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.

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.

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.

Perioperative multimodal analgesic injection for patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion surgery.

Purpose: This retrospective cohort study compared postoperative as-needed (PRN) opioid consumption pre and postimplementation of a perioperative multimodal analgesic injection composed of ropivacaine, epinephrine, ketorolac, and morphine in patients undergoing posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Secondary outcomes include pain score measurements, time to ambulation, length of stay, blood loss, 90-day complication rate, operating room time, nonopioid medication usage, and total inpatient medication cost before and after the initiation of this practice.

Methods: Consecutive patients weighing ≥ 20 kg who underwent PSF for a primary diagnosis of AIS between January 2017 and December 2020 were included.

Dissecting Phenotype from Genotype with Clinical Isolates of SARS-CoV-2 First Wave Variants.

The emergence and availability of closely related clinical isolates of SARS-CoV-2 offers a unique opportunity to identify novel nonsynonymous mutations that may impact phenotype. Global sequencing efforts show that SARS-CoV-2 variants have emerged and then been replaced since the beginning of the pandemic, yet we have limited information regarding the breadth of variant-specific host responses. Using primary cell cultures and the K18-hACE2 mouse, we investigated the replication, innate immune response, and pathology of closely related, clinical variants circulating during the first wave of the pandemic.

Statistical Methods Inspired by Challenges in Pediatric Cancer Multi-omics.

Pediatric cancer multi-omics is a uniquely rewarding and challenging domain of biomedical research. Public generosity bestows an abundance of resources for the study of extremely rare diseases; this unique dynamic creates a research environment in which problems with high-dimension and low sample size are commonplace. Here, we present a few statistical methods that we have developed for our research setting and believe will prove valuable in other biomedical research settings as well.

SAMHD1 single nucleotide polymorphisms impact outcome in children with newly diagnosed acute myeloid leukemia.

Cytarabine arabinoside (Ara-C) has been the cornerstone of acute myeloid leukemia (AML) chemotherapy for decades. After cellular uptake, it is phosphorylated into its active triphosphate form (Ara-CTP), which primarily exerts its cytotoxic effects by inhibiting DNA synthesis in proliferating cells. Interpatient variation in the enzymes involved in the Ara-C metabolic pathway has been shown to affect intracellular abundance of Ara-CTP and, thus, its therapeutic benefit.

Analysis of , thermal and pressure pain thresholds, and stress in sickle cell disease.

Aim: In patients with sickle cell disease (SCD), negative physical and emotional experiences result from intense chronic and acute pain episodes, but factors underlying these, and their interactions, are not well understood. The arginine vasopressin receptor 1a gene () single nucleotide polymorphism rs10877969 has been previously associated with aspects of acute pain and stress related pain. In this study, we tested for associations between this SNP, thermal and pressure pain thresholds, clinical pain, and stress in people with SCD.