Management of Hereditary Transthyretin Amyloidosis (ATTRv) Patients and Asymptomatic Carriers in Spain: The EMPATIa Study.

Hereditary transthyretin amyloidosis (ATTRv) is an autosomal-dominant systemic disease, where amyloid fibrils accumulate especially in the peripheral and autonomic nervous systems and in the heart. The aim of the present work was to outline the follow-up and type of management received by asymptomatic carriers (ACs) and stage 1 ATTRv patients in Spain. A cross-sectional, non-interventional study was conducted throughout seven experienced hospitals in Spain.

Carrot-Derived Rhamnogalacturonan-I Consistently Increases the Microbial Production of Health-Promoting Indole-3-Propionic Acid Ex Vivo.

Background: Using dietary interventions to steer the metabolic output of the gut microbiota towards specific health-promoting metabolites is often challenging due to interpersonal variation in treatment responses.

Methods: In this study, we combined the ex vivo SIFR (Systemic Intestinal Fermentation Research) technology with untargeted metabolite profiling to investigate the impact of carrot-derived rhamnogalacturonan-I (cRG-I) on ex vivo metabolite production by the gut microbiota of 24 human adults.

Results: The findings reveal that at a dose equivalent to 1.

Protein purification with light via a genetically encoded azobenzene side chain.

Affinity chromatography is the method of choice for the rapid purification of proteins from cell extracts or culture supernatants. Here, we present the light-responsive Azo-tag, a short peptide comprising p-(phenylazo)-L-phenylalanine (Pap), whose side chain can be switched from its trans-ground state to the metastable cis-configuration by irradiation with mild UV light. Since only trans-Pap shows strong affinity to α-cyclodextrin (α-CD), a protein exhibiting the Azo-tag selectively binds to an α-CD chromatography matrix under daylight or in the dark but elutes quickly under physiological buffer flow when illuminating the column at 355 nm.

A robust benchmark for detecting low-frequency variants in the HG002 Genome In A Bottle NIST reference material.

Somatic mosaicism is an important cause of disease, but mosaic and somatic variants are often challenging to detect because they exist in only a fraction of cells. To address the need for benchmarking subclonal variants in normal cell populations, we developed a benchmark containing mosaic variants in the Genome in a Bottle Consortium (GIAB) HG002 reference material DNA from a large batch of a normal lymphoblastoid cell line. First, we used a somatic variant caller with high coverage (300x) Illumina whole genome sequencing data from the Ashkenazi Jewish trio to detect variants in HG002 not detected in at least 5% of cells from the combined parental data.

Imaging Findings and Management Strategies for Liver Masses in Children with Predisposition Disorders: A Review by the Pediatric LI-RADS Group.

Liver masses in children with underlying systemic disease or a predisposing syndrome can be benign or malignant, ranging from focal fat to hepatocellular carcinoma (HCC). Knowledge of the underlying condition, the pathophysiologic effect on the liver, and the development of liver disease and specific liver lesions allows radiologists to guide imaging with regard to modality and frequency and give recommendations for biopsy when appropriate. In some predisposition disorders, such as Beckwith Wiedemann spectrum, familial adenomatous polyposis syndrome, and tuberous sclerosis complex, established guidelines for imaging screening exist.

Multi-Functional Descriptor Design of V-Based Double Atomic Catalysts for Room Temperature Sodium-Sulfur Batteries.

Double atomic catalysts (DACs) have emerged as a promising approach for addressing the shuttle effect and sluggish kinetics in room temperature sodium-sulfur batteries (RT-SSBs). However, identifying optimal metal combinations to meet the multiple requirements for RT-SSBs is challenging. Herein, a method for designing V-based DACs catalysts (DAC-VX, X = metal atoms) is presented by distilling descriptors through first-principle calculations and Multi-Task Learning-Sure Independence Screening and Sparsifying Operator.

Generation of chimeric antigen receptor T cells targeting p95HER2 in solid tumors.

The redirection of T lymphocytes against tumor-associated or tumor-specific antigens, using bispecific antibodies or chimeric antigen receptors (CAR), has shown therapeutic success against certain hematological malignancies. However, this strategy has not been effective against solid tumors. Here, we describe the development of CAR T cells targeting p95HER2, a tumor-specific antigen found in HER2-amplified solid tumors.

Arthroscopic Debridement After Total Knee Arthroplasty Is More Effective for Synovitis Than for Ankylosis.

Purpose: To investigate the effects of arthroscopy surgery on ankylosis and synovitis after total knee arthroplasty (TKA), with patient satisfaction as the main outcome measure.

Methods: A single surgeon's database was queried for all knee arthroscopy procedures done from 2002 to 2024 using the , and , codes for ankylosis or synovitis and Current Procedural Terminology codes 29884 and 29876. Patients were excluded if they did not have a previous TKA, had a TKA but arthroscopy was done for multiple or other indications, were <2 months from TKA, lacked medical records, or were worker's compensation cases.

Comprehensive genome analysis and variant detection at scale using DRAGEN.

Research and medical genomics require comprehensive, scalable methods for the discovery of novel disease targets, evolutionary drivers and genetic markers with clinical significance. This necessitates a framework to identify all types of variants independent of their size or location. Here we present DRAGEN, which uses multigenome mapping with pangenome references, hardware acceleration and machine learning-based variant detection to provide insights into individual genomes, with ~30 min of computation time from raw reads to variant detection.

Unravelling the intramolecular n → σ* interaction in ultra-electron deficient naphthalenediimides and their radical ions.

In this work, the role of non-covalent n → σ* intramolecular interactions in bestowing stabilization to exceptionally low-lying LUMO molecules of Naphthalenediimides (NDI) and their radical ions have been investigated utilizing different electronic structure calculation methods at the DFT level of theory and X-ray crystallography. We compared the effect of electron donating groups (EDGs) and electron-withdrawing groups (EWGs), , OMe and F, respectively, at the -positon of the phenylphosphonium groups integrated at the 2,6-positions of the NDI scaffold on the intramolecular P-O interactions and the evolving electronic effects. The natural bond orbital (NBO) analysis exhibited strong charge transfer from the imide O atoms of the NDI to the phosphorus atom of the phosphonium groups validating a donor-acceptor type of orbital interaction.

Recurrence following successful eradication of neoplasia with endoscopic mucosal resection compared with endoscopic submucosal dissection in Barrett's esophagus: a retrospective comparison.

Background: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are effective treatments for Barrett's neoplasia. However, little is known about recurrence rates following these techniques. We compared long-term neoplasia recurrence rates following EMR and ESD.

Challenges Facing Two Outbreaks of Carbapenem-Resistant : From Cefiderocol Susceptibility Testing to the Emergence of Cefiderocol-Resistant Mutants.

Carbapenem-resistant (CRAB) infections are associated with poor outcomes depending on patient's conditions, clinical severity and type of infection, and treatment is challenging given the limited therapeutic options available. The aim of this study was to describe the clinical and microbiological characteristics of two outbreaks caused by CRAB in an intensive care unit (ICU). In addition, the mechanisms of resistance detected in these strains and the treatment chosen according to the available therapeutic options were analyzed.

Dupilumab Improves Facial Pain and Reduces Rescue Treatments in Patients with CRSwNP and Recalcitrant Frontal Sinusitis.

Recalcitrant frontal sinusitis in patients with chronic rhinosinusitis and nasal polyps (CRSwNP) has a negative impact on their quality of life due to frontal pain and a high risk of sinus occlusion, thus necessitating antibiotics, systemic corticosteroids, and multiple surgeries. The aim of this study was to assess the efficacy of dupilumab in reducing frontal pain and the need for rescue treatments for recalcitrant frontal sinusitis in patients with CRSwNP. We enrolled a cohort of 10 patients with severe uncontrolled CRSwNP and concomitant recurrent frontal sinusitis associated with severe facial pain measured by MIDAS score who were treated with dupilumab 300 mg every 2 weeks and followed for at least 12 months.

New Intravesical Agents for BCG-Unresponsive High-Risk Non-Muscle Invasive Bladder Cancer.

Background: With the exception of the FDA-approved valrubicin and pembrolizumab, there are no standard second-line treaments for BCG-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC).

Objectives: To provide a systematic review of the novel intravesically administered therapeutic agents for the salvage treatment of BCG-unresponsive NMIBC.

Methods: Online search of the PubMed, EMBASE and Web of Science databases was performed.

Incidence of type 1 diabetes in Sardinian children aged 0-14 years has almost doubled in the last twenty years. On top of the world.

Aims: The primary objectives were to investigate the incidence rate (IR) of type 1 diabetes (T1D) in Sardinian children aged 0-14 years in 2019-2022 and to examine the temporal trend from 1989-1999.

Methods: Data from new-onset T1D patients aged 0-14 years who were residents of Sardinia were collected from all pediatric diabetology clinics. The overall, sex- and age specific (groups 0-4, 5-9, and 10-14 years), and calendar year IRs were calculated.

Biological basis of critical illness subclasses: from the bedside to the bench and back again.

Critical illness syndromes including sepsis, acute respiratory distress syndrome, and acute kidney injury (AKI) are associated with high in-hospital mortality and long-term adverse health outcomes among survivors. Despite advancements in care, clinical and biological heterogeneity among patients continues to hamper identification of efficacious therapies. Precision medicine offers hope by identifying patient subclasses based on clinical, laboratory, biomarker and 'omic' data and potentially facilitating better alignment of interventions.

Multiregional transcriptomics identifies congruent consensus subtypes with prognostic value beyond tumor heterogeneity of colorectal cancer.

Intra-tumor heterogeneity compromises the clinical value of transcriptomic classifications of colorectal cancer. We investigated the prognostic effect of transcriptomic heterogeneity and the potential for classifications less vulnerable to heterogeneity in a single-hospital series of 1093 tumor samples from 692 patients, including multiregional samples from 98 primary tumors and 35 primary-metastasis sets. We show that intra-tumor heterogeneity of the consensus molecular subtypes (CMS) is frequent and has poor-prognostic associations independently of tumor microenvironment markers.