tbuckley/cabot-search huggingface dataset:
Full‐Scale Osteochondral Regeneration by Sole Graft of Tissue‐Engineered Hyaline Cartilage without Co‐Engraftment of Subchondral Bone Substitute
Authors: Xiaolei Nie, Jian Yang, Yon Jin Chuah, Wenzhen Zhu, Yvonne Peck, Pengfei He, Dong‐An Wang
Journal: Advanced Healthcare Materials (2019)

Abstract In this study, full‐scale osteochondral defects are hypothesized, which penetrate the articular cartilage layer and invade into subchondral bones, and can be fixed by sole graft of tissue‐engineered hyaline cartilage without co‐engraftment of any subchondral bone substitute. It is hypothesized that given a finely regenerated articular cartilage shielding on top, the restoration of subchondral bones can be fulfilled via spontaneous self‐remodeling in situ. Hence, the key challenge of osteochondral regeneration lies in restoration of the non‐self‐regenerative articular cartilage. Here, traumatic osteochondral lesions to be repaired in rabbit knee models are endeavored using novel tissue‐engineered hyaline‐like cartilage grafts that are produced by 3D cultured porcine chondrocytes in vitro. Comparative trials are conducted in animal models that are implanted with living hyaline cartilage grafts (LhCG) and decellularized LhCG (dLhCG). Sound osteochondral regeneration is gradually revealed from both LhCG and dLhCG‐implanted samples 50–100 d after implantation. Quality regeneration in both zones of articular cartilage and subchondral bones are validated by the restored osteochondral composition, structure, phenotype, and mechanical property, which validate the hypothesis of this study.
Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type
Authors: Irene Franco, Hafdis T. Helgadottir, Aldo Moggio, Malin Larsson, Peter Vrtačnik, Anna Johansson, Nina Norgren, Pär Lundin, David Mas-Ponte, Johan Nordström, Torbjörn Lundgren, Peter Stenvinkel, Lars Wennberg, Fran Supek, Maria Eriksson
Journal: Genome biology (2019)

The lifelong accumulation of somatic mutations underlies age-related phenotypes and cancer. Mutagenic forces are thought to shape the genome of aging cells in a tissue-specific way. Whole genome analyses of somatic mutation patterns, based on both types and genomic distribution of variants, can shed light on specific processes active in different human tissues and their effect on the transition to cancer.To analyze somatic mutation patterns, we compile a comprehensive genetic atlas of somatic mutations in healthy human cells. High-confidence variants are obtained from newly generated and publicly available whole genome DNA sequencing data from single non-cancer cells, clonally expanded in vitro. To enable a well-controlled comparison of different cell types, we obtain single genome data (92% mean coverage) from multi-organ biopsies from the same donors. These data show multiple cell types that are protected from mutagens and display a stereotyped mutation profile, despite their origin from different tissues. Conversely, the same tissue harbors cells with distinct mutation profiles associated to different differentiation states. Analyses of mutation rate in the coding and non-coding portions of the genome identify a cell type bearing a unique mutation pattern characterized by mutation enrichment in active chromatin, regulatory, and transcribed regions.Our analysis of normal cells from healthy donors identifies a somatic mutation landscape that enhances the risk of tumor transformation in a specific cell population from the kidney proximal tubule. This unique pattern is characterized by high rate of mutation accumulation during adult life and specific targeting of expressed genes and regulatory regions.
Correlation between tumour infiltration lymphocyte and PDL-1 expression in laryngeal cancer and its prognostic significance: A prospective, non-interventional trial
Authors: M. Ismail, H.E.l. Wakiel, D. AbdEl Ghany, M.M. Shakweer, A. Lotfy, A.M. Gaballah
Journal: Annals of Oncology (2019)
HER2-HER3 Heterodimer Quantification by FRET-FLIM and Patient Subclass Analysis of the COIN Colorectal Trial
Authors: Paul R Barber, Gregory Weitsman, Katherine Lawler, James E Barrett, Mark Rowley, Manuel Rodriguez-Justo, David Fisher, Fangfei Gao, Iain D C Tullis, Jinhai Deng, Louise Brown, Richard Kaplan, Daniel Hochhauser, Richard Adams, Timothy S. Maughan, Borivoj Vojnovic, Anthony C C Coolen, Tony Ng
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background The phase III MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve patient stratification and reveal previously hidden subgroups of patients who had differing disease progression and treatment response. Methods HER2-HER3 dimerization was quantified by fluorescence lifetime imaging microscopy in primary tumor samples from 550 COIN trial patients receiving oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab. Bayesian latent class analysis and covariate reduction was performed to analyze the effects of HER2-HER3 dimer, RAS mutation, and cetuximab on progression-free survival and overall survival (OS). All statistical tests were two-sided. Results Latent class analysis on a cohort of 398 patients revealed two patient subclasses with differing prognoses (median OS = 1624 days [95% confidence interval [CI] = 1466 to 1816 days] vs 461 days [95% CI = 431 to 504 days]): Class 1 (15.6%) showed a benefit from cetuximab in OS (hazard ratio = 0.43, 95% CI = 0.25 to 0.76, P = .004). Class 2 showed an association of increased HER2-HER3 with better OS (hazard ratio = 0.64, 95% CI = 0.44 to 0.94, P = .02). A class prediction signature was formed and tested on an independent validation cohort (n = 152) validating the prognostic utility of the dimer assay. Similar subclasses were also discovered in full trial dataset (n = 1630) based on 10 baseline clinicopathological and genetic covariates. Conclusions Our work suggests that the combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (&amp;gt;10%) who will have better prognosis following chemotherapy. A larger prospective cohort will be required to confirm its utility in predicting the outcome of anti-EGFR treatment.
Epigenomic analysis of gastrulation identifies a unique chromatin state for primed pluripotency
Authors: Yunlong Xiang, Yu Zhang, Qianhua Xu, Chen Zhou, Bofeng Liu, Zhenhai Du, Ke Zhang, Bingjie Zhang, Xiaoxiao Wang, Srimonta Gayen, Ling Liu, Yao Wang, Yuanyuan Li, Qiujun Wang, Sundeep Kalantry, Lei Li, Wei Xie
Journal: Nature Genetics (2019)
Thinking about time and number: An application of the dual-systems approach to numerical cognition
Authors: Karoline Lohse, Elena Sixtus, Jan Lonnemann
Journal: Behavioral and Brain Sciences (2019)

Abstract Based on the notion that time, space, and number are part of a generalized magnitude system, we assume that the dual-systems approach to temporal cognition also applies to numerical cognition. Referring to theoretical models of the development of numerical concepts, we propose that children's early skills in processing numbers can be described analogously to temporal updating and temporal reasoning.
Fli-1 Transcriptionally Integrates Microenvironmental Cues Sensing By Self-Renewing Hematopoietic Stem and Progenitor Cells
Authors: Tomer Itkin, Chaitanya R Badwe, Sean Houghton, Yang Lin, Ying Liu, Peipei Guo, Jesus M Gomez-Salinero, Fuqiang Geng, Jae-Hung Shieh, David Redmond, Yen-Michael S. Hsu, Brandon Hadland, Shahin Rafii
Journal: Blood (2019)
Results From a Phase I Study of MK-1308 (ANTI–CTLA-4) Plus Pembrolizumab in Previously Treated Advanced Small Cell Lung Cancer
Authors: B.C. Cho, K. Yoh, J. Bar, A. Nagrial, D.R. Spigel, M. Gutierrez, D.-W. Kim, D. Kotasek, D. Rasco, J. Niu, M. Satouchi, M.-J. Ahn, D.H. Lee, C. Maurice-Dror, S. Siddiqi, X. Li, J. Cyrus, R.A. Altura, R. Perets
Journal: Annals of Oncology (2019)
Clinical outcomes of metastasic melanoma patients treated with ipilimumab and nivolumab: A single institution experience
Authors: H.K. Oberoi Oberoi, C.M. Vila, A. Rodriguez, D. Pesantez Coronel, F. Aya Moreno, M.C. Font Puig, A.M. Arance Fernandez
Journal: Annals of Oncology (2019)
Abstract A12: The establishment, maintenance, and maladaptive role of epigenetic memory in mediating pancreatic tumorigenesis
Authors: David J. Falvo, Rohit Chandwani
Journal: Cancer Research (2019)

Abstract Cellular decision-making is highly dependent on cues present in the environment. As such, biologic systems have evolved efficient ways to respond to salient and often transient stimuli by encoding and transducing relevant extracellular information to chromatin. Additionally, accumulating evidence suggests that cells are capable of remembering previously experienced stimuli, allowing them to adjust their behaviors appropriately when confronted in the future with a similar or different stimulus. However, the ability of cells to respond to a transient stimulus and to encode a persistent record of that experience following its resolution has yet to be explored comprehensively in a preneoplastic context. Here we determine the lasting effect in the pancreas of an acinar-to-ductal metaplasia (ADM) event, to elucidate the impact of prior inflammation on tissue function and subsequent tumorigenesis. In a lineage-traced model of acinar cell dedifferentiation, we demonstrate that following ADM, histologically normal acinar cells exhibit broad gains in chromatin accessibility that persist well after exposure to the initial ADM-inducing stimulus. We show that the effect on chromatin is not reflected in the transcriptional state of acinar cells. Moreover, we employ extensive flow-cytometry based analysis of immune cell and niche acinar populations to show there is no long-term cell-extrinsic population, nor a significant expansion of either the Dclk1+ or Nk1r+ acinar populations. Finally, we employ single-cell RNA-seq analyses to define the alterations to epithelial cells and the associated microenvironment long after regeneration following an episode of pancreatitis. These data suggest that inflammation-exposed acinar cells are capable of establishing an altered, persistently accessible chromatin state that lasts long after the initial lineage destabilizing event. Currently we are defining if, following resolution of pancreatitis, activation of mutant Kras will be sufficient to induce premalignant transformation within the acinar compartment that manifests as pancreatic intraepithelial neoplasia (PanIN)—the most common precursor lesion to pancreatic ductal adenocarcinoma (PDAC). Understanding how this postinflammatory chromatin state synergizes with oncogenic stress will further explain why inflammation is a hallmark risk factor for cancer development. Together, our studies will characterize the establishment, maintenance, and maladaptive role of epigenetic memory in the development of pancreatic cancer. Citation Format: David J. Falvo, Rohit Chandwani. The establishment, maintenance, and maladaptive role of epigenetic memory in mediating pancreatic tumorigenesis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A12.
Abstract A29: Bicompartmental regulation of disease-related gene networks by histone deacetylase inhibition curbs pancreatic cancer progression
Authors: Gaoyang Liang, Nasun Hah, Yu Shi, Morgan L. Truitt, Corina E. Antal, Annette R. Atkins, Cory Fraser, Ester Banayo, Senada Bashi, Yang Dai, Mara Sherman, Christopher Liddle, Ruth T. Yu, Tony Hunter, Haiyong Han, Daniel D. Von Hoff, Michael Downes, Ronald M. Evans
Journal: Cancer Research (2019)

Abstract A challenge for effective pancreatic ductal adenocarcinoma (PDAC) therapy is to target the aggressive neoplasm that is shrouded by the dense fibrotic stroma. Epigenetic modulation has the potential to regulate genes or gene networks causing disease phenotypes. Here we show that the HDAC inhibitor entinostat (Ent) provides therapeutic benefits by regulating the gene networks important for PDAC in both the stromal and epithelial compartments. While an HDAC inhibitor is anticipated to broadly open chromatin and activate genes, in stromal pancreatic stellate cells (PSCs), Ent unexpectedly restricts chromatin accessibility on and represses the gene networks essential for PSC activation, leading to proliferation arrest and reduced myofibroblast properties, including lower production of extracellular matrix and inflammatory and protumorigenic cytokines. Furthermore, Ent also attenuates the transcriptional responses of cancer-associated fibroblasts (CAFs) to injury-related cytokines from the tumor microenvironment including TGF-beta and TNF-alpha. In the neoplastic epithelium, Ent induces cytostasis and de novo vulnerability in DNA repair pathways by systematically suppressing cell cycle and DNA repair genes. Notably, the bicompartmental effects of Ent were found to arrest cancer progression, prolong survival, and synergize with DNA damage-inducing agent cisplatin in genetically engineered mouse model (GEMM) of PDAC. Overall, our study not only establishes Ent as a novel therapeutic agent for PDAC but also reveals the mechanisms underlying its benefits. Citation Format: Gaoyang Liang, Nasun Hah, Yu Shi, Morgan L. Truitt, Corina E. Antal, Annette R. Atkins, Cory Fraser, Ester Banayo, Senada Bashi, Yang Dai, Mara Sherman, Christopher Liddle, Ruth T. Yu, Tony Hunter, Haiyong Han, Daniel D. Von Hoff, Michael Downes, Ronald M. Evans. Bicompartmental regulation of disease-related gene networks by histone deacetylase inhibition curbs pancreatic cancer progression [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A29.
Randomized Study to Evaluate the Impact of Telemedicine Care in Patients With Type 1 Diabetes With Multiple Doses of Insulin and Suboptimal HbA1c in Andalusia (Spain): PLATEDIAN Study
Authors: Maria S. Ruiz de Adana, Maria Rosa Alhambra-Expósito, Araceli Muñoz-Garach, Inmaculada Gonzalez-Molero, Natalia Colomo, Isabel Torres-Barea, Manuel Aguilar-Diosdado, Florentino Carral, Manuel Serrano, Maria A. Martínez-Brocca, Ana Duran, Rafael Palomares
Journal: Diabetes Care (2019)

OBJECTIVE To assess the impact of a telemedicine visit using the platform Diabetic compared with a face-to-face visit on clinical outcomes, patients’ health-related quality of life (HRQoL), and physicians’ satisfaction in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS PLATEDIAN (Telemedicine on Metabolic Control in Type 1 Diabetes Mellitus Andalusian Patients) (NCT03332472) was a multicenter, randomized, 6-month follow-up, open-label, parallel-group controlled study performed in patients with type 1 diabetes with suboptimal metabolic control (HbA1c &amp;lt;8% [&amp;lt;64 mmol/mol]), treated with multiple daily injections. A total of 388 patients were assessed for eligibility; 379 of them were randomized 1:1 to three face-to-face visits (control cohort [CC]) (n = 167) or the replacement of an intermediate face-to-face visit by a telemedicine visit using Diabetic (intervention cohort [IC]) (n = 163). The primary efficacy end point was the mean change of HbA1c levels from baseline to month 6. Other efficacy and safety end points were mean blood glucose, glucose variability, episodes of hypoglycemia and hyperglycemia, patient-reported outcomes, and physicians’ satisfaction. RESULTS At month 6, the mean change in HbA1c levels was −0.04 ± 0.5% (−0.5 ± 5.8 mmol/mol) in the CC and 0.01 ± 0.6% (0.1 ± 6.0 mmol/mol) in the IC (P = 0.4941). The number of patients who achieved HbA1c &amp;lt;7% (&amp;lt;53 mmol/mol) was 73 and 78 in the CC and IC, respectively. Significant differences were not found regarding safety end points at 6 months. Changes in HRQoL between the first visit and final visit did not differ between cohorts, and, regarding fear of hypoglycemia (FH-15 score ≥28), statistically significant differences observed at baseline remained unchanged at 6 months (P &amp;lt; 0.05). CONCLUSIONS The use of telemedicine in patients with type 1 diabetes with HbA1c &amp;lt;8% (&amp;lt;64 mmol/mol) provides similar efficacy and safety outcomes as face-to-face visits.
MBE Emerging Classics 2020
Authors: Sudhir Kumar, Heather Rowe
Journal: Molecular Biology and Evolution (2019)

Since 2013, Molecular Biology and Evolution has experimented with criteria to identify “Citation Classics” as a means of celebrating papers with powerful impact on our community as reflected by accumulated citations. We learned from these experiments that our “Early” or “Golden” citation classics remain fairly static from year to year. Some manuscripts have such a strong and lasting impact on our scientific thought and approaches that a yearly affirmation of their influence is unnecessary. Moving forward, MBE will provide yearly recognition to the more recently published manuscripts that have made the strongest impression on scientific literature since their publication, and will revisit the most enduring manuscripts after longer intervals. Below, we highlight ten discovery, five methods and five resource publications as “Emerging Classics” based on citations accrued per fractional years since print publication. Articles are listed from most recent to oldest publication date. Total citation counts were obtained from Web of Science on November 12, 2019. We congratulate these authors on the significance of their contributions and look forward to seeing new classics emerge in the years to come.
New Therapy for Rare Anemia
Authors: Feyza Sancar
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cystic Fibrosis: Emergence of Highly Effective Targeted Therapeutics and Potential Clinical Implications
Authors: Marcus A. Mall, Nicole Mayer-Hamblett, Steven M. Rowe
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Section:ChooseTop of pageAbstract <<ContentsEvolution of CF Pathogene...Transformation of CF Ther...Transformation of CF Ther...ConclusionsReferencesCITING ARTICLES
Correction to: De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017
Authors: G. Curigliano, H.J. Burstein, E.P. Winer, M. Gnant, P. Dubsky, S. Loibl, M. Colleoni, M.M. Regan, M. Piccart-Gebhart, H -J Senn, B. Thürlimann, F. André, J. Baselga, J. Bergh, H. Bonnefoi, S.Y. Brucker, F. Cardoso, L. Carey, E. Ciruelos, J. Cuzick, C. Denkert, A. Di Leo, B. Ejlertsen, P. Francis, V. Galimberti, J. Garber, B. Gulluoglu, P. Goodwin, N. Harbeck, D.F. Hayes, C -S Huang, J. Huober, H. Khaled, J. Jassem, Z. Jiang, P. Karlsson, M. Morrow, R. Orecchia, K.C. Osborne, O. Pagani, A.H. Partridge, K. Pritchard, J. Ro, E.J.T. Rutgers, F. Sedlmayer, V. Semiglazov, Z. Shao, I. Smith, M. Toi, A. Tutt, G. Viale, T. Watanabe, T.J. Whelan, B. Xu
Journal: Annals of Oncology (2018)

Ann Oncol 2017; 28: 1700–1712 (doi: 10.1093/annonc/mdx308) In the original article, panel member H. Khaled’s first and surnames were transposed. This has now been corrected. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017Annals of OncologyVol. 28Issue 8PreviewThe 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. Full-Text PDF Open Archive
LBA1 Clinical efficacy of atezolizumab (atezo) in biomarker subgroups by SP142, SP263 and 22C3 PD-L1 immunohistochemistry (IHC) assays and by blood tumour mutational burden (bTMB): Results from the IMpower110 study
Authors: R.S. Herbst, F. de Marinis, G. Giaccone, N. Reinmuth, A. Vergnenegre, C.H. Barrios, M. Morise, E. Felip, Z. Andric, S. Geater, M. Ozguroglu, S. Mocci, M. McCleland, W. Zou, I. Enquist, K. Komatsubara, Y. Deng, H. Kuriki, D.R. Spigel, J. Jassem
Journal: Annals of Oncology (2019)
Impact of aspirin on takotsubo syndrome: a propensity score‐based analysis of the InterTAK Registry
Authors: Fabrizio D'Ascenzo, Sebastiano Gili, Maurizio Bertaina, Mario Iannaccone, Victoria L. Cammann, Davide Di Vece, Ken Kato, Andrea Saglietto, Konrad A. Szawan, Antonio H. Frangieh, Beatrice Boffini, Margherita Annaratone, Annahita Sarcon, Rena A. Levinson, Jennifer Franke, L. Christian Napp, Milosz Jaguszewski, Michel Noutsias, Thomas Münzel, Maike Knorr, Susanne Heiner, Hugo A. Katus, Christof Burgdorf, Heribert Schunkert, Holger Thiele, Johann Bauersachs, Carsten Tschöpe, Burkert M. Pieske, Lawrence Rajan, Guido Michels, Roman Pfister, Alessandro Cuneo, Claudius Jacobshagen, Gerd Hasenfuß, Mahir Karakas, Wolfgang Koenig, Wolfgang Rottbauer, Samir M. Said, Ruediger C. Braun‐Dullaeus, Adrian Banning, Florim Cuculi, Richard Kobza, Thomas A. Fischer, Tuija Vasankari, K.E. Juhani Airaksinen, Grzegorz Opolski, Rafal Dworakowski, Philip MacCarthy, Christoph Kaiser, Stefan Osswald, Leonarda Galiuto, Filippo Crea, Wolfgang Dichtl, Wolfgang M. Franz, Klaus Empen, Stephan B. Felix, Clément Delmas, Olivier Lairez, Ibrahim El‐Battrawy, Ibrahim Akin, Martin Borggrefe, John D. Horowitz, Martin Kozel, Petr Tousek, Petr Widimský, Ekaterina Gilyarova, Alexandra Shilova, Mikhail Gilyarov, Giuseppe Biondi‐Zoccai, David E. Winchester, Christian Ukena, Michael Neuhaus, Jeroen J. Bax, Abhiram Prasad, Carlo Di Mario, Michael Böhm, Mauro Gasparini, Frank Ruschitzka, Eduardo Bossone, Rodolfo Citro, Mauro Rinaldi, Gaetano Maria De Ferrari, Thomas Lüscher, Jelena R. Ghadri, Christian Templin
Journal: European Journal of Heart Failure (2019)