Novel insights into taxane pharmacology: An update on drug resistance mechanisms, immunomodulation and drug delivery strategies.

Taxanes are effective in several solid tumors. Paclitaxel, the main clinically available taxane, was approved in the early nineties, for the treatment of ovarian cancer and later on, together with the analogs docetaxel and cabazitaxel, for other malignancies. By interfering with microtubule function and impairing the separation of sister cells at mitosis, taxanes act as antimitotic agents, thereby counteracting the high proliferation rate of cancer cells.

Core domain set for chronic and/or recurrent manifestations of calcium pyrophosphate deposition disease: OMERACT delphi survey to establish consensus.

Objective: To agree on important domains for the Outcome Measures in Rheumatology (OMERACT) core domain set for chronic and/or recurrent manifestations of calcium pyrophosphate deposition (CPPD) disease.

Methods: Patient research partners (PRPs) and other participants (mainly clinicians and researchers) contributed to three rounds of a consensus survey using Delphi methodology. Consensus was defined if ≥70% of both patients and other participants scored the domain as 'critically important domain to include'.

Exploring the impact and acceptability of gamified tools to address educational needs in decoding and writing skills: A pilot study.

The use of assistive technology in the field of inclusive education has expanded significantly. This exploratory study examines the impact and acceptability of two gamified digital tools in enhancing motivation and engagement, as well as supporting the acquisition of decoding and writing skills over a 12-hour intervention period. The project involves children aged 8-10 years old with special educational needs (SEN) in school and clinical settings.

First-line treatment of locally advanced cervical carcinoma: An updated systematic review and Bayesian network meta-analysis.

Introduction: Locally advanced cervical carcinoma (LACC) remains a significant global health issue, particularly in low- and middle-income countries (LMICs), where disease burden is highest. While cisplatin-based chemoradiotherapy (CTRT) has long been the cornerstone of first-line treatment, its toxicities, including nephrotoxicity and hematologic adverse events, limit its use in certain patients. Advances in systemic therapies, including immune checkpoint inhibitors and induction chemotherapy, offer new avenues for improving outcomes.

The evolving landscape of stage III unresectable non-small cell lung cancer "between lights and shadows".

Despite PACIFIC set a new milestone in the clinical management of unresectable stage III non-small cell lung cancer (NSCLC), it left some critical questions pending for clinical research: the efficacy of durvalumab in the real-world setting; the activity of less intensive regimens for frail populations; the role of targeted therapies in oncogene-addicted tumors; the selection of subsequent strategies at immunotherapy failure; the efficacy of novel and intensified treatments; the role of molecular biomarkers for patients' selection. This review aims to describe the evolving landscape of unresectable stage III NSCLC and provides an updated overview of the available evidence, analyzing lights and shadows emerging from recent clinical trials and discussing the most relevant challenges of post-PACIFIC era.

Kinematic effects of a back-assistance exoskeleton during human locomotion.

In the last years, Industry 5.0 has proposed a sustainable and resilient industry model, where the human-centric approach places human needs at the center of the production process. Wearable robots have been designed to assist users, providing support for the entire body or specific regions during task performance.

Observers translate information about other agents' higher-order goals into expectations about their forthcoming action kinematics.

Social perception relies on the ability to understand the higher-order goals that drive other people's behaviour. Under predictive coding views, this ability relies on a Bayesian-like hypothesis-testing mechanism, which translates prior higher-order information about another agent's goals into perceptual predictions of the actions with which these goals can be realised and tests these predictions against the actual behaviour. We tested this hypothesis in three preregistered experiments.

Efficacy and safety of entrectinib in children with extracranial solid or central nervous system (CNS) tumours harbouring NTRK or ROS1 fusions.

Background: Entrectinib, a central nervous system (CNS)-penetrant TRK/ROS1 inhibitor, has demonstrated clinical activity in children with NTRK1/2/3 or ROS1 fusion-positive extracranial solid and CNS tumours. We present integrated data of entrectinib in children with NTRK or ROS1 fusion-positive tumours from the STARTRK-NG, TAPISTRY, and STARTRK-2 trials.

Methods: Efficacy analyses were undertaken on TRK/ROS1 inhibitor-naïve patients aged <18 years with metastatic/locally advanced NTRK1/2/3 or ROS1 fusion-positive extracranial solid or CNS tumours who received ≥1 entrectinib dose and had ≥6 months of follow-up from enrolment.

Immunotherapy in advanced non-small cell lung cancer: What to do for the 'Invisible' patients after IPSOS trial results?

Background: Immune checkpoint inhibitors (ICIs) are currently included in the standard of care of the first-line treatment of advanced/metastatic non-small cell lung cancer (NSCLC). However, a relevant group of clinically unfit patients, including poor Performance Status, Elderly, and those with relevant comorbidities, are not represented in most pivotal clinical trials.

Methods: An expert panel meeting commentary was virtually held to point out the key issues in treating such 'invisible' patients and to review the available evidence.

MITAPIVAT METABOLICALLY REPROGRAMS HUMAN BETA-THALASSEMIC ERYTHROBLASTS, INCREASING THEIR RESPONSIVENESS TO OXIDATION.

beta-thalassemia (beta-thal) is a worldwide hereditary red cell disorder characterized by severe chronic anemia. Recently, the pyruvate kinase (PK) activator mitapivat has been shown to improve anemia and ineffective erythropoiesis in a mouse model of beta-thal and in non-transfusion dependent thalassemic patients. Here, we showed that in vitro CD34+ derived erythroblasts from beta-thal (codb039) patients are characterized by persistent expression of two PK isoforms, PKR and PKM2, when compared to healthy cells.

Genetic and reproductive strategies to prevent mitochondrial diseases.

Mitochondrial DNA (mtDNA) diseases pose unique challenges for genetic counselling and require tailored approaches to address recurrence risks and reproductive options. The intricate dynamics of mtDNA segregation and heteroplasmy shift significantly impact the chances of having affected children. In addition to natural pregnancy, oocyte donation, and adoption, IVF-based approaches can reduce the risk of disease transmission.

Nonequilibrium Relaxation Inequality on Short Timescales.

An integral relation is derived from the Fokker-Planck equation which connects the steady-state probability currents with the dynamics of relaxation on short timescales in the limit of small perturbation fields. As a consequence of this integral relation, a general lower bound on the steady-state entropy production is obtained. Two particular ensembles of perturbation fields are then considered, respectively constant gradients and density displacements, and correspondingly two different averaging-based thermodynamic bounds are derived from the integral relation.

Spin Self-Organization in an Optical Cavity Facilitated by Inhomogeneous Broadening.

We study the onset of collective spin self-organization in a thermal ensemble of driven two-level atoms confined in an optical cavity. The atoms spontaneously form a spin pattern above a critical driving strength that sets a threshold and is determined by the cavity parameters, the initial temperature, and the transition frequency of the atomic spin. Remarkably, we find that inhomogeneous Doppler broadening facilitates the onset of spin self-organization.

Black Hole Spectroscopy in Environments: Detectability Prospects.

The ringdown phase following a binary black hole coalescence is a powerful tool for measuring properties of the remnant black hole. Future gravitational wave detectors will increase the precision of these measurements and may be sensitive to the environment surrounding the black hole. This work examines how environments affect the ringdown from a binary coalescence.

Single versus the Repetitive Penrose Process in a Kerr Black Hole.

Extracting the rotational energy from a Kerr black hole (BH) is one of the crucial topics in relativistic astrophysics. Here, we give special attention to the Penrose ballistic process based on the fission of a massive particle μ_{0} into two particles μ_{1} and μ_{2}, occurring in the ergosphere of a Kerr BH. Bardeen et al.

Nuclear Astrophysics in the Storage Ring: Background Suppressed Simultaneous Measurement of (p,γ) and (p,n) Reactions.

We report the application of the new elimination of Rutherford elastic scattering technique for the measurement of proton-induced reaction cross sections utilizing stored ions decelerated to astrophysical energies. This approach results in a background reduction factor of about 1 order of magnitude, enabling the first measurement of a (p, n) cross section in a storage ring. Here, the reaction channels ^{124}Xe(p,n) and ^{124}Xe(p,γ) have been studied just above the neutron threshold energy.

First Determination of the Spin-Parity of Ξ_{c}(3055)^{+,0} Baryons.

The Ξ_{b}^{0(-)}→Ξ_{c}(3055)^{+(0)}(→D^{+(0)}Λ)π^{-} decay chains are observed, and the spin-parity of Ξ_{c}(3055)^{+(0)} baryons is determined for the first time. The measurement is performed using proton-proton collision data at a center-of-mass energy of sqrt[s]=13  TeV, corresponding to an integrated luminosity of 5.4  fb^{-1}, recorded by the LHCb experiment between 2016 and 2018.

Estimating the Burden of Common Mental Disorders Attributable to Lifestyle Factors: Protocol for the Global Burden of Disease Lifestyle and Mental Disorder (GLAD) Project.

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) collects and calculates risk-outcome data for modifiable lifestyle exposures (eg, dietary intake) and physical health outcomes (eg, cancers). These estimates form a critical digital resource tool, the GBD VizHub data visualization tool, for governments and policy makers to guide local, regional, and global health decisions. Despite evidence showing the contributions of lifestyle exposures to common mental disorders (CMDs), such as depression and anxiety, GBD does not currently generate these lifestyle exposure-mental disorder outcome pairings.

Baseline and 10-year change in the number of ideal cardiovascular health metrics and sudden cardiac death in the community.

Background And Aims: adherence to an ideal cardiovascular health (CVH) might contribute to lower the burden of sudden cardiac death (SCD) in the community. We aimed to examine the association between the number of ideal CVH metrics at baseline and of its change over 10 years with the risk of SCD.

Methods: the Copenhagen City Heart Study is a community based prospective cohort study.

Impact of VRE-active perioperative prophylaxis in liver transplant patients colonized by Vancomycin-Resistant Enterococci.

Background: Data regarding the effectiveness of vancomycin resistant Enterococci (VRE) active prophylaxis for preventing early post-liver transplant (LT) VRE infections in VRE-colonized patients are scarce.

Methods: One-hundred-thirty-one pre-LT VRE colonized patients who underwent liver transplantation were enrolled in a retrospective, observational, multicenter study. The incidence of early-onset VRE infections was compared between patients who received active prophylaxis for VRE and those who did not.

A minimal model for multigroup adaptive SIS epidemics.

We propose a generalization of the adaptive N-Intertwined Mean-Field Approximation (aNIMFA) model studied in Achterberg and Sensi [Nonlinear Dyn. 111, 12657-12670 (2023)] to a heterogeneous network of communities. In particular, the multigroup aNIMFA model describes the impact of both local and global disease awareness on the spread of a disease in a network.

Combining exchangeable -values.

The problem of combining -values is an old and fundamental one, and the classic assumption of independence is often violated or unverifiable in many applications. There are many well-known rules that can combine a set of arbitrarily dependent -values (for the same hypothesis) into a single -value. We show that essentially all these existing rules can be strictly improved when the -values are exchangeable, or when external randomization is allowed (or both).

Clinical aspects and recent advances in fungal diseases impacting human health.

Fungal diseases are of growing clinical concern in human medicine as the result of changes in the epidemiology, diversity in clinical presentation, emergence of new pathogens, difficulties in diagnosis and increasing resistance to antifungals of current available classes. There is a need for high disease awareness among the public and healthcare physicians, improvement in diagnostic methods and the development of drugs from new therapeutic classes with an improved resistance profile. In this article, we will explore some key aspects of fungal diseases in humans and provide a general overview of this important topic.