Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.

End-to-end deep-learning model for the detection of coronary artery stenosis on coronary CT images.

Purpose: We examined whether end-to-end deep-learning models could detect moderate (≥50%) or severe (≥70%) stenosis in the left anterior descending artery (LAD), right coronary artery (RCA) or left circumflex artery (LCX) in iodine contrast-enhanced ECG-gated coronary CT angiography (CCTA) scans.

Methods: From a database of 6293 CCTA scans, we used pre-existing curved multiplanar reformations (CMR) images of the LAD, RCA and LCX arteries to create end-to-end deep-learning models for the detection of moderate or severe stenoses. We preprocessed the images by exploiting domain knowledge and employed a transfer learning approach using EfficientNet, ResNet, DenseNet and Inception-ResNet, with a class-weighted strategy optimised through cross-validation.

Protocol for the development of a global core outcome set for the surgical treatment of differentiated thyroid cancer: a literature review and international Delphi survey.

Introduction: There is a lack of consensus on the optimal surgical strategy for differentiated thyroid cancer (DTC), partly due to inconsistent reporting of outcomes. This limits the ability to compare study results, hindering the ability to draw conclusions regarding novel treatment strategies. The development of a core outcome set (COS) reduces heterogeneity in the selection and reporting of clinical trial outcomes.

Association between endostatin and mortality in patients with acute dyspnoea, with or without congestive heart failure: a single-centre, prospective, observational study.

Objective: The aim of this study was to assess associations between endostatin levels and short-term mortality in unsorted acute hospitalised dyspnoea patients with or without congestive heart failure (CHF), adjusted for common cardiovascular risk factors.

Design, Setting And Participants: In this prospective observational study, 723 hospitalised patients who visited the emergency department at Skåne University Hospital, Sweden, between 2013 and 2018 were included. Of these, 276 had a history of CHF.

Safe Implementation of Treatments in Stroke: a study on intravenous thrombolysis in patients over 80 years of age with acute ischaemic stroke.

Objectives: To investigate the safety and efficacy outcomes of intravenous thrombolysis (IVT) in patients aged >80 years with acute ischaemic stroke (AIS) after IVT was approved in this patient population in several European and non-European countries during 2018-2019.

Design: This is an observational registry study using prospectively collected data from the Safe Implementation of Treatment in Stroke (SITS) registry. Comparisons will be performed between patients treated post-approval (July 2018 to December 2021) period with those treated pre-approval (June 2015 to June 2018) period using propensity score matching (PSM).

Engaging with young professionals in transfusion medicine: Insights from a needs assessment survey targeting an international cohort.

Background And Objectives: Professionals who work or study in transfusion medicine under 40 years of age are considered young professionals (YPs) by the International Society of Blood Transfusion (ISBT). While the ISBT provides opportunities for YPs, their needs have to be assessed to customize initiatives in a way that could potentially improve their engagement. This survey aimed to assess the needs of YPs in transfusion medicine and understand their perspectives on future ISBT initiatives.

Comparison of cell-scaffold interactions in a biological and a synthetic wound matrix.

Wound healing is a central physiological process that restores the barrier properties of the skin after injury, comprising close coordination between several cell types (including fibroblasts and macrophages) in the wound bed. The complex mechanisms involved are executed and regulated by an equally complex, reciprocal signalling network involving numerous signalling molecules such as catabolic and anabolic inflammatory mediators (e.g.

Burden of vascular risk factors by age, sex, ethnicity and deprivation in young adults with and without newly diagnosed type 2 diabetes.

Aims: Do associations between age at diagnosis of type 2 diabetes and vascular risk factors vary by ethnicity and deprivation?

Methods: Utilising the Clinical Practice Research Datalink, we matched 16-50-year-old individuals with newly diagnosed type 2 diabetes to ∼10 individuals without using sex, age and primary care practice. Differences in BMI, obesity, LDL-cholesterol, HbA1c, and hypertension between individuals with vs without type 2 diabetes across sex, age, ethnicity and deprivation quintiles were explored using generalised linear models.

Results: We included 108,061 individuals (45.

The brain interactome of a permissive prion replication substrate.

Bank voles are susceptible to prion strains from many different species, yet the molecular mechanisms underlying the ability of bank vole prion protein (BVPrP) to function as a universal prion acceptor remain unclear. Potential differences in molecular environments and protein interaction networks on the cell surface of brain cells may contribute to BVPrP's unusual behavior. To test this hypothesis, we generated knock-in mice that express physiological levels of BVPrP (M109 isoform) and employed mass spectrometry to compare the interactomes of mouse (Mo) PrP and BVPrP following mild in vivo crosslinking of brain tissue.

Peripherally administered TNF inhibitor is not protective against α-synuclein-induced dopaminergic neuronal death in rats.

The underlying cause of neuronal loss in Parkinson's disease (PD) remains unknown, but evidence implicates neuroinflammation in PD pathobiology. The pro-inflammatory cytokine soluble tumor necrosis factor (TNF) seems to play an important role and thus has been proposed as a therapeutic target for modulation of the neuroinflammatory processes in PD. In this regard, dominant-negative TNF (DN-TNF) agents are promising antagonists that selectively inhibit soluble TNF signaling, while preserving the beneficial effects of transmembrane TNF.

Sickness absence and disability pension in patients treated with mechanical thrombectomy.

Background: Stroke patients with large vessel occlusions risk long-term or permanent sickness absence. We aimed to analyze the proportions and days of sickness absence and disability pension in thrombectomy-treated patients.

Methods: A register-based nationwide longitudinal cohort study of stroke patients treated with mechanical thrombectomy in 2016-2021 in Sweden (identified through the Swedish Board of Health and Welfare procedural code for care interventions, KVÅ:AAL15).

Quantification of 3D microstructures in Achilles tendons during in situ loading reveals anisotropic fiber response.

While the number of studies investigating Achilles tendon pathologies has grown exponentially, more research is needed to gain a better understanding of the complex relation between its hierarchical structure, mechanical response, and failure. At the microscale, collagen fibers are, with some degree of dispersion, primarily aligned along the principal loading direction. However, during tension, rearrangements and reorientations of these fibers are believed to occur.

Risk of colorectal cancer associated with frequency of colorectal polyp diagnosis in relatives.

Background & Aims: We aimed to evaluate the association of frequency of polyp diagnosis in relatives with the risk of overall and early-onset colorectal cancer (CRC).

Methods: We leveraged data from nationwide Swedish family cancer datasets (1964-2018) to calculate standardized incidence ratios (SIRs) for individuals with a family history of polyp by frequency of polyp diagnosis in family members.

Results: We followed up 11,676,043 individuals for up to 54 years.

Hazelnut oral immunotherapy desensitizes hazelnut but not other tree nut allergies (Nut CRACKER Study).

Background: Data on oral immunotherapy (OIT) for hazelnut allergy is limited and its potential to cross-desensitize for other nuts is unknown.

Objective: To study the efficacy and safety of hazelnut OIT in desensitizing hazelnut and additional tree nuts.

Methods: A prospective observational study of 30 hazelnut allergic patients aged ≥4 years who underwent hazelnut OIT.

Assessing the scientific integrity of the collected work of one author or author-group.

Objective: No published methods for research integrity review include both statistical techniques applied to groups of randomised trials and individual assessment of papers. We propose a method based on practical experience of investigating data integrity across the collected papers of one author or author-group.

Study Design And Setting: We report our approach to investigating the collected papers of an author or author-group suspected of academic misconduct.

Research participation effects and where to find them: a systematic review of studies on alcohol.

Objective: The term 'research participation effects' (RPEs) is intended to capture features and artefacts of study design that may affect measured outcomes in ways that introduce bias into research findings, impacting inference and outcome validity. This systematic review aims to identify which RPEs have been studied in the context of alcohol research and provide an overview of estimates of RPEs on self-reported alcohol consumption.

Study Design And Setting: This systematic review summarises the available evidence on research participation effects in alcohol research.

Endometriosis and risk of depression among oral contraceptive users: a pooled analysis of cohort studies from 13 countries.

Study Question: Does endometriosis affect the mental health of women using oral contraceptives?

Summary Answer: Among oral contraceptive users, women with endometriosis have a higher risk of depression compared to those without endometriosis, although the absolute risk increase is small.

What Is Known Already: Previous studies have suggested a potential link between endometriosis and mental health issues, but the impact of endometriosis on depression among oral contraceptive users remains unclear.

Study Design, Size, Duration: A secondary pooled cohort study utilizing data from two longitudinal patient-centric studies (INAS-VIPOS and PRO-E2) was conducted across 11 European countries, Colombia and Australia.

Work and health-related determinants of midwives' intention to leave: Nationwide cross-sectional and prospective cohort studies in sweden.

Background: Midwives are essential for achieving the Sustainable Development Goal on sexual and reproductive health. However, midwifery shortage challenge healthcare organisations globally. The aim was to analyse cross-sectional and prospective associations between independent variables: 'possibilities of development'; 'quality of work'; 'role conflict'; 'recognition'; 'self-rated health' and 'burnout' and dependent variables: 'intention to leave current position' and 'intention to quit midwifery'.

Fear extinction retention in children, adolescents, and adults.

Past results suggest that fear extinction and the return of extinguished fear are compromised in adolescents. However, findings have been inconclusive as there is a lack of fear extinction and extinction retention studies including children, adolescents and adults. In the present study, 36 children (6-9 years), 40 adolescents (13-17 years) and 44 adults (30-40 years), underwent a two-day fear conditioning task.

Childhood residential and neighbourhood mobility: Consequences for educational attainment in young adulthood.

Research on the consequences of residential mobility for educational outcomes is inconclusive about when and for whom moving is detrimental or beneficial. Whether moving during childhood impacts educational attainment depends on how often, how far and at which age one moves; and on whether the neighbourhood conditions improve or decline with the move. This study aims to better understand under which circumstances moving during childhood impacts educational attainment by studying residential mobility and neighbourhood trajectories of children born in different types of neighbourhoods and how this is associated with completion of tertiary education.

Mandibular trabecular bone pattern before and two years after medical or surgical obesity treatment in young Swedish women.

Objective: To investigate if changes in body mass index (BMI) result in changes of the mandibular trabecular bone structure.

Materials And Methods: Females (18-35 years at baseline, mean BMI 42,3) were followed from before (n = 117) until two years (n = 66) after obesity treatment (medical or surgical). The mandibular bone trabeculation was classified as sparse, dense, or mixed on intraoral radiographs (Lindh's index).

Low impact of Zostera marina meadows on sediment and water microbiota under brackish conditions.

Background: Zostera marina is an important ecosystem engineer influencing shallow water environments and possibly shaping the microbiota in surrounding sediments and water. Z. marina is typically found in marine systems, but it can also proliferate under brackish conditions.