Perceptions about alcohol harm and alcohol-control strategies among people with high risk of alcohol consumption in Alberta, Canada and Queensland, Australia

Objectives: To explore alcohol perceptions and their association hazardous alcohol use in the populations of Alberta, Canada and Queensland, Australia. Methods: Data from 2500 participants of the 2013 Alberta Survey and the 2013 Queensland Social Survey was analyzed. Regression analyses were used to explore the association between alcohol perceptions and its association with hazardous alcohol use. Results: Greater hazardous alcohol use was found in Queenslanders than Albertans (p<0.001). Overall, people with hazardous alcohol were less likely to believe that alcohol use contributes to health problems (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.27 to 0.78; p<0.01) and to a higher risk of injuries (OR, 0.54; 95% CI, 0.33 to 0.90; p<0.05). Albertans with hazardous alcohol use were less likely to believe that alcohol contributes to health problems (OR, 0.48; 95% CI, 0.26 to 0.92; p<0.05) and were also less likely to choose a highly effective strategy as the best way for the government to reduce alcohol problems (OR, 0.63; 95% CI, 0.43 to 0.91; p=0.01). Queenslanders with hazardous alcohol use were less likely to believe that alcohol was a major contributor to injury (OR, 0.39; 95% CI, 0.20 to 0.77; p<0.01). Conclusions: Our results suggest that people with hazardous alcohol use tend to underestimate the negative effect of alcohol consumption on health and its contribution to injuries. In addition, Albertans with hazardous alcohol use were less in favor of strategies considered highly effective to reduce alcohol harm, probably because they perceive them as a potential threat to their own alcohol consumption. These findings represent valuable sources of information for local health authorities and policymakers when designing suitable strategies to target alcohol-related problems

Exploring long COVID condition in Latin America: Its impact on patients’ activities and associated healthcare use

"Background: Studies exploring long COVID condition (LCC) in low- and middle-income countries are scarce. Further characterization of LCC patients experiencing activity limitations and their associated healthcare use is needed. This study aimed to describe LCC patients’ characteristics, its impact on activities, and associated healthcare use in Latin America (LATAM). Participants: Individuals who (cared for someone or) had COVID-19 and could read, write, and comprehend Spanish and lived in a LATAM country were invited to complete a virtual survey. Sociodemographic characteristics, COVID-19 and LCC symptoms, activity limitations, and healthcare use. Results: Data from 2,466 people from 16 countries in LATAM were analyzed (females = 65.9%; mean age of 39.5 ± 53.3 years). 1,178 (48%) of the respondents had LCC symptoms (≥3 months). These were more likely to have COVID-19 earlier in the pandemic, were older, had no COVID vaccines, had more comorbidities, needed supplementary oxygen, and reported significantly more COVID-19 symptoms during the infectious period. 33% of the respondents visited a primary care provider, 13% went to the emergency department, 5% were hospitalized, 21% visited a specialist, and 32% consulted ≥1 therapist for LCC symptoms mainly extreme fatigue, sleep difficulties, headaches, muscle or joint pain, and shortness of breath with activity. The most consulted therapists were respiratory therapists (15%) and psychologists (14%), followed by physical therapists (13%), occupational therapists (3%), and speech pathologists (1%). One-third of LCC respondents decreased their regular activities (e.g., work, school) and 8% needed help with activities of daily living (ADLs). LCC respondents who reduced their activities reported more difficulty sleeping, chest pain with activity, depression, and problems with concentration, thinking, and memory, while those who needed help with ADLs were more likely to have difficulty walking, and shortness of breath at rest. Approximately 60% of respondents who experienced activity limitations sought a specialist and 50% consulted therapists. Conclusions and relevance: Results supported previous findings in terms of the LCC demographics, and provided insight into LCC impact on patients’ activities and healthcare services used in LATAM. This information is valuable to inform service planning and resource allocation in alignment with the needs of this population.

Correction : Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer

Osimertinib is efficacious in lung cancer patients with epidermal growth factor receptor (EGFR) mutations and acquired resistance (AR) to EGFR tyrosine kinase inhibitors due to EGFR -T790M mutation (T790M). We sought to describe T790M changes in serum/plasma during osimertinib therapy and correlate these changes with treatment outcomes. Serum/plasma from EGFR -mutant lung cancer patients with T790M-AR was collected before and during osimertinib treatment. Changes in T790M were evaluated using a peptide-nucleic acid-PCR assay, and correlated with clinical and radiographic response. Thirteen patients were included. Median time on osimertinib treatment was 10.6 months with a median progression-free survival of 13.6 months. Best response to osimertinib was partial response (PR), stable disease (SD) or progression (PD) in 46.1%, 30.8% and 23.1% of patients, respectively. Most of the patients were paucisymptomatic at baseline. Symptom improvement was reported in 66.6% of responder patients; while symptoms remained stable in 75% of patients with SD, and 66% of patients with PD had clinical deterioration. Three patterns of T790M changes during osimertinib treatment were identified. T790 remained detectable with PD or a short-lasting SD in 15.4% of the patients. T790M disappeared in 69.2% of patients with PR or SD. T790M disappeared, despite clinical and/or radiographic progression in 15.4% of the patients. Changes of T790M in serum/plasma in EGFR -mutant lung cancer patients with T790M-AR might be a useful marker of symptomatic and radiographic outcome to osimertinib. Longer follow-up is needed to establish if subsequent emergence of T790M could be a marker of resistance

Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer

Osimertinib is efficacious in lung cancer patients with epidermal growth factor receptor (EGFR) mutations and acquired resistance (AR) to EGFR tyrosine kinase inhibitors due to EGFR -T790M mutation (T790M). We sought to describe T790M changes in serum/plasma during osimertinib therapy and correlate these changes with treatment outcomes. Serum/plasma from EGFR -mutant lung cancer patients with T790M-AR was collected before and during osimertinib treatment. Changes in T790M were evaluated using a peptide-nucleic acid-PCR assay, and correlated with clinical and radiographic response. Thirteen patients were included. Median time on osimertinib treatment was 10.6 months with a median progression-free survival of 13.6 months. Best response to osimertinib was partial response (PR), stable disease (SD) or progression (PD) in 46.1%, 30.8% and 23.1% of patients, respectively. Most of the patients were paucisymptomatic at baseline. Symptom improvement was reported in 66.6% of responder patients; while symptoms remained stable in 75% of patients with SD, and 66% of patients with PD had clinical deterioration. Three patterns of T790M changes during osimertinib treatment were identified. T790 remained detectable with PD or a short-lasting SD in 15.4% of the patients. T790M disappeared in 69.2% of patients with PR or SD. T790M disappeared, despite clinical and/or radiographic progression in 15.4% of the patients. Changes of T790M in serum/plasma in EGFR -mutant lung cancer patients with T790M-AR might be a useful marker of symptomatic and radiographic outcome to osimertinib. Longer follow-up is needed to establish if subsequent emergence of T790M could be a marker of resistance

Exploring long COVID condition in Latin America: Its impact on patients’ activities and associated healthcare use

BackgroundStudies exploring long COVID condition (LCC) in low- and middle-income countries are scarce. Further characterization of LCC patients experiencing activity limitations and their associated healthcare use is needed. This study aimed to describe LCC patients’ characteristics, its impact on activities, and associated healthcare use in Latin America (LATAM).ParticipantsIndividuals who (cared for someone or) had COVID-19 and could read, write, and comprehend Spanish and lived in a LATAM country were invited to complete a virtual survey. Sociodemographic characteristics, COVID-19 and LCC symptoms, activity limitations, and healthcare use.ResultsData from 2,466 people from 16 countries in LATAM were analyzed (females = 65.9%; mean age of 39.5 ± 53.3 years). 1,178 (48%) of the respondents had LCC symptoms (≥3 months). These were more likely to have COVID-19 earlier in the pandemic, were older, had no COVID vaccines, had more comorbidities, needed supplementary oxygen, and reported significantly more COVID-19 symptoms during the infectious period. 33% of the respondents visited a primary care provider, 13% went to the emergency department, 5% were hospitalized, 21% visited a specialist, and 32% consulted ≥1 therapist for LCC symptoms mainly extreme fatigue, sleep difficulties, headaches, muscle or joint pain, and shortness of breath with activity. The most consulted therapists were respiratory therapists (15%) and psychologists (14%), followed by physical therapists (13%), occupational therapists (3%), and speech pathologists (1%). One-third of LCC respondents decreased their regular activities (e.g., work, school) and 8% needed help with activities of daily living (ADLs). LCC respondents who reduced their activities reported more difficulty sleeping, chest pain with activity, depression, and problems with concentration, thinking, and memory, while those who needed help with ADLs were more likely to have difficulty walking, and shortness of breath at rest. Approximately 60% of respondents who experienced activity limitations sought a specialist and 50% consulted therapists.Conclusions and relevanceResults supported previous findings in terms of the LCC demographics, and provided insight into LCC impact on patients’ activities and healthcare services used in LATAM. This information is valuable to inform service planning and resource allocation in alignment with the needs of this population

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics