Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC.

Identification of the conditions and minimum requirements necessary for the release of autologous fresh CAR T-cell products under hospital exemption: a position paper from the WP-bioproduction of the UNITC consortium.

The accessibility of CAR-T cells in centralized production models faces significant challenges, primarily stemming from logistical complexities and prohibitive costs. However, European Regulation EC No. 1394/2007 introduced a pivotal provision known as the hospital exemption.

Multidimensional library for the improved identification of per- and polyfluoroalkyl substances (PFAS).

As the occurrence of human diseases and conditions increase, questions continue to arise about their linkages to chemical exposure, especially for per-and polyfluoroalkyl substances (PFAS). Currently, many chemicals of concern have limited experimental information available for their use in analytical assessments. Here, we aim to increase this knowledge by providing the scientific community with multidimensional characteristics for 175 PFAS and their resulting 281 ion types.

MAPK4 inhibits the early aberrant activation of B cells in rheumatoid arthritis by promoting the IRF4-SHIP1 signaling pathway.

The involvement of B lymphocytes in the pathogenesis of rheumatoid arthritis (RA) is well-established, with their early and aberrant activation being a crucial factor. However, the mechanisms underlying this abnormal activation in RA remain incompletely understood. In this study, we identified a significant reduction in MAPK4 expression in both RA patients and collagen-induced arthritis (CIA) mouse models, which correlates with disrupted B cell activation.

Genetic variation in IL-4 activated tissue resident macrophages determines strain-specific synergistic responses to LPS epigenetically.

How macrophages in the tissue environment integrate multiple stimuli depends on the genetic background of the host, but this is still poorly understood. We investigate IL-4 activation of male C57BL/6 and BALB/c strain specific in vivo tissue-resident macrophages (TRMs) from the peritoneal cavity. C57BL/6 TRMs are more transcriptionally responsive to IL-4 stimulation, with induced genes associated with more super enhancers, induced enhancers, and topologically associating domains (TAD) boundaries.

Effects of Electronic Cigarettes on Periodontal Health: A Systematic Review and Meta-Analysis.

Objectives: The use of electronic cigarettes "e-cigarettes," or vaping is growing in popularity, especially among adolescents and young adults. While the effects of cigarette smoking on oral health are well-established, the exact impact that e-cigarettes may have on dental tissues is still uncertain. The aim of the current review was to summarize evidence related to the effect of vaping on the periodontal health status of e-cigarette users.

Dermatofibrosarcoma protuberans arising in the lower labial mucosa: a case report and literature review.

Dermatofibrosarcoma protuberans (DFSP) is a low-grade, malignant, spindle cell tumour with an infiltrative growth pattern and a high local recurrence rate. Cases of oral DFSP are rare. This report describes a case of DFSP occurring in the labial mucosa.

Urine proteomics defines an immune checkpoint-associated nephritis signature.

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients.

Efficacy and Safety of Endovenous Microwave Ablation versus Endovenous Laser Ablation for Varicose Veins in Chronic Great Saphenous Vein Insufficiency: A Meta-Analysis.

Background: Although guidelines have established endovenous laser ablation (EVLA) as the first-line option for patients with varicose veins (VVs) in chronic Great saphenous vein (GSV) insufficiency, however, Chronic Vein Insufficiency (CVI) remains a significant healthcare burden. Endovenous microwave ablation (EMA) is a promising alternative. This review aims to analyze the Endovenous Microwave Ablation versus Endovenous Laser Ablation for Varicose Veins in Chronic Great Saphenous Vein Insufficiency METHODS: Randomized controlled trials (RCTs) and cohort studies across PubMed, Scopus, Science Direct, and the Cochrane Library up to November 11, 2024 was searched.

Arterial Stiffness and Subsequent Incidence of CKD and Kidney Function Decline in a Large Longitudinal Community Cohort: The Atherosclerosis in Communities (ARIC) Study.

Rationale & Objective: Arterial stiffness is associated with prevalent chronic kidney disease (CKD). Whether arterial stiffness is prospectively associated with incident CKD is inconclusive.

Study Design: Longitudinal cohort study.

Impella versus Non-Impella for Non-emergent High-Risk Percutaneous Coronary Intervention: Impella vs. Non-Impella for HR-PCI.

Background: The benefit of mechanical circulatory support (MCS) with Impella (Abiomed, Inc, Danvers, MA) for patients undergoing non-emergent, high-risk percutaneous coronary intervention (HR-PCI) is unclear and currently the subject of a large randomized clinical trial (RCT), PROTECT IV. While contemporary registry data from PROTECT III demonstrated improvement of outcomes with Impella when compared with historical data (PROTECT II), there is lack of direct comparison to the HR-PCI cohort that did not receive Impella support.

Methods: We retrospectively identified patients from our institution meeting PROTECT III inclusion criteria (left ventricular ejection fraction [LVEF] <35% with unprotected left main or last remaining vessel or LVEF <30% undergoing multivessel PCI), and compared this group (NonIMP) to the published outcomes data from the PROTECT III registry (IMP).

Osteonecrosis of the Humerus: Trends in Surgical Management of a Nationwide Sample From 2010 to 2021.

Introduction: The humeral head is the second most common site for osteonecrosis but its epidemiology is poorly described. This study aimed to better understand its treatment in the United States by 1) evaluating total operative procedures with rates normalized to the annual surgical volume; 2) determining trends of non-joint preserving (shoulder arthroplasty) vs. joint preserving procedures; and 3) quantifying rates of operative techniques in different aged cohorts (<50 vs.

Long Term Results of a Comparative Study of Percutaneous and Surgically Created Proximal Forearm Arteriovenous Fistulae.

Objective: This retrospective, single centre, comparative effectiveness study aimed to compare the long term outcomes of percutaneous arteriovenous fistulae (pAVF) and surgically created arteriovenous fistulae (sAVF) created in the proximal forearm for haemodialysis access.

Methods: Data were reviewed from a prospectively maintained database on patients who underwent pAVF or sAVF creation from September 2017 to September 2023. A total of 217 pAVFs (61 WavelinQ and 156 Ellipsys) and 158 sAVFs were analysed.

Parathyroid hormone levels following denosumab vs. zoledronic acid therapy for osteoporosis.

The objective of this retrospective, database study was to characterize the rate, magnitude and timeline of increases in parathyroid hormone (PTH) levels post-denosumab (DMAb) vs. zoledronic acid (ZA) injection in patients with osteoporosis and near normal baseline PTH. Included were osteoporotic females, ≥50 years, initiating treatment with 60 mg DMAb or 5 mg ZA.

TARGETING LUNG HEME IRON BY AEROSOL HEMOPEXIN ADMINSTRATION IN SICKLE CELL DISEASE PULMONARY HYPERTENSION.

Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH.

Contemporary Approach to the Diagnosis and Classification of Intestinal T-cell Lymphomas.

We provide an overview of recent advances in the diagnosis and classification of intestinal T- and NK-cell lymphomas and lymphoproliferative disorders that primarily involve the gastrointestinal (GI) tract. It should be mentioned that systemic T- and NK-cell lymphomas can present initially in the GI tract but are not the focus of this review. Here, we focus on the clinical and pathologic findings of enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, intestinal T-cell lymphoma not otherwise specified, indolent T-cell lymphoproliferative disorder of the GI tract and indolent NK-cell lymphoproliferative disorder of the GI tract (previously known as NK-cell enteropathy).

Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation.

Purpose: Proton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate (ultra-high [UHDR] vs. conventional [CONV]) and beam configuration (shoot-through [ST] vs.

Unique considerations in the assessment and management of traumatic brain injury in older adults.

The age-specific incidence of traumatic brain injury in older adults is rising in high-income countries, mainly due to an increase in the incidence of falls. The severity of traumatic brain injury in older adults can be underestimated because of a delay in the development of mass effect and symptoms of intracranial haemorrhage. Management and rehabilitation in older adults must consider comorbidities and frailty, the treatment of pre-existing disorders, the reduced potential for recovery, the likelihood of cognitive decline, and the avoidance of future falls.

Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial.

Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.

Tuberculosis and people who use drugs: why focus on this overlooked population is important and why adapted interventions are necessary.

People who use drugs show a higher incidence and prevalence of tuberculosis than people who do not use drugs in areas where Mycobacterium tuberculosis is endemic. However, this population is largely neglected in national tuberculosis programmes. Strategies for active case finding, screening, and linkage to care designed for the general population are not adapted to the needs of people who use drugs, who are stigmatised and difficult to reach.

Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection.

More than 50% of families with suspected rare monogenic diseases remain unsolved after whole-genome analysis by short-read sequencing (SRS). Long-read sequencing (LRS) could help bridge this diagnostic gap by capturing variants inaccessible to SRS, facilitating long-range mapping and phasing and providing haplotype-resolved methylation profiling. To evaluate LRS's additional diagnostic yield, we sequenced a rare-disease cohort of 98 samples from 41 families, using nanopore sequencing, achieving per sample ∼36× average coverage and 32-kb read N50 from a single flow cell.

Structures and mRNP remodeling mechanism of the TREX-2 complex.

mRNAs are packaged with proteins into messenger ribonucleoprotein complexes (mRNPs) in the nucleus. mRNP assembly and export are of fundamental importance for all eukaryotic gene expression. Before export to the cytoplasm, mRNPs undergo dynamic remodeling governed by the DEAD-box helicase DDX39B (yeast Sub2).

Treatment of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in stormwater using polishing columns with biochar and granular activated carbon.

Polycyclic Aromatic Hydrocarbons (PAHs) and Polychlorinated Biphenyls (PCBs) are recalcitrant organic pollutants often detected in stormwater. Various stormwater control measures (SCMs) can remove PAHs and PCBs by filtration, adsorption, and biodegradation. However, dissolved PAHs and PCBs remain present in the treated outflow of SCMs.

MixDeR: A SNP mixture deconvolution workflow for forensic genetic genealogy.

The generation of forensic DNA profiles consisting of single nucleotide polymorphisms (SNPs) is now being facilitated by wider adoption of next-generation sequencing (NGS) methods in casework laboratories. At the same time, and in part because of this advance, there is an intense focus on the generation of SNP profiles from evidentiary specimens for so-called forensic or investigative genetic genealogy (FGG or IGG) applications. However, FGG methods are constrained by the algorithms for genealogical database searches, which were designed for use with single-source profiles, and the fact that many forensic samples are mixtures.