The Role of Childhood Obesity in Acute Presentations and Outcomes of Hospitalized COVID-19 Patients.

Background and objective The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has affected all regions, demographics, and age groups worldwide. However, few studies have investigated the prevalence of childhood obesity and severe COVID-19 presentation in a predominately Hispanic population. In light of this, we investigated the role of underlying obesity in COVID-19 presentations and outcomes at a tertiary care children's hospital by using subcategories based on patients' body mass index (BMI). Methods We conducted a single-center retrospective study involving 77 pediatric patients aged 18 years and younger, who were hospitalized with suspected or verified COVID-19 between February 2020 and January 2021. We collected data on height, weight, and BMI and categorized patients based on the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) definition(s) of obesity. We also collected data on demographics, mode of presentation, need for pediatric intensive care unit (PICU) admission, the severity of illness at the time of PICU admission, and data related to outcomes. We analyzed the data using logistical regression with Firth's biased reduction method wherever applicable. Results In our cohort, over 85% of the patients identified as belonging to Hispanic ethnicity (n=66); the median age of the cohort was 8.69 years, and 50.65% were classified as obese (n=39). We found a statistically significant relationship between underlying obesity and one or more comorbidities (p<0.001). BMI classification was significantly dependent on the incidence of multisystem inflammatory syndrome in children (MIS-C) (p=0.0353). Furthermore, the bivariate analysis confirmed that acute kidney injury (AKI) (p=0.048) and MIS-C predictors (p<0.001) were significantly associated with PICU admission status. The combined model confirmed a significant relationship between MIS-C and both PICU admission status (p<0.001) and obese BMI classification (p=0.002). PICU admission status led to increased hospital length of stay (LOS) (p<0.001). Patient age (p=0.003), underweight BMI (p=0.034), and obese BMI (P=0.008) were significant predictors of PICU LOS. Of note, the survival rate among admitted COVID-19 patients was 93.5%. Conclusion Based on our findings on the prevalence of underlying obesity in admitted COVID-19 patients at the Children's Hospital of San Antonio, over 50% of pediatric patients were obese and predominately Hispanic. Obesity was significantly associated with patient age, comorbidities, MIS-C status, and PICU LOS. Hospital mortality in pediatric COVID-19 patients was low (6.49%) and consistent with other studies in the literature showing lower rates of mortality in children versus mortality in adult patients with COVID-19.

Jean Lau Chin (1944-2020).

Memorializes Jean Lau Chin (1944-2020). Jean was an academic leader. At the time of her death, Jean was Professor of Psychology, Gordon F. Derner School of Psychology, Adelphi University, where she served as Dean for 4 years. Prior to Adelphi, Jean was Dean of the California School of Professional Psychology, Alliant International University, where she administered more than 15 doctoral and master's programs in clinical psychology, marriage and family therapy, and clinical counseling across six campuses in California, Mexico City, Japan, and Hong Kong. She served as President of the National Council of Schools and Programs of Professional Psychology. Jean was also a leader in health and mental health service delivery. She had been the Regional Director, Massachusetts Behavioral Health Partnership; the Executive Director, South Cove Community Health Center in Boston; and Co-Director, the Thom Child Guidance Clinic, Boston. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Biodiversity conservation in an anthropized landscape: Trees, not patch size drive, bird community composition in a low-input agro-ecosystem.

One of the most typical agro-ecosystems in the Llanos de Ojuelos, a semi-arid region of central Mexico, is that of fruit-production orchards of nopales (prickly pear cacti). This perennial habitat with complex vertical structure provides refuge and food for at least 112 species of birds throughout the year. Nopal orchards vary in their internal structure, size and shrub/tree composition, yet these factors have unknown effects on the animals that use them. To further understand the conservation potential of this agro-ecosystem, we evaluated the effects of patch-size and the presence of trees on bird community composition, as well as several habitat variables, through an information-theoretical modelling approach. Community composition was obtained through a year of census transects in 12 orchards. The presence of trees in the orchards was the major driver of bird communities followed by seasonality; bird communities are independent of patch size, except for small orchard patches that benefit black-chin sparrows, which are considered a sensitive species. At least 55 species of six trophic guilds (insectivores, granivores, carnivores, nectivores, omnivores, and frugivores) used the orchards. Orchards provide adequate habitat and food resources for several sensitive species of resident and migratory sparrows. The attributes that make orchards important for birds: trees, shrubs, herb seeds, and open patches can be managed to maintain native biodiversity in highly anthropized regions with an urgent need to find convergence between production and biological conservation.

Genomic Landscape Established by Allelic Imbalance in the Cancerization Field of a Normal Appearing Airway.

Visually normal cells adjacent to, and extending from, tumors of the lung may carry molecular alterations characteristics of the tumor itself, an effect referred to as airway field of cancerization. This airway field has been postulated as a model for early events in lung cancer pathogenesis. Yet the genomic landscape of somatically acquired molecular alterations in airway epithelia of lung cancer patients has remained unknown. To begin to fill this void, we sought to comprehensively characterize the genomic architecture of chromosomal alterations inducing allelic imbalance (AI) in the airway field of the most common type of lung tumors, non-small cell lung cancer (NSCLC). To do so, we conducted a genome-wide survey of multiple spatially distributed normal-appearing airways, multiregion tumor specimens, and uninvolved normal tissues or blood from 45 patients with early-stage NSCLC. We detected alterations in airway epithelia from 22 patients, with an increased frequency in NSCLCs of squamous histology. Our data also indicated a spatial gradient of AI in samples at closer proximity to the NSCLC. Chromosome 9 displayed the highest levels of AI and comprised recurrent independent events. Furthermore, the airway field AI included oncogenic gains and tumor suppressor losses in known NSCLC drivers. Our results demonstrate that genome-wide AI is common in the airway field of cancerization, providing insights into early events in the pathogenesis of NSCLC that may comprise targets for early treatment and chemoprevention. Cancer Res; 76(13); 3676-83. ©2016 AACR.

Transcriptomic architecture of the adjacent airway field cancerization in non-small cell lung cancer.

BACKGROUND: Earlier work identified specific tumor-promoting abnormalities that are shared between lung cancers and adjacent normal bronchial epithelia. We sought to characterize the yet unknown global molecular and adjacent airway field cancerization (FC) in early-stage non-small cell lung cancer (NSCLC). METHODS: Whole-transcriptome expression profiling of resected early-stage (I-IIIA) NSCLC specimens (n = 20) with matched tumors, multiple cytologically controlled normal airways with varying distances from tumors, and uninvolved normal lung tissues (n = 194 samples) was performed using the Affymetrix Human Gene 1.0 ST platform. Mixed-effects models were used to identify differentially expressed genes among groups. Ordinal regression analysis was performed to characterize site-dependent airway expression profiles. All statistical tests were two-sided, except where noted. RESULTS: We identified differentially expressed gene features (n = 1661) between NSCLCs and airways compared with normal lung tissues, a subset of which (n = 299), after gene set enrichment analysis, statistically significantly (P < .001) distinguished large airways in lung cancer patients from airways in cancer-free smokers. In addition, we identified genes (n = 422) statistically significantly and progressively differentially expressed in airways by distance from tumors that were found to be congruently modulated between NSCLCs and normal lung tissues. Furthermore, LAPTM4B, with statistically significantly increased expression (P < .05) in airways with shorter distance from tumors, was upregulated in human immortalized cells compared with normal bronchial epithelial cells (P < .001) and promoted anchorage-dependent and -independent lung cancer cell growth. CONCLUSIONS: The adjacent airway FC comprises both site-independent profiles as well as gradient and localized airway expression patterns. Profiling of the airway FC may provide new insights into NSCLC oncogenesis and molecular tools for detection of the disease.

ETS2 mediated tumor suppressive function and MET oncogene inhibition in human non-small cell lung cancer.

PURPOSE: The ETS2 transcription factor is an evolutionarily conserved gene that is deregulated in cancer. We analyzed the transcriptome of lung adenocarcinomas and normal lung tissue by expression profiling and found that ETS2 was significantly downregulated in adenocarcinomas. In this study, we probed the yet unknown functional role of ETS2 in lung cancer pathogenesis. EXPERIMENTAL DESIGN: Lung adenocarcinomas (n = 80) and normal lung tissues (n = 30) were profiled using the Affymetrix Human Gene 1.0 ST platform. Immunohistochemical (IHC) analysis was conducted to determine ETS2 protein expression in non-small cell lung cancer (NSCLC) histologic tissue specimens (n = 201). Patient clinical outcome, based on ETS2 IHC expression, was statistically assessed using the log-rank and Kaplan-Meier tests. RNA interference and overexpression strategies were used to assess the effects of ETS2 expression on the transcriptome and on various malignant phenotypes. RESULTS: ETS2 expression was significantly reduced in lung adenocarcinomas compared with normal lung (P < 0.001). Low ETS2 IHC expression was a significant predictor of shorter time to recurrence in NSCLC (P = 0.009, HR = 1.89) and adenocarcinoma (P = 0.03, HR = 1.86). Moreover, ETS2 was found to significantly inhibit lung cancer cell growth, migration, and invasion (P < 0.05), and microarray and pathways analysis revealed significant (P < 0.001) activation of the HGF pathway following ETS2 knockdown. In addition, ETS2 was found to suppress MET phosphorylation and knockdown of MET expression significantly attenuated (P < 0.05) cell invasion mediated by ETS2-specific siRNA. Furthermore, knockdown of ETS2 augmented HGF-induced MET phosphorylation, cell migration, and invasion. CONCLUSION(S): Our findings point to a tumor suppressor role for ETS2 in human NSCLC pathogenesis through inhibition of the MET proto-oncogene.

Characterizing the molecular spatial and temporal field of injury in early-stage smoker non-small cell lung cancer patients after definitive surgery by expression profiling.

Gene expression alterations in response to cigarette smoke have been characterized in normal-appearing bronchial epithelium of healthy smokers, and it has been suggested that adjacent histologically normal tissue displays tumor-associated molecular abnormalities. We sought to delineate the spatial and temporal molecular lung field of injury in smoker patients with early-stage non-small cell lung cancer (NSCLC; n = 19) who were accrued into a surveillance clinical trial for annual follow-up and bronchoscopies within 1 year after definitive surgery. Bronchial brushings and biopsies were obtained from six different sites in the lung at the time of inclusion in the study and at 12, 24, and 36 months after the first time point. Affymetrix Human Gene 1.0 ST arrays were used for whole-transcript expression profiling of airways (n = 391). Microarray analysis identified gene features (n = 1,165) that were nonuniform by site and differentially expressed between airways adjacent to tumors relative to more distant samples as well as those (n = 1,395) that were significantly altered with time up to 3 years. In addition, gene interaction networks mediated by phosphoinositide 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK)1/2 were modulated in adjacent compared with contralateral airways and the latter network with time. Furthermore, phosphorylated AKT and ERK1/2 immunohistochemical expression were significantly increased with time (nuclear pAKT, P = 0.03; cytoplasmic pAKT, P < 0.0001; pERK1/2, P = 0.02) and elevated in adjacent compared with more distant airways (nuclear pAKT, P = 0.04; pERK1/2, P = 0.03). This study highlights spatial and temporal cancer-associated expression alterations in the molecular field of injury of patients with early-stage NSCLCs after definitive surgery that warrant further validation in independent studies.

G-protein coupled receptor family C, group 5, member A (GPRC5A) expression is decreased in the adjacent field and normal bronchial epithelia of patients with chronic obstructive pulmonary disease and non-small-cell lung cancer.

INTRODUCTION: Understanding oncogenes and tumor suppressor genes expression patterns is essential for characterizing lung cancer pathogenesis. We have previously demonstrated that mGprc5a/hGPRC5A is a lung-specific tumor suppressor evidenced by inflammation-mediated tumorigenesis in Gprc5a-knockout mice. The implication of GPRC5A in human lung cancer pathogenesis, including that associated with inflammatory chronic obstructive pulmonary disease (COPD), a risk factor for the malignancy, remains elusive. METHODS: We sought to examine GPRC5A immunohistochemical expression in histologically normal bronchial epithelia (NBE) from lung disease-free never- and ever-smokers (n = 13 and n = 18, respectively), from COPD patients with (n = 26) and without cancer (n = 24) and in non-small cell lung cancers (NSCLCs) (n = 474). Quantitative assessment of GPRC5A transcript expression in airways (n = 6), adjacent NBEs (n = 29) and corresponding tumors (n = 6) from 6 NSCLC patients was also performed. RESULTS: GPRC5A immunohistochemical expression was significantly lower in tumors compared to uninvolved NBE (p < 0.0001) and was positively associated with adenocarcinoma histology (p < 0.001). GPRC5A airway expression was highest in lung disease-free NBE, decreased and intermediate in NBE of cancer-free COPD patients (p = 0.004) and further attenuated and lowest in epithelia of COPD patients with adenocarcinoma and SCC (p < 0.0001). Furthermore, GPRC5A mRNA was significantly decreased in NSCLCs and corre sponding NBE compared to uninvolved normal lung (p = 0.03). CONCLUSIONS: Our findings highlight decreased GPRC5A expression in the field cancerization of NSCLC, including that associated with lung inflammation. Assessment of the use of GPRC5A expression as a risk factor for NSCLC development in COPD patients is warranted.

A Postnatal Pax7 Progenitor Gives Rise to Pituitary Adenomas.

Pituitary adenomas are classified into functioning and nonfunctioning (silent) tumors on the basis of hormone secretion. However, the mechanism of tumorigenesis and the cell of origin for pituitary adenoma subtypes remain to be elucidated. Employing a tamoxifen-inducible mouse model, we demonstrate that a novel postnatal Pax7(+) progenitor cell population in the pituitary gland gives rise to silent corticotroph macro-adenomas when the retinoblastoma tumor suppressor is conditionally deleted. While Pax transcriptional factors are critical for embryonic patterning as well as postnatal stem cell renewal for many organs, we have discovered that Pax7 marks a restricted cell population in the postnatal pituitary intermediate lobe. This Pax7(+) early progenitor cell population is overlapping but ontologically downstream of the Nestin(+) pituitary stem cell population, yet upstream of another newly discovered Myf6(+) late progenitor cell population. Interestingly, the Pax7(+) progenitor cell population is evolutionarily conserved in primates and humans, and Pax7 expression is maintained not only in murine tumors but also in human functioning and silent corticotropinomas. Taken together, our results strongly suggest that human silent corticotroph adenomas may in fact arise from a Pax7 lineage of the intermediate lobe, a region of the human pituitary bearing closer scientific interest as a reservoir of pituitary progenitor cells.