Adjuvant Use of Pembrolizumab for Stage III Melanoma in a Real-World Setting in Europe.

Background: Although data on patients treated with pembrolizumab are available from clinical trials and single-country real-world reports, to our knowledge no multi-country real-world studies have investigated the use of pembrolizumab as an adjuvant treatment for stage III melanoma.

Methods: We used the European Melanoma Registry (EUMelaReg), a disease entity-based registry specific for melanoma, to examine treatment and outcomes for adult patients with stage III melanoma with lymph node involvement who had complete resection and received adjuvant treatment with pembrolizumab. The primary objectives were to describe the demographic and clinical characteristics of the included patients as well as time on adjuvant pembrolizumab treatment (TOT), real-world recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) from adjuvant pembrolizumab initiation.

Exploring the relationships between ground observations and remotely sensed hazelnut spring phenology.

Crop phenology is very important in regular crop monitoring. Generally, phenology is monitored through field observation surveys or satellite data. The relationships between ground observations and remotely sensed derived phenological data can enable near-real-time monitoring over large areas, which has never been attempted on hazelnuts.

Phenotyping patients with chronic obstructive pulmonary disease and heart failure.

Aims: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are prevalent comorbidities associated with significant morbidity/mortality. We assessed prevalence of, patient profiles and outcomes associated with COPD across the ejection fraction (EF) spectrum.

Methods: HF patients enrolled in the Swedish HF registry between 2005 and 2021 were considered.

QCD challenges from pp to AA collisions: 4th edition.

This paper is a write-up of the ideas that were presented, developed and discussed at the fourth International Workshop on QCD Challenges from pp to AA, which took place in February 2023 in Padua, Italy. The goal of the workshop was to focus on some of the open questions in the field of high-energy heavy-ion physics and to stimulate the formulation of concrete suggestions for making progresses on both the experimental and theoretical sides. The paper gives a brief introduction to each topic and then summarizes the primary results.

Mindfulness and mental health: the importance of a clinical intervention to prevent the effects of a traumatic event. A pilot study.

Numerous research studies show that mindfulness can mitigate the negative impact of trauma on mental health by reducing symptoms of anxiety, mediating the relationship between trauma exposure and mental health, and treating symptoms resulting from traumatic events. During the COVID-19 pandemic, which was considered a traumatic event, the wellbeing of adults and children was severely compromised. Although children seem less vulnerable to the physical effects of the virus, this does not seem to be true for the psychological effects.

Embedding patient engagement in the R&D process of a life sciences company through co-creation with a patient expert R&D board: a case study.

Patient involvement is crucial in healthcare, a factor increasingly recognised by life sciences companies and research institutes. This article presents a case study on Servier, a life sciences company that founded a patient expert board, ahead of launching a new research and development (R&D) institute. The aim was to foster a patient-centric culture within the company.

Improvements for the solution of crack evolution using extended finite element method.

It is demonstrated that the eXtended Finite Element Method (XFEM) is of remarkable efficiency in simulating crack evolution by eliminating the need for remeshing and refinement. In this paper, it is shown how to enhance the solution efficiency through a comprehensive mathematical investigation of the solution process using XFEM. A typical example is presented to illustrate the disparities in nodal displacements along the two symmetric faces of the crack resulting from the approximation of XFEM.

Coenzyme A fueling with pantethine limits autoreactive T cell pathogenicity in experimental neuroinflammation.

Background: Immune cell metabolism governs the outcome of immune responses and contributes to the development of autoimmunity by controlling lymphocyte pathogenic potential. In this study, we evaluated the metabolic profile of myelin-specific murine encephalitogenic T cells, to identify novel therapeutic targets for autoimmune neuroinflammation.

Methods: We performed metabolomics analysis on actively-proliferating encephalitogenic T cells to study their overall metabolic profile in comparison to resting T cells.

Healthy longevity-associated protein improves cardiac function in murine models of cardiomyopathy with preserved ejection fraction.

Aims: Aging is influenced by genetic determinants and comorbidities, among which diabetes increases the risk for heart failure with preserved ejection fraction. There is no therapy to prevent heart dysfunction in aging and diabetic individuals. In previous studies, a single administration of the longevity-associated variant (LAV) of the human BPIFB4 gene halted heart decline in older and type 2 diabetic mice.

The power of 810 nm near-infrared photobiomodulation therapy for human asthenozoospermia.

Sperm motility is a crucial factor in male fertility. Photobiomodulation (PBM) has been reported to increase sperm motility, but a consistent approach suitable for identifying standardizable protocols is lacking. We collected asthenozoospermic (n = 70) and normozoospermic (n = 20) semen.

Menopausal symptoms in breast cancer survivors on adjuvant endocrine therapy compared with those of menopausal women.

Objectives: To compare menopausal symptoms of breast cancer survivors on adjuvant endocrine therapy with those of menopausal women.

Study Design: In a retrospective nested case-control study menopausal symptoms were compared of breast cancer survivors in pre-, peri- or post-menopause at the time of diagnosis, on tamoxifen or an aromatase inhibitor, plus a gonadotrophin-releasing hormone analogue, if pre- or peri-menopausal, and age-matched control women either in the late peri-menopause, or in surgical or in physiological post-menopause on no hormone replacement therapy. Differences between women on tamoxifen and those on aromatase inhibitors were also evaluated.

Parkinson disease therapy: current strategies and future research priorities.

Parkinson disease (PD) is the fastest growing neurological disorder globally and poses substantial management challenges owing to progressive disability, emergence of levodopa-resistant symptoms, and treatment-related complications. In this Review, we examine the current state of research into PD therapies and outline future priorities for advancing our understanding and treatment of the disease. We identify two main research priorities for the coming years: first, slowing the progression of the disease through the integration of sensitive biomarkers and targeted biological therapies, and second, enhancing existing symptomatic treatments, encompassing surgical and infusion therapies, with the goal of postponing complications and improving long-term patient management.

Disentangling Neurodegeneration From Aging in Multiple Sclerosis Using Deep Learning: The Brain-Predicted Disease Duration Gap.

Background And Objectives: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS.

Combined intraocular and intravenous gene delivery for therapy of gyrate atrophy of the choroid and retina.

Gyrate atrophy of the choroid and retina (GACR) is due to ornithine aminotransferase (OAT) deficiency, which causes hyperornithinemia, leading to retinal pigment epithelium, followed by choroidal and retinal degeneration. Adeno-associated virus serotype 8 (AAV8) vector-mediated OAT (AAV8-OAT) liver gene transfer reduces ornithinemia in the Oat mouse model of GACR and improves retinal function and structure. Since OAT is expressed in various tissues including the retina, we investigated the efficacy of restoration of OAT expression in either retina or liver or both tissues on the retinal phenotype of Oat mice.

Navigating the changing landscape of BTK-targeted therapies for B cell lymphomas and chronic lymphocytic leukaemia.

The B cell receptor (BCR) signalling pathway has an integral role in the pathogenesis of many B cell malignancies, including chronic lymphocytic leukaemia, mantle cell lymphoma, diffuse large B cell lymphoma and Waldenström macroglobulinaemia. Bruton tyrosine kinase (BTK) is a key node mediating signal transduction downstream of the BCR. The advent of BTK inhibitors has revolutionized the treatment landscape of B cell malignancies, with these agents often replacing highly intensive and toxic chemoimmunotherapy regimens as the standard of care.

Hanle Effect for Lifetime Determinations in the Soft X-Ray Regime.

By exciting a series of 1s^{2} ^{1}S_{0}→1snp^{1}P_{1} transitions in heliumlike nitrogen ions with linearly polarized monochromatic soft x rays at the Elettra facility, we found a change in the angular distribution of the fluorescence sensitive to the principal quantum number n. In particular it is observed that the ratio of emission in directions parallel and perpendicular to the polarization of incident radiation increases with higher n. We find this n dependence to be a manifestation of the Hanle effect, which served as a practical tool for lifetime determinations of optical transitions since its discovery in 1924.

Longitudinal analysis of the gut microbiota during anti-PD-1 therapy reveals stable microbial features of response in melanoma patients.

Immune checkpoint inhibitors (ICIs) improve outcomes in advanced melanoma, but many patients are refractory or experience relapse. The gut microbiota modulates antitumor responses. However, inconsistent baseline predictors point to heterogeneity in responses and inadequacy of cross-sectional data.