Eco Friendly and Budget Smart: An Economic and Environmental Evaluation of Alternative PD-1 and PD-L1 Inhibitor Dosing Regimens.

Background: Immune checkpoint inhibitors (ICIs) are clinically beneficial but associated with high costs that represent a growing challenge for healthcare budgets and may affect affordability, especially in resource-limited settings. Moreover, the healthcare sector is a significant source of greenhouse gas emissions, and medication-related waste-such as that from vial-based therapies-has been identified as a contributing factor. Alternative dosing strategies could reduce the environmental and financial impact of ICI therapy while maintaining clinical safety and efficacy.

Nuanced Public Support for Rationing Treatments by Withdrawing and Withholding Due to Negative Reimbursement Decisions.

When treatments are deemed not to be cost-effective and face non-reimbursement, policymakers in publicly funded healthcare systems may decide to ration treatments by withholding it from future patients. However, they must also address a critical question: should they also ration treatments by withdrawing it from patients already having access to the treatment, or is there an ethical difference between withdrawing and withholding treatments? To explore this question, we conducted a behavioural experiment (n=1404), examining public support for withdrawing and withholding treatments in reimbursement decisions across eleven different circumstances. Overall, public support for rationing by withdrawing and withholding was low, with no general perceived difference between withdrawing and withholding treatments.

Direct Effects of Polyploidization on Floral Scent.

Polyploidy is an important driver of the evolution and diversification of flowering plants. Several studies have shown that established polyploids differ from diploids in floral morphological traits and that polyploidization directly affects these traits. However, for floral scent, which is key to many plant-pollinator interactions, only a few studies have quantified differences between established cytotypes, and the direct effects of polyploidization on floral scent are not yet known.

On sperm length mean-variance relationships.

Sperm length is highly variable within ejaculates, between males, populations and across species. While theory makes strong predictions about expected mean sperm size, there is less clarity on variation in sperm, although studies have reported sperm-length variation consistent with some theoretical expectations. Typically, the coefficient of variation (CV) is used in these investigations to control for mean-variance scaling.

ATOR-4066, a bispecific antibody targeting CD40 and CEACAM5, induces strong myeloid and T cell-dependent tumor immunity and synergizes with PD-1 blockade.

Despite recent progress within the field of immuno-oncology, immune suppression in the tumor microenvironment, defective antigen presentation, and low levels of tumor-specific T cells are key limitations of current cancer immunotherapies. CD40-targeting immunotherapies hold promises for addressing these limitations across solid tumors. Here, we describe ATOR-4066, a bispecific antibody that targets CD40 and CEACAM5 developed for immunotherapy of cancer using the Neo-X-Prime platform.

Genomic insights into a diarrheal outbreak in Bangladesh reveal novel ETEC lineages and expansion of CS23 colonization factor.

Enterotoxigenic (ETEC), a leading cause of diarrhea, is defined by heat-stable (ST) and/or heat-labile (LT) toxins and associated colonization factors (CFs). However, there is still a knowledge gap in understanding ETEC's evolution, particularly in endemic regions like Bangladesh. This study investigates the genomic attributes contributing to the rise of ETEC-associated diarrhea in Bangladesh during 2022-2023.

Core-Level Photoelectron Angular Distributions from Bulk-Solvated to Surface-Active Aqueous Potassium Carboxylate Salts.

Photoelectron angular distributions are reported for a series of aqueous potassium carboxylate solutions, ranging from bulk-solvated to strongly surface-active species. The quantitative information determined from this work demonstrates how the measured photoelectron angular distributions are influenced by the ions' increasing propensity for the surface in aqueous solutions. Our study provides insight into the relative depth and location of the carboxylate functional group, which is valuable for investigating the adsorption of organic molecules at liquid-vapor interfaces.

Predicting Remission in Schizophrenia Using Machine Learning-Assessing the Impact of Sample Size and Predictor Overinclusion.

Introduction: Machine learning studies sometimes include a high number of predictors relative to the number of training cases. This increases the risk of overfitting and poor generalizability. A recent study hypothesized that between-trial heterogeneity precluded generalizable outcome prediction in schizophrenia from being achieved.

A New Family of Ternary Intermetallic Compounds with Dualistic Atomic Ordering - The ZIP Phases.

A new family of nanostructured ternary intermetallic compounds - named the ZIP phases - is introduced in this work. The ZIP phases exhibit dualistic atomic ordering, i.e.

Spatial Difference-in-Differences with Bayesian Disease Mapping Models.

Bayesian disease-mapping models are widely used in small-area epidemiology to account for spatial correlation and stabilize estimates through spatial smoothing. In contrast, difference-in-differences (DID) methods-commonly used to estimate treatment effects from observational panel data-typically ignore spatial dependence. This paper integrates disease mapping models into an imputation-based DID framework to address spatially structured residual variation and improve precision in small-area evaluations.

Unraveling psychosis risk in sexual minorities: temporal dynamics of social defeat and suspiciousness in adolescence.

Background: Previous research suggests that sexual minorities are at higher risk for psychotic experiences, possibly due to repeated social defeat experiences. However, empirical research investigating this hypothesis is largely lacking. This study examined how experiences of "feeling excluded" and "not belonging" impact the prospective development of psychotic experiences in an adolescent sexual minority group, defined here as non-heterosexual attraction to others.

Patterns and Processes of Genomic Evolution Inferred From the Ten Smallest Vertebrate Genomes.

Pufferfish exhibit the smallest vertebrate genomes, making them ideal models for investigating evolutionary patterns and processes that affect genome size. While the Takifugu rubripes genome was fully sequenced two decades ago, key evolutionary drivers remain elusive. We sequenced 10 pufferfish genomes and generated 35 transcriptomes and 13 methylomes to understand genomic evolutionary mechanisms.

Predictive Value of Plasma Biomarkers in Tau-PET Transitions.

Objective: The objective of this study was to determine the predictive value of amyloid-positron emission tomography (PET) versus the plasma ratio of phosphorylated tau at threonine 217 (p-tau217) to non-phosphorylated tau217 (%p-tau217) for tau-PET transitions (T- to T+). The added value of combining plasma amyloid-β 42 and amyloid-β 40 (Aβ42/40) and %p-tau217 into an amyloid probability score (APS2) was also assessed.

Methods: Mayo Clinic Study of Aging (MCSA) participants had plasma markers measured at via mass spectrometry (MS), an amyloid-PET scan, and a tau-PET (meta-temporal region of interest [ROI]) negative scan (standardized uptake value ratio [SUVR] <1.

Job control and working life expectancy in Sweden.

Objectives: This study aimed to investigate the impact of low job control on labor market participation expressed through working life expectancy (WLE) and working years lost (WYL) among men and women in Sweden.

Methods: A random sample of 100 000 individuals was drawn from the Swedish Work, Illness, and labor market Participation (SWIP) cohort of the registered Swedish population in 2005 born 1945 to 1975. The multi-state estimated labor market affiliation method was used to estimate WLE and WYL due to unemployment, sickness absence, other, disability pension, early old-age pension, and death over a 15-year period (2006-2020).

Pregnancy, Delivery, and Neonatal Outcomes in Women with Tourette Syndrome or Chronic Tic Disorder.

Background: Adverse pregnancy and neonatal outcomes in women with Tourette syndrome or chronic tic disorder (TS/CTD) have not been systematically studied. This Swedish population-based study investigated associations between maternal TS/CTD and pregnancy, delivery, and neonatal outcomes.

Methods: We included all singleton births at ≥22 weeks between 2001 and 2021.

Similar Outcome With Haploidentical, Matched Sibling, or Matched Unrelated Donor Hematopoietic Cell Transplantation for Adult Patients With Adverse-Risk TP53-Mutated Acute Myeloid Leukemia in First Remission: A Comparative Study From the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Given the dismal prognosis for patients with TP53-mutated acute myeloid leukemia (AML), the optimal donor for those undergoing allogeneic hematopoietic cell transplantation (allo-HCT) remains unclear. We retrospectively analyzed adult patients with TP53-mutated AML who underwent first allo-HCT in CR1 between 2010 and 2021. Outcomes were compared among using a haploidentical donor (Haplo), a matched sibling donor (MSD), and a 10/10 matched unrelated donor (MUD).

Preclinical dementia rating scores are associated with plasma phosphorylated tau-217.

Introduction: Simple screening tools are critical for assessing Alzheimer's disease (AD)-related pre-dementia changes. This study investigated longitudinal scores from the Quick Dementia Rating System (QDRS), a brief study partner-reported measure, in relation to baseline levels of the AD biomarker plasma pTau217 in individuals unimpaired at baseline.

Methods: Data from the Wisconsin Registry for Alzheimer's Prevention (N = 639) were used to examine whether baseline plasma pTau217 (ALZpath assay on Quanterix platform) modified QDRS or Preclinical Alzheimer's Cognitive Composite (PACC3) trajectories (mixed-effects models; time = age).

Glycan dysregulation as one of major metabolic subtypes is associated with TERC overexpression and poor outcomes in cervical cancer.

Background: Metabolic reprogramming is an important hallmark of cervical cancer (CC), and extensive studies have provided important information for translational and clinical oncology. Here we sought to determine metabolic association with molecular aberrations, telomere maintenance and outcomes in CC.

Methods: RNA sequencing data from TCGA cohort of CC was analyzed for their metabolic gene expression profile and consensus clustering was then performed to classify tumors into different groups/subtypes.

Where to restore: Connectivity forest for spatial prioritization in forest landscape restoration.

Forest loss, fragmentation, and transformation negatively impact forest biodiversity and ecosystem functionality worldwide. Improving landscape intactness and connectivity through restoration is critical. Determining where to restore remains, however, a challenge.

Compliance of pre-packaged food products with Nigerian food labelling guidelines: the NigeFE study.

Background: Food labelling policy has become increasingly important in public health due to the rising burden of diet-related diseases. This study examines the compliance of pre-packaged foods sold in Nigerian markets with national food labelling guidelines.

Methods: A total of 883 pre-packaged foods from broad categories were purposively enlisted from selected Nigerian stores and supermarkets.

Preserved ratio impaired spirometry, dysanapsis and airflow obstruction with low forced expiratory volume in 1 s in childhood asthma.

Background: Airway obstruction is a characteristic spirometric finding in asthma but the clinical significance of other abnormal spirometric patterns is less well described. We aimed to explore pre- and post-bronchodilator (BD) prevalences and clinical characteristics of preserved ratio impaired spirometry (PRISm), dysanapsis and airflow obstruction with low forced expiratory volume in 1 s (FEV) in children diagnosed with asthma.

Methods: We extracted specialist care data (clinical and spirometry) from the Swedish National Airway Register (n=3301, age 5-17 years).

Electrochemical Droplet Sculpturing of Short Carbon Fiber Nanotip Electrodes for Neurotransmitter Detection.

Carbon fiber nanotip electrodes (CFNEs) are crucial for electrochemical recordings of neurotransmission release in confined spaces, such as synapses and intracellular measurements. However, fabricating CFNEs with small surface area to minimize noise remains challenging due to inconsistent tip size control, low reproducibility, and low fabrication success rate. Here, we present a reliable, user-friendly method with high reproducibility and success rate for precise CFNE fabrication using microscopy-guided electrochemical etching of cylindrical carbon fiber microelectrodes in a potassium hydroxide droplet.

Plasma membrane labelling efficiency, internalization and partitioning of functionalized fluorescent lipids as a function of lipid structure.

Labeling the plasma membrane for advanced imaging remains a significant challenge. For time-lapse live cell imaging, probe internalization and photobleaching are major limitations affecting most membrane-specific dyes. In fixed or permeabilized cells, many membrane probes either lose signal after fixation or fail to remain localized to the plasma membrane.