tbuckley/cabot-search huggingface dataset:
Relationship of Timing of Anterior Cruciate Ligament (ACL) Reconstruction Surgery with Meniscal Tears, Chondral Injuries, Functional and Patient Reported Outcomes. A Systematic Review
Authors: A. Prodromidis, N. Zreik, G. Thivaios, A. Waqar, P. Dey, C. Charalambous
Journal: International Journal of Surgery (2017)
Androgen deprivation therapy and risk of rheumatoid arthritis in patients with localized prostate cancer
Authors: D.D. Yang, A. Krasnova, K.T. Nead, T.K. Choueiri, J.C. Hu, K.E. Hoffman, J.B. Yu, D.E. Spratt, F.Y. Feng, Q.-D. Trinh, P.L. Nguyen
Journal: Annals of Oncology (2017)
A prospective phase II study of combined androgen blockade in patients with androgen receptor-positive metastatic or locally advanced unresectable salivary gland carcinoma
Authors: C. Fushimi, Y. Tada, H. Takahashi, T. Nagao, H. Ojiri, T. Masubuchi, T. Matsuki, K. Miura, D. Kawakita, H. Hirai, E. Hoshino, S. Kamata, T. Saotome
Journal: Annals of Oncology (2017)

BackgroundThere is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC).Patients and methodsWe conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg. Patients were treated until progressive disease or unacceptable toxicities.ResultsThirty-six eligible patients were enrolled. Thirty-three patients had RM disease and three patients had LA disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% [n = 15, 95% confidence interval (CI), 25.5%–59.2%], the clinical benefit rate was 75.0% (n = 27, 95% CI, 57.8%–87.9%). The median progression-free survival was 8.8 months (95% CI, 6.3–12.3 months) and the median overall survival was 30.5 months (95% CI, 16.8 months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient.ConclusionThis study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive RM or unresectable LA SGC compared with conventional chemotherapy, which warrants further study.Clinical Trial RegistrationUMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703
Imipenem–Relebactam and Meropenem–Vaborbactam: Two Novel Carbapenem-β-Lactamase Inhibitor Combinations
Authors: George G. Zhanel, Courtney K. Lawrence, Heather Adam, Frank Schweizer, Sheryl Zelenitsky, Michael Zhanel, Philippe R. S. Lagacé-Wiens, Andrew Walkty, Andrew Denisuik, Alyssa Golden, Alfred S. Gin, Daryl J. Hoban, Joseph P. Lynch, James A. Karlowsky
Journal: Drugs (2017)
Mucous Membrane Pemphigoid with Ocular Involvement
Authors: Hon Shing Ong, Jane F. Setterfield, Darwin C. Minassian, John K. Dart, Debbie Booth, Elaina Reid, Nicole Carnt, Stefano Gugliemetti, Vijay Shanmuganathan, Martin Watson, Valerie Saw, Mark Wilkins, Vicky McCudden, Saj Ahmad, Virginia Calder, Naushin Waseem, Beverly Scott, Catey Bunce, William Gage, Mike Gleeson, Valerie Lund, Guri Sandhu
Journal: Ophthalmology (2017)
Phenotypes of symptomatic airways disease in China and New Zealand
Authors: James Fingleton, Kewu Huang, Mark Weatherall, Yanfei Guo, Stefan Ivanov, Piet Bruijnzeel, Hong Zhang, Wei Wang, Richard Beasley, Chen Wang
Journal: European Respiratory Journal (2017)

It is uncertain whether phenotypes of asthma and chronic obstructive pulmonary disease (COPD) vary between populations with different genetic and environmental characteristics. Here, our objective was to compare the phenotypes of airways disease in two separate populations. This was a cross-sectional observational study in adult populations from New Zealand and China. Participants aged 40–75 years who reported wheeze and breathlessness in the last 12 months were randomly selected from the general population and underwent detailed characterisation. Complete data for cluster analysis were available for 345 participants. Hierarchical cluster analysis was undertaken, based on 12 variables: forced expiratory volume in 1 s (FEV 1 ), FEV 1 /forced vital capacity ratio, bronchodilator reversibility, peak expiratory flow variability, transfer coefficient of the lung for carbon monoxide, exhaled nitric oxide fraction, total IgE, C-reactive protein, age of symptom onset, body mass index, health status and cigarette smoke exposure. Cluster analysis of the combined dataset described five phenotypes: “severe late-onset asthma/COPD overlap group”, “moderately severe early-onset asthma/COPD overlap group”, “moderate to severe asthma group with type 2 predominant disease”, and two groups with minimal airflow obstruction, differentiated by age of onset. Separate analyses by country showed similar patterns; however, a distinct obese/comorbid group was observed in the New Zealand population. Cluster analysis of adults with symptomatic airways disease suggests the presence of similar asthma/COPD overlap phenotypes within populations with different genetic and environmental characteristics, and an obese/comorbid phenotype in a Western population.
GOG0076-GG: A limited access phase II trial of pemetrexed (LY231514) (NSC #698037) in combination with cisplatin (NSC #119875) in the treatment of advanced, persistent, or recurrent carcinoma of the cervix—A Gynecologic Oncology Group study.
Authors: David S. Miller, John A. Blessing, Lois M. Ramondetta, Huyen Pham, Krishnansu Sujata Tewari, Lisa Michelle Landrum, Jubilee Brown, Robert S. Mannel
Journal: Journal of Clinical Oncology (2013)

5527 Background: To estimate the antitumor activity of Pemetrexed and cisplatin with objective tumor response (partial and complete) in patients with advanced, persistent, or recurrent carcinoma of the cervix and to determine the nature and degree of toxicity of this regimen. Secondarily, to determine the effects of this regimen on progression-free survival and overall survival. Methods: Eligible, consenting patients received pemetrexed 500mg/m2 and cisplatin 50 mg/m2 IV repeated every 21 days until disease progression or adverse effects prohibited further therapy. Patients had received no prior therapeutic chemotherapy, except when administered concurrent with primary radiation therapy. Subsequent doses were adjusted according to observed toxicity and protocol guidelines. Adverse events were assessed with CTCAE v 3.0. Primary measure of efficacy was tumor response by RECIST. The study was stratified by prior radiation therapy. Results: From September 2008 to November 2011, 55 patients were enrolled by 5 GOG member institutions. Of those, 49 patients were eligible and assessable. The regimen was well tolerated with 14 (29%) receiving &gt;9 cycles. Common grade &gt;2 toxicities were neutropenia 35%, leukopenia 28%, and metabolic 28%. The overall response rate was 31% (one complete and 16 partial responses). The median response duration was 7 months and survival 12 months. Conclusions: Pemetrexed in combination with cisplatin has demonstrated activity in the treatment of advanced, persistent, or recurrent carcinoma of the cervix. Additional study of this regimen in a phase III setting is justified in this patient population. Clinical trial information: NCT00691301.
Care pathways for the selection of a biologic in severe asthma
Authors: Jean Bousquet, Guy Brusselle, Roland Buhl, William W. Busse, Alvaro A. Cruz, Ratko Djukanovic, Christian Domingo, Nicola A. Hanania, Marc Humbert, Andrew Menzies Gow, Wanda Phipatanakul, Ulrich Wahn, Michael E. Wechsler
Journal: European Respiratory Journal (2017)

Patients with severe asthma generally benefit from consultations with an asthma specialist to optimise their management, which may include the potential initiation of biologic agents that have made a breakthrough in the treatment of severe disease. Physicians need care pathways to select a biologic in type 2 severe asthma (omalizumab, mepolizumab, reslizumab) <http://ow.ly/pygw30gB7Bv>
Identification of Ser465 as a novel PINK1 autophosphorylation site
Authors: Ji-feng Guo, Ling-yan Yao, Qi-ying Sun, Yi-ting Cui, Yang Yang, Qian Xu, Xin-xiang Yan, Bei-sha Tang
Journal: Translational Neurodegeneration (2017)

PINK1 (PTEN-induced putative kinase 1) gene is the causal gene for recessive familial type 6 of Parkinson's disease (PARK6), which is an early-onset autosomal recessive inherited neurodegenerative disease. PINK1 has been reported to exert both autophosphorylation and phosphorylation activity, affecting cell damage under stress and other physiological responses. However, there has been no report on the identification of PINK1 autophosphorylation sites and their physiological functions. (1) We adopted mass spectrometry assay to identify the autophosphorylation site of PINK1, and autoradiography assay was further conducted to confirm this result. (2) Kinase activity assay was used to compare the kinase activity of both Ser465 mutant PINK1 and disease-causing mutant PINK1. (3) We use Pulse-chase analysis to measure whether Ser465 may affect PINK1 degradation. (4) Immunocytochemistry staining was used to study the PINK1 subcellular localization and Parkin transition in subcellular level. In our study, we identified the 465th serine residue (Ser465) as one of the autophosphorylation sites in PINK1 protein. The inactivation of Ser465 can decrease the kinase activity of PINK1. Either dissipated or excessive Ser465 site phosphorylation of PINK1 can slow down its degradation. PINK1 autophosphorylation contributes to the transit of Parkin to mitochondria, and has no effect on its subcellular localization. PARK6 causal mutations, T313 M and R492X, display the same characteristics as Ser465A mutation PINK1 protein, such as decreasing PINK1 kinase activity and affecting its interaction with Parkin. Ser465 was identified as one of the autophosphorylation sites of PINK1, which affected PINK1 kinase activity. In addition, Ser465 is involved in the degradation of PINK1 and the transit of Parkin to mitochondria. T313 M and R492X, two novel PARK6 mutations on Thr313 and Arg492, were similar to Ser465 mutation, including decreasing PINK1 phosphorylation activity and Parkin subcellular localization.
Genetic studies as a tool for identifying novel potential targets for treatment of COPD
Authors: Ani Manichaikul, Jennifer N. Nguyen
Journal: European Respiratory Journal (2017)

Chronic obstructive pulmonary disease (COPD), characterised by chronic airflow limitation and abnormal response to noxious particles or gases [1], is currently the fourth leading cause of death worldwide [2] and the only major cause of death that has seen continued increases in recent years. While smoking cessation, oxygen therapy and bronchodilators offer some relief from the symptoms of disease, and medications are available to prevent COPD exacerbations [3], there are currently no treatments available to slow or stop progression, reflecting a limited understanding of the molecular underpinnings of the disease. In this issue of the European Respiratory Journal , Obeidat et al. [4] identify surfactant protein-D (SP-D) as a potentially causal risk factor for COPD. Their paper is presented in multiple distinct parts, beginning with a genome-wide association study (GWAS) to identify single-nucleotide polymorphisms (SNPs) from three genomic regions (on chromosomes 6, 10 and 16) associated with circulating levels of SP-D, followed by a Mendelian randomisation study demonstrating that genetically determined lower levels of SP-D are associated with increased risk of COPD based on results from a large-scale consortium based on a GWAS of up to ∼11 000 COPD cases and ∼37 000 controls recently published by the International COPD Genetics Consortium [5]. The results from the study of Obeidat et al. [4] are promising and open new potential avenues for early diagnosis and treatment of this disease. How did we get to this novel finding, what steps remain to carry this finding forward towards establishing the role of SP-D in COPD, and how can we stimulate additional discovery of novel therapeutic targets? Genetic studies are a useful tool for identification of novel causal biomarkers and therapeutic targets for COPD <http://ow.ly/zZKC30fNecz>
STPs are based on flawed financial assumptions
Authors: John W L Puntis
Journal: BMJ (2017)

Oliver says that sustainability and transformation partnerships (STPs) could “in theory” deliver benefits, while acknowledging that they have been criticised for “being rushed, for overpromising savings, and for lacking clinical engagement.”1 The key words are “in theory,” as STPs have much more fundamental problems. 

As the mechanism for delivering the new models of …
Abstract A03: Novel polyisoprenylated small molecules as potential new therapies for triple negative breast cancer
Authors: Olufisayo O. Salako, Augustine T. Nkembo, Elizabeth Ntantie, Nazarius S. Lamango
Journal: Cancer Research (2017)

Abstract Breast cancer patients whose tumors do not overexpress estrogen, progesterone or HER2 receptors do not benefit from the effective therapies targeting these receptors. Knowing what drives the tumors in the latter group of patients, known as triple negative breast cancer (TNBC), is important for developing more effective and less toxic therapies directed at these drivers. We have developed a novel class of compounds, the polyisoprenylated cysteinyl amide inhibitors (PCAIs) that target the aberrant growth signaling by EGFR and/or constitutively active mutant K-Ras in a significant proportion of TNBC and other aggressive cancers such as of the pancreas, colon and lungs. The PCAIs induced apoptotic cell death with EC50 values ranging from 2.2 to 2.7 µM. The PCAIs induced apoptosis in MDA-MB-231 spheroids as well as inhibited the spheroid formation at 1 and 2 µM, respectively. The PCAIs, at 1 µM, inhibited over 80% colony formation in MDA-MB-231 cells. At 1 and 2 µM, MDA-MB-231 Transwell cell invasion was inhibited by 80 and 94%, respectively. The PCAIs blocked tube formation in cultured HUVEC cells at 0.2 to 0.5 µM and vessel formation in chick embryos at 0.12 µg/egg. The PCAIs can thus be used as targeted therapies to inhibit tumor growth, cell migration and angiogenesis in TNBC and other cancers with excessive growth factors receptor and mutant K-Ras signaling. Citation Format: Olufisayo O. Salako, Augustine T. Nkembo, Elizabeth Ntantie, Nazarius S. Lamango. Novel polyisoprenylated small molecules as potential new therapies for triple negative breast cancer [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 A03.
Artifactual Hepatic Metastasis on FDG PET/CT Secondary to Cryoablation for Adrenal Metastasis
Authors: Joseph Frankl, Naghmehossadat Eshghi, Tamara F. Lundeen, Phillip H. Kuo
Journal: Clinical Nuclear Medicine (2017)

A 65-year-old woman with metastatic lung cancer was referred for CT-guided cryoablation of a right adrenal metastasis. For cryoablation, probes were placed into the adrenal region. FDG PET/CT 3 months later showed new activity in hepatic segment 6 initially suspected to be metastasis. Proximity of the hepatic lesion to the adrenal metastasis was a strange coincidence and prompted review of imaging from the cryoablation. CT showed the probe entered the liver, and postablation image demonstrated injury to the liver adjacent to the adrenal metastasis. Careful review of treatment history and imaging from ablation procedures are important to avoid this pitfall.
Abstract 21117: Comparison of Clinical Outcomes Between Clopidogrel and New P2Y12 Antagonist in Acute Myocardial Infarction Patients Treated With Percutaneous Coronary Intervention
Authors: Jung-Hee Lee, Hongju Kim, Sungyun Jung, Kang-Un Choi, Chan-Hee Lee, Ung Kim, Jang-Won Son, Jong-Seon Park, Dong-Gu Shin
Journal: Circulation (2017)

Background: Recent studies have suggested new P2Y12 antagonists (prasugrel /ticagrelor) are more effective in high thrombotic conditions than conventional clopidogrel The aim of this study was to compare the clinical outcomes between clopidogrel abd new P2Y12 antagonist in acute myocardial infarction patients treated with percutaneous coronary intervention (PCI). Methods: Between November 2011 and January 2016, a total of 11,731 AMI patients treated with PCI (7580 patients were prescribed clopidogrel and 4151 patients new P2Y12 antagonists) were enrolled in the Korean Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) database. Propensity score matching was performed to adjust for differences in baseline clinical variables. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial infarction, target-lesion revascularization (TLR), and stroke. Results: After propensity matching (4151 pairs), the rate of MACCEs were more frequently occurred in the clopidogrel group than in the new P2Y12 (8.2% vs. 6.4%, p=0.002). The difference in MACCE between two groups was driven by cardiac death (4.7% vs. 3.3%, p&lt;0.001). There was no significant difference in myocardial infarction (0.7% vs. 0.6%, p=0.783), TLR (2.4% vs. 1.8%, p=0.337), and stroke (0.8% vs. 0.7%, p=0.336). However, the incidences of Thrombolysis In Myocardial Infarction (TIMI) minor bleeding showed a trend toward a lower incidence in the clopidogrel group (13.8% vs. 17.3%, p=0.057). Conclusion: Our study shows that new P2Y12 antagonist was associated lower rate of MACCE and cardiac mortality in AMI patients treated with PCI.
Abstract B31: The role of HIV protein Nef in the development of HIV/AIDS-associated lymphomas
Authors: Shaheen Mowla, Nontlantla Mdletshe
Journal: Cancer Research (2017)

Abstract Introduction: The pathogenesis HIV-associated lymphomas involve a complex interplay of biological factors, including the immerging role of HIV encoded proteins. These proteins have been shown to have oncogenic potential and to enhance the pathogenesis of HIV-associated malignancies. However, very little is known about the molecular mechanisms involved in this interaction. Here, we investigate the effect of HIV protein Negative Factor (Nef) on the expression of c-MYC and activation-induced cytidine deaminase (AID) in lymphoblasts and lymphoma cells. Methods: Native histidine-tagged HIV Nef was produced in a bacterial system and used to treat (1) an EBV-immortalized B lymphoblastoid cell line (L1439A) and (2) the established lymphoma cell line Ramos, at various concentrations and for various time points. Changes in the expressions of c-MYC and AID were measured at both the mRNA and proteins levels using qPCR and western blotting respectively. The ability of Nef to regulate the promoter of these two genes was determined using luciferase reporter assays. Furthermore, confocal microscopy was used to investigate the downstream effects of Nef exposure. Results: In L1439A cells, a general decrease in the expression of c-MYC and AID was observed. After 1 and 3 hours of exposure to HIV-Nef both c-MYC and AID mRNA levels reduced by approximately 0.5-fold. In contrast, the expressions of both genes increased significantly upon these treatments in the lymphoma cell line Ramos. After 3 hours of exposure, c-MYC expression increased by ~1.9-fold, while AID expression increased up to 4.6-fold. The protein expression followed a similar pattern, as indicated by western blotting. Furthermore, luciferase reporter assays showed that the effect on c-MYC expression is likely to be direct since the activity of the c-MYC promoter increased in a dose-dependent manner in the presence of Nef. c-MYC translocated to the nucleus, which is indicative of an active protein. Furthermore, an increase in gamma H2AX foci on DNA, indicative of double strand breaks, shows that the increase in AID lead to genomic instability. Conclusion: This study demonstrates a differential effect of HIV Nef on normal immortalized lymphoblasts versus lymphoma cells. More importantly, it shows for the first time that HIV Nef may enhance the pathogenesis of lymphomas by triggering pathways and mechanisms which increase the expression of c-MYC and AID. Citation Format: Shaheen Mowla, Nontlantla Mdletshe. The role of HIV protein Nef in the development of HIV/AIDS-associated lymphomas [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 B31.
Abstract 14190: Percutaneous Coronary Intervention at Hospitals With and Without On-site Cardiothoracic Surgery Focusing on SYNTAX Score Grade
Authors: Naoyuki Abe, Takashi Miura
Journal: Circulation (2016)

Background: Percutaneous coronary intervention (PCI) at hospitals without on-site cardiothoracic (CT) surgery has been established. The aim of this study was to investigate the difference of clinic...
Abstract 19873: Emotional Distress is a Predictor of Poor Long-Term Statin Adherence at Two Years After a Myocardial Infarction
Authors: Claudia T Lissåker, John Wallert, Claes Held, Erik Olsson
Journal: Circulation (2016)

Introduction:  Statin use after a myocardial infarction (MI) has been shown to effectively reduce cardiovascular events and mortality and is first line therapy. However, evidence shows suboptimal treatment adherence. Emotional distress (ED) has been found to affect adherence to cardiac medication, but less has been done to assess its influence in adherence to statin medication. We hypothesized that self-reported ED short-term after the MI would predict lower statin adherence at approximately one year, as well as at two years after the MI event.   Methods:  We utilized data from the SWEDEHEART registries. To characterize ED, we used the EuroQoL-5D question pertaining to anxiety and depression given to participants 6-10 weeks after the MI event and approximately one year later. We calculated medication adherence using the Swedish National Prescription Register. Adherence was defined as having enough pills dispensed to cover at least 80% of the time interval measured. Our sample consisted of individuals, under 75 years of age, who had complete data for ED and statin adherence, as well as for potential confounders. For the initial analysis, 5288 individual pairs were matched from a total of 15,154 based on their propensity scores. Unadjusted logistic regressions were done on the balanced sample. We repeated the propensity score analysis for adherence two years after the MI event (n=4341 pairs), as well as for ED measured approximately one year after the MI event and adherence one year later, i.e. 2 years after the MI event (n=3306 pairs).   Results:  ED reported at 6-10 weeks was not associated with statin adherence one year later (OR 0.96; 95% CI: 0.85-1.07), but was associated with lower statin adherence two years after the MI (OR 0.89; 95% CI: 0.80-0.99). Further, ED reported one year after the MI was associated with lower statin adherence in the following year (OR 0.81; 95% CI: 0.72-0.91).   Conclusions:  Emotional distress reported following an MI was not associated with a decrease in statin adherence at one year. However, emotional distress assessed early or at one year were both associated with lower adherence to statins two years after the MI event. Our study shows that self-reported emotional distress is an important predictor of poor long-term statin adherence.
The Presence of Pleural Effusion at Diagnosis Predicts Poor Outcomes in Diffuse Large B-Cell Lymphoma Patients with MYC -Rearrangement or Double Protein Expression
Authors: Hideaki Nitta, Akihiko Gotoh, Masaru Tanaka, Tomonori Ochiai, Yasunori Ota, Norio Komatsu
Journal: Blood (2017)