bluuebunny/crossref_metadata_2025 huggingface dataset:
LRIG1 engages ligand VISTA and impairs tumor-specific CD8
+
T cell responses
Authors: Ta Hieu Minh , Roy Dia , Zhang Keman , Alban Tyler , Juric Ivan , Dong Juan , Parthasarathy Prerana B. , Patnaik Sachin , Delaney Elizabeth , Gilmour Cassandra , Zakeri Amin , Shukla Nidhi , Rupani Amit , Phoon Yee Peng , Liu Caini , Avril Stefanie , Gastman Brian , Chan Timothy , Wang Li Lily
Published: May 2024

Immune checkpoint blockade is a promising approach to activate antitumor immunity and improve the survival of patients with cancer. V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint target; however, the downstream signaling mechanisms are elusive. Here, we identify leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) as a VISTA binding partner, which acts as an inhibitory receptor by engaging VISTA and suppressing T cell receptor signaling pathways. Mice with T cell–specific LRIG1 deletion developed superior antitumor responses because of expansion of tumor-specific cytotoxic T lymphocytes (CTLs) with increased effector function and survival. Sustained tumor control was associated with a reduction of quiescent CTLs (TCF1
+
CD62L
hi
PD-1
low
) and a reciprocal increase in progenitor and memory-like CTLs (TCF1
+
PD-1
+
). In patients with melanoma, elevated LRIG1 expression on tumor-infiltrating CD8
+
CTLs correlated with resistance to immunotherapies. These results delineate the role of LRIG1 as an inhibitory immune checkpoint receptor and propose a rationale for targeting the VISTA/LRIG1 axis for cancer immunotherapy.
Dual β-lactam for treatment of pulmonary
Mycobacterium abscessus
in a child
Authors: Becken Bradford , Dousa Khalid M. , Johnson John L. , Holland Steven M. , Bonomo Robert A.
Published: May 2024

Treatment of
Mycobacterium abscessus
infection presents significant challenges, exacerbated by the emergence of macrolide-resistant strains that necessitate the use of multiple antimicrobials in combination and carry the potential for significant toxic effects. Select dual beta-lactam combinations, with or without beta-lactamase inhibitors, have been shown to be highly active
in vitro
. Herein, we describe a 6-year-old child with underlying mild bilateral lower lobe cylindrical bronchiectatic lung disease who developed pulmonary
Mycobacterium abscessus
infection and was treated with a multi-drug regimen including two β-lactam antibiotics, achieving both early clinical and microbiological cure. This case highlights the potential benefit of dual β-lactam therapy for the treatment of drug-resistant
Mycobacterium abscessus
infection.
Applying improved ddPCR to reliable quantification of MPXV in clinical settings
Authors: Liang Chudan , Yang Huiqin , Yang Xiaofeng , Long Zhenyu , Zhou Yuandong , Wang Jian , Fan Linjin , Zeng Mou , Wang Yulong , Zheng Haipeng , Wang Zequn , Ye Pengfei , Lin Jingyan , Shi Wendi , Huang Hongxin , Yan Huijun , Qian Jun , Li Linghua , Liu Linna
Published: May 2024

Monkeypox virus (MPXV) poses a global health threat. Droplet digital PCR (ddPCR) holds potential as an accurate diagnostic tool for clinical microbiology. However, there is limited literature on the applicability of ddPCR in clinical settings. In this study, the clinical features of patients with MPXV during the initial outbreak in China in June 2023 were reviewed, and an optimized ddPCR method with dilution and/or inhibitor removal was developed to enhance MPXV detection efficiency. Eighty-two MPXV samples were tested from nine different clinical specimen types, including feces, urine, pharyngeal swabs, anal swabs, saliva, herpes fluid, crust, and semen, and the viral load of each specimen was quantified. A comparative analysis was performed with qPCR to assess sensitivity and specificity and to investigate the characteristics of MPXV infection by analyzing viral loads in different clinical specimens. Consequently, common pharyngeal and gastrointestinal symptoms were observed in patients with MPXV. The optimized ddPCR method demonstrated relatively high sensitivity for MPXV quantification in the clinical materials, with a limit of detection of 0.1 copies/μL. This was particularly evident in low-concentration samples like whole blood, semen, and urine. The optimized ddPCR demonstrated greater detection accuracy compared with normal ddPCR and qPCR, with an area under the curve (AUC) of 0.939. Except for crust samples, viral loads in the specimens gradually decreased as the disease progressed. Virus levels in feces and anal swabs kept a high detection rate at each stage of post-symptom onset, and feces and anal swabs samples may be suitable for clinical diagnosis and continuous monitoring of MPXV.

IMPORTANCE

The ddPCR technique proved to be a sensitive and valuable tool for accurately quantifying MPXV viral loads in various clinical specimen types. The findings provided valuable insights into the necessary pre-treatment protocols for MPXV diagnosis in ddPCR detection and the potentially suitable sample types for collection. Therefore, such results can aid in comprehending the potential characteristics of MPXV infection and the usage of ddPCR in clinical settings.
Clinical trial design and treatment effects: a meta-analysis of randomised controlled and single-arm trials supporting 437 FDA approvals of cancer drugs and indications
Authors: Michaeli Daniel Tobias , Michaeli Thomas , Albers Sebastian , Michaeli Julia Caroline
Published: May 2024

Objectives

This study aims to analyse the association between clinical trial design and treatment effects for cancer drugs with US Food and Drug Administration (FDA) approval.

Design

Cross-sectional study and meta-analysis.

Setting

Data from Drugs@FDA, FDA labels, ClincialTrials.gov and the Global Burden of Disease study.

Participants

Pivotal trials for 170 drugs with FDA approval across 437 cancer indications between 2000 and 2022.

Main outcome measures

Treatment effects were measured in HRs for overall survival (OS) and progression-free survival (PFS), and in relative risk for tumour response. Random-effects meta-analyses and meta-regressions explored the association between treatment effect estimates and clinical trial design for randomised controlled trials (RCTs) and single-arm trials.

Results

Across RCTs, greater effect estimates were observed in smaller trials for OS (�=0.06, p<0.001), PFS (�=0.15, p<0.001) and tumour response (�=-3.61, p<0.001). Effect estimates were larger in shorter trials for OS (�=0.08, p<0.001) and PFS (�=0.09, p=0.002). OS (�=0.04, p=0.006), PFS (�=0.10, p<0.001) and tumour response (�=-2.91, p=0.004) outcomes were greater in trials with fewer centres. HRs for PFS (0.54 vs 0.62, p=0.011) were lower in trials testing the new drug to an inactive (placebo/no treatment) rather than an active comparator. The analysed efficacy population (intention-to-treat, per-protocol, or as-treated) was not consistently associated with treatment effects. Results were consistent for single-arm trials and in multivariable analyses.

Conclusions

Pivotal trial design is significantly associated with measured treatment effects. Particularly small, short, single-centre trials testing a new drug compared with an inactive rather than an active comparator could overstate treatment outcomes. Future studies should verify results in unsuccessful trials, adjust for further confounders and examine other therapeutic areas. The FDA, manufacturers and trialists must strive to conduct robust clinical trials with a low risk of bias.
Preoxygenation with non-invasive ventilation versus high-flow nasal cannula oxygen therapy for intubation of patients with acute hypoxaemic respiratory failure in ICU: the prospective randomised controlled FLORALI-2 study protocol
Authors: Frat Jean-Pierre , Ricard Jean-Damien , Coudroy Rémi , Robert René , Ragot Stéphanie , Thille Arnaud W
Published: May 2024

Introduction

Endotracheal intubation in intensive care unit (ICU) is a procedure at high risk of life-threatening complications. Among them, severe oxygen desaturation, usually defined as a drop of pulse oxymetry (SpO2) below 80%, is the most common. Preoxygenation enables delaying oxygen desaturation occurring during apnea induced by anaesthetic drugs. Data suggest that non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) oxygen therapy could further increase PaO2before intubation procedure and prevent oxygen desaturation episodes as compared with standard oxygen. However, no recommendation favours one technique rather than the other, since they have never been compared. Hence, whether a strategy of preoxygenation with NIV or HFNC is more effective than the other in patients with acute hypoxaemic respiratory failure remains to be established.

Methods and analysis

The FLORALI-2 study is a multicentre randomised controlled trial comparing a preoxygenation strategy with either NIV or HFNC in patients with acute hypoxaemic respiratory failure needing intubation in ICU. The 320 patients will be randomised with a ratio 1:1 in two groups according to the strategy of preoxygenation. The primary outcome is the occurrence of an episode of severe oxygen desaturation defined by a drop of SpO2below 80% during the intubation procedure. Secondary outcomes include feasibility of the two strategies, immediate and late complications related to intubation.

Ethics and dissemination

The study has been approved by the central ethics committee (Ethics Committee Ouest-III, Poitiers, France) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.

Trial registration number

NCT02668458; Pre-results.
LEAK study: design of a nationwide randomised controlled trial to find the best way to treat wound leakage after primary hip and knee arthroplasty
Authors: Löwik Claudia A M , Wagenaar Frank-Christiaan , van der Weegen Walter , Poolman Rudolf W , Nelissen Rob G H H , Bulstra Sjoerd K , Pronk Yvette , Vermeulen Karin M , Wouthuyzen-Bakker Marjan , van den Akker-Scheek Inge , Stevens Martin , Jutte Paul C
Published: May 2024

Introduction

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are highly successful treatment modalities for advanced osteoarthritis. However, prolonged wound leakage after arthroplasty is linked to prosthetic joint infection (PJI), which is a potentially devastating complication. On the one hand, wound leakage is reported as a risk factor for PJI with a leaking wound acting as aporte d’entréefor micro-organisms. On the other hand, prolonged wound leakage can be a symptom of PJI. Literature addressing prolonged wound leakage is scarce, contradictory and of poor methodological quality. Hence, treatment of prolonged wound leakage varies considerably with both non-surgical and surgical treatment modalities. There is a definite need for evidence concerning the best way to treat prolonged wound leakage after joint arthroplasty.

Methods and analysis

A prospective nationwide randomised controlled trial will be conducted in 35 hospitals in the Netherlands. The goal is to include 388 patients with persistent wound leakage 9–10 days after THA or TKA. These patients will be randomly allocated to non-surgical treatment (pressure bandages, (bed) rest and wound care) or surgical treatment (debridement, antibiotics and implant retention (DAIR)). DAIR will also be performed on all non-surgically treated patients with persistent wound leakage at day 16–17 after index surgery, regardless of amount of wound leakage, other clinical parameters or C reactive protein. Clinical data are entered into a web-based database. Patients are asked to fill in questionnaires about disease-specific outcomes, quality of life and cost effectiveness at 3, 6 and 12 months after surgery. Primary outcome is the number of revision surgeries due to infection within a year of arthroplasty.

Ethics and dissemination

The Review Board of each participating hospital has approved the local feasibility. The results will be published in peer-reviewed scientific journals.

Trial registration number

NTR5960;Pre-results.
Can weSave the rectum by watchful waiting orTransAnal microsurgery following (chemo)Radiotherapy versusTotal mesorectal excision for earlyREctalCancer (STAR-TREC study)?: protocol for a multicentre, randomised feasibility study
Authors: Rombouts Anouk J M , Al-Najami Issam , Abbott Natalie L , Appelt Ane , Baatrup Gunnar , Bach Simon , Bhangu Aneel , Garm Spindler Karen-Lise , Gray Richard , Handley Kelly , Kaur Manjinder , Kerkhof Ellen , Kronborg Camilla Jensenius , Magill Laura , Marijnen Corrie A M , Nagtegaal Iris D , Nyvang Lars , Peters Femke P , Pfeiffer Per , Punt Cornelis , Quirke Philip , Sebag-Montefiore David , Teo Mark , West Nick , de Wilt Johannes H W
Published: May 2024

Introduction

Total mesorectal excision (TME) is the highly effective standard treatment for rectal cancer but is associated with significant morbidity and may be overtreatment for low-risk cancers. This study is designed to determine the feasibility of international recruitment in a study comparing organ-saving approaches versus standard TME surgery.

Methods and analysis

STAR-TREC trial is a multicentre international randomised, three-arm parallel, phase II feasibility study in patients with biopsy-proven adenocarcinoma of the rectum. The trial is coordinated from Birmingham, UK with national hubs in Radboudumc (the Netherlands) and Odense University Hospital Svendborg UMC (Denmark). Patients with rectal cancer, staged by CT and MRI as ≤cT3b (up to 5 mm of extramural spread) N0 M0 can be included. Patients will be randomised to either standard TME surgery (control), organ-saving treatment using long-course concurrent chemoradiation or organ-saving treatment using short-course radiotherapy. For patients treated with an organ-saving strategy, clinical response to (chemo)radiotherapy determines the next treatment step. An active surveillance regime will be performed in the case of a complete clinical regression. In the case of incomplete clinical regression, patients will proceed to local excision using an optimised platform such as transanal endoscopic microsurgery or other transanal techniques (eg, transanal endoscopic operation or transanal minimally invasive surgery). The primary endpoint of this phase II study is to demonstrate sufficient international recruitment in order to sustain a phase III study incorporating pelvic failure as the primary endpoint. Success in phase II is defined as randomisation of at least four cases per month internationally in year 1, rising to at least six cases per month internationally during year 2.

Ethics and dissemination

The medical ethical committees of all the participating countries have approved the study protocol. Results of the primary and secondary endpoints will be submitted for publication in peer-reviewed journals.

Trial registration number

ISRCTN14240288, 20 October 2016.NCT02945566; Pre-results, October 2016.
Exercise and adiposity in overweight and obese children and adolescents: protocol for a systematic review and network meta-analysis of randomised trials
Authors: Kelley George A , Kelley Kristi S , Pate Russell R
Published: May 2024

Introduction

Overweight and obesity is a worldwide public health problem among children and adolescents. However, the magnitude of effect, as well as hierarchy of exercise interventions (aerobic, strength training or both), on selected measures of adiposity is not well established despite numerous trials on this issue. The primary purposes of this study are to use the network meta-analytical approach to determine the effects and hierarchy of exercise interventions on selected measures of adiposity in overweight and obese children and adolescents.

Methods and analysis

Randomised exercise intervention trials >4 weeks, available in any language up to 31 August 2017 and which include direct and/or indirect evidence, will be included. Studies will be located by searching seven electronic databases, cross-referencing and expert review. Dual selection and abstraction of data will occur. The primary outcomes will be changes in body mass index (in kg/m2), fat mass and percent body fat. Risk of bias will be assessed using the Cochrane Risk of Bias assessment instrument while confidence in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation instrument for network meta-analysis. Network meta-analysis will be performed using multivariate random-effects meta-regression models. The surface under the cumulative ranking curve will be used to provide a hierarchy of exercise treatments (aerobic, strength or both).

Ethics and dissemination

This study does not require ethics approval. Findings will be presented at a professional conference and published in a peer-reviewed journal.

PROSPERO registration number

CRD42017073103.
Interrupted versus continuous suturing for vesicourethral anastomosis during radical prostatectomy: protocol for a systematic review and meta-analysis
Authors: Kowalewski Karl Friedrich , Tapking Christian , Hetjens Svetlana , Nickel Felix , Mandel Philipp , Ritter Manuel , Kriegmair Maximilian Christian
Published: May 2024

Introduction

Radical prostatectomy is the mainstay of treatment for prostate cancer. The vesicourethral anastomosis is a critical step, which most likely impacts urinary continence and urethral stenosis. To date, it still remains unclear whether interrupted and continuous suturing for the anastomosis have different outcomes. Therefore, the aim of this systematic review and meta-analysis is to compare different suture techniques for vesicourethral anastomosis in terms of surgical and functional parameters.

Methods and analysis

A comprehensive literature search will be conducted covering MEDLINE, Embase, Web of Science, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. Studies comparing interrupted versus continuous suturing will be included in the analyses. No language restrictions will be applied. Screening, data extraction, statistical analysis and reporting will be done in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Quality assessment will be performed with the help of the Cochrane Collaboration’s tool for assessing risk of bias and the Newcastle-Ottawa Scale for assessing quality of non-randomised studies. The quality of evidence will be evaluated with the Grading of Recommendations Assessment, Development and Evaluation. The primary outcome will be the time until removal of the urinary catheter. Secondary outcomes include rate of extravasation, length of hospital stay, time needed to perform the anastomosis, continence level at defined postoperative intervals and development of urethral strictures. Quantitative analysis will be calculated if meaningful.

Ethics and dissemination

In order to meet the highest ethical and methodological standards. we followed the PRISMA Protocol 2015 checklist. Each item was answered appropriately. For systematic reviews the ethical issues are strictly methodological as only data that were published earlier will be used. The full manuscript will be submitted to a peer-reviewed journal. Furthermore, the results will be presented on national and international congresses.

Trial registration number

International prospective register of systematic reviews PROSPERO CRD42017076126.
DARE-ISC model for prediction of 1-year ischaemic stroke risk in the general population and atrial fibrillation patients: a Danish nationwide cohort study
Authors: Bruun-Jensen Mikkel , Winther Simon , Schmidt Samuel Emil , Møller Dahl Christian
Published: May 2024

Objectives

To develop a risk assessment model (DAnish REgister Ischaemic Stroke Classifier, DARE-ISC) for predicting 1-year primary ischaemic stroke/systemic embolism (SE) in the general population. Secondly, to validate the accuracy DARE-ISC in atrial fibrillation (AF) patients where well-established models and risk scores exist.

Design

Retrospective cohort study. DARE-ISC was developed using gradient boosting decision trees with information from 375 covariates including baseline information on relevant diagnoses, demographic characteristics, registered health-services, lifestyle-related covariates, hereditary stroke components, drug prescriptions and stress proxies.

Setting

Danish nationwide registries.

Participants

All Danish individuals aged ≥18 from 2010 to 2017 (n=35 519 348 person-years). The model was trained on the 2010–2016 cohorts with validation in the 2017 cohort.

Primary and secondary outcome measures

Model optimisation and validation were performed through comparison of the area under the receiver operating characteristic curve (AUC) and average precision scores. Additionally, the relative importance of the model covariates was derived using SHAP values.

Results

DARE-ISC had an AUC (95% CI) of 0.874 (0.871 to 0.876) in the general population. In AF patients, DARE-ISC was superior to the GARFIELD-AF risk model and CHA2DS2-VASc score with AUC of 0.779 (95% CI 0.75 to 0.806), 0.704 (95% CI 0.674 to 0.732) and 0.681 (95% CI 0.652 to 0.709), respectively. Furthermore, in AF patients, DARE-ISC had an average threefold and fourfold higher ratio of correctly identified strokes compared with the GARFIELD-AF risk model and CHA2DS2-VASc score, as indicated by average precision scores of 0.119, 0.041 and 0.034, respectively.

Conclusions

DARE-ISC had a very high stroke prediction accuracy in the general population and was superior to the GARFIELD-AF risk model and CHA2DS2-VASc score for predicting ischaemic stroke/SE in AF patients.
Anaesthetic and perioperative considerations for extrapleural pneumonectomy and extended pleurectomy/decortication: a scoping review protocol
Authors: Yip Sui Wah Sean , Weinberg Laurence , Gooi Julian , Sivenayagam Siven , Coulson Tim G , Barnett Stephen A , Knight Simon R , Ludski Jarryd , Lee Dong Kyu
Published: May 2024

Introduction

Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant pleural tumours such as pleural mesothelioma, non-mesothelioma pleural malignancies such as thymoma and sarcoma, and rarely for pleural tuberculosis, in a more limited fashion. Despite extensive studies on both surgical techniques and consequences, a significant knowledge gap remains regarding how best to approach the perioperative anaesthesia challenges for EPP and ePD.

It is unknown if the risk stratification processes for such surgeries are standardised or what types of functional and dynamic cardiac and pulmonary tests are employed preoperatively to assist in the perioperative risk stratification. Further, it is unknown whether the types of anaesthesia and analgesia techniques employed, and the types of haemodynamic monitoring tools used, impact on outcomes. It is also unknown whether individualised haemodynamic protocols are used to guide the rational use of fluids, vasoactive drugs and inotropes.

Finally, there is a dearth of evidence regarding how best to monitor these patients postoperatively or what the most effective enhanced recovery protocols are to best mitigate postoperative complications and accelerate hospital discharge. To increase our knowledge of the perioperative and anaesthetic treatment for patients undergoing EPP/ePD, this scoping review attempts to synthesise the literature and identify these knowledge gaps.

Methods and analysis

This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols methodology. Electronic databases, OVID Medline, EMBASE and the Cochrane Library, will be systematically searched for relevant literature corresponding to EPP or ePD and perioperative or anaesthetic management. Data will be analysed and summarised descriptively and organised according to the three perioperative stages: preoperative, intraoperative and postoperative factors in clinical care.

Ethics and dissemination

Ethics approval was not required. The findings will be disseminated through professional networks, conference presentations and publications in scientific journals.
Effect of metformin use on graft and patient survival in kidney transplant recipients with type 2 diabetes: a systematic review protocol
Authors: Shamshad Farooq , Tungsanga Somkanya , Senior Peter , Shojai Soroush , Ghimire Anukul , Ye Feng , Kung Janice Y , Hariramani Vinash K , Abdulrahman Abdullah , Penney Matthew , Sultana Naima , Muneer Shezel , Okpechi Ikechi , Bello Aminu K
Published: May 2024

Introduction

Metformin is a first-line antihyperglycaemic agent for type 2 diabetes (T2DM). In addition to glycaemic control, it offers benefits related to cardiovascular health, weight neutrality and metabolic syndrome. However, its benefits in kidney transplant recipients remain unclear as metformin use is controversial in this population due to a lack of evidence and there are recommendations against its use in patients with poor kidney function. Hence, we seek to describe a protocol for a systematic review, which will assess the impact of metformin use on graft survival and mortality in kidney transplant recipients.

Methods

This protocol was guided by the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015. We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL and Web of Science Core Collection for relevant studies conducted in kidney transplant recipients using metformin, which report outcomes related to graft and patient survival. All studies meeting these criteria in adults and published in English from inception to 2023 will be included in our review. We will employ the Cochrane Risk of Bias Tool 2 for randomised controlled trials and the Risk of Bias in Non-randomised Studies of Intervention for non-randomised studies. We will present our data and study characteristics in a table format and determine if a meta-analysis can be performed by clinical and methodological heterogeneity, using the I2statistics. If a meta-analysis cannot be performed, we will provide a narrative synthesis of included studies using the Synthesis Without Meta-Analysis Reporting Guideline.

Ethics and dissemination

Ethical approval will not be required for this review as the data used will be extracted from already published studies with publicly accessible data. As this study will assess the impact of metformin use on graft and patient survival in kidney transplant recipients, evidence gathered through it will be disseminated using traditional approaches that include open-access peer-reviewed publication, scientific presentations and a report. We will also disseminate our findings to appropriate academic bodies in charge of publishing guidelines related to T2DM and transplantation, as well as patient and research centred groups.

PROSPERO registration number

CRD42023421799.
Birang Daruganora: what do Aboriginal and Torres Strait Islander communities need in a new hospital? A qualitative study
Authors: Austin Elizabeth E , Carrigan Ann , Holden Narelle , Grigg Shai , Maka Katherine , Clay-Williams Robyn , Hibbert Peter D , Loy Graeme , Braithwaite Jeffrey
Published: May 2024

Objectives

To elicit the Aboriginal community’s cultural and healthcare needs and views about six prominent and emerging models of care, to inform the development of a new hospital.

Design

Cross-sectional qualitative study co-designed and co-implemented by Aboriginal team members.

Setting

Western Sydney, New South Wales, Australia.

Participants

Aboriginal and Torres Strait Islander healthcare providers (n=2) and community members (n=18) aged between 21 and 60+ years participated in yarning circles (20 participants; 14 female, 6 male).

Results

Handwritten notes from yarning circles were inductively analysed to synthesise the cultural and healthcare needs of providers and community members in relation to a new hospital and six models of care. Three primary themes emerged in relation to future hospitals. These were ‘culturally responsive spaces’, ‘culturally responsive systems’ and ‘culturally responsive models of care’. Strengths (eg, comfort, reduced waiting time, holistic care), barriers (eg, logistics, accessibility, literacy) and enablers (eg, patient navigator role, communication pathways, streamlined processes) were identified for each of the six models of care.

Conclusions

Aboriginal and Torres Strait Islander community members and providers are invested in the co-creation of an innovative, well-integrated hospital that meets the needs of the community. Common themes of respect and recognition, relationships and partnering, and capacity building emerged as important consumer and provider considerations when developing and evaluating care services. Participants supported a range of models citing concerns about accessibility and choice when discussing evidence-based models of care.
Explorative observational study of Dutch patient–clinician interactions: operationalisation of personal perspective elicitation as part of shared decision-making in real-life audio-recorded consultations
Authors: Rake Ester A , Meinders Marjan J , Brand Guus , Dreesens Dunja , Kremer Jan A M , Elwyn Glyn , Aarts Johanna W M
Published: May 2024

Objectives

Patients’ preferences, values and contexts are important elements of the shared decision-making (SDM) process. We captured those elements into the concept of ‘personal perspective elicitation’ (PPE), which reflects the need to elicit patients’ preferences, values and contexts in patient–clinician conversations. We defined PPE as: ‘the disclosure (either elicited by the clinician or spontaneously expressed by the patient) of information related to the patient’s personal preferences, values and/or contexts potentially relevant to decision-making’. Our goal was to operationalise the concept of PPE through the evaluation of preferences, values and contexts and explore how PPE occurs in clinical encounters.

Design

Cross-sectional study: observational coding based on a novel coding scheme of audio-recorded outpatient clinical encounters where encounter patient decision aids were applied.

Setting

We audio-recorded patient–clinician interactions at three Dutch outpatient clinics. PPE was analysed using a novel observational coding scheme, distinguishing preferences, contexts and four Armstrong taxonomy value types (global, decisional, external and situational). We measured SDM using the Observer OPTION5.

Participants

Twenty patients who suffered from psoriasis or ovarian cysts; four clinicians.

Results

We included 20 audio-recordings. The mean Observer OPTION5score was 57.5 (SD:10.1). The audio-recordings gave a rich illustration of preferences, values and contexts that were discussed in the patient–clinician interactions. Examples of identified global values: appearance, beliefs, personality traits. Decisional values were related to the process of decision-making. External values related to asking advice from for example, the clinician or significant others. An identified situational value: a new job ahead. Contexts related to how the illness impacted the life (eg, sexuality, family, sports, work life) of patients.

Conclusions

The operationalisation of PPE, an important aspect of SDM, explores which preferences, values and contexts were discussed during patient–clinician interactions where an ePDA was used. The coding scheme appeared feasible to apply but needs further refinement.
Effectiveness of combining prevention psychological interventions with interventions that address the social determinants of mental health in low and middle-income countries: protocol of a systematic review and meta-analysis
Authors: Prina Eleonora , Bano Beatrice , Singh Rakesh , Albanese Emiliano , Trujillo Daniela , Dedios Sanguineti María Cecilia , Sorsdahl Katherine , Luitel Nagendra P , Garman Emily C , Purgato Marianna , Barbui Corrado , Jordans Mark J D , Lund Crick
Published: May 2024

Introduction

Common mental health conditions (CMHCs), including depression, anxiety and post-traumatic stress disorder (PTSD), are highly prevalent in low and middle-income countries (LMICs). Preventive strategies combining psychological interventions with interventions addressing the social determinants of mental health may represent a key strategy for effectively preventing CMHCs. However, no systematic reviews have evaluated the effectiveness of these combined intervention strategies for preventing CMHCs.

Methods and analysis

This systematic review will include randomised controlled trials (RCTs) focused on the effectiveness of interventions that combine preventive psychological interventions with interventions that address the social determinants of mental health in LMICs. Primary outcome is the frequency of depression, anxiety or PTSD at postintervention as determined by a formal diagnostic tool or any other standardised criteria. We will search Epistemonikos, Cochrane Controlled Trials Register (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL, Global Index Medicus, ClinicalTrials.gov (Ctgov), International Clinical Trials Registry Platform (ICTRP). Two reviewers will independently extract the data and evaluate the risk of bias of included studies using the Cochrane risk of bias tool 2. Random-effects meta-analyses will be performed, and certainty of evidence will be rated using the Grading of Recommendations Assessment, Development and Evaluation approach.

Ethics and dissemination

This study uses data from published studies; therefore, ethical review is not required. Findings will be presented in a published manuscript.

Trial registration number

CRD42023451072
An observational study protocol to capture, validate and characterise lucid episodes in people living with advanced dementia receiving hospice care
Authors: Gilmore-Bykovskyi Andrea , Dillon Kayla , Coulson Alison , Fehland Jess , Benson Clark , Sanson-Miles Leah , Mueller Kimberly
Published: May 2024

Introduction

Lucid episodes (LEs) in advanced neurodegenerative disease, characterised by a transient recovery of abilities, have been reported across neurological conditions, including Alzheimer’s disease and related dementias. Evidence on LEs in dementia is extremely limited and draws predominantly from retrospective case reports. Lucidity in dementia has received growing attention given the clinical, caregiving and potential epidemiological implications of even a temporary return of abilities in advanced disease. Following a funding initiative by the National Institute on Aging, several new investigations are focused on establishing foundational evidence on lucidity in dementia. The objectives of this study are to capture, characterise and validate potential LEs via audiovisual observation, computational linguistic and timed-event coding of audiovisual data, and informant case review for face validation of LEs.

Methods and analysis

This prospective multifaceted observational study will investigate LEs in advanced dementia through longitudinal audiovisual observation within an inpatient hospice unit. Audiovisual data will be coded to generate variables of participant verbal output, verbal expressions, non-verbal communicative actions and functional behaviours to enable measurement of features that can be used to characterise LEs. Multiple methods will be used to identify potential LEs including field interviews with caregivers/clinicians who witness significant events during data collection, reports from research staff who witness significant events during data collection and detection by researchers during video data processing procedures. Potential LEs will undergo a structured case review with informants familiar with the participant to facilitate validation and enable triangulation across measures generated through coding.

Ethics and dissemination

This study will be conducted in accordance with all Federal Policies for the Protection of Human Subjects and the protocol (ID 2021-1243) has been approved by the University of Wisconsin-Madison Institutional Review Board. Findings will be disseminated via scientific conferences, journal publications and newsletters shared with participants and through dementia-focused and caregiver-focused networks.
Enhancing thromboresistance of neurovascular nickel-titanium devices with responsive heparin hydrogel coatings
Authors: Maitz Manfred F , Kaiser Daniel P O , Cuberi Ani , Weich Hernández Rafaela , Mühl-Benninghaus Ruben , Tomori Toshiki , Gawlitza Matthias
Published: May 2024

Background

Neurointerventional devices, particularly laser-cut thin-strut stents made of self-expanding nickel-titanium alloy, are increasingly utilized for endovascular applications in intracranial arteries and dural venous sinuses. Preventing thrombosis and stroke necessitates systemic anticoagulant and antiplatelet therapies with the risk of bleeding complications. Antithrombotic coatings present a promising solution.

Methods

In this study, we investigated the potential of hydrogels composed of four-armed poly(ethylene glycol) (starPEG) and heparin, with or without coagulation-responsive heparin release, as coatings for neurovascular devices to mitigate blood clot formation. We evaluated the feasibility and efficacy of these coatings on neurovascular devices through in vitro Chandler-Loop assays and implantation experiments in the supra-aortic arteries of rabbits.

Results

Stable and coagulation-responsive starPEG-heparin hydrogel coatings exhibited antithrombotic efficacy in vitro, although with a slightly reduced thromboprotection observed in vivo. Furthermore, the hydrogel coatings demonstrated robustness against shear forces encountered during deployment and elicited only marginal humoral and cellular inflammatory responses compared with the reference standards.

Conclusion

Heparin hydrogel coatings offer promising benefits for enhancing the hemocompatibility of neurointerventional devices made of self-expanding nickel-titanium alloy. The variance in performance between in vitro and in vivo settings may be attributed to differences in low- and high-shear blood flow conditions inherent to these models. These models may represent the differences in venous and arterial systems. Further optimization is warranted to tailor the hydrogel coatings for improved efficacy in arterial applications.
Exploring the dynamics of a four-dimensional Chua-like system: Numerical simulations and hardware investigations
Authors: Antunes Vinicius F. R. , Manchein Cesar , Albuquerque Holokx A. , Mello Luis Fernando , Hoff Anderson
Published: May 2024

In this work, we employ simulations to investigate deterministic and stochastic dynamics of a system governed by four coupled nonlinear ordinary differential equations (ODEs) derived from the canonical three-dimensional Chua model, replacing the piecewise nonlinearity with a cubic function. We employed two simulation approaches: (i) using software — where we performed numerical simulations (digital computation) in the ODEs model, and (ii) using hardware — where we performed experimental studies (analog computation) in the ODEs model. In the initial software-based approach for simulations, we performed stability and bifurcation analyses of the trivial equilibrium point, which were analytically conducted, along with the numerical continuation method. We solved the model using digital computation and explored its intricate dynamical behavior through nonlinear dynamics techniques applied to the parameter planes. In the second approach, employing hardware for simulations through analog computation, we designed an electronic circuit using analog electronics to solve the model in a continuous-time integration. The experimental setup mirrored the numerical simulations, yielding comparable results in terms of dynamical behaviors. This study underscores significant agreement between numerical and experimental findings, highlighting the robustness of the model across digital and analog contexts and offering practical insights into the various nonlinear dynamics presented in this system.
Diagnosis of Arrhythmia from Compressively Sensed ECG Signals Using Machine Learning Algorithms
Authors: Mathew Nimmy Ann , Jose Renu
Published: May 2024

Cardiovascular diseases (CVDs) represent a significant health concern in the present era, with Electrocardiogram (ECG) serving as a crucial bio-signal for their detection. Efficient health monitoring necessitates rapid and precise diagnosis, thereby mandating the utilization of Compressive Sensing (CS) alongside Machine Learning (ML) algorithms. CS functions as a sensing methodology that reduces sample numbers by capturing sparse or compressible representations, simplifying and expediting the acquisition process. In this proposed study, ECG signals are compressively sensed and preprocessed using CS reconstruction algorithms, followed by the application of various ML algorithms for diagnostic purposes. The assessment of the reconstructed ECG signal entails the assessment of Peak Signal-to-Noise Ratio (PSNR) values and Percentage Root-mean-square Difference (PRD). Concurrently, ML algorithms are evaluated based on metrics including accuracy, specificity, and sensitivity.

This work demonstrates exceptional performance in terms of acquisition time and computational complexity through the application of CS technology. Comparative analysis with the existing methodologies for CVD diagnosis reveals the proposed approach’s remarkable efficacy. Notably, the reduction in data volume and hardware complexity serves as a significant advantage over conventional methods. The integration of CS and ML algorithms in the proposed methodology proves highly effective in diagnosing CVDs, achieving a classification accuracy of 94.7%. These results underscore the methodology’s ability to deliver both speed and accuracy in diagnosis, positioning it as a promising approach for health monitoring.
Predicting Flight-Driving Attitudes through EEG-Based Models
Authors: Wang Pengbo , Wang Hongxi , Zhang Heming , Wang Yawen
Published: May 2024

This paper investigates the correlation between a pilot’s brain electroencephalographic (EEG) activity and his driving posture, addressing the intricate relationship between cognition and behavior in aviation. We designed and implemented a simulated experiment that recorded the fly pilot’s attitude and collected EEG information as experimental data. The experiment is only based on EEG data to predict flight posture (pull, down, left, right). We propose a flight-driving attitude prediction model (CA-FAP) based on CEBRA and self-attention mechanism, with a prediction accuracy of 0.83. This model is better than common spatial pattern (CSP) and uniform manifold approximation and projection (UMAP) dimension reduction methods in the experiment. Moreover, a better effect can be obtained in the larger attitude radian dataset (accuracy is 0.85), and the effect is not obvious in the dataset of closing the six-axis motion platform, indicating that the model prediction of flight attitude is closely related to the pilot position transformation. By comparing the prediction effect of each category, the pull-up and drop are better than the steering prediction result. The study can help pilots adjust their posture and decisions, and serve as a basis for studying flight pilot cognitive load, mental load, mood changes, and flight performance.
Fine-Grained Entity-Type Completion Based on Neighborhood-Attention and Cartesian–Polar Coordinates Mapping
Authors: Zhang Xiaoming , Li Xinrui , Wang Huiyong
Published: May 2024

Entities refer to things that exist objectively, and entity types are concepts abstracted from entities that have the same features or properties. However, the entity types in the knowledge graph are always incomplete. Currently, the main approach for predicting missing entity types is to learn structured representations of entities and types separately, which ignores neighborhood semantic knowledge of the entity. Therefore, this paper proposes the aggregation neighborhood semantics model for type completion (ANSTC), which extracts neighborhood triple features of target entities with two attentional mechanisms. Meanwhile, the spatial mapping module in ANSTC maps entities from Cartesian coordinate to Polar coordinate system, which can map similar vectors onto a concentric circle and then rotate the angle according to the fine-grained difference to achieve entity-to-type transformation. Moreover, we add semantic features from text to the entity representations to enrich semantics. Through experimental comparison on the FB15K and YAGO43K dataset, we get similar results to the baseline. We also construct person dataset in computer domain, and the values of MRR, Hit@1, Hit@3 and Hit@10 are improved compared with the ConnectE model. The experimental results demonstrate that our model can effectively predict the fine-grained entity types in the domain dataset, and achieve state-of-the-art performance.
Investigation of the dynamics of interaction of a cluster of primordial black holes with stellar cluster
Authors: Belotsky Konstantin , Krasnov Maxim , Pugachev Stanislav
Published: May 2024

In this paper, we revise dynamical constraint on primordial black hole (PBH) abundance following the effect of their interaction with stellar cluster in dwarf galaxy Eridanus II in case of PBH clustering. We consider scattering of stars on PBH cluster as a whole, dynamical friction of stars inside cluster and finally we are taking into account tidal forces’ effects due to the finite size of PBH cluster. We obtain the rate of change of kinetic energy of the stars and PBHs to make conclusion about constraints on clusters.
Fully extremal black holes: A black hole graveyard?
Authors: Di Filippo Francesco , Liberati Stefano , Visser Matt
Published: May 2024

While the standard point of view is that the ultimate endpoint of black hole evolution is determined by Hawking evaporation, there is a growing evidence that classical and semi-classical instabilities affect both black holes with inner horizons as well as their ultra-compact counterparts. In this paper we start from this evidence pointing towards extremal black holes as stable endpoints of the gravitational collapse, and develop a general class of spherical and axisymmetric solutions with multiple extremal horizons. Excluding more exotic possibilities, entailing regular cores supporting wormhole throats, we argue that these configurations could be the asymptotic graveyard, the end-point, of dynamical black hole evolution — albeit the timescale of such evolution are still unclear and possibly long and compatible with current astrophysical observations.
OPTIMIZING LOCATIONS FOR RECORDING BIOMECHANICAL AND VISCOELASTIC PROPERTIES OF SOLEUS MUSCLE AND PLANTAR FASCIA
Authors: Muckelt Paul E. , Wragg Naomi , Hussey Charlotte , Bigg Gemma , Haysom Abigail , Heinel Isabel , Brown Simon , Stokes Maria , Warner Martin B.
Published: May 2024

Introduction: MyotonPRO technology is a clinically accessible tool for objectively monitoring the biomechanical and viscoelastic properties of musculoskeletal tissues. This study aimed to identify the level of accuracy needed for recording from specified measurement sites on the soleus muscle and plantar fascia (PF), which are important for postural control and gait.

Methods: In 20 healthy adults, MyotonPRO measurements were taken 1 cm above and below a standardized point on the soleus and PF. Ultrasound scans were also taken at each site to measure subcutaneous tissue thickness to aid interpretation of MyotonPRO findings.

Results: Biomechanical and viscoelastic properties of the soleus and PF, measured using the MyotonPRO, were not affected by the change in the recording site. Subcutaneous tissue thickness above the PF changed significantly ([Formula: see text] < 0.001) by 0.61 cm when moving distally by 2 cm, whilst above the soleus, these did not differ significantly ([Formula: see text] = 0.175) when moving distally by 2 cm.

Conclusion: Changing the recording site 1 cm above or below the standardized site did not affect either the MyotonPRO results (soleus and PF) or ultrasound results for soleus, whilst this same distance affected ultrasound measurements of subcutaneous tissue thickness above the PF significantly. Moving away from the musculoskeletal junction reduces the need for precision in relocating the recording site for measuring soleus. These findings allow for quicker and easier measurement of soleus or PF using the MyotonPRO.