Adjuvant Immunotherapy After Resected Melanoma: Survival Outcomes, Prognostic Factors and Patterns of Relapse.

Background: Anti-PD-1-based immunotherapy has improved outcomes in stage IIB to IV resected melanoma patients in clinical trials. However, little is known about real-world outcomes, prognostic factors and patterns of relapse.

Methods: This is a retrospective multicenter observational study including patients with resected melanoma treated with subsequent anti-PD-1-based adjuvant immunotherapy.

Hypoxia Compromises the Differentiation of Human Osteosarcoma Cells to CAR-R, a Hydroxylated Derivative of Lithocholic Acid and Potent Agonist of the Vitamin D Receptor.

The active metabolite of vitamin D3, calcitriol (1,25D), is widely recognised for its direct anti-proliferative and pro-differentiation effects. However, 1,25D is calcaemic, which restricts its clinical use for cancer treatment. Non-calcaemic agonists of the vitamin D receptor (VDR) could be better candidates for cancer treatment.

Platelet Mitochondrial Function and Endogenous Coenzyme Q Levels Could Be Used as Markers of Mitochondrial Health in Infertile Men: A Pilot Study.

Fertility disorders are a worldwide problem affecting 8-12% of the population, with the male factor substantially contributing to about 40-50% of all infertility cases. Mitochondria, crucial organelles for cellular viability, play a pivotal role in the processes of spermatogenesis and significantly affect sperm quality and their fertilizing ability. Mitochondrial oxidative phosphorylation (OXPHOS) dysfunction, reduced energy supply for sperm, reduced endogenous coenzyme Q (CoQ) levels, and oxidative stress are among the main factors that contribute to male infertility.

Machine learning can predict surgical indication: new clustering model from a large adult spine deformity database.

Purpose: The choice of the best management for Adult Spine Deformity (ASD) is challenging. Health-related quality of life (HRQoL), comorbidities, symptoms and spine geometry, along with surgical risk and potential residual disability play a role, and a definite algorithm for patient management is lacking. Machine learning allows to analyse complex settings more efficiently than other available statistical tools.

The Association of SLC16A1 (MCT1) Gene Polymorphism with Body Composition Changes during Weight Loss Interventions: A Randomized Trial with Sex-Dependent Analysis.

Monocarboxylates, transported by monocarboxylate transporters (MCTs), have been proposed to influence energy homeostasis and exhibit altered metabolism during exercise. This study investigated the association between the Asp490Glu (T1470A) (rs1049434) polymorphism of the SLC16A1 (MCT1) gene and changes in body composition in males and females with overweight or obesity. The 173 participants (56.

Harmonization of alcohol use data and mortality across a multi-national HIV cohort collaboration.

Background: Alcohol use is measured in diverse ways across settings. Harmonization of measures is necessary to assess effects of alcohol use in multi-cohort collaborations, such as studies of people with HIV (PWH).

Methods: Data were combined from 14 HIV cohort studies (nine European, five North American) participating in the Antiretroviral Therapy Cohort Collaboration.

Comparison of clinical variables and outcome of 2 natural equine herpesvirus myeloencephalopathy outbreaks induced by equine herpesvirus-1 A2254/N752 strain in sport horses.

Background: Understanding of equine herpesvirus-1 (EHV-1) myeloencephalopathy (EHM) is complicated by disparities among studies.

Objective: Compare clinical findings and outcome in horses involved in 2 recent EHM outbreaks.

Animals: Twenty-five and 10 horses affected during 2 natural EHM outbreaks were admitted to a veterinary teaching hospital (VTH) in 2021 and 2023, respectively.

Challenges in multinational rare disease clinical studies during COVID-19: regulatory assessment of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease.

PROPEL (ATB200-03; NCT03729362) compared the efficacy and safety of cipaglucosidase alfa plus miglustat (cipa + mig), a two-component therapy for late-onset Pompe disease (LOPD), versus alglucosidase alfa plus placebo (alg + pbo). The primary endpoint was change in 6-min walk distance (6MWD) from baseline to week 52. During PROPEL, COVID-19 interrupted some planned study visits and assessment windows, leading to delayed visits, make-up assessments for patients who missed ≥ 3 successive infusions before planned assessments at weeks 38 and 52, and some advanced visits (end-of-study/early-termination visits).

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

Demographic-Based Personalized Left Ventricular Hypertrophy Thresholds for Hypertrophic Cardiomyopathy Diagnosis.

Background: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death. Current diagnosis emphasizes the detection of left ventricular hypertrophy (LVH) using a fixed threshold of ≥15-mm maximum wall thickness (MWT). This study proposes a method that considers individual demographics to adjust LVH thresholds as an alternative to a 1-size-fits-all approach.

Detection of Hepatitis C Virus Infection from Patient Sera in Cell Culture Using Semi-Automated Image Analysis.

The study of hepatitis C virus (HCV) replication in cell culture is mainly based on cloned viral isolates requiring adaptation for efficient replication in Huh7 hepatoma cells. The analysis of wild-type (WT) isolates was enabled by the expression of SEC14L2 and by inhibitors targeting deleterious host factors. Here, we aimed to optimize cell culture models to allow infection with HCV from patient sera.

The Photocatalytic Degradation of Enrofloxacin Using an Ecofriendly Natural Iron Mineral: The Relationship Between the Degradation Routes, Generated Byproducts, and Antimicrobial Activity of Treated Solutions.

The use of ecofriendly natural minerals in photocatalytic processes to deal with the antimicrobial activity (AA) associated with antibiotics in aqueous systems is still incipient. Therefore, in this work, the capacity of a natural iron material (NIM) in photo-treatments, generating reactive species, to remove the antibiotic enrofloxacin and decrease its associated AA from water is presented. Initially, the fundamental composition, oxidation states, bandgap, point of zero charge, and morphological characteristics of the NIM were determined, denoting the NIM's feasibility for photocatalytic processes.

Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity.

A series of novel carnosic acid derivatives incorporating urea moieties at the C-20 position was synthesized and evaluated for their antiproliferative activity against the HCT116 colorectal cancer cell line. Most derivatives demonstrated enhanced antiproliferative activity compared to that of carnosic acid . The most promising derivatives were tested in other colorectal cancer cell lines (SW480, SW620, and Caco-2), melanoma (A375), and pancreatic cancer (MiaPaca-2).

Pervasiveness of Microprotein Function Amongst Small Open Reading Frames (SMORFS).

Small Open Reading Frames (smORFs) of less than 100 codons remain mostly uncharacterised. About a thousand smORFs per genome encode peptides and microproteins about 70-80 aa long, often containing recognisable protein structures and markers of translation, and these are referred to as short Coding Sequences (sCDSs). The characterisation of individual sCDSs has provided examples of smORFs' function and conservation, but we cannot infer the functionality of all other metazoan smORFs from these.

Does a Specific Sequential Combination of Antiseptic Solutions for Chemical Debridement in Periprosthetic Joint Infection Improve Outcomes vs. Solution Alone? An In Vivo Study.

: Chemical debridement is a fundamental step during the surgical treatment of both acute and chronic periprosthetic joint infection (PJI). However, there is no consensus on the optimal solution, nor is there sufficient evidence on the optimal irrigation time and combination of solutions. In an in vitro study, our group recently demonstrated that sequential combination debridement (SCD) with 3% acetic acid (AA) followed by 10% povidone iodine (PI) and 5 mM hydrogen peroxide (HO) was the best strategy for reducing bacterial load.

Real-World Data of Patients with V600E-Mutated Metastatic Colorectal Cancer Treated with Trifluridine/Tipiracil.

Background: For patients with refractory metastatic colorectal cancer (mCRC), trifluridine/tipiracil (FTD-TPI) has been associated with a significant improvement in overall survival (OS). However, data are lacking regarding the activity of FTD-TPI in patients with -mutated mCRC.

Methods: This retrospective, multicenter, international cohort included patients with -mutated mCRC treated with FTD-TPI in a real-life setting in Spain and Italy.

Association Between Oxidative Potential of Particulate Matter Collected by Personal Samplers and Systemic Inflammation Among Asthmatic and Non-Asthmatic Adults.

With the rationale that the oxidative potential of particulate matter (PM-OP) may induce oxidative stress and inflammation, we conducted the ASTHMA-FENOP study in which 44 asthmatic patients and 37 matched controls wore a personal sampler for 24 h, allowing the collection of fine and coarse PM fractions separately, to determine PM-OP by the dithiothreitol (DTT) and ascorbic acid (AA) methods. The levels of Interleukin 6 (IL-6) and the IL-6/IL-10 ratio, as indicators of pro- and anti-inflammatory statuses, were determined by calculating the mean differences (MDs), odds ratios (ORs) and p-trends adjusted for sex, age, study level and body mass index. Positive associations for IL-6 levels in the form of adjusted MDs and ORs were obtained for all PM-OP metrics, reaching statistical significance for both OP-DTT and OP-AA in the fine fraction, with adjusted OR = 5.

Reducing Dietary Protein Levels with Amino Acid Supplementation in Duroc Sire Line Finishing Pigs: Growth Performances, Carcass and Meat Traits and Nitrogen Balance in Males and Females.

Crude protein (CP) reduction and amino acid (AAs) supplementation is an interesting cost-reducing strategy for environmental compliance. The objective of this work is to study productive performances of heavy Duroc X (Landrace X Large white) male and female pigs during the finishing stage under a 2% CP reduction with crystalline AA supplementation. A total of 60 entire male and 60 female pigs (means ± standard deviations: 109 ± 4.

Oncological resection and perioperative outcomes of robotic, laparoscopic and open pancreatoduodenectomy for ampullary adenocarcinoma: a propensity score matched international multicenter cohort study.

Background: Ampullary adenocarcinoma (AAC) typically presents at an early stage due to biliary obstruction and therefore might be specifically suitable for minimally invasive pancreatoduodenectomy (MIPD). However, studies assessing MIPD specifically for AAC, including the robotic and laparoscopic approach, are limited. The aim of this study is to compare short- and long-term oncological resection and perioperative outcomes of robotic (RPD), laparoscopic (LPD) and open pancreatoduodenectomy (OPD) performed specifically for AAC.

Regular human insulins versus rapid-acting insulin analogues in children and adolescents with type 1 diabetes: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis.

Background: Type 1 diabetes is a serious, chronic disorder with an increasing incidence among children and adolescents. Glycemic control in individuals with type 1 diabetes is better managed through a basal-bolus regimen with either regular human or rapid-acting insulin analogues administered as a bolus at mealtimes. Rapid-acting insulin analogues have been hypothesized to cause optimal glycemic control and less risk of hypoglycemic episodes compared to regular human insulins.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Association of novel ERLIN2 gene variants with hereditary spastic paraplegia.

Two ERLIN2 variants (NM_007175.8:c.660delA and NM_007175.

Recovery and purification of acetic acid from extremely diluted solutions using a mixed bed ion exchange resin - technical feasibility.

A downstream process for the recovery and purification of acetic acid (AA) from an extremely diluted solution (100 mg L) also containing a mixture of contaminating inorganic salts in the form of bicarbonates, phosphates, sulfates and chlorides (DPM medium) has been developed, showing its technical feasibility. The process involves two successive steps based on the use of a mixed bed ion exchange (IEX) resin. The first step, a demineralization treatment to remove the inorganic anions that could potentially interfere with the recovery and purification of AA, involves a combined treatment of calcium precipitation, acidification with the Amberlite IR-120 resin and treatment with the Amberlite MB20 mixed bed resin.

Equine piroplasmosis in different geographical areas in France: Prevalence heterogeneity of asymptomatic carriers and low genetic diversity of Theileria equi and Babesia caballi.

Equine piroplasmosis is a worldwide tick-borne disease caused by the parasites Theileria equi sensu lato and Babesia caballi, with significant economic and sanitary consequences. These two parasites are genetically variable, with a potential impact on diagnostic accuracy. Our study aimed to evaluate the frequency of asymptomatic carriers of these parasites in France and describe the circulating genotypes.

Implementing a closed loop clinical decision support system for sustainable preoperative care.

Unnecessary preoperative testing poses a risk to patient safety, causes surgical delays, and increases healthcare costs. We describe the effects of implementing a fully EHR-integrated closed-loop clinical decision support system (CDSS) for placing automatic preprocedural test orders at two teaching hospitals in Madrid, Spain. Interrupted time series analysis was performed to evaluate changes in rates of preoperative testing after CDSS implementation, which took place from September 2019 to December 2019.