tbuckley/cabot-search huggingface dataset:
Abstract 11411: Parental Age of Hypertension Onset and Risk of Hypertension in the Offspring: The Framingham Heart Study
Authors: Teemu J Niiranen, Elizabeth L McCabe, Martin G Larson, Ramachandran S Vasan, Susan Cheng
Journal: Circulation (2016)

Introduction: Parental hypertension (HTN) is known to predict HTN in offspring. However, the relative impact of objectively diagnosed early- vs. late-onset parental HTN on risk of HTN in the community is unknown. Hypothesis: We hypothesized that parental early- vs. late-onset HTN is associated with a substantially greater risk of HTN in offspring. Methods: We analyzed serially collected blood pressure data in the Original cohort (since 1948) and in the Offspring cohort (since 1971) of Framingham Heart Study participants. We identified 1635 non-hypertensive Offspring (32±9 years, 54% women) with longitudinal blood pressure data available for both parents. We defined HTN onset as blood pressure ≥140/90 mmHg or taking antihypertensive medication at ≥2 consecutive exams, and early-onset HTN as onset age &lt;55 years. We analyzed the risk for HTN in Offspring in relation to their parental HTN status: (1) no parents with HTN (N=107); (2) ≥1 parent with late-onset HTN (N=480); (3) 1 parent with early-onset HTN (N=721); and, (4) both parents with early-onset HTN (N=327). Results: Incident HTN was most common in Offspring whose both parents had early-onset HTN (Figure, log-rank p&lt;0.0001). Incidence rates for HTN per 1000 person-years increased across the 4 groups: 5.9 in group 1, 8.3 in group 2, 11.0 in group 3, and 18.9 in group 4. In a multivariable-adjusted discrete logistic model, Offspring HTN risk increased from group 1 (referent) to group 2 (hazard ratio [HR] 1.50, 95% confidence interval [CI] 0.85-2.68), and from group 3 (HR 2.04, 95% CI 1.18-3.54) to group 4 (HR 3.45, 95% CI 1.93-6.14). In 463 Offspring who developed HTN, a 10-year lower parental age of HTN onset was associated with a 1.28-fold (95% CI 1.02-1.61) greater odds of early-onset HTN. Conclusions: Early-onset and not late-onset HTN in parents is a strong risk factor for HTN in offspring. It may be important to differentiate between early- and late-onset parental HTN when estimating an individual’s HTN risk.
Final results of a multi-institutional phase II trial of reirradiation with concurrent weekly cisplatin and cetuximab for recurrent or second primary squamous cell carcinoma of the head and neck
Authors: M.J. Awan, L. Nedzi, D. Wang, V. Tumati, B. Sumer, X.-J. Xie, I. Smith, J. Truelson, R. Hughes, L.L. Myers, P. Lavertu, S. Wong, M. Yao
Journal: Annals of Oncology (2018)
Chemical modifications of nucleic acid drugs and their delivery systems for gene‐based therapy
Authors: Changmai Chen, Zhenjun Yang, Xinjing Tang
Journal: Medicinal Research Reviews (2018)

Abstract Gene‐based therapy is one of essential therapeutic strategies for precision medicine through targeting specific genes in specific cells of target tissues. However, there still exist many problems that need to be solved, such as safety, stability, selectivity, delivery, as well as immunity. Currently, the key challenges of gene‐based therapy for clinical potential applications are the safe and effective nucleic acid drugs as well as their safe and efficient gene delivery systems. In this review, we first focus on current nucleic acid drugs and their formulation in clinical trials and on the market, including antisense oligonucleotide, siRNA, aptamer, and plasmid nucleic acid drugs. Subsequently, we summarize different chemical modifications of nucleic acid drugs as well as their delivery systems for gene‐based therapeutics in vivo based on nucleic acid chemistry and nanotechnology methods.
Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis
Authors: Francesc Coll, Jody Phelan, Grant A. Hill-Cawthorne, Mridul B. Nair, Kim Mallard, Shahjahan Ali, Abdallah M. Abdallah, Saad Alghamdi, Mona Alsomali, Abdallah O. Ahmed, Stephanie Portelli, Yaa Oppong, Adriana Alves, Theolis Barbosa Bessa, Susana Campino, Maxine Caws, Anirvan Chatterjee, Amelia C. Crampin, Keertan Dheda, Nicholas Furnham, Judith R. Glynn, Louis Grandjean, Dang Minh Ha, Rumina Hasan, Zahra Hasan, Martin L. Hibberd, Moses Joloba, Edward C. Jones-López, Tomoshige Matsumoto, Anabela Miranda, David J. Moore, Nora Mocillo, Stefan Panaiotov, Julian Parkhill, Carlos Penha, João Perdigão, Isabel Portugal, Zineb Rchiad, Jaime Robledo, Patricia Sheen, Nashwa Talaat Shesha, Frik A. Sirgel, Christophe Sola, Erivelton Oliveira Sousa, Elizabeth M. Streicher, Paul Van Helden, Miguel Viveiros, Robert M. Warren, Ruth McNerney, Arnab Pain, Taane G. Clark
Journal: Nature Genetics (2018)
Non-coding RNAs: key regulators of smooth muscle cell fate in vascular disease
Authors: Nicholas J Leeper, Lars Maegdefessel
Journal: Cardiovascular Research (2017)

The vascular smooth muscle cell (SMC) is one of the most plastic cells in the body. Understanding how non-coding RNAs (ncRNAs) regulate SMC cell-fate decision making in the vasculature has significantly enhanced our understanding of disease development, and opened up exciting new avenues for potential therapeutic applications. Recent studies on SMC physiology have in addition challenged our traditional view on their role and contribution to vascular disease, mainly in the setting of atherosclerosis as well as aneurysm disease, and restenosis after angioplasties. The impact of SMC behaviour on vascular disease is now recognized to be context dependent; SMC proliferation and migration can be harmful or beneficial, whereas their apoptosis, senescence, and switching into a more macrophage-like phenotype can promote inflammation and disease progression. This is in particular true for atherosclerosis-related diseases, where proliferation of SMCs was believed to promote lesion formation, but may also prevent plaque rupture by stabilizing the fibrous cap. Based on newer findings of genetic lineage tracing studies, it was revealed that SMC phenotypic switching can result in less-differentiated forms that lack classical SMC markers while exhibiting functions more related to macrophage-like cells. This switching can directly promote atherogenesis. The aim of this current review is to summarize and discuss how ncRNAs (mainly microRNAs and long ncRNAs) are involved in SMC plasticity, and how they directly affect vascular disease development and progression. Finally, we want to critically assess where potential future therapies could be useful to influence the burden of vascular diseases.
Abstract P062: Impact of Second-line Antidiabetic Treatments on the Risk of Microvascular Complications: Analysis of Real-world Data for 94,685 Patients Type 2 Diabetes
Authors: Kyoung Hwa Ha, Bongseong Kim, Hansol Choi, Dae Jung Kim, Hyeon Chang Kim
Journal: Circulation (2017)

Objective: To compare the risk of microvascular complications associated with second-line anti-diabetic medications by analyzing the national health insurance claim database. Methods: The Korean National Health Insurance (NHI) Service is the single payer which covers all Korean citizens and residents. We identified all patients who used sulphonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP4I), or thiazolidinedione (TZD) as a second-line oral anti-diabetic medication added to metformin (MET) therapy between January 2011 and June 2015 in the NHI database. Cox’s proportional hazard regression model was used to estimate hazard ratio and its 95% confidence interval for developing microvascular complications according to the types of second-line medications. Age, gender, calendar index year, duration of metformin treatments, comorbidities of hypertension and dyslipidemia, and Charlson Comorbidity Index were adjusted as potential confounders. Results: A total of 94685 initiators of a second-line add-on to MET of either a SU (n = 28887), DPP4I (n = 60780) or TZD (n = 5018) were identified. Diagnoses of diabetic retinopathy (n=7139), diabetic nephropathy (n=5290), and diabetic neuropathy (n=4265) were identified from the NHI claim database over a mean of 1.3 years of follow-up. Compared to the SU+MET, adjusted hazard ratio (95% confidence interval) for diabetic retinopathy was 1.03 (0.96-1.10) for the DPP4I+MET and 1.26 (1.10-1.44) for the TZD+MET. Adjusted hazard ratio (95% confidence interval) for diabetic nephropathy was 1.30 (1.19-1.42) for the DPP4I+MET and 1.63 (95% CI: 1.40-1.91) for the TZD+MET, compared with the SU+MET. Adjusted hazard ratio (95% confidence interval) for diabetic neuropathy was 0.78 (95% CI: 0.71-0.85) for the DPP-4i+MET and 0.81 (95% CI: 0.66-0.99) for the TZD+MET, compared with the SU+MET. Conclusion: In this analysis of nationwide real-world data, DPP4I+MET and TZD+MET therapies were associated with higher risk of diabetic retinopathy and nephropathy, but lower risk of diabetic neuropathy compared to SU+MET therapy.
Evaluation of Overall Response Rate and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Immunotherapy Trials
Authors: Sirisha L. Mushti, Flora Mulkey, Rajeshwari Sridhara
Journal: Clinical Cancer Research (2018)

Purpose: With the approval of immunotherapies for a variety of indications, methods to assess treatment benefit addressing the response patterns observed are important. We evaluated RECIST criteria-based overall response rate (ORR) and progression-free survival (PFS) as potential surrogate endpoints of overall survival (OS), and explored a modified definition of PFS by altering the threshold percentage determining disease progression to assess the association with survival benefit in immunotherapy trials.Experimental Design: Thirteen randomized, multicenter, active-control trials containing immunotherapeutic agents submitted to the FDA were analyzed. Associations between treatment effects of ORR, PFS, modified PFS, and OS were evaluated at individual and trial levels. Patient-level responder analysis was performed for PFS and OS.Results: The coefficient of determination (R²) measured the strength of associations, where values near 1 imply surrogacy and values close to 0 suggest no association. At the trial level, the association between hazard ratios (HR) of PFS and OS was R2 = 0.1303, and between the odds ratio (OR) of ORR and HR of OS was R2 = 0.1277. At the individual level, the Spearman rank correlation coefficient between PFS and OS was 0.61. Trial-level associations between modified PFS and OS ranged between 0.07 and 0.1, and individual-level correlations were approximately 0.6. HRs of PFS and OS for responders versus nonresponders were 0.129 [95% confidence interval (CI), 0.11-0.15] and 0.118 (95% CI, 0.11-0.13), respectively.Conclusions: Although responders exhibited longer survival and PFS than nonresponders, the trial-level and individual-level associations were weak between PFS/ORR and OS. Modifications to PFS did not improve associations. Clin Cancer Res; 24(10); 2268-75. ©2018 AACRSee related commentary by Korn and Freidlin, p. 2239.
RETRACTED ARTICLE: Upregulation of the long non-coding RNA AFAP1-AS1 affects the proliferation, invasion and survival of tongue squamous cell carcinoma via the Wnt/β-catenin signaling pathway
Authors: Ze-you Wang, Min Hu, Min-hui Dai, Jing Xiong, Shuai Zhang, Han-jiang Wu, Shan-shan Zhang, Zhao-jian Gong
Journal: Molecular Cancer (2018)

Long non-coding RNA (lncRNA) actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) is oriented in an antisense direction to the protein-coding gene AFAP1 in the opposite strand. Previous studies showed that lncRNA AFAP1-AS1 was upregulated and acted as an oncogene in a variety of tumors. However, the expression and biological functions of lncRNA AFAP1-AS1 in tongue squamous cell carcinoma (TSCC) are still unknown. The expression level of AFAP1-AS1 was measured in 103 pairs of human TSCC tissues and corresponding adjacent normal tongue mucous tissues. The correlation between AFAP1-AS1 and the clinicopathological features was evaluated using the chi-square test. The effects of AFAP1-AS1 on TSCC cells were determined via a CCK-8 assay, clone formation assay, flow cytometry, wound healing assay and transwell assay. Furthermore, the effect of AFAP1-AS1 knockdown on the activation of the Wnt/β-catenin signaling pathway was investigated. Finally, CAL-27 cells with AFAP1-AS1 knockdown were subcutaneously injected into nude mice to evaluate the effect of AFAP1-AS1 on tumor growth in vivo. In this study, we found that lncRNA AFAP1-AS1 was increased in TSCC tissues and that patients with high AFAP1-AS1 expression had a shorter overall survival. Short hairpin RNA (shRNA)-mediated AFAP1-AS1 knockdown significantly decreased the proliferation of TSCC cells. Furthermore, AFAP1-AS1 silencing partly inhibited cell migration and invasion. Inhibition of AFAP1-AS1 decreased the activity of the Wnt/β-catenin pathway and suppressed the expression of EMT-related genes (SLUG, SNAIL1, VIM, CADN, ZEB1, ZEB2, SMAD2 and TWIST1) in TSCC cells. In addition, CAL-27 cells with AFAP1-AS1 knockdown were injected into nude mice to investigate the effect of AFAP1-AS1 on tumorigenesis in vivo. Downregulation of AFAP1-AS1 suppressed tumor growth and inhibited the expression of EMT-related genes (SLUG, SNIAL1, VIM, ZEB1, NANOG, SMAD2, NESTIN and SOX2) in vivo. Taken together, our findings present a road map for targeting the newly identified lncRNA AFAP1-AS1 to suppress TSCC progression, and these results elucidate a novel potential therapeutic strategy for TSCC.
Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis
Authors: Yutaka Hasegawa, Kenji Ikeda, Yong Chen, Diana L. Alba, Daniel Stifler, Kosaku Shinoda, Takashi Hosono, Pema Maretich, Yangyu Yang, Yasushi Ishigaki, Jingyi Chi, Paul Cohen, Suneil K. Koliwad, Shingo Kajimura
Journal: Cell Metabolism (2018)
Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models
Authors: Michael L Schulte, Allie Fu, Ping Zhao, Jun Li, Ling Geng, Shannon T Smith, Jumpei Kondo, Robert J Coffey, Marc O Johnson, Jeffrey C Rathmell, Joe T Sharick, Melissa C Skala, Jarrod A Smith, Jordan Berlin, M Kay Washington, Michael L Nickels, H Charles Manning
Journal: Nature Medicine (2018)
Inner City Severe Allergic Asthma: Differential Clinical Markers in Eosinophilic Low Cohort (LC, &lt;150 uL) vs Medium Cohort (MC, 150-300 uL) vs High Cohort (HC, &gt; 300 uL)
Authors: Muhammad Ahmad, James Mantas, Muhammad Salman Aslam, Ahmad Arslan, Tushar Thakur, Nikhil Tambe, Radha Dhingra, Edward S. Schulman
Journal: Journal of Allergy and Clinical Immunology (2018)
Human primary osteoclasts and preosteoclast cells (FLG 29.1) express functional c-kit receptors and interact with osteoblast and stromal cells via membrane-bound stem cell factor (mb-SCF)
Authors: V Gattei, D Aldinucci, Quinn Jmw., M Degan, M Cozzi, V Perin, A DeJuliis, S Juzbasic, N A Athanasou, L K Ashman, A Pinto
Journal: Blood (1995)
Mutations in PI3K110δ cause impaired natural killer cell function partially rescued by rapamycin treatment
Authors: Raquel Ruiz-García, Alexander Vargas-Hernández, Ivan K. Chinn, Laura S. Angelo, Tram N. Cao, Zeynep Coban-Akdemir, Shalini N. Jhangiani, Qingchang Meng, Lisa R. Forbes, Donna M. Muzny, Luis M. Allende, Mohammed S. Ehlayel, Richard A. Gibbs, James R. Lupski, Gulbu Uzel, Jordan S. Orange, Emily M. Mace
Journal: Journal of Allergy and Clinical Immunology (2018)
Treatment of allergic rhinitis using mobile technology with real‐world data: The <scp>MASK</scp> observational pilot study
Authors: J. Bousquet, P. Devillier, S. Arnavielhe, A. Bedbrook, G. Alexis‐Alexandre, M. van Eerd, R. Murray, G. W. Canonica, M. Illario, E. Menditto, G. Passalacqua, C. Stellato, M. Triggiani, P. Carreiro‐Martins, J. Fonseca, M. Morais Almeida, L. Nogueira‐Silva, A. M. Pereira, A. Todo Bom, I. Bosse, D. Caimmi, P. Demoly, J. F. Fontaine, J. Just, G. L. Onorato, M. L. Kowalski, P. Kuna, B. Samolinski, J. M. Anto, J. Mullol, A. Valero, P. V. Tomazic, K. C. Bergmann, T. Keil, L. Klimek, R. Mösges, S. Shamai, T. Zuberbier, E. Murphy, P. McDowall, D. Price, D. Ryan, A. Sheikh, N. H. Chavannes, W. J. Fokkens, V. Kvedariene, A. Valiulis, C. Bachert, P. W. Hellings, I. Kull, E. Melen, M. Wickman, C. Bindslev‐Jensen, E. Eller, T. Haahtela, N. G. Papadopoulos, I. Annesi‐Maesano, M. Bewick, S. Bosnic‐Anticevich, A. A. Cruz, G. De Vries, B. Gemicioglu, D. Larenas‐Linnemann, D. Laune, E. Mathieu‐Dupas, R. E. O'Hehir, O. Pfaar, F. Portejoie, V. Siroux, O. Spranger, E. Valovirta, O. VandenPlas, A. Yorgancioglu
Journal: Allergy (2018)

Abstract Background Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect “real‐world” everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real‐life treatment of allergic rhinitis (AR) using mobile technology. Methods A mobile phone app ( Allergy Diary , freely available in Google Play and Apple App stores) collects the data of daily visual analog scales ( VAS ) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter ( OTC )) for rhinitis customized for 15 countries. Results A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1‐antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control). Conclusions This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment ( VAS ) on a mobile phone, shows novel findings, and generates new hypotheses.
All-in-One Theranostic Nanoplatform Based on Hollow MoS<sub>x</sub> for Photothermally-maneuvered Oxygen Self-enriched Photodynamic Therapy
Authors: Jinping Wang, Li Liu, Qing You, Yilin Song, Qi Sun, Yidan Wang, Yu Cheng, Fengping Tan, Nan Li
Journal: Theranostics (2018)

Photodynamic therapy (PDT) kills cancer cells by converting tumor-dissolved oxygen into reactive singlet oxygen (1O2) using a photosensitizer under laser irradiation. However, pre-existing hypoxia in tumors and oxygen consumption during PDT can result in an inadequate oxygen supply, which in turn hampers PDT efficacy. Herein, an O2 self-sufficient nanotheranostic platform based on hollow MoSx nanoparticles (HMoSx) with oxygen-saturated perfluorohexane (O2@PFH) and surface-modified human serum albumin (HSA)/chloride aluminium phthalocyanine (AlPc) (O2@PFH@HMoSx-HSA/AlPc), has been designed for the imaging and oxygen self-enriched photodynamic therapy (Oxy-PDT) of cancer.The in vitro anti-cancer activity and intracellular 1O2 generation performance of the nanoparticles were examined using 4T1 cells. We also evaluated the multimodal imaging capabilities and anti-tumor efficiency of the prepared nanoparticles in vivo using a 4T1 tumor-bearing nude mouse model.This nanoplatform could achieve the distinct in vivo fluorescence (FL)/photoacoustic (PA)/X-ray computed tomography (CT) triple-model imaging-guided photothermally-maneuvered Oxy-PDT. Interestingly, the fluorescence and Oxy-PDT properties of O2@PFH@HMoSx-HSA/AlPc were considerably quenched; however, photothermal activation by 670 nm laser irradiation induced a significant increase in temperature, which empowered the Oxy-PDT effect of the nanoparticles. In this study, O2@PFH@HMoSx-HSA/AlPc demonstrated a great potential to image and treat tumors both in vitro and in vivo, showing complete tumor-inhibition over 16 days after treatment in the 4T1 tumor model.O2@PFH@HMoSx-HSA/AlPc is promising to be used as novel multifunctional theranostic nanoagent for triple-modal imaging as well as single wavelength NIR laser triggered PTT/Oxy-PDT synergistic therapy.
The Rise and Fall of Mandatory Cardiac Bundled Payments
Authors: Rishi K. Wadhera, Robert W. Yeh, Karen E. Joynt Maddox
Journal: JAMA (2018)

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Inhaled corticosteroid use to prevent severe vaso‐occlusive episode recurrence in children between 1 and 4 years of age with sickle cell disease: a multicenter feasibility trial
Authors: Leah Vance Utset, Zalaya Ivy, Shaina M. Willen, Mark Rodeghier, Amanda Watt, Leann Schilling, Chantel L. Jenkins, Stefanie Pepper, Barbara Speller‐Brown, Deepika S. Darbari, Suvankar Majumdar, Olufolake Adisa, Michael R. DeBaun
Journal: American Journal of Hematology (2018)
Increased leisure-time physical activity associated with lower onset of diabetes in 44 828 adults with impaired fasting glucose: a population-based prospective cohort study
Authors: Xiang Qian Lao, Han-Bing Deng, Xudong Liu, Ta-Chien Chan, Zilong Zhang, Ly-yun Chang, Eng-Kiong Yeoh, Tony Tam, Martin Chi Sang Wong, G Neil Thomas
Journal: British Journal of Sports Medicine (2018)

Aims To evaluate the effects of habitual leisure-time physical activity (LTPA) on incident type 2 diabetes in a prospective cohort of Chinese adults with impaired fasting glucose (IFG). Methods 44 828 Chinese adults aged 20–80 years with newly detected IFG but free from cardiovascular and cerebrovascular disease were recruited and followed up from 1996 to 2014. Incident type 2 diabetes was identified by fasting plasma glucose ≥7 mmol/L. The participants were classified into four categories based on their self-reported weekly LTPA: inactive, low, moderate, or high. Hazard ratios (HRs) and population attributable fractions (PAFs) were estimated with adjustment for established diabetic risk factor. Results After 214 148 person-years of follow-up, we observed an inverse dose–response relationship between LTPA and diabetes risk. Compared with inactive participants, diabetes risk in individuals reporting low, moderate and high volume LTPA were reduced by 12% (HR 0.88, 95% CI 0.80 to 0.99; P=0.015), 20% (HR 0.80, 95% CI 0.71 to 0.90; P&lt;0.001), and 25% (HR 0.75, 95% CI 0.67 to 0.83; P&lt;0.001), respectively. At least 19.2% (PAF 19.2%, 95% CI 5.9% to 30.6%) of incident diabetes cases could be avoided if the inactive participants had engaged in WHO recommendation levels of LTPA. This would correspond to a potential reduction of at least 7 million diabetic patients in the Greater China area. Conclusions Our results show higher levels of LTPA are associated with a lower risk of diabetes in IFG subjects. These data emphasise the urgent need for promoting physical activity as a preventive strategy against diabetes to offset the impact of population ageing and the growing obesity epidemic.