Basic Science and Pathogenesis.

Background: Protein metabolism and turnover can be monitored using tracer methods, notably stable isotope labeling kinetics (SILK) based on 13C-leucine incorporation. This approach has been used in Alzheimer's disease, specifically analyzing the turnover in cerebrospinal fluid of biomarkers of interest, including amyloid peptides, leading to major pathophysiological insights (Nature medicine 12:856-861). This was achieved using immunoprecipitation mass spectrometry, which enables to track a small number of targets present in low concentration.

A High-Performance Electrochemical Sensor Based on Ni-Pt Bimetallic Nanoparticles doped Metal Organic Framework ZIF-8 for The Detection of Dopamine.

In this paper, microporous Zn-based zeolitic imidazolate framework with the sodalite cage structure (SOD-ZIF-8) was synthesized by the solvothermal method. Powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and N2 adsorption were employed to characterize the synthesized material. An ultra-sensitive electrochemical sensor based on highly dispersed bimetallic Ni-Pt nanoparticles immobilized on zeolitic metal-organic framework ZIF-8 for dopamine quantification is introduced for the first time.

The METACER national cohort study of brain metastases in gastrointestinal cancers prospectively establishes prognostic factors.

Purpose: Availability data are scarce and primarily retrospective in patients with brain metastasis (BM) from gastrointestinal (GI) cancers. The objective of this cohort was to determine prognostic factors for survival outcomes in patients with BM from GI cancers.

Methods: METACER is a national multicentric prospective cohort study which included patients with BM diagnosis during a histologically proven digestive cancer follow-up between 2010 and 2014.

E4F1 coordinates pyruvate metabolism and the activity of the elongator complex to ensure translation fidelity during brain development.

Pyruvate metabolism defects lead to severe neuropathies such as the Leigh syndrome (LS) but the molecular mechanisms underlying neuronal cell death remain poorly understood. Here, we unravel a connection between pyruvate metabolism and the regulation of the epitranscriptome that plays an essential role during brain development. Using genetically engineered mouse model and primary neuronal cells, we identify the transcription factor E4F1 as a key coordinator of AcetylCoenzyme A (AcCoA) production by the pyruvate dehydrogenase complex (PDC) and its utilization as an essential co-factor by the Elongator complex to acetylate tRNAs at the wobble position uridine 34 (U).

EGLN1 mutations in Cis can induce congenital erythrocytosis with thromboses by increasing protein instability.

Hereditary congenital erythrocytosis results from constitutive activation of the hypoxia pathway. This pathway is controlled by regulation of the α isoforms of the hypoxia-inducible factor α/β heterodimer, notably via hydroxylation by prolyl hydroxylase domain 2 (PHD2). Mutations affecting PHD2 are involved in Type 3 erythrocytosis.

Intractable conflicts over end-of-life decisions: A descriptive and ethical analysis of French case-law.

Context: In European and Anglo-Saxon countries, life-sustaining treatment (LST) limitation decisions precede more than 80% of ICU deaths. However, there is now increasing evidence of disagreement and conflict between clinical teams and family members over LST limitation decisions. In some cases, these conflicts are brought to the courts.

Ampullary composite gangliocytoma/neuroma and neuroendocrine tumor management.

Ampullary composite gangliocytoma/neuroma and neuroendocrine tumor (CoGNET), previously called ampullary gangliocytic paragangliomas (GP) are a rare entity, with only few reported cases in the literature. This is a multicentric retrospective cohort of patients treated with endoscopy or surgery for ampullary CoGNET. A literature review of ampullary CoGNET was also performed.

Sarcomas developed in patients with Lynch Syndrome are enriched in pleomorphic soft-tissue sarcomas and are sensitive to immunotherapy.

Background: Sarcomas do not belong to the Lynch Syndrome (LS)-tumour spectrum. A growing body literature has reported sarcomas in patients with LS. Clinical and tumour characteristics of these patients remain unknown.

X*Y females exhibit steeper reproductive senescence in the African pygmy mouse.

A wave of studies has recently emphasized the influence of sex chromosomes on both lifespan and actuarial senescence patterns across vertebrates and invertebrates. Basically, the heterogametic sex (XY males in XX/XY systems or ZW females in ZW/ZZ systems) typically displays a lower lifespan and a steeper rate of actuarial senescence than the homogametic sex. However, whether these effects extend to the senescence patterns of other phenotypic traits or physiological functions is yet to be determined.

Transjugular Intrahepatic Portosystemic Shunt (TIPS): A Bridge to Bariatric Surgery in Morbidly Obese Patients with Cirrhosis and Clinically Significant Portal Hypertension.

Background: In cirrhotic patients, portal hypertension increases mortality after surgery. We evaluated the impact of pre-operative transjugular intrahepatic portosystemic shunt (TIPS) on the outcomes of bariatric surgery in cirrhosis.

Methods: Multicentric retrospective cohort.

A new type III effector from Bradyrhizobium sp. DOA9 encoding a putative SUMO-protease blocks nodulation in Arachis hypogaea L.

Effector proteins secreted via the type III secretion system (T3SS) of nitrogen-fixing rhizobia are key determinants of symbiotic compatibility in legumes. Previous report revealed that the T3SS of Bradyrhizobium sp. DOA9 plays negative effects on Arachis hypogaea symbiosis.

The histamine analogue clobenpropit modulates IRF7 phosphorylation and interferon production by targeting CXCR4 in systemic lupus erythematosus models.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an overactive immune response, particularly involving excessive production of type I interferons. This overproduction is driven by the phosphorylation of IRF7, a crucial factor in interferon gene activation. Current treatments for SLE are often not very effective and can have serious side effects.

Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer's disease and behavioral-variant frontotemporal dementia.

Introduction: The differentiation between Alzheimer's disease (AD) and behavioral-variant frontotemporal dementia (bvFTD) can be complicated in the initial phase by shared symptoms and pathophysiological traits. Nevertheless, advancements in understanding AD's diverse pathobiology suggest the potential for establishing blood-based methods for differential diagnosis.

Methods: We devised a novel assay combining immunoprecipitation and mass spectrometry (IP-MS) to quantify Amyloid-beta (Aβ) peptides in plasma.

A quantitative benchmark of neural network feature selection methods for detecting nonlinear signals.

Classification and regression problems can be challenging when the relevant input features are diluted in noisy datasets, in particular when the sample size is limited. Traditional Feature Selection (FS) methods address this issue by relying on some assumptions such as the linear or additive relationship between features. Recently, a proliferation of Deep Learning (DL) models has emerged to tackle both FS and prediction at the same time, allowing non-linear modeling of the selected features.

Nanopore Sequencing as a Cutting-Edge Technology for Medulloblastoma Classification.

Background: Medulloblastoma (MB) is one of the most prevalent embryonal malignant brain tumors. Current classification organizes these tumors into four molecular subgroups (WNT, SHH, Group 3, and Group 4 MB). Recently, a comprehensive classification has been established, identifying numerous subtypes, some of which exhibit a poor prognosis.

Feasibility and safety of ultra-low volume ventilation (≤ 3 ml/kg) combined with extra corporeal carbon dioxide removal (ECCOR) in acute respiratory failure patients.

Background: Ultra-protective ventilation is the combination of low airway pressures and tidal volume (Vt) combined with extra corporeal carbon dioxide removal (ECCOR). A recent large study showed no benefit of ultra-protective ventilation compared to standard ventilation in ARDS (Acute Respiratory Distress Syndrome) patients. However, the reduction in Vt failed to achieve the objective of less than or equal to 3 ml/kg predicted body weight (PBW).

The endoplasmic reticulum as a cradle for virus and extracellular vesicle secretion.

Extracellular vesicles (EVs) are small membranous carriers of protein, lipid, and nucleic acid cargoes and play a key role in intercellular communication. Recent work has revealed the previously under-recognized participation of endoplasmic reticulum (ER)-associated proteins (ERAPs) during EV secretion, using pathways reminiscent of viral replication and secretion. Here, we present highlights of the literature involving ER/ERAPs in EV biogenesis and propose mechanistic parallels with ERAPs exploited during viral infections.

Lactoferrin as a Versatile Agent in Nanoparticle Applications: From Therapeutics to Agriculture.

Nanoparticles (NPs) have emerged as a potent choice for various applications, from drug delivery to agricultural studies, serving as an alternative and promising methodology for future advancements. They have been widely explored in delivery systems, demonstrating immense promise and high efficiency for the delivery of numerous biomolecules such as proteins and anticancer agents, either solely or modified with other compounds to enhance their capabilities. In addition, the utilization of NPs extends to antimicrobial studies, where they are used to develop novel antibacterial, antifungal, and antiviral formulations with advanced characteristics.

Comprehensive mapping of genetic variation at Epromoters reveals pleiotropic association with multiple disease traits.

There is growing evidence that a wide range of human diseases and physiological traits are influenced by genetic variation of cis-regulatory elements. We and others have shown that a subset of promoter elements, termed Epromoters, also function as enhancer regulators of distal genes. This opens a paradigm in the study of regulatory variants, as single nucleotide polymorphisms (SNPs) within Epromoters might influence the expression of several (distal) genes at the same time, which could disentangle the identification of disease-associated genes.

Prognostic value of tertiary lymphoid structures in triple-negative breast cancer: integrated analysis with the tumor microenvironment and clinicopathological features.

Background: In triple-negative breast cancer (TNBC), the most immunogenic breast cancer type, tumor-infiltrating lymphocytes (TILs) are an independent prognostic factor. Tertiary lymphoid structures (TLS) are an important TILs source, but they are not integrated in the current prognostic criteria.

Methods: In this retrospective study, TLS were assessed in hematein-eosin-saffron-stained (HES) histological sections from 397 early, chemotherapy-naive TNBC samples after primary surgical resection.

Distinct pathophysiological pathways support stratification of Sjögren's disease based on symptoms, clinical, and routine biological data.

Objective: Recently, three distinct phenotypes of Sjögren's disease (SjD) patients have been described, based on cluster analysis: B-cell active with low symptoms (BALS), high systemic activity (HSA), and low systemic activity with high symptoms (LSAHS). We aimed to assess whether these clusters were associated with distinct biomarkers and the prognostic value of IFN signature.

Methods: The ASSESS cohort is a 20-year prospective cohort of SjD patients.

On the parameterized complexity of the median and closest problems under some permutation metrics.

Genome rearrangements are events where large blocks of DNA exchange places during evolution. The analysis of these events is a promising tool for understanding evolutionary genomics, providing data for phylogenetic reconstruction based on genome rearrangement measures. Many pairwise rearrangement distances have been proposed, based on finding the minimum number of rearrangement events to transform one genome into the other, using some predefined operation.

Effect of oral nintedanib vs placebo on epistaxis in hereditary hemorrhagic telangiectasia: the EPICURE multicenter randomized double-blind trial.

Epistaxis greatly affects patients with hereditary hemorrhagic telangiectasia (HHT). Although few systemic treatment exist, nintedanib, is a good candidate thanks to its anti-angiogenic activity. Our main objective was to evaluate the efficacy of oral nintedanib on epistaxis duration in HHT patients with moderate to severe epistaxis.

Increase of niche filling with increase of host richness for plant-infecting mastreviruses.

Now that it has been realized that viruses are ubiquitous, questions have been raised on factors influencing their diversity and distribution. For phytoviruses, understanding the interplay between plant diversity and virus species richness and prevalence remains cardinal. As both the amplification and the dilution of viral species richness due to increasing host diversity have been theorized and observed, a deeper understanding of how plants and viruses interact in natural environments is needed to explore how host availability conditions viral diversity and distributions.