Structure activity relationship exploration of imidazo[1,2-a]pyridine series to reverse isoform selectivity and identify potent SIK1 selective inhibitors.

The salt-inducible kinase (SIK) family encompasses three isoforms, SIK1, SIK2, and SIK3, which are members of the AMP-activated protein kinase (AMPK) family of serine/threonine protein kinases. SIK inhibition has emerged as a potential therapeutic approach across multiple indications, as SIKs regulate a diverse set of physiological processes such as metabolism, bone remodeling, immune response, malignancies, skin pigmentation, and circadian rhythm. Within isoform-specific SIK inhibitors there is a need to understand the distinct role of each protein, and here we describe the first SIK1 selective inhibitors.

Global Burden of Psoriasis from 1990 to 2021 and Potential Factors: A Systematic Analysis.

Psoriasis is a chronic, immune-mediated inflammatory skin disorder affecting approximately 100 million people worldwide. This study aimed to understand the global impact of psoriasis on health and economics over the past three decades. we analyzed trends in psoriasis cases, its effects on people's quality of life, and the associated costs.

[Comparison of live-birth rate after Freeze-All strategy between PCOS and non-PCOS patients].

Objective: Polycystic Ovarian Syndrome (PCOS) is a common pathology and the most frequent cause of infertility linked to dysovulation. These patients have a high ovarian reserve and, as a result, oocyte collection is often excessive. Following medically assisted reproduction techniques, i.

Modelling challenges to unlock the power of phototrophic systems for wastewater valorization.

Phototrophic microorganisms are gaining prominence for their dual role in wastewater treatment and resource recovery, converting wastewater into valuable bioproducts. However, their effective deployment needs robust modelling frameworks capable of predicting performance across complex, real-world scenarios. Despite significant advances, key challenges hinder the development and application of such models.

Supplementary Material for Projected Global Clinical, Humanistic, and Economic Impact of Metabolic Dysfunction-Associated Steatohepatitis (MASH): The Cost of Inaction Based on Data from Nine Countries.

Background And Aim: Although the clinical burden of MASH is well known, its economic burden is less well described. We estimated MASH's economic burden in several regions of the world including the US, Germany, Spain, France, Italy, and United Kingdom (UK), Japan, Saudi Arabia, and Brazil over the next two decades.

Methods: A one-year cycle Markov model projected MASH progression from 2021 to 2040, incorporating 2020 prevalent cases and annual incident cases (2021-2040).

Real-world use of terlipressin in cirrhosis and acute kidney injury: frequent use beyond hepatorenal syndrome.

Background & Aims: Terlipressin is indicated to treat hepatorenal syndrome (HRS)-acute kidney injury (AKI), but is likely used outside this primary indication in clinical practice. We aimed to investigate real-world practice patterns on the use of terlipressin in AKI in cirrhosis.

Methods: International prospective study including patients hospitalized for decompensated cirrhosis.

Recent Insights into the Pathomechanisms of Cataract Development in Diabetic Patients.

Diabetes mellitus (DM), a prevalent metabolic disorder characterized by chronic hyperglycemia, disrupts systemic homeostasis and affects multiple tissues, including the eye lens, where cataract is a common diabetic complication. Crystallin proteins constitute the majority of the proteins in the eye lens. One of their characteristics is a long lifespan, which makes them susceptible to the accumulation of physical and chemical damage, particularly in the context of diabetes.

Blood transcriptomic analysis reveals a distinct molecular subtype of treatment resistant depression compared to non-treatment resistant depression.

Treatment-resistant depression (TRD) is a severe condition characterized by chronic and recurrent depressive symptoms, leading to significant morbidity and a considerable socio-economic impact. Genetic and biological studies suggest that TRD is associated with distinct biological characteristics. In this study, we analysed whole-transcriptome differences in 293 patients with major depressive disorder (MDD) to compare TRD (N = 150) vs non-TRD (N = 143) cases.

Facial cues of sickness reduce trustworthiness judgements, with stronger effects in women.

A behavioral defense against disease involves detecting sickness cues in others and responding adaptively, such as by avoiding social interactions. While studies have shown that humans can discriminate sickness cues above chance in faces after sickness induction, whether this discrimination affects approach-avoidance behaviors remains uncertain. Here, we investigated how facial sickness cues influence judgments of trustworthiness, serving as a proxy measure for social avoidance.

Population pharmacokinetics of intravenous ampicillin in awake and anesthetised dogs.

The aim of this study is to describe a population pharmacokinetic model for intravenous ampicillin-sulbactam in awake and anaesthetized dogs in these two treatment scenarios and to compute PK/PD cut-offs (PK/PD). This was a prospective clinical trial in 20 client-owned dogs, either treated by ampicillin after post-surgical infection, or in the context of surgical antimicrobial prophylaxis. All animals received 20mg/kg of ampicillin by slow iv route.

Genotype-phenotype correlations of COL2A1 and COL11A1 patients.

Purpose: To describe and compare the ophthalmological and extra-ophthalmological features of patients with Stickler syndrome due to pathogenic variants in COL2A1 and COL11A1.

Design: Retrospective cross-sectional study nested in a multicentric cohort study.

Methods: Records of patients with a confirmed molecular diagnosis of Stickler syndrome followed-up in the ophthalmology department at Necker-Enfants Malades and Cochin University hospitals (Paris) between 2016 and 2024 were retrospectively reviewed.

Fixed point method for PET reconstruction with learned plug-and-play regularization.

Deep learning has shown great promise for improving medical image reconstruction, including PET. However, concerns remain about the stability and robustness of these methods, especially when trained on limited data. This work aims to explore the use of the Plug-and-Play (PnP) framework in PET reconstruction to address these concerns.

Bi-allelic deleterious variants in SNAPIN, which encodes a retrograde dynein adaptor, cause a prenatal-onset neurodevelopmental disorder.

Fetal brain anomalies identified by prenatal ultrasound and/or magnetic resonance imaging represent a considerable healthcare burden with ∼1-2/1,000 live births. To identify the underlying etiology, trio prenatal exome sequencing or genome sequencing (ES/GS) has emerged as a comprehensive diagnostic paradigm with a reported diagnostic rate up to ∼32%. Here, we report five unrelated families with six affected individuals that presented neuroanatomical, craniofacial, and skeletal anomalies, all harboring rare, bi-allelic deleterious variants in SNAPIN, which encodes SNARE-associated protein.

The Arp2/3 complex maintains gut epithelial integrity under mechanical challenge.

Epithelia are specialized and selective tissue barriers that separate the organism's interior from the external environment. Among adult tissues, the gut epithelium must withstand microbial and biochemical insults but also mechanical stresses imposed by luminal contents and gastrointestinal motility. In addition, the continuous renewal of the intestinal epithelium creates tension that must be withstood by cell-cell junctions and the actomyosin cytoskeleton to preserve barrier integrity.

A potent NLRP3 inhibitor effective against both MCC950-sensitive and -resistant inflammation.

The nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome detects a broad spectrum of pathogen- and damage-associated molecular patterns (PAMPs and DAMPs), initiating inflammatory responses through caspase-1 activation and interleukin (IL)-1β/IL-18 release. Dysregulated NLRP3 activation is implicated in a range of diseases, including infectious diseases, autoinflammatory disorders, metabolic disorders, and cancer, making it an attractive therapeutic target. Here, we identify ZAP-180013 as a potent and selective small-molecule inhibitor of NLRP3 through high-throughput chemical screening.

Multi-modal image analysis for large-scale cancer tissue studies within IMMUcan.

In cancer research, multiplexed imaging allows detailed characterization of the tumor microenvironment (TME) and its link to patient prognosis. The integrated immunoprofiling of large adaptive cancer patient cohorts (IMMUcan) consortium collects multi-modal imaging data from thousands of patients with cancer to perform broad molecular and cellular spatial profiling. Here, we describe and compare two workflows for multiplexed immunofluorescence (mIF) and imaging mass cytometry (IMC) developed within IMMUcan to enable the generation of standardized data for cancer tissue analysis.

Bronchiectasis in France: data on disease characteristics in 630 patients from the European Bronchiectasis registry (EMBARC).

Background: Little is known about the characteristics of adults with bronchiectasis in France.

Methods: A descriptive cross-sectional study was conducted to describe the characteristics of adults (≥18 years) with clinically-significant bronchiectasis, diagnosed on a combination of respiratory symptoms and CT scan findings, and followed in 18 participating centers. Data on, etiology, lung function, symptoms, microbiology, treatments and quality of life were collected.

Pneumococcal colonization rates in children and adults in two developing countries: A prospective cross-sectional hospital-based study.

Introduction: Streptococcus pneumoniae is a major cause of lower respiratory infections, especially in children under 5 years old. While pneumococcal conjugate vaccines (PCVs) have reduced disease burden in many countries, data from low- and middle-income countries are still limited. The objective of this prospective, hospital-based, cross -sectional study was to measure the prevalence of pneumococcal colonization and identify circulating serotypes among children <5 years and their caregivers in Cambodia and India.

Occurrence of dMMR/MSI-H tumor during follow-up in Lynch syndrome patients treated with immune checkpoint inhibitors for metastatic digestive cancer between 2015 and 2024: a retrospective analysis of a monocentric prospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) represent a paradigm shift and a therapeutic revolution in the management of mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC), and therefore for patients with Lynch syndrome (LS). The risk of developing metachronous cancers and colorectal polyps in a population of LS patients treated with ICI(s) is not well understood.

Materials And Methods: In a single-center cohort study, we retrospectively reviewed 93 LS patients from the prospective 'ImmunoMSI' cohort, who were diagnosed with dMMR/MSI-H gastrointestinal cancer and were treated with ICIs for index metastatic gastrointestinal cancer between February 2015 and April 2024.

Optical Coherence Tomography to Better Assess Chronic Total Occlusion Percutaneous Intervention Results: The PERFECTO Study.

Background: Angioplasty of coronary chronic total occlusions (CTOs) was a breakthrough, but there is a lack of data concerning stent healing after these complex procedures.

Objectives: The main aim of the PERFECTO (Post-stEnting assessment of Reendothelialization with optical Frequency domain imaging aftEr CTO procedure) study is to assess, for the first time, stent strut apposition at the index CTO procedure and at 3-month follow-up using frequency-domain optical coherence tomography (FD-OCT).

Methods: From March 2018 to January 2020, 114 consecutive patients who underwent successful CTO recanalization >20 mm in length were prospectively included in 7 centers.

Are olfactory stimuli able to induce emotional responses in a positive context in ewes?

The perception of olfactory stimuli can influence animal emotions and behaviours, which are critical for survival and adaptation. This study explored the properties of three olfactory stimuli (orange essential oil, wolf faeces, and cadaverine) to induce emotion in sheep, in a non-stressful environment enriched with social and food resources. Contrary to expectations, wolf faeces, while repellent, did not trigger overt stress behaviours such as increased vocalisations or agitation.

Subcutaneous enucleation of the radial neck in a Monteggia-like fracture: an exceptional variant.

Introduction And Importance: Monteggia lesions combine a fracture of the ulna with dislocation of the radial head. Monteggia-like variants add a radial head fracture. We report a unique Monteggia-like injury with a bifocal radial fracture and subcutaneous enucleation of the radial neck, which does not fit existing classifications.

Trends in cell collection and apheresis practices: Insights from a cross-sectional study on the use of Spectra Optia in collection and transplant centers.

Background: This study, conducted among collection and transplant centers in France, Germany, Japan, the United Kingdom (UK), and the United States (USA), aimed to better understand current trends, challenges, and future directions in cell collection and apheresis practices, focusing on the Spectra Optia™ Apheresis System.

Methods: This cross-sectional study was conducted from July to November 2023 among facilities using the Spectra Optia™ Apheresis System, which could also be using other comparable cell collection technologies, with expertise in cell collection and therapeutics. Respondents completed an online questionnaire.

EndoChat: Grounded multimodal large language model for endoscopic surgery.

Recently, Multimodal Large Language Models (MLLMs) have demonstrated their immense potential in computer-aided diagnosis and decision-making. In the context of robotic-assisted surgery, MLLMs can serve as effective tools for surgical training and guidance. However, there is still a deficiency of MLLMs specialized for surgical scene understanding in endoscopic procedures.