Calcium Coordination Solids for pH-Triggered Release of Olsalazine

Calcium coordination solids were synthesized and evaluated for delivery of olsalazine (H_4olz), an anti-inflammatory compound used for treatment of ulcerative colitis. The materials include one-dimensional Ca(H_2olz)⋅4 H_2O chains, two-dimensional Ca(H_2olz)⋅2 H_2O sheets, and a three-dimensional metal-organic framework Ca(H_2olz)⋅2DMF (DMF=N,N-dimethylformamide). The framework undergoes structural changes in response to solvent, forming a dense Ca(H_2olz) phase when exposed to aqueous HCl. The compounds Ca(H_2olz)⋅x H_2O (x=0, 2, 4) were each pressed into pellets and exposed to simulated gastrointestinal fluids to mimic the passage of a pill from the acidic stomach to the pH-neutral intestines. All three calcium materials exhibited a delayed release of olsalazine relative to Na_2(H_2olz), the commercial formulation, illustrating how formulation of a drug within an extended coordination solid can serve to tune its solubility and performance

Calcium Coordination Solids for pH-Triggered Release of Olsalazine

Calcium coordination solids were synthesized and evaluated for delivery of olsalazine (H_4olz), an anti-inflammatory compound used for treatment of ulcerative colitis. The materials include one-dimensional Ca(H_2olz)⋅4 H_2O chains, two-dimensional Ca(H_2olz)⋅2 H_2O sheets, and a three-dimensional metal-organic framework Ca(H_2olz)⋅2DMF (DMF=N,N-dimethylformamide). The framework undergoes structural changes in response to solvent, forming a dense Ca(H_2olz) phase when exposed to aqueous HCl. The compounds Ca(H_2olz)⋅x H_2O (x=0, 2, 4) were each pressed into pellets and exposed to simulated gastrointestinal fluids to mimic the passage of a pill from the acidic stomach to the pH-neutral intestines. All three calcium materials exhibited a delayed release of olsalazine relative to Na_2(H_2olz), the commercial formulation, illustrating how formulation of a drug within an extended coordination solid can serve to tune its solubility and performance

Global declines in coral reef calcium carbonate production under ocean acidification and warming

Ocean warming and acidification threaten the future growth of coral reefs. This is because the calcifying coral reef taxa that construct the calcium carbonate frameworks and cement the reef together are highly sensitive to ocean warming and acidification. However, the global-scale effects of ocean warming and acidification on rates of coral reef net carbonate production remain poorly constrained despite a wealth of studies assessing their effects on the calcification of individual organisms. Here, we present global estimates of projected future changes in coral reef net carbonate production under ocean warming and acidification. We apply a meta-analysis of responses of coral reef taxa calcification and bioerosion rates to predicted changes in coral cover driven by climate change to estimate the net carbonate production rates of 183 reefs worldwide by 2050 and 2100. We forecast mean global reef net carbonate production under representative concentration pathways (RCP) 2.6, 4.5, and 8.5 will decline by 76, 149, and 156%, respectively, by 2100. While 63% of reefs are projected to continue to accrete by 2100 under RCP2.6, 94% will be eroding by 2050 under RCP8.5, and no reefs will continue to accrete at rates matching projected sea level rise under RCP4.5 or 8.5 by 2100. Projected reduced coral cover due to bleaching events predominately drives these declines rather than the direct physiological impacts of ocean warming and acidification on calcification or bioerosion. Presently degraded reefs were also more sensitive in our analysis. These findings highlight the low likelihood that the world’s coral reefs will maintain their functional roles without near-term stabilization of atmospheric CO2 emissions

Anxious-depression among Hispanic/Latinos from different backgrounds: results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Anxious-depression is a constellation of symptoms, frequently encountered among patients in primary care centers. There is a need to study how anxious-depression presents among Hispanic/Latinos of different backgrounds

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

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

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

Effects of a LPG stove and fuel intervention on adverse maternal outcomes: a multi-country randomized controlled trial conducted by the Household Air Pollution Intervention Network (HAPIN)

Household air pollution from solid cooking fuel use during gestation has been associated with adverse pregnancy and birth outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial of free liquefied petroleum gas (LPG) stoves and fuel in Guatemala, Peru, India, and Rwanda. A primary outcome of the main trial was to report the effects of the intervention on infant birth weight. Here we evaluate the effects of a LPG stove and fuel intervention during pregnancy on spontaneous abortion, postpartum hemorrhage, hypertensive disorders of pregnancy, and maternal mortality compared to women who continued to use solid cooking fuels. Pregnant women (18-34 years of age; gestation confirmed by ultrasound at 9-19 weeks) were randomly assigned to an intervention (n = 1593) or control (n = 1607) arm. Intention-to-treat analyses compared outcomes between the two arms using log-binomial models. Among the 3195 pregnant women in the study, there were 10 spontaneous abortions (7 intervention, 3 control), 93 hypertensive disorders of pregnancy (47 intervention, 46 control), 11 post postpartum hemorrhage (5 intervention, 6 control) and 4 maternal deaths (3 intervention, 1 control). Compared to the control arm, the relative risk of spontaneous abortion among women randomized to the intervention was 2.32 (95% confidence interval (CI): 0.60, 8.96), hypertensive disorders of pregnancy 1.02 (95% CI: 0.68, 1.52), postpartum hemorrhage 0.83 (95% CI: 0.25, 2.71) and 2.98 (95% CI: 0.31, 28.66) for maternal mortality. In this study, we found that adverse maternal outcomes did not differ based on randomized stove type across four country research sites

The Lantern, 2018-2019

The Treasure Buried in Ponce de Leon\u27s Fountain of Youth Archaeological Park • High Cards on the Low River • Sestina of a Vagina left in the microwave too long • Keeps on Tripping • The Auction • Nuclear Meltdown on Seedship C5B.6 • Cock Fight • An Interview with God • Minimum Wage • Star-Crossed Lovers • Romeo Echo Alpha • PM Entertainment, or Action Beats • The Gospel of Aggregates • Hel Hath no Fury • Crossing the Line • Mango de la hora • Stress Judgment • Perception (Part 2) • Rain Falling Up • Church: the Italian Market • Landscape with the Fall of Hillary • Forced to Ponder • Morally Upright • Adulthood • Migration in Tandem • Hospital Bed • To Autumn (After Keats) • Selected Tweets • Hidden Moments • Mysteries are Wrong • Jukebox Memory • Flames • A Simple Moment • The Farmhouse • Lord, Let Me Catch a Fish • Sun-Kissed • Five • The Thing • The Moons of Mars • You are Weak • You Kept Me Quiet • Offer Her a Seat • Sacraments • Cigar • The Lake George Mafia • Houses • Spun Out • To Romanticize the Restless • 12/25/17 • skylight • lanternflies • Goo Girls • Toi Le • Lovers, Thinkers, Rebels • home in paradise • Irreverence • The Fisherman • St Mary Episcopal Cathedral, Edinburgh • Mirror 2https://digitalcommons.ursinus.edu/lantern/1187/thumbnail.jp