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.

First-line immune-based combinations or sunitinib in favorable-risk metastatic renal cell carcinoma: a real-world retrospective comparison from the ARON-1 study.

Introduction: Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria.

Materials And Methods: This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib.

ESAIC focused guidelines for the management of the failing epidural during labour epidural analgesia.

Background: Labour epidural analgesia reportedly fails in up to 10 to 25% of cases. A joint taskforce of European Society of Anaesthesiology and Intensive Care (ESAIC) experts was created to develop this focused guideline on the management of failing epidural analgesia in a previously well functioning epidural catheter.

Design: Six clinical questions were defined using a PICO (Population/Intervention/Comparison/Outcome) strategy to conduct a systematic literature search.

Uncovering metabolic dysregulation in schizophrenia and cannabis use disorder through untargeted plasma lipidomics.

Cannabis use disorder affects up to 42% of individuals with schizophrenia, correlating with earlier onset, increased positive symptoms, and more frequent hospitalizations. This study employed an untargeted lipidomics approach to identify biomarkers in plasma samples from subjects with schizophrenia, cannabis use disorder, or both (dual diagnosis), aiming to elucidate the metabolic underpinnings of cannabis abuse and schizophrenia development. The use of liquid chromatography-high resolution mass spectrometry enabled the annotation of 119 metabolites, with the highest identification confidence level achieved for 16 compounds.

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.

Salivary oxytocin and amygdalar alterations in functional neurological disorders.

Individuals diagnosed with functional neurological disorder experience abnormal movement, gait, sensory processing or functional seizures, for which research into the pathophysiology identified psychosocial contributing factors as well as promising biomarkers. Recent pilot studies suggested that (epi-)genetic variants may act as vulnerability factors, for example, on the oxytocin pathway. This study set out to explore endogenous oxytocin hormone levels in saliva in a cohort of 59 functional neurological disorder patients and 65 healthy controls comparable in sex and age.

Effectiveness of the BNT162b2 XBB.1.5-adapted vaccine against COVID-19 hospitalization related to the JN.1 variant in Europe: a test-negative case-control study using the id.DRIVE platform.

Background: Prior studies have reported lower effectiveness of XBB.1.5-adapted vaccines against hospitalization related to the Omicron JN.

Adult height in girls with idiopathic central precocious puberty treated with triptorelin.

Objective: Idiopathic central precocious puberty (CPP) precipitates epiphyseal fusion of growth plates in long bones, leading to reduced adult stature. Gonadotropin-releasing hormone analogues (GnRHa) are the treatment of choice for idiopathic CPP, but their benefit on height gain is unclear. We aimed to elucidate the effects of GnRHa treatment on adult height in girls with idiopathic CPP.

Impact of gender on the willingness to participate in clinical trials and undergo related procedures in individuals from an Alzheimer's prevention research cohort.

Background: Although there is growing evidence of the association between gender and early diagnosis of preclinical Alzheimer's disease, little attention has been given to the enrolment ratio of men and women in clinical trials and data reporting.

Methods: This study aims to analyze gender differences in sociodemographic factors associated with the willingness to participate in clinical trials and undergo specific procedures in the context of an Alzheimer's disease prevention research cohort. 2544 cognitively unimpaired participants from the ALFA parent cohort (age 45-75 years) of the Barcelonaβeta Brain Research Center were contacted through a structured phone call to determine their willingness to participate in Alzheimer's disease clinical trials and undergo trial-related procedures (magnetic resonance imaging, lumbar puncture, positron emission tomography, and cognitive assessment).

Covered Stent Correction for Sinus Venosus Atrial Septal Defects, an Emerging Alternative to Surgical Repair: Results of an International Registry.

Background: Covered stent correction for a sinus venosus atrial septal defect (SVASD) was first performed in 2009. This innovative approach was initially viewed as experimental and was reserved for highly selected patients with unusual anatomic variants. In 2016, increasing numbers of procedures began to be performed, and in several centers, it is now offered as a standard of care option alongside surgical repair.

QTL mapping provides new insights into emamectin benzoate resistance in salmon lice, Lepeophtheirus salmonis.

Background: The salmon louse (Lepeophtheirus salmonis) is a parasite of wild and farmed salmonid fish, causing huge economic damage to the commercial farming of Atlantic salmon (Salmo salar) in the northern hemisphere. The avermectin emamectin benzoate (EMB) is widely used for salmon delousing. While resistance to EMB is widespread in Atlantic populations of L.

Plastic input and dynamics in industrial composting.

Green and biowaste, processed within large facilities into compost, is a key fertilizer for agricultural and horticultural soils. However, due to improper waste disposal of plastic, its residues often remain or even lead to the formation ofmicroplastics (1 µm - 5 mm, MiPs) in the final compost product. To better understand the processes, we first quantified 'macroplastics' (> 20 mm, MaPs) input via biowaste collection into an industrial composting plant, and, then determined MiP concentrations at five stages during the composting process (before and after shredding and screening processes), and in the water used for irrigation.

Structural Commonalities Determined by Physicochemical Principles in the Complex Polymorphism of the Amyloid State of Proteins.

Advances in solid-state nuclear magnetic resonance (ssNMR) spectroscopy and cryogenic electron microscopy (cryoEM) have revealed the polymorphic nature of the amyloid state of proteins. Given the association of amyloid with protein misfolding disorders, it is important to understand the principles underlying this polymorphism. To address this problem, we combined computational tools to predict the specific regions of the sequence forming the β-spine of amyloid fibrils with the availability of 30, 83 and 24 amyloid structures deposited in the Protein Data Bank (PDB) and Amyloid Atlas (AA) for the amyloid β (Aβ) peptide, α-synuclein (αS), and the 4R isoforms of tau, associated with Alzheimer's disease, Parkinson's disease, and various tauopathies, respectively.

Long-term follow-up of patients with a first clinical demyelinating event (clinically isolated syndrome) who received cladribine tablets in CLASSIC-MS: Findings for the ORACLE-MS cohort.

Background: CLASSIC-MS explored long-term outcomes of patients treated with cladribine tablets.

Objective: Assess long-term efficacy in patients previously enrolled in ORACLE-MS, a Phase III parent trial.

Methods: ORACLE-MS included patients with a first clinical demyelinating event (FCDE or clinically isolated syndrome) who received ⩾1 course of cladribine tablets or placebo.

Development of a natural rubber latex-based biodevice with mesenchymal stem cells as a potential treatment for skeletal muscle regeneration in gestational diabetes-induced myopathy.

Women with gestational diabetes mellitus show a high risk of developing Gestational Diabetes Induced Myopathy (GDiM). GDiM is characterized by significant pelvic floor skeletal muscle atrophy and urinary incontinence. This study aimed to develop a natural rubber latex (NRL) based biodevice with mesenchymal/stromal stem cells (MSCs) for skeletal muscle regeneration for women with GDiM.

Pharmaco-Invasive Strategy With Half-Dose Tenecteplase in Patients With STEMI: Prespecified Pooled Analysis of Patients Aged ≥75 Years in STREAM-1 and 2.

Background: In STREAM-1 (Strategic Reperfusion Early After Myocardial Infarction), excess intracranial hemorrhage occurred in patients aged ≥75 years receiving full-dose tenecteplase as part of a pharmaco-invasive strategy, whereas no further intracranial hemorrhage occurred after halving the tenecteplase dose. In STREAM-2 (Second Strategic Reperfusion Early After Myocardial Infarction), half-dose tenecteplase was an effective and safe pharmaco-invasive strategy in older patients with ST-segment-elevation myocardial infarction presenting within <3 hours, compared with primary percutaneous coronary intervention (PCI). We prespecified evaluating the efficacy and safety of a half-dose versus full-dose pharmaco-invasive strategy and compared the half-dose pharmaco-invasive strategy to primary PCI in patients aged ≥75 years.

Identification of Predictors of Shift Work Adaptation and Its Association With Immune, Hormonal and Metabolite Biomarkers.

We explored predictors of shift work adaptation and how it relates to disease risk biomarker levels. These analyses included 38 male, rotating shift workers, sampled twice at the end of a 3-week night shift and a 3-week day shift rotation. Participants collected all 24-h urine voids, wore activity sensors, and responded to questionnaires during each shift.

In Vivo Selection of S/MAR Sequences to Favour AAV Episomal Maintenance in Dividing Cells.

Adeno-associated viral (AAV) vector-mediated gene therapy has emerged as a promising alternative to liver transplantation for monogenic metabolic hepatic diseases. AAVs are non-integrative vectors that are maintained primarily as episomes in quiescent cells like adult hepatocytes. This quality, while advantageous from a safety perspective due to a decreased risk of insertional mutagenesis, becomes a disadvantage when treating dividing cells, as it inevitably leads to the loss of the therapeutic genome.

Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer's Amyloidosis.

Background/objectives: Alzheimer's disease (AD), a leading cause of dementia, lacks effective long-term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Aβ) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut.