tbuckley/cabot-search huggingface dataset:
Vertical ridge augmentation in the esthetic zone
Authors: Isabella Rocchietta, Luca Ferrantino, Massimo Simion
Journal: Periodontology 2000 (2018)

Abstract The reconstruction of deficient alveolar ridges using vertical and/or horizontal guided bone regeneration techniques allows for ideal implant placement, which is crucial for function and also for esthetically successful outcomes. Unlike in the past, when meeting a patient's functional demands was sufficient, many patients now have greater expectations from their implant restoration. Hence, it is no longer enough simply to restore the edentulous space with a functioning tooth or teeth. It has been suggested that patients now measure their final restoration using the contralateral natural tooth as the gold standard. Both subjective and objective levels of patient information on dental implants have increased significantly in the last decade. As a result of this demand, implant literature has inherited and developed specific esthetic parameters and patient‐centered outcomes from studies in the restorative field. Unfortunately, studies reporting on guided bone regeneration in the esthetic zone entirely lack such parameters and outcomes. Currently, there is a strong need for a consensus on objective and well‐defined parameters to assess the esthetics in bone regeneration and subsequently on implant dentistry.
Evolutionary analysis indicates that DNA alkylation damage is a byproduct of cytosine DNA methyltransferase activity
Authors: Silvana Rošić, Rachel Amouroux, Cristina E. Requena, Ana Gomes, Max Emperle, Toni Beltran, Jayant K. Rane, Sarah Linnett, Murray E. Selkirk, Philipp H. Schiffer, Allison J. Bancroft, Richard K. Grencis, Albert Jeltsch, Petra Hajkova, Peter Sarkies
Journal: Nature Genetics (2018)

Methylation at the 5 position of cytosine in DNA (5meC) is a key epigenetic mark in eukaryotes. Once introduced, 5meC can be maintained through DNA replication by the activity of ‘maintenance’ DNA methyltransferases (DNMTs). Despite their ancient origin, DNA methylation pathways differ widely across animals, such that 5meC is either confined to transcribed genes or lost altogether in several lineages. We used comparative epigenomics to investigate the evolution of DNA methylation. Although the model nematode Caenorhabditis elegans lacks DNA methylation, more basal nematodes retain cytosine DNA methylation, which is targeted to repeat loci. We found that DNA methylation coevolved with the DNA alkylation repair enzyme ALKB2 across eukaryotes. In addition, we found that DNMTs introduced the toxic lesion 3-methylcytosine into DNA both in vitro and in vivo. Alkylation damage is therefore intrinsically associated with DNMT activity, and this may promote the loss of DNA methylation in many species. The authors report that DNA methylation coevolves with the DNA alkylation repair enzyme ALKB2 across eukaryotes. They also show that DNA methyltransferases cause alkylation damage in vitro and in vivo by introducing 3-methylcytosine into DNA.
Bladder cancer rapid autopsy: A mechanism for collecting metastatic tumor tissue and establishing xenograft models of metastatic disease.
Authors: Hung-Ming Lam, Funda Vakar-Lopez, Andrew Caleb Hsieh, Eva Corey, Robert B. Montgomery, Jonathan L. Wright
Journal: Journal of Clinical Oncology (2018)

478 Background: Patients with metastatic bladder cancer have a poor prognosis with a median survival of only 9-15 months. Understanding the biology of metastatic bladder cancer has been historically difficult due to a paucity of specimens and models that recapitulate human disease. We established a bladder cancer rapid autopsy program to systemically acquire metastases, and build patient-derived xenograft (PDX) and organoid models for biological studies. Methods: Patients with metastatic bladder cancer were consented and a rapid autopsy was performed 2-6 hours after death to allow acquisition of normal and metastasis specimens. Frozen and formalin-fixed and paraffin embedded specimens were collected and pathological evaluation was performed on each specimen. Additionally, tumors were implanted subcutaneously into SCID mice to establish PDXs. Once PDXs were developed, PDXs were dissociated for companion organoid culture. Clinical history and treatment information was documented for each patient. Results: We have performed 10 bladder cancer rapid autopsies to date, and have acquired 105 metastatic and 45 normal specimens. The pathological subtypes of patients include urothelial cell carcinoma (5/10), squamous cell carcinoma (3/10), and plasmacytoid variant of urothelial carcinoma (2/10). The cohort has been treated BCG only (1/10), chemotherapy (3/10), and chemotherapy and immune checkpoint inhibitors (6/10). The leading site of metastasis was the liver (7/10) and lung (7/10), followed by lymph node (5/10), bone (5/10), intestine (4/10), and omentum (2/10). Half (5/10) of the patients had extensive liver metastases that allow acquisition of multiple tumor foci. For the first time, PDX and organoids from two independent metastases (omentum – CoCaB 14.1 and liver –CoCaB 14.2) from the same patient were successfully developed. Conclusions: This bladder cancer rapid autopsy program provides an important volume of metastatic tumor specimens for study. Importantly, the first bladder cancer PDX derived from metastasis has been developed. The availability of metastatic bladder cancer specimens, PDXs, and organoids will allow biological studies of advanced disease.
IMPACTON MI RATE IN RELATION TO DRUG ELUTING STENT STRUT THICKNESS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Micaela Iantorno, Michael Lipinski, Kuku Kayode, Kyle Buchanan, M. Chadi Alraies, Deepakraj Gajanana, Rebecca Torguson, Hector Garcia Garcia, Ron Waksman
Journal: Journal of the American College of Cardiology (2018)
P086 Adipocytokines linking obesity and osteoarthritis
Authors: M-L Hülser, C Schreiyaeck, Y Luo, A Bozec, G Schett, E Neumann, U Müller-Ladner
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> In the Western society, obesity and the resulting metabolic changes are an increasing field of medical research. Both conditions alter the expression of adipokines such as adiponectin, visfatin or leptin, which can modulate key pathways of the immune system or the progress of osteoarthritis (OA). <h3>Objectives</h3> To evaluate cross-linking influences of the abovementioned comorbidities, we combined a high-fat diet (HFD) with the DMM osteoarthritis mouse model (Destabilisation of the <b><i>M</i></b>edial <b><i>M</i></b>eniscus). The serologic as well as local tissue effects of HFD at different stages of OA development were correlated to the local and systemic adipokine expression. <h3>Methods</h3> ND (normal diet) and HFD were fed to C57Bl/6 mice over a period of 3 months followed by surgical OA induction (time point 0). Tissues and sera were collected 4, 6, and 8 weeks after surgery. Serum levels of adipokines were measured by ELISA. Liver fat was scored to evaluate metabolic changes. Arthritis progression was scored and quantified based on histologic stainings of the joints (H/E, safranin O, Pappenheim and Masson-Goldner's trichrome). Immunohistochemical stainings of the joints were performed to evaluate local distribution of adipokine positive cells. Metabolic parameters were correlated to the progression of OA. <h3>Results</h3> At all time points, OA could be induced in all settings, especially when combined with HFD (e.g.: OA score at 6 weeks HFD 3.7 vs. ND 1.4). Systemically, leptin levels were significantly higher in HFD compared to ND, suggesting a leptin and established insulin resistance. However, DMM led to decreased leptin levels at all time points, independent from diet (e.g. 4 weeks: HFD healthy 18.4 ng/ml vs. HFD DMM 3.7 ng/ml). Systemic leptin levels and fatty-liver score were positively correlated. Interestingly, the systemic increase of adiponectin mediated by DMM was only visible at week 8 (HFD healthy 5176 ng/ml vs. HFD DMM 6149 ng/ml). HFD, DMM or the combination of both did not show significant effects on serum levels of adiponectin, visfatin or IL-6. The local adipokine distribution in the joints was independent from systemic parameters. <h3>Conclusions</h3> Our data show that similar to observations in humans, OA is deteriorated by HFD. This is reflected by increased numbers of adipokine positive cells in areas of destruction. This phenomenon appears to be based on local mechanisms as systemic adipokine levels did not reflect the intraarticular adipokine distribution. <h3>Disclosure of interest</h3> None declared
Invasive lobular (ILC) versus invasive ductal (IDC) breast cancer (BC): Clinical-pathologic features and clinical outcomes in monoinstitutional series.
Authors: Antonella Ferro, Claudio Eccher, Alessia Caldara, Renza Triolo, Mattia Barbareschi, Lucia Veronica Cuorvo, MariaChiara DiPasquale, Nicola L Decarli, Salvatore Mussari, Enzo Galligioni
Journal: Journal of Clinical Oncology (2012)

e21102 Background: ILC is less common than IDC and is usually diagnosed at a later stage Purpose:The aim of our study was to investigate different clinico-biological behavior associated to ILC compared to IDC and to evaluate implications on survival outcomes Methods: We analyzed data from 3749 consecutive cases of IBC treated from 1995 to 2008 and classified as ILC, IDC and mixed/other. Relationships with clinical-pathological variables and the impact of ILC/IDC types on Event Free Survival (EFS), Overall Survival (OS) and Post-Progression Survival (PPS) were analyzed. Results: We have identified 445 ILC BC (12%), 3021 IDC (80.5%), 149 mixed (3.9%) and 134 other histotypes (3.6%). Median age was 61 (25-97) years. ILC presented a significantly (p&lt;0.001) larger tumor size (T≥2: 46% vs 34%) and more frequent axilla involvement (43% vs 37%) compared to IDC. It was usually associated with intermediate grade, low ki67, positive ER and negative HER2 status. Mastectomy was more frequently required for ILC (45%) than IDC (37%). Adjuvant hormonal (± previous chemo) therapy was more frequently given (77 vs 64%) to ILC pts due to higher ER expression than IDC. At a median follow up of 77 (0-272) months (ms), there were not significant differences in EFS (81.4 vs 82.1%, p=0.7) and OS (82.8 vs 84.6%; p=0.19) between ILC vs IDC. Local and Distant Relapses were 15 (3.3%) and 50 (11.2%) in ILC vs 179 (5.9%) and 225 (7.4%) in IDC; preferential sites of first distant relapses were similar in both histotypes. Contralateral and second tumors were 9 (2%) and 22 (5%) in ILC vs 84 (2.8%) and 174 (5.7%) in IDC. Median time to first event was 38.3 ms in ILC vs 35.23 in IDC. PPS was 16.5 ms (0-100) in ILC compared to 22.2 (0-187) in IDC. Prognosis in term of OS was consistently worse for ILC pts, compared to IDC, when considering the luminal A (86.9 vs 93.5%; p=0.003), luminal C (70.4 vs 88.5%; p=0.028) and in triple negative subgroups (50 vs 73.1%; p=0.021). No difference in OS was seen for age, size, hormonal and nodal status, except in N&gt;3 ILC pts, in whom a trend of worse prognosis (55.6 vs 60.2%) was observed. Conclusions: ILC pts did not show in our series a better outcome than IDC pts, despite a quite favorable biological pattern.
US National Trends in Mortality From Acute Myocardial Infarction and Heart Failure
Authors: Paula Chatterjee, Karen E. Joynt Maddox
Journal: JAMA Cardiology (2018)

Hospitals in the United States have been subject to mandatory public reporting of mortality rates for acute myocardial infarction (AMI) and heart failure (HF) since 2007 and to value-based payment programs for these conditions since 2011. However, whether hospitals with initially poor baseline performance have improved relative to other hospitals under these programs, and whether patterns of improvement differ by condition, is unknown. Understanding trends within public reporting and value-based payment can inform future efforts in these areas.To examine patterns in 30-day mortality from AMI and HF and determine whether they differ for baseline poor performers (worst quartile in 2009 and 2010 in public reporting, prior to value-based payment) compared with other hospitals.Retrospective cross-sectional study at US acute care hospitals from 2009 to 2015 that included 2751 and 3796 hospitals with publicly reported mortality data for AMI and HF, respectively.Public reporting and value-based purchasing.Hospital-level risk-adjusted 30-day mortality rates.We identified 422 and 600 baseline poor-performing hospitals for AMI and HF, respectively. Baseline poor performers for AMI were more often public and for-profit and less often teaching hospitals. Baseline poor performers for HF were less often large hospitals. For AMI, 30-day mortality among baseline poor performers was higher at baseline but improved more over time compared with other hospitals (18.6% in 2009 to 14.6% in 2015; -0.74% per year; P < .001 vs 15.7% in 2009 to 14.0% in 2015; -0.26% per year; P < .001; P for interaction <.001). In contrast, for HF, baseline poor performers improved over time (13.5%-13.0%; -0.12% per year; P < .001), but mean mortality among all other HF hospitals increased during the study period (10.9%-12.0%; 0.17% per year; P < .001; P for interaction, <.001).Despite being subject to identical policy pressures, mortality trends for AMI and HF differed markedly between 2009 and 2015.
Long-Term Outcomes After Out-of-Hospital Cardiac Arrest in Young Patients With Myocardial Infarction
Authors: Ersilia M. DeFilippis, Avinainder Singh, Ankur Gupta, Gloria Ayuba, David Biery, Sanjay Divakaran, Bradley L. Collins, Arman Qamar, Amber Fatima, Jon Hainer, Josh Klein, Khurram Nasir, Marcelo F. Di Carli, Deepak L. Bhatt, Ron Blankstein
Journal: Circulation (2018)
INTRAVASCULAR ULTRASOUND MECHANISMS OF IN-STENT RESTENOSIS IN SAPHENOUS VEIN GRAFT LESIONS
Authors: Rafal Wolny, Gary Mintz, Mitsuaki Matsumura, Masaru Ishida, Yasir Parviz, Khady Fall, Tamim Nazif, Manish Parikh, Leroy Rabbani, Michael Collins, Philip Green, Ziad Ali, Dimitrios I. Karmpaliotis, David Brogno, Susheel K. Kodali, Torsten Vahl, Sahil Parikh, Lauren Privitera, Martin B. Leon, Gregg Stone, Ajay Kirtane, Jeffrey Moses, Akiko Maehara
Journal: Journal of the American College of Cardiology (2018)
Trends in mortality from idiopathic pulmonary fibrosis in the European Union: an observational study of the WHO mortality database from 2001–2013
Authors: Dominic C. Marshall, Justin D. Salciccioli, Barry S. Shea, Praveen Akuthota
Journal: European Respiratory Journal (2018)

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias and is characterised by progressive accumulation of scar tissue in the lungs. The objective of this study was to describe the current mortality rates due to IPF in Europe, based on the World Health Organization (WHO) mortality database. We used country-level data for IPF mortality, identified in the WHO mortality database using International Classification of Diseases 10th Edition (ICD-10) codes, for the period 2001–2013. Joinpoint analysis was performed to describe trends throughout the observation period. The median mortality was 3.75 per 100 000 (interquartile range (IQR) 1.37–5.30) and 1.50 per 100 000 (IQR 0.65–2.02) for males and females, respectively. IPF mortality increased in the majority of the European Union (EU) countries with the exceptions of Denmark, Croatia, Austria and Romania. There was a significant disparity in rates across Europe, in the range 0.41–12.1 per 100 000 for men and 0.24–5.63 per 100 000 for women. The most notable increases were observed in the United Kingdom and Finland. Rates were also substantially higher in males, with sex disparity increasing across the period. The reported IPF mortality appears to be increasing across the EU; however, there is substantial variation in mortality trends and overall reported mortality rates between countries.
Do accountable care organizations affect race mediated differences in cancer screening?
Authors: Daniel Lee, Sunita Thapa, Amy J Graves, Melinda Buntin, David F. Penson, Matthew J. Resnick
Journal: Journal of Clinical Oncology (2018)

131 Background: Accountable care organizations (ACO) reflect a payment innovation aimed to orient incentives to improve quality and reduce waste. The objective of this study was to determine whether ACO enrollment affects racial disparities in cancer screening, and to characterize the impact on the appropriateness of prostate cancer screening in minority populations. Methods: We built a cohort of Medicare beneficiaries from 2007 to 2013 were comprising a cohort of 11,087,056 person-years among ACO beneficiaries and 37,187,979 person-years among non-ACO beneficiaries. A difference-in-difference-in-differences (DDD) approach was utilized to identify the effect of ACO enrollment on cancer screening in racial/ethnic minorities relative to non-Hispanic whites. We then characterized differences in screening appropriateness after ACO enrollment using age (65-74 vs. 75+) and predicted survival (top vs. bottom quartile). Results: ACO enrollment was associated with approximately a 5% reduction in prostate cancer overscreening for white beneficiaries, namely among the elderly and those with unfavorable predicted survival. Compared to white men in the lowest quartile of predicted survival, Asian and Hispanic men with similarly low survival had a 4.8% and 13.0% relative increase in prostate cancer screening associated with ACO enrollment (DDD p = 0.015, p = 0.011, respectively). Prostate cancer overscreening was common among Asian men, with 46% of elderly Asian men attributed to an ACO undergoing cancer screening compared to 28% of elderly white men. Furthermore, ACO enrollment was associated with a 2.7% increase in screening relative to whites (DDD p = 0.0005). Compared to white beneficiaries, black men had consistently lower rates of prostate cancer screening. ACO enrollment did not narrow the disparity of prostate cancer screening between healthier (DDD p = 0.75) or younger (DDD p = 0.27) black and white beneficiaries. Conclusions: This study provides evidence of ACO-mediated increases in low-value screening for prostate cancer among sick and elderly Hispanics and Asians. Furthermore, ACO enrollment did not narrow known disparities in high-value prostate cancer screening among healthier and younger black men.
Development and validation of the SIMPLE endoscopic classification of diminutive and small colorectal polyps
Authors: Marietta Iacucci, Cristina Trovato, Marco Daperno, Oluseyi Akinola, David Greenwald, Seth Gross, Arthur Hoffman, Jeffrey Lee, Brendan Lethebe, Mark Lowerison, Jennifer Nayor, Helmut Neumann, Timo Rath, Silvia Sanduleanu, Prateek Sharma, Ralf Kiesslich, Subrata Ghosh, John Saltzman
Journal: Endoscopy (2018)

Abstract Background Prediction of histology of small polyps facilitates colonoscopic treatment. The aims of this study were: 1) to develop a simplified polyp classification, 2) to evaluate its performance in predicting polyp histology, and 3) to evaluate the reproducibility of the classification by trainees using multiplatform endoscopic systems. Methods In phase 1, a new simplified endoscopic classification for polyps – Simplified Identification Method for Polyp Labeling during Endoscopy (SIMPLE) – was created, using the new I-SCAN OE system (Pentax, Tokyo, Japan), by eight international experts. In phase 2, the accuracy, level of confidence, and interobserver agreement to predict polyp histology before and after training, and univariable/multivariable analysis of the endoscopic features, were performed. In phase 3, the reproducibility of SIMPLE by trainees using different endoscopy platforms was evaluated. Results Using the SIMPLE classification, the accuracy of experts in predicting polyps was 83 % (95 % confidence interval [CI] 77 % – 88 %) before and 94 % (95 %CI 89 % – 97 %) after training (P = 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value after training were 97 %, 88 %, 95 %, and 91 %. The interobserver agreement of polyp diagnosis improved from 0.46 (95 %CI 0.30 – 0.64) before to 0.66 (95 %CI 0.48 – 0.82) after training. The trainees demonstrated that the SIMPLE classification is applicable across endoscopy platforms, with similar post-training accuracies for narrow-band imaging NBI classification (0.69; 95 %CI 0.64 – 0.73) and SIMPLE (0.71; 95 %CI 0.67 – 0.75). Conclusions Using the I-SCAN OE system, the new SIMPLE classification demonstrated a high degree of accuracy for adenoma diagnosis, meeting the ASGE PIVI recommendations. We demonstrated that SIMPLE may be used with either I-SCAN OE or NBI.
Abstract OI-1: Tackling Breast Cancer Diversity
Authors: NC Turner
Journal: Cancer Research (2018)

Abstract Breast cancer is a highly diverse disease with multiple subtypes and driver mutations. Further diversity may develop, particularly in metastatic breast cancer, due to the selective pressure of treatment. In ER positive breast cancer, activating mutations of the oestrogen receptor (ESR1), along with mutations in the NF1, KRAS and FGFR genes, are all enriched in endocrine resistant breast cancer, although rare in untreated primary breast cancer. This diversity presents a substantial challenge to the treatment of metastatic breast cancer, with new therapeutic approaches required to tackle this heterogeneity. Circulating tumour DNA analysis, to identify selected mutations in the tumour and guide matching targeted therapy, has preliminary evidence of clinical utility. Targeting common phenotypes presents an alterative therapeutic approach, targeting the dependence of luminal breast cancer on CDK4/6 to initiate cell cycle entry. Pre-clinical evidence supports combining CDK4/6 inhibition with mutation-targeted therapies, although implementing these combinations presents a substantial clinical translational challenge. A novel approach to overcoming tumour heterogeneity is to identify and target micro-metastatic cancer in the adjuvant setting. Micro-metastatic cancer can be detected with highly sensitive circulating tumour DNA analysis for minimal residual disease (MRD) detection. This may open up a new paradigm of treatment guided by MRD monitoring, potentially treating cancer in a setting where the cancer may be less genetically diverse, with lower potential to develop resistance to therapy. Citation Format: Turner NC. Tackling Breast Cancer Diversity [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OI-1.
A Capsule‐Type Microrobot with Pick‐and‐Drop Motion for Targeted Drug and Cell Delivery
Authors: Seungmin Lee, Soyeun Kim, Sangwon Kim, Jin‐Young Kim, Cheil Moon, Bradley J. Nelson, Hongsoo Choi
Journal: Advanced Healthcare Materials (2018)

Abstract A capsule‐type microrobot exhibits “pick‐and‐drop” (P&amp;D) motion to hold a particle within a confined volume and transports it via a corkscrewing motion. The P&amp;D motion is possible because the capsule‐type microrobot has two parts: a plunger and a cap. The fabricated microrobots are wirelessly controlled by a magnetic manipulator. Drugs or cells can be encapsulated in the container of the capsule‐type microrobot by the P&amp;D motion or attached to the surface of the cap, which can be used as a supporting structure. Therefore, the capsule‐type microrobot can deliver suspended or adherent cells. The drug or cells are minimally exposed or not completely exposed to the surrounding fluid and do not experience shear force when encapsulated in the container. As a proof‐of‐concept, secure transportation of microparticles in the confined volume of the capsule via P&amp;D motion is demonstrated. In addition, the cap is used as a scaffold for neuronal cell culture on a rat brain slice to demonstrate its biocompatibility and feasibility for targeted cell delivery. The proposed capsule‐type microrobot is suitable for diverse applications, as it protects the encapsulated materials.