Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer.

Background: The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.

Methods: In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.

Autophagy in Plant Health and Disease.

Autophagy has emerged as an essential quality control pathway in plants that selectively and rapidly removes damaged or unwanted cellular components to maintain cellular homeostasis. It can recycle a broad range of cargoes, including entire organelles, protein aggregates, and even invading microbes. It involves the de novo biogenesis of a new cellular compartment, making it intimately linked to endomembrane trafficking pathways.

Mitochondrial respiratory complex III sustains IL-10 production in activated macrophages and promotes tumor-mediated immune evasion.

The cytokine interleukin-10 (IL-10) limits the immune response and promotes resolution of acute inflammation. Because of its immunosuppressive effects, IL-10 up-regulation is a common feature of tumor progression and metastasis. Recently, IL-10 regulation has been shown to depend on mitochondria and redox-sensitive signals.

Perinatal dysfunction of innate immunity in cystic fibrosis.

In patients with cystic fibrosis (CF), repeated cycles of infection and inflammation eventually lead to fatal lung damage. Although diminished mucus clearance can be restored by highly effective CFTR modulator therapy, inflammation and infection often persist. To elucidate the role of the innate immune system in CF etiology, we investigated a CF pig model and compared these results with those for preschool children with CF.

Life satisfaction around the world: Measurement invariance of the Satisfaction With Life Scale (SWLS) across 65 nations, 40 languages, gender identities, and age groups.

The Satisfaction With Life Scale (SWLS) is a widely used self-report measure of subjective well-being, but studies of its measurement invariance across a large number of nations remain limited. Here, we utilised the Body Image in Nature (BINS) dataset-with data collected between 2020 and 2022 -to assess measurement invariance of the SWLS across 65 nations, 40 languages, gender identities, and age groups (N = 56,968). All participants completed the SWLS under largely uniform conditions.

Interpretation of Viscoelastic Hemostatic Assays in Cardiac Surgery Patients: Importance of Clinical Context.

Background: Rotational thromboelastometry (ROTEM) is widely used for point-of-care coagulation testing to reduce blood transfusions. Accurate interpretation of ROTEM data is crucial and requires substantial training. This study investigates the inter- and intrarater reliability of ROTEM interpretation among experts and compares their interpretations with a ROTEM-guided algorithm.

Regional changes in cerebral blood flow between the upright and supine posture and over 3 days of bed rest.

A reduction in cerebral blood flow (CBF) has been observed during spaceflight and bed rest. We aimed to examine the magnitude and regional heterogeneity of the decrease in CBF during bed rest compared to posture changes on Earth. Seventeen participants (age, 29 ± 9 years, 7 females) were studied in the upright and supine posture and over 3 days of bed rest.

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 .