Toward target 2035: EUbOPEN - a public-private partnership to enable & unlock biology in the open.

Target 2035 is a global initiative that seeks to identify a pharmacological modulator of most human proteins by the year 2035. As part of an ongoing series of annual updates of this initiative, we summarise here the efforts of the EUbOPEN project whose objectives and results are making a strong contribution to the goals of Target 2035. EUbOPEN is a public-private partnership with four pillars of activity: (1) chemogenomic library collections, (2) chemical probe discovery and technology development for hit-to-lead chemistry, (3) profiling of bioactive compounds in patient-derived disease assays, and (4) collection, storage and dissemination of project-wide data and reagents.

Outbreak of the novel IIγA11 linked to salad bars in Sweden, December 2023.

We report a foodborne outbreak of the previously undetected subtype IIγA11. In December 2023, notifications of cryptosporidiosis cases increased in Sweden, prompting the initiation of a national outbreak investigation, and a case-control study was performed to identify the source. We identified 60 cases between 15 December 2023 and 1 January 2024.

IPECAD Modeling Workshop 2023 Cross-Comparison Challenge on Cost-Effectiveness Models in Alzheimer's Disease.

Objectives: Decision-analytic models assessing the value of emerging Alzheimer's disease (AD) treatments are challenged by limited evidence on short-term trial outcomes and uncertainty in extrapolating long-term patient-relevant outcomes. To improve understanding and foster transparency and credibility in modeling methods, we cross-compared AD decision models in a hypothetical context of disease-modifying treatment for mild cognitive impairment (MCI) due to AD.

Methods: A benchmark scenario (US setting) was used with target population MCI due to AD and a set of synthetically generated hypothetical trial efficacy estimates.

Long axial-range double-helix point spread functions for 3D volumetric super-resolution imaging.

Single-molecule localization microscopy (SMLM) is a powerful tool for observing structures beyond the diffraction limit of light. Combining SMLM with engineered point spread functions (PSFs) enables 3D imaging over an extended axial range, as has been demonstrated for super-resolution imaging of various cellular structures. However, super-resolving structures in 3D in thick samples, such as whole mammalian cells, remains challenging as it typically requires acquisition and post-processing stitching of multiple slices to cover the entire sample volume or more complex analysis of the data.

Test-retest reliability, practice effects and estimates of change: A study on the Mindmore digital cognitive assessment tool.

The present study aimed to establish test-retest reliability and investigate practice effects of the Mindmore cognitive assessment tool, a digital adaptation of traditional pencil and paper tests designed for self-administration. Additionally, normative change scores for the most frequently used tests were derived. A total of 149 healthy Swedish adults (aged 20-79) completed the test battery twice, 1 month apart.

Associations of modifiable and non-modifiable risk factors with cognitive functions - a prospective, population-based, 17 years follow-up study of 3,229 individuals.

Background: Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype.

Methods: Participants from a large, prospective, population-based, Swedish study were included (n = 3,229).

Multimodal illumination platform for 3D single-molecule super-resolution imaging throughout mammalian cells.

Single-molecule super-resolution imaging is instrumental in investigating cellular architecture and organization at the nanoscale. Achieving precise 3D nanometric localization when imaging structures throughout mammalian cells, which can be multiple microns thick, requires careful selection of the illumination scheme in order to optimize the fluorescence signal to background ratio (SBR). Thus, an optical platform that combines different wide-field illumination schemes for target-specific SBR optimization would facilitate more precise 3D nanoscale studies of a wide range of cellular structures.

Lysine Demethylase 4A is a Centrosome Associated Protein Required for Centrosome Integrity and Genomic Stability.

Centrosomes play a fundamental role in nucleating and organizing microtubules in the cell and are vital for faithful chromosome segregation and maintenance of genomic stability. Loss of structural or functional integrity of centrosomes causes genomic instability and is a driver of oncogenesis. The lysine demethylase 4A (KDM4A) is an epigenetic 'eraser' of chromatin methyl marks, which we show also localizes to the centrosome with single molecule resolution.

Outbreak of Typhimurium linked to Swedish pre-washed rocket salad, Sweden, September to November 2022.

In September 2022, the Public Health Agency of Sweden observed an increase in domestic Typhimurium cases through the Swedish electronic notification system, and an outbreak strain was identified with whole genome sequencing. Overall, 109 cases with symptom onset between 17 September and 24 November 2022 were reported from 20 of 21 Swedish regions. The median age of cases was 52 years (range 4-87 years) and 62% were female.

Survival and Quality of Life after Isolated Hepatic Perfusion with Melphalan as a Treatment for Uveal Melanoma Liver Metastases - Final Results from the Phase III Randomized Controlled Trial SCANDIUM.

Objective: To investigate overall survival (OS) and health-related quality of life (HRQOL) of first-line isolated hepatic perfusion (IHP) compared to best alternative care (BAC) for patients with uveal melanoma liver metastases.

Summary Background Data: Approximately half of patients with uveal melanoma develop metastatic disease, most commonly in the liver and systemic treatment options are limited. Isolated hepatic perfusion (IHP) is a locoregional therapy with high response rates but with unclear effect on overall survival (OS).

Multimodal illumination platform for 3D single-molecule super-resolution imaging throughout mammalian cells.

Single-molecule super-resolution imaging is instrumental for investigating cellular architecture and organization at the nanoscale. Achieving precise 3D nanometric localization when imaging structures throughout mammalian cells, which can be multiple microns thick, requires careful selection of the illumination scheme in order to optimize the fluorescence signal to background ratio (SBR). Thus, an optical platform that combines different wide-field illumination schemes for target-specific SBR optimization would facilitate more precise, 3D nanoscale studies of a wide range of cellular structures.

The costs of chronic pain-Long-term estimates.

Background: Chronic pain is a condition with severe impact on many aspects of life, including work, functional ability and quality of life, thereby reducing physical, mental and social well-being. Despite the high prevalence and burden of chronic pain, it has received disproportionally little attention in research and public policy and the societal costs of chronic pain remain largely unknown. This study aimed to describe the long-term healthcare and work absence costs of individuals with and without self-identified chronic pain.

Developing sustainable service user involvement practices in mental health services in Sweden: the "Userinvolve" research program protocol.

Background: The purpose of this paper is to outline the protocol for the research program "UserInvolve," with the aim of developing sustainable, service user involvement practices in mental health services in Sweden.

Methods: This protocol outlines the knowledge gap and aim of the UserInvolve-program. It further provides an overview of the research infrastructure, with specific focus on the organization and management of the program as well as the design of the six underlying research projects.

Phenotypic Diversity in Domesticated and Wild Timothy Grass, and Closely Related Species for Forage Breeding.

Timothy grass ( L.) is one of the most important forage crops in temperate regions. Forage production, however, faces many challenges, and new cultivars adapted to a changing climate are needed.

Disease severity and mortality in Alzheimer's disease: an analysis using the U.S. National Alzheimer's Coordinating Center Uniform Data Set.

Background: Evidence on the relative risk of death across all stages of Alzheimer's disease (AD) is lacking but greatly needed for the evaluation of new interventions. We used data from the Uniform Data Set (UDS) of the National Alzheimer's Coordinating Center (NACC) to assess the expected survival of a person progressing to a particular stage of AD and the relative risk of death for a person in a particular stage of AD compared with cognitively normal (CN) people.

Methods: This was a retrospective observational cohort study of mortality and its determinants in participants with incident mild cognitive impairment (MCI) due to AD or AD dementia compared with CN participants.

Single-molecule imaging in the primary cilium.

The primary cilium is an important signaling organelle critical for normal development and tissue homeostasis. Its small dimensions and complexity necessitate advanced imaging approaches to uncover the molecular mechanisms behind its function. Here, we outline how single-molecule fluorescence microscopy can be used for tracking molecular dynamics and interactions and for super-resolution imaging of nanoscale structures in the primary cilium.

Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results.

Background: Inflammation is a key driver of heart failure with preserved left ventricular ejection fraction. AZD4831 inhibits extracellular myeloperoxidase, decreases inflammation, and improves microvascular function in preclinical disease models.

Methods And Results: In this double-blind phase 2a study (Safety and Tolerability Study of AZD4831 in Patients With Heart Failure [SATELLITE]; NCT03756285), patients with symptomatic heart failure, left ventricular ejection fraction of ≥40%, and elevated B-type natriuretic peptides were randomized 2:1 to once-daily oral AZD4831 5 mg or placebo for 90 days.

Effect of mortality in cost-effectiveness modeling of disease-modifying treatment for Alzheimer's disease.

Introduction: We examined (1) the magnitude of mortality attributed to Alzheimer's disease (AD), and (2) the effect of mortality in cost-effectiveness modeling of hypothetical disease-modifying treatment (DMT) in AD.

Method: Data were derived from Swedish Dementia Registry ( = 39,308). Mortality was analyzed with survival analysis and multinomial logistic regression.

A hierarchical pathway for assembly of the distal appendages that organize primary cilia.

Distal appendages are nine-fold symmetric blade-like structures attached to the distal end of the mother centriole. These structures are critical for formation of the primary cilium, by regulating at least four critical steps: ciliary vesicle recruitment, recruitment and initiation of intraflagellar transport (IFT), and removal of CP110. While specific proteins that localize to the distal appendages have been identified, how exactly each protein functions to achieve the multiple roles of the distal appendages is poorly understood.