tbuckley/cabot-search huggingface dataset:
Sanitation workers: covid-19’s forgotten frontline
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Sanitation workers such as Iliyasu Abbas (pictured), a pit latrine and septic tank emptier in Nigeria's Kano state, have been largely forgotten during the covid-19 pandemic, despite risking their lives every day to provide a service essential to public health, the charity WaterAid says.In a report the charity said that, while many such workers have continued to work in hospitals and quarantine centres throughout the pandemic, few have received extra training or support from their employers, and personal protective equipment has often been scarce or unfit for purpose. 1 The workers' access to safe water, decent sanitation, and good hygiene facilities has also been poor.WaterAid is calling on governments, local authorities, employers, and the general public to protect, respect, support, and invest in these essential staff. 1 WaterAid.Sanitation workers: The forgotten frontline workers during the covid-19 pandemic.https://washmatters.wateraid.org/
DDRE-06. TARGETING THE SPHINGOLIPID BALANCE VIA ACID CERAMIDASE INHIBITION TO DECREASE GROWTH OF TMZ-RESISTANT GLIOBLASTOMA AND BLOCK MIGRATION
Authors: Cyntanna Hawkins, Amber Jones, Julia Ziebro, Emily Gordon, Catherine Libby, Sarah Williford, Jeremy Allegood, Sara Cooper, Sasanka Ramanadham, Ninh Doan, Anita Hjelmeland
Journal: Neuro-Oncology (2021)

Abstract Dysregulated sphingolipid metabolism is associated with many cancers; allowing cells to evade apoptosis through increases in sphingosine-1-phosphate (S1P) and decreases in ceramides. Ceramides can be hydrolyzed by ceramidases to sphingosine, which can then be phosphorylated by sphingosine kinases to S1P. S1P allows cells to evade apoptosis and increase migration, while shifts toward ceramides favor cell death. Glioblastoma (GBM) exhibits shifts in the sphingolipid balance towards S1P, contributing to chemoresistance and migration. Understanding of sphingolipid metabolism in GBM is still limited, and currently, there are no approved treatments to target the dysregulation. Acid ceramidase (ASAH1), a key enzyme in the production of S1P, is highly expressed in GBM and is associated with worse survival of GBM patients, as per The Cancer Genome Atlas data. To address the altered sphingolipid metabolism and therapeutic resistance in GBM, we explored the efficacy of pharmacologic and genetic inhibition of ASAH1 in both parental and temozolomide (TMZ)-resistant patient-derived xenografts. Cells were infected with ASAH1 shRNA or treated with ASAH1 inhibitors and assessed for cell growth and migration. Our work suggests that pharmacologic inhibition of ASAH1 induces cell death and that this effect is maintained in TMZ-resistant cells. Furthermore, we find a novel role for carmofur, an ASAH1 inhibitor, in the inhibition of GBM migration. Together, these data suggest the potential utility of normalizing the sphingolipid balance in the context of GBM TMZ resistance.
Collateral cardiovascular damage during the COVID-19 pandemic
Authors: Ramesh Nadarajah, Chris P. Gale
Journal: Nature Reviews Cardiology (2021)

Care pathways for ST-segment elevation myocardial infarction (STEMI) were interrupted during the coronavirus disease 2019 (COVID-19) pandemic. A new cardiac MRI study has revealed that increased total ischaemic time for patients with STEMI during major public health restrictions was associated with increased infarct size and other markers of myocardial damage.
Abstract 12676: Hypertrophic Cardiomyopathy in Infants of Diabetic Mothers is Associated With Significantly Worse In-Hospital Outcomes: A Multicenter Analysis
Authors: Ronnie T Collins, Elizabeth G Bond, Elijah H Bolin
Journal: Circulation (2021)

Introduction: Hypertrophic cardiomyopathy (HCM) is a known complication among infants of diabetic mothers (IDMs). Ventricular outflow tract obstruction is common in these newborns, often necessitating therapy with beta-blockers. Because of relatively small sample sizes, the in-hospital outcomes of IDMs with HCM are unknown. Hypothesis: HCM in IDM is associated with increased in-hospital mortality. Methods: We performed an analysis of all newborns with a diagnostic code for IDM admitted from 2004 to 2020 to one of the 49 children’s hospitals in the Pediatric Hospital Information System. Those with a diagnostic code for HCM were assigned to the HCM, and those without were assigned to the comparison group (No-HCM). Outcomes of interest included vasopressor use, cardiac arrest, use of extracorporeal membrane oxygenation (ECMO), length of stay, mechanical ventilation, and in-hospital mortality. Standard statistical techniques were used to assess differences between groups. Results: There were 37,085 IDMs (55% male) in the study cohort, 677 (1.8%) with a diagnosis of HCM. Prematurity was more common in No-HCM (43% versus 33%, p&lt;0.001), and birthweight was lower in No-HCM (3.3 kg [IQR: 2.5-3.9] versus 4.0 kg [IQR: 3.4-4.6], p&lt;0.001). HCM was twice as common in Black IDMs (3.1%) compared to White IDMs (1.6%)(p&lt;0.001). As shown in the Table, HCM was associated with all study outcomes of interest. Conclusions: HCM is diagnosed twice as often in Black IDMs as White IDMs. HCM in IDMs is associated with multiple negative, in-hospital outcomes, including mortality. Further investigation is needed to determine if specific management strategies can ameliorate these negative outcomes.
Phosphoglycerate Dehydrogenase Is Required for Germinal Center Formation and Is a Therapeutic Target in <i>MYC-</i>driven Lymphoma
Authors: Annalisa D'Avola, Nathalie Legrave, Mylene Tajan, Probir Chakravarty, Ryan Shearer, Hamish King, Eric Cheung, Andrew James Clear, Arief Suryono Gunawan, Lingling Zhang, Louisa James, James MacRae, John Gribben, Dinis Pedro Calado, Karen Vousden, John C. Riches
Journal: Blood (2021)
Nedd8-Activating Enzyme Inhibition Enhances Anti-Tumor Immunity and PD1 Blockade in <i>In Vivo</i> lymphoma Models
Authors: Xiaoguang Wang, Vi Lam, Dan Vuong, Tingting Liu, Olga Danilova, Tanya Siddiqi, Allison J Berger, Lili Wang, Alexey V. Danilov
Journal: Blood (2021)
Medicaid expansion and variability in mortality in the USA: a national, observational cohort study
Authors: Brian P Lee, Jennifer L Dodge, Norah A Terrault
Journal: The Lancet Public Health (2021)

BackgroundThe expansion of the Medicaid public health insurance programme has varied by state in the USA. Longer-term mortality and factors associated with variability in outcomes after Medicaid expansion are under-studied. We aimed to investigate the association of state Medicaid expansion with all-cause mortality.MethodsThis was a population-based, national, observational cohort study capturing all reported deaths among adults aged 25–64 years via death certificate data in the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database in the USA from Jan 1, 2010, to Dec 31, 2018. We obtained national demographic and mortality data for adults aged 25–64 years, and state-level demographics and 2010–18 mortality estimates for the overall population by linking federally maintained registries (CDC WONDER, Behavioral Risk Factor Surveillance System, Health Resources and Services Administration, US Census Bureau, and Bureau of Labor Statistics). States were categorised as Medicaid expansion or non-expansion states as classified by the Kaiser Family Foundation. Multivariable difference-in-differences analysis assessed the absolute difference in the annual, state-level, all-cause mortality per 100 000 adults after Medicaid expansion.FindingsAmong 32 expansion states and 17 non-expansion states, Medicaid expansion was associated with reductions in all-cause mortality (−11·8 deaths per 100 000 adults [95% CI −21·3 to −2·2]). There was variability in changes in all-cause mortality associated with Medicaid expansion by state (ranging from −63·8 deaths per 100 000 adults [95% CI −134·1 to −42·9] in Delaware to 30·4 deaths per 100 000 adults [–39·8 to 51·4] in New Mexico). State-level proportions of women (−17·8 deaths per 100 000 adults [95% CI −26·7 to −8·8] for each percentage point increase in women residents) and non-Hispanic Black residents (−1·4 deaths per 100 000 adults [–2·4 to −0·3] for each percentage point increase in non-Hispanic Black residents) were associated with greater adjusted reductions in all-cause mortality among expansion states.InterpretationAfter 4 years of implementation, Medicaid expansion remains associated with significant reductions in all-cause mortality, but reductions are variable by state characteristics. These results could inform policy makers to provide broad-based equitable improvements in health outcomes.FundingUniversity of Southern California Research Center for Liver Diseases.
Abstract 9356: The Effect of Intraoperative Oxygenation on Vascular Reactivity in Human Resistance Arterioles
Authors: Marcos G Lopez, Arvind K Pandey, Matthew S Shotwell, David G Harrison, Frederic T Billings
Journal: Circulation (2021)

Introduction: Hyperoxia during surgery is common and may promote oxidative stress. Oxidative stress uncouples endothelial nitric oxide synthase and may impair vascular reactivity, a key regulator of tissue perfusion. Hypothesis: Hyperoxia during cardiac surgery impairs vascular reactivity compared to normoxia. Methods: We isolated resistance-level arterioles from mediastinal fat collected from subjects in a clinical trial of hyperoxia versus normoxia during cardiac surgery. Tissue was obtained at the end of surgery, and arterioles from 24 subjects were mounted on a wire myograph. After norepinephrine contraction, we measured the endothelium-dependent response to acetylcholine and the endothelium-independent response to sodium nitroprusside. To further identify if hyperoxygenation impairs nitric oxide mediated vasodilation via oxidation of the soluble guanylyl cyclase heme moiety, we measured the response to the heme-independent soluble guanylyl cyclase activator cinaciguat. We compared relaxation to increasing doses of each vasodilator in normoxia vs. hyperoxia treated arterioles using repeated measures ANOVA and nonlinear mixed effects regression. Results: The acetylcholine response was uniformly impaired (P=0.98, Figure ). The sodium nitroprusside response was selectively impaired in hyperoxia treatment vs. normoxia as reflected by a higher EC50 (EC50: 50.1±6.3 x10-8 M for hyperoxia vs. 7.9 ± 0.8 x 10-8 M for normoxia, P=0.02) and decreased peak response. In striking contrast to the response to sodium nitroprusside, vasodilation evoked by cinaciguat was not impaired and was slightly enhanced for hyperoxia vs. normoxia (EC50: 7.9±0.8 x10-8 M vs. 15.8±6.2 x10-8 M; P=0.07, Figure). Conclusions: Intraoperative hyperoxia impaired human arteriole vasodilation likely via oxidation of the soluble guanylyl cyclase heme moiety. These data provide additional mechanistic insight into potential harmful effects of intraoperative hyperoxia.
The NLPHL Tumor Microenvironment Is Markedly Enriched in the Tigit and PD-1 Signalling Axes Compared to Classical Hodgkin Lymphoma
Authors: Jay Gunawardana, Muhammed B. Sabdia, Karolina Bednarska, Soi C. Law, Sandra Brosda, Hennes Tsang, Lilia Merida De Long, Andreea Zaharia, Justina Lee, Emily Jude, Eliza Hawkes, Karthik Nath, Clare Gould, Melinda Lea Burgess, Fiona Swain, Joshua W.D. Tobin, Colm Keane, Simone Birch, Dipti Talaulikar, Sanjiv Jain, Mohamed Shanavas, Cameron Snell, Maher Gandhi
Journal: Blood (2021)
Abstract 12511: Differential Regulation of Circulating Damage-Associated Molecular Patterns in Patients With Coronary Artery Ectasia
Authors: James N Tsoporis, Andreas Triantafyllis, Sahil Gupta, Shehla Izhar, Eleftherios Sakadakis, Angelos G Rigopoulos, Thomas G Parker, Ioannis Rizos
Journal: Circulation (2021)

Introduction: Coronary artery ectasia (CAE) defined as localized or diffuse non-obstructive coronary lesions is a rare but well-recognized pathological entity of the coronary arteries and characterized as a variant of coronary atherosclerosis. CAE commonly coexists with coronary artery disease (CAD). Although inflammation appears to be involved, the pathophysiology behind CAE remains unclear. Danger-associated molecular patterns (DAMPs) are altered metabolism products of necrotic or stressed cells, which are deemed as alarm signals by the innate immune system. Inflammatory agents are DAMP generators and DAMPs create a pro-inflammatory state. Hypothesis: We aimed to investigate the different patterns of serum DAMPs in patients with CAE, obstructive CAD and normal coronary arteries and the prognostic role of these in the pathogenesis of CAE. Methods: In this prospective cross-sectional study, 28 patients with CAE and nonobstructive CAD were enrolled in the study, 19 patients with obstructive CAD but without CAE, and 18 control subjects with normal coronary arteries that have been matched with the CAE patients for age and sex were also enrolled in our study population. Venous blood samples of the participants were collected for serum DAMP evaluation. Results: Patients with CAE and non-obstructive CAD had increased (30-35%) serum levels of the DAMPs, the receptor for advanced glycation end products (RAGE) ligand S100B and the toll-like receptor 4 ligand heat shock protein (HSP)70 compared to control subjects and patients with CAD. Additionally, CAE and non-obstructive CAD patients had decreased (30-40%) serum levels of potential DAMPs, the antioxidant DJ-1 and soluble (s)RAGE, a decoy molecule that bind excess RAGE ligands, compared to control subjects and CAD patients. Positive correlations were observed between S100B and HSP70 (p=00564), and DJ-1 and sRAGE (p=0.00461). All evaluated serum DAMPs were not different in CAD patients compared to control subjects. Conclusion: The differential regulation of the DAMPs S100B, HSP70, DJ-1 and sRAGE in CAE versus CAD makes them attractive novel biomarkers as therapeutic targets and therapeutics.
Practical Computer Vision Application to Compute Total Body Surface Area Burn
Authors: Jeff Choi, Advait Patil, Edward Vendrow, Gavin Touponse, Layla Aboukhater, Joseph D. Forrester, David A. Spain
Journal: JAMA Surgery (2021)

<h3>Importance</h3> Critical burn management decisions rely on accurate percent total body surface area (%TBSA) burn estimation. Existing %TBSA burn estimation models (eg, Lund-Browder chart and rule of nines) were derived from a linear formula and a limited number of individuals a century ago and do not reflect the range of body habitus of the modern population. <h3>Objective</h3> To develop a practical %TBSA burn estimation tool that accounts for exact burn injury pattern, sex, and body habitus. <h3>Design, Setting, and Participants</h3> This population-based cohort study evaluated the efficacy of a computer vision algorithm application in processing an adult laser body scan data set. High-resolution surface anthropometry laser body scans of 3047 North American and European adults aged 18 to 65 years from the Civilian American and European Surface Anthropometry Resource data set (1998-2001) were included. Of these, 1517 participants (49.8%) were male. Race and ethnicity data were not available for analysis. Analyses were conducted in 2020. <h3>Main Outcomes and Measures</h3> The contributory %TBSA for 18 body regions in each individual. Mobile application for real-time %TBSA burn computation based on sex, habitus, and exact burn injury pattern. <h3>Results</h3> Of the 3047 individuals aged 18 to 65 years for whom body scans were available, 1517 (49.8%) were male. Wide individual variability was found in the extent to which major body regions contributed to %TBSA, especially in the torso and legs. Anterior torso %TBSA increased with increasing body habitus (mean [SD], 15.1 [0.9] to 19.1 [2.0] for male individuals; 15.1 [0.8] to 18.0 [1.7] for female individuals). This increase was attributable to increase in abdomen %TBSA (mean [SD], 5.3 [0.7] to 8.7 [1.8]) among male individuals and increase in abdomen (mean [SD], 4.6 [0.6] to 6.8 [1.7]) and pelvis (mean [SD], 1.5 [0.2] to 2.9 [0.9]) %TBSAs among female individuals. For most body regions, Lund-Browder chart and rule of nines estimates fell outside the population's measured interquartile ranges. The mobile application tested in this study, Burn Area, facilitated accurate %TBSA burn computation based on exact burn injury pattern for 10 sex and body habitus-specific models. <h3>Conclusions and Relevance</h3> Computer vision algorithm application to a large laser body scan data set may provide a practical tool that facilitates accurate %TBSA burn computation in the modern era.
Abstract 14124: Long-term Cardiovascular Mortality Disparities By Race In The Us Adult Population
Authors: Srikanta Banerjee, David Harvey, Karen Banerjee, Michael Schwab
Journal: Circulation (2021)

Cardiovascular disease remains the leading cause of mortality and disproportionately affects vulnerable populations. Among disparities in overall mortality, Black Americans experience higher mortality rates than White Americans. However, it is unknown, if the same disparities persist after long-term follow-up. In this study, we assessed the hypothesis that Non-Hispanic Black Americans experience higher 10-year cardiovascular disease (CVD) mortality follow-up than Non-Hispanic White Americans. We analyzed data on adults (≥ 20 years) from the 1999-2010 National Health and Nutrition Examination Survey, with mortality data obtained through 2015. The causes of death for adults (N=4037) were defined using the International Classification of Disease coding (ICD-10). Complex Samples Cox regression was used to assess if diabetes status modified the relationship between race and CVD-mortality. Out of the respondents (N=4037), 17.7% of Non-Hispanic Blacks individuals died from CVD versus 16.4% among Non-Hispanic White counterparts. During the 11-year follow-up, the hazard ratio (HR) for CVD-mortality among Non-Hispanic Black Adults, with adjustment for age and gender only, was 1.36; 95% confidence interval [CI: 1.11, 1.67]. Over the age of 20, there is higher CVD-mortality in Non-Hispanic Black men (HR, 1.15; 95% CI, 0.91–2.05, p &gt; .05) and women (HR, 2.50; 95% CI, 1.56–3.99, p &lt; .01) than in their White counterparts even after controlling for medical (obesity, CVD, diabetes) and demographic (education, age, food insecurity level, and poverty level) variables. In conclusion, Black Americans experience higher probability of death from cardiovascular disease in 10-year follow-up than other races. Due to the chronicity of CVD, disparities are compounded over a long period of time. The observed ethnic disparities in treatment and control, with the relative deficits observed in Black Americans, are potentially due to ethnic differences in healthcare-seeking behaviors and access to care. Policy considerations should address how to improve equitable screening and prevention, as it pertains to race.
Abstract 10234: Exaggerated Blood Pressure Response to Static Exercise Following Muscle Ischemia-Reperfusion: A Time-Course Investigation
Authors: Lu Qin, Jianhua Li
Journal: Circulation (2021)

Background: Peripheral artery disease (PAD) is one of the major cardiovascular concerns and dramatically reduces the blood flow supply in the affected limbs. A combination of revascularization surgery in the femoral artery and supervised exercise intervention is among the most general approaches for the treatment of PAD. However, the effects of ischemia-reperfusion (IR), which is one of the most predominant complications resulting from the revascularization surgery, on exercise-induced arterial blood pressure (BP) response are poorly understood. Methods: We examined the BP response to static muscle contraction in rats at different time points after the IR procedure. Four groups were included: 1. Sham rats; 2. Rats with 18 hours following IR (IR 18h); 3. Rats with 66 hours following IR (IR 66h); 4. Rats with 114 hours following IR (IR 114h). One-way ANOVA with LSD post-hoc test was applied to analyze the difference among groups. Data were presented as Mean ± Standard Deviation. Results: Compared with Sham group, the BP response to static muscle contraction was significantly increased in rats with all the investigated time points. The response of mean arterial pressure was 19±3 mmHg in Sham rats (n=6); 29±9 mmHg in IR 18h rats (n=8); 26±7 mmHg in IR 66h rats (n=10); 26±4 mmHg in IR 114h rats (n=9) ( P &lt;0.05; the groups at three time courses vs. Sham). There was no significant difference observed in the peak developed tension during muscle contraction among all the groups (Sham rats: 543±101g; IR 18h rats: 520±28g; IR 66h rats: 554±66g; IR 114h rats: 562±45g; P &gt;0.05). Conclusions: IR significantly exaggerates the static exercise-induced BP response. Whereas the BP response tends to decrease with the prolonged IR time, the exaggerated BP response remains through time points from post IR 18 hours to 114 hours. The data suggest that a chronic time course should be considered to alleviate IR-induced ischemic injury in PAD patients for clinical interventions appropriated and exercise.
Abstract 13101: Bleeding Complications in Patients Undergoing Percutaneous Coronary Intervention With Intra-Aortic Balloon Pump and/or Impella Support: A System Wide Analysis
Authors: Md Bhuiyan, Tia Bimal, Puneet Gandotra, Joanna Fishbein, Samy Selim, Lawrence Ong, Luis Gruberg
Journal: Circulation (2021)

Background: Mechanical circulatory support (MCS) devices are used to provide temporary hemodynamic support in patients undergoing percutaneous coronary interventions (PCI). Currently, the most used percutaneous devices are the intra-aortic balloon pump (IABP) and the Impella micro-axial flow device. Aim: To assess bleeding complications associated with IABP and/or Impella in patients undergoing PCI. Methods: Between 12/2010 and 03/2018 a total of 883 patient underwent PCI with MCS at 6 hospitals in our system. Patients were divided into three groups: IABP (n=679), Impella (n=171) and IABP with Impella (n=33). Bleeding complications were classified according to the Bleeding Academic Research Consortium (BARC). BARC Type 4 (coronary bypass grafting-related) and BARC Type 5 (fatal bleeding) bleeding events were excluded. Chi-square tests and logistic regression were utilized with p&lt;0.05 significance level. Multiple pairwise comparisons using Bonferroni-adjusted p-value threshold of p&lt;0.0167 for level of significance was also performed. A multiple variable analysis will be presented. Results: Clinical characteristics, bleeding complications and in-hospital outcomes are shown in the Table. There were significant differences in these variables except age and gender among the three groups. A minority of patients (4%) were treated simultaneously with both devices, however 45% of these patients had a significant bleeding event and 33% died in the hospital. No significant difference in bleeding complications between IABP and Impella (each alone) was found (p=0.38). Conclusions: In patients undergoing PCI, use of a combination of IABP and Impella was associated with significantly higher rate of intermediate or major bleeding complications when compared with patients treated with either device alone. Furthermore, these patients had significantly higher in-hospital mortality rates.