Muscle Loss During First-Line Chemotherapy Impairs Survival in Advanced Pancreatic Cancer Despite Adapted Physical Activity.

Background: Advanced pancreatic ductal adenocarcinoma (aPDAC) is often accompanied by significant muscle mass loss, contributing to poor prognosis. SarcAPACaP, an ancillary study of the GERCOR-APACaP phase III trial, evaluated the role of adapted physical activity (APA) in aPDAC Western patients receiving first-line chemotherapy. The study aimed to assess (1) the potential impact of computed tomography (CT)-quantified muscle mass before and during treatments on health-related quality of life (HRQoL) and overall survival (OS) and (2) the role of APA in mitigating muscle mass loss.

Emergence of Neuroendocrine Tumors in Patients Treated with Androgen Receptor Pathway Inhibitors for Metastatic Prostate Cancer: A Systematic Review and Meta-analysis.

Background And Objective: It has been shown that androgen receptor pathway inhibitor (ARPIs) treatment for metastatic castration-resistant prostate cancer (mCRPC) improves overall survival rates, but ARPIs appear to be associated with a higher frequency of treatment-related neuroendocrine prostate cancer (t-NEPC). Our aim was to quantify the proportion of prostate adenocarcinoma cases that transition to t-NEPC following ARPI therapy.

Methods: We conducted a comprehensive search of the literature on t-NEPC using databases including MEDLINE and Scopus.

Early treatment discontinuation in patients with deficient mismatch repair or microsatellite instability high metastatic colorectal cancer receiving immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 years, without a compelling rationale. A shorter treatment duration has the potential to improve patients' quality of life and reduce both toxicity and cost without compromising efficacy.

BRAF + EGFR +/- MEK inhibitors after immune checkpoint inhibitors in BRAF V600E mutated and deficient mismatch repair or microsatellite instability high metastatic colorectal cancer.

Background: Immune checkpoint inhibitors (ICIs) are the guideline endorsed first choice for patients with deficient mismatch repair or microsatellite instability high (dMMR/MSI-H) mCRC, however a significant proportion experience primary or secondary resistance. BRAF V600E mutated (BRAFm) and dMMR/MSI-H mCRC can be treated with BRAF + EGFR inhibitors but specific data on the efficacy after progression to ICIs are missing.

Methods: We collected consecutive patients with BRAFm dMMR/MSI-H mCRC treated from 2017 to 2024 with a combination of BRAFi+EGFRi+/-MEKi, after disease progression on ICIs.

Development and Validation of an Inflammatory Prognostic Index to Predict Outcomes in Advanced/Metastatic Urothelial Cancer Patients Receiving Immune Checkpoint Inhibitors.

Background: Immune checkpoint inhibitors (ICIs) improve overall survival (OS) in advanced/metastatic urothelial cancer (a/mUC) patients. Preliminary evidence suggests a prognostic role of inflammatory biomarkers in this setting. We aimed to develop a disease-specific prognostic inflammatory index for a/mUC patients on ICIs.

Fascin-1 expression is associated with neuroendocrine prostate cancer and directly suppressed by androgen receptor.

Background: Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer, arising from resistance to androgen-deprivation therapies. However, the molecular mechanisms associated with NEPC development and invasiveness are still poorly understood. Here we investigated the expression and functional significance of Fascin-1 (FSCN1), a pro-metastasis actin-bundling protein associated with poor prognosis of several cancers, in neuroendocrine differentiation of prostate cancer.

Predictive biomarkers for immune checkpoint inhibitor response in urothelial cancer.

Immune checkpoint inhibitors (ICIs) are commonly used to treat patients with advanced urothelial cancer. However, a significant number of patients do not respond to ICI, and the lack of validated predictive biomarkers impedes the success of the ICI strategy alone or in combination with chemotherapy or targeted therapies. In addition, some patients experience potentially severe adverse events with limited clinical benefit.

A simple method for poly-D-lysine coating to enhance adhesion and maturation of primary cortical neuron cultures .

Introduction: Glass coverslips are used as a substrate since Harrison's initial nerve cell culture experiments in 1910. In 1974, the first study of brain cells seeded onto polylysine (PL) coated substrate was published. Usually, neurons adhere quickly to PL coating.

Prognostic Value of the Lung Immune Prognosis Index Score for Patients Treated with Immune Checkpoint Inhibitors for Advanced or Metastatic Urinary Tract Carcinoma.

Few prognostic factors have been identified in patients with metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs). The Lung Immune Prognostic Index (LIPI) was associated with clinical outcomes for ICIs in several tumor types. We aim to assess the value of the LIPI in patients with mUC treated with ICIs.

KI and TEDA influences towards the retention of radiotoxic CHI by activated carbons.

Activated carbons (AC) are widely used within the ventilation networks of nuclear facilities to trap volatile iodine species. In this paper, the performances of various commercial activated carbons towards the trapping of γ-labelled methyl iodide were evaluated in semi-pilot scale under different R.H.

Treatments Outcomes in Histological Variants and Non-Urothelial Bladder Cancer: Results of a Multicenter Retrospective Study.

Introduction: Less than one-third of bladder cancers are non-pure urothelial carcinoma [with variant histological (VH) or non-urothelial carcinoma (non-UC)] for which no treatment guidelines are available. We aim to evaluate the efficacy of systemic treatments in VH or non-UC bladder cancers.

Materials: Multicenter retrospective analysis of patients treated for advanced or metastatic VH or non-UC bladder cancers.

Quantification and prediction of water uptake by soot deposited on ventilation filters during fire events.

Soot samples from different fuels were produced in small and pilot combustion test benches at various O concentrations, and were then characterized in terms of primary particle diameter, specific surface area and oxygen content/speciation. Water sorption measurements were then carried out for soot compacted into pellet form and in powder form, using both a gravimetric microbalance and a manometric analyser. Water adsorption isotherms are all found to be Type V, and reveal the central role of the specific surface area and the oxygen content of soot.

A comprehensive overview of promising biomarkers in stage II colorectal cancer.

Colon cancer (CC) has the highest incidence rate among gastrointestinal cancers and ranks the third in mortality among all cancers, which contributes to the current CC burden and constitutes a major public health issue. While therapeutic strategies for stage I, III, and IV CC are standardized, those for stage II CC remain debatable. The choice of adjuvant chemotherapy for patients with stage II CC depends on stage (pT4) and grade (high) of the disease, the presence of venous, perinervous, and/or lymphatic emboli, or the need of suboptimal surgery (tumor with initial occlusion or perforation needing emergency surgeries, <12 lymph nodes harvested).

New rising entities in cancer of unknown primary: Is there a real therapeutic benefit?

Cancers of Unknown Primary Site (CUP) account for approximately 1-3 % of all malignant neoplasms. It represents a heterogeneous group of malignancies without a detectable primary and is characterized by aggressive clinical behavior. Patients with CUP are presumably categorized into prognostic subsets according to their clinical and pathological characteristics.

Interplay between Orientation at Electrodes and Copper Activation of Laccase for O Reduction.

Multicopper oxidases (MCOs) catalyze the oxidation of a variety of substrates while reducing oxygen into water through four copper atoms. As an additional feature, some MCOs display an enhanced activity in solution in the presence of Cu. This is the case of the hyperthermophilic laccase HB27 from , the physiologic role of which is unknown.

De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability.

Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration.

Autism spectrum disorder recurrence, resulting of germline mosaicism for a CHD2 gene missense variant.

Germline mosaicism for a novel missense variant p.Thr645Met located in the SNF2-related ATP dependent helicase domain of CHD2 in 2 affected siblings with autism spectrum disorder.

Progressive Atrial Conduction Defects Associated With Bone Malformation Caused by a Connexin-45 Mutation.

Background: Inherited cardiac conduction disease is a rare bradyarrhythmia associated with mutations in various genes that affect action potential propagation. It is often characterized by isolated conduction disturbance of the His-Purkinje system, but it is rarely described as a syndromic form.

Objectives: The authors sought to identify the genetic defect in families with a novel bradyarrhythmia syndrome associated with bone malformation.

Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK Signaling.

Background: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified mutations in 50% of patients with CM-AVM.

De Novo Disruption of the Proteasome Regulatory Subunit PSMD12 Causes a Syndromic Neurodevelopmental Disorder.

Degradation of proteins by the ubiquitin-proteasome system (UPS) is an essential biological process in the development of eukaryotic organisms. Dysregulation of this mechanism leads to numerous human neurodegenerative or neurodevelopmental disorders. Through a multi-center collaboration, we identified six de novo genomic deletions and four de novo point mutations involving PSMD12, encoding the non-ATPase subunit PSMD12 (aka RPN5) of the 19S regulator of 26S proteasome complex, in unrelated individuals with intellectual disability, congenital malformations, ophthalmologic anomalies, feeding difficulties, deafness, and subtle dysmorphic facial features.

First in-flight synchrotron X-ray absorption and photoemission study of carbon soot nanoparticles.

Many studies have been conducted on the environmental impacts of combustion generated aerosols. Due to their complex composition and morphology, their chemical reactivity is not well understood and new developments of analysis methods are needed. We report the first demonstration of in-flight X-ray based characterizations of freshly emitted soot particles, which is of paramount importance for understanding the role of one of the main anthropogenic particulate contributors to global climate change.