tbuckley/cabot-search huggingface dataset:
Efficacy and tolerability of an investigational nitric oxide–releasing topical gel in patients with molluscum contagiosum: A randomized clinical trial
Authors: Adelaide A. Hebert, Elaine C. Siegfried, Todd Durham, Emily N. de León, Teresa Reams, Elizabeth Messersmith, Tomoko Maeda-Chubachi
Journal: Journal of the American Academy of Dermatology (2019)

Although a variety of ablative, topical, and systemic therapies are used for molluscum contagiosum (MC), none has been well studied or approved by the US Food and Drug Administration.To compare the efficacy and tolerability of topical SB206 (berdazimer sodium gel coadministered with hydrogel) with vehicle.A 12-week, phase 2, multicenter, randomized, double-blind, vehicle-controlled clinical trial of topical SB206.A total of 256 patients (mean age, approximately 7 years) participated. Of patients who completed 12 weeks of treatment (n = 217), all MC lesions cleared in 20.0% of patients who received vehicle compared with 13.2%, 41.0%, and 35.1% of patients treated with twice daily SB206 4%, 8%, and 12%, respectively, and 41.9% of patients treated with once daily SB206 12%. Application-site erythema occurred in 10.6% of patients treated with SB206. Application-site reactions were the most common adverse events leading to treatment discontinuation, affecting 2 patients (approximately 4%) in each of the SB206 4%, 8%, and 12% twice daily groups and 0 patients in the vehicle or SB206 12% once daily groups.A larger study is needed to confirm the efficacy of SB206 12% once daily and provide additional safety assessments.Of the doses studied, SB206 12% applied once daily provided the best balance between MC lesion clearance and tolerability for evaluation in a larger study.
Spatio-temporal separation of tumor infiltrating CD8+ T-cells and HER2/neu+ tumor cells in tumor-immune milieu of infiltrating ductal carcinoma of the breast
Authors: S. Sreedharan, M. Biswas, S. Thiyagarajan, N.P. Basak, A. Basu, P.S. Ghosh
Journal: Annals of Oncology (2019)
Emergency admissions and bad news disclosure as precipitators of suicide: A territory-wide cohort analysis of 458 oncology patients who completed suicides
Authors: T.C. Lam, E. Kwan, H. Luo, P.S. Yip
Journal: Annals of Oncology (2019)

Background: Cancer patients are known to have higher average risk of suicide compared with general population.Acute clinical stressors, caused by deteriorating physical condition, may precipitate suicidal attempts in cancer patients.Methods: Coroner's files of all 4613 suicidal deaths of Hong Kong in 2012-2016 were reviewed.The files contained detailed reports on demographics, autopsy, police investigations and medical summary.Cancer was recorded in coroner's files in 458 subjects (9.9%).Medical records of these 458 subjects were reviewed manually in a territorywide electronic patient record system which covered 80% of all cancer care.Results: More than half (56%) were diagnosed to have metastatic or incurable cancer at the time of suicide (advanced cancer patients).Advanced cancer patients had significantly higher health resources utilization compared with early-staged patients in terms of emergency room visit, clinic attendance and hospitalization.Emergency admissions, which represented symptom crisis, was temporally related to suicide.Ninety percent of suicide episodes occurred within 100 days of emergency admissions (median 12 days).Disclosure of bad news may represent another emotional stressor.Among advanced cancer patients, suicide occurred at a median time of 6 months after disclosure of bad news of metastases (median 182 days, interquartile range (IQR) 46-534 days).Suicide occurred at 2 months after the bad news of cessation of active cancer treatments (median 60 days, IQR 24-196 days).For psychiatric risk factors, advanced cancer patients had lower rate of psychiatric diagnosis compared with early-staged cancer patients (12.5% vs 23.7% p ¼ 0.003).Similar trend was observed in other factors including gambling, debt and history of self-harm (2.3% vs 0.0%, p ¼ 0.03; 2.8% vs 0.3%, p ¼ 0.02; 4.4% vs 1.3%, p ¼ 0.08 respectively).Conclusions: Emergency admissions and bad news disclosure represent acute stressors that may precipitate suicidal attempts in cancer patients.Such temporal relationship was particularly strong in advanced cancer patients, suggesting a critical window for suicidal prevention interventions.Legal entity responsible for the study: The authors.
Synergistic killing in pancreatic cancer cell lines of the combination of a MEK inhibitor and DNA methylation inhibitor.
Authors: Matlock Arizona Jeffries, Carla Kurkjian
Journal: Journal of Clinical Oncology (2013)

e15025 Background: A growing body of evidence implicates aberrant DNA methylation in the etiology of a number of cancers, including pancreatic. Previous reports link defective ERK signaling with reduced DNA methylation via DNMT1. Here, we examined the ability of the MEK inhibitor U0126 to alter expression of DNMTs in k-RAS mutant and wild type pancreatic cancer cell lines and assess additive cytotoxicity of U0126, the hypomethylating agent 5-Azacytidine and two HDAC inhibitors. Methods: DNMT levels were quantified in AsPC1 and BxPC3 lines 2 days after adding 25 umolar U0126 using real-time RT-PCR. Significance was calculated using a Student t-test. For survival, agents were added singly and in combination: U0126, 25 umol; 5-Aza, 10 umol; Valproic acid 1 mmol and Trichostatin-A 5 umol. Survival was assessed using a colorimetric MTS method at 1, 2, 3, and 4 days. Expected cell survival and synergism were calculated via relative risk ratios, and significance via a Student t-test. Results: U0126 treatment reduced expression of DNMT1 significantly in AsPC1: 2.06 ± 0.3 vs. 1.09 ± 0.08, p = 0.004 (mean ± S.D., arbitrary units). No change was seen in BxPC3. Increased expression of de novo DNMT3a and DNMT3b was seen: AsPC1 1.28 ± 0.3 vs. 3.13 ± 0.8, p = 0.02; BxPC3 1.78 ± 0.3 vs. 4.14 ± 1, p = 0.02; AsPC1 1.26 ± 0.3 vs. 2.66 ± 0.4, p = 0.006, respectively. DNMT3b in BxPC3 was not altered significantly. U0126 and 5-Aza were individually cytotoxic in both cell lines, and synergism was observed in combination. In AsPC1, the observed vs. expected combination survival was 13% ± 3% vs. 29% ± 2%, p = 0.001; for BxPC3, 7% ± 2% vs. 62% ± 3%, p = 0.002, both at 4d. No synergism was found when adding Valproic acid or Trichostatin-A. Conclusions:Treatment of k-RAS mutant pancreatic cancer cell lines with the MEK inhibitor U0126 results in significantly reduced expression of DNMT1 and increased DNMT3a and DNMT3b. U0126 combined with 5-Aza produced synergistic cytotoxicity, which may be due to enhanced hypomethylation activity. Although no significant change in expression of DNMT1 was found in the BxPC3 cells, we noted synergistic cytotoxicity when treated with both U0126 and 5-Aza.
Environmental Factors in Successful Aging: The Potential Impact of Air Pollution
Authors: Charles W. Schmidt
Journal: Environmental Health Perspectives (2019)

Global demographic trends are coalescing around an unprecedented milestone in human history: It is estimated that by 2020, people over age 60 will for the first time outnumber children under the age of 5 years old. 1 Global fertility rates have fallen by half over the last half-century from an average of 5 children per woman in 1960 to 2.5 today. 2 In addition, major advances against what were once the world's top killers-infectious diseases and acute threats to child and maternal health-are allowing more people to live longer than ever before. 3his demographic shift has sparked growing interest in how people age and, in particular, their capacity for what those in the geriatrics field call "successful aging"-with vitality, resilience, and good health.Seen this way, the number of years lived is not as important as how many of those years can be lived free of disease and disability. 4,5remature declines in cognitive and physical functioning pose threats to successful aging, and mounting evidence indicates that environmental exposures may play a part in such declines. 6,7,8,9et older adults have been long understudied in environmental health. 10In addition, toxicologists rarely test chemicals in older animals, so mechanistic insights into their effects on aging bodies are "Successful aging" means retaining vitality, resilience, and good health throughout one's later years.As the global population shifts toward more older people than children, investigators want to understand the environmental and genetic factors that influence how "successfully" an individual ages.
SAT-290-Association of liver inflammation and fibrosis score with noninvasive biomarkers in non-alcoholic fatty liver disease: Preliminary results from the MAST4HEALTH study
Authors: Konstantinos Apostolou-Karampelis, Charalampia Amerikanou, Angela Barone, Milica Medic-Stojanoska, Natasa Milic, Mladen Bjelan, Stefan Stojanoski, Maja MilanoviC, Natasa Milosevic, Andriana Kaliora, Iraklis Varlamis, Ilias Smirnioudis, Lucia Cesarini, Luca S. Belli, Angelo Vanzulli, Jonica Campolo, Chara Vezou, Maria Giovanna Trivella, Amalia Gastaldelli, Rajarshi Banerjee, George Dedoussis
Journal: Journal of Hepatology (2019)
Phase II study of pembrolizumab with enzalutamide (Enz) in metastatic, castration-resistant prostate cancer (mCRPC): 30 patient expansion with examination of tumour-infiltrating immune cells and fecal microbiota
Authors: J.N. Graff, A.E. Moran, R.E. Slottke, G.V. Thomas, J.J. Alumkal, R.F. Thompson, M.A. Wood, L.B. Peiffer, R.C. Bergan, K.S. Sfanos, T.M. Beer
Journal: Annals of Oncology (2019)
Adult Recipients of Matched Related Donor Blood Cell Transplants Given Pretransplant Antithymocyte Globulin Have Less Graft-Versus-Host Disease and Transplant-Related Mortality: Follow-Up of a Matched Pair Analysis.
Authors: James A. Russell, Loree M. Larratt, A. Robert Turner, M. Ahsan Chaudhry, Oluyeme Jeje, Donald Morris, Christopher Brown, Diana M. Quinlan, Douglas A. Stewart
Journal: Blood (2006)
Vaginal microbiome transplantation in women with intractable bacterial vaginosis
Authors: Ahinoam Lev-Sagie, Debra Goldman-Wohl, Yotam Cohen, Mally Dori-Bachash, Avner Leshem, Uria Mor, Jacob Strahilevitz, Allon E. Moses, Hagit Shapiro, Simcha Yagel, Eran Elinav
Journal: Nature Medicine (2019)
S. aureus colonization in healthy Australian adults receiving an investigational S. aureus 3-antigen vaccine
Authors: Helen S. Marshall, James Baber, Peter Richmond, Michael Nissen, Sepehr Shakib, Barry N. Kreiswirth, Edward T. Zito, Joseph Severs, Joseph Eiden, William Gruber, Kathrin U. Jansen, C. Hal Jones, Annaliesa S. Anderson
Journal: Journal of Infection (2019)

ObjectivesAssess Staphylococcus aureus (S. aureus) colonization in healthy Australian adults receiving an investigational S. aureus 3-antigen vaccine (SA3Ag).MethodsIn this phase 1, double-blind, sponsor-unblinded study, participants were randomized to receive a single dose (1 of 3 dose levels) of SA3Ag or placebo and a booster dose or placebo at 6 months. S. aureus isolates from nasal, perineal, and oropharyngeal swabs before and through 12 months post-vaccination were identified.ResultsBaseline S. aureus colonization prevalence was 30.6% (any site), with nasal carriage (27.0%) more common than oropharyngeal/perineal (3.2% each). Following initial vaccination (low-dose: 102; mid-dose: 101; high-dose: 101; placebo: 102) and booster (low-dose: 45; mid-dose: 44; high-dose: 27; placebo: 181), placebo and SA3Ag groups showed similar S. aureus carriage through 12 months. Most colonized participants (74.0%) were colonized by single spa types. Placebo and SA3Ag groups had similar persistence of colonization, with 19.6–30.7% due to single spa types. Acquisition was observed in mid- and high-dose recipients (∼20%) and low-dose and placebo recipients (∼12%). Vaccination resulted in substantial increases in antibodies to all 3 antigens, irrespective of carriage status.ConclusionsBased on descriptive analyses of this small study, SA3Ag vaccination did not impact S. aureus acquisition or carriage. Carriage status did not impact antibody responses to SA3Ag.
佛山地区中青年民营企业主294人血压、血脂、肥胖及血糖情况调查
Authors: 陈家一, 邱泽明
Journal: BMJ (2009)

我国改革开放30年来涌现出大批的民营企业主,这个特殊群体的原发性高血压、高脂血症、2型糖尿病、肥胖症患病率是否较普通人群高,目前尚缺乏相关资料.本次调查旨在为该人群心脑血管病的防治工作提供参考资料。
Phase II multicenter open label study of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study)
Authors: H. Jespersen, R. Olofsson Bagge, G. Ullenhag, A. Carneiro, H. Helgadottir, I. Ljuslinder, M. Levin, C. All-Eriksson, B. Andersson, U. Stierner, L.M. Nilsson, J.A. Nilsson, L. Ny
Journal: Annals of Oncology (2019)
Cisplatin reduces costs and provides more quality adjusted life years (QALYs) than cetuximab in chemoradiotherapy for patients with HPV-positive oropharyngeal cancer (HPV+OPC)
Authors: D.A. Jones, H. Mehanna, P. Mistry, M. Dalby, T. Fulton-Lieuw, A.H. Kong, J. Dunn, A. Gray
Journal: Annals of Oncology (2019)
mTOR mutations are not associated with shorter PFS and OS in patients treated with mTOR inhibitors
Authors: C. Suarez Rodriguez, J.A. Arranz Arija, R. Morales Barrera, J. Puente, O. Reig, L. Faez, A. González del Alba, B.P. Valderrama, E. Gallardo, B. Mellado, E. Esteban, J. Jimenez, A. Vivancos, J. Carles
Journal: Annals of Oncology (2019)
First-line versus second-line immunotherapy in recurrent/metastatic squamous cell carcinoma of the head and neck
Authors: C. Even, N. Torossian, T. Ibrahim, N. Martin, L. Mayache Badis, F.R. Ferrand, M. Iacob, J. Guigay, C Le Tourneau, A. Daste, E. Saada-Bouzid, K. Saleh
Journal: Annals of Oncology (2019)
Abstract 17729: Cumulative Effect of Echocardiographic Markers of Elevated Left Ventricular Filling Pressure on Future Cardiovascular Events in Subjects with Diabetes
Authors: Bryan Wai, Sheila K Patel, Michelle Ord, Piyush M Srivastava, Louise M Burrell
Journal: Circulation (2011)

Background: Type 2 diabetes mellitus (T2DM) is a strong and independent risk factor for the development of major adverse cardiovascular events (MACE). An elevated left ventricular filling pressure (LVFP) measured by various echocardiographic (echo) parameters is associated with poor outcomes. This study investigated the cumulative effect of various echo measures of elevated LVFP and the risk of MACE. Methods: We prospectively recruited 1308 subjects (subs) (age 63.5± 11.7 years, 60% male) with T2DM attending a complications surveillance program at a single tertiary center (21 subs excluded due to inadequate echo imaging). Baseline resting echocardiogram was performed and subs were followed for a median of 4.4 years [interquartile range 3.2, 5.9]. Elevated LVFP was defined by the following echo measures: left atrial area &gt; 20cm2, peak early diastolic (dia) mitral velocity (E) to peak mitral annular velocity ratio ≥ 10, pulmonary vein (PV) peak dia velocity &gt; systolic velocity, peak PV atrial reversal &gt;35cm/s, PV atrial reversal duration minus late dia mitral inflow wave duration &gt;30msec and mitral E/A change &gt;/= 0.5 with Valsalva. The primary outcome was MACE defined as hospitalization for acute coronary syndrome, stroke or heart failure, coronary or peripheral vessel revascularization or death. Results: Over the follow-up period, 27% of subs experienced at least one MACE and 15% experienced heart failure or death. After adjusting for age, gender, presence of macrovascular complications and cardiovascular risk factors, each additional echo measure of elevated LVFP was associated with a 29% increased risk of MACE. After the same covariate adjustment, subs with &gt;3 measures of elevated LVFP had a higher hazard ratio of 2.7 (95% CI 1.9-3.8, P&lt;0.001) for MACE compared to subs with &lt;2 measures of elevated LVFP. Conclusions: Echo features of elevated LVFP predict future MACE. The presence of &gt;3 features of elevated LVFP is associated with poorer outcomes in T2DM.
3-year follow-up of a phase III trial comparing the efficacy and safety of neoadjuvant and adjuvant trastuzumab and its biosimilar CT-P6 in HER2 positive early breast cancer (EBC)
Authors: J. Stebbing, Y. Baranau, V. Baryash, A. Manikhas, V. Moiseyenko, G. Dzagnidze, E. Zhavrid, D. Boliukh, D. Stroyakovskiy, J. Pikiel, A. Eniu, D. Komov, S.J. Lee, M.J. Kim, S. Kim, S. Park, J.H. Bae, F.J. Esteva
Journal: Annals of Oncology (2019)
Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC)
Authors: E.C. Dees, P.G. Aftimos, Houven van Oordt, E.G.E. De Vries, P. Neven, M.D. Pegram, R. Iqbal, J. Boers, J. Xiao, C. Sipes, C. Li, J.A. Sorrentino, R. Malik, A.P. Beelen, C.W. Menke-van der
Journal: Annals of Oncology (2019)
Targeting ARG2 as a novel therapeutic approach for cancer
Authors: M.M. Grzybowski, J. Pęczkowicz-Szyszka, P. Wolska, P.S. Stańczak, M. Welzer, E. Nikolaev, A.M. Siwińska, R. Błaszczyk, B. Borek, M. Dzięgielewski, A. Gzik, J. Nowicka, J. Brzezińska, K. Jędrzejczak, J. Chrzanowski, A. Gołębiowski, J. Olczak, K. Dzwonek, P. Dobrzański
Journal: Annals of Oncology (2019)
Antecedent of cancer and mortality after the first ST segment elevation acute myocardial infarction treated with primary coronary angioplasty. A prospective cohort study
Authors: I.D. Sillero, M. López Flores, L.F. Sánchez-Cousido, M. Rojas Piedra, I. Prieto-Salvador, A. López González, C. Castañón González, A. García-Palomo, F. Fernández Vazquez, I. Iglesias
Journal: Annals of Oncology (2019)
Tissue Damage and Lymphoma Derived Chemoattractive Signals Impact Regulatory T Cell Trafficking After Allogeneic Hematopoietic Cell Transplantation.
Authors: Christoph Dürr, Dietmar Pfeifer, Annette Schmitt-Gräff, Rainer Claus, Ulrike Gerlach, Ralph Graeser, Armin Gerbitz, Robert Negrin, Jürgen Finke, Robert Zeiser
Journal: Blood (2009)
Treatment outcomes of 3rd treatment in a real-world metastatic castration resistant prostate cancer (mCRPC) population: Results from the Dutch CAPRI-registry
Authors: J.C.L. Notohardjo, M.C.P. Kuppen, H.M. Westgeest, A.J.M. van den Eertwegh, J. Van Moorselaar, N. Mehra, J.L. Coenen, I. van Oort, A.C.M. van den Bergh, K.K.H. Aben, D.M. Somford, R. de Wit, A.M. Bergman, L. Lavalaye, C. Uyl-de Groot, W.R. Gerritsen
Journal: Annals of Oncology (2019)
NIVOREN GETUG-AFU 26 translational study: CD8 infiltration and PD-L1 expression are associated with outcome in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) treated with nivolumab (N)
Authors: Y. Vano, N. Rioux-Leclercq, C. Dalban, C. Sautès-Fridman, A. Bougoüin, N. Chaput, S. Chouaib, B. Beuselinck, C.M. Chevreau, M. Gross-Goupil, S. Negrier, B. Laguerre, D. Borchiellini, I. Colina-Moreno, W.H. Fridman, S. Chabaud, F. Tantot, J. Barros Monteiro, B. Escudier, L. Albiges
Journal: Annals of Oncology (2019)
Treatment with BLU-667, a potent and selective RET inhibitor, provides rapid clearance of ctDNA in patients with RET-altered non-small cell lung cancer (NSCLC) and thyroid cancer
Authors: G. Curigliano, V. Subbiah, J.F. Gainor, D.H. Lee, M.H. Taylor, V. Zhu, R.C. Doebele, G. Lopes, C. Baik, E. Garralda, S.M. Gadgeel, D.-W. Kim, C.D. Turner, M. Palmer, S. Miller
Journal: Annals of Oncology (2019)
B cell dissemination patterns during the germinal center reaction revealed by whole-organ imaging
Authors: Liat Stoler-Barak, Adi Biram, Natalia Davidzohn, Yoseph Addadi, Ofra Golani, Ziv Shulman
Journal: The Journal of Experimental Medicine (2019)

Germinal centers (GCs) are sites wherein B cells proliferate and mutate their immunoglobulins in the dark zone (DZ), followed by affinity-based selection in the light zone (LZ). Here, we mapped the location of single B cells in the context of intact lymph nodes (LNs) throughout the GC response, and examined the role of BCR affinity in dictating their position. Imaging of entire GC structures and proximal single cells by light-sheet fluorescence microscopy revealed that individual B cells that previously expressed AID are located within the LN cortex, in an area close to the GC LZ. Using in situ photoactivation, we demonstrated that B cells migrate from the LZ toward the GC outskirts, while DZ B cells are confined to the GC. B cells expressing very-low-affinity BCRs formed GCs but were unable to efficiently disperse within the follicles. Our findings reveal that BCR affinity regulates B cell positioning during the GC response.
A first-in-human phase I/II trial of the oral HIF-2a inhibitor PT2977 in patients with advanced RCC
Authors: E. Jonasch, E.R. Plimack, T. Bauer, J.R. Merchan, K.P. Papadopoulos, D.F. McDermott, M.D. Michaelson, L.J. Appleman, S. Thamake, N. Zojwalla, T.K. Choueiri
Journal: Annals of Oncology (2019)
Long term follow-up (F/U) report of symptomatic cardiac events (SCEs) in 2,809 breast cancer (BC) patients (pts) treated with adjuvant trastuzumab (T) in real world (RW) practice
Authors: S. Di Cosimo, A. Trama, I. Merlo, P. Minicozzi, L. Tarantini, G. Apolone, G. Corrao, M. Franchi
Journal: Annals of Oncology (2019)
Abstract 2526: Comparison of 4 Years Efficacy and Durability of Drug-Eluting Stent Implantation in Non-Bifurcation and Bifurcation Lesion of Unprotected Left Main Coronary Arteries: Multicenter Registry in Asia
Authors: Sunao Nakamura, Hisao Ogawa, Jang-Ho Bae, Yeo Hans Cahyadi, Wasan Udayachalerm, Damras Tresukosol, Sudaratana Tansuphaswadikul
Journal: Circulation (2008)

Aim : The aim of this study is to compare the 4 years safety and durability of drug-eluting stent implantation in non-bifurcation (ostium and/or mid shaft) (N-Bifur) and bifurcation (Bifur) lesion of unprotected left main coronary arteries (LMT). Methods : A prospective analysis of 448 patients with LMT stenosis (324 Bifur and 124 N-Bifur) in five high volume Asian centers after successful stenting in LMT was performed. LMT was treated with 5 strategies (single stenting 195 cases, T-stenting 47 cases, crush stenting 38 cases, Mini-crush stenting 93 cases, culotte stenting 54 cases, kissing stenting 21 cases). Complete clinical follow-up to 4 years is being analyzed for all 448 patients. Results : The baseline clinical characteristics between 2 groups were similar. Angiographic and clinical success were achieved in all patients without any major complication. At 4 years overall cardiac events of N-Bifur (14.5%) were significantly lower than Bifur (28.0%) (p=0.011). See figure for clinical results. Conclusion : The use of drug-eluting stent in patients with LMT was safe and feasible with low acute complication and low incidence of restenosis. Drug-eluting stent implantation in non-bifurcation lesion of LMT showed lesser incidence of cardiac events (death, myocardial infarction, CABG and PCI) compared with those of bifurcation lesion at 4 years clinical follow-up.
Effect of selumetinib plus AZD8186 treatment on cabazitaxel sensitivity in docetaxel-acquired resistant metastatic prostate cancer cell lines
Authors: V. Ruiz de Porras, F. Laguía, M. Marín-Aguilera, N. Jiménez, B. Mellado, J.L. Ramirez, E. Martinez-Balibrea, A. Font
Journal: Annals of Oncology (2019)