tbuckley/cabot-search huggingface dataset:
Abstract A15: The relationship between cervical cancer associated genes and human papilloma viruses in rural Africans in Zaria
Authors: John Idoko, Mohammed Faruk, Jigo Dangude Yaro, James Oluwa Enemari, Peter Akpulu
Journal: Cancer Research (2017)

Abstract Cervical cancer is a major public health problem and one of the leading gynecological cancers in developing nations. Reports from Nigeria, the largest black nation in the world by population, show that the national incidence of cervical cancer is 250/100,000. We sought to evaluate the relationship between cervical cancer associated genes and human papilloma viruses from rural Africans in Zaria, Nigeria using immunohistochemistry and molecular phylogenetics. Selected cervical cancer associated genes sequences which include Ki-67 (NM_002417.4), p53 (AB082923.1), EGFR (NM_005228.3), MYC (M25803.1), KRAS (EF471957.1), TGF-B (AF254794.1) and RB (AH002963.2) genes and HPV 16 (KJ869425.1 E6 and E7 variants), HPV 18 (KJ869426.1), HPV 45 (S40261.1), HPV 6 (A25369.1), HPV 11 (J04351.1), HPV 31 (KJ869427.1) and HPV 33 (KJ869428.1) sequences were retrieved from the gene bank data base. The sequences were aligned and bootstrap at 2000 bp to create a molecular phylogenetic tree. Haematoxylin and Eosin together with immunohistochemistry were performed on fifty formalin-fixed paraffin-embedded (FFPE) tissue blocks using Anti- Ki-67, p53, EGFR, MYC, KRAS, TGF-B and RB monoclonal antibodies. Result from the phylogenetic analysis reveals trichotomized tree showing apparent significant evolutionary relationship between cladogram of HPV16 and MYC; HPV18, HPV6 and KRAS genes; EGFR gene and HPV45. Immunohistochemistry results show multivariate expression of Ki-67, p53, EGFR, MYC, KRAS, TGF-B and RB of proteins from the cervical cancer tissue blocks used. Combination of Ki-67 biomarker and other cervical cancer associated genes together with HPV subtypes-genotyping can serve as useful instruments in proper management of the disease. Citation Format: John Idoko, Mohammed Faruk, Jigo Dangude Yaro, James Oluwa Enemari, Peter Akpulu. The relationship between cervical cancer associated genes and human papilloma viruses in rural Africans in Zaria [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A15.
Expansion of tumor specific tumor-infiltrating lymphocytes (TIL) from sarcoma and the potential benefit of anti-CD137 stimulation: A prerequisite for adoptive cell transfer (ACT) immunotherapy
Authors: M. Nielsen, A. Krarup-Hansen, D. Hovgaard, M.M. Petersen, A.C. Loya, M.C.W. Westergaard, I.M. Svane, N. Junker
Journal: Annals of Oncology (2017)
Biodegradable Nanoparticles Enhanced Adhesiveness of Mussel‐Like Hydrogels at Tissue Interface
Authors: Nikhil Pandey, Amirhossein Hakamivala, Cancan Xu, Prashant Hariharan, Boris Radionov, Zhong Huang, Jun Liao, Liping Tang, Philippe Zimmern, Kytai T. Nguyen, Yi Hong
Journal: Advanced Healthcare Materials (2017)

Abstract Popular bioadhesives, such as fibrin, cyanoacrylate, and albumin–glutaraldehyde based materials, have been applied for clinical applications in wound healing, drug delivery, and bone and soft tissue engineering; however, their performances are limited by weak adhesion strength and rapid degradation. In this study a mussel‐inspired, nanocomposite‐based, biodegradable tissue adhesive is developed by blending poly(lactic‐co‐glycolic acid) (PLGA) or N‐hydroxysuccinimide modified PLGA nanoparticles (PLGA‐NHS) with mussel‐inspired alginate–dopamine polymer (Alg‐Dopa). Adhesive strength measurement of the nanocomposites on porcine skin–muscle constructs reveals that the incorporation of nanoparticles in Alg‐Dopa significantly enhances the tissue adhesive strength compared to the mussel‐inspired adhesive alone. The nanocomposite formed by PLGA‐NHS nanoparticles shows higher lap shear strength of 33 ± 3 kPa, compared to that of Alg‐Dopa hydrogel alone (14 ± 2 kPa). In addition, these nanocomposites are degradable and cytocompatible in vitro, and elicit in vivo minimal inflammatory responses in a rat model, suggesting clinical potential of these nanocomposites as bioadhesives.
Rhabdomyosarcoma, Ewing Sarcoma, and Other Round Cell Sarcomas
Authors: Alberto S. Pappo, Uta Dirksen
Journal: Journal of Clinical Oncology (2017)

Several recent advances have been made in the diagnosis and therapy of malignant small round cell tumors that affect children, particularly in rhabdomyosarcoma, Ewing sarcoma, and other round cell sarcomas. These advances have provided new insights into the pathologic, histologic, and genomic characterization of specific tumor subtypes, which has led to the identification of novel therapeutic targets and improved stratification of risk. This has, in turn, led to improved efficacy in clinical trials of new drug combinations, thereby increasing the survival of patients with newly diagnosed and refractory or recurrent round cell sarcomas. Here, we review the progress that has been made using genomics to identify novel pathologic genomic rearrangements, as well as therapeutic targets. We also describe how clinical and molecular factors have helped refine risk stratification and therapies that have led to improved clinical outcomes in patients with round cell sarcomas.
Abstract 13075: Histopathological Analysis of Two Major Ascending Aortopathies: Implication of Vasa Vasorum Degeneration in Their Pathogenesis
Authors: Hiroaki Osada, Katsuaki Meshii, Kaori Kato, Naoki Kanemitsu, Masahisa Kyogoku
Journal: Circulation (2016)

Introduction: Aortic medial weakness is a major predisposing factor in the development of aortic dissection or aortic aneurysm. Impaired vasa vasorum (VV) or venous vasa vasorum (VVV) function may induce hypoxia and malnutrition, possibly resulting in aortic medial weakness. Hypothesis: We hypothesized that the start of ascending aortopathy could be identified by histopathological analysis. Methods: We retrospectively evaluated 69 consecutive patients (28 men, 41 women; mean age 68.2 ± 12.1 years) who underwent ascending aortic repair from 2008 to 2015. The patients were divided into group AD (type A aortic dissection, n=47 ) and group AA (ascending aortic aneurysm, n=22). We evaluated patient characteristics and graded VV/VVV degeneration of the adventitia (none = 0, trivial = 0.5, mild = 1, moderate = 1.5, severe = 2) regarding elastoma formation, smooth muscle cell proliferation, myomatous change, and sclerosis. Results: There were no significant differences between the two groups regarding age, sex, body surface area, history of hypertension, or diameter of the ascending aorta before surgery. Four patients in group AD had gene-related aortic dissection (Marfan syndrome, three patients; bicuspid aortic valve, one patient). Nine patients in group AA had a bicuspid aortic valve. There were significant differences between the two groups in regard to smooth muscle cell proliferation [VV (group AD: 1.40 ± 0.49 points; group AA: 0.98 ± 0.19 points; p&lt;0.001); VVV (group AD: 1.40 ± 0.55 points, group AA: 1.04 ± 0.51 points, p=0.013] and total degeneration score (VV: group AD: 3.17 ± 1.42 points, group AA: 2.39 ± 1.41 points, p=0.036). There were no significant differences between the two groups regarding myomatous change or sclerosis. Conclusions: Degeneration of the VV and, especially, smooth muscle cell proliferation of the VV and VVV appear to be responsible for aortic dissection. Elucidation of the smooth muscle degeneration pathway may lead to identifying the turning point at which aortic wall weakness induces dissection or enlargement.
Abstract 14853: Left Ventricular Rotational Mechanics in Children With Dilated Cardiomyopathy
Authors: Andrea Montero, Matthew J O’Connor, Natesa G Pandian, Anirban Banerjee
Journal: Circulation (2016)

Introduction:  Counterclockwise rotation of LV apex and clockwise rotation of its base lead to twisting of LV in systole (wringing pump) and untwisting in diastole. In adult dilated cardiomyopathy (DCM), abnormal rotation of apex and base in same direction leads to the LV resembling a “roller” pump rather than a wringing pump. This phenomenon is described as rigid body rotation (RBR). Studies on rotational mechanics in children with DCM are lacking.   Hypothesis:  Children with DCM may exhibit decreased rotational mechanics and may display RBR.   Methods:  We analyzed 2D speckle tracking images of apex and base in 14 DCM patients (age: 0.7-18 yrs). Rotational indices and torsion-radial displacement (T-D) loops were calculated (Fig. 1A).   Results:  In 6 out of 14 (43%) DCM patients, LV apex showed “reversed” rotation resulting in RBR (Fig 2). Other 8 patients showed normal apical rotation, but had decreased rotational indices (Table 1). LVEF was similar in both RBR and non-RBR groups (41.4±14.3% vs 42.5±13.1%, p>0.05). Untwisting was decreased and quite delayed (Fig. 1B).   Conclusions:  Children with DCM exhibit impaired rotational mechanics. Almost half lose normal twist pattern resulting in RBR. Area of T-D loop decreases significantly in DCM. Longitudinal studies are needed to determine whether RBR and abnormal T-D loops are signals of impending deterioration of LV function in children with DCM.
Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer
Authors: Mark Lawler, Deborah Alsina, Richard A Adams, Annie S Anderson, Gina Brown, Nicola S Fearnhead, Stephen W Fenwick, Stephen P Halloran, Daniel Hochhauser, Mark A Hull, Viktor H Koelzer, Angus G K McNair, Kevin J Monahan, Inke Näthke, Christine Norton, Marco R Novelli, Robert J C Steele, Anne L Thomas, Lisa M Wilde, Richard H Wilson, Ian Tomlinson
Journal: Gut (2017)

Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes.
Four versus five chemotherapy courses in patients with low risk acute myeloid leukemia: A Children’s Oncology Group report.
Authors: Kelly D. Getz, Todd Allen Alonzo, Lillian Sung, Soheil Meshinchi, Robert B Gerbing, Susana Raimondi, Betsy A Hirsch, Samir B Kahwash, John Choi, E. Anders Kolb, Alan S. Gamis, Richard Aplenc
Journal: Journal of Clinical Oncology (2017)

10515 Background: For pediatric patients with low risk (LR) acute myeloid leukemia (AML), the Children’s Oncology Group (COG) trial AAML1031 used a 4-course chemotherapy backbone consisting of two induction courses of cytarabine/daunorubicin/etoposide, a third course of cytarabine/etoposide and a fourth course of cytarabine/mitoxantrone. The prior COG trial, AAML0531, included the same four courses plus a fifth course of high dose cytarabine. Removal of course 5 from AAML1031 was based in part on prior studies that suggested no benefit from a fifth course. Methods: We compared overall survival (OS), disease free survival (DFS), and relapse risk (RR) for LR patients receiving four versus five chemotherapy courses in a pooled analysis of comparable patients treated on AAML0531 and AAML1031. LR was defined as the presence of inv(16)/t(16;16) or t(8;21) cytogenetic features, NPM1 or CEBPA mutations, or MRD &lt; 0.1% post-Induction I in those with no high risk features. AAML0531 patients assigned to gemotuzumab were excluded. Follow-up for outcomes began at the start of course 4. Cox (OS and EFS) and risk (RR) regressions were used to estimate unadjusted hazard ratios (HR) comparing outcomes for patients who received only four versus five chemotherapy courses. Start of a fifth chemotherapy course was assessed as a time-varying exposure in all analyses to avoid exposure misclassification. Results: A total of 921 LR patients (225 from AAML0531, 696 from AAML1031) were included; 191 (21%) received a fifth course. There were no significant differences in distributions of sex, age, race, or ethnicity between patients treated with four or five courses. Median times to absolute neutrophil count and platelet count recovery after course 4 were also comparable. Patients who received only four courses had significantly lower OS (HR = 1.83, 95% CI: 1.22-2.74, p = 0.003), DSF (HR = 1.49, 95% CI: 1.13-1.97, p = 0.005), and higher RR (HR = 1.42, 95% CI: 1.08-1.88, p = 0.013) compared to those who received five courses. Conclusions: Removal of a fifth cytarabine-containing course appears to result in worse OS, DFS, and RR in pediatric patients with LR AML. Multivariable analyses to further refine the estimates are ongoing.
Effectiveness of a lifestyle intervention led by female community health volunteers versus usual care in blood pressure reduction (COBIN): an open-label, cluster-randomised trial
Authors: Dinesh Neupane, Craig S McLachlan, Shiva Raj Mishra, Michael Hecht Olsen, Henry B Perry, Arjun Karki, Per Kallestrup
Journal: The Lancet Global Health (2017)

Elevated blood pressure greatly contributes to cardiovascular deaths in low-income and middle-income countries. We aimed to investigate the effectiveness of a population-level intervention led by existing community health workers in reducing the burden of hypertension in a low-income population.We did a community-based, open-label, two-group, cluster-randomised controlled trial in Nepal. Using computer-generated codes, we randomly assigned (1:1) 14 clusters to a lifestyle intervention led by female community health volunteers (FCHVs) or usual care (control group). In the intervention group, 43 FCHVs provided home visits every 4 months for lifestyle counselling and blood pressure monitoring. Eligible participants had been involved in a previous population-based survey, were aged 25-65 years, did not have plans to migrate outside the study area, and were not severely ill or pregnant. The primary outcome was mean systolic blood pressure at 1 year. We included all participants who remained in the trial at 1 year in the primary analysis. This trial is registered with ClinicalTrials.gov, number NCT02428075.Between April 1, 2015, and Dec 31, 2015, we recruited 1638 participants (939 assigned to intervention; 699 assigned to control). At 1 year, 855 participants remained in the intervention group (425 were normotensive, 175 were prehypertensive, and 255 had hypertension) and 613 remained in the control group (305 were normotensive, 128 were prehypertensive, and 180 had hypertension). The mean systolic blood pressure at 1 year was significantly lower in the intervention group than in the control group for all cohorts: the difference was -2·28 mm Hg (95% CI -3·77 to -0·79, p=0·003) for participants who were normotensive, -3·08 mm Hg (-5·58 to -0·59, p=0·015) for participants who were prehypertensive, and -4·90 mm Hg (-7·78 to -2·00, p=0·001) for participants who were hypertensive.A simple, FCHV-led lifestyle intervention coupled with monitoring of blood pressure is effective for reduction of blood pressure in individuals with hypertension and ameliorates age-related increases in blood pressure in adults without hypertension in the general population of Nepal.Aarhus University, Jayanti Memorial Trust.
Antibacterial prophylaxis with ciprofloxacin for patients with multiple myeloma and lymphoma undergoing autologous haematopoietic cell transplantation: a quasi-experimental single-centre before-after study
Authors: M. Yeshurun, I. Vaxman, L. Shargian, D. Yahav, J. Bishara, O. Pasvolsky, O. Wolach, M. Lahav, R. Gurion, H. Magen, L. Vidal, C. Herscovici, A. Peck, M. Moshe, M. Sela-Navon, E. Naparstek, P. Raanani, U. Rozovski
Journal: Clinical Microbiology and Infection (2017)
Atrial Infarction and Ischemic Mitral Regurgitation Contribute to Post-MI Remodeling of the Left Atrium
Authors: Jaume Aguero, Carlos Galan-Arriola, Rodrigo Fernandez-Jimenez, Javier Sanchez-Gonzalez, Nina Ajmone, Victoria Delgado, Jorge Solis, Gonzalo J. Lopez, Antonio de Molina-Iracheta, Roger J. Hajjar, Jeroen J. Bax, Valentin Fuster, Borja Ibáñez
Journal: Journal of the American College of Cardiology (2017)

Left atrial (LA) remodeling after an acute myocardial infarction (MI) is poorly characterized regarding its determinants or its effect on ischemic mitral regurgitation (MR) development. The purpose of this study was: 1) to compare LA structural remodeling in experimental MI swine models recapitulating the effects of left ventricular (LV) dysfunction, ischemic MR, and left atrial infarction (LAI); and 2) to analyze how LA remodeling influences ischemic MR development. Three models of MI were generated: 1) proximal left circumflex (LCx) coronary artery occlusion involving the LA branch (LAI group); 2) proximal LCx occlusion not involving the LA branch (LCx group); and 3) left anterior descending (LAD) occlusion (LAD group). Serial cardiac magnetic resonance scans were performed to define LA and LV remodeling and ischemic MR, and were correlated with histology. Occlusion of the LA branch (LAI group) induced a greater degree of LA dilation at 1 and 8 weeks post-MI than the LCx and LAD groups, along with early and severe impairment of LA function. In the LCx and LAD groups, LA dysfunction was less pronounced and not consistent. Development of ischemic MR was more pronounced in the LAI group than in the LCx group. Histology confirmed atrial infarction with extensive fibrosis in the LAI group and interstitial fibrosis in the LCx group. In the LAD group, LA remodeling was not observed by cardiac magnetic resonance or histology. We provide the first experimental evidence of the deleterious effect of acute LAI on atrial structural remodeling, characterized by early LA dilation, dysfunction, and fibrosis, and early occurrence of ischemic MR.
Single-nucleotide polymorphisms of IFITM3, TLR3, CD55 , and TLR4 and risk for severe outcomes in patients with influenza A (H7N9) and (H1N1) pdm09 in China: a multicentre cohort study
Authors: Nelson Lee, Bin Cao, Changwen Ke, Hongzhou Lu, Yunwen Hu, Claudia H T Tam, Ronald C W Ma, Dawei Guan, Zhaoqin Zhu, Hui Li, Mulei Lin, Rity Y K Wong, Irene M H Yung, Tin-Nok Hung, Kirsty Kwok, Peter Horby, David S C Hui, Martin C W Chan, Paul K S Chan
Journal: The Lancet (2017)
Noninvasive Gene Expression Testing in Amelanotic Melanoma
Authors: Maria V. Childs
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Employment Status and Health Characteristics of Adults With Expanded Medicaid Coverage in Michigan
Authors: Renuka Tipirneni, Susan D. Goold, John Z. Ayanian
Journal: JAMA Internal Medicine (2017)

Results | Inequality in median household income between the top and bottom percentiles appeared to vary randomly over time (Figure ,A).The ratio of the 99th percentile to the 1st percentile ranged from 4.12 at its highest in 1989 to 3.64 in 2010 at its lowest.Racial inequality between counties rose over time (Figure, B).The ratio of the counties with the fewest percentage of minorities and counties with highest percentage of minorities went from 4.38 in 1990 at its lowest to 5.48 in 2010 at its highest.Discussion | This analysis showed that income inequality did not rise over time but rather varied over the years, suggesting that the rise in life expectancy inequality indeed is not solely related to the (purported) rise in income inequality.However, racial inequality has been rising over time-in fact, at a rate very similar to that of life expectancy inequality (Figure 3B in Dwyer-Lindgren et al 2 ).This is a visible demonstration that it is not simply behavioral and metabolic risk factors that play a role in longevity.There are likely multiple potential routes (including socioeconomic) to more equitable health outcomes, and many of these factors are integrally connected to each other.For example, those with higher income are much more likely to quit smoking than those with lower income. 4The converse is true as well, inextricably linking socioeconomic and behavioral risk factors.Furthermore, income equality shows only a slice of the disparities in economic status; the gap in assets and wealth-in particular between white individuals compared with black and Hispanic individuals-is appallingly large. 5Combining this with the increasing residential segregation occurring based on wealth 6 -leading rich counties to become even richer-shows how difficult it is to unchain all these variables from each other.The various factors associated with life expectancy inequality, then, are not necessarily confounders, but perhaps rather mediators between class and health.Likely, a multifaceted approach is needed in reducing inequalities in longevity and beyond.
Preclinical activity of SL-801, a reversible inhibitor of Exportin-1 (XPO1)/Chromosome Region Maintenance-1 (CRM1) in solid and hematologic cancers.
Authors: Janice Chen, Christopher L. Brooks, Peter McDonald, Jonathan D. Schwartz, Keiichi Sakakibara, Naoya Saito, Takuji Sato, Takumi Kawabe, Eric Keith Rowinsky
Journal: Journal of Clinical Oncology (2015)

e13543 Background: XPO1 controls key cellular processes by regulating nuclear export of proteins and RNA. XPO1 is overexpressed in many cancers, causing dysregulated protein localization, aberrant growth, and resistance to apoptosis. Recent work has revealed XPO1 to be a clinically relevant target, and nuclear export inhibitors have emerged as a new class of anti-cancer agents with clinical activity in multiple indications. SL-801 is a structurally novel small molecule that binds covalently but reversibly to XPO1, blocking binding of substrate cargos. The kinetics of target binding and preclinical activity of SL-801 in multiple tumor types are reported here. Methods: SL-801 activity was evaluated against 240 tumor cell lines using the OncoPanel platform and in human tumor xenografts in SCID mice. Pull-down assays with biotinylated SL-801 were used to assess SL-801 binding to XPO1. Results: SL-801 demonstrated broad and potent activity across numerous tumor cell lines. GI50s in hematologic cancers ranged from 3-93 nM in leukemias, 1-103 nM in lymphomas, and 3-11 nM in multiple myelomas. SL-801 also inhibited solid tumor growth, with GI50s ≤ 10 nM in breast, brain, cervical, ovarian, gastric, kidney, liver, lung, melanoma, prostate, and sarcoma lines. SL-801 exhibited substantial activity in vivo. In an ARH-77 multiple myeloma xenograft, 90% of mice treated with SL-801 in a multi-dose regimen survived 150 days, while the median survival of vehicle-treated mice was 40 days. SL-801 was also active in human acute lymphoblastic leukemia, non-small cell lung cancer, and prostate carcinoma xenograft models. Pull-down assays showed that SL-801 binding to XPO1 decreased after 2 hours, whereas the prototypical XPO1 inhibitor leptomycin B bound tightly to XPO1 for at least 8 hours. Conclusions: SL-801 is a promising clinical candidate that inhibits a novel target and possesses potent and broad anti-cancer activity. The reversible binding of SL-801 to XPO1 may offer the potential to develop dosing schedules to enable recovery in normal tissues, broadening the therapeutic index of this class of agents. IND-enabling work is underway to support entry into clinical trials.