Widespread Hypomethylation Occurs Early and Synergizes with Gene Amplification during Esophageal Carcinogenesis

Although a combination of genomic and epigenetic alterations are implicated in the multistep transformation of normal squamous esophageal epithelium to Barrett esophagus, dysplasia, and adenocarcinoma, the combinatorial effect of these changes is unknown. By integrating genome-wide DNA methylation, copy number, and transcriptomic datasets obtained from endoscopic biopsies of neoplastic progression within the same individual, we are uniquely able to define the molecular events associated progression of Barrett esophagus. We find that the previously reported global hypomethylation phenomenon in cancer has its origins at the earliest stages of epithelial carcinogenesis. Promoter hypomethylation synergizes with gene amplification and leads to significant upregulation of a chr4q21 chemokine cluster and other transcripts during Barrett neoplasia. In contrast, gene-specific hypermethylation is observed at a restricted number of loci and, in combination with hemi-allelic deletions, leads to downregulatation of selected transcripts during multistep progression. We also observe that epigenetic regulation during epithelial carcinogenesis is not restricted to traditionally defined “CpG islands,” but may also occur through a mechanism of differential methylation outside of these regions. Finally, validation of novel upregulated targets (CXCL1 and 3, GATA6, and DMBT1) in a larger independent panel of samples confirms the utility of integrative analysis in cancer biomarker discovery

Pregnancy in Obese Mice Protects Selectively against Visceral Adiposity and Is Associated with Increased Adipocyte Estrogen Signalling

Maternal obesity is linked with increased adverse pregnancy outcomes for both mother and child. The metabolic impact of excessive fat within the context of pregnancy is not fully understood. We used a mouse model of high fat (HF) feeding to induce maternal obesity to identify adipose tissue-mediated mechanisms driving metabolic dysfunction in pregnant and non-pregnant obese mice. As expected, chronic HF-feeding for 12 weeks preceding pregnancy increased peripheral (subcutaneous) and visceral (mesenteric) fat mass. However, unexpectedly at late gestation (E18.5) HF-fed mice exhibited a remarkable normalization of visceral but not peripheral adiposity, with a 53% reduction in non-pregnant visceral fat mass expressed as a proportion of body weight (P<0.001). In contrast, in control animals, pregnancy had no effect on visceral fat mass proportion. Obesity exaggerated glucose intolerance at mid-pregnancy (E14.5). However by E18.5, there were no differences, in glucose tolerance between obese and control mice. Transcriptomic analysis of visceral fat from HF-fed dams at E18.5 revealed reduced expression of genes involved in de novo lipogenesis (diacylglycerol O-acyltransferase 2--Dgat2) and inflammation (chemokine C-C motif ligand 20--Ccl2) and upregulation of estrogen receptor α (ERα) compared to HF non pregnant. Attenuation of adipose inflammation was functionally confirmed by a 45% reduction of CD11b+CD11c+ adipose tissue macrophages (expressed as a proportion of all stromal vascular fraction cells) in HF pregnant compared to HF non pregnant animals (P<0.001). An ERα selective agonist suppressed both de novo lipogenesis and expression of lipogenic genes in adipocytes in vitro. These data show that, in a HF model of maternal obesity, late gestation is associated with amelioration of visceral fat hypertrophy, inflammation and glucose intolerance, and suggest that these effects are mediated in part by elevated visceral adipocyte ERα signaling

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Nitrate and phosphate from various depths throughout the water column inside and outside a kelp forest near the Monterey Peninsula, California, USA from June to August 2018 and 2019

Dataset: Water column nutrients - Inside and outside kelpThis dataset includes nitrate and phosphate from various depths throughout the water column collected at mooring sites inside and outside a kelp forest near the Monterey Peninsula, California, USA. Data were collected from June to August in 2018 and 2019. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/863702NSF Division of Ocean Sciences (NSF OCE) OCE-1737096, NSF Division of Ocean Sciences (NSF OCE) OCE-173717

CTD casts paired with bi-weekly water sampling events at instrument mooring sites near the Monterey Peninsula, California, USA from June to August 2018 and 2019

Dataset: Water column CTD - Inside and outside kelpThese data were obtained from CTD casts paired with bi-weekly water sampling events at instrument mooring sites near the Monterey Peninsula, California, USA. Data were collected from June to August in 2018 and 2019. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/863637NSF Division of Ocean Sciences (NSF OCE) OCE-1737096, NSF Division of Ocean Sciences (NSF OCE) OCE-173717

Temperature data from Onset HOBO U22 loggers deployed at various depths on instrument moorings inside and outside of kelp forests near the Monterey Peninsula, California, USA from June to August 2018 and 2019

Dataset: HOBO U22 water column temperature - Inside and outside kelpThese data are from Onset HOBO U22 data loggers recording at 1-minute intervals deployed at various depths on instrument moorings from June to August in 2018 and 2019. Moorings were located inside and outside of a kelp forests near the Monterey Peninsula, California, USA. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/864813NSF Division of Ocean Sciences (NSF OCE) OCE-1737096, NSF Division of Ocean Sciences (NSF OCE) OCE-173717

Dissolved oxygen and temperature from PME miniDOT sensors recording at 1-minute intervals at various depths on instrument moorings inside and outside of kelp forests near the Monterey Peninsula, California, USA from June to August 2018 and 2019

Dataset: Dissolved oxygen and temperature (miniDOT) - Inside and outside kelpThese data are from PME miniDOT sensors recording dissolved oxygen and temperature at 1-minute intervals at various depths on instrument moorings from June to August in 2018 and 2019. Data were collected at mooring sites inside and outside of kelp forests near the Monterey Peninsula, California, USA. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/864402NSF Division of Ocean Sciences (NSF OCE) OCE-1737096, NSF Division of Ocean Sciences (NSF OCE) OCE-173717

Water level and seafloor temperature from Onset HOBO U20L loggers deployed on the seafloor adjacent to instrument moorings inside and outside of kelp forests near the Monterey Peninsula, California, USA from June to August 2018 and 2019

Dataset: HOBO U20L water level and seafloor temperature - Inside and outside kelpThese data are from Onset HOBO U20L data loggers recording at 1-minute intervals deployed on the seafloor from June to August in 2018 and 2019. The HOBO loggers were deployed adjacent to instrument moorings inside and outside of kelp forests near the Monterey Peninsula, California, USA. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/864720NSF Division of Ocean Sciences (NSF OCE) OCE-1737096, NSF Division of Ocean Sciences (NSF OCE) OCE-173717

Photosynthetically active radiation (PAR) from PME miniPAR loggers deployed at the seafloor near instrument moorings inside and outside of kelp forests near the Monterey Peninsula, California, USA from June to August 2018 and 2019

Dataset: Seafloor PAR - Inside and outside kelp forestThis data includes photosynthetically active radiation (PAR) at the seafloor near instrument moorings inside and outside of kelp forests from June to August in 2018 and 2019. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/865018NSF Division of Ocean Sciences (NSF OCE) OCE-1737096, NSF Division of Ocean Sciences (NSF OCE) OCE-173717

Temperature data from SeaBird SBE56 sensors deployed at various depths on instrument moorings inside and outside of kelp forests near the Monterey Peninsula, California, USA from June to August 2018 and 2019

Dataset: SBE56 water column temperature - Inside and outside kelpThese data are from SeaBird SBE56 sensors recording at 1-minute intervals deployed at various depths on instrument moorings from June to August in 2018 and 2019. Moorings were located inside and outside of kelp forests near the Monterey Peninsula, California, USA. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/865073NSF Division of Ocean Sciences (NSF OCE) OCE-1737096, NSF Division of Ocean Sciences (NSF OCE) OCE-173717