Clinical Phenotype and Prognosis of Asymptomatic Patients With Transthyretin Cardiac Amyloid Infiltration.

Importance: Patients with transthyretin (ATTR) cardiac amyloid infiltration are increasingly diagnosed at earlier disease stages with no heart failure (HF) symptoms and a wide range of cardiac amyloid infiltration.

Objective: To characterize the clinical phenotype and natural history of asymptomatic patients with ATTR cardiac amyloid infiltration.

Design, Setting, And Participants: This cohort study analyzed data of all patients at 12 international centers for amyloidosis from January 1, 2008, through December 31, 2023.

Ravulizumab demonstrates long-term efficacy, safety and favorable patient survival in patients with paroxysmal nocturnal hemoglobinuria.

Ravulizumab is a second-generation complement component 5 (C5) inhibitor (C5i) approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) following positive results from two pivotal trials in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH. In both trials, after the 26week primary evaluation period, all patients received ravulizumab for up to 6 years. To report ravulizumab treatment outcomes in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH treated for up to 6 years.

Effect of Lipidation on the Structure, Oligomerization, and Aggregation of Glucagon-like Peptide 1.

Lipidated analogues of glucagon-like peptide 1 (GLP-1) have gained enormous attention as long-acting peptide therapeutics for type 2 diabetes and also antiobesity treatment. Commercially available therapeutic lipidated GLP-1 analogues, semaglutide and liraglutide, have the great advantage of prolonged half-lives of hours and days instead of minutes as is the case for native GLP-1. A crucial factor in the development of novel lipidated therapeutic peptides is their physical stability, which greatly influences manufacturing and drug product development.

Layer-specific control of inhibition by NDNF interneurons.

Neuronal processing of external sensory input is shaped by internally generated top-down information. In the neocortex, top-down projections primarily target layer 1, which contains NDNF (neuron-derived neurotrophic factor)-expressing interneurons and the dendrites of pyramidal cells. Here, we investigate the hypothesis that NDNF interneurons shape cortical computations in an unconventional, layer-specific way, by exerting presynaptic inhibition on synapses in layer 1 while leaving synapses in deeper layers unaffected.

Synergistic effect of ligand-cluster structure and support in gold nanocluster catalysts for selective hydrogenation of alkynes.

In the field of nanocluster catalysis, it is crucial to understand the interplay of different parameters, such as ligands, support and pretreatment and their effect on the catalytic process. In this study, we chose the selective hydrogenation of phenylacetylene as a model reaction and employed two gold nanoclusters as catalysts, the phosphine protected Au and the thiolate protected Au, each with different binding motifs. They were supported on MgO, AlO and a hydrotalcite (HT), chosen for their different acidity.

Understanding factors that affect dislodgeable foliar residues of pyrimethanil and their dissipation: How relevant is the crop-type for human exposure?

Pesticide dislodgeable foliar residues (DFR) and their dissipation half-time (DT) after application are important parameters for exposure and risk assessment from intended reentry activities or unintended dermal contact with treated crops. To understand the impact of agronomic factors on residue level a statistical based evaluation was conducted using ten DFR studies, with pyrimethanil applied in Scala to strawberries, raspberries, peppers, apples, and grapes, 30 trials in total. Influences on initial DFR (DFR0) and DT were investigated by multivariate linear regression analysis.

Variable temocillin protein binding and pharmacokinetics in different clinical conditions: Implications for target attainment.

Aims: The beta-lactam antibiotic temocillin is increasingly used to treat extended-spectrum beta-lactamase (ESBL-producing) strains; however, its protein binding is complex. This study aims to predict unbound temocillin concentrations in various participant groups to determine its impact on the probability of target attainment (PTA) and to improve dosing recommendations.

Methods: The plasma pharmacokinetics were analysed using non-linear mixed-effects modelling.

Structure, Oligomerization, and Thermal Stability of a Recently Discovered Old Yellow Enzyme.

The Old Yellow Enzyme from Ferrovum sp. JA12 (FOYE) displays an unusual thermal stability for an enzyme isolated from a mesophilic organism. We determined the crystal structure of this enzyme and performed bioinformatic characterization to get insights into its thermal stability.

Circulating tumor DNA (ctDNA) trajectories predict survival in trifluridine/tipiracil-treated metastatic colorectal cancer patients.

Late-line treatment in metastatic colorectal cancer (mCRC) can improve prognosis. However, not every patient has a benefit and may experience severe side effects. Thus, predictive/prognostic biomarkers are urgently needed.

Low-energy electron driven reactions in 2-bromo-5-nitrothiazole.

Thiazole derivatives are biologically relevant molecules, used also in pharmaceutical applications. Herein, we report results for electron attachment to 2-bromo-5-nitrothiazole (BNT) in the gas phase. Employing two crossed electron-molecule beam experiments, we determined the efficiency curves of various fragment anions as a function of the initial electron energy between about 0 and 10 eV as well as the emission angle and kinetic energy distributions of Br- and NO2- ions formed from a resonance near 4 eV.

Urolithiasis management: An umbrella review on the efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) versus the ureteroscopic approach.

This Umbrella Review aims to gather high-quality evidence on urolithiasis outcomes and complications, comparing extracorporeal shockwave lithotripsy (ESWL), ureteroscopic lithotripsy (URSL), and retrograde intrarenal surgery (RIRS). We incorporated systematic reviews, some containing meta-analyses, into two separate reports, focusing on quantitative and qualitative results. Additionally, when data permitted, a secondary meta-analysis was conducted using final effect estimates from multiple meta-analyses.

Significant Efficiency Enhancements in Non-Y Series Acceptors by the Addition of Outer Side Chains.

Most current highly efficient organic solar cells utilize small molecules like Y6 and its derivatives as electron acceptors in the photoactive layer. In this work, a small molecule acceptor, SC8-IT4F, is developed through outer side chain engineering on the terminal thiophene of a conjugated 6,12-dihydro-dithienoindeno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (IDTT) central core. Compared to the reference molecule C8-IT4F, which lacks outer side chains, SC8-IT4F displays notable differences in molecule geometry (as shown by simulations), thermal behavior, single-crystal packing, and film morphology.

The importance of preclinical models for cholangiocarcinoma drug discovery.

Introduction: Biliary tract cancer (BTC) comprises a clinically diverse and genetically heterogeneous group of tumors along the intra- and extrahepatic biliary system (intrahepatic and extrahepatic cholangiocarcinoma) and gallbladder cancer with the common feature of a poor prognosis, despite increasing molecular knowledge of associated genetic aberrations and possible targeted therapies. Therefore, the search for even more precise and individualized therapies is ongoing and preclinical tumor models are central to the development of such new approaches.

Areas Covered: The models described in the current review include simple and advanced in vitro and in vivo models, including cell lines, 2D monolayer, spheroid and organoid cultures, 3D bioprinting, patient-derived xenografts, and more recently, machine-perfusion platform-based models of resected liver specimens.

Innovative Infrared Spectroscopic Technologies for the Prediction of Deoxynivalenol in Wheat.

Mycotoxin contamination in cereals is a global food safety concern. One of the most common mycotoxins in grains is deoxynivalenol (DON), a secondary metabolite produced by the fungi and . Exposure to DON can lead to adverse health effects in both humans and animals including vomiting, dizziness, and fever.

Neuropathology in 1984: a deadly shot into the heart of Europe.

Just 40 years ago, Europe was divided into the Eastern communist bloc, which included the Czechoslovak Socialist Republic (ČSSR) and was dominated by the now historical Soviet Union, and the Western bloc comprising democracies such as Austria. The Iron Curtain, a heavily guarded and deadly border zone, separated the two blocs and constrained, in prison style, the populations of the Eastern bloc. The present neuropathological article relates the sad fate of František Faktor, a 33 years-old Czech who was shot by ČSSR border guards when attempting to flee to Austria at the border between and .

The Feasibility of Omega-3 Supplementation Compared to Placebo in the Management of Long COVID Symptoms Among Healthcare Workers: A Randomized Controlled Trial.

Background:  COVID-19 is known to cause significant multisystem inflammatory responses, leading to symptoms beyond the acute phase of illness. These "long COVID" symptoms affect quality of life and interfere with daily activities. This pilot study looks at the feasibility, tolerability, and safety of omega-3 (docosahexaenoic acid+eicosapentaenoic acid, EPA) among healthcare workers with long COVID symptoms in New Jersey.

Review of cancer cell volatile organic compounds: their metabolism and evolution.

Cancer is ranked as the top cause of premature mortality. Volatile organic compounds (VOCs) are produced from catalytic peroxidation by reactive oxygen species (ROS) and have become a highly attractive non-invasive cancer screening approach. For future clinical applications, however, the correlation between cancer hallmarks and cancer-specific VOCs requires further study.

NR2F6 regulates stem cell hematopoiesis and myelopoiesis in mice.

Nuclear receptors regulate hematopoietic stem cells (HSCs) and peripheral immune cells in mice and humans. The nuclear orphan receptor NR2F6 (EAR-2) has been shown to control murine hematopoiesis. Still, detailed analysis of the distinct stem cell, myeloid, and lymphoid progenitors in the bone marrow in a genetic loss of function model remains pending.

Case report: Reversible splenial lesion syndrome preceding the onset of multiple sclerosis.

Background: The reversible splenial lesion syndrome is frequently associated with systemic and central nervous system infections. Whether an infection associated with the occurrence of the reversible splenial lesion syndrome could play a role in the later development of multiple sclerosis is unknown.

Methods: Case Report.

Olfactory dysfunction as potential biomarker in neurodegenerative diseases: a narrative review.

Neurodegenerative diseases represent a group of disorders characterized by progressive degeneration of neurons in the central nervous system, leading to a range of cognitive, motor, and sensory impairments. In recent years, there has been growing interest in the association between neurodegenerative diseases and olfactory dysfunction (OD). Characterized by a decline in the ability to detect or identify odors, OD has been observed in various conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS).

The modified crABCDE treatment algorithm as recommendation in extreme cold.

Trauma care prioritizes life-threatening conditions using the ABCDE algorithm based on the principle "treat first what kills first". As for catastrophic hemorrhage, a leading preventable cause of death in trauma, modifications of this algorithm are necessary in specific cases. In cold climates, life-threatening hypothermia poses additional challenges.

Current practices in prevention, screening, and treatment of diabetes in kidney transplant recipients: European survey highlights from the ERA DESCARTES Working Group.

Background: Although post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplantation, there are few data on prevention, optimal screening, and treatment strategies.

Methods: The European Renal Association's DESCARTES working group distributed a web-based survey to European transplant centres to gather information on risk assessment, screening procedures, and management practices for preventing and treating PTDM in kidney transplant recipients.

Results: Answers were obtained from 121/241 transplant centres (50%) across 15 European countries.