Maternal Smoking Around Birth Is a Risk Factor for Gastrointestinal Diseases in Offspring: A Mendelian Randomization Study.

Background: The effect of maternal smoking around birth (MSAB) on gastrointestinal (GI) diseases in the offspring is still not fully understood.

Aim: We conducted a rigorous Mendelian randomization (MR) study to examine the association between MSAB and 24 GI diseases in offspring.

Methods: Single nucleotide polymorphisms (SNPs) associated with MSAB were obtained from a recent study.

The global, regional, and national burden of colorectal cancer attributable to smoking from 1990 to 2021: a population-based study.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide, with smoking being a significant risk factor. Understanding the temporal and spatial patterns of the CRC burden attributable to smoking is crucial for global public health strategies. Data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 were used to calculate the number of deaths, disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR) per 100 000 population, and age-standardized disability-adjusted life year rate (ASDR).

Integrative pan-cancer analysis and experiment validation identified GLS as a biomarker in tumor progression, prognosis, immune microenvironment, and immunotherapy.

Glutaminase (GLS), a crucial gene regulating glutaminolysis, has received much attention as it was found to regulate tumor metabolism and copper-induced cell death. However, its biological roles and mechanisms in human cancers remain obscure. Consequently, the integrated pan-cancer analyses and biological experiments were conducted to elucidate its oncological functions.

Genome-wide CRISPR screen identifies AraC-Dauno-Eto (ADE) response modulators that predicts outcome in pediatric AML.

Cytarabine, daunorubicin, and etoposide (ADE) have been the standard backbone of induction chemotherapy regimens for acute myeloid leukemia (AML) patients for over five decades. However, chemoresistance is still a major concern, and a significant proportion of AML becomes resistant to ADE treatment leading to relapse and poor survival. Therefore, there is a significant need to identify mechanisms mediating drug resistance to overcome chemoresistance.

Long-read epigenomic diagnosis and prognosis of Acute Myeloid Leukemia.

Acute Myeloid Leukemia (AML) is an aggressive cancer with dismal outcomes, vast subtype heterogeneity, and suboptimal risk stratification. In this study, we harmonized DNA methylation data from 3,314 patients across 11 cohorts to develop the Acute Leukemia Methylome Atlas (ALMA) of diagnostic relevance that predicted 27 WHO 2022 acute leukemia subtypes with an overall accuracy of 96.3% in discovery and 90.

Hypoxia-related bioinformatic signatures associated with prognosis and tumor microenvironment of pancreatic cancer: Current status, concerns, and future perspectives.

Pancreatic cancer (PC), a highly lethal tumor with nearly identical incidence and mortality rates, has become the sixth leading cause of cancer-related deaths. Hypoxia is an important malignant factor in PC, as it regulates angiogenesis, metabolic reprogramming, tumor progression, and metastasis. Disrupting the hypoxic microenvironment can enhance the efficacy of antitumor therapy and improve the prognosis of patients with PC.

Comprehensive genomic analysis reveals molecular heterogeneity in pediatric ALK-positive anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase (ALK) rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL (ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA sequencing, and DNA methylation profiling.

No genetic causality between appendectomy and gastrointestinal cancers: a Mendelian randomization study and meta-analysis in European population.

The impact of appendectomy on the risk of gastrointestinal cancers remains unknown. We aimed to systematically estimate the causal relationship between appendectomy and gastrointestinal cancers in the European population using two-sample Mendelian randomization (TSMR) study methods and meta-analysis. As part of the discovery cohort analysis, we identified independent genetic variants strongly associated with appendectomy from the UK Biobank (50,105 cases) to serve as instrumental variables (IVs).

Exploring the causality of appendectomy and ischaemic heart disease: a Mendelian randomization study and meta-analysis.

Background: The risk of ischaemic heart disease (IHD) is increased in appendectomy patients, but it is not clear whether there is a causal relationship. We aimed to systematically estimate the causal relationship between appendectomy and IHD and its subtypes, acute myocardial infarction (AMI) and angina pectoris (AP), using Mendelian randomization (MR) study methods and meta-analysis.

Methods: As the discovery cohort analysis, we extracted independent genetic variants strongly associated with appendectomy from the FinnGen study (28,601 cases) as instrumental variables (IVs).

Integrated drug resistance and leukemic stemness gene-expression scores predict outcomes in large cohort of over 3500 AML patients from 10 trials.

In this study, we leveraged machine-learning tools by evaluating expression of genes of pharmacological relevance to standard-AML chemotherapy (ara-C/daunorubicin/etoposide) in a discovery-cohort of pediatric AML patients (N = 163; NCT00136084 ) and defined a 5-gene-drug resistance score (ADE-RS5) that was predictive of outcome (high MRD1 positivity p = 0.013; lower EFS p < 0.0001 and OS p < 0.

Pharmacogenomic Score Effectively Personalizes Treatment of Acute Myeloid Leukemia.

Purpose: Cytarabine (also known as ara-C) has been the backbone of acute myeloid leukemia (AML) chemotherapy for more than five decades. Recent pharmacogenomics-based 10-SNP ara-C (ACS10) scores showed low ACS10 (≤0) to be associated with poor outcomes in patients with AML treated with standard chemotherapy. Here, we evaluated the ACS10 score in the context of three different induction I regimens in patients with pediatric AML.

Pharmacogenomics, Race, and Treatment Outcome in Pediatric Acute Myeloid Leukemia.

Importance: Disparities in outcomes exist between Black and White patients with acute myeloid leukemia (AML), with Black patients experiencing poorer prognosis compared with their White counterparts.

Objective: To assess whether varying intensity of induction therapy to treat pediatric AML is associated with reduced disparities in treatment outcome by race.

Design, Setting, And Participants: A comparative effectiveness analysis was conducted of 86 Black and 359 White patients with newly diagnosed AML who were enrolled in the AML02 trial from 2002 to 2008 or the AML08 trial from 2008 to 2017.

Comprehensive genomic analysis reveals molecular heterogeneity in pediatric ALK-positive anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase ( rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL(ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA-sequencing, and DNA methylation profiling.

Genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA as noninvasive diagnostic markers for gastric cancer.

Background: 5-Hydroxymethylcytosine-enriched gene profiles and regions show tissue-specific and tumor specific. There is a potential value to explore cell-free DNA 5-hydroxymethylcytosine feature biomarkers for early gastric cancer detection.

Methods: A matched case‒control study design with 50 gastric cancer patients and 50 controls was performed to sequence the different 5-hydroxymethylcytosine modification features of cell free DNA.

Appraising associations between signature lipidomic biomarkers and digestive system cancer risk: novel evidences from a prospective cohort study of UK Biobank and Mendelian randomization analyses.

Background: The roles of serum lipids on digestive system cancer (DSC) risk were still inconclusive. In this study, we systematically assessed indicative effects of signature lipidomic biomarkers (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)) on DSC (oesophagus, stomach, colorectal, liver, gallbladder, and pancreas cancers) risk.

Methods: HDL-C, LDL-C, and TG concentration measurements were respectively analyzed with enzyme immunoinhibition, enzymatic selective protection, and GPO-POD methods in AU5800 supplied from Beckman Coulter.

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy.

Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence and mortality, deprives countless patients of health and even life. According to global cancer statistics, there were an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths in 2020, with the age-standardized incidence and mortality rates of 201.

The Relationship Between Uncertainty and Psychological Distress Among Family Caregivers of Patients With Delirium in Intensive Care Units: A Cross-Sectional Survey.

Background: Although family caregivers experienced negative psychological symptoms associated with witnessing intensive care unit delirium in their loved ones, there is a lack of clear understanding of how delirium is associated with family caregiver psychological distress. Uncertainty could be a factor contributed to this association.

Objectives: The aim of this study was to examine the relationship between uncertainty and psychological distress among family caregivers of patients with delirium in intensive care units.

The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.

The occurrence and progression of tumors are inseparable from glucose metabolism. With the development of tumors, the volume increases gradually and the nutritional supply of tumors cannot be fully guaranteed. The tumor microenvironment changes and glucose deficiency becomes the common stress environment of tumors.

Early clinical indicators of acute kidney injury caused by administering high-dose methotrexate therapy to juvenile pigs.

Introduction: Early identification of compromised renal clearance caused by high-dose methotrexate (HDMTX) is essential for initiating timely interventions that can reduce acute kidney injury and MTX-induced systemic toxicity.

Methods: We induced acute kidney injury (AKI) by infusing 42 juvenile pigs with 4 g/kg (80 g/m2) of MTX over 4 hours without high-volume alkalinizing hydration therapy. Concentrations of serum creatinine and MTX were measured at 15 time points up to 148 hours, with 10 samples collected during the first 24 hours after the start of the HDMTX infusion.

The potential of epigallocatechin gallate in the chemoprevention and therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), one of the most notorious malignancies globally, has a high fatality and poor prognosis. Though remarkable breakthroughs have been made in the therapeutic strategies recently, the overall survival of HCC remains unsatisfactory. Consequently, the therapy of HCC remains a great challenge.

Upper Respiratory Infection Drives Clinical Signs and Inflammatory Responses Following Heterologous Challenge of SARS-CoV-2 Variants of Concern in K18 Mice.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of several variants of concern (VOC) with increased immune evasion and transmissibility. This has motivated studies to assess protection conferred by earlier strains following infection or vaccination to each new VOC. We hypothesized that while NAbs play a major role in protection against infection and disease, a heterologous reinfection or challenge may gain a foothold in the upper respiratory tract (URT) and result in a self-limited viral infection accompanied by an inflammatory response.

A cuproptosis-related lncRNA signature to predict prognosis and immune microenvironment of colon adenocarcinoma.

Cuproptosis is a novel cell death modality but its regulatory role in the colon cancer remains obscure. This study is committed to establishing a cuproptosis-related lncRNA (CRL) signature to forecast the prognosis for colon adenocarcinoma (COAD). The Cancer Genome Atlas (TCGA) samples were randomly divided into training and validation cohorts.