Metabolic rewiring in skin epidermis drives tolerance to oncogenic mutations.

Skin epithelial stem cells correct aberrancies induced by oncogenic mutations. Oncogenes invoke different strategies of epithelial tolerance; while wild-type cells outcompete β-catenin-gain-of-function (βcatGOF) cells, Hras cells outcompete wild-type cells. Here we ask how metabolic states change as wild-type stem cells interface with mutant cells and drive different cell-competition outcomes.

Immunotherapy for advanced-stage squamous cell lung cancer: the state of the art and outstanding questions.

Immune-checkpoint inhibitors (ICIs) have transformed the treatment paradigm for advanced-stage squamous non-small-cell lung cancer (LUSC), a histological subtype associated with inferior outcomes compared with lung adenocarcinoma. However, only a subset of patients derive durable clinical benefit. In the first-line setting, multiple ICI regimens are available, including anti-PD-(L)1 antibodies as monotherapy, in combination with chemotherapy, or with an anti-CTLA4 antibody with or without chemotherapy.

Deep Learning Analysis of White Matter Hyperintensity and its Association with Comprehensive Vascular Factors in Two Large General Populations.

Although the relationships between basic clinical parameters and white matter hyperintensity (WMH) have been studied, the associations between vascular factors and WMH volume in general populations remain unclear. We investigated the associations between clinical parameters including comprehensive vascular factors and WMH in two large general populations. This retrospective, cross-sectional study involved two populations: individuals who underwent general health examinations at the Asan Medical Center (AMC) and participants from a regional cohort, the Korean Genome and Epidemiology Study (KoGES).

Mechanistic and therapeutic insights into the function of N6-methyladenosine in arthritic diseases.

Objective: Arthritis is a class of diseases, characterized by joint and surrounding inflammation, accompanied by joint swelling, pain, dysfunction. According to different factors, arthritis can be divided into osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and so on. N6-methyladenosine (m6A) is the most common internal modification of eukaryotic mRNA and is involved in splicing, stabilization, output and degradation of RNA metabolism.

Peer-Led Adjunctive Interventions for Increasing the Reach of HIV Prevention and Care Interventions to Latino/x/e Men Who Have Sex with Men: a Scoping Review.

Purpose Of Review: Latino/x/e men who have sex with men (LMSM) in the United States are disproportionately affected by HIV. Peer-led adjunctive interventions show promise for enhancing engagement in HIV prevention and care among LMSM, but their effectiveness and implementation remain underexplored. This scoping review aimed to map existing evidence on peer-led interventions, identify gaps, and inform future research for enhancing HIV prevention and care among LMSM.

Prediction of checkpoint inhibitor immunotherapy efficacy for cancer using routine blood tests and clinical data.

Predicting whether a patient with cancer will benefit from immune checkpoint inhibitors (ICIs) without resorting to advanced genomic or immunologic assays is an important clinical need. To address this, we developed and evaluated SCORPIO, a machine learning system that utilizes routine blood tests (complete blood count and comprehensive metabolic profile) alongside clinical characteristics from 9,745 ICI-treated patients across 21 cancer types. SCORPIO was trained on data from 1,628 patients across 17 cancer types from Memorial Sloan Kettering Cancer Center.

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.

Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.

The MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient-reported outcomes and pharmacodynamic effects in PN biopsies.

Soil fluoride enrichment process and the possible adaptation prevention principle in coal-burning fluorosis area in Southwest China.

Coal-burning fluorosis prevails in southwest China and other provinces. Although clay used as binder of briquettes was proven to cause coal-burning fluorosis, its enrichment processes remain unknown. The soils and rocks on typical geological units were sampled and simulation experiments were performed to detect the forming process of high-fluoride clay.

SMYD3 drives cell cycle and epithelial-mesenchymal transition pathways through dual gene transcriptional repression and activation in HPV-negative head and neck cancer.

Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type in the world and is associated with an overall poor prognosis. The protein methyltransferase SET and MYND domain-containing 3 (SMYD3), which trimethylates H3K4, activates gene transcription and enhances several oncogenic pathways, including epithelial-mesenchymal transition and cell cycle related pathways, in various cancer types. It was also recently shown that SMYD3 is overexpressed in HPV-negative HNSCC, and represses the expression of type I IFN response genes, contributing to resistance to anti-PD-1 checkpoint blockade in this disease.

Lebrikizumab is associated with improvements in patient-reported symptoms and quality-of-life measures across Eczema Area and Severity Index response categories: pooled results from phase-3 randomized ADvocate1 and ADvocate2 studies in patients with moderate-to-severe atopic dermatitis.

Background: Lebrikizumab monotherapy significantly improved signs and symptoms in patients with moderate-to-severe atopic dermatitis (AD) in phase 3 Advocate1 and ADvocate2 studies.

Objective: To evaluate improvements in patient-reported symptoms and quality-of-life (QoL) measures by Eczema Area and Severity Index (EASI) response categories using pooled Advocate1 and ADvocate2 data (post hoc analysis).

Methods: In the 52-week (W) (16-W induction + 36-W maintenance) double-blind, placebo-controlled ADvocate1 and ADvocate2 studies, patients were randomized (2:1) to receive subcutaneous lebrikizumab 250 mg or placebo every 2 weeks.

Clinicopathological Features and Oncological Outcomes of Germline Partner and Localizer of Breast Cancer 2-Mutated Breast Cancer in Korea.

Purpose: The partner and localizer of breast cancer 2 (PALB2) mutation is a predisposition to breast cancer development. However, limited clinical data are available for the Korean population. Therefore, this study aimed to compare the characteristics and oncological outcomes of patients with PALB2-mutated and non-mutated PALB2 in Korea.

Adverse childhood experiences and adult alcohol use during pregnancy - 41 U.S. jurisdictions, 2019-2023.

Introduction: Adverse childhood experiences (ACEs) are preventable, potentially traumatic events that occur in childhood. Alcohol use during pregnancy can result in miscarriage, stillbirth, preterm birth, and a range of lifelong behavioral, intellectual, and physical disabilities in the child. Limited research has examined the relationship between ACEs and alcohol use in pregnancy; available studies might not reflect current trends in this relationship.

Adipokines and Transitions in Metabolic Health Over Time: The Atherosclerosis Risk In Communities (ARIC) Study.

Context: Transitions in metabolic health status over time are strongly linked to risk for cardiovascular events, particularly among individuals with obesity. Adipokines are proteins with metabolic effects, but their role in transitions in metabolic health status over time is unknown.

Objective: To evaluate the associations of adiponectin and leptin with metabolic risk transitions over time.

Mutational and Co-Mutational Landscape of Early Onset Colorectal Cancer.

Introduction: Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades.

Methods: Using a cohort of 10,000 patients, this study investigates the clinical, mutational, and co-mutational features of CRC in early-onset (EOCRC, < 50 years) compared to late-onset (LOCRC, ≥ 50 years).

Results: EOCRC was associated with a higher prevalence of Asian and Hispanic patients, rectal or left-sided tumors (72% vs.

Unraveling Caco-2 Cells through Functional and Transcriptomic Assessments.

The static Caco-2 monolayer is an extensively utilized model for predicting the permeability of small molecules during the drug development process. While these cells can differentiate and develop key functional and morphological features that emulate human enterocytes, they do not fully replicate the complexity of human intestinal physiology. In this study, we investigated functional and morphological aspects of Caco-2 cells, alongside their transcriptomic profiles, with a particular emphasis on genes encoding drug-metabolizing enzymes and drug transporters.

Proton Beam Therapy for Pancreatic Tumors: A Consensus Statement from the Particle Therapy Cooperative Group Gastrointestinal Subcommittee.

Objectives: Radiotherapy manages pancreatic cancer in various settings; however, the proximity of gastrointestinal (GI) luminal organs-at-risk (OAR) poses challenges to conventional radiotherapy. Proton beam therapy (PBT) may reduce toxicities compared to photon therapy. This consensus statement summarizes PBT's safe and optimal delivery for pancreatic tumors.

Metagenomic next-generation sequencing on treatment strategies and prognosis of patients with lower respiratory tract infections: a systematic review and meta-analysis.

Objectives: Controversy exists regarding the benefits of metagenomic next-generation sequencing (mNGS) in lower respiratory tract infections (LRTIs). We assessed the impact of mNGS on the treatment and prognosis of LRTI patients through a systematic review and meta-analysis.

Methods: A literature search was conducted in PubMed, Embase and CENTRAL databases up to February 19, 2024.

Structural and Functional Insights into UDP-N-acetylglucosamine-enolpyruvate Reductase (MurB) from Brucella ovis.

The peptidoglycan biosynthetic pathway involves a series of enzymatic reactions in which UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) plays a crucial role in catalyzing the conversion of UDP-N-acetylglucosamine-enolpyruvate (UNAGEP) to UDP-N-acetylmuramic acid. This reaction relies on NADPH and FAD and, since MurB is not found in eukaryotes, it is an attractive target for the development of antimicrobials. MurB from Brucella ovis, the causative agent of brucellosis in sheep, is characterized here.

Role of CTRP14/C1QL1 in motor coordination and learning across the lifespan.

C1q/TNF-related protein 14 (CTRP14), also known as C1q-like 1 (C1QL1), is a synaptic protein predominantly expressed in the brain. It plays a critical role in the formation and maintenance of the climbing fiber-Purkinje cell synapses, ensuring that only one single winning climbing fiber from the inferior olivary neuron synapses with the proximal dendrites of Purkinje cells during the early postnatal period. Loss of CTRP14/C1QL1 results in incomplete elimination of supernumerary climbing fibers, leading to multiple persistent climbing fibers synapsing with the Purkinje cells.

Diffusion tensor imaging with free-water correction reveals distinctions between severe and attenuated subtypes in Mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disorder leading to deleterious brain effects. While animal models suggested that MPS I severely affects white matter (WM), whole-brain diffusion tensor imaging (DTI) analysis was not performed due to MPS-related morphological abnormalities. 3T DTI data from 28 severe (MPS IH, treated with hematopoietic stem cell transplantation-HSCT), 16 attenuated MPS I patients (MPS IA) enrolled under the study protocol NCT01870375, and 27 healthy controls (HC) were analyzed using the free-water correction (FWC) method to resolve macrostructural partial volume effects and unravel differences in DTI metrics accounting for microstructural abnormalities.

Assessing the Impact of Multidisciplinary Cancer Consultations on Cancer Quality Metrics.

Objective: Multidisciplinary cancer consultations play a critical role in the delivery of quality cancer care by promoting treatment planning and collaborative decision-making. The objective of this study was to evaluate associations between multidisciplinary cancer consultations and receipt of guideline-recommended adjuvant treatments among breast, colorectal, or non-small cell lung cancer patients and assess these associations between and within racial and ethnic groups.

Methods: This is a population-based retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER), Medicare-linked data (2006-2016) to identify Medicare beneficiaries diagnosed with nonmetastatic breast, colorectal, or non-small cell lung cancer.

Effectiveness of transcranial direct current stimulation (tDCS) in treating drug-resistant focal epilepsy: A systematic review and meta-analysis.

Introduction Epilepsy is a prevalent neurological disorder globally, with about 30% of patients developing resistance despite optimal antiseizure drug therapies (ASD). Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique and offers a potential therapeutic alternative for drug-resistant focal epilepsy, aiming to reduce seizure frequency and improve patient quality of life. Methods Following PRISMA guidelines; a search was performed on MEDLINE, Web of Science, and Cochrane Library from inception to June 2024.