tbuckley/cabot-search huggingface dataset:
Abstract 3307: Induction of autophagy as a mechanism of therapeutic resistance in head and neck cancer
Authors: Jaimee C. Eckers, Adam D. Swick, Tyler Fowler, Justin Skiba, Kwangok P. Nickel, Randall J. Kimple
Journal: Cancer Research (2017)

Abstract Background: In the curative setting for head and neck cancer (HNC) a commonly used treatment is radiation combined with the anti-EGFR monoclonal antibody cetuximab (CTX). However, despite decades of research into improved treatments, therapeutic resistance remains a major challenge for this malignancy with roughly 40% of patients developing recurrent disease. We are studying the molecular mechanisms by which radiation and cetuximab induce autophagy and how this process can be modulated to improve the efficacy of therapy. Methods: We evaluated a panel of both human papillomavirus (HPV) positive and negative HNC cell lines for autophagic response to both CTX treatment and ionizing radiation (XRT). Induction of autophagy was detected by immunoblot flux assays for LC3 and p62 and by immunofluorescent staining of autophagic vesicles. siRNA knockdown of EGFR, LAMPT4B, ULK1, Beclin1 and others was used to probe the involvement of different signaling molecules. The addition of specific autophagy inhibitors, such as the ULK1 inhibitor SBI-0206965, to CTX or XRT treatment was tested to determine whether the reduction of autophagic response reduced cell survival in a clonogenic survival assay. Induction of apoptosis was analyzed by immunoblot against cleaved Caspase and PARP and AnnexinV staining. Results: Flux assays revealed that both CTX and XRT induced autophagy in a time and dose dependent manner. Immunofluorescent staining of LC3 to identify autophagic vesicles showed that a relatively small fraction of the total cell population is able to induce this response. Specific siRNA knockdown of EGFR and LAMPT4B was able to abrogate the induction of autophagy in response to both CTX and XRT. Involvement of alternative downstream pathways involving either ULK1 and Beclin1 or p53 in response to either treatment is under investigation. To determine whether blockade of cytoprotective autophagy can help overcome therapeutic resistance, we tested specific autophagy inhibitors in combination with either CTX or XRT treatment. The addition of the ULK1 inhibitor to CTX or XRT induced apoptosis as shown by caspase activity, AnnexinV staining, and reduced cell survival in clonogenic assays. Conclusions: Autophagy may play a critical and protective role in how head and neck cancers respond to therapeutic stress. The addition of specific autophagy inhibitors to standard treatments may provide a way to overcome resistance to therapy. Citation Format: Jaimee C. Eckers, Adam D. Swick, Tyler Fowler, Justin Skiba, Kwangok P. Nickel, Randall J. Kimple. Induction of autophagy as a mechanism of therapeutic resistance in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3307. doi:10.1158/1538-7445.AM2017-3307
Abstract 157: Unique Features of Cortical Bone Stem Cells Associated With Enhanced Cardiac Repair
Authors: Sadia Mohsin, Constantine D Troupes, Timothy Starosta, Thomas E Sharp, Shavon Smith, Elorm J Agra, Hajime Kubo, Remus M Berretta, Steven R Houser
Journal: Circulation Research (2015)

Rationale: Adoptive transfer of bone marrow and cardiac derived stem cells (CDCs) into failing human hearts has been shown to be safe, yet these cells have only induced modest improvements after myocardial infarction (MI). Recently we have shown in a mouse model that cortical bone derived stem cells (CBSCs) induced a greater enhancement of cardiac function after MI through enhanced paracrine signaling and transdifferentiation of CBSCs into new cardiac tissue. However, the reparative potential of CBSCs relative to other stem cell types including bone marrow derived mesenchymal stem cells (MSCs) and CDCs is not known. Objective: To characterize surface marker expression, proliferation, survival, migration and differentiation capacity of swine CBSCs relative to MSCs and CDCs. Methods and Results: CBSCs, MSCs and CDCs were isolated from Gottingen miniswine. CBSCs were morphologically distinct from MSCs and CDCs, with differences in length to width ratio and overall cell surface area. Cell surface marker profiling using RT-PCR analysis revealed that CBSCs express some of the classical MSC markers such as CD106, CD271, CD105, CD90 and CD29 and are negative for CD45 and CD11-b. CBSCs had an enhanced proliferation capacity versus CDCs and MSCs, measured by CyQuant assay. Concurrently CBSCs had significantly decreased population-doubling time (3.57 and 1.26 fold decrease) as compared to MSC and CDCs. CBSCs exhibit enhanced survival after exposure to apoptotic stimuli as compared to MSCs measured by Annexin-V staining. A significantly greater % of CBSCs expressed markers of cardiac lineage commitment when exposed to dexamethasone than did CDCs or MSCs. Markers of cardiac lineages including GATA-4, α SMA, Troponin T, sm22 were measured with RT-PCR and immunocytochemistry. Conclusion: CBSCs have enhanced proliferative, survival capacity and cardiac lineage commitment versus CDCs and MSCs that could account for their enhanced effects on cardiac regeneration after myocardial infarction.
National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13–17 Years — United States, 2017
Authors: Tanja Y. Walker, Laurie D. Elam-Evans, David Yankey, Lauri E. Markowitz, Charnetta L. Williams, Sarah A. Mbaeyi, Benjamin Fredua, Shannon Stokley
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of persons aged 11-12 years with human papillomavirus (HPV) vaccine, quadrivalent meningococcal conjugate vaccine (MenACWY), and tetanus and reduced diphtheria toxoids and acellular pertussis vaccine (Tdap). A booster dose of MenACWY is recommended at age 16 years (1), and catch-up vaccination is recommended for hepatitis B vaccine (HepB), measles, mumps, and rubella vaccine (MMR), and varicella vaccine (VAR) for adolescents whose childhood vaccinations are not up to date (UTD) (1). ACIP also recommends that clinicians may administer a serogroup B meningococcal vaccine (MenB) series to adolescents and young adults aged 16-23 years, with a preferred age of 16-18 years (2). To estimate U.S. adolescent vaccination coverage, CDC analyzed data from the 2017 National Immunization Survey-Teen (NIS-Teen) for 20,949 adolescents aged 13-17 years.* During 2016-2017, coverage increased for ≥1 dose of HPV vaccine (from 60.4% to 65.5%), ≥1 dose of MenACWY (82.2% to 85.1%), and ≥2 doses of MenACWY (39.1% to 44.3%). Coverage with Tdap remained stable at 88.7%. In 2017, 48.6% of adolescents were UTD with the HPV vaccine series (HPV UTD) compared with 43.4% in 2016.† On-time vaccination (receipt of ≥2 or ≥3 doses of HPV vaccine by age 13 years) also increased. As in 2016, ≥1-dose HPV vaccination coverage was lower among adolescents living in nonmetropolitan statistical areas (MSAs) (59.3%) than among those living in MSA principal cities (70.1%).§ Although HPV vaccination initiation remains lower than coverage with MenACWY and Tdap, HPV vaccination coverage has increased an average of 5.1 percentage points annually since 2013, indicating that continued efforts to target unvaccinated teens and eliminate missed vaccination opportunities might lead to HPV vaccination coverage levels comparable to those of other routinely recommended adolescent vaccines.
Perfusion Imaging Distinguishes Exercise Pulmonary Arterial Hypertension at Rest
Authors: Puja Kohli, Vanessa J. Kelly, Ekaterina G. Kehl, Josanna Rodriguez-Lopez, Kathryn A. Hibbert, Mamary Kone, David M. Systrom, Aaron B. Waxman, Jose G. Venegas, Richard Channick, Tilo Winkler, R. Scott Harris
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Vaccination Coverage Among Children Aged 19–35 Months — United States, 2016
Authors: Holly A. Hill, Laurie D. Elam-Evans, David Yankey, James A. Singleton, Yoonjae Kang
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Vaccination is the most effective intervention to reduce morbidity and mortality from vaccine-preventable diseases in young children (1). Data from the 2016 National Immunization Survey-Child (NIS-Child) were used to assess coverage with recommended vaccines (2) among children aged 19-35 months in the United States. Coverage remained ≥90% for ≥3 doses of poliovirus vaccine (91.9%), ≥1 dose of measles, mumps, and rubella vaccine (MMR) (91.1%), ≥1 dose of varicella vaccine (90.6%), and ≥3 doses of hepatitis B vaccine (HepB) (90.5%). Coverage in 2016 was approximately 1-2 percentage points lower than in 2015 for ≥3 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP), ≥3 doses of poliovirus vaccine, the primary Haemophilus influenzae type b (Hib) series, ≥3 HepB doses, and ≥3 and ≥4 doses of pneumococcal conjugate vaccine (PCV), with no changes for other vaccines. More direct evaluation of trends by month and year of birth (3) found no change in coverage by age 2 years among children included in combined data from the 2015 and 2016 NIS-Child (born January 2012 through January 2015). The observed decreases in annual estimates might result from random differences in vaccination coverage by age 19 months between children sampled in 2016 and those sampled in 2015, among those birth cohorts eligible to be sampled in both survey years. For most vaccines, 2016 coverage was lower among non-Hispanic black* (black) children than among non-Hispanic white (white) children, and for children living below the federal poverty level† compared with those living at or above the poverty level. Vaccination coverage was generally lower among children insured by Medicaid (2.5-12.0 percentage points), and was much lower among uninsured children (12.4-24.9 percentage points), than among children with private insurance. The Vaccines for Children§ (VFC) program was designed to increase access to vaccines among children who might not otherwise be vaccinated because of inability to pay. Greater awareness and facilitating use of VFC might be helpful in reducing these disparities. Efforts should also be focused on minimizing breaks in continuity of health insurance and eliminating missed opportunities to vaccinate children during visits to health care providers. Despite the observed disparities and small changes in coverage from 2015, vaccination coverage among children aged 19-35 months remained high and stable in 2016.
Abstract 13433: Angiotensin II Type 2 Receptor Regulates Skeletal Myoblast Differentiation: Implications for treatment of Cachexia and Skeletal Muscle Wasting
Authors: Tadashi Yoshida, Patrice Delafontaine
Journal: Circulation (2014)

Patients with advanced congestive heart failure (CHF) or chronic kidney disease (CKD) often have increased angiotensin II (Ang II) levels and cachexia. We previously demonstrated that Ang II infusion in rodents causes skeletal muscle wasting and decreases muscle regenerative potential via Ang II type 1 receptor (AT1R) signaling, likely contributing to cachexia in CHF and CKD. However, the potential role of Ang II type 2 receptor (AT2R) signaling in skeletal muscle physiology remains unknown. We found that AT2R expression was robustly increased in mouse skeletal myoblasts during differentiation, suggesting that the AT2R plays an important role in skeletal muscle regeneration. To test this hypothesis, we infused mice with AT2R antagonist PD123319 (PD, 30 mg/kg/d) or agonist CGP123319 (CGP, 1 μg/kg/min) during cardiotoxin (CTX)-induced muscle injury and regeneration. PD reduced the size of regenerating myofibers (727.5±54.6 and 516.0±37.0 μm2 in sham and PD, respectively, p&lt;0.05) and expression of the myoblast differentiation markers myogenin and eMyHC (56.9% and 40.2% decrease in PD, respectively. p&lt;0.01), whereas CGP had the opposite effects. siRNA mediated AT2R knockdown in mouse primary myoblasts suppressed the increase of myogenin and desmin, resulting in lowered differentiation. We analyzed changes in phosphoprotein levels in myoblasts after AT2R knockdown by phosphoprotein array and identified multiple changes, including increased phospho-ERK1/2 levels. Importantly, inhibition of ERK1/2 restored normal myoblast differentiation in the setting of AT2R knockdown, suggesting the AT2R positively regulates myoblast differentiation by reducing ERK1/2 activity. Furthermore, we found that skeletal muscle regeneration was reduced (decreased regenerating myofiber size and myogenin/desmin expression) in a mouse myocardial infarction model of CHF, concomitantly with markedly blunted increase of AT2R expression, strongly suggesting that the AT2R plays an important role in the reduction of skeletal muscle function in CHF. These data indicate that AT2R signaling positively regulates myoblast differentiation and potentiates skeletal muscle regeneration, providing a new therapeutic target in wasting disorders such as CHF and CKD.
Role of TLR4 in the Activation of a Pro-Tumor Phenotype of Mesenchymal Stromal Cells in Mutiple Myeloma
Authors: Cesarina Giallongo, Daniele Tibullo, Nunziatina Laura Parrinello, Giuseppina Camiolo, Piera La Cava, Alessandra Romano, Fabrizio Puglisi, Giuseppe Sapienza, Concetta Conticello, Giuseppe A. Palumbo, Francesco Di Raimondo
Journal: Blood (2018)
P1.09-013 Profiling Response to Chemotherapy in Malignant Pleural Mesothelioma Among Hispanics (MeSO-CLICaP)
Authors: A. Cardona, O. Arrieta, L. Rojas, L. Corrales, B. Wills, G. Oblitas, L. Bacon, C. Martin, M. Cuello, L. Mas, C. Vargas, H. Carranza, J. Otero, M.A. Pérez, L. González, L. Chirinos, R. Rosell
Journal: Journal of Thoracic Oncology (2017)
Abstract 20519: Effects of Obstructive Sleep Apnea on the Outcomes of Atrial Fibrillation: A Nationwide Analysis
Authors: Syed A Ahsan, Seyed Hamed Hosseini Dehkordi, Shawn Lee, Farid Gholitabar, Alejandro Lemor, Navid Gholitabar, Eyal Herzog
Journal: Circulation (2017)

Introduction: Recent studies suggest patients with atrial fibrillation (AF) who suffer from obstructive sleep apnea (OSA) have varied responses to ablative procedures, as AF substrates in these patients might be different from patients with primary AF. We investigated the effects of coexistence of these two conditions on mortality and hospital costs in patients who underwent AF ablation. We hypothesized there would be significant differences in mortality between the two populations. Methods: This is a retrospective cohort study using the 2013 National Inpatient Sample (NIS) of males and females over 18 hospitalized with AF who underwent ablation, based on ICD-9 codes. The population was divided into patients with and without a concomitant diagnosis of OSA. The primary outcome was all cause inpatient mortality and secondary outcomes were mean length of stay (LOS), and total hospital costs. The multivariate logistic regression model was used to adjust for potential confounders including age, gender, race, h...
Status of Research Funded by the American Diabetes Association—Year 4
Authors: Mayer B. Davidson
Journal: Diabetes Care (2003)

In 1998, the American Diabetes Association (ADA) announced an ambitious Five Year Plan for funding for research, namely that by Fiscal Year 2003, one of every three Total Public Support dollars raised by the ADA would be allocated to Research Awards and Grants. Since 1998, I have kept the Professional Section apprised of progress toward that goal by yearly letters published in this journal. The results of the 4th year, Fiscal Year 2002, are included in Table 1.

The reason for keeping the Professional Section informed …
Abstract 007: Comparative Effectiveness of Blood Pressure Lowering Drugs in Reducing Cardiovascular Events: Results From a Network Meta-Analysis
Authors: Jingkai Wei, Karla I Galaviz, Alysse Kowalski, Matthew J Magee, J. Sonya Haw, K.M. Venkat Narayan, Mohammed K Ali
Journal: Circulation (2018)

Introduction: Blood pressure lowering drugs help prevent cardiovascular events though less is known about the comparative effectiveness of different drug classes. We aimed to compare the effect of different blood pressure lowering drugs classes on cardiovascular risk. Hypothesis: We hypothesized that the cardiovascular preventive effects of blood pressure lowering drugs would vary among different types of drug classes. Methods: PubMed, EMBASE, and Cochrane Library databases were searched for articles published between January 1, 1990 and June 30, 2014. Study eligibility criteria included randomized controlled trials testing blood pressure-lowering drugs, including angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, calcium-channel blockers, beta-blockers, and thiazide diuretics that reported cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, coronary revascularization and composite cardiovascular events) with at least 6 months of follow-up. Data from studies that met inclusion criteria were independently extracted by two reviewers using a standardized extraction form. For each outcome, a Frequentist, random effects network meta-analysis model was used to compare risk reductions between drug classes. The relative ranking probability of each blood pressure lowering drug class being the most effective was estimated using rankogram curves, surface under the cumulative ranking curves, and mean ranks. Results: A total of 102 trials that included 415,047 participants (mean age 65.1 years, 60.0% male) met inclusion criteria. Compared to placebo, blood pressure lowering drugs reduced the risk of composite cardiovascular events by 11-18% in aggregate. Calcium channel blockers were the most effective in reducing composite cardiovascular events risk (RR=0.82, 95% CI: 0.77, 0.88), stroke (RR=0.68, 95% CI: 0.61, 0.75) and revascularization (RR=0.84, 95% CI: 0.77, 0.92); angiotensin-converting-enzyme inhibitors were the most effective in reducing cardiovascular death (RR=0.85, 95% CI: 0.80, 0.91) and myocardial infarction (RR=0.83, 95% CI: 0.77, 0.91). Effects of drugs were influenced by blood pressure, where each 10mmHg reduction in systolic and diastolic blood pressure, regardless of drug class, was associated with a 2.5% (95% CI: -3.8, -1.2) and 5.4% (95% CI: -8.0, -2.4) lower risk of composite cardiovascular events, respectively. Conclusion: Angiotensin-converting-enzyme inhibitors had an advantage over other blood pressure lowering drugs in preventing myocardial infarction and cardiovascular death, while calcium channel blockers were more effective in preventing overall cardiovascular events, stroke and revascularization. Future studies should compare the effectiveness of combination of drug classes in reducing cardiovascular events.
305 STRATEGY TO OVERCOME CHEMORESISTANCE IN HEPATOCELLULAR TUMOURS BY ENHANCING THE EXPRESSION OF THE DRUG TRANSPORTER OATP1B1
Authors: O. Briz, E. Herraez, L. Sanchez-Vicente, J. Vaquero, E. Lozano, S. Jimenez, B. Castaño, J.J.G. Marin
Journal: Journal of Hepatology (2012)
Abstract 12273: High Prevalence of Brugada Syndrome Among Thai Migrant Workers in Israel
Authors: Wittawin Chantapoh, Pattara Rattanawong, Tachapong Ngamukos, Ross J Simpson, Punnapat Thawepornpuripong, Mongkol Kunaporn, Piyamitr Sritara, Prin Vathesatogkit, Eugene Chung
Journal: Circulation (2017)

Background: According to the report of Thailand-Israel cooperation on the placement of workers, an incidence of unclear etiology sudden unexpected death (SUD) in Thai migrant workers in Israel betw...
Progress Toward Global Eradication of Dracunculiasis—January 2011- June 2012
Journal: JAMA (2013)

Dracunculiasis (Guinea worm disease) is caused by Dracunculus medinensis, a parasitic worm. Approximately 1 year after a person acquires infection from contaminated drinking water, the worm will emerge through the skin, usually on the lower limb. Pain and secondary bacterial infection can cause temporary or permanent disability that disrupts work and schooling. In 1986, the World Health Assembly called for dracunculiasis elimination. The global Guinea Worm Eradication Program, supported by The Carter Center, World Health Organization (WHO), UNICEF, CDC, and other partners, began assisting ministries of health of countries in which dracunculiasis is endemic in meeting this goal. At that time, an estimated 3.5 million cases occurred each year in 20 countries in Africa and Asia. This report updates published (3-5) and unpublished surveillance data reported by ministries of health and describes progress toward dracunculiasis eradication. A total of 148 cases were reported in 2013 from five countries (in order of prevalence: South Sudan, Chad, Mali, Ethiopia, and Sudan) compared with 542 cases in 2012 from four countries (South Sudan, Chad, Mali, and Ethiopia). The disease remains endemic in four countries in 2014 (South Sudan, Chad, Mali, and Ethiopia), but the overall incidence is falling faster in 2013 compared with 2012 (by 73%) and continues to fall faster in the first 6 months of 2014 (by 71%) compared with the same period in 2013. Failures in surveillance and containment, lack of clean drinking water, insecurity in Mali and parts of South Sudan, and an unusual epidemiologic pattern in Chad are the main remaining challenges to dracunculiasis eradication.