The phenotypic spectrum of gene variants.

Introduction: Classically, Usher syndrome is characterized by the association of sensorineural hearing loss (SNHL), retinitis pigmentosa (RP) and possible vestibular dysfunction. Pathogenic bi-allelic variants in cause atypical autosomal recessive Usher syndrome, which is associated with SNHL and photoreceptors dysfunction without vestibular signs. To date, only 19 scattered descriptions have been reported.

Minimal residual disease as a target for liquid biopsy in patients with solid tumours.

Metastasis is the leading cause of cancer-related death in patients with solid tumours. Current imaging technologies are not sufficiently sensitive to detect minimal residual disease (MRD; also known as measurable or molecular residual disease) after initial surgery or chemotherapy, pointing to the need for more sensitive tests to detect remaining traces of cancer in the body. Liquid biopsy, or the analysis of tumour-derived or tumour-induced cells or cellular products in the blood or other body fluids, has opened a new diagnostic avenue to detect and monitor MRD.

Incidence and duration of human papillomavirus infections in young women: insights from a bimonthly follow-up cohort.

Background: We studied the duration of HPV detection and risk of (re-) detection for 25 HPV genotypes in a cohort of 132 women followed every eight weeks for up to two years between 2016 and 2020. Participants were between 18 and 25 years old at inclusion and half of them were vaccinated against HPV. They were recruited near the University and the STI detection centre in Montpellier, France.

Perforation of the host cell plasma membrane during invasion requires rhoptry exocytosis.

is an obligate intracellular parasite, and the delivery of effector proteins from the parasite into the host cell during invasion is critical for invasion itself and for parasite virulence. The effector proteins are released from specialized apical secretory organelles known as rhoptries. While much has been learned recently about the structure and composition of the rhoptry exocytic machinery and the function of individual rhoptry effector proteins that are exocytosed, virtually nothing is known about how the released proteins are translocated across the host cell plasma membrane.

The efficacy and safety of first-line metastatic melanoma treatment with ipilimumab + nivolumab versus nivolumab in a real-world setting.

Background: The Checkmate 067 randomized controlled trial, published in 2015, demonstrated improved progression-free survival and numerically, although not statistically, superior overall survival for ipilimumab + nivolumab. The objective of this study was to compare the efficacy and safety of nivolumab to ipilimumab + nivolumab as first-line treatment for metastatic melanoma in a real-world setting.

Methods: Patients were prospectively included in the French Melbase cohort from 2013 to 2022.

Dexamethasone is associated with reduced frequency and intensity of cytokine release syndrome compared with alternative corticosteroid regimens as premedication for glofitamab in patients with relapsed / refractory large B-cell lymphoma.

Not available.

Transmissibility and control of tuberculosis in school outbreaks: a modeling study based on four outbreaks in China.

Background: The elevated incidence of tuberculosis (TB) outbreaks in schools poses a significant challenge to prevention and control efforts in China. The commonality among most outbreaks is the failure to isolate patients at an early stage. Early isolation of TB cases is crucial for reducing the spread of TB within schools.

Effects of acclimation to long-term shading on photosynthesis in grapevines: roles of non-structural carbohydrates and stomatal conductance.

Plant acclimation to varying light environments can enhance productivity. However, limited research exists on how plants re-acclimate to sunlight after shading, despite the increasing use of transient crop shading techniques to mitigate climate change impacts. This study focused on grapevine, a species highly responsive to shade, to explore the effects of prolonged shading on photosynthetic re-acclimation of plants upon sun re-exposure.

GMP-Compliant Automated Radiolabeling and Quality Controls of [Ga]Ga-FAPI-46 for Fibroblast Activation Protein-Targeted PET Imaging in Clinical Settings.

In nuclear medicine, molecular imaging of the tumor microenvironment using radiopharmaceuticals (RPs) targeting cancer-associated fibroblasts is gaining significant interest. Among these RPs, [Ga]Ga-FAPI-46 for positron emission tomography (PET) imaging is frequently used in clinical research protocols. To ensure that the production of this RP complies with good manufacturing practices, process automation is widely adopted.

Supramalleolar osteotomy: technical note.

Supramalleolar osteotomy (SMO) aims to correct extra-articular deformities of the distal lower leg. There are several indications, the most common being varus osteoarthritis of the ankle. The rationale in this indication is to modify talocrural stress and pressure distribution by reorienting the limb axis.

Design of Experiments to Tailor the Potential of BSA-Coated Peptide Nanocomplexes for Temozolomide/p53 Gene Co-Delivery.

Gene therapy can be viewed as a promising/valuable therapeutic approach directed to cancer treatment, including glioblastoma. Concretely, the combination of gene therapy with chemotherapy could increase its therapeutic index due to a synergistic effect. In this context, bovine serum albumin (BSA)-coated temozolomide (TMZ)-peptide (WRAP5)/p53 gene-based plasmid DNA complexes were developed to promote payload co-delivery.

Stabilization and Solidification of Beryllium Waste: Influence of the Cement Composition on the Corrosion of Be Metal.

Beryllium metal is used as neutron moderator and reflector or multiplier in certain types of fission or fusion reactors. Dismantling of these reactors will produce radioactive beryllium waste, classified as low- or intermediate-level waste, that will need to be stabilised and solidified before being sent to disposal. The cementation process is under consideration because it may offer a good compromise between simplicity of implementation, cost, and quality of the final cemented wasteform.

Infertility, IL-17, IL-33 and Microbiome Cross-Talk: The Extended ARIA-MeDALL Hypothesis.

Infertility, defined as the inability to obtain pregnancy after 12 months of regular unprotected sexual intercourse, has increased in prevalence over the past decades, similarly to chronic, allergic, autoimmune, or neurodegenerative diseases. A recent ARIA-MeDALL hypothesis has proposed that all these diseases are linked to dysbiosis and to some cytokines such as interleukin 17 (IL-17) and interleukin 33 (IL-33). Our paper suggests that endometriosis, a leading cause of infertility, is linked to endometrial dysbiosis and two key cytokines, IL-17 and IL-33, which interact with intestinal dysbiosis.

Quantitative Evaluation of a Fully Automated Planning Solution for Prostate-Only and Whole-Pelvic Radiotherapy.

: To evaluate an end-to-end pipeline for normo-fractionated prostate-only and whole-pelvic cancer treatments that requires minimal human input and generates a machine-deliverable plan as an output. : In collaboration with TheraPanacea, a treatment planning pipeline was developed that takes as its input a planning CT with organs-at-risk (OARs) and planning target volume (PTV) contours, the targeted linac machine, and the prescription dose. The primary components are (i) dose prediction by a single deep learning model for both localizations and (ii) a direct aperture VMAT plan optimization that seeks to mimic the predicted dose.

Serological evidence of sarbecovirus exposure along Sunda pangolin trafficking pathways.

Background: Early in the coronavirus disease 2019 (COVID-19) pandemic, Sunda pangolins (Manis javanica) involved in the illegal wildlife trade in mainland China were identified as hosts of severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Although it is unconfirmed whether pangolins or other traded wildlife served as intermediate hosts for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the trafficking of pangolins presents a clear risk for transmission of viruses with zoonotic and epizootic potential regardless. We have investigated the origins of pangolin carcasses seized in Hong Kong and have evaluated their potential exposure to SARSr-CoVs, other coronaviruses, and paramyxoviruses, aiming to address a gap in our knowledge with regard to the role of wildlife trade in the maintenance and emergence of pathogens with zoonotic and epizootic potential.

[Between the normal and the pathological: The concept of pre-disease applied to systemic autoimmune rheumatic diseases].

The incidence of systemic autoimmune diseases is constantly rising. They are chronic diseases requiring prolonged treatment, with considerable psychosocial impact. While attention to the promising results obtained with CAR-T cells in refractory patients is justified, it seems important not to overlook the opportunities for prevention based on the identification of a pre-disease state.

Mechano-dependent sorbitol accumulation supports biomolecular condensate.

Condensed droplets of protein regulate many cellular functions, yet the physiological conditions regulating their formation remain largely unexplored. Increasing our understanding of these mechanisms is paramount, as failure to control condensate formation and dynamics can lead to many diseases. Here, we provide evidence that matrix stiffening promotes biomolecular condensation in vivo.

Predicting Response to [177Lu]Lu-PSMA Therapy in mCRPC Using Machine Learning.

Background/objectives: Radioligandtherapy (RLT) with [177Lu]Lu-PSMA has been newly introduced as a routine treatment for metastatic castration-resistant prostate cancer (mCRPC). However, not all patients can tolerate the entire therapeutic sequence, and in some cases, the treatment may prove ineffective. In real-world conditions, the aim is to distinguish between patients who fully benefit from treatment (those who respond effectively and tolerate the entire therapeutic sequence) and those who do not respond or cannot tolerate the entire sequence.

Prognostic factors for patients with cancer-associated dermatomyositis: a retrospective, multicenter cohort study of 73 patients.

Objectives: To investigate factors associated with dermatomyositis (DM) complete clinical response and overall survival with a focus on the use of immunosuppressive therapies in patients with cancer-associated DM.

Methods: We performed a multicentre, retrospective cohort study. Multivariable survival analyses used a Cox model with time-dependent covariates and adjustments with inverse probability censoring weighting.

Analysis of a shark reveals ancient, Wnt-dependent, habenular asymmetries in vertebrates.

The mode of evolution of left-right asymmetries in the vertebrate habenulae remains largely unknown. Using a transcriptomic approach, we show that in a cartilaginous fish, the catshark Scyliorhinus canicula, habenulae exhibit marked asymmetries, in both their medial and lateral components. Comparisons across vertebrates suggest that those identified in lateral habenulae reflect an ancestral gnathostome trait, partially conserved in lampreys, and independently lost in tetrapods and neopterygians.

Thyroidectomy without radioiodine in patients with low-risk thyroid cancer: 5 years of follow-up of the prospective randomised ESTIMABL2 trial.

Background: ESTIMABL2, a multicentre randomised phase 3 trial in patients with low-risk differentiated thyroid cancer (ie, pT1am or pT1b, N0 [no evidence of regional nodal involvement] or Nx [involvement of regional lymph nodes that cannot be assessed in the absence of neck dissection]), showed the non-inferiority of a follow-up strategy without radioactive iodine (I) administration compared with a postoperative I administration at 3 years post-randomisation. Here, we report a pre-specified analysis after 5 years of follow-up.

Methods: Patients treated with total thyroidectomy with or without prophylactic neck lymph node dissection, without postoperative suspicious findings on neck ultrasonography, were randomly assigned to the no-radioiodine group or to the radioiodine group (1·1 GBq-30 mCi after recombinant human thyrotropin-stimulating hormone).