bluuebunny/crossref_metadata_2025 huggingface dataset:
Guidelines for the development and validation of patient-reported outcome measures: a scoping review
Authors: Jung Andres , Challoumas Dimitris , Pagels Larissa , Armijo-Olivo Susan , Braun Tobias , Luedtke Kerstin
Published: May 2024

Objective

The objectives of this scoping review were to provide an overview of existing guidelines for the development and validation of patient-reported outcome measures (PROMs), review them for comprehensiveness and clarity and provide recommendations for their use based on the goals of the instrument developers.

Design

Scoping review.

Methods

A literature search was performed in PubMed, Scopus, PsycInfo and Google Scholar up to 2 June 2023 to identify guidelines for the development and validation of PROMs. Screening of records and reports as well as data extraction were performed by two reviewers. To assess the comprehensiveness of the included guidelines, a mapping synthesis was performed and steps to develop and validate a measurement instrument outlined in the included guidelines were mapped to an a priori framework including 20 steps, which was based on the guideline by de Vetet al.

Results

A total of 40 guidelines were included. Statistical advice (at least partially) was provided in 98% of the guidelines (39/40) and 88% (35/40) of the guidelines included examples for steps required to develop and validate PROMs. However, 78% (31/40) of the guidelines were not comprehensive and two essential steps in PROM development (‘consideration and elaboration of the measurement model’ and ‘responsiveness’) were not included in 80% and 72% of the guidelines, respectively. Three guidelines included all 20 steps and six included almost all steps (≥90% of steps) for developing and validating a PROM.

Discussion

Most guidelines on PROM development and validation do not appear to be comprehensive, and some crucial steps are missing in most guidelines. Nevertheless, for some purposes of PROMs, many guidelines provide helpful advice and support.

Conclusion

At least 15 guidelines may be recommended, including three comprehensive guidelines that can be recommended for the development and validation of PROMs for most purposes (eg, to discriminate between subjects with a particular condition and subjects without that condition, to evaluate the effects of treatments (between a pre and post time-points) or to evaluate a status quo).
The state of mental health among Ebola virus disease survivors through a cross-sectional study in Sierra Leone
Authors: Schindell Brayden G , Fredborg Bev , Kowalec Kaarina , Shaw Souradet , Kangbai Jia B , Kindrachuk Jason
Published: May 2024

Background

The West African Ebola virus disease (EVD) epidemic resulted in >28 000 disease cases and >11 000 fatalities. The unprecedented number of survivors from this epidemic has raised questions about the long-term mental health impacts of EVD survivorship and the capacity to meet these needs.

Objectives

Assess the frequency and factors associated with mental health consequences of EVD survivorship in Sierra Leone.

Methods

A cross-sectional study of 595 EVD survivors and 403 close contacts (n=998) from Sierra Leone assessed via in-person survey between November 2021 and March 2022. The assessment included validated mental health screening tools (Patient Health Questionnaire-9, PTSD Checklist-5, Alcohol Use Disorders Identification Test, Drug Abuse Screening Test-20) to indicate the presence/absence of disorder. The frequency of each disorder and factors associated with each disorder were assessed.

Findings

EVD-associated post-traumatic stress disorder (PTSD) was reported by 45.7% (n=257) of EVD survivors. Moreover, 3.9% (n=22) and 12.0% (n=67) of EVD survivors reported major depression (MD) and substance use, respectively; all mental health outcomes were higher than baseline rates in the region (PTSD: 6%–16%, MD: 1.1%, substance use: 2.2%). PTSD among EVD survivors was associated with acute EVD duration of ≥21 days (adjusted OR, AOR 2.24, 95% CI 1.16 to 4.43), 35–44 years of age (AOR 3.31, 95% CI 1.33 to 8.24; AOR 2.99, 95% CI 1.09 to 8.24) and residential mobility (AOR 4.16, 95% CI 2.35 to 7.35).

Conclusions

Concerningly, the levels of mental health disorders among EVD survivors in Sierra Leone remained elevated 6–8 years after recovery.

Clinical implications

Results can be used to inform policy efforts and target resources to address mental health in EVD survivors.
Illness perception in functional neurological disorder: low illness coherence and personal control
Authors: Joos Andreas , Popkirov Stoyan , Lahmann Claas , Jöbges Michael , Herrmann Christoph , Maner Philipp , Schörner Kai , Birke Gunnar , Hartmann Armin
Published: May 2024

Introduction

Illness perception refers to patients’ subjective representations and appraisals of somatic and mental symptoms. These are relevant for self-management and outcome. In clinical practice, patients with functional neurological disorder (FND) often encounter a fragmented biomedical attitude, which leaves them without clear concepts. In this context, illness perception is relevant.

Methods

Illness perception was assessed in FND patients and compared with samples of psychosomatic patients (PSM) as well as poststroke patients (STR). The three samples (FND, n=87; PSM, n=97 and STR, n=92) were almost all in inpatient treatment or rehabilitation. Illness perception was assessed with the revised German version of the Illness Perception Questionnaire (IPQ-R). For assessments of correlations, depressive symptoms were tested with the Patient Health Questionnaire-9, dissociative and functional neurological symptoms by the German adaption of the Dissociative Experiences Scale and biopsychosocial complexity by the INTERMED Self-Assessment questionnaire.

Results

Apart from the chronicity subscale, all dimensions of the IPQ-R differed between groups. FND patients perceived lower illness coherence and personal control than both other groups and attributed their illness more to chance than to behavioural risk factors. PSM patients had the strongest emotional representations. There were only few correlations with dissociative scores and biopsychosocial complexity.

Conclusion

Illness perception is an important issue in patients with FND with particular emphasis on low illness coherence and personal control. Missing associations with biopsychosocial complexity suggest that subjective illness perception is an important complementary but separate issue, which likely influences therapeutic alliance and self-management in FND. Future studies should assess its influences on outcome.

Trial registration number

DRKS00024685; German Clinical Trials Register;www.drks.de.
Inhaled Nitric Oxide ReDuce postoperatIve pulmoNAry complicaTions in patiEnts with recent COVID-19 infection (INORDINATE): protocol for a randomised controlled trial
Authors: Zheng Ziyu , Wang Lini , Wang Shuxiu , Fan Qianqian , Zhang Hui , Luo Gang , Gao Baobao , Yang Xue , Zhao Bingqing , Wang Xiaomei , Dong Hailong , Nie Huang , Lei Chong
Published: May 2024

Background

A history of SARS-CoV-2 infection has been reported to be associated with an increased risk of postoperative pulmonary complications (PPCs). Even mild PPCs can elevate the rates of early postoperative mortality, intensive care unit (ICU) admission and prolong the length of ICU and/or hospital stays. Consequently, it is crucial to develop perioperative management strategies that can mitigate these increased risks in surgical patients who have recently been infected with SARS-CoV-2. Accumulating evidence suggests that nitric oxide (NO) inhalation might be effective in treating COVID-19. NO functions in COVID-19 by promoting vasodilation, anticoagulation, anti-inflammatory and antiviral effects. Therefore, our study hypothesises that the perioperative use of NO can effectively reduce PPCs in patients with recent SARS-CoV-2 infection.

Method and analysis

A prospective, double-blind, single-centre, randomised controlled trial is proposed. The trial aims to include participants who are planning to undergo surgery with general anaesthesia and have been recently infected with SARS-CoV-2 (within 7 weeks). Stratified allocation of eligible patients will be performed at a 1:1 ratio based on the predicted risk of PPCs using the Assess Respiratory Risk in Surgical Patients in Catalonia risk index and the time interval between infection and surgery.

The primary outcome of the study will be the presence of PPCs within the first 7 days following surgery, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm and aspiration pneumonitis. The primary outcome will be reported as counts (percentage) and will be compared using a two-proportion χ2test. The common effect across all primary components will be estimated using a multiple generalised linear model.

Ethics and dissemination

The trial is approved by the Institutional Review Board of Xijing Hospital (KY20232058-F1). The findings, including positive, negative and inconclusive results, will be published in scientific journals with peer-review processes.

Trial registration number

NCT05721144.
Survival status and predictors of mortality among preterm neonates admitted in Bench Sheko Zone, Sheka Zone and Keffa Zone Governmental Hospitals, Southwest Ethiopia (2021): prospective follow-up study
Authors: Mihretu Esmelealem , Genie Yalemtsehay Dagnaw , Adugnaw Emebet , Shibabaw Aster Tadesse
Published: May 2024

Introduction

Prematurity presents a significant challenge to the global community due to the rapid increase in its incidence and its disproportionate contribution to increased infant mortality rates.

Objective

To assess the survival status and predictors of mortality among preterm neonates.

Design

A multicentre prospective follow-up study was used.

Setting

625 preterm neonates were admitted to hospitals for secondary level of care. The study covers the Bench Maji Zone, Keffa Zone, Sheka Zone, nearby woredas and portions of the Gambella area in Southwest Ethiopia.

Participants

614 preterm neonates with gestational age less than 37 weeks were entered for follow-up and 400 neonates were censored. Neonates with severe fetal malformations and neonates who need urgent referral were excluded from the study.

Results

Overall, 200 (32.57%) participants died with an incidence rate of 61.69 deaths per 1000 person-day observations (95% CI: 53.71 to 70.86). Poor kangaroo mother care (KMC) services (adjusted HR (AHR)=0.19, 95% CI: 0.12 to 0.29), sex (AHR=0.66, 95%, CI: 0.47 to 0.94), not initiating breast feeding (HR=2.78, 95% CI: 1.8 to 4.28), hypothermia (AHR=0.63, 95% CI: 0.44 to 0.92), anaemia (AHR=6.2, 95% CI: 2.34 to 16.43) and gestational age less than 28 weeks (AHR=9.28, 95% CI: 1.78 to 48.42) were independent predictors.

Conclusion and recommendation

The rate of preterm neonatal mortality was high compared with the Ethiopia Demographic and Health Survey report nationally. Healthcare workers should encourage KMC services and breastfeeding initiation and prevent preterm neonates from being anaemic to increase their chances of survival.
Health risks of exposure to air pollution in areas where coal-fired power plants are located: protocol for a scoping review
Authors: Mahlangeni Nomfundo , Kapwata Thandi , Laban Tracey , Wright Caradee Yael
Published: May 2024

Introduction

Coal-fired power plants are major sources of air pollution which impact human health. Coal combustion byproducts released into the air include particulate matter, nitrogen oxides and sulphur dioxide. Exposure to fine particulate matter is associated with increased risk of mortality. This scoping review will examine and summarise the current literature on the health risks of exposure to air pollution in areas in which coal-fired power plants exist.

Methods and analysis

This scoping review will be conducted according to the Joanna Briggs Institute methodological framework and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Five electronic databases (PubMed, ScienceDirect, Scopus, Web of Science and Google Scholar) will be searched for relevant articles. Studies will be included up until 31 January 2024. There will be no restriction on geographical area. The searches will be limited to studies published in English. Title, abstract, full-text screening and data extraction of relevant articles will be done by two independent reviewers. Discrepancies will be resolved by group discussion. The findings will be presented in tables with a narrative summary. This review will consider epidemiological studies and grey literature that report on the health risks of exposure to air pollution in areas where coal-fired power plants exist.

Ethics and dissemination

All data will be collected from published and grey literature. Ethics approval is therefore not required. We will submit our findings for publication in a peer-reviewed journal.
Artificial intelligence-based prediction of diabetic retinopathy evolution (EviRed): protocol for a prospective cohort
Authors: Tadayoni Ramin , Massin Pascale , Bonnin Sophie , Magazzeni Stéphanie , Lay Bruno , Le Guilcher Alexandre , Vicaut Eric , Couturier Aude , Quellec Gwenolé , Investigators EviRed
Published: May 2024

Introduction

An important obstacle in the fight against diabetic retinopathy (DR) is the use of a classification system based on old imaging techniques and insufficient data to accurately predict its evolution. New imaging techniques generate new valuable data, but we lack an adapted classification based on these data. The main objective of the Evaluation Intelligente de la Rétinopathie Diabétique, Intelligent evaluation of DR (EviRed) project is to develop and validate a system assisting the ophthalmologist in decision-making during DR follow-up by improving the prediction of its evolution.

Methods and analysis

A cohort of up to 5000 patients with diabetes will be recruited from 18 diabetology departments and 14 ophthalmology departments, in public or private hospitals in France and followed for an average of 2 years. Each year, systemic health data as well as ophthalmological data will be collected. Both eyes will be imaged by using different imaging modalities including widefield photography, optical coherence tomography (OCT) and OCT-angiography. The EviRed cohort will be divided into two groups: one group will be randomly selected in each stratum during the inclusion period to be representative of the general diabetic population. Their data will be used for validating the algorithms (validation cohort). The data for the remaining patients (training cohort) will be used to train the algorithms.

Ethics and dissemination

The study protocol was approved by the French South-West and Overseas Ethics Committee 4 on 28 August 2020 (CPP2020-07-060b/2020-A01725-34/20.06.16.41433). Prior to the start of the study, each patient will provide a written informed consent documenting his or her agreement to participate in the clinical trial. Results of this research will be disseminated in peer-reviewed publications and conference presentations. The database will also be available for further study or development that could benefit patients.

Trial registration number

NCT04624737
Perils and payoffs for patients in serious illness conversations as described by physicians: a qualitative study
Authors: Baxter Rebecca , Pusa Susanna , Andersson Sofia , Sandgren Anna
Published: May 2024

Background

The Serious Illness Care Programme was developed to promote more, better and earlier serious illness conversations. Conversations about goals and values are associated with improved experiences and outcomes for seriously ill patients. Clinicians’ attitudes and beliefs are thought to influence the uptake and performance of serious illness conversations, yet little is known about how clinicians perceive the impact of these conversations on patients. This study aimed to explore physicians’ perceptions regarding the impact of serious illness conversations for patients.

Methods

The Serious Illness Care Programme was implemented as a quality improvement project in two hospitals in Southern Sweden. Focus group evaluation discussions were conducted with 14 physicians and inductive thematic analysis was undertaken.

Results

The results revealed that physicians considered potential perils and optimised potential payoffs for patients when engaging in serious illness conversations. Potential perils encompassed inappropriate timing, damaging emotions and shattering hopes. Potential payoffs included reflection time, secure space, and united understandings.

Conclusions

Physicians depicted a balance in evaluating the perils and payoffs of serious illness conversations for patients and recognised the interrelation of these possibilities through continual assessment and adjustment.
Impact of geographical cohorting, multidisciplinary rounding and incremental case management support on hospital length of stay and readmission rates: a propensity weighted analysis
Authors: Jolly Graham Aubrey , Platt Alyssa , Knutsen Kristian , Fletcher Emily , Gallagher David
Published: May 2024

Hospital length of stay (LOS) in the USA has been increasing since the start of the COVID-19 pandemic, with numerous negative outcomes, including decreased quality of care, worsened patient satisfaction and negative financial impacts on hospitals. While many proposed factors contributing to prolonged LOS are challenging to modify, poor coordination of care and communication among clinical teams can be improved.

Geographical cohorting of provider teams, patients and other clinical staff is proposed as a solution to prolonged LOS and readmissions. However, many studies on geographical cohorting alone have shown no significant impact on LOS or readmissions. Other potential benefits of geographical cohorting include improved quality of care, learning experience, communication, teamwork and efficiency.

This paper presents a retrospective study at Duke University Hospital (DUH) on the General Medicine service, deploying a bundled intervention of geographical cohorting of patients and their care teams, twice daily multidisciplinary rounds and incremental case management support. The quality improvement study found that patients in the intervention arm had 16%–17% shorter LOS than those in the control arms, and there was a reduction in 30-day hospital readmissions compared with the concurrent control arm. Moreover, there was some evidence of improved accuracy of estimated discharge dates in the intervention arm.

Based on these findings, the health system at DUH recognised the value of geographical cohorting and implemented additional geographically based medicine units with multidisciplinary rounds. Future studies will confirm the sustained impact of these care transformations on hospital throughput and patient outcomes, aiming to reduce LOS and enhance the quality of care provided to patients.
Swallowed topical steroid therapy for eosinophilic oesophagitis in children: practical, evidence-based guidance by the BSPGHAN Eosinophilic Oesophagitis Working Group
Authors: Chan Joseph , Flynn Diana M , Gordon Morris , Parmar Raj , Moolenschot Kerryn , Jackman Lucy , Gaynor Ed , Epstein Jenny , Cordell Amanda , Kannappan Hema , Furman Mark , Thompson Julie , Gasparetto Marco , Auth Marcus K H
Published: May 2024

Objective

To develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment.

Methods

A systematic literature review using Cochrane guidance was carried out by the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Eosinophilic Oesophagitis (EoE) Working Group (WG) and research leads to determine the evidence base for preparation, dosing and duration of use of swallowed topical steroid (STS) formulations in EoE. Seven themes relating to pEoE were reviewed by the WG, alongside the Cochrane review this formed the evidence base for consensus recommendations for pEoE in the UK. We provide an overview of practical considerations including treatment regimen and dosing. Oral viscous budesonide (OVB) and, if agreed by local regulatory committees, orodispersible budesonide (budesonide 1 mg tablets) were selected for ease of use and with most improvement in histology. A practical ‘how to prepare and use’ OVB appendix is included. Side effects identified included candidiasis and adrenal gland suppression. The use of oral systemic steroids in strictures is discussed briefly.

Results

2638 citations were identified and 18 randomised controlled trials were included. Evidence exists for the use of STS for induction and maintenance therapy in EoE, especially regarding histological improvement. Using the Appraisal of Guidelines, Research and Evaluation criteria, dosing of steroids by age (0.5 mg two times per day <10 years and 1 mg two times per day ≥10 years) for induction of at least 3 months was suggested based on evidence and practical consideration. Once histological remission is achieved, maintenance dosing of steroids appears to reduce the frequency and severity of relapse, as such a maintenance weaning regimen is proposed.

Conclusion

A practical, evidence-based flow chart and guidance recommendations with consensus from the EoE WG and education and research representatives of BSPGHAN were developed with detailed practical considerations for use in the UK.
A greener gastroenterology service in a greener NHS
Authors: Donnelly Leigh
Published: May 2024

The current climate crisis is the biggest risk to health in recent years. As a result the National Health Service (NHS) has a commitment to reduce carbon emissions to net zero by 2040. As healthcare professionals in Gastroenterology, we have a responsibility to ensure that our services are sustainable. By making changes to practice and re-examine the way we deliver patient care, we can safeguard a greener NHS for future generations.
Enhancing IgA-mediated neutrophil cytotoxicity against neuroblastoma by CD47 blockade
Authors: Chan Chilam , Stip Marjolein , Nederend Maaike , Jansen Marco , Passchier Elsemieke , van den Ham Femke , Wienke Judith , van Tetering Geert , Leusen Jeanette
Published: May 2024

Background

Approximately half of the neuroblastoma patients develop high-risk neuroblastoma. Current treatment involves a multimodal strategy, including immunotherapy with dinutuximab (IgG ch14.18) targeting GD2. Despite achieving promising results, the recurrence rate remains high and poor survival persists. The therapeutic efficacy of dinutuximab is compromised by suboptimal activation of neutrophils and severe neuropathic pain, partially induced by complement activation.

Methods

To enhance neutrophil cytotoxicity, IgG ch14.18 was converted to the IgA isotype, resulting in potent neutrophil-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), without complement activation. However, myeloid checkpoint molecules hamper neutrophil cytotoxicity, for example through CD47 that is overexpressed on neuroblastomas and orchestrates an immunosuppressive environment upon ligation to signal regulatory protein alpha (SIRPα) expressed on neutrophils. In this study, we combined IgA therapy with CD47 blockade.

Results

In vitro killing assays showed enhanced IgA-mediated ADCC by neutrophils targeting neuroblastoma cell lines and organoids in comparison to IgG. Notably, when combined with CD47 blockade, both IgG and IgA therapy were enhanced, though the combination with IgA resulted in the greatest improvement of ADCC. Furthermore, in a neuroblastoma xenograft model, we systemically blocked CD47 with a SIRPα fusion protein containing an ablated IgG1 Fc, and compared IgA therapy to IgG therapy. Only IgA therapy combined with CD47 blockade increased neutrophil influx to the tumor microenvironment. Moreover, the IgA combination strategy hampered tumor outgrowth most effectively and prolonged tumor-specific survival.

Conclusion

These promising results highlight the potential to enhance immunotherapy efficacy against high-risk neuroblastoma through improved neutrophil cytotoxicity by combining IgA therapy with CD47 blockade.
Exosomal circPOLQ promotes macrophage M2 polarization via activating IL-10/STAT3 axis in a colorectal cancer model
Authors: Sun Zhenqiang , Xu Yanxin , Shao Bo , Dang Pengyuan , Hu Shengyun , Sun Haifeng , Chen Chen , Wang Chaoguan , Liu Jinbo , Liu Yang , Hu Junhong
Published: May 2024

Background

Accumulating evidence demonstrates that an increased tumor-associated macrophage abundance is often associated with poor prognosis in colorectal cancer (CRC). The mechanism underlying the effect of tumor-derived exosomes on M2 macrophage polarization remains elusive.

Results

The novel circular RNA circPOLQ exhibited significantly higher expression in CRC tissues than in paired normal tissues. Higher circPOLQ expression was associated with poorer prognosis in patients with CRC. In vitro and in vivo experiments showed that tumor-derived exosomal circPOLQ did not directly regulate CRC cell development but promoted CRC metastatic nodule formation by enhancing M2 macrophage polarization. circPOLQ activated the interleukin-10/signal transducer and activator of transcription 3 axis by targeting miR-379–3 p to promote M2 macrophage polarization.

Conclusion

circPOLQ can enter macrophages via CRC cell-derived exosomes and promote CRC metastatic nodule formation by enhancing M2 macrophage polarization. These findings reveal a tumor-derived exosome-mediated tumor–macrophage interaction potentially affecting CRC metastatic nodule formation.
Dose escalation study of a personalized peptide-based neoantigen vaccine (EVX-01) in patients with metastatic melanoma
Authors: Mørk Sofie Kirial , Skadborg Signe Koggersbøl , Albieri Benedetta , Draghi Arianna , Bol Kalijn , Kadivar Mohammad , Westergaard Marie Christine Wulff , Stoltenborg Granhøj Joachim , Borch Annie , Petersen Nadia Viborg , Thuesen Nikolas , Rasmussen Ida Svahn , Andreasen Lars Vibe , Dohn Rebecca Bach , Yde Christina Westmose , Noergaard Nis , Lorentzen Torben , Soerensen Anders Bundgaard , Kleine-Kohlbrecher Daniela , Jespersen Anders , Christensen Dennis , Kringelum Jens , Donia Marco , Hadrup Sine Reker , Marie Svane Inge
Published: May 2024

Background

Neoantigens can serve as targets for T cell-mediated antitumor immunity via personalized neopeptide vaccines. Interim data from our clinical studyNCT03715985showed that the personalized peptide-based neoantigen vaccine EVX-01, formulated in the liposomal adjuvant, CAF09b, was safe and able to elicit EVX-01-specific T cell responses in patients with metastatic melanoma. Here, we present results from the dose-escalation part of the study, evaluating the feasibility, safety, efficacy, and immunogenicity of EVX-01 in addition to anti-PD-1 therapy.

Methods

Patients with metastatic melanoma on anti-PD-1 therapy were treated in three cohorts with increasing vaccine dosages (twofold and fourfold). Tumor-derived neoantigens were selected by the AI platform PIONEER and used in personalized therapeutic cancer peptide vaccines EVX-01. Vaccines were administered at 2-week intervals for a total of three intraperitoneal and three intramuscular injections. The study’s primary endpoint was safety and tolerability. Additional endpoints were immunological responses, survival, and objective response rates.

Results

Compared with the base dose level previously reported, no new vaccine-related serious adverse events were observed during dose escalation of EVX-01 in combination with an anti-PD-1 agent given according to local guidelines. Two patients at the third dose level (fourfold dose) developed grade 3 toxicity, most likely related to pembrolizumab. Overall, 8 out of the 12 patients had objective clinical responses (6 partial response (PR) and 2 CR), with all 4 patients at the highest dose level having a CR (1 CR, 3 PR). EVX-01 induced peptide-specific CD4+ and/or CD8+T cell responses in all treated patients, with CD4+T cells as the dominating responses. The magnitude of immune responses measured by IFN-γ ELISpot assay correlated with individual peptide doses. A significant correlation between the PIONEER quality score and induced T cell immunogenicity was detected, while better CRs correlated with both the number of immunogenic EVX-01 peptides and the PIONEER quality score.

Conclusion

Immunization with EVX-01-CAF09b in addition to anti-PD-1 therapy was shown to be safe and well tolerated and elicit vaccine neoantigen-specific CD4+and CD8+ T cell responses at all dose levels. In addition, objective tumor responses were observed in 67% of patients. The results encourage further assessment of the antitumor efficacy of EVX-01 in combination with anti-PD-1 therapy.
Development and validation of a SCORing systEm for pre-thrombectomy diagnosis of IntraCranial Atherosclerotic Disease (Score-ICAD)
Authors: A Tarek Mohamed , Damiani Monteiro Mateus , Mohammaden Mahmoud H , Martins Pedro N , Sheth Sunil A , Dolia Jaydevsinh , Pabaney Aqueel , Grossberg Jonathan A , Nahhas Michael , A De La Garza Carlos , Salazar-Marioni Sergio , Rangaraju Srikant , Nogueira Raul G , Haussen Diogo C
Published: May 2024

Background

Early identification of intracranial atherosclerotic disease (ICAD) may impact the management of patients undergoing mechanical thrombectomy (MT). We sought to develop and validate a scoring system for pre-thrombectomy diagnosis of ICAD in anterior circulation large vessel/distal medium vessel occlusion strokes (LVOs/DMVOs).

Methods

Retrospective analysis of two prospectively maintained comprehensive stroke center databases including patients with anterior circulation occlusions spanning 2010–22 (development cohort) and 2018–22 (validation cohort). ICAD cases were matched for age and sex (1:1) to non-ICAD controls.

Results

Of 2870 MTs within the study period, 348 patients were included in the development cohort: 174 anterior circulation ICAD (6% of 2870 MTs) and 174 controls. Multivariable analysis β coefficients led to a 20 point scale: absence of atrial fibrillation (5); vascular risk factor burden (1) for each of hypertension, diabetes, smoking, and hyperlipidemia; multifocal single artery stenoses on CT angiography (3); absence of territorial cortical infarct (3); presence of borderzone infarct (3); or ipsilateral carotid siphon calcification (2). The validation cohort comprised 56 ICAD patients (4.1% of 1359 MTs): 56 controls. Area under the receiver operating characteristic curve was 0.88 (0.84–0.91) and 0.82 (0.73–0.89) in the development and validation cohorts, respectively. Calibration slope and intercept showed a good fit for the development cohort although with overestimated risk for the validation cohort. After intercept adjustment, the overestimation was corrected (intercept 0, 95% CI −0.5 to –0.5; slope 0.8, 95% CI 0.5 to 1.1). In the full cohort (n=414), ≥11 points showed the best performance for distinguishing ICAD from non-ICAD, with 0.71 (95% CI 0.65 to 0.78) sensitivity and 0.82 (95% CI 0.77 to 0.87) specificity, and 3.92 (95% CI 2.92 to 5.28) positive and 0.35 (95% CI 0.28 to 0.44) negative likelihood ratio. Scores ≥12 showed 90% specificity and 63% sensitivity.

Conclusion

The proposed scoring system for preprocedural diagnosis of ICAD LVOs and DMVOs presented satisfactory discrimination and calibration based on clinical and non-invasive radiological data.
Dynamic internal jugular vein venography: a descriptive study in 89 patients with suspected cerebral venous outflow disorders
Authors: Fargen Kyle M , Midtlien Jackson P , Margraf Connor , Kiritsis Nicholas R , Chang Emily , Hui Ferdinand
Published: May 2024

Background

Internal jugular vein (IJV) stenosis has recently been recognized as a plausible source of symptom etiology in patients with cerebral venous outflow disorders (CVD). Diagnosis and determining surgical candidacy remains difficult due to a poor understanding of IJV physiology and positional symptom exacerbation often reported by these patients.

Methods

A retrospective single-center chart review was conducted on adult patients who underwent diagnostic cerebral venography with rotational IJ venography from 2022 to 2024. Patients were divided into three groups for further analysis based on symptoms and diagnostic criteria: presumed jugular stenosis, near-healthy venous outflow, and idiopathic intracranial hypertension.

Results

Eighty-nine patients were included in the study. Most commonly, ipsilateral rotation resulted in ipsilateral IJV stenosis and gradient development at C4–6 and contralateral stenosis and gradient appearance in the contralateral IJV at C1, with stenosis and gradient development in bilateral IJVs at C1–3 bilaterally during chin flexion. In all patients, 93.3% developed at least moderate dynamic stenosis of at least one IJV, more than two-thirds (69.7%) developed either severe or occlusive stenosis during rightward and leftward rotation, and 81.8% developed severe or occlusive stenosis with head flexion. Dynamic gradients of at least 4 mmHg were seen in 68.5% of patients, with gradients of at least 8 mmHg in 31.5% and at least 10 mmHg in 12.4%.

Conclusion

This study is the first to document dynamic changes in IJV caliber and gradients in different head positions, offering insights into the complex nature of venous outflow and its impact on CVD.
iTRAQ-based mass spectrometry screen to identify serum biomarkers in systemic lupus erythematosus
Authors: Vanarsa Kamala , Zhang Ting , Hutcheson Jack , Kumar Sneha Ravi , Nukala Satyavani , Inthavong Haleigh , Stanley Bruce , Wu Tianfu , Mok C C , Saxena Ramesh , Mohan Chandra
Published: May 2024

Objective

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disorder with no reliable serum biomarkers currently available other than autoantibodies.

Methods

In the present study, isobaric tags for relative and absolute quantitation-based mass spectrometry was used to screen the sera of patients with SLE to uncover potential disease biomarkers.

Results

85 common proteins were identified, with 16 being elevated (≥1.3) and 23 being decreased (≤0.7) in SLE. Of the 16 elevated proteins, serum alpha-1-microglobulin/bikunin precursor (AMBP), zinc alpha-2 glycoprotein (AZGP) and retinol-binding protein 4 (RBP4) were validated in independent cross-sectional cohorts (Cohort I, N=52; Cohort II, N=117) using an orthogonal platform, ELISA. Serum AMBP, AZGP and RBP4 were validated to be significantly elevated in both patients with inactive SLE and patients with active SLE compared with healthy controls (HCs) (p<0.05, fold change >2.5) in Cohort I. All three proteins exhibited good discriminatory power for distinguishing active SLE and inactive SLE (area under the curve=0.82–0.96), from HCs. Serum AMBP exhibited the largest fold change in active SLE (5.96) compared with HCs and correlated with renal disease activity. The elevation in serum AMBP was validated in a second cohort of patients with SLE of different ethnic origins, correlating with serum creatinine (r=0.60, p<0.001).

Conclusion

Since serum AMBP is validated to be elevated in SLE and correlated with renal disease, the clinical utility of this novel biomarker warrants further analysis in longitudinal cohorts of patients with lupus and lupus nephritis.
Nuclear industry family study:methods and description of a United Kingdom study linking occupational information held by employers to reproduction and child health.
Authors: Maconochie N , Doyle P , Roman E , Davies G , Smith P G , Beral V
Published: May 2024

OBJECTION: To describe the methods used in the nuclear industry family study for which a comprehensive database has been assembled that links employment in the nuclear industry and dosimetry records to information on employees' reproductive health and the health of their children. To discuss the response rates and characteristics of the study population. METHODS: Occupational cohort design leading to a retrospective cohort study of reproductive outcomes reported by 46 396 current and former employees of both sexes in the nuclear industry. Employees of nuclear establishments in the United Kingdom operated by the Atomic Energy Authority, the Atomic Weapons Establishment, and British Nuclear Fuels were surveyed with postal questionnaires ot collect information on pregnancies, children,and periods of infertility. Information on employment and monitoring for ionising radiation was supplied by the employing nuclear authority and was linked to pregnancies and periods of infertility with unique personal identification numbers. RESULTS: The design and completion of this study resulted in high quality data on a representative population of the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels workforces. The response to the survey was extremely good (82% for male workers and 88% for female workers, excluding undelivered questionnaires), and a unique relational database has been created which will enable infertility, pregnancy, and child health outcomes to be examined with respect to the employment and radiation monitoring characteristics of parents. CONCLUSION: This is the first United Kingdom study to link detailed reproductive history data to occupational information held by employers. The methods developed for the study were found to be feasible and successful. The design can be adapted for other investigations of reproductive hazards to men and women in the workplace and is currently in use to survey over 100 000 armed forces personnel in an investigation of reproductive outcome among veterans of the Gulf war.
Heart disease in pregnancy and risk of pre-eclampsia: a Swedish register-based study
Authors: Bergman Karl , Svanvik Teresia , Basic Carmen , Rosengren Annika , Zverkova Sandström Tatiana , Celind Jimmy , Sjöland Helen , Wikström Anna-Karin , Schaufelberger Maria , Thunström Erik
Published: May 2024

Background and aims

Pre-eclampsia complicates 3–5% of pregnancies worldwide and is associated with adverse outcomes for the mother and the offspring. Pre-eclampsia and heart failure have common risk factors, including hypertension, obesity and diabetes. It is not known whether heart failure increases the risk of pre-eclampsia. This study examines whether pregestational heart failure increases the risk of pre-eclampsia.

Methods

In a registry-based case–cohort study that included all pregnancies in Sweden (n=3 125 527) between 1990 and 2019, all pregnancies with pre-eclampsia (n=90 354) were identified and up to five control pregnancies (n=451 466) for each case were chosen, matched on the mother’s birth year. Multiple logistic regression analysis was used to evaluate the impact of heart failure on the risk of pre-eclampsia, with adjustment for established risk factors and other cardiovascular diseases.

Results

Women with heart failure had no increased risk for pre-eclampsia, OR 1.02 (95% CI 0.69 to 1.50). Women with valvular heart disease had an increased OR of preterm pre-eclampsia, with an adjusted OR of 1.78 (95% CI 1.04 to 3.06). Hypertension and diabetes were independent risk factors for pre-eclampsia. Obesity, multifetal pregnancies, in vitro fertilisation, older age, Nordic origin and nulliparity were more common among women who developed pre-eclampsia compared with controls.

Conclusion

Women with heart failure do not have an increased risk of pre-eclampsia. However, women with valvular heart disease prior to pregnancy have an increased risk of developing preterm pre-eclampsia independent of other known risk factors.
Role of histone deacetylases and sirtuins in the ischaemic stroke: a protocol for a systematic review and meta-analysis of animal studies
Authors: Majdi Ali , Mostafavi Hossein , Moharrami Ali , Yaraghi Shahin , Ghaffari Tabrizi Amirreza , Dojahani Morteza , Alirezapour Erfan , Mansori Kamyar
Published: May 2024

Background

Stroke is a major cause of global mortality and disability. Currently, the treatment of acute ischaemic stroke through reperfusion has posed several challenges, raising the need for complementary options to protect the ischaemic penumbra. Recent investigations have indicated that certain epigenetic factors, specifically, histone deacetylases (HDACs) and sirtuins, can be promising for ischaemic stroke therapy, with recent studies suggesting that inhibitors of HDACs or sirtuins may provide neuronal protection after ischaemic stroke. However, the impact of specific HDAC/sirtuin isoforms on the survival of neuronal cells following stroke is still uncertain. This study aims to provide a comprehensive overview of the function of HDACs and their modulators in the treatment of acute ischaemic stroke.

Methods

This systematic review and meta-analysis will encompass animal intervention studies that explore the efficacy of modulation of HDACs and sirtuins in the acute phase of ischaemic stroke. The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches will be conducted in PubMed, Web of Science and Scopus, with subsequent screening by independent reviewers based on the established eligibility criteria. Methodological quality will be evaluated using the SYRCLE risk of bias tool. The primary outcomes will be infarct volume and functional response, with the secondary outcomes established a priori. Data pertaining to infarct volume will be used for random-effects meta-analysis. Additionally, a descriptive summary will be conducted for the functional response and secondary outcomes.

Discussion

No systematic review and meta-analysis on the treatment of ischaemic stroke through HDAC modulation has been conducted to date. A comprehensive analysis of the available literature on the relevant preclinical investigations can yield invaluable insights in discerning the most effective trials and in further standardisation of preclinical studies.

Systematic review registration

This systematic review has been recorded in the International Prospective Register of Systematic Reviews (PROSPERO), with the assigned reference number: CRD42023381420
Research on Positioning Tracking Mode of Sports Rehabilitation Training Based on Self-Powered Sensor Based on Particle Swarm Optimization Algorithm
Authors: Chen Hua , Liu Shaohua
Published: May 2024

The theme of today’s world is peace and development. A stable external environment has made people’s average life expectancy gradually increased, and the world is rapidly aging. Aging has brought many problems, such as the increase in the number of patients with limb dysfunction due to various diseases, which has gradually increased the demand for rehabilitation training. With traditional rehabilitation training methods, the training scenes are single and boring, and patients are prone to resisting. This paper designs and implements a real-time rehabilitation training guidance system based on self-powered sensors for the rehabilitation training needs of stroke patients. The system uses self-powered sensors to collect human motion information in real time, and compares it with the key posture sequences in the standard motion library to obtain corresponding matching results and guide patients to perform correct rehabilitation training. Using the rotation quaternion of 25 bone points in the patient’s rehabilitation exercise to calculate and update the rotation quaternion of the corresponding bone point of the character model, the function of the character model to follow the patient’s mirror motion is realized. This allows patients to control the completion of their rehabilitation movements without the need for medical staff to accompany them. And the stability of the system is optimized based on the particle swarm optimization algorithm. After traversal optimization, the current sensitivity coefficient of the model is reduced by about 75% compared with that before the correction, indicating that the current stability of the model obtained at this time has been improved to a certain extent. However, in the regression model of the self-powered sensor established by the particle swarm optimization algorithm, its parameters are reduced by about 82% compared with those before the correction, which shows that the current stability of the model has been greatly improved at this time, and the operating current of the receiving loop has been greatly improved.
DYNAMICS OF OPTICAL WAVE PROFILES TO THE FRACTIONAL THREE-COMPONENT COUPLED NONLINEAR SCHRÖDINGER EQUATION
Authors: YOUNAS USMAN , SULAIMAN TUKUR A. , ALI QASIM , MAJEED AFRAZ H. , KEDZIA KRZYSTOF , JAN AHMED Z.
Published: May 2024

This paper explores the truncated [Formula: see text]-fractional three-component coupled nonlinear Schrödinger (tc-CNLS) equation, that regulates the behavior of optical pulses in optical fibers. These equations are utilized in various scientific and engineering fields, including nonlinear fiber optics, electromagnetic field waves, and signal processing through optical fibers. The study of multi-component NLS equations has gained significant attention due to their ability to elucidate various complex physical phenomena and exhibit more dynamic structures of localized wave solutions. The freshly invented integration tools, known as the fractional modified Sardar subequation method (MSSEM) and fractional enhanced modified extended tanh-expansion method (eMETEM), are employed to ensure the solutions. The study focuses on extracting various types of optical solitons, including bright, dark, singular, bright-dark, complex, and combined solitons. Optical soliton propagation in optical fibers is currently a subject of great interest due to the multiple prospects for ultrafast signal routing systems and short light pulses in communications. In nonlinear dispersive media, optical solitons are stretched electromagnetic waves that maintain their intensity due to a balance between the effects of dispersion and nonlinearity. Furthermore, hyperbolic, periodic and exponential solutions are generated. The utilized methodology is effective in explaining fractional nonlinear partial differential equations (FNLPDEs) as it offers pre-existing solutions and additionally derives novel exact solutions by mixing outcomes from various procedures. Furthermore, we plot the visualizations of solutions by plotting 3D, 2D, and contour graphs with the corresponding parameter values. The findings of this paper can improve the understanding of the nonlinear dynamical behavior of a specific system and demonstrate the efficacy of the methodology used. We anticipate that our study will provide substantial benefits to a considerable group of engineering model experts. The findings demonstrate the efficacy, efficiency, and applicability of the computational method employed, particularly in dealing with intricate systems.
COMPLEXITY-BASED ANALYSIS OF THE VARIATIONS IN THE BRAIN RESPONSE OF PORN-ADDICTED AND HEALTHY INDIVIDUALS UNDER DIFFERENT FUNCTION TASKS
Authors: PAKNIYAT NAJMEH , RAMADOSS JANARTHANAN , KARTHIKEYAN ANITHA , MAREK PENHAKER , KREJCAR ONDREJ , NAMAZI HAMIDREZA
Published: May 2024

The examination of brain responses in individuals with a pornography addiction compared to those without sheds light on the neurobiological aspects associated with this behavior. Neuroscientific studies utilizing techniques such as electroencephalography (EEG) have shown that porn-addicted individuals may exhibit alterations in neural pathways related to reward processing and impulse control. In this paper, we analyzed the variations in the brain response of porn-addicted versus healthy individuals under five function tasks including baseline, emotional state, memorize task, executive task, and recall task. For this purpose, we analyzed the complexity of EEG signals using fractal theory, approximate entropy (ApEn), and sample entropy. The results showed that the EEG signals of porn-addicted teenagers are more complex than the ones for healthy individuals, which reflects a higher level of brain activity for porn-addicted teenagers. This method of analysis can be extended to examine the brain activity of other types of addiction versus healthy brains.