Unveiling the molecular profile of a prostate carcinoma: implications for personalized medicine.

Background: Prostate cancer is the most common diagnosed tumor and the fifth cancer related death among men in Europe. Although several genetic alterations such as ERG-TMPRSS2 fusion, MYC amplification, PTEN deletion and mutations in p53 and BRCA2 genes play a key role in the pathogenesis of prostate cancer, specific gene alteration signature that could distinguish indolent from aggressive prostate cancer or may aid in patient stratification for prognosis and/or clinical management of patients with prostate cancer is still missing. Therefore, here, by a multi-omics approach we describe a prostate cancer carrying the fusion of TMPRSS2 with ERG gene and deletion of 16q chromosome arm.

Assessment of the efficacy of palliative sedation in advanced cancer patients by evaluating discomfort levels: a prospective, international, multicenter observational study.

Background: Palliative sedation involves the intentional proportional lowering of the level of consciousness in patients with life-limiting disease who are experiencing refractory suffering. The efficacy of palliative sedation needs to be monitored to ensure patient comfort. The aim of this study was to evaluate the efficacy using discomfort levels combined with sedation/agitation levels.

Identification of progressive pulmonary fibrosis: consensus findings from a modified Delphi study.

Background: We sought consensus among practising respiratory physicians on the prediction, identification and monitoring of progression in patients with fibrosing interstitial lung disease (ILD) using a modified Delphi process.

Methods: Following a literature review, statements on the prediction, identification and monitoring of progression of ILD were developed by a panel of physicians with specialist expertise. Practising respiratory physicians were sent a survey asking them to indicate their level of agreement with these statements on a binary scale or 7-point Likert scale (- 3 to 3), or to select answers from a list.

EGFR status assessment using reflex testing targeted next-generation sequencing for resected non-squamous non-small cell lung cancer.

EGFR status assessment is mandatory for adjuvant decision-making of resected stage IB-IIIA non-squamous non-small cell lung cancer (NS-NSCLC). It is questionable whether single-gene RT-PCR versus next-generation sequencing (NGS) should be used for this evaluation. Moreover, co-occurring mutations have an impact on tumor behavior and may influence future therapeutic decision-making.

Longitudinal changes in reinforcement learning during smoking cessation: a computational analysis using a probabilistic reward task.

Despite progress in smoking reduction in the past several decades, cigarette smoking remains a significant public health concern world-wide, with many smokers attempting but ultimately failing to maintain abstinence. However, little is known about how decision-making evolves in quitting smokers. Based on preregistered hypotheses and analysis plan ( https://osf.

Evolution of SARS-CoV-2 spike trimers towards optimized heparan sulfate cross-linking and inter-chain mobility.

The heparan sulfate (HS)-rich extracellular matrix (ECM) serves as an initial interaction site for the homotrimeric spike (S) protein of SARS-CoV-2 to facilitate subsequent docking to angiotensin-converting enzyme 2 (ACE2) receptors and cellular infection. More recent variants, notably Omicron, have evolved by swapping several amino acids to positively charged residues to enhance the interaction of the S-protein trimer with the negatively charged HS. However, these enhanced interactions may reduce Omicron's ability to move through the HS-rich ECM to effectively find ACE2 receptors and infect cells, raising the question of how to mechanistically explain HS-associated viral movement.

A computational deep learning investigation of animacy perception in the human brain.

The functional organization of the human object vision pathway distinguishes between animate and inanimate objects. To understand animacy perception, we explore the case of zoomorphic objects resembling animals. While the perception of these objects as animal-like seems obvious to humans, such "Animal bias" is a striking discrepancy between the human brain and deep neural networks (DNNs).

An isothermal calorimetry assay for determining steady state kinetic and Ensitrelvir inhibition parameters for SARS-CoV-2 3CL-protease.

This manuscript details the application of Isothermal Titration Calorimetry (ITC) to characterize the kinetics of 3CL, the main protease from the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), and its inhibition by Ensitrelvir, a known non-covalent inhibitor. 3CL is essential for producing the proteins necessary for viral infection, which led to the COVID-19 pandemic. The ITC-based assay provided rapid and reliable measurements of 3CL activity, allowing for the direct derivation of the kinetic enzymatic constants K and k by monitoring the thermal power required to maintain a constant temperature as the substrate is consumed.

Membrane-targeted push-pull azobenzenes for the optical modulation of membrane potential.

We introduce a family of membrane-targeted azobenzenes (MTs) with a push-pull character as a new tool for cell stimulation. These molecules are water soluble and spontaneously partition in the cell membrane. Upon light irradiation, they isomerize from trans to cis, changing the local charge distribution and thus stimulating the cell response.

Exploring the competencies of nephrology nurses: A comprehensive scoping review.

Background: Chronic kidney disease (CKD) presents a significant global health challenge. Nephrology nurses, possessing specialized competencies, play an essential role in providing high-quality care to CKD patients.

Aim: This scoping review aims to comprehensively map and synthesize literature on the competencies of nephrology nurses worldwide.

Bioengineering Innovations in Global Dental Infection Control: Applications and Adaptations in Clinical Settings.

Introduction And Aims: Dental practices pose a high risk of microbial contamination due to frequent exposure to bodily fluids like saliva and blood. Bioengineering innovations have emerged as vital tools to enhance infection control in dental settings. This review aims to assess the global applications and effectiveness of these innovations, particularly focusing on antimicrobial biomaterials, sterilization techniques, and personal protective equipment (PPE).

The management of splanchnic vein thrombosis in acute pancreatitis: a global DELPHI consensus study.

Background: Splanchnic vein thrombosis (SpVT) occurs in 17%-23 % of acute pancreatitis cases. Serious sequelae include hepatic and bowel ischaemia. However, management with therapeutic anticoagulation remains controversial due to potential bleeding risk.

Prevalence and impact of multidrug resistance in a cohort of patients admitted to emergency department for urinary tract-infections: The UTILY study, a prospective multicentre study.

Background And Aim: The aim of the present study was to evaluate the prevalence and to identify the independent predictors of multi-drug resistance among a cohort of patients admitted to emergency department for urinary tract infections (UTI), and to assess the impact of antimicrobial resistance on the clinical outcomes.

Methods: We conducted a prospective multicentre study enrolling all adult patients admitted to one of the eight emergency departments participating in the study with a microbiologically confirmed diagnosis of UTI from February 2023 to July 2024. The primary outcome evaluated was 30-day mortality; secondary outcomes included 7-day mortality and clinical response.

Comparison of the performance of myopia control in European children and adolescents with defocus incorporated multiple segments (DIMS) and highly aspherical lenslets (HAL) spectacles.

Purpose: A performance comparison of two myopia control spectacle lens designs, defocus incorporated multiple segments (DIMS) and highly aspherical lenslets (HAL), at slowing myopia progression in a European child/adolescent population. Previous research directly comparing these designs has been limited to Chinese participants and 1-year follow-up. The prevalence of myopia in European child/adolescent has been estimated at 22.

Synovitis scoring in hand osteoarthritis with ultrasonography: the performance of the Global OMERACT/EULAR Ultrasound Synovitis Score (GLOESS) is comparable to synovial thickening alone.

Background: Inflammation is increasingly recognised as a treatment target in hand osteoarthritis, and therefore correct measurement of local inflammation is essential. This study aimed to assess ultrasound scoring of synovitis and the additional value of the Global OMERACT/EULAR Ultrasound Synovitis Score (GLOESS) in hand osteoarthritis.

Methods: Data from the randomised, double-blinded Hand Osteoarthritis Prednisolone Efficacy (HOPE) trial were used.

Does tocilizumab eliminate inflammation in GCA? A cohort study on repeated temporal artery biopsies.

Background: Vascular inflammation persists in temporal artery biopsy (TAB) of giant cell arteritis (GCA) patients even after prolonged glucocorticoid (GC) therapy. We aimed to evaluate the histological impact of adding tocilizumab (TCZ) to GCs.

Methods: We enrolled all consecutive GCA patients with an inflammed TAB at diagnosis who were treated with TCZ and GCs for ≥6 months and followed from December 2017 to December 2023.

Perfusion Instability During Hyperthermic Intraperitoneal Chemotherapy: The Utility of a Problem-solving Flowchart.

Background/aim: During hyperthermic intra-peritoneal chemotherapy (HIPEC), perfusion instability (PI) is defined as the inability to maintain a proper perfusion flow without impairment of the target temperature. The management and resolution of this adverse event is underreported and poorly investigated. The study aimed to evaluate the incidence of PI during closed cytoreductive surgery (CRS)-HIPEC and how a problem-solving approach might limit the effects of this adverse event.

A Narrative Review of the Role of Immunotherapy in Metastatic Carcinoma of the Colon Harboring a BRAF Mutation.

Patients affected by metastatic carcinoma of the colon/rectum (mCRC) harboring mutations in the BRAF gene (MBRAF) respond poorly to conventional therapy and have a prognosis worse than that of patients without mutations. Despite the promising outcomes of targeted therapy utilizing multi-targeted inhibition of the mitogen-activated protein kinase (MAPK) signaling system, the therapeutic efficacy, especially for the microsatellite stable/DNA proficient mismatch repair (MSS/PMMR) subtype, remains inadequate. Patients with MBRAF/mCRC and high microsatellite instability or DNA deficient mismatch repair (MSI-H/DMMR) exhibit a substantial tumor mutation burden, suggesting a high probability of response to immunotherapy.

Exon 19 Insertions: Do Patients Respond to Tyrosine Kinase Inhibitor Treatment?

Background/aim: Epidermal growth factor receptor (EGFR) exon 19 insertions are very rare mutations and their response to tyrosine kinase inhibitors (TKIs) is uncertain. We report our experience concerning two patients, along with a literature review.

Patients And Methods: A total of 1,046 non-small-cell lung cancer tumor tissue samples were screened for EGFR mutations, using direct sequencing or next-generation sequencing.

How to Predict Recurrence After Resection of Hepatocellular Carcinoma.

Background/aim: Predictors of recurrence following resection of hepatocellular carcinoma (HCC) are not fully established. This study investigated potential risk factors and prognostic scores for this situation.

Patients And Methods: In 297 patients undergoing resection of HCC between 2000 and 2021, risk scores and potential additional risk factors for intrahepatic and extrahepatic recurrence were assessed.

Prevention of Stroke in Intracerebral Haemorrhage Survivors with Atrial Fibrillation: Rationale and Design for PRESTIGE-AF Trial.

Adequate secondary prevention in survivors of intracerebral hemorrhage (ICH) who also have atrial fibrillation (AF) is a long-standing clinical dilemma because these patients are at increased risk of recurrent ICH as well as of ischemic stroke. The efficacy and safety of oral anticoagulation, the standard preventive medication for ischemic stroke patients with AF, in ICH patients with AF are uncertain. PRESTIGE-AF is an international, phase 3b, multi-center, randomized, open, blinded end-point assessment (PROBE) clinical trial that compared the efficacy and safety of direct oral anticoagulants (DOACs) with no DOAC (either no antithrombotic treatment or any antiplatelet drug).

Preoperative and Postoperative Midline Index Ratio and Pre- and Postoperative Variation of the Hematoma Thickness Accurately Predict Surgical Recurrence of Chronic Subdural Hematomas.

Background:  Chronic subdural hematoma (cSDH) is a common pathology in daily practice of neurosurgery. Surgical management usually offers a significant clinical recovery. However, the recurrence rate is still high.

Cervical lower motor neuron syndromes: A diagnostic challenge.

Cervical lower motor neuron (LMN) syndromes, also known as brachial paresis, are characterized by muscle atrophy, weakness, and decreased reflexes in the upper limbs, devoid of sensory symptoms. These syndromes can stem from various factors, including degenerative conditions, immune-mediated diseases, infections, toxic exposures, metabolic disorders, and vascular anomalies. Clinical presentations vary, with motor neuron involvement potentially limited to the cervical area or extending to other regions, affecting prognosis.