Oncological resection and perioperative outcomes of robotic, laparoscopic and open pancreatoduodenectomy for ampullary adenocarcinoma: a propensity score matched international multicenter cohort study.

Background: Ampullary adenocarcinoma (AAC) typically presents at an early stage due to biliary obstruction and therefore might be specifically suitable for minimally invasive pancreatoduodenectomy (MIPD). However, studies assessing MIPD specifically for AAC, including the robotic and laparoscopic approach, are limited. The aim of this study is to compare short- and long-term oncological resection and perioperative outcomes of robotic (RPD), laparoscopic (LPD) and open pancreatoduodenectomy (OPD) performed specifically for AAC.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Toolbox of Clickable Benzylguanines for Labeling of HoxB8-Derived Macrophages via SNAP-Tag and Bioorthogonal Chemistry.

Inflammation is a dynamic process which importantly involves migration of immune cells. Understanding the onset, acute phase and resolution of inflammation is greatly facilitated by their imaging. However, immune cells are sensitive, difficult to genetically manipulate and prone to changes in response to contact, hindering the application of well-established cell labeling methods.

Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial.

Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes.

Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 10 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone).

Pharmacological targeting of caspase-8/c-FLIP heterodimer enhances complex II assembly and elimination of pancreatic cancer cells.

Extrinsic apoptotic network is driven by Death Ligand (DL)-mediated activation of procaspase-8. Recently, we have developed the first-in class small molecule, FLIPinB, which specifically targets the key regulator of extrinsic apoptosis, the protein c-FLIP, in the caspase-8/c-FLIP heterodimer. We have shown that FLIPinB enhances DL-induced caspase-8 activity and apoptosis.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

PSMA-PET/CT Findings in Patients With High-Risk Biochemically Recurrent Prostate Cancer With No Metastatic Disease by Conventional Imaging.

Importance: The phase 3 randomized EMBARK trial evaluated enzalutamide with or without leuprolide in high-risk nonmetastatic hormone-sensitive prostate cancer. Eligibility relied on conventional imaging, which underdetects metastatic disease compared with prostate-specific membrane antigen-positron emission tomography (PSMA-PET).

Objective: To describe the staging information obtained by PSMA-PET/computed tomography (PSMA-PET/CT) in a patient cohort eligible for the EMBARK trial.

First-line immune-based combinations or sunitinib in favorable-risk metastatic renal cell carcinoma: a real-world retrospective comparison from the ARON-1 study.

Introduction: Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria.

Materials And Methods: This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib.

R(3780) Resonance Interpreted as the 1^{3}D_{1}-Wave Dominant State of Charmonium from Precise Measurements of the Cross Section of e^{+}e^{-}→Hadrons.

We report the precise measurements of the cross section of e^{+}e^{-}→hadrons at center-of-mass energies from 3.645 to 3.871 GeV.

A multi-omics approach to unravel the interaction between heat and drought stress in the holobiont.

The impact of combined heat and drought stress was investigated in and compared to individual stresses to reveal additive effects and interactions. A combination of plant metabolomics and root and rhizosphere bacterial metabarcoding were used to unravel effects at the plant holobiont level. Hierarchical cluster analysis of metabolomics signatures pointed out two main clusters, one including heat and combined heat and drought, and the second cluster that included the control and drought treatments.

Chemical Probes for Investigating the Endocannabinoid System.

Cannabis sativa has been used therapeutically since early civilizations, with key cannabinoids Δ-tetrahydrocannabinol (THC) 3.1 and cannabidiol characterized in the 1960s, leading to the discovery of cannabinoid receptors type 1 (CBR) and type 2 (CBR) and the endocannabinoid system (ECS) in the 1990s. The ECS, involving endogenous ligands like 2-arachidonoylglycerol (2-AG) 1.

ESAIC focused guidelines for the management of the failing epidural during labour epidural analgesia.

Background: Labour epidural analgesia reportedly fails in up to 10 to 25% of cases. A joint taskforce of European Society of Anaesthesiology and Intensive Care (ESAIC) experts was created to develop this focused guideline on the management of failing epidural analgesia in a previously well functioning epidural catheter.

Design: Six clinical questions were defined using a PICO (Population/Intervention/Comparison/Outcome) strategy to conduct a systematic literature search.

Developing Gingerol-Based Analogs against Infections.

(), a Gram-negative opportunistic pathogen, produces virulent factors and forms biofilms through a quorum sensing (QS) mechanism. Modulating QS networks is considered an effective strategy for treating infections. Particularly, the system, one of the QS networks, can be a potential target in treating patients with chronic infections.

Glyphosate binding and speciation at the water-goethite interface: A surface complexation model consistent with IR spectroscopy and MO/DFT.

Binding of glyphosate (PMG) to metal (hydr)oxides controls its availability and mobility in natural waters and soils, and these minerals are often suggested for the removal of PMG from wastewaters. However, a solid mechanistic and quantitative description of the adsorption behavior and surface speciation on these surfaces is still lacking, while it is essential for understanding PMG behavior in aquatic and terrestrial systems. This study gives new insights through advanced surface complexation modeling of new and previously published adsorption data, supplemented with MO/DFT calculations of the geometry, thermochemistry and theoretical infrared (IR) spectra of the surface complexes.

Revealing novel protein interaction partners of glyphosate in Escherichia coli.

Despite all debates about its safe use, glyphosate remains the most widely applied active ingredient in herbicide products, with renewed approval in the European Union until 2033. Non-target organisms are commonly exposed to glyphosate as a matter of its mode of application, with its broader environmental and biological impacts remaining under investigation. Glyphosate displays structural similarity to phosphoenolpyruvate (PEP), thereby competitively inhibiting the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), crucial for the synthesis of aromatic amino acids in plants, fungi, bacteria, and archaea.

Bullet characterization using Photon-Counting detector CT: A phantom study with intact bullets.

Objectives: Photon-counting detector CT (PCD-CT) is expected to substantially improve and expand CT-imaging applicability due to its intrinsic spectral capabilities, increased spatial resolution, reduced electronic noise, and improved image contrast. The current study aim is to evaluate PCD-CT efficacy in characterizing bullets based on their dimensions, shape, and material composition.

Materials And Methods: This is an observational phantom study examining 11 unfired, intact bullets of various common calibers, placed in ballistic gelatin.

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.

Effectiveness of the BNT162b2 XBB.1.5-adapted vaccine against COVID-19 hospitalization related to the JN.1 variant in Europe: a test-negative case-control study using the id.DRIVE platform.

Background: Prior studies have reported lower effectiveness of XBB.1.5-adapted vaccines against hospitalization related to the Omicron JN.

Role of amino acid substitutions on proteolytic stability of histatin 5 in the presence of secreted aspartyl proteases and salivary proteases.

Histatin 5 (Hst5) is a 24-amino-acid peptide naturally present in human saliva that has been proposed as a potential antifungal therapeutic. However, Hst5 is susceptible to degradation by secreted aspartyl proteases (Saps) produced by Candida albicans, which could limit its efficacy as a therapeutic. To better understand the role of the lysine residues of Hst5 in proteolysis by C.

Trimethylamine-N-oxide accelerates osteoporosis by PERK activation of ATF5 unfolding.

Imbalances in gut microbiota and their metabolites have been implicated in osteoporotic disorders. Trimethylamine-n-oxide (TMAO), a metabolite of L-carnitine produced by gut microorganisms and flavin-containing monooxygenase-3, is known to accelerate tissue metabolism and remodeling; however, its role in bone loss remained unexplored. This study investigates the relationship between gut microbiota dysbiosis, TMAO production, and osteoporosis development.