprocedural pain scores, and analgesic administration data.

Results

309 patients were included in the final analysis. Opioids were required significantly less frequently intraprocedurally and postprocedurally across subgroups. The proportion of patients who received opioids during their hospital course was significant between block and non-block patients, respectively: bone cyst: 62.7% vs 100% (p<0.001); venous and lymphatic malformation: 65.7% vs 97.4% (p<0.001). Average maximum postanesthesia care unit (PACU) pain scores were significantly lower in bone cyst patients with no significant difference seen in pain scores among venous and lymphatic malformation patients. There were no reported nerve block-related complications.

Discussion

Nerve blocks demonstrated an opioid-sparing effect intraprocedurally and postprocedurally for all subgroups. Their use among bone cyst patients was associated with significant reductions in average maximum PACU pain scores. Nerve blocks may constitute an effective opioid-sparing component of multimodal analgesia in pediatric patients undergoing IR sclerosis procedures. Prospective data are needed to establish the optimal utility of nerve blocks in the IR setting.
Bring on the heat: thermal ecology of Tropidurus semitaeniatus in the Northeast of Brazil
Authors: Bruinjé Andre C. , Paiva Tales M.A. , Coelho Felipe E.A. , Costa Gabriel C.
Published: June 2024

Body temperature is a key physiological trait for individual fitness. Its effects on behavior and metabolism determine organismal activity. Optimal body temperature can vary among individuals, and consequent activity asynchrony can thus enable the co-occurrence of otherwise competing social strategies. Here, we combine ex-situ experiments with environmental data to test whether variability in thermal traits can explain the maintenance of the alternative reproductive strategies of Tropidurus semitaeniatus (Spix, 1825) male morphs. We predict that morphs and sexes differ in thermal traits. Thus, we tested for differences in their behaviorally determined thermal traits: preferred ( Tp), body ( Tb), and habitat temperatures; basking cover preference (Coverpref); and physiological limits (critical thermal minimum CTmin; and maximum, CTmax). We also calculated T. semitaeniatus’ thermal tolerance traits and compiled a list of Tp for Tropidurids. We found that T. semitaeniatus maintains its Tb below Tp. In addition, and contrary to theoretical predictions for tropical lizards, we found that T. semitaeniatus has a high warming tolerance (8.3 °C) and thermal safety margin (2.4 °C). We found no thermal differences between morphs indicating that thermal ecology does not play a role in the co-existence of color morphs.
Strictly nef divisors on singular threefolds
Authors: Wang Juanyong , Zhong Guolei
Published: June 2024

Let [Formula: see text] be a normal projective variety with klt singularities and [Formula: see text] a strictly nef [Formula: see text]-divisor on [Formula: see text]. In this paper, we study the singular version of Serrano’s conjecture, i.e. the ampleness of [Formula: see text] for [Formula: see text]. We show that, if [Formula: see text] is a [Formula: see text]-factorial Gorenstein terminal threefold, then [Formula: see text] is ample for [Formula: see text] unless [Formula: see text] is a weak Calabi–Yau variety (i.e. the canonical divisor [Formula: see text] is a [Formula: see text]-torsion and the augmented irregularity [Formula: see text] vanishes) with [Formula: see text].
SOME DIAMOND INTEGRAL REVERSE HÖLDER-TYPE INEQUALITIES ASSOCIATED WITH SPECHT’S RATIO ON TIME SCALES
Authors: LIANG JIANSUO , CHEN GUANGSHENG , LUO WENTING
Published: June 2024

This paper is devoted to studying some new reverse Hölder-type inequalities associated with the dynamic integral called diamond on time scale, which is expressed as an ‘approximate’ symmetric integral on time scales. Some related inequalities are also presented. The obtained inequalities extend known results related with discrete and continuous forms.
Local Convolutional Neural Network Based Pop-Up Text Recognition and Sentiment Analysis
Authors: Zhou Xiukao , Li Wen
Published: June 2024

Pop-ups are a recently popular way of human-computer interaction, allowing viewers to actively participate in the discussion of a film video, but pop-ups can be deleted due to exceeding the size limit of the pop-up pool, and pop-up data is difficult to obtain in its entirety. To this end, this paper proposes a local convolutional neural network (CNN) based pop-up text sub-recognition algorithm. Finally, the fuzzed data is reconstructed into a data look-up table and the contents of the data look-up table are formatted for output. The results of this text classification and recognition algorithm are compared with those of four commonly used domestic and international search engines by subjective evaluation method, and the proposed text classification and recognition algorithm is found to be advanced.
Development and Application of 3D Printing Manufacturing Technology in Intelligent Vehicle Design
Authors: Yao Wenji , Ruan Yue
Published: June 2024

With the rapid development of intelligent vehicle technology, traditional vehicle design and manufacturing methods are facing many challenges. Traditional vehicle design and manufacturing methods have problems such as high cost, long development cycle and lack of personalized design. This paper took advantage of the high degree of flexibility, rapid customization and cost savings of 3D printing technology, which can provide entirely new solutions for intelligent vehicle design. This paper mainly analyzed the application of three-dimensional (3D) printing and manufacturing technology in intelligent vehicle design. In intelligent vehicle design, 3D printing can carry out 3D printed body structure design to make parts lightweight. The displacement sensor in the intelligent sensor can measure the displacement, deformation and vibration of the body components, and detect whether the body structure exceeds the safety range, which can provide safety feedback to the owner. 3D printing technology has been involved in automotive dashboard, interior design and customization. In this paper, the effects of vehicles designed under traditional methods and vehicles designed under 3D printing manufacturing technology were compared. The research and development cycle of class A, Class B, Class C and Class D in brand 1 under traditional manufacturing was 3.85 years, 3.13 years, 4.27 years and 4.32 years respectively. The R&D (research and development) cycle of grade A, B, C and D in brand 1 under 3D printing technology was 2.43 years, 2.05 years, 1.64 years and 1.73 years respectively. Under the traditional method, the average R&D cost of different levels of vehicles in brand 1, brand 2 and brand 3 was 191,000 yuan, 20900 yuan and 227,200 yuan respectively. Under 3D printing technology, the average R&D cost of different levels of vehicles in brand 1, brand 2 and brand 3 was 132,600 yuan, 145,300 yuan and 157,500 yuan respectively. The results of this paper emphasize that the application of 3D printing manufacturing technology shortens the development cycle of intelligent vehicles, reduces the development cost, and can be customized, which can be more in line with the needs of users.
Missing Data Filling of Model Based on Neural Network
Authors: Tang Hongjie
Published: June 2024

Today’s society has entered the pace of information development era. All kinds of information are digitized, while the loss of information data also directly affects the normal operation of the application system and has become the biggest obstacle to the development of information technology. The existing missing filling methods do not take into account the time-series information of the data set. Based on the neural network method for filling missing data in time series, an end-to-end missing data filling method for time series based on the residual of regression equation is proposed. Under the assumption that the activation function and the noise diffusion coefficient function are satisfied, the exponential stability of the complex-valued stochastic inertial neural network systems with additive time-varying delays is studied. The bipartite graph model of the time series data missing value filling method of the countermeasure network and the filling cyclic neural unit are generated. According to the end-to-end time series data missing value filling method of the self encoder, the corresponding low-dimensional feature vector can be automatically generated for each time series data. It avoids overfitting by using nonlinear methods directly in low-dimensional space. Experiments show that the method proposed in this paper uses Monte Carlo to fill data missing at different proportions. In data gap filling process, the coefficient variance is less than 0.05, which enhances the rationality of filling data. It is of great research value and practical significance to reasonably fill in the missing values of time series data. The research can accelerate the improvement of big data system, improve the level and effectiveness of database management, and is an important means of computing capacity of existing data centers.
A Differential Game Approach to Investment in Greentech Innovation in a Duopoly with Network Externality
Authors: Ma Shengbiao , Li Huiquan
Published: June 2024

In this paper, we revisit a well-known differential game model to investigate the R&D activity for Greentech innovation in a duopoly market with network externality. In our study, firms carry out independent R&D or Cartel R&D for Greentech innovation which aims to reduce end-of-pipe emission and network externality effects play a role in the R&D activity via the inverse demand functions. Firms are concerned not only with their own profits, but also with the relative profits. At the steady-state equilibrium, the efforts for Greentech innovation under independent R&D are higher than that under Cartel R&D when the degree of altruism is higher than the degree of technological R&D spillover, and the network size under independent R&D is lower than that under Cartel R&D. Moreover, under a given market structure, whether profits under independent R&D are higher than under Cartel R&D depends on the initial network size, which means that at the initial moment firms can decide to undertake independent or Cartel R&D activities based on the initial network size.