Building a modular and multi-cellular virtual twin of the synovial joint in Rheumatoid Arthritis.

Rheumatoid arthritis is a complex disease marked by joint pain, stiffness, swelling, and chronic synovitis, arising from the dysregulated interaction between synoviocytes and immune cells. Its unclear etiology makes finding a cure challenging. The concept of digital twins, used in engineering, can be applied to healthcare to improve diagnosis and treatment for complex diseases like rheumatoid arthritis.

Diverse polysaccharide production and biofilm formation abilities of clinical Klebsiella pneumoniae.

Klebsiella pneumoniae infections have become a growing threat for human health. The lack of understanding of the relationship between antibiotic resistance, mucoviscosity, and biofilm formation impedes our abilities to effectively predict K. pneumoniae infection outcomes.

Frailty assessment in geriatric trauma patients: comparing the predictive value of the full and a condensed version of the Fried frailty phenotype.

Background: Frailty is associated with multiple negative outcomes in geriatric trauma patients. Simultaneously, frailty assessment including physical measurements for weakness (grip strength) and slowness (gait speed) poses challenges in this vulnerable patient group. We aimed to compare the full 5-component Fried Frailty Phenotype (fFP) and a condensed model (cFP) without physical measurements, with regard to predicting hospital length of stay (LOS) and discharge disposition (DD).

Mantle oxidation by sulfur drives the formation of giant gold deposits in subduction zones.

Oxidation of the sub-arc mantle driven by slab-derived fluids has been hypothesized to contribute to the formation of gold deposits in magmatic arc environments that host the majority of metal resources on Earth. However, the mechanism by which the infiltration of slab-derived fluids into the mantle wedge changes its oxidation state and affects Au enrichment remains poorly understood. Here, we present the results of a numerical model that demonstrates that slab-derived fluids introduce large amounts of sulfate (S) into the overlying mantle wedge that increase its oxygen fugacity by up to 3 to 4 log units relative to the pristine mantle.

Mass Spectrometry-Based Workflow for the Identification and Quantification of Alternative and Canonical Proteins in Pancreatic Cancer Cells.

The identification of small proteins and proteins produced from unannotated open reading frames (called alternative proteins or AltProts) has changed our vision of the proteome and has attracted more and more attention from the scientific community. Despite several studies investigating particular AltProts in diseases and demonstrating their importance in such context, we are still missing data on their expression and functions in many pathologies. Among these, pancreatic ductal adenocarcinoma (PDAC) is a particularly relevant case to study alternative proteins.

Reductive Activation of Artefenomel (OZ439) by Fe(II)-Heme, Related to Its Antimalarial Activity.

The 1,2,4-trioxolane antimalarial drug, OZ439 (artefenomel), exhibits cross-resistance to artemisinins with similar survival rates of artemisinin-resistant parasites after dihydroartemisinin or OZ439 exposure, suggesting that this drug shares some mechanisms of action with artemisinins. In this way, we investigated the reductive activation of OZ439 by heme in the presence of dithionite, demonstrating the formation of covalent heme-drug adducts. However, in the presence of the biologically abundant reductant glutathione instead of dithionite, heme-drug adducts were not detected, contrary to artemisinin that efficiently alkylates heme regardless of the reductant used.

Gaps between Open Science activities and actual recognition systems: Insights from an international survey.

There are global movements aiming to promote reform of the traditional research evaluation and reward systems. However, a comprehensive picture of the existing best practices and efforts across various institutions to integrate Open Science into these frameworks remains underdeveloped and not fully known. The aim of this study was to identify perceptions and expectations of various research communities worldwide regarding how Open Science activities are (or should be) formally recognised and rewarded.

Evidence of Epigenetic Oncogenesis: A Turning Point in Cancer Research.

In cancer research, the term epigenetics was used in the 1970s in its modern sense encompassing non-genetic events modifying the chromatin state, mainly to oppose the emerging oncogene paradigm. However, starting from the establishment of this prominent concept, the importance of these epigenetic phenomena in cancer rarely led to questioning the causal role of genetic alterations. Only in the last 10 years, the accumulation of problematic data, better experimental technologies, and some ambitious models pushed the idea that epigenetics could be at least as important as genetics in early oncogenesis.

Congenital absence of vas deferens: Anatomical and embryological inputs from a series of autopsies reported in Europe throughout the 18th and 19th century.

Congenital absence of the vas deferens (CAVD) is a syndrome with a heterogeneous presentation: bilateral (CBAVD) or unilateral (CUAVD), complete or partial and associated or not with other anomalies of the male urogenital system. A turning point came in 1968 when CBAVD was associated with cystic fibrosis and its CFTR gene mutations. Genetic studies then revealed that a minority of CBAVD but a majority of CUAVD are CFTR-independent.

A new species of Neblinaphryne (Anura: Brachycephaloidea: Neblinaphrynidae) from Serra do Imeri, Amazonas state, Brazil.

The highlands of the Guiana Shield (Pantepui) in northern South America harbor a unique fauna and flora. However, this diversity remains poorly documented, as many Pantepui massifs remain little explored or unexplored, mainly because their access is very challenging. Considering amphibians, 11 genera are endemic or sub-endemic to Pantepui, and one of them, Neblinaphryne, is monospecific and was recently described from the Neblina massif, at the border between Brazil and Venezuela.

Human colonic organoids for understanding early events of familial adenomatous polyposis pathogenesis.

Patients with familial adenomatous polyposis (FAP) harbor mutations in the APC gene and will develop adenoma and early colorectal cancer. There is no validated treatment, and animal models are not sufficient to study FAP. Our aim was to investigate the early events associated with FAP using the intestinal organoid model in a single-center study using biopsies from nonadenomatous and adenomatous colonic mucosa of FAP patients and from healthy controls (HCs).

Advanced characterization of confined electrochemical interfaces in electrochemical capacitors.

The advancement of high-performance fast-charging materials has significantly propelled progress in electrochemical capacitors (ECs). Electrochemical capacitors store charges at the nanoscale electrode material-electrolyte interface, where the charge storage and transport mechanisms are mediated by factors such as nanoconfinement, local electrode structure, surface properties and non-electrostatic ion-electrode interactions. This Review offers a comprehensive exploration of probing the confined electrochemical interface using advanced characterization techniques.

A Pan-European study of the bacterial plastisphere diversity along river-to-sea continuums.

Microplastics provide a persistent substrate that can facilitate microbial transport across ecosystems. Since most marine plastic debris originates from land and reaches the ocean through rivers, the potential dispersal of freshwater bacteria into the sea represents a significant concern. To address this question, we explored the plastisphere on microplastic debris (MPs) and on pristine microplastics (pMPs) as well as the bacteria living in surrounding waters, along the river-sea continuum in nine major European rivers sampled during the 7 months of the Tara Microplastics mission.

Managing linguistic obstacles in multidisciplinary, multinational, and multilingual research projects.

Environmental challenges are rarely confined to national, disciplinary, or linguistic domains. Convergent solutions require international collaboration and equitable access to new technologies and practices. The ability of international, multidisciplinary and multilingual research teams to work effectively can be challenging.

TRPV4 stimulates colonic afferents through mucosal release of ATP and glutamate.

Background And Purpose: Abdominal pain is a leading cause of morbidity for people living with gastrointestinal disease. Whereas the transient receptor potential vanilloid 4 (TRPV4) ion channel has been implicated in the pathogenesis of abdominal pain, the relative paucity of TRPV4 expression in colon-projecting sensory neurons suggests that non-neuronal cells may contribute to TRPV4-mediated nociceptor stimulation.

Experimental Approach: Changes in murine colonic afferent activity were examined using ex vivo electrophysiology in tissues with the gut mucosa present or removed.

Immune digital twins for complex human pathologies: applications, limitations, and challenges.

Digital twins represent a key technology for precision health. Medical digital twins consist of computational models that represent the health state of individual patients over time, enabling optimal therapeutics and forecasting patient prognosis. Many health conditions involve the immune system, so it is crucial to include its key features when designing medical digital twins.

Fluopyram SDHI pesticide alters fish physiology and behaviour despite low in vitro effects on mitochondria.

Pollution from pesticides is an increasing concern for human health and biodiversity conservation. However, there is lack of knowledge about some emerging molecules such as SDHI fungicides (succinate dehydrogenase inhibitors) that are widely used but potentially highly toxic for vertebrates. Boscalid, fluopyram, and bixafen are 3 frequent SDHI molecules commonly detected in surface waters, which may pose risks to aquatic species.

Circulating tumor-reactive KIRCD8 T cells suppress anti-tumor immunity in patients with melanoma.

Effective anti-tumor immunity is driven by cytotoxic CD8 T cells with specificity for tumor antigens. However, the factors that control successful tumor rejection are not well understood. Here we identify a subpopulation of CD8 T cells that are tumor-antigen-specific and can be identified by KIR expression but paradoxically impair anti-tumor immunity in patients with melanoma.

Transcriptomics profiling of the non-small cell lung cancer microenvironment across disease stages reveals dual immune cell-type behaviors.

Background: Lung cancer is the leading cause of cancer death worldwide, with poor survival despite recent therapeutic advances. A better understanding of the complexity of the tumor microenvironment is needed to improve patients' outcome.

Methods: We applied a computational immunology approach (involving immune cell proportion estimation by deconvolution, transcription factor activity inference, pathways and immune scores estimations) in order to characterize bulk transcriptomics of 62 primary lung adenocarcinoma (LUAD) samples from patients across disease stages.

Juno Observations of Jupiter's Magnetodisk Plasma: Implications for Equilibrium and Dynamics.

The Jovian magnetodisk plays an essential role in the dynamics of the Jupiter system by coupling its various components. Here, we investigate the Juno (JADE, JEDI, and MAG) observations of the magnetodisk within 20-80 Jupiter radii ( ) in the 0-6 hr local time sector. JADE and JEDI data are combined to generate equatorial plane distributions of density, pressure, temperature, and anisotropy of electrons, protons, and heavy ions.