tbuckley/cabot-search huggingface dataset:
Abstract #478: Functional assay for MutYH variants using MutY deficient E.coli.
Authors: Hideki Shimodaira, Masanobu Takahashi, Hiroshi Soeda, Keigo Komine, Chikashi Ishioka
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

MutYH associated polyposis (MAP) is an autosomal recessive type of adenomatous polyposis caused by inheriting biallelic inactivation of MutYH genes. Loss of functional MutYH protein will accumulate G:T mismatched DNA resulted from the oxidative damages. While Y165C and G382D are the 2 most prevalent MutYH mutations in Northern Europeans, more than 60 MutYH missense variants were detected from MAP patients, sporadic colorectal cancers or normal populations. In the genetic diagnosis of MAP, these variants are difficult to determine whether disease causing mutations or single nucleotide polymorphisms. To understand the functional consequence of these variants, we made 48 MutYH gene variations by site directed mutagenesis, then, expressed proteins in the MutY disrupted E. coli and accessed the ability to complement the functional deficiency of the E. coli cells by monitoring the spontaneous mutation rate. While majority of variants showed intermediate complementation compared with wild type, we detected some variants severely interfered in this complementation such as W117R, R168H, R168C, R231H and L374P. On the other hand, some variants such as V22M, G25D, D91N, I209V, V232F, A267V G272E, Q324H, L406M, L515M and R520Q retained almost similar function with wild type. Structural prediction of MutYH based on MutY protein structure allowed us to interpret the effect to the protein stability or catalytic activity of MutYH. In silico prediction functional effects caused by single base alteration showed a good correlation with our functional evaluation for MutYH variants in this study. These data must be useful to evaluate the functional consequence of missense MutYH variants detected in the patients suspected to be affected by MAP.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 478.
Impact of environmental factors on alloimmunity and transplant fate
Authors: Leonardo V. Riella, Jessamyn Bagley, John Iacomini, Maria-Luisa Alegre
Journal: Journal of Clinical Investigation (2017)

Although gene-environment interactions have been investigated for many years to understand people's susceptibility to autoimmune diseases or cancer, a role for environmental factors in modulating alloimmune responses and transplant outcomes is only now beginning to emerge. New data suggest that diet, hyperlipidemia, pollutants, commensal microbes, and pathogenic infections can all affect T cell activation, differentiation, and the kinetics of graft rejection. These observations reveal opportunities for novel therapeutic interventions to improve graft outcomes as well as for noninvasive biomarker discovery to predict or diagnose graft deterioration before it becomes irreversible. In this Review, we will focus on the impact of these environmental factors on immune function and, when known, on alloimmune function, as well as on transplant fate.
E.R.A.S. pathway in colorectal surgery in elderly: Our experience: A retrospective cohort study
Authors: Basilio Pirrera, Andrea Lucchi, Carlo Gabbianelli, Vincenzo Alagna, Giacomo Martorelli, Pierluigi Berti, Ilaria Panzini, Elisabetta Fabbri, Gianluca Garulli
Journal: International Journal of Surgery (2017)
Abstract 331: Mir-433 Controls Cardiac Fibrosis
Authors: Lichan Tao, Xiaoting Wu, Ping Chen, Shanshan Li, Xiaomin Zhang, Yihua Bei, Tianzhao Xu, Junjie Xiao, Xinli Li
Journal: Circulation Research (2015)

Background: Cardiac fibrosis, a result of multiple injurious insults in heart, is a final common manifestation of chronic heart diseases and can lead to end-stage cardiac failure. MicroRNAs (miRNAs, miRs) participate in many essential biological processes and their dysfunction has been implicated in a variety of cardiovascular diseases including fibrosis. miR-433 has recently been implicated in renal fibrosis, however, its role in cardiac fibrosis is unclear. Methods and results: miR-433 was increased in heart samples from dilated cardiomyopathy patients as determined by qRT-PCRs. In addition, miR-433 was also consistently upregulated in mice model of cardiac fibrosis after myocardial infarction or heart failure. Additionally, miR-433 was found to be enriched in fibroblasts compared to cardiomyocytes. In neonatal cardiac fibroblasts, forced expression of miR-433 promoted cell proliferation as indicated by EdU and Ki-67 staining. Moreover, miR-433 overexpression promoted the transdifferentiation of fibroblasts into myofibroblasts as determined by qRT-PCR and western blot for α-SMA and collagen whether in the presence of TGF-β or not, indicating that miR-433 is sufficient to induce fibrosis. In addition, knockdown of miR-433 inhibited proliferation and the transdifferentiation into myofibroblasts, indicating that miR-433 is required for cardiac fibrosis. Interestingly, miR-433 did not affect the migration of cardiac fibroblast. Importantly, miR-433 antagomir could partially attenuate cardiac fibrosis induced by myocardial infarction in mice. Conclusion: both in vitro and in vivo. Inhibition of miR-433 represents a novel therapeutic strategy for cardiac fibrosis.
Rapid fluorescence imaging of spinal cord following epidural administration of a nerve-highlighting fluorophore
Authors: Wanguo Liu, Rui Gu, Qingsan Zhu, Chunsheng Xiao, Lanfeng Huang, Xinming Zhuang, Jingzhe Zhang, Lidi Liu, Ben Ma, Huailin Yang, Jianchao Ma, Zhipeng Hu, Chenglin Tang, Shuhua Zhao, Xuesi Chen
Journal: Theranostics (2017)

Iatrogenic spinal cord injury (SCI) is the most devastating complication of spine surgery, which usually results in permanent and serious disabilities of patients.Improvement of the visualization and discrimination of the spinal cord is critical for accuracy and safety during surgery; however, to date, there is no suitable technology to fulfill this clinical need.Here, we first show an efficient and rapid fluorescence imaging of the spinal cord in rabbit by epidural administration of a nerve-highlighting fluorophore, i.e. (E, E)-1,4-bis(p-aminostryl)-2-methoxy benzene (BMB).The BMB is firstly encapsulated into polymeric micelles to form a BMB-micelle (BMB-m) formulation with well-dispersion in normal saline solution.After epidural administration of BMB-m, BMB is transported by the flow of cerebrospinal fluid (CSF) and binds to the peripheral region of the white matter thus facilitating rapid staining of the spinal cord.Furthermore, this BMB imaging technology also holds great potential for visually monitoring the integrity of the spinal cord in real time and promptly identifying acute SCI during spine surgery.
Identification and Characterization of Novel Rare Nucleophosmin (NPM1) Gene Mutations in Acute Myeloid Leukemia (AML) By a Combinatorial Approach of Immunohistochemistry and Molecular Analyses
Authors: Maria Paola Martelli, Roberta Rossi, Emanuela Varasano, Giorgina Specchia, Francesco Di Raimondo, Giuseppe Avvisati, Enrico Tiacci, Franca Falzetti, Paolo Sportoletti, Brunangelo Falini
Journal: Blood (2016)
Intradiscal Glucocorticoid Injection for Patients With Chronic Low Back Pain Associated With Active Discopathy
Authors: Christelle Nguyen, Isabelle Boutron, Gabriel Baron, Katherine Sanchez, Clémence Palazzo, Raphaël Benchimol, Guillaume Paris, Étienne James-Belin, Marie-Martine Lefèvre-Colau, Johann Beaudreuil, Jean-Denis Laredo, Anne Béra-Louville, Anne Cotten, Jean-Luc Drapé, Antoine Feydy, Philippe Ravaud, François Rannou, Serge Poiraudeau
Journal: Annals of Internal Medicine (2017)

Active discopathy is associated with a specific phenotype of chronic low back pain (LBP). Local inflammation has a role in active discopathy-associated symptoms.To assess the efficacy of a single glucocorticoid intradiscal injection (GC IDI) in patients with chronic LBP with active discopathy.Prospective, parallel-group, double-blind, randomized, controlled study. (ClinicalTrials.gov: NCT00804531).3 tertiary care centers in France.135 patients with chronic LBP with active discopathy on magnetic resonance imaging (MRI).A single GC IDI (25 mg prednisolone acetate) during discography (n = 67) or discography alone (n = 68).The primary outcome was the percentage of patients with LBP intensity less than 40 on an 11-point numerical rating scale (0 [no pain] to 100 [maximum pain] in 10-point increments) in the previous 48 hours at 1 month after the intervention. The main secondary outcomes were LBP intensity and persistent active discopathy on MRI at 12 months and spine-specific limitations in activities, health-related quality of life, anxiety and depression, employment status, and use of analgesics and nonsteroidal anti-inflammatory drugs at 1 and 12 months.All randomly assigned patients were included in the primary efficacy analysis. At 1 month after the intervention, the percentage of responders (LBP intensity <40) was higher in the GC IDI group (36 of 65 [55.4%]) than the control group (21 of 63 [33.3%]) (absolute risk difference, 22.1 percentage points [95% CI, 5.5 to 38.7 percentage points]; P = 0.009). The groups did not differ in LBP intensity at 12 months and in most secondary outcomes at 1 and 12 months.Tertiary care setting.In chronic LBP associated with active discopathy, a single GC IDI reduces LBP at 1 month but not at 12 months.French Ministry of Health.
Endocytoscopy can be used to assess histological healing in ulcerative colitis
Authors: Yoshihiro Nakazato, Makoto Naganuma, Shinya Sugimoto, Rieko Bessho, Mari Arai, Hiroki Kiyohara, Keiko Ono, Kosaku Nanki, Makoto Mutaguchi, Shinta Mizuno, Taku Kobayashi, Naoki Hosoe, Masayuki Shimoda, Takayuki Abe, Nagamu Inoue, Haruhiko Ogata, Yasushi Iwao, Takanori Kanai
Journal: Endoscopy (2017)

Abstract Background and study aim Endocytoscopy (ECS) is used in the in vivo microscopic inspection of microstructural mucosal features and enables endoscopists to assess the histological severity of ulcerative colitis (UC). The aim of this study was to assess histological healing in UC patients by using ECS. Patients and methods A total of 64 patients in clinical and endoscopic remission who underwent ECS were selected. The correlation between the ECS score and Geboes score at the rectum was evaluated in patients with a Mayo endoscopic score (MES) of 0. The diagnostic accuracy of the ECS score for histological remission (Geboes score ≤ 2) was also assessed. Results The ECS score ranged from 0 to 5 in patients with endoscopic remission on conventional white-light images (MES of 0). The agreement between histological remission regarding the ECS score and the Geboes score had a κ value of 0.72, and the ECS score showed high accuracy for histological remission, with a sensitivity of 0.77, a specificity of 0.97, and a diagnostic accuracy of 0.86. Conclusion ECS can be used to assess histological healing in patients with UC without the need for biopsy specimens.
Oncogenic RAS Regulates Long Noncoding RNA <i>Orilnc1</i> in Human Cancer
Authors: Dongmei Zhang, Gao Zhang, Xiaowen Hu, Lawrence Wu, Yi Feng, Sidan He, Youyou Zhang, Zhongyi Hu, Lu Yang, Tian Tian, Weiting Xu, Zhi Wei, Yiling Lu, Keith T. Flaherty, Xiaomin Zhong, Gordon B. Mills, Phyllis A. Gimotty, Xiaowei Xu, Meenhard Herlyn, Lin Zhang
Journal: Cancer Research (2017)

RAS and its downstream cascades transmit cellular signals, resulting in increased transcription of genes involved in cell growth and division. Protein-coding gene targets of RAS signaling have been characterized extensively, but long noncoding RNAs (lncRNA) regulated by these processes have not. Using a custom-designed lncRNA microarray, we identified the lncRNA Orilnc1 as a genetic target of RAS that is critical for RAS oncogenicity. Orilnc1 expression was regulated by RAS-RAF-MEK-ERK signaling via the transcription factor AP1. Orilnc1 was highly expressed in BRAF-mutant cancers, such as melanoma. Silencing of Orilnc1 blocked tumor cell proliferation and growth in vitro and in vivo In addition, Orilnc1 blockade reduced expression of cyclin E1 and induced G1-S cell-cycle arrest in tumor cells. Taken together, our results identify Orilnc1 as a novel, nonprotein mediator of RAS/RAF activation that may serve as a therapeutic target in RAS/RAF-driven cancers. Cancer Res; 77(14); 3745-57. ©2017 AACR.
Effect of ivabradine in patients with heart failure with preserved ejection fraction: the <scp>EDIFY</scp> randomized placebo‐controlled trial
Authors: Michel Komajda, Richard Isnard, Alain Cohen-Solal, Marco Metra, Burkert Pieske, Piotr Ponikowski, Adriaan A. Voors, Fabienne Dominjon, Cécile Henon-Goburdhun, Matthieu Pannaux, Michael Böhm
Journal: European Journal of Heart Failure (2017)
Increasing Diversity in Dermatology Residencies—Reply
Authors: Chen (Amy) Chen, Kanade Shinkai
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Orthopaedic special tests and diagnostic accuracy studies: house wine served in very cheap containers
Authors: Eric J Hegedus, Alexis A Wright, Chad Cook
Journal: British Journal of Sports Medicine (2017)

House wine is the abstruse alcoholic drink sold by restaurants to thirsty, unquestioning individuals who are looking for the path of least resistance. House wine is easily accessible, simplifies an oft-complex process and ‘feels’ like its highbrow cousins. House wine is alluring to sellers of wine because it appeals to the masses and is profitable. House wine meets a need; but its packaging (usually a box) is generally looked down upon by discerning consumers since it signals lack of quality.

> Unfortunately, orthopedic special tests are the house wine of the research community and diagnostic accuracy studies are the cheap containers in which they are served.

Before you object too strenuously, we submit the following case (or box, sticking with the theme). Like cheap wine, orthopaedic special tests are ubiquitous. Our quick search of PubMed using ‘diagnostic accuracy and orthopaedic tests’ revealed 539 articles (most of them relevant). Beyond primary literature, a Google search for orthopaedic special tests elicited 967, 000 results including textbooks and websites. Textbooks frequently introduce a litany of tests; often including similar tests with variable names and no discriminating properties. YouTube is laden with demonstrations of selected tests. This popularity begs the question, ‘Why?’

For the sellers of the ‘house wine’, for example, researchers and journals, orthopaedic tests …
The IL-27/Wsx-1 Axis Modulates T Cell Responses and Regulates Acute Graft-Versus-Host Disease after Allogeneic Bone Marrow Transplantation
Authors: Shoubao Ma, Huanle Gong, Shuangzhu Liu, Jingjing Han, Zhinan Yin, Haiyan Liu, Depei Wu
Journal: Blood (2016)
Optimal Brain 99mTc–Ethyl Cysteinate Dimer SPECT Imaging and Analysis to Detect Misery Perfusion on 15O PET Imaging in Patients With Chronic Occlusive Disease of Unilateral Major Cerebral Artery
Authors: Yoshiyasu Matsumoto, Kohki Oikawa, Jun-ichi Nomura, Daigo Kojima, Sotaro Oshida, Masakazu Kobayashi, Kazunori Terasaki, Yoshitaka Kubo, Kuniaki Ogasawara
Journal: Clinical Nuclear Medicine (2017)

Misery perfusion is defined as marginally sufficient cerebral blood supply relative to cerebral metabolic demand. The aim of the present study was to determine the optimal brain Tc-ethyl cysteinate dimer (ECD) SPECT imaging and analysis to detect misery perfusion on O PET imaging in patients with chronic occlusive disease of unilateral internal carotid or middle cerebral artery (MCA).For 97 patients, cerebral blood flow, cerebral metabolic rate of oxygen, and oxygen extraction fraction were measured using O PET; Tc-ECD SPECT was performed using dynamic scanning with a scan duration of 10 minutes each for 50 minutes after tracer administration. A region of interest was placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres in all standardized images using a 3-dimensional stereotaxic region-of-interest template and affected-to-contralateral asymmetry ratio in the MCA territory (ARMCA) and contralateral-to-affected asymmetry ratio in the cerebellar hemisphere (ARcbl) were calculated.The ARMCA or ARcbl on Tc-ECD SPECT with a scan time of 20 to 30 minutes after tracer administration (ARMCA20-30 or ARcbl20-30) was correlated with ARMCA on PET cerebral blood flow (r = 0.654) or ARMCA on PET cerebral metabolic rate of oxygen (r = 0.576), respectively, more strongly than with other scan times. The area under the receiver operating characteristic curve for detecting abnormally elevated ARMCA on PET oxygen extraction fraction was significantly greater for ARcbl20-30/ARMCA20-30 (0.947) than for ARMCA20-30 alone (0.780) (difference between areas, 0.167; P = 0.0001) on Tc-ECD SPECT.Combination of asymmetries in the cerebellar and cerebral hemispheres on Tc-ECD SPECT in a scan time of 20 to 30 minutes after tracer administration optimally detects misery perfusion in unilateral internal carotid artery or MCA occlusive disease.
Amb a 1 isoforms: Unequal siblings with distinct immunological features
Authors: M. Wolf, T. E. Twaroch, S. Huber, M. Reithofer, M. Steiner, L. Aglas, M. Hauser, I. Aloisi, C. Asam, H. Hofer, M. A. Parigiani, C. Ebner, B. Bohle, P. Briza, A. Neubauer, F. Stolz, B. Jahn‐Schmid, M. Wallner, F. Ferreira
Journal: Allergy (2017)

Ragweed pollen represents a major allergy risk factor. Ragweed extracts contain five different isoforms of the major allergen Amb a 1. However, the immunological characteristics of Amb a 1 isoforms are not fully investigated. Here, we compared the physicochemical and immunological properties of three most important Amb a 1 isoforms.After purification, the isoforms were physicochemically characterized, tested for antibody binding and induction of human T-cell proliferative responses. Their immunological properties were further evaluated in vitro and in vivo in a mouse model.Amb a 1 isoforms exhibited distinct patterns of IgE binding and immunogenicity. Compared to Amb a 1.02 or 03 isoforms, Amb a 1.01 showed higher IgE-binding activity. Isoforms 01 and 03 were the most potent stimulators of patients' T cells. In a mouse model of immunization, Amb a 1.01 induced higher levels of IgG and IgE antibodies when compared to isoforms 02 and 03. Interestingly, ragweed-sensitized patients also displayed an IgG response to Amb a 1 isoforms. However, unlike therapy-induced antibodies, sensitization-induced IgG did not show IgE-blocking activity.The present study showed that naturally occurring isoforms of Amb a 1 possess different immunogenic and sensitizing properties. These findings should be considered when selecting sequences for molecule-based diagnosis and therapy for ragweed allergy. Due to its high IgE-binding activity, isoform Amb a 1.01 should be included in diagnostic tests. In contrast, due to their limited B- and T-cell cross-reactivity patterns, a combination of different isoforms might be a more attractive strategy for ragweed immunotherapy.
Medical Journals, Publishers, and Conflict of Interest
Authors: Thomas J. Easley
Journal: JAMA (2017)

Publishers of scientific journals must be as invested as editors in defining and managing conflict of interest policies and practices, because the credibility and integrity of their publications constitute their most important asset. How and why a publisher engages in this effort are increasingly complex, given the exponential changes in biomedical journalism over the last 15 years. In addition, the world of medical journalism is affected by wider cultural trends in the media; in general, issues around conflict of interest have arguably never been more prominent. The veracity, independence, and objectivity of the media are under siege, with public confidence in the “fourth estate” reaching dangerous lows. At the same time, the public has become increasingly cynical, and public disillusionment centered on conflict of interest is on the rise.
Abstract P101: MEGA Analysis of Alcohol Consumption: The PAGE Study
Authors: Kristin L Young, Lani Park, Iona Cheng, Yuqing Li, Dan Stram, Loic Le Marchand, Stephanie Bien, Claudia Schurmann, Ulrike Peters, Kari North, Tara Matise, Steve Buyske
Journal: Circulation (2017)

Harmful use of alcohol results in 3.3 million deaths annually and 139 million disability-adjusted life years, and is a risk factor for obesity, hypertension, cardiomyopathy, and stroke. According to the NIAAA, while some minority groups (African Americans and Hispanics) are more likely to abstain from alcohol, those who do drink have higher rates of alcohol consumption and binge drinking. In addition, most genetic studies of alcohol have focused on dependence phenotypes. In populations of European and East Asian ancestry, genes related to alcohol metabolism, including ADH and ALDH , have been identified, and AUTS2 and SLC6A1 have been associated with alcohol consumption. Studies focused on diverse populations are necessary to provide insight into population-specific genetic variability and guide precision screening and intervention efforts. We aim to further efforts in precision medicine using The Multi-Ethnic Genotyping Array (MEGA), a custom array designed to capture genetic variants in minority populations to allow for imputation to low minor allele frequencies (MAF) across ancestries, as well as clinically relevant variants and deep genotyping of previously identified GWAS regions associated with complex diseases. We performed the first discovery study for alcohol traits using MEGA genotype data in African American, Hispanic, Asian, Native Hawaiian, and Native American PAGE participants to discover novel genetic variants influencing alcohol consumption. Our preliminary results focus on non-pregnant women over 21 (N=21,641), with phenotype data on drinks/week in study-specific single variant additive regression models controlling for age, PCs, and study center. Study-specific results were then meta-analyzed in METAL. Four variants on chromosome 8 (R 2 =0.33-0.81) passed our chip-wide significance threshold of p=2.8E-8. Of these, rs115165977 showed the strongest association with drinks/week (beta=1.93, se=0.32, p=1.70E-09). This variant is monomorphic in European and East Asian reference populations, but has a MAF between 0.01-0.03 in non-Asian PAGE populations. Rs115165977 is near ZFPM2 , a gene previously associated with cardiomyopathy that codes for a transcription factor regulating GATA proteins important for heart morphogenesis. This mouse ortholog of ZFPM2 has also been associated with alcohol acceptance and alcohol-induced loss of the righting reflex. Future work will focus on analysis of alcohol consumption using PAGE imputed data in the full sample, as well as fine-mapping known alcohol-related loci typed on the MEGA chip.