Including carer health-related quality of life in NICE health technology assessments in the United Kingdom.

The impact of health technologies may extend beyond the patient and affect the health of people in their network, like their informal carers. The National Institute for Health and Care Excellence (NICE) methods guide explicitly allows the inclusion of health-related quality of life (HRQoL) effects on carers in economic evaluations when these effects are substantial, but the proportion of NICE appraisals that includes carer HRQoL remains small. This paper discusses when inclusion of carer HRQoL is justified, how inclusion can be substantiated, and how carer HRQoL can be measured and included in health economic models.

Toxin-mediated depletion of NAD and NADP drives persister formation in a human pathogen.

Toxin-antitoxin (TA) systems are widespread in bacteria and implicated in genome stability, virulence, phage defense, and persistence. TA systems have diverse activities and cellular targets, but their physiological roles and regulatory mechanisms are often unclear. Here, we show that the NatR-NatT TA system, which is part of the core genome of the human pathogen Pseudomonas aeruginosa, generates drug-tolerant persisters by specifically depleting nicotinamide dinucleotides.

Estimating the Prognostic Value of the NTRK Fusion Biomarker for Comparative Effectiveness Research in The Netherlands.

Objectives: We evaluated the prognostic value of the neurotrophic tyrosine receptor kinase (NTRK) gene fusions by comparing the survival of patients with NTRK+ tumours with patients without NTRK+ tumours.

Methods: We used genomic and clinical registry data from the Center for Personalized Cancer Treatment (CPCT-02) study containing a cohort of cancer patients who were treated in Dutch clinical practice between 2012 and 2020. We performed a propensity score matching analysis, where NTRK+ patients were matched to NTRK- patients in a 1:4 ratio.

Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial.

Background: In CheckMate 9LA, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy regardless of tumor PD-L1 expression or histology. We report updated efficacy and safety in all randomized patients with a minimum 4-year follow-up and an exploratory treatment-switching adjustment analysis in all treated patients who received chemotherapy and subsequent immunotherapy.

Methods: Adults with stage IV/recurrent non-small cell lung cancer (NSCLC), no sensitizing alterations, and ECOG performance status ≤1 were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with chemotherapy (two cycles) or chemotherapy (four cycles, with optional maintenance pemetrexed for the nonsquamous population).

Impact of coppicing on microclimate and understorey vegetation diversity in an ancient Mediterranean oak forest.

Coppicing is one of the oldest silvicultural practices and is still widely applied to produce renewable energy from broadleaf forests. However, the consequences on microclimate and understorey vegetation are still poorly understood, especially in Mediterranean oak forests. With the ongoing changes in the climate system and global biodiversity loss, a better understanding of how the forest temperature buffering capacity and below-canopy plant community are impacted by coppicing is crucial.

Depth-driven patterns in lytic viral diversity, auxiliary metabolic gene content, and productivity in offshore oligotrophic waters.

Introduction: Marine viruses regulate microbial population dynamics and biogeochemical cycling in the oceans. The ability of viruses to manipulate hosts' metabolism through the expression of viral auxiliary metabolic genes (AMGs) was recently highlighted, having important implications in energy production and flow in various aquatic environments. Up to now, the presence and diversity of viral AMGs is studied using -omics data, and rarely using quantitative measures of viral activity alongside.

metaGOflow: a workflow for the analysis of marine Genomic Observatories shotgun metagenomics data.

Background: Genomic Observatories (GOs) are sites of long-term scientific study that undertake regular assessments of the genomic biodiversity. The European Marine Omics Biodiversity Observation Network (EMO BON) is a network of GOs that conduct regular biological community samplings to generate environmental and metagenomic data of microbial communities from designated marine stations around Europe. The development of an effective workflow is essential for the analysis of the EMO BON metagenomic data in a timely and reproducible manner.

The founding charter of the Omic Biodiversity Observation Network (Omic BON).

Omic BON is a thematic Biodiversity Observation Network under the Group on Earth Observations Biodiversity Observation Network (GEO BON), focused on coordinating the observation of biomolecules in organisms and the environment. Our founding partners include representatives from national, regional, and global observing systems; standards organizations; and data and sample management infrastructures. By coordinating observing strategies, methods, and data flows, Omic BON will facilitate the co-creation of a global omics meta-observatory to generate actionable knowledge.

Societal Utilities for Cognitive Impairment in Schizophrenia: Developing a Preference-Based Scoring Algorithm Based on the Schizophrenia Cognition Rating Scale.

Introduction: Loss of cognitive function is a common feature in schizophrenia. However, generic measures of health-related quality of life favored by decision-makers, such as the EQ-5D, are not designed to detect changes in cognitive function. We report the valuation of the Schizophrenia Cognition Rating Scale (SCoRS), a schizophrenia-specific measure of cognitive impairment.

Informal Care Costs According to Age and Proximity to Death to Support Cost-Effectiveness Analyses.

Background: Costs of informal care are ignored in many cost-effectiveness analyses (CEAs) conducted from a societal perspective; however, these costs are relevant for lifesaving interventions targeted at the older population. In this study, we estimated informal care costs by age and proximity to death across European regions and showed how these estimates can be included in CEAs.

Methods: We estimated informal care costs by age and proximity to death using generalised linear mixed-effects models.

Potential Utilization of Bacterial Consortium of Symbionts Marine Sponges in Removing Polyaromatic Hydrocarbons and Heavy Metals, Review.

Toxic materials in waste generally contain several components of the global trending pollutant category, especially PAHs and heavy metals. Bioremediation technology for waste management that utilizes microorganisms (bacteria) has not been fully capable of breaking down these toxic materials into simple and environmentally friendly chemical products. This review paper examines the potential application of a consortium of marine sponge symbionts with high performance and efficiency in removing PAHs and heavy metal contaminants.

In search of a 'pan-European value set'; application for EQ-5D-3L.

Objectives: Country-specific value sets for the EQ-5D are available which reflect preferences for health states elicited from the general population. This allows the transformation of responses on EQ-5D to health state utility values. Only twelve European countries possess country-specific value sets and no value set reflecting the preferences of Europe exists.

Cost-Effectiveness Analysis of Treating Patients With NTRK-Positive Cancer With the Histology-Independent Therapy Entrectinib.

Objectives: This study tackles several challenges of evaluating histology-independent treatments using entrectinib as an example. Histology-independent treatments are provided based on genetic marker(s) of tumors, regardless of the tumor type. We evaluated the lifetime cost-effectiveness of testing all patients for NTRK fusions and treating the positive cases with entrectinib compared with no testing and standard of care (SoC) for all patients.

Investigation of Global Trends of Pollutants in Marine Ecosystems around Barrang Caddi Island, Spermonde Archipelago Cluster: An Ecological Approach.

High-quality marine ecosystems are free from global trending pollutants' (GTP) contaminants. Accuracy and caution are needed during the exploitation of marine resources during marine tourism to prevent future ecological hazards that cause chain effects on aquatic ecosystems and humans. This article identifies exposure to GTP: microplastic (MP); polycyclic aromatic hydrocarbons (PAH); pesticide residue (PR); heavy metal (HM); and medical waste (MW), in marine ecosystems in the marine tourism area (MTA) area and Barrang Caddi Island (BCI) waters.

The Use of Experimental Evolution to Study the Response of Pseudomonas aeruginosa to Single or Double Antibiotic Treatment.

The widespread use of antibiotics promotes the evolution and dissemination of drug resistance and tolerance. Both mechanisms promote survival during antibiotic exposure and their role and development can be studied in vitro with different assays to document the gradual adaptation through the selective enrichment of resistant or tolerant mutant variants. Here, we describe the use of experimental evolution in combination with time-resolved genome analysis as a powerful tool to study the interaction of antibiotic tolerance and resistance in the human pathogen Pseudomonas aeruginosa .

Defining Proteomic Signatures to Predict Multidrug Persistence in Pseudomonas aeruginosa.

Bacterial persisters are difficult to eradicate because of their ability to survive prolonged exposure to a range of different antibiotics. Because they often represent small subpopulations of otherwise drug-sensitive bacterial populations, studying their physiological state and antibiotic stress response remains challenging. Sorting and enrichment procedures of persister fractions introduce experimental biases limiting the significance of follow-up molecular analyses.

Bioactivity and composition of lipophilic metabolites extracted from Antarctic macroalgae.

Macroalgae comprise a vast group of aquatic organisms known for their richness in phytochemicals. In this sense, the lipophilic profile of five Antarctic seaweed species was characterized by chromatographic and spectroscopic analysis and their antioxidant and antimicrobial potential was evaluated. Results showed there were 31 lipophilic substances, mainly fatty acids (48.

Evolution of Antibiotic Tolerance Shapes Resistance Development in Chronic Pseudomonas aeruginosa Infections.

The widespread use of antibiotics promotes the evolution and dissemination of resistance and tolerance mechanisms. To assess the relevance of tolerance and its implications for resistance development, we used evolution and analyzed the inpatient microevolution of , an important human pathogen causing acute and chronic infections. We show that the development of tolerance precedes and promotes the acquisition of resistance , and we present evidence that similar processes shape antibiotic exposure in human patients.

Right Atrium Mass Assessed with 18F-FDG PET/CT Scan Turns Out to Be an Uncommon Relapse of Testicular Diffuse Large B-cell Lymphoma: A Case Report.

We report the case of a 71-year-old man affected by testicular large B-cell lymphoma (DLBCL), treated with right orchiectomy and first-line chemotherapy (R-CHOP, 8 cycles). A complete remission was obtained after therapy. Twenty-two months after the primary diagnosis the patient suddenly presented dyspnoea and superior vena cava syndrome; thus, he underwent a CT scan that revealed a large mass in the right atrium, expanding to the superior vena cava.

Mineral and Fatty Acid Content Variation in White Oat Genotypes Grown in Brazil.

A healthy diet is directly associated with a nutrient-rich and toxic contaminant poor intake. A diet poor in diversity can lead to micronutrient deficiency. The intake of functional foods can provide benefits in the prevention and treatment of diseases.

ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia.

Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naïve cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize the risk of GvHD and provide graft-versus-infection and -leukemia activity. Safety and efficacy of ATIR101 administered after T-cell-depleted haploidentical HSCT (TCD-haplo + ATIR101) without posttransplant immunosuppressors were evaluated in a Phase 2, multicenter study of 23 patients with acute leukemia and compared with an observational cohort undergoing TCD-haplo alone (n = 35), matched unrelated donor (MUD; n = 64), mismatched unrelated donor (MMUD; n = 37), and umbilical cord blood (UCB; n = 22) HSCT.

Prokaryotic and eukaryotic microbial community responses to N and P nutrient addition in oligotrophic Mediterranean coastal waters: Novel insights from DNA metabarcoding and network analysis.

The effects of the abrupt input of high quantities of dissolved inorganic nitrogen and phosphorus on prokaryotic and eukaryotic microbial plankton were investigated in an attempt to simulate the nutrient disturbances caused by eutrophication and climate change. Two nutrient levels were created through the addition of different quantities of dissolved nutrients in a mesocosm experiment. During the developed blooms, compositional differences were found within bacteria and microbial eukaryotes, and communities progressed towards species of faster metabolisms.

DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer.

Background: Genetic aberrations in DNA repair genes are linked to cancer, but less is reported about epigenetic regulation of DNA repair and functional consequences. We investigated the intragenic methylation loss at the three prime repair exonuclease 2 (TREX2) locus in laryngeal (n = 256) and colorectal cancer cases (n = 95) and in pan-cancer data from The Cancer Genome Atlas (TCGA).

Results: Significant methylation loss at an intragenic site of TREX2 was a frequent trait in both patient cohorts (p = 0.

Automated Synthesis of 68Ga-DOTA-TOC with a Cationic Purification System: Evaluation of Methodological and Technical Aspects in Routine Preparations.

Background And Objective: Gallium-68 is a PET isotope available in each nuclear medicine departments, even those not equipped with a cyclotron, since it is easily obtained by eluting compact and transportable generator system. The preparation of Ga-68 DOTA-labeled compounds is performed by remotely controlled automated systems developed in order to ensure production efficiency, reproducibility of the results, fast reaction time, to facilitate the synthesis and minimize the radiation exposure. Many automatic synthesis systems are available on the radiopharmaceutical market, however, they requires some technical adaptations for routine use.