Comparison of clinical outcomes in patients with refractory ascites treated with either TIPS, tunneled peritoneal catheter, or ascites pump.

Background: Refractory ascites (RA) remains a serious complication in patients with cirrhosis. Currently, the insertion of a TIPS is considered the standard of care in these patients. To achieve symptom control in those with TIPS contraindications, tunneled peritoneal catheters (PeCa) or ascites pumps were introduced.

Exploring the Activation of Atomically Precise [Pt(CO)(PPh)] Clusters: Mechanism and Energetics in Gas Phase and on an Inert Surface.

Atomically precise clusters such as [Pt(CO)(PPh)] ( = 1,2) (PPh is triphenylphosphine) are known as precursors for making oxidation catalysts. However, the changes occurring to the cluster upon thermal activation during the formation of the active catalyst are poorly understood. We have used a combination of hybrid mass spectrometry and surface science to map the thermal decomposition of [Pt(CO)(PPh)](NO).

Evaluation of Cereblon-Directing Warheads for the Development of Orally Bioavailable PROTACs.

PROTACs usually occupy physicochemical space outside the one defined by classical drug-like molecules, which often presents considerable challenges in their optimization and development for oral administration. We have previously reported phenyl glutarimide (PG)-based BET PROTAC SJ995973, with improved overall degradation and antiproliferative activities compared to its direct thalidomide-based analogue dBET1, but similarly poor pharmacokinetic profile. To further demonstrate the PG utility, we describe here optimization efforts that led to the discovery of an orally bioavailable BET-PROTAC SJ44236 (), and results of a comprehensive comparative study with analogues containing alternative CRBN-directing warheads.

Discovery of Laacher See eruption in speleothem record synchronizes Greenland and central European Late Glacial climate change.

To assess the impact of ongoing, historically unprecedented Arctic ice melting, precisely synchronized chronologies are indispensable for past analogs of abrupt climate change. Around 12,900 years before present (B.P.

Prior knowledge changes initial sensory processing in the human spinal cord.

Prior knowledge changes how the brain processes sensory input. Whether knowledge influences initial sensory processing upstream of the brain, in the spinal cord, is unknown. Studying electric potentials recorded invasively and noninvasively from the human spinal cord at millisecond resolution, we find that the cord generates electric potentials at 600 hertz that are modulated by prior knowledge about the time of sensory input, as early as 13 to 16 milliseconds after stimulation.

Impact of developmental temperature on neural growth, connectivity, and function.

Environmental temperature dictates the developmental pace of poikilothermic animals. In , slower development at lower temperatures results in higher brain connectivity, but the generality of such scaling across temperatures and brain regions and its impact on function are unclear. Here, we show that brain connectivity scales continuously across temperatures, in agreement with a first-principle model that postulates different metabolic constraints for the growth of the brain and the organism.

Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Antiamyloid antibody treatments modestly slow disease progression in mild dementia due to AD. Emerging evidence shows that homeostatic dysregulation of the brain immune system, especially that orchestrated by microglia, plays an important role in disease onset and progression.

Epithelial OPA1 links mitochondrial fusion to inflammatory bowel disease.

Dysregulation at the intestinal epithelial barrier is a driver of inflammatory bowel disease (IBD). However, the molecular mechanisms of barrier failure are not well understood. Here, we demonstrate dysregulated mitochondrial fusion in intestinal epithelial cells (IECs) of patients with IBD and show that impaired fusion is sufficient to drive chronic intestinal inflammation.

Merging motoneuron and postural synergies in prosthetic hand design for natural bionic interfacing.

Despite the advances in bionic reconstruction of missing limbs, the control of robotic limbs is still limited and, in most cases, not felt to be as natural by users. In this study, we introduce a control approach that combines robotic design based on postural synergies and neural decoding of synergistic behavior of spinal motoneurons. We developed a soft prosthetic hand with two degrees of actuation that realizes postures in a two-dimensional linear manifold generated by two postural synergies.

Maternal characteristics and their relation to early mother-child interaction and cognitive development in toddlers.

Early mother-infant interaction is believed to have a significant impact on the social, cognitive, and emotional development of children. These interactions are not only influenced by child and contextual factors but also by the mother's personality traits and strain. In this study, we investigated the relation between maternal factors such as personality, depressive symptoms, or experiencing of emotions, and (i) children's early cognitive development and (ii) interaction patterns in a sample of 116 mother-child dyads (mean child age = 18.

Phytochemical Profile, Acute and Subacute Toxicity of Spray-Dried Hydroethanolic Extract from Punica granatum Leaves.

This study aimed to provide a comprehensive understanding of the acute and subacute safety and phytochemical profile of pomegranate leaves, aligning with the growing interest in sustainable, plant-based therapeutics. The phytochemical composition, the acute and subacute toxicity of a spray-dried hydroethanolic extract from pomegranate leaves (SDE) were investigated using experimental animal models. Utilizing UV-visible spectrophotometry and liquid chromatography-mass spectrometry (LC-MS), a diverse array of tannins and flavonoids, totaling 38 compounds, was identified.

Tuning the electronic structure and SMSI by integrating trimetallic sites with defective ceria for the CO reduction reaction.

Heterogeneous catalysts have emerged as a potential key for closing the carbon cycle by converting carbon dioxide (CO) into value-added chemicals. In this work, we report a highly active and stable ceria (CeO)-based electronically tuned trimetallic catalyst for CO to CO conversion. A unique distribution of electron density between the defective ceria support and the trimetallic nanoparticles (of Ni, Cu, Zn) was established by creating the strong metal support interaction (SMSI) between them.

The effect of conflict on damage to medical facilities in Mariupol, Ukraine: A quasi-experimental study.

Medical facilities are civilian objects specially protected by international humanitarian law. Despite the need for systematic documentation of the effects of war on medical facilities for judiciary accountability, current methods for surveilling damage to protected civilian objects during ongoing armed conflict are insufficient. Satellite imagery damage assessment confers significant possibilities for investigating patterns of war.

Design, Synthesis, and Unprecedented Interactions of Covalent Dipeptide-Based Inhibitors of SARS-CoV-2 Main Protease and Its Variants Displaying Potent Antiviral Activity.

The main protease (M) of SARS-CoV-2 is a key drug target for the development of antiviral therapeutics. Here, we designed and synthesized a series of small-molecule peptidomimetics with various cysteine-reactive electrophiles. Several compounds were identified as potent SARS-CoV-2 M inhibitors, including compounds (IC = 0.

Maintenance treatment with trofosfamide in patients with advanced soft tissue sarcoma - a retrospective single-centre analysis.

Background: The prognosis of patients with advanced soft tissue sarcoma (STS) remains dismal. Trofosfamide (TRO) has been proposed as a well-tolerated oral maintenance therapy. This retrospective analysis aims to determine the value of this therapy.

Effectiveness and Safety of Adalimumab in Patients With Very Early-Onset Inflammatory Bowel Disease: A Retrospective Study on Behalf of the Porto Inflammatory Bowel Disease Working Group of European Society for Pediatric Gastroenterology Hepatology and Nutrition.

Background And Aims: Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset < 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking.

Disease-State Dependent Associations Between Intrinsic Brain Function and Symptoms of Fatigue, Depression, and Anxiety in Crohn's Disease.

Background: Extraintestinal symptoms (EIS) in inflammatory bowel diseases, including fatigue, depression and anxiety, are highly prevalent, but poorly understood. Alterations of brain function may contribute to EIS, but their association with disease activity is unclear. This study analyzed intrinsic neural activity (INA) of individuals with Crohn's disease (CD) in different disease states and examined the relationship between INA and EIS.

Global research trends in biological therapy for ankylosing spondylitis: A comprehensive visualization and bibliometric study (2004-2023).

Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the spine and pelvic bones. Recently, many researchers have confirmed that biological therapy is effective for AS patients, which provides a new perspective for the treatment of AS. This study aimed to evaluate the characteristics of scientific research on AS and biological therapy worldwide and investigate research hotspots and the direction of future trends.

Thermal Enhanced Electrokinetic Bacterial Transport in Porous Media.

Soil bacterial communities are crucial to various ecosystem services, with significant implications for environmental processes and human health. Delivering functional bacterial strains to target locations enhances the preferred ecological features. However, the delivery process is often constrained by limited bacterial transport through low-permeability soil.

High-Resolution OCT Reveals Age-Associated Variation in the Region Posterior to the External Limiting Membrane.

Purpose: To evaluate visibility of a sub-band posterior to the external limiting membrane (ELM) and assess its age-associated variation.

Methods: In a retrospective cross-sectional study, normal eyes were imaged using a high-resolution spectral-domain optical coherence tomography (SD-OCT) prototype (2.7-µm axial resolution).

From Lesions to Lessons: Two Decades of Filamentous Plant Pathogen Genomics.

Filamentous plant pathogens pose a severe threat to food security. Current estimates suggest up to 23% yield losses to pre- and post-harvest diseases and these losses are projected to increase due to climate change (Singh et al. 2023; Chaloner et al.

Observing Changes in Motoneuron Characteristics Following Distorted Sensorimotor Input via Blood Flow Restriction.

Disruption of the blood supply to a limb in conjunction with active movement boosts muscle growth, aids in rehabilitation, and allows controlled exploration of the sensorimotor system. Yet, the underlying neuromechanical changes have not been observed in great detail. This study aims to report the acute neuromuscular effects of temporary blood flow restriction (BFR) through behavioral changes at the level of motor units (MUs) using high-density surface electromyography on the abductor digiti minimi muscle during 20 trapezoidal and sinusoidal isometric force tracking tasks (5 pre-BFR, 5 during BFR, and 10 post-BFR).

Bio- and Chemoinformatic Approaches for Metabolomics Data Analysis.

Metabolomics data analysis includes, next to the preprocessing, several additional repetitive tasks that can however be heavily dataset dependent or experiment setup specific due to the vast heterogeneity in instrumentation, protocols, or also compounds/samples that are being measured. To address this, various toolboxes and software packages in Python or R have been and are being developed providing researchers and analysts with bioinformatic/chemoinformatic tools to create their own workflows tailored toward their specific needs. This chapter presents tools and example workflows for common tasks focusing on the functionality provided by R packages developed as part of the RforMassSpectrometry initiative.

Quality Assurance in Metabolomics and Metabolic Profiling.

Metabolic profiling (untargeted metabolomics) aims for a global unbiased analysis of metabolites in a cell or biological system. It remains a highly useful research tool used across various analytical platforms. Incremental improvements across multiple steps in the analytical process may have large consequences for the end quality of the data.