Ribosome profiling shows variable sensitivity to detect open reading frames for conventional and different types of cryptic T cell antigens.

T cell-based immunotherapies targeting antigens on tumor cells have shown efficacy as anti-cancer treatments. While neoantigens are created by somatic mutations acquired during tumorigenesis, allogeneic stem cell transplantation as treatment for hematological malignancies exploits minor histocompatibility antigens encoded by genetic differences between patients and donors. Screening methods to predict neoantigens and minor histocompatibility antigens typically consider only conventional antigens created by nonsynonymous mutations or polymorphisms coding for amino acid changes in canonical open reading frames (ORFs).

Roles for the long non-coding RNA / in pancreatic beta cell function.

Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of beta cell function. Here, we show that an lncRNA-transcribed antisense to Pax6, annotated as Pax6os1/PAX6-AS1, was upregulated by high glucose concentrations in human as well as murine beta cell lines and islets. Elevated expression was also observed in islets from mice on a high-fat diet and patients with type 2 diabetes.

Cost-effectiveness of follow-up algorithms for chronic thromboembolic pulmonary hypertension in pulmonary embolism survivors.

Introduction: Achieving an early diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) in pulmonary embolism (PE) survivors results in better quality of life and survival. Importantly, dedicated follow-up strategies to achieve an earlier CTEPH diagnosis involve costs that were not explicitly incorporated in the models assessing their cost-effectiveness. We performed an economic evaluation of 11 distinct PE follow-up algorithms to determine which should be preferred.

The effect of active exoskeleton support with different lumbar-to-hip support ratios on spinal musculoskeletal loading and lumbar kinematics during lifting.

While active back-support exoskeletons can reduce mechanical loading of the spine, current designs include only one pair of actuated hip joints combined with a rigid structure between the pelvis and trunk attachments, restricting lumbar flexion and consequently intended lifting behavior. This study presents a novel active exoskeleton including actuated lumbar and hip joints as well as subject-specific exoskeleton control based on a real-time active low-back moment estimation. We evaluated the effect of exoskeleton support with different lumbar-to-hip (L/H) support ratios on spine loading, lumbar kinematics, and back muscle electromyography (EMG).

Validation of the 5-SNP score for the prediction of venous thromboembolism in a Danish fast-track cohort of 6789 total hip and total knee arthroplasty patients.

Background: Venous thromboembolism (VTE) is a serious complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Despite improvements with fast-track treatment protocols, 0.5% of patients still develop a VTE within 90-days postoperatively.

Cannabis Use Cessation and the Risk of Psychotic Disorders: A Case-Control Analysis from the First Episode Case-Control EU-GEI WP2 Study: L'arrêt de l'utilisation du cannabis et le risque de troubles psychotiques: Une analyse cas-témoins tirée de l'étude cas-témoins EU-GEI WP2 centrée sur les premiers épisodes psychotiques.

Objectives: To establish whether the risk of psychotic disorders in cannabis users changes with time following cannabis cessation using data from the European Network of National Networks studying Gene-Environment Interactions in Schizophrenia (EU-GEI) case-control study.

Methods: The EU-GEI case-control study collected data from first episode psychosis patients and population controls across sites in Europe and Brazil between May 2010 and April 2015. Adjusted logistic regressions were applied to examine whether the odd of psychosis case status changed: (1) with time following cannabis cessation and (2) across different cannabis use groups.

Toward a phylogenomic classification of magnoliids.

Premise: Magnoliids are a strongly supported clade of angiosperms. Previous phylogenetic studies based primarily on analyses of a limited number of mostly plastid markers have led to the current classification of magnoliids into four orders and 18 families. However, uncertainty remains regarding the placement of several families.

Gains and pains: a qualitative study on the implications of value-based health care for professionals.

Background: While aiming to optimize patient value, the shift towards Value-Based Health Care (VBHC) in hospitals worldwide has been argued to benefit healthcare professionals as well. However, robust evidence regarding VBHC's workforce implications is lacking. This gap is problematic, as the motivation and health of healthcare professionals are central to the quality of care and crucial amidst contemporary workforce challenges.

Governance and resilience as entry points for transforming food systems in the countdown to 2030.

Due to complex interactions, changes in any one area of food systems are likely to impact-and possibly depend on-changes in other areas. Here we present the first annual monitoring update of the indicator framework proposed by the Food Systems Countdown Initiative, with new qualitative analysis elucidating interactions across indicators. Since 2000, we find that 20 of 42 indicators with time series have been trending in a desirable direction, indicating modest positive change.

Enabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably in melanoma. However, its wider application and efficacy has been restricted by the limited accessibility, proliferative capacity and effector function of tumor-specific TIL. Here, we develop a platform for the efficient identification of tumor-specific TCR genes from diagnostic tumor biopsies, including core-needle biopsies frozen in a non-viable format, to enable engineered T cell therapy.

Investigating socioeconomic disparities in prescribing new diabetes medications in individuals with type 2 diabetes and very high cardiovascular risk in the Netherlands.

Aims: This study aims to analyze prescription patterns of new diabetes medication and assess socioeconomic disparities in their initiation among individuals with T2DM with very high cardiovascular risk.

Methods: Individuals diagnosed with T2DM and very high cardiovascular risk were identified (N = 10,768) based on general practitioner's electronic health record data. SGLT-2is and GLP-1RAs prescription patterns were examined.

Contextualizing the Upper Paleolithic of the Armenian Highlands: New data from Solak-1, central Armenia.

As a potential corridor connecting Southwest Asia with western and northern Europe, the Armenian Highlands and southern Caucasus hold great potential for increasing our understanding of Upper Paleolithic behavioral and cultural variability. However, given the dearth of Upper Paleolithic sites, we lack the data necessary to answer basic questions regarding the timing and nature of the Upper Paleolithic in this region. Solak-1 is an open-air site located along the upper Hrazdan Valley (1635 m above sea level) in central Armenia.

Analysis of the social-epistemological dimensions of a Clinical Teaching Unit and Small Private Online Course compared to a traditional clerkship Internal Medicine.

Clinical workplace learning is often suboptimal due to the dynamics of the clinical learning environment and several challenges encountered in clinical practice. At LUMC, clinical teachers introduced a novel blended learning program that included both the introduction of a Clinical Teaching Unit (CTU) and Small Private Online Course (SPOC). This study aimed to analyze the educational content and design of our educational interventions, by categorizing and comparing the dimensions of the learning program before and after the interventions.

Adverse health outcomes and health-related quality of life (HRQoL) among long-term adolescent and young adult (AYA) brain tumour survivors: results from the population-based SURVAYA study.

Purpose: Adolescent and young adult (AYA) malignant brain tumour (BT) survivors are at risk of adverse health outcomes, which may impact their health-related quality of life (HRQoL). This study aimed to investigate the (1) prevalence of physical and psychological adverse health outcomes, (2) the HRQoL, and (3) the association of adverse health outcomes and HRQoL among long-term AYA-BT survivors. Adverse health outcomes and HRQoL were compared to other AYA cancer (AYAC) survivors.

Veterans' experiences of somatic experiencing and prolonged exposure therapies for post-traumatic stress disorder: A qualitative analysis.

Purpose: Despite the proliferation of research into evidence based treatment for military PTSD there is little evidence for treatment assignment criterion and military based PTSD still demonstrates low remission rates.

Method: Thirty participants in a randomized control trial comparing Prolonged Exposure (PE) and Somatic Experiencing (SE) were interviewed on their experiences in therapy and their responses assessed using a descriptive phenomenological analysis approach to delineate the central tenets of the two therapeutic approaches.

Results: Results indicated that participants from both therapies covered themes of the experience of change, the experience of the therapeutic relationship and the therapeutic process.

Angiographic Characterization and Sex-Related Anatomical Differences of Atrial Coronary Arteries Anatomy-A Proposal of Systematic Classification.

Background: The coronary atrial circulation is the network of vessels that supply blood to the atria, originating from the left circumflex and right coronary arteries. Current descriptions of this arterial system are based on anatomical studies with a limited number of patients, predominantly male. In addition, there is a lack of consensus its angiographic nomenclature.

DIAMACC: protocol of a prospective diagnostic accuracy study of the maximal systolic acceleration to detect peripheral arterial disease in patients with diabetes-related foot ulceration in the Netherlands.

Introduction: Foot ulcers are one of the most serious complications of diabetes, leading to significant risks on amputation and mortality. Peripheral arterial disease (PAD) is an important factor for the development and the outcome of diabetic foot ulcers (DFU). Although prompt and accurate detection of PAD is critical to reduce complications, its diagnosis can be challenging with currently used bedside tests (such as ankle-brachial index and toe pressure) due to medial arterial calcification.

Safe, effective and cost-effective oxygen saturation targets for children and adolescents with respiratory distress: protocol for a randomised controlled trial (OxyKids study).

Introduction: Little is known about the effectiveness and safety of oxygen saturation (SpO2) thresholds in children admitted with respiratory distress. The current 90%-94% threshold could lead to prolonged administration of supplemental oxygen, increased duration of hospital admissions, distress for children and families, and healthcare costs. To balance reducing unnecessary oxygen administration and preventing hypoxia, a lower SpO2 threshold of 88% for oxygen supplementation in children has been suggested.

Risk prediction tools for pressure injury occurrence: an umbrella review of systematic reviews reporting model development and validation methods.

Background: Pressure injuries (PIs) place a substantial burden on healthcare systems worldwide. Risk stratification of those who are at risk of developing PIs allows preventive interventions to be focused on patients who are at the highest risk. The considerable number of risk assessment scales and prediction models available underscores the need for a thorough evaluation of their development, validation, and clinical utility.

The impact of clinical phenotypes of coronary artery disease on outcomes in patients with atrial fibrillation: A post-hoc analysis of GLORIA-AF registry.

Background: Coronary artery disease (CAD) and atrial fibrillation (AF) often coexist, but the impact of clinical phenotypes of CAD on outcomes in AF patients in the non-vitamin K antagonist oral anticoagulant drugs (NOACs) era is less well understood.

Methods: This was a post-hoc of the GLORIA-AF registry, a global, multicenter, prospective AF registry study. Patients were divided into three groups: prior history of myocardial infarction (MI)/unstable angina group (Group 1); stable angina group (Group 2); and a control group without stable angina or history of MI/unstable angina.

Arrhythmogenic Right Ventricular Cardiomyopathy: the importance of biventricular strain in risk-stratification.

Despite arrhythmogenic right ventricular cardiomyopathy (ARVC) being predominantly a right ventricular (RV) disease, concomitant left ventricular (LV) involvement has been recognized. ARVC is diagnosed by the RV-centric 2010 Task Force Criteria(TFC) using routine echocardiography, but previous studies have suggested that strain imaging may be more sensitive to detect RV and LV dysfunction. No data however are available regarding the additional value of combining biventricular strain for risk stratification.

Albendazole-ivermectin co-formulation for the treatment of Trichuris trichiura and other soil-transmitted helminths: a randomised phase 2/3 trial.

Background: Treatments for soil-transmitted helminthiases face challenges, especially in addressing Trichuris trichiura. Combination regimens, particularly of ivermectin and albendazole, are promising. We aimed to assess the safety, efficacy, and palatability of a combination tablet for the treatment of T trichiura, hookworm, and Strongyloides stercoralis infections among school-aged children in Ethiopia, Kenya, and Mozambique.

Floodplain forests drive fruit-eating fish diversity at the Amazon Basin-scale.

Unlike most rivers globally, nearly all lowland Amazonian rivers have unregulated flow, supporting seasonally flooded floodplain forests. Floodplain forests harbor a unique tree species assemblage adapted to flooding and specialized fauna, including fruit-eating fish that migrate seasonally into floodplains, favoring expansive floodplain areas. Frugivorous fish are forest-dependent fauna critical to forest regeneration via seed dispersal and support commercial and artisanal fisheries.

Overcoming the threat of anti-bias interventions: Combining self-report and psychophysiological measures to capture the process of change.

Anti-bias interventions do not always have the intended results and can even backfire. In light of research on the psychology of morality, we examined whether confronting people with evidence of their own (group's) bias causes a (psychophysiological) threat response, and how to overcome this. We focused on an intervention addressing gender bias in teacher evaluations.