Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial.

Background: CheckMate 8HW prespecified dual primary endpoints, assessed in patients with centrally confirmed microsatellite instability-high or mismatch repair-deficient status: progression-free survival with nivolumab plus ipilimumab compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab compared with nivolumab alone, regardless of previous systemic treatment for metastatic disease. In our previous report, nivolumab plus ipilimumab showed superior progression-free survival versus chemotherapy in first-line microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer in the CheckMate 8HW trial. Here, we report results from the prespecified interim analysis for the other primary endpoint of progression-free survival for nivolumab plus ipilimumab versus nivolumab across all treatment lines.

Chromosome-scale genome assembly reveals how repeat elements shape non-coding RNA landscapes active during newt limb regeneration.

Newts have large genomes harboring many repeat elements. How these elements shape the genome and relate to newts' unique regeneration ability remains unknown. We present here the chromosome-scale assembly of the 20.

VAE-Surv: A novel approach for genetic-based clustering and prognosis prediction in myelodysplastic syndromes.

Background And Objectives: Several computational pipelines for biomedical data have been proposed to stratify patients and to predict their prognosis through survival analysis. However, these analyses are usually performed independently, without integrating the information derived from each of them. Clustering of survival data is an underexplored problem, and current approaches are limited for biomedical applications, whose data are usually heterogeneous and multimodal, with poor scalability for high-dimensionality.

Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced Merkel Cell Carcinoma.

Aim: Merkel Cell Carcinoma (MCC) is a rare skin cancer with a rising incidence worldwide. Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are effective for the treatment of advanced MCC. This study examines patterns of response / progression of advanced MCC to anti-PD-(L)1 therapies and describes subsequent management.

Cancer-specific utility instrument for health economic evaluations: A synopsis of the EORTC QLU-C10D user manual and current validity evidence.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Utility - Core 10 Dimensions (QLU-C10D) adds a preference-based scoring algorithm to the EORTC measurement portfolio. It is built on the most widely used health-related quality of life (HRQoL) measure in oncology, the EORTC Quality of Life Questionnaire - Core 30 (QLQ-C30), allowing for the calculation of both HRQoL profiles and health utilities. This is an important advancement for integrating cancer-specific values into health economic evaluations and decision making, offering greater content validity and statistical power than some generic measures.

Non-comparability and unplannability as material topoi in antenatal care conversations.

Objective: This paper studies argumentation and its function to establish common ground in pregnancy counseling conversations during the third trimester of the pregnancy, focusing on two material topoi: Non-comparability and Unplannability.

Methods: We take a conversation-analytical and interactional approach and draw on 37 natural occurring counseling conversations, videorecorded during two periods at a university hospital. The conversations are typically between the midwife and the pregnant woman.

Freshwater browning as a hidden threat - Transcriptomic responses in fish gills exposed to fulvic acid.

Human activities and climate change have significantly increased humic substances in freshwater ecosystems over the last few decades. This increase is particularly concerning during seasonal changes or after heavy rainfall, when concentrations can easily increase up to tenfold. This phenomenon, known as "browning," has unknown consequences for aquatic organisms.

Rational choices elicit stronger sense of agency in brain and behavior.

The sense of agency is the subjective feeling of control over one's own actions and the associated outcomes. Here, we asked whether and to what extent the reasons behind our choices (operationalized by value differences, expected utility, and counterfactual option sets) drive our sense of agency. We simultaneously tested these three dimensions during a novel value-based decision-making task while recording explicit (self-reported) and implicit (brain signals) measures of agency.

What makes a trauma 'pathological'? - Perceived peritraumatic threat influences the development of intrusive memories.

Intrusions are a hallmark symptom of posttraumatic stress disorder (PTSD). While dysfunctional cognitions are known posttraumatic contributors, peritraumatic processes are less understood. Perceived threat, alongside emotional factors, is theorized as significant, but experimental studies are lacking.

Elucidating therapist differences: Therapists' interpersonal skills and their effect on treatment outcome.

Objective: Therapists differ in their average treatment outcomes. However, it remains unclear which characteristics differentiate more from less effective therapists. This study examined the association between therapist interpersonal skills and treatment outcome as well as the moderating effect of initial impairment.

The cost of fear: Impairments of decision-making in specific phobia.

Background: Decision-making processes may play a pivotal role in the etiology and maintenance of specific phobia. However, empirical evidence is limited. This study examined whether decision-making is only impaired in presence of fear-related stimuli or whether general impairments exist but are more pronounced in the presence of fear-related stimuli.

Oil palm smallholders and the road to certification: Insights from Indonesia.

Smallholder-managed oil palm plantations are a major driver of economic welfare and rural development. However, compared to industrial producers, smallholders are associated with lower farm productivity and disproportionately higher rates of illegal land clearing. Therefore, a balance must be struck between mitigating adverse externalities and strengthening favorable outcomes to ensure smallholders' sustainable integration into the palm oil industry.

Designing an online BCI forum: insights from researchers and end-users.

Objective: Brain-computer interfaces (BCIs) can support non-muscular communication and device control for severely paralyzed people. However, efforts that directly involve potential or actual end-users and address their individual needs are scarce, demonstrating a translational gap. An online BCI forum supported by the BCI Society could initiate and sustainably strengthen interactions between BCI researchers and end-users to bridge this gap.

Differential effects of warming on carbon budget, photosynthetic yield and biochemical composition of cold-temperate and Arctic isolates of Laminaria digitata (Phaeophyceae).

Cold-temperate and Arctic hard bottom coastal ecosystems are dominated by kelp forests, which have a high biomass production and provide important ecosystem services, but are subject to change due to ocean warming. However, the photophysiological response to increasing temperature of ecologically relevant species, such as Laminaria digitata, might depend on the local thermal environment where the population has developed. Therefore, the effects of temperature on growth rate, biochemical composition, maximum quantum yield, photosynthetic quotient and carbon budget of young cultured sporophytes of Laminaria digitata from the Arctic at Spitsbergen (SPT; cultured at 4, 10 and 16 °C) and from the cold-temperate North Sea island of Helgoland (HLG; cultured at 10, 16 and 22 °C) were comparatively analyzed.

Attachment of Hydrogel Patches to Eye Tissue through Gel Transfer using Flexible Foils.

Glaucoma, a leading cause of blindness, demands innovative and effective treatments that surpass the limitations of current drug and surgical interventions to lower intraocular pressure. This study describes the generation of cell-repellent hydrogel patches, their deposition on the ocular surface, and a photoinduced chemical binding between the patches and the collagens of the eye. The hydrophilic and protein-repellent hydrogel patch is composed of a copolymer made from dimethylacrylamide and a comonomer unit with anthraquinone moieties.

Role of Tailored Timing and Frequency Prompts on the Efficacy of an Internet-Delivered Stress Recovery Intervention for Health Care Workers: Randomized Controlled Trial.

Background: Prompts offer a promising strategy to promote client engagement in internet-delivered cognitive behavioral therapy (ICBT). However, if the prompts do not meet the needs of clients, they can potentially be more obtrusive rather than helpful.

Objective: The aim of this study was to test if prompts tailored based on timing and frequency, aligned with preintervention goal setting, can increase usage and the efficacy of a therapist-supported ICBT stress recovery intervention for health care workers.

Cross-Platform Ecological Momentary Assessment App (JTrack-EMA+): Development and Usability Study.

Background: Traditional in-clinic methods of collecting self-reported information are costly, time-consuming, subjective, and often limited in the quality and quantity of observation. However, smartphone-based ecological momentary assessments (EMAs) provide complementary information to in-clinic visits by collecting real-time, frequent, and longitudinal data that are ecologically valid. While these methods are promising, they are often prone to various technical obstacles.

The Social Construction of Categorical Data: Mixed Methods Approach to Assessing Data Features in Publicly Available Datasets.

Background: In data-sparse areas such as health care, computer scientists aim to leverage as much available information as possible to increase the accuracy of their machine learning models' outputs. As a standard, categorical data, such as patients' gender, socioeconomic status, or skin color, are used to train models in fusion with other data types, such as medical images and text-based medical information. However, the effects of including categorical data features for model training in such data-scarce areas are underexamined, particularly regarding models intended to serve individuals equitably in a diverse population.

Digital Information Exchange Between the Public and Researchers in Health Studies: Scoping Review.

Background: Information exchange regarding the scope and content of health studies is becoming increasingly important. Digital methods, including study websites, can facilitate such an exchange.

Objective: This scoping review aimed to describe how digital information exchange occurs between the public and researchers in health studies.

The Use of Acellular Dermal Matrix May Not Increase 30-Day Complications in Direct-to-Implant Breast Reconstruction: A Multi-institutional Analysis of 10,177 Cases.

Background: Direct-to-implant (DTI) breast reconstruction offers immediate aesthetic and psychological benefits, but the role of acellular dermal matrix (ADM) remains debated. Using a multi-institutional database, this study evaluates and compares outcomes between ADM-assisted and non-ADM DTI procedures.

Methods: The American College of Surgeons National Surgical Quality Improvement Program database from 2008 to 2022 was queried to identify female patients who underwent DTI breast reconstruction for oncological purposes.

Acute effect of short-duration static stretching exercises on dynamic balance in U-14 female athletes.

: The acute effects of static stretching (SS) on dynamic balance, a key fitness component that contributes to injury prevention, has been a subject of significant debate. This study aimed to investigate the acute effect of short-duration SS exercises on dynamic balance following different recovery durations in youth female volleyball players. : Thirteen volunteers U-14 female players were included.

Deciphering the complex clonal heterogeneity of polycythemia vera and the response to interferon alpha.

Interferon alpha (IFNa) is approved for the therapy of patients (pts) with polycythemia vera (PV), a subtype of myeloproliferative neoplasms (MPN). Some pts achieve molecular responses (MR), but clonal factors sensitizing for MR remain elusive. We integrated colony formation and differentiation assays with single-cell RNA seq and genotyping in PV-derived cells vs.

Higher Risk Renal Angiomyolipomas: Surveillance Remains a Safe Management Option.

Purpose: This retrospective study furthers our understanding of risk factors associated with hemorrhage and intervention in renal angiomyolipomas (R-AMLs), particularly in larger tumors (≥ 4 cm) and in childbearing-age (CBA; younger than 50 years) women. The objective was to refine risk stratification and optimize patient management.

Methods: Review of our institutional database identified patients with radiographic R-AML from 1997 to 2023.

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS) of the European Association for Cardio-Thoracic Surgery Fourth report: Focus on standardized outcome ratios.

Objectives: This fourth report aimed to provide insights into patient characteristics, outcomes, and standardized outcome ratios of patients implanted with durable Mechanical Circulatory Support across participating centers in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) registry.

Methods: All registered patients receiving durable mechanical circulatory support up to August 2024 were included. Expected number of events were predicted using penalized logistic regression.

Evaluation of Global South's efficiency at the Summer Olympics.

States differ significantly in international sports competitions in how they use the resources they have and whether they do so in an efficient manner. In this paper, we investigate the efficiency of the nations from the so-called "Global South", in total 52 states, during the 2000-2024 Summer Olympics. By doing this, our paper is the first using the Bayesian stochastic frontier analysis for exploring the performance of the states of the Global South.