tbuckley/cabot-search huggingface dataset:
Genome-Wide Analysis of DNA Methylation and Acute Coronary Syndrome
Authors: Jun Li, Xiaoyan Zhu, Kuai Yu, Haijing Jiang, Yizhi Zhang, Siyun Deng, Longxian Cheng, Xuezhen Liu, Jia Zhong, Xiaomin Zhang, Meian He, Weihong Chen, Jing Yuan, Ming Gao, Yansen Bai, Xu Han, Bing Liu, Xiaoting Luo, Wenhua Mei, Xiaosheng He, Shunchang Sun, Liyun Zhang, Hesong Zeng, Huizhen Sun, Chuanyao Liu, Yanjun Guo, Bing Zhang, Zhihong Zhang, Jinyan Huang, An Pan, Yu Yuan, Francesca Angileri, Bingxia Ming, Fang Zheng, Qiutang Zeng, Xiaobo Mao, Yudong Peng, Yi Mao, Ping He, Qing K. Wang, Lu Qi, Frank B. Hu, Liming Liang, Tangchun Wu
Journal: Circulation Research (2017)

Acute coronary syndrome (ACS) is a leading cause of death worldwide. Immune functions play a vital role in ACS development; however, whether epigenetic modulation contributes to the regulation of blood immune cells in this disease has not been investigated.We conducted an epigenome-wide analysis with circulating immune cells to identify differentially methylated genes in ACS.We examined genome-wide methylation of whole blood in 102 ACS patients and 101 controls using HumanMethylation450 array, and externally replicated significant discoveries in 100 patients and 102 controls. For the replicated loci, we further analyzed their association with ACS in 6 purified leukocyte subsets, their correlation with the expressions of annotated genes, and their association with cardiovascular traits/risk factors. We found novel and reproducible association of ACS with blood methylation at 47 cytosine-phosphoguanine sites (discovery: false discovery rate <0.005; replication: Bonferroni corrected P<0.05). The association of methylation levels at these cytosine-phosphoguanine sites with ACS was further validated in at least 1 of the 6 leukocyte subsets, with predominant contributions from CD8+ T cells, CD4+ T cells, and B cells. Blood methylation of 26 replicated cytosine-phosphoguanine sites showed significant correlation with expressions of annotated genes (including IL6R, FASLG, and CCL18; P<5.9×10-4), and differential gene expression in case versus controls corroborated the observed differential methylation. The replicated loci suggested a role in ACS-relevant functions including chemotaxis, coronary thrombosis, and T-cell-mediated cytotoxicity. Functional analysis using the top ACS-associated methylation loci in purified T and B cells revealed vital pathways related to atherogenic signaling and adaptive immune response. Furthermore, we observed a significant enrichment of the replicated cytosine-phosphoguanine sites associated with smoking and low-density lipoprotein cholesterol (Penrichment≤1×10-5).Our study identified novel blood methylation alterations associated with ACS and provided potential clinical biomarkers and therapeutic targets. Our results may suggest that immune signaling and cellular functions might be regulated at an epigenetic level in ACS.
Propagation of Tau Aggregates and Neurodegeneration
Authors: Michel Goedert, David S. Eisenberg, R. Anthony Crowther
Journal: Annual Review of Neuroscience (2017)

A pathway from the natively unfolded microtubule-associated protein Tau to a highly structured amyloid fibril underlies human Tauopathies. This ordered assembly causes disease and represents the gain of toxic function. In recent years, evidence has accumulated to suggest that Tau inclusions form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of pathology is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighboring cells. In mice, the intracerebral injection of Tau inclusions induces the ordered assembly of monomeric Tau, followed by its spreading to distant brain regions. Conformational differences between Tau aggregates from transgenic mouse brain and in vitro assembled recombinant protein account for the greater seeding potency of brain aggregates. Short fibrils constitute the major species of seed-competent Tau in the brains of transgenic mice. The existence of multiple human Tauopathies with distinct fibril morphologies has led to the suggestion that different molecular conformers (or strains) of aggregated Tau exist.
The rate of <i>RET</i> mutation testing in medullary thyroid cancer in the Republic of Ireland.
Authors: Eoghan Ruadh Malone, David James Gallagher
Journal: Journal of Clinical Oncology (2015)

e12516 Background: Medullary thyroid cancer (MTC) accounts for approximately 4% of all thyroid cancers. It typically presents late and does not respond to TSH inhibition or radio-iodine. Approximately 20% of MTCs are associated with one of three inherited syndromes (multiple endocrine neoplasia (MEN) 2A, MEN 2B and familial medullary thyroid cancer) caused by germline mutations in the RET proto-oncogene, and all patients with MTC should be screened for RET mutations. Unaffected individuals who carry a germline RET mutation should undergo prophylactic thyroidectomy. We investigated referral rate for germline RET testing in an Irish MTC population. Methods: The total number and type of thyroid cancers diagnosed in Ireland from 1998-2012 was obtained from the National Cancer Registry. The majority of germline genetic testing data in Ireland is completed through the National Centre of Medical Genetics (NCMG) and data on all RET tests ordered was extracted from NCMG records. These two databases were compared to determine the number of RET tests ordered on MTC cases during this time period. Results: A total of 80 cases of MTC were diagnosed in Ireland during a 14 year period. Thirty-five RET full sequencing tests were requested during this time period. Additional RET mutation tests may have been ordered independent of NCMG. Eighteen cases of MTC were diagnosed in those under the age of 40, of these six had RET mutation testing performed. Conclusions: Optimal prevention of MTC requires routine RET mutation testing of all affected individuals. This study suggests that not all Irish patients with MTC were offered RET mutation testing. A protocol of reflex referral of all cases for genetic testing should be implemented.
Détection améliorée des adénomes du colon droit avec une rétroflexion additionnelle suivant 2 visualisations en vision directe: une étude prospective.
Journal: Endoscopy (2017)

La coloscopie permet par la détection d’adénomes la prévention du cancer colorectal. Les études publiées montrent que ce dépistage est plus performant pour le colon gauche. Ceci serait peut-être dû à la présence de polypes plans dans le colon droit difficile à voir derrière certaines haustrations coliques.
Folic Acid for the Prevention of Neural Tube Defects
Authors: Helga Refsum, A. David Smith
Journal: JAMA Pediatrics (2017)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
MEDU-22. IDENTIFYING DRIVERS OF CHEMORESISTANCE IN GROUP 3 MEDULLOBLASTOMA THROUGH A CRISPR/CAS9 GENOME-WIDE ACTIVATION SCREEN
Authors: Anne Song, Stephen Mack, Jeremy Rich
Journal: Neuro-Oncology (2017)

Medulloblastoma (MB) is the most common malignant brain tumor in children, accounting for nearly 20% of all pediatric brain cancers. Based on transcriptional profiling studies, MB has been characterized into four molecular subgroups--WNT, SHH, Group 3, and Group 4--that have distinct genetics, patient demographics, histology, and clinical outcomes. Group 3 MB carries the worst prognosis, with 5-year survival rates of 50%. Current therapy for MB consists of maximal safe surgical resection, radiation, and chemotherapy, with cisplatin, vincristine, and cyclophosphamide comprising a standard chemotherapy regimen. However, Group 3 MB commonly develops resistance and becomes refractory to standard therapy. As these mechanisms of resistance remain poorly understood, I am using the CRISPR/Cas9-based synergistic activation mediator (SAM) system to conduct a genome-wide, gain-of-function, positive selection screen to identify the specific drivers of chemoresistance in Group 3 MB. I cloned and sequenced a library consisting of 70,290 single-guide RNAs (sgRNAs) targeting each of the 23,430 coding isoforms from the human RefSeq database. I have transduced this library into a Group 3 MB patient-derived model stably expressing the other SAM components (dCas9, VP64, MS2, p65, and HSF1) and then selected with standard-of-care chemotherapy conditions: (1) cisplatin; (2) vincristine; (3) 4-hydroperoxycyclophosphamide; and (4) combination of cisplatin, vincristine, and 4-hydroperoxycyclophosphamide. Modulators of chemotherapy sensitivity will be prioritized by sgRNAs that have activated genes conferring chemoresistance, and I will perform next-generation sequencing to identify those sgRNAs. I will then validate the top hits from our screen and also cross-reference them with recently published whole-genome sequencing data on six pairs of human diagnostic and post-therapy Group 3 MBs. These findings will provide insights into the mechanisms of resistance in Group 3 MB and inform novel therapeutic targets that may sensitize the tumor to chemotherapy and improve future treatment response.
Next government should not ditch STPs, says policy expert
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The next government should back the sustainability and transformation partnerships (STPs) in England, regardless of which political party wins the general election, a senior adviser on health policy has urged.

Speaking at a King’s Fund event on the next steps for implementing STPs, Hugh Alderwick, senior policy adviser at the fund, said that the partnerships between local councils and NHS services remained the most credible option for improving the delivery of health and care in England and should …
Is it language (yet)? The allure of the gesture-language binary
Authors: Marie Coppola, Ann Senghas
Journal: Behavioral and Brain Sciences (2017)

Abstract Goldin-Meadow &amp; Brentari (G-M&amp;B) challenge the traditional separation between gestural and categorical language by modality, but they retain a binary distinction. However, multiple dimensions, particularly discreteness and combinatoriality, better carve up the range of linguistic and nonlinguistic human communication. Investigating transformation over time along these dimensions will reveal how the nature of language reflects human minds, rather than the world to which language refers.
Safety and Efficacy Evaluation of 4SCAR19 Chimeric Antigen Receptor-Modified T Cells Targeting B Cell Acute Lymphoblastic Leukemia - Three-Year Follow-up of a Multicenter Phase I/II Study
Authors: Lung-Ji Chang, Lujia Dong, Yu-Chen Liu, Shih-Ting Tsao, Ya-Chen Li, Li Liu, Zhiyong Gao, Xiyou Tan, Dao-Pei Lu, Jian-Ping Zhang, Jing-Bo Wang, Yu-Ming Ying, Le-Ping Zhang, Huyong Zheng, Kai Wang, Xiao-Li Zheng, Heng-Xiang Wang, Xun Lai, Dong Li
Journal: Blood (2016)
Deregulated expression of myotonic dystrophy protein kinase (DMPK) in cervical cancer
Authors: Subhash Chauhan, Jie Yang, Namita Vinayek, Michael Koch, Michelle Harmon, Teresa Bohlmeyer, Meena Jaggi, M. Perryman
Journal: Cancer Research (2007)

5094    Objective:  Myotonic dystrophy protein kinase (DMPK) is a member of a ubiquitous protein kinase family that is known to be involved in regulation of cell size, shape and cellular differentiation. DMPK is known to be highly expressed in heart and skeletal tissues but its expression profile in cancerous tissues is by and large unknown thus far, due to the paucity of immunological reagents with high affinity and well-defined specificity. In the present study we determined the role of DMPK in cervical cancer.   Methods:  Recently, our group has developed a novel monoclonal antibody using a coil-coiled domain of DMPK. This antibody was used to determine the expression profile of DMPK on a tissue microarray slide containing cervical cancer samples of different stages by immunohistochemistry. DMPK expression and subcellular localization was analyzed in cervical cancer cell lines and in normal primary human keratinocytes (PHK) by immunoblotting and confocal microscopy. The effect of exogenous overexpression of on cell proliferation and cell cycle in cervical cancer lines DMPK was investigated using the Cell Titer 96 Aqueous One Solution  (Promega Corporation) and Flow cytometry, respectively.   Results:  The immunohistochemical expression profile suggests a progressive repression of DMPK in cervical intraepithelial neoplasia (CIN) and invasive squamous carcinoma samples compared to the normal cervical epithelium. Among invasive squamous carcinoma samples, DMPK suppression was predominant in non-keratinized lesions compared to the keratinized lesions. In cultured cells DMPK expression was predominantly observed on the nuclear membrane in cancer cells while in PHK cells it was localized in the cytoplasm and on the nuclear membrane. Exogenous expression of DMPK in HeLa cells effectively inhibited cell proliferation via arresting cells in G2/M phase.   Conclusion:  We have determined that DMPK is dysregulated in cervical cancer and can serve as a surrogate marker of early onset of cervical cancer. Overexpression of DMPK inhibits cervical cancer cell proliferation via modulation of cell cycle. This data suggest that DMPK may be a potential therapeutic target for gene therapy of cervical cancer.
Multilevel genomics of colorectal cancers with microsatellite instability—clinical impact of JAK1 mutations and consensus molecular subtype 1
Authors: Anita Sveen, Bjarne Johannessen, Torstein Tengs, Stine A. Danielsen, Ina A. Eilertsen, Guro E. Lind, Kaja C. G. Berg, Edward Leithe, Leonardo A. Meza-Zepeda, Enric Domingo, Ola Myklebost, David Kerr, Ian Tomlinson, Arild Nesbakken, Rolf I. Skotheim, Ragnhild A. Lothe
Journal: Genome Medicine (2017)

Approximately 15% of primary colorectal cancers have DNA mismatch repair deficiency, causing a complex genome with thousands of small mutations-the microsatellite instability (MSI) phenotype. We investigated molecular heterogeneity and tumor immunogenicity in relation to clinical endpoints within this distinct subtype of colorectal cancers.
L’échange d’eau au cours d’une coloscopie de dépistage augmente le taux de détection des adénomes: une étude multicentrique en double aveugle contrôlée randomisée
Journal: Endoscopy (2017)

Le taux de détection des adénomes coliques est un critère majeur reflétant la qualité de la coloscopie. Les adénomes manqués sont un facteur indépendant prédictif de la survenue des cancers colorectaux (CCR) d’intervalle.
The First in Class, Alkylator-Histone-Deacetylase-Inhibitor Fusion Molecule Edo-S101 in Combination with Proteasome Inhibitors Induces Highly Synergistic Pro-Apoptotic Signaling through UPR Activation and Suppression of c-Myc and BCL2 in Multiple Myeloma
Authors: Lenka Besse, Marianne Kraus, Andrej Besse, Juergen Bader, Thomas Mehrling, Christoph Driessen
Journal: Blood (2016)
Characterization of Reentrant Circuit in Macroreentrant Right Atrial Tachycardia After Surgical Repair of Congenital Heart Disease
Authors: Hiroshi Nakagawa, Nayyar Shah, Kagari Matsudaira, Edward Overholt, Krishnaswamy Chandrasekaran, Karen J. Beckman, Peter Spector, James D. Calame, Arun Rao, Can Hasdemir, Kenichiro Otomo, Zulu Wang, Ralph Lazzara, Warren M. Jackman
Journal: Circulation (2001)

The purpose of this study was to characterize the circuit of macroreentrant right atrial tachycardia (MacroAT) in patients after surgical repair of congenital heart disease (SR-CHD).Sixteen patients with atrial tachycardia (AT) after SR-CHD were studied (atrial septal defect in 6, tetralogy of Fallot in 4, and Fontan procedure in 6). Electroanatomic right atrial maps were obtained during 15 MacroATs in 13 patients, focal AT in 1 patient, and atrial pacing in 2 patients without stable AT. A large area of low bipolar voltage (</=0.5 mV) involved most of the free wall in all patients and contained 2 to 7 dense scars or lines of double potentials, forming 29 narrow channels (width </=2.7 cm) between scars in all but 1 patient, who had a single scar and only focal AT. All 15 MacroATs were propagated through narrow channels. Ablation within the channel eliminated all 15 MacroATs with 1 to 3 (median 1) radiofrequency applications. Ablation was performed in 9 other channels identified during MacroAT (5 patients) and in 5 channels identified during atrial pacing (2 patients). Conduction block was obtained across 28 of 29 channels. After ablation, reproducible sustained right AT was not induced in any patient. During follow-up (median 13.5 months), new MacroATs, atrial fibrillation, or palpitations occurred in 3 of 16 patients.MacroAT after SR-CHD requires a large area of low voltage containing >/=2 scars forming narrow channels. Ablation within the channels eliminates MacroAT.
DIPG-38. CORTICOSPINAL TRACT TOLERANCE TO CATHETER POSITIONING FOR CONVECTION ENHANCED DELIVERY IN THE BRAIN STEM
Authors: Peter Morgenstern, Eva Wembacher-Schroeder, Mark Souweidane
Journal: Neuro-Oncology (2017)

INTRODUCTION: Convection enhanced delivery (CED) has recently been explored as a therapeutic strategy for children with diffuse intrinsic pontine glioma (DIPG). An anterior or supratentorial approach for catheter positioning risks conflict with descending white matter bundles where they become concentrated in the internal capsule and crural pyramid. We describe our experience planning catheter trajectories in the context of eloquent structures and outcomes this patient population. METHODS: As part of a Phase 1 clinical trial using CED with 124I-8H9, a radiolabeled monoclonal antibody (NCT01502917), a flexible step-design infusion catheter (Brainlab Flexible Catheter, BrainLab, Munich, Germany) was surgically placed via a supratentorial approach. Surgical planning was conducted based on 3D T1, T2, and SWI sequences. A fully compatible MR-guidance platform was used for trajectory planning catheter deployment. A neurologic exam was performed immediately post-procedure, prior to initiating infusion, to assess for procedure-related deficits. Intra- and post-procedural MR images were analyzed for the anatomic position of catheter trajectories. Conflicts between the catheter tract and the posterior limb of the internal capsule and the pyramid of the crus cerebri were recorded. Correlation between motor deficits and the catheter path was evaluated. RESULTS: Thirty-three catheter insertions were performed for 28 children with DIPG. One patient experienced a slight worsening of an existing ipsilateral facial palsy likely related to the course of facial nerve fibers in the brainstem. The posterior limb of the internal capsule and the pyramid of the crus cerebri frequently overlapped the catheter tract without incident. CONCLUSIONS: Transgression of descending corticospinal motor tracts by catheters for intracranial infusion is acceptable. We observed that a supratentorial approach to the brainstem crossing eloquent fibers resulted in one neurologic deficit. There does not appear to be a functional risk requiring a need for avoidance of the dominant motor fiber tracts during trajectory planning.
French comment on article Growth rate of small pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: results from an endoscopic ultrasound based cohort study1 Taux de croissance des petites tumeurs neuroendocrines pancréatiques dans les néoplasie endocriniennes multiples de type 1: résultats d une étude de cohorte évaluant l'intérêt de l échoendoscopie
Journal: Endoscopy (2017)

La croissance tumorale des tumeurs endocrines pancréatiques (TEP) dans le cadre du syndrome de NEM1 est peu connue. Le traitement dépend du caractère sécrétant de la tumeur et de sa taille:
Abstract 85: A Novel Mitochondrial Targeted Fusion Protein Containing Endonuclease III Protects the Heart Against Myocardial Infarction and Pressure Overload Heart Failure
Authors: Jessica M Bradley, Hiroyuki Otsuka, Chelsea L Organ, Shashi Bhushan, David J Polhemus, Glenn L Wilson, David J Lefer
Journal: Circulation Research (2015)

Background: Oxidative stress is a primary cause of mitochondrial DNA (mtDNA) damage and plays a role in myocardial cell death. mtDNA repair enzymes are crucial for mtDNA repair and cell survival. We tested the efficacy of a novel, mitochondrial targeted fusion protein that traffics Endonuclease III (Exscien1-III) in murine models of myocardial ischemia/reperfusion (MI/R) injury and transverse aortic constriction (TAC) heart failure (HF). We previously demonstrated that Exscien1-III administered at R reduced myocardial infarct size and preserved left ventricular ejection fraction (LVEF) following MI/R. We hypothesized that delayed administration of Exscien1-III would promote mtDNA repair and protect the myocardium against MI/R and TAC heart failure. Methods: Male C57/BL6J (10-12 wks) were subjected to 45 min of MI and 24 hrs of R. Exscien1-III (4 mg/kg, i.p., n=13) or vehicle (VEH, n=13) was administered 30 min after R. Male C57/BL6J were subjected to TAC (27 g needle) and Exscien1-III (4 mg/kg/d, i.p., n=10) or VEH (n=6) were administered starting at 3 wks post TAC. Echocardiography was performed at baseline and following TAC to assess LVEF. Results: Exscien1-III reduced myocardial INF/AAR by 24% (p &lt; 0.05 vs. VEH). Exscien1-III preserved LVEF (49.1 ± 4.0% vs. 32.9 ± 3.2%, p &lt; 0.01) and reduced LV dilation (LVEDD/LVESD; 3.8/2.8 vs. 4.4/3.4, p &lt; 0.05) at 8 wks compared to vehicle. Conclusion: These results demonstrate that delayed administration of Exscien1-III significantly attenuates myocardial cell death and preserves LV function in acute MI and HF. Studies are currently underway to define the molecular mechanisms involved in Exscien1-III induced cardioprotection.
Comparison of Stroke- and Bleed-Specific Healthcare Resource Utilization and Costs Among Patients with Non-Valvular Atrial Fibrillation, Newly Treated with Dabigatran or Warfarin
Authors: Xue Song, Pranav Gandhi, Adrienne M Gilligan, Prachi Arora, Caroline Henriques, Cheng Wang, Stephen Sander, David M Smith
Journal: Blood (2016)