bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of perceived injustice-targeted pain neuroscience education compared with biomedically focused education in breast cancer survivors: a study protocol for a multicentre randomised controlled trial (BCS-PI trial)
Authors: Roose Eva , Huysmans Eva , Leysen Laurence , Mostaqim Kenza , Van Wilgen Paul , Beckwée David , De Couck Marijke , Timmermans Annick , Bults Rinske , Nijs Jo , Lahousse Astrid
Published: January 2024

Introduction

Current treatments for pain in breast cancer survivors (BCSs) are mostly biomedically focused rather than biopsychosocially driven. However, 22% of BCSs with pain are experiencing perceived injustice, which is a known predictor for adverse pain outcomes and opioid prescription due to increased maladaptive pain behaviour. Educational interventions such as pain neuroscience education (PNE) are suggested to target perceived injustice. In addition, motivational interviewing can be an effective behavioural change technique. This trial aims to examine whether perceived injustice-targeted PNE with the integration of motivational interviewing is superior to biomedically focused pain education in reducing pain after 12 months in BCS with perceived injustice and pain. In addition, improvements in quality of life, perceived injustice and opioid use are evaluated, and a cost-effectiveness analysis will finally result in a recommendation concerning the use of perceived injustice-targeted PNE in BCSs with perceived injustice and pain.

Methods and analysis

This two-arm multicentre randomised controlled trial will recruit female BCS (n=156) with pain and perceived injustice. Participants will be randomly assigned to perceived injustice-targeted PNE or biomedically focused pain education in each centre. Both interventions include an online session, an information leaflet and three one-to-one sessions. The primary outcome (pain), secondary outcomes (quality of life, perceived injustice and outcomes for cost-effectiveness analysis) and explanatory outcomes (pain phenotyping, sleep, fatigue and cognitive-emotional factors) will be assessed at baseline and at 0, 6, 12 and 24 months postintervention using self-reported questionnaires online. Treatment effects over time will be evaluated using linear mixed model analyses. Additionally, a cost-utility analysis will be done from a healthcare payer and societal perspective.

Ethics and dissemination

The ethical agreement was obtained from the Main Ethics Committee (B.U.N.1432020000068) at the University Hospital Brussels and all other participating hospitals. Study results will be disseminated through presentations, conferences, social media, press and journals.

Trial registration number

NCT04730154.
Sexual violence victimisation and response among university students in sub-Saharan Africa: a scoping review protocol
Authors: Mzilangwe Ester Steven , Chande Mallya Rehema , Lindkvist Marie , Kaaya Sylvia , Nkulu Kalengayi Faustine Kyungu
Published: January 2024

Introduction

Sexual violence (SV) is highly prevalent among university campuses across the globe, despite of several initiatives implemented to address it. Several studies have been published focusing on various aspects of SV on campuses. However, no review has been retrieved from the Joanna Briggs Institute (JBI) Database, Cochrane Library or Ovid examining evidence synthesis on prevalence, risk factors, victims and perpetrators, policies, laws and universities responses to SV in sub-Saharan Africa (SSA). This review aims to map the existing literature on SV victimisation among university students in SSA, related response strategies, and identify gaps in the evidence.

Methods and analysis

This review will follow JBI guidelines and will be conducted from 1 July 2023 to 31 December 2023. A team of five reviewers will screen eligible documents and articles for relevance from various data sources including electronic databases such as MEDLINE, EMBASE, PsycINFO, CINAHL, Google Scholar, PubMed and websites for government and agencies. Standard information for each study will be collected and a common analytical framework for all the primary documents will be conducted.

Ethics and dissemination

This review will involve analysis of published data only and therefore does not require ethics approval. The results will be published in a peer-reviewed journal.

Registration

This review has been registered with the Open Science Framework.
The Brazilian COVID-19 vaccination campaign: a modelling analysis of sociodemographic factors on uptake
Authors: Li Sabrina L , Prete Carlos A , Zarebski Alexander E , de Souza Santos Andreza Aruska , Sabino Ester C , Nascimento Vitor H , Wu Chieh-Hsi , Messina Jane P
Published: January 2024

Objective

Dose shortages delayed access to COVID-19 vaccination. We aim to characterise inequality in two-dose vaccination by sociodemographic group across Brazil.

Design

This is a cross-sectional study.

Setting

We used data retrieved from the Brazilian Ministry of Health databases published between 17 January 2021 and 6 September 2021.

Methods

We assessed geographical inequalities in full vaccination coverage and dose by age, sex, race and socioeconomic status. We developed a Campaign Optimality Index to characterise inequality in vaccination access due to premature vaccination towards younger populations before older and vulnerable populations were fully vaccinated. Generalised linear regression was used to investigate the risk of death and hospitalisation by age group, socioeconomic status and vaccination coverage.

Results

Vaccination coverage is higher in the wealthier South and Southeast. Men, people of colour and low-income groups were more likely to be only partially vaccinated due to missing or delaying a second dose. Vaccination started prematurely for age groups under 50 years which may have hindered uptake in older age groups. Vaccination coverage was associated with a lower risk of death, especially in older age groups (ORs 9.7 to 29.0, 95% CI 9. 4 to 29.9). Risk of hospitalisation was greater in areas with higher vaccination rates due to higher access to care and reporting.

Conclusions

Vaccination inequality persists between states, age and demographic groups despite increasing uptake. The association between hospitalisation rates and vaccination is attributed to preferential delivery to areas of greater transmission and access to healthcare.
Is male gynaecomastia associated with an increased risk of death? A nationwide register-based cohort study
Authors: Bräuner Elvira V , Uldbjerg Cecilie , Lim Youn-Hee , Beck Astrid , Hueg Trine , Juul Anders
Published: January 2024

Objective

Recent evidence supports that gynaecomastia may predict long-term morbidity, but evidence on the association with death and causes of death in males with gynaecomastia is lacking. The objective of this work is to estimate the risk of death in men diagnosed with gynaecomastia and evaluate whether this was conditional on underlying aetiologies of gynaecomastia.

Design

A nationwide register-based cohort study.

Setting

Nationwide Danish national health registries.

Participants

Males were diagnosed with incident gynaecomastia (n=23 429) from 1 January 1995 to 30 June 2021, and each was age and calendar matched to five randomly population-based males without gynaecomastia (n=117 145).

Interventions

Not applicable.

Primary and secondary outcomes

Gynaecomastia was distinguished between maleswithout(idiopathic) and maleswitha known pre-existing risk factor. Cox regression models and Kaplan-Meier analyses estimated associations between gynaecomastia and death (all cause/cause specific).

Results

We identified a total of 16 253 males withidiopathicgynaecomastia and 7176 with gynaecomastia anda known pre-existing risk factor. Of these, 1093 (6.7%) and 1501 (20.9%) died during follow-up, respectively. We detected a 37% increased risk of all-cause death in males with gynaecomastia in theentire cohort(HR 1.37; 95% CI 1.31 to 1.43). Death risk was highest in males diagnosed with gynaecomastia and aknown pre-existing risk factor(HR 1.75; 95% CI 1.64 to 1.86) compared with males withidiopathicgynaecomastia (HR 1.05; 95% CI 0.98 to 1.13). Specific causes of increased death were malignant neoplasms and circulatory, pulmonary and gastrointestinal diseases. Of the latter, an over fivefold risk of death from liver disease was detected (HR 5.05; 95% CI 3.97 to 6.42).

Conclusions

Males diagnosed with gynaecomastia are at higher risk of death, observed mainly in males with a known pre-existing risk factor of gynaecomastia. These findings will hopefully stimulate more awareness among healthcare providers to potentially apply interventions that aid in alleviating underlying risk factors in males with this condition.
Role matters in understanding ‘quality’ in palliative care: a qualitative analysis of patient, caregiver and practitioner perspectives
Authors: Holdsworth Laura M , Giannitrapani Karleen , Gamboa Raziel C , O’Hanlon Claire , Singh Nainwant , Walling Anne , Lindvall Charlotta , Lorenz Karl
Published: January 2024

Objectives

To compare the discussions from two panels on the concept of palliative care quality for patients with advanced cancer, exploring the priorities reflected in each group’s perspectives.

Design

We convened two RAND-UCLA appropriateness panel discussions on palliative care quality in advanced cancer. Discussions were audio-recorded and transcribed verbatim. Panel transcripts were analysed thematically using a matrix approach to examine perceptions and experiences of quality.

Setting

Discussions were framed within the context of advanced cancer care and palliative care.

Participants

The patient–caregiver panel had 9 patients with current or a history of cancer and caregivers, and the practitioner panel had 10 expert practitioners representing fields of oncology, primary care, social work, palliative care, nursing, pain management and ethics.

Results

Our analysis identified three thematic categories for understanding quality common across both groups and nine subthemes within those categories. At the highest level, quality was conceived as: (1) the patient and caregiver experience of care, (2) technical competence and (3) the structure of health system. Among the subthemes, four were present in only one of the two group’s discussions: ‘purpose and action’ was specific to the patient–caregiver panel, whereas ‘adhering to best medical practice’, ‘mitigating unintended consequences and side effects’, and ‘health system resources and costs’ were specific to the practitioner panel.

Conclusions

While both panels aligned on the three key domains of quality, the particular dimensions through which they perceived quality varied in relation to their experience and role as a professional provider of care versus recipient of healthcare services. These differences suggest the importance of adopting a collaborative approach to quality measurement and improvement so that the values of all interested parties are represented in improvement efforts.
Thematic analysis to explore patients’ experiences with long COVID-19: a conceptual model of symptoms and impacts on daily lives
Authors: Rofail Diana , Somersan-Karakaya Selin , Choi Julia Y , Przydzial Krystian , Zhao Yuming , Hussein Mohamed , Norton Thomas D , Podolanczuk Anna J , Mylonakis Eleftherios , Geba Gregory P
Published: January 2024

Objectives

There is limited qualitative research on patients’ experiences with long COVID-19, and how specific symptoms impact their daily lives. The study aimed to understand patients’ lived experiences of long COVID-19 and to develop a conceptual model representing the symptoms and their impact on overall quality of life.

Setting

Qualitative study consisting of a comprehensive literature review, and in-depth clinician and patient semistructured interviews.

Participants

Forty-one adult patients with long COVID-19, of whom 18 (44%) were recruited through Regeneron Pharmaceuticals’s clinical trials and 23 (56%) through recruitment agencies; 85.4% were female and 73.2% were White. Five independent clinicians treating patients with long COVID-19 were interviewed. Concept saturation was also assessed.

Primary and secondary outcomes

Interview transcripts were analysed thematically to identify concepts of interest spontaneously mentioned by patients, including symptoms and their impacts on daily life, to guide the development of the conceptual model.

Results

Findings from the literature review and clinician and patient interviews resulted in the development of a conceptual model comprising two overarching domains: symptoms (upper respiratory tract, lower respiratory tract, smell and taste, systemic, gastrointestinal, neurocognitive and other) and impacts (activities of daily living, instrumental activities of daily living, physical impacts, emotional, social/leisure activities and professional impacts). Saturation was achieved for the reported impacts. The symptoms reported were heterogenic; neurocognitive symptoms, such as numbness, ringing in ears, haziness, confusion, forgetfulness/memory problems, brain fog, concentration, difficulties finding the right word and challenges with fine motor skills, were particularly pertinent for several months.

Conclusion

The conceptual model, developed based on patient experience data of long COVID-19, highlighted numerous symptoms that impact patients’ physical and mental well-being, and suggests humanistic unmet needs. Prospective real-world studies are warranted to understand the pattern of long COVID-19 experienced in larger samples over longer periods of time.
Exploring the motivation of self-directed learning of hospital pharmacists: a multicentre qualitative study
Authors: Wang Xiangyu , Wen Linlin , Fu Hang , Yin Zhao
Published: January 2024

Objective

Self-directed learning (SDL) has been embraced by the medical community as a core professional competency, with motivation considered a crucial component of SDL. However, little is known about how hospital pharmacists perceive motivation in SDL in the workplace. This study aimed to examine the intrinsic and external motivation of hospital pharmacists in SDL.

Design

This study employed a multicentre qualitative design, which lasted 13 months from May 2020 to June 2021. The interviews were audiorecorded, transcribed verbatim and analysed in NVivo V.12.0. Thematic analysis method was used to analyse the data.

Setting

The study took place in nine public hospitals located in urban areas of Henan Province.

Participants

Sixteen hospital pharmacists were enrolled from the pharmacy departments of the sample hospitals, using a purposive sampling method.

Results

Sixteen one-on-one semistructured interviews were conducted, identifying intrinsic and extrinsic motivation in SDL for hospital pharmacists in the workplace. Intrinsic motivation includes curiosity and interest, achievement, self-efficacy and personal growth. Extrinsic motivation includes a more comprehensive set of elements, such as interpersonal motivations, work-related motivations and career-related motivations.

Conclusions

Personal interests, the influence of surrounding individuals (directly or indirectly), work-related requirements and pressures, and professional development requirements and pressures are the main intrinsic or extrinsic motivations for SDL among hospital pharmacists in China. Future research may focus on these aspects to enhance the SDL competence of hospital pharmacists and other medical personnel.
Promoting maternal-child health by increasing breastfeeding rates: a National Canadian Baby-Friendly Initiative Quality Improvement Collaborative Project
Authors: LeDrew Michelle , Benoit Britney , O'Grady Kathleen , Ustianov Jennifer , Edwards Candi , Gallant Claire , Loring Sally , Clément Louise , Aziz Khalid , Green Marina , O’Sullivan Pam , Nickel Nathan Christopher
Published: January 2024

While breastfeeding has long been an important, globally recognized aspect of population health, disparities exist across Canada. The Baby-Friendly Initiative (BFI) is a WHO/UNICEF best-practice program that helps ensure families receive evidence-based perinatal care and is associated with improved breastfeeding rates. However, <10% of hospitals in Canada are designated as ‘Baby-Friendly’.

The Breastfeeding Committee for Canada (BCC) aimed to increase the number of hospitals that moved towards BFI designation by implementing a National BFI Quality Improvement Collaborative Project. Key activities included (1) implementing and evaluating the BFI Project with 25 hospital teams across Canada and (2) making recommendations for scaling up BFI in Canada.

As of December 2023, three hospitals in the BFI Project have attained designation and six have started the official process towards designation with the BCC. Breastfeeding initiation rates remained high and stable (>80%); however, breastfeeding exclusivity rates did not meet targets. All BFI care indicators improved across participating facilities. All skin-to-skin indicators improved, with rates of immediate and sustained skin-to-skin meeting targets of >80% for vaginal births. BFI care indicators of documented assistance and support with breastfeeding within 6 hours of birth, rooming-in and education about community supports also met target levels. Leadership buy-in, parent partner engagement and collaborative activities of workshops, webinars and mentoring with BFI Project leadership were viewed as valuable.

This BFI Project demonstrated that hospitals could successfully implement Baby-Friendly practices in various Canadian settings despite challenges introduced by the COVID-19 pandemic. Indicators collected as part of this work demonstrate that delivery of Baby-Friendly care improved in participating facilities. Sustainability and scaling up BFI implementation in both hospitals and community health services across Canada through implementation of a BFI Coach Mentor Program is ongoing to enable continued progress and impact on breastfeeding and maternal-child health.
Mixed methods study of attitudes on location of gynaecological oncology outpatient care: a patient and healthcare professional questionnaire
Authors: Newhouse Rebecca , Cullimore Victoria , Hotton Emily , Maxwell Hilary , Jones Eleanor , Morrison Jo
Published: January 2024

Objective

Gynaecological oncology place of care is often based on evolution of services, along historical professional boundaries, rather than user needs or preferences. We aimed to assess existing evidence, gather views of patients in the UK on their preferred place of outpatient care for gynaecological malignancies and evaluate alignment with preferences of healthcare professionals (HCP).

Methods

We performed a mixed methods study, including a scoping review, a patient survey and a healthcare practitioner questionnaire. We collected quantitative and qualitative data, performing content analysis to determine current practice and impact on patients.

Results

No studies were identified in our scoping review. We received responses from 159 patients and 54 gynaecological oncology HCPs. There was a strong preference for a dedicated gynaecological oncology setting (89% somewhat or very happy) (p<0.0001). Fifty-three percent of patients were somewhat or very unhappy to have care colocated with general obstetrics and gynaecology services. Specifically, two key themes were identified through content analysis of qualitative data from patients: ‘environment and getting this right is vital’; and ‘our cancer should be the priority’. HCPs underestimated the strong patient preference to be seen in dedicated units. Of those who see patients within general obstetrics and gynaecology, only 50% said patients were seen at separate times/locations from obstetric patients.

Conclusion

This study demonstrates the significant impact of place of care on gynaecological oncology patients, which may be underestimated by HCPs.
Normal saline for children with bronchiolitis: study protocol for a randomised controlled non-inferiority trial
Authors: Schmidt Marika Nathalie , Daugberg Rie , Nygaard Ulrikka , Nielsen Xiaohui Chen , Chawes Bo , Rytter Maren Heilskov , Schoos Ann-Marie Malby
Published: January 2024

Introduction

Bronchiolitis is one of the most common reasons for hospital admissions in early childhood. As supportive treatment, some treatment guidelines suggest using nasal irrigation with normal saline (NS) to facilitate clearance of mucus from the airways. In addition, most paediatric departments in Denmark use nebulised NS for the same purpose, which can mainly be administered as inpatient care. However, no studies have ever directly tested the effect of saline in children with bronchiolitis.

Methods and analysis

The study is an investigator-initiated, multicentre, open-label, randomised, controlled non-inferiority trial and will be performed at six paediatric departments in eastern Denmark. We plan to include 300 children aged 0–12 months admitted to hospital with bronchiolitis. Participating children are randomised 1:1:1 to nebulised NS, nasal irrigation with NS or no saline therapy. All other treatment will be given according to standard guidelines.

The primary outcome is duration of hospitalisation, analysed according to intention-to-treat analysis using linear regression and Cox regression analysis. By including at least 249 children, we can prove non-inferiority with a limit of 12 hours admission, alpha 2.5% and a power of 80%. Secondary outcomes are need for respiratory support with nasal continuous positive airway pressure or high-flow oxygen therapy and requirement of fluid supplements (either by nasogastric tube or intravenous).

Ethics and dissemination

This study may inform current practice for supportive treatment of children with bronchiolitis. First, if NS is found to be helpful, it may be implemented into global guidelines. If no effect of NS is found, we can stop spending resources on an ineffective treatment. Second, if NS is effective, but nasal irrigation is non-inferior to nebulisation, it may reduce the workload of nurses, and possible duration of hospitalisation because the treatment can be delivered by the parents at home.

Trial registration number

NCT05902702.
Initial intravenous immunoglobulin therapy without aspirin for acute Kawasaki disease: a retrospective cohort study with a Bayesian inference
Authors: Hayashi Ken , Miyakoshi Chisato , Hoshino Shinsuke , Kobayashi Naho , Nakajima Ryo , Sagawa Hironori , Hayashiya Toshikazu , Suzuki Atsushi , Aota Chie , Nishijima Setsuko , Shimizu Yasuyo , Yamakawa Masaru , Tsuda Etsuko
Published: January 2024

Objective

To clarify the necessity of acetylsalicylic acid (ASA) administration combined with intravenous immunoglobulin (IVIG) therapy in the treatment of acute Kawasaki disease.

Design

Retrospective cohort study.

Setting

Multicentre.

Participants

This study included 735 patients with Kawasaki disease aged ≤10 years and hospitalised between 4 and 10 days of illness in eight Japanese hospitals from January 2016 to December 2020.

Exposures

High-dose (HD) ASA was administered with initial IVIG to 333 patients in 6 hospitals (HD group). ASA was not administered routinely to 402 patients in the other two hospitals, and low-dose ASA was only administered when patients developed coronary artery lesions or pericardial effusion (non-HD group).

Primary and secondary outcome measures

The primary outcome was the presence of coronary artery lesions, defined as a coronary artery diameter >+2.5 SD of body surface area within 1 month of onset. The secondary outcome was responsiveness to the initial IVIG therapy. Adjusted risk ratios for the outcomes were calculated using modified Poisson regression models. Bayesian analysis was conducted to estimate the posterior probability of the treatment effect of HD ASA under several prior distributions.

Results

The incidence of coronary artery lesions was not significantly higher in the HD group than in the non-HD group (12/333 (3.6%) vs 15/402 (4.0%)). The proportion of non-responders to initial IVIG was similar between the two groups (HD group: 78/333 (23%); non-HD group: 83/402 (22%)). In the Bayesian analysis, considering a difference of ≤2% to be of no clinical importance, there was only a 9.3% chance of reduced risk of coronary artery lesions in the HD group compared with the non-HD group even with a strongly enthusiastic prior for HD treatment.

Conclusions

Compared with HD ASA treatment, treatment without ASA in the acute phase of Kawasaki disease was not associated with increased complications from Kawasaki disease.
Oral bacteria accelerate pancreatic cancer development in mice
Authors: Saba Elias , Farhat Maria , Daoud Alaa , Khashan Arin , Forkush Esther , Menahem Noam Hallel , Makkawi Hasnaa , Pandi Karthikeyan , Angabo Sarah , Kawasaki Hiromichi , Plaschkes Inbar , Parnas Oren , Zamir Gideon , Atlan Karine , Elkin Michael , Katz Lior , Nussbaum Gabriel
Published: January 2024

Objective

Epidemiological studies highlight an association between pancreatic ductal adenocarcinoma (PDAC) and oral carriage of the anaerobic bacterium
Porphyromonas gingivalis
, a species highly linked to periodontal disease. We analysed the potential for
P. gingivalis
to promote pancreatic cancer development in an animal model and probed underlying mechanisms.

Design

We tracked
P. gingivalis
bacterial translocation from the oral cavity to the pancreas following administration to mice. To dissect the role of
P. gingivalis
in PDAC development, we administered bacteria to a genetically engineered mouse PDAC model consisting of inducible acinar cell expression of mutant
Kras
(
Kras
+
/LSL-G12D; Ptf1a-CreER, iKC mice). These mice were used to study the cooperative effects of
Kras
mutation and
P. gingivalis
on the progression of pancreatic intraepithelial neoplasia (PanIN) to PDAC. The direct effects of
P. gingivalis
on acinar cells and PDAC cell lines were studied in vitro.

Results

P. gingivalis
migrated from the oral cavity to the pancreas in mice and can be detected in human PanIN lesions. Repetitive
P. gingivalis
administration to wild-type mice induced pancreatic acinar-to-ductal metaplasia (ADM), and altered the composition of the intrapancreatic microbiome. In iKC mice,
P. gingivalis
accelerated PanIN to PDAC progression. In vitro,
P. gingivalis
infection induced acinar cell ADM markers SOX9 and CK19, and intracellular bacteria protected PDAC cells from reactive oxygen species-mediated cell death resulting from nutrient stress.

Conclusion

Taken together, our findings demonstrate a causal role for
P. gingivalis
in pancreatic cancer development in mice.
Comparison of efficacy discrepancy between early-phase clinical trials and phase III trials of PD-1/PD-L1 inhibitors
Authors: Li Xiang , Zhou Yangzhong , Xu Bing , Qin Yunhe , Zhao Jiuliang , Li Mengtao , Xu Jiachen , Li Guanqiao
Published: January 2024

Background

Phase III clinical trials are pivotal for evaluating therapeutics, yet a concerning failure rate has been documented, particularly impacting oncology where accelerated approvals of immunotherapies are common. These failures are predominantly attributed to a lack of therapeutic efficacy, indicating overestimation of results from phase II studies. Our research aims to systematically assess overestimation in early-phase trials involving programmed cell death-1 (PD-1)/programmed cell death-ligand 1(PD-L1) inhibitors compared with phase III trials and identify contributing factors.

Methods

We matched 51 pairs of early-phase and phase III clinical trials from a pool of over 9,600 PD-1/PD-L1 inhibitor trials. The matching criteria included identical treatment regimens, cancer types, treatment lines, and biomarker enrichment strategies. To assess overestimation, we compared the overall response rates (ORR) between early-phase and phase III trials. We established independent variables related to eligibility criteria, and trial design features of participants to analyze the factors influencing the observed discrepancy in efficacy between the two phases through univariable and multivariable logistic analyses.

Result

Early-phase trial outcomes systematically overestimated the subsequent phase III results, yielding an odds ratio (OR) comparing ORR in early-phase versus phase III: 1.66 (95% CI: 1.43 to 1.92, p<0.05). This trend of inflated ORR was consistent across trials testing PD-1/PD-L1 monotherapies and combination therapies involving PD-1/PD-L1. Among the examined factors, the exclusion of patients with autoimmune diseases was significantly associated with the disparity in efficacy between early-phase trials and phase III trials (p=0.023). We calculated a Ward statistic of 2.27 to validate the effectiveness of the model.

Conclusion

These findings underscore the tendency of overestimation of efficacy in early-phase trials involving immunotherapies. The observed differences could be attributed to variations in the inclusion of patients with autoimmune disorders in early-phase trials. These insights have the potential to inform stakeholders in the future development of cancer immunotherapies.
Lower frequencies of circulating suppressive regulatory T cells and higher frequencies of CD4+naïve T cells at baseline are associated with severe immune-related adverse events in immune checkpoint inhibitor-treated melanoma
Authors: Kovacsovics-Bankowski Magdalena , Sweere Johanna M , Healy Connor P , Sigal Natalia , Cheng Li-Chun , Chronister William D , Evans Shane A , Marsiglio John , Gibson Berit , Swami Umang , Erickson-Wayman Alyssa , McPherson Jordan P , Derose Yoko S , Eliason Annaleah Larson , Medina Carlos O , Srinivasan Ramji , Spitzer Matthew H , Nguyen Ngan , Hyngstrom John , Hu-Lieskovan Siwen
Published: January 2024

Background

Immune-related adverse events (irAEs) are major barriers of clinical management and further development of immune checkpoint inhibitors (ICIs) for cancer therapy. Therefore, biomarkers associated with the onset of severe irAEs are needed. In this study, we aimed to identify immune features detectable in peripheral blood and associated with the development of severe irAEs that required clinical intervention.

Methods

We used a 43-marker mass cytometry panel to characterize peripheral blood mononuclear cells from 28 unique patients with melanoma across 29 lines of ICI therapy before treatment (baseline), before the onset of irAEs (pre-irAE) and at the peak of irAEs (irAE-max). In the 29 lines of ICI therapy, 18 resulted in severe irAEs and 11 did not.

Results

Unsupervised and gated population analysis showed that patients with severe irAEs had a higher frequency of CD4+naïve T cells and lower frequency of CD16+natural killer (NK) cells at all time points. Gated population analysis additionally showed that patients with severe irAEs had fewer T cell immunoreceptor with Ig and ITIM domain (TIGIT+) regulatory T cells at baseline and more activated CD38+CD4+central memory T cells (TCM) and CD39+and Human Leukocyte Antigen-DR Isotype (HLA-DR)+CD8+TCM at peak of irAEs. The differentiating immune features at baseline were predominantly seen in patients with gastrointestinal and cutaneous irAEs and type 1 diabetes. Higher frequencies of CD4+naïve T cells and lower frequencies of CD16+NK cells were also associated with clinical benefit to ICI therapy.

Conclusions

This study demonstrates that high-dimensional immune profiling can reveal novel blood-based immune signatures associated with risk and mechanism of severe irAEs. Development of severe irAEs in melanoma could be the result of reduced immune inhibitory capacity pre-ICI treatment, resulting in more activated TCM cells after treatment.
Comparison of a covered stent and pipeline embolization device in intracranial aneurysm: a propensity score matching analysis
Authors: Tong Xin , Xue Xiaopeng , Sun Mingjiang , Han Mingyang , Jiang Peng , Liu Aihua
Published: January 2024

Background

The Willis covered stent (WCS) and pipeline embolization device (PED) have partly overlapping therapeutic indications. However, the differences of effect between these two treatments remain unclear.

Objective

To compare clinical outcome, angiographic outcome, and complications following treatment with a WCS versus PED.

Methods

Patients with intracranial aneurysms treated by a WCS or PED between January 2015 and December 2020 were included. The primary outcomes were complications, clinical outcome (modified Rankin Scale score >2), and angiographic outcome (incomplete aneurysm occlusion). Propensity score matching was conducted to adjust for potential confounding factors.

Results

A total of 94 aneurysms treated by WCS and 698 aneurysms by PED were included. Compared with the PED group, patients in the WCS group are younger, a greater number have a poor condition at admission, a larger proportion of ruptured, non-saccular, and anterior circulation aneurysms, a smaller aneurysm neck width, and less coiling assistance is required. A total of 42 (44.7%) branches were covered by WCS. After adjustment for age, sex, aneurysm type, rupture status, neck size, aneurysm location, and coiling, 50 WCS and PED pairs were examined for internal carotid artery aneurysms. No significant differences were observed in clinical (10.4% vs 2.1%, P=0.206) and angiographic outcomes (12.8% vs 18.2%, P=0.713). However, 27 branches covered by WCS, including 22 ophthalmic arteries and five posterior communicating arteries. Patients in the WCS group had a higher intraoperative complication rate than those in the PED group (28% vs 6%, P=0.008), especially in the occlusion rate of covered branches (51.9% vs 11.1%, P<0.001).

Conclusion

The comparable clinical and angiographic outcomes of WCS or PED demonstrate the therapeutic potential of WCS as a viable alternative for aneurysms. However, the complication of occlusion of covered branches might not be negligible.
Cardiology researchers’ practices and perceived barriers to open science: an international survey
Authors: Cobey Kelly D , Alayche Mohsen , Saba Sara , Barnes Nana Yaa , Ebrahimzadeh Sanam , Alarcón Emilio , Hibbert Benjamin , Moher David
Published: January 2024

Objective

Open science is a movement and set of practices to conduct research more transparently. Implementing open science will significantly improve public access and supports equity. It also has the potential to foster innovation and reduce duplication through data and materials sharing. Here, we survey an international group of researchers publishing in cardiovascular journals regarding their perceptions and practices related to open science.

Methods

We identified the top 100 ‘Cardiology and Cardiovascular Medicine’ subject category journals from the SCImago journal ranking platform. This is a publicly available portal that draws from Scopus. We then extracted the corresponding author’s name and email from all articles published in these journals between 1 March 2021 and 1 March 2022. Participants were sent a purpose-built survey about open science. The survey contained primarily multiple choice and scale-based questions for which we report count data and percentages. For the few text-based responses we conducted thematic content analysis.

Results

198 participants responded to our survey. Participants had a mean response of 6.8 (N=197, SD=1.8) on a 9-point scale with endpoints, not at all familiar (1) and extremely familiar (9), when indicating how familiar they were with open science. When asked about where they obtained open science training, most participants indicated this was done on the job self-initiated while conducting research (n=103, 52%), or that they had no formal training with respect to open science (n=72, 36%). More than half of the participants indicated they would benefit from practical support from their institution on how to perform open science practices (N=106, 54%). A diversity of barriers to each of the open science practices presented to participants were acknowledged. Participants indicated that funding was the most essential incentive to adopt open science.

Conclusions

It is clear that policy alone will not lead to the effective implementation of open science. This survey serves as a baseline for the cardiovascular research community’s open science performance and perception and can be used to inform future interventions and monitoring.
Colchicine in acute myocardial infarction: cardiovascular events at 1-year follow up
Authors: Bouleti Claire , Viscogliosi Simon , Bresson Didier , Leboube Simon , Bochaton Thomas , El-Jonhy Naoual , AMAZ Camille , Prunier Fabrice , Bidaux Gabriel , Roubille Francois , Angoulvant Denis , Mewton Nathan
Published: January 2024

Objective

In the COVERT-MI randomised placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days in acute ST-elevated myocardial infarction did not reduce infarct size but was associated with a significant increase in left ventricular thrombus (LVT) in comparison to placebo. We aimed to assess the 1-year clinical outcomes of the study population.

Methods

This study is a follow-up analysis of the COVERT-MI study on prespecified secondary clinical endpoints at 1 year. The primary endpoint of this study was a composite of major adverse cardiovascular events (MACEs), including all-cause death, acute coronary syndromes, heart failure events, ischaemic strokes, sustained ventricular arrhythmias and acute kidney injury at 1-year follow-up. The quality of life (QOL) and the drug therapy prescription were also assessed.

Results

At 1 year, 192 patients (101 patients in the colchicine group, 91 in the placebo group) were followed up. Seventy-six (39.6%) MACEs were reported in the study population. There was no significant difference regarding the number of MACEs between groups: 36 (35.6%) in the colchicine group and 40 (44.1%) in the placebo group (p=0.3). There were no differences in the occurrence of ischaemic strokes between the colchicine group and the control group (3 (3%) vs 2 (2.2%), respectively, p=0.99). There was a trend towards fewer heart failure events in the colchicine group compared with the placebo group (12 (11.9%) vs 18 (19.8%), p=0.20). There was no significant difference in QOL scores at 1 year (75.8±15.7 vs 72.7±16.2 respectively, p=0.18).

Conclusions

There was no significant difference between the colchicine and placebo groups at 1 year regarding MACEs, especially concerning deaths or ischaemic strokes. No excess of ischaemic adverse events was observed despite the initial increase in LVT in the colchicine group.

Trial registration number

NCT0315681.
PD-1/PD-L1 governed cross-talk of exhausted CD8+T and memory B cells in systemic lupus erythematosus
Authors: Wang Kaiwen , Zhao Jiangfeng , Feng Xuemei , He Shuangjun , Li Jia , Sun Fangfang , Xu Zhangling , Yang Haiting , Ye Jiaer , Cao Liou , Ye Shuang
Published: January 2024

Background

Indeterminate readout of the quantitative interferon-γ release test (QFT) forMycobacterium tuberculosisscreening is a specific laboratory finding for systemic lupus erythematosus (SLE), which may be due to T-cell exhaustion and abnormal programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) signalling.

Methods

We enrolled 104 patients with SLE and 225 with other rheumatic musculoskeletal diseases (RMDs) who presented to the outpatient clinic between 2020 and 2023. Twenty healthy donors served as the controls. The QFT was performed in all participants, and those with indeterminate results were compared among the groups. Immunophenotyping and functional assays were performed using blood mononuclear cells. Interferon (IFN)-γ was detected in vitro and ex vivo in patients with SLE with indeterminate or negative QFT results, before or after rituximab therapy.

Results

104 patients with SLE had a significantly higher rate of indeterminate QFT results was significantly higher (17.31%) than that of 225 patients with RMD (3.56%). Patients with SLE with indeterminate QFT had more active disease (SLEDAI-2K, mean 10.94 vs 4.02, p<0.0001), including a higher incidence of active nephritis (55.56% vs 29.07%). Indeterminate QFT in SLE is mainly caused by an insufficient IFN-γ response in CD8+T cells with exhausted immunophenotypes. The abnormal interaction between exhausted PD-1 high CD8+T cells and activated PD-L1 low memory B cells in SLE can be reversed with a PD-1 agonist or increased PD-L1 expression. Rituximab treatment indirectly reversed this IFN-γ response.

Conclusion

The PD-1/PD-L1 signalling pathway, which governs the crosstalk between exhausted CD8+T cells and activated memory B cells, is a mechanistic explanation for insufficient interferon-γ response in patients with SLE.
Improving estimates of the illicit cigarette trade through collaboration: lessons from two studies of Malaysia
Authors: Kunji Koya Ridzuan , Branston J Robert , Gallagher Allen W A , Bui Wency Kher Thinng , Ross Hana , Mohamed Nor Norashidah
Published: January 2024

This paper critically analyses contrasting estimates of Malaysia’s illicit cigarette trade in 2011, 2015 and 2019 by Buiet aland Koyaet alwho previously produced independent estimates at about the same time using tax gap analysis. Collaboration between the two authors’ teams emerged due to the discrepancies in their results, generating this paper to explore the methodological issues identified and hence produce revised estimates of the rate of illicit. Key issues identified were: Buiet al’s assessment of legally imported cigarettes impacting all years; their exclusion of ad valorem duty affecting the 2011 and 2015 estimates; Koyaet aloverlooked the value of cigarettes for export market in their ad valorem calculation and used the sales value of imported tobacco/tobacco products, not just cigarettes, both of which impact estimates for 2011 and 2015. Recalculations using Koyaet al’s consumption data reveal that in 2019, illicit cigarettes accounted for about 70% of the market, which is higher than Buiet al’s estimate (38%) but slightly lower than Koyaet al’s (72%). For 2011 and 2015 where ad valorem applied, the corrected estimates show a share of the illicit cigarette market of approximately 41.1% and 52.7%, respectively, differing from Buiet al’s 0% in 2011 and 29.6% in 2015, and Koyaet al’s 51% in 2011 and 55% in 2015. This paper provides essential lessons for addressing methodological issues between authors’ teams and updated estimates of Malaysia’s illicit cigarette trade, verifying that Malaysia faces a substantial illicit cigarette trade problem.
Centrifuge and analytical modeling of counterweight retaining walls under translation mode
Authors: Wang Tengfei , Luo Qiang , El Naggar M. Hesham , Liu Hongyang , Liu Kaiwen
Published: January 2024

Counterweight retaining walls (CRWs) are a variant of gravity-retaining walls that feature a pressure relief platform (RP) on the backfill side to reduce total earth pressure, offering a cost-effective option compared to traditional forms. However, the intricate interactions between CRWs and backfill, coupled with the lack of clear design guidelines, have restricted their use. This study examines the behavior of CRWs in translation mode using three different centrifuge model tests, each with varying fill heights. Observations show a slightly concave slip surface through the wall heel and a nearly planar slip surface extending from the edge of the RP to the back of the wall in an active limit state. Backfill movement can be classified into translation, sliding, and stable zones. Earth pressure distribution on the upper wall follows a trapezoidal pattern, whereas the pressure on the lower wall exhibits a triangular distribution. Earth pressure on the RP is approximately linear, peaking near the RP’s edge. Introducing a friction angle mobilization factor for the potential first slip surface improves accuracy in calculating earth pressure. The tests were replicated to validate the analytical model for earth pressure calculations, using the adaptive finite-element limit analysis method.
A novel three-dimensional SCR motion simulator for modelling the catenary riser–seabed interaction in a centrifuge
Authors: Ng Charles Wang Wai , Le Yi , Baghbanrezvan Sina , Van Laak Paul
Published: January 2024

Steel catenary risers (SCRs) provide a cost-effective solution for deepwater oil and gas production. However, SCRs are susceptible to potential fatigue failure due to the cyclic motions of floating platforms. Previous studies on the physical modelling of cyclic SCR–seabed interactions have primarily focused on either the continuous cyclic motion of an SCR or a single rest period between two SCR motion packets. However, our understanding of the development of seabed trenches and excess pore pressure and their effects on SCR fatigue during multiple episodes of SCR motion and soil reconsolidation remains limited. This study presents a newly developed model container capable of modelling three-dimensional SCR motions including heave, surge, sway, and vortex-induced vibration in a geotechnical centrifuge. A centrifuge test is conducted to investigate the vertical cyclic SCR–seabed interaction, considering five vertical cyclic motion packets with intervening periods of reconsolidation. The results indicate that ignoring the effects of reconsolidation leads to an overestimation of the fatigue life of an SCR. In this test, the SCR fatigue life is reduced by 18%–23% after five episodic SCR motion packets and intervening reconsolidation.
Exploring a new approach to hadronic parity violation from lattice QCD
Authors: Petschlies Marcus , Schlage Nikolas , Sen Aniket , Urbach Carsten
Published: January 2024

The long-range, parity-odd nucleon interaction generated by single-pion exchange is captured in the parity-odd pion–nucleon coupling $$h^{1}_{\pi }$$

h
π
1

. Its calculation in lattice QCD requires the evaluation of four-quark operator nucleon three-point functions. We investigate a new numerical approach to compute $$h^{1}_{\pi }$$

h
π
1

based on nucleon matrix elements of parity-even four-quark operators and related to the parity-violating electroweak theory by partial conservation of axial current (PCAC) and chiral perturbation theory. This study is performed with 2+1+1 dynamical flavors of twisted mass fermions at pion mass $$m_{\pi } \approx 260 \,\text {MeV}$$

m
π

≈
260

MeV

in a lattice box of $$L \approx 3 \,\text {fm}$$

L
≈
3

fm

and with lattice spacing of $$a \approx 0.091 \,\text {fm}$$

a
≈
0.091

fm

. From a calculation excluding fermion loop diagrams we find a bare coupling of $$h^{1}_{\pi }= 8.08 \,(98) \cdot 10^{-7}$$

h
π
1

=
8.08

(
98
)

·

10

-
7

.
A Survey on Variant Domination Problems in Geometric Intersection Graphs
Authors: Xu Shou-Jun , Wang Cai-Xia , Yang Yu
Published: January 2024

Given a graph [Formula: see text] with vertex set [Formula: see text], a subset [Formula: see text] of [Formula: see text] is called a dominating set of [Formula: see text] if every vertex is either in [Formula: see text] or is adjacent to a vertex in [Formula: see text]. There are a lot of variants for dominating sets, such as connected dominating sets, total dominating sets, total restricted dominating sets, secure (connected, total) dominating sets, etc. Geometric intersection graphs are graphs for which there is a bijection [Formula: see text] between the vertices and a set [Formula: see text] of geometric objects (for example, disks, rectangles, etc.) such that there is an edge between two vertices [Formula: see text] and [Formula: see text] if and only if the objects [Formula: see text] and [Formula: see text] intersect. In this paper, we offer a survey about complexity and algorithmic results on variant domination problems in geometric intersection graphs.