tbuckley/cabot-search huggingface dataset:
Recent developments in neurology
Authors: F I Ojini
Journal: BMJ (2002)

This review aims to highlight the significant developments in neuroscience and clinical neurology that have been recorded in the past few years.Original research and reviews were identified by searching PubMed for articles published from January 1995 using the following search terms: recent, developments, advances, progress, neurology, and neuroscience.Notable strides have been made in the management of neurological conditions like stroke and epilepsy. There is also greater understanding of the pathogenesis of the neurodegenerative diseases, and some form of treatment is now available for previously 'untreatable' conditions like motor neuron disease and Alzheimer's disease. The application of the techniques of molecular genetics and molecular cell biology has advanced the understanding and diagnosis of several neurological disorders, such as Huntington's disease and myotonic dystrophy. Clinical neurology has also profited from the huge advances in structural and functional brain imaging that have taken place in recent years. Areas of current research include the potential use of stem cells to treat a wide variety of neurological disorders, and the use of nerve growth factors to promote regeneration of neurons in the central nervous system.Current advances in neurology and neuroscience hold the promise of new approaches to the understanding and management of neurological diseases.
Early‐life house dust mite allergens, childhood mite sensitization, and respiratory outcomes
Authors: I. C. Asselbergs, H. C. Eikenboom, J. B. Wartna, B. W. Koes, L. Casas, J. Sunyer, C. Tischer, U. Gehring, M. Wickman, R. Garcia‐Esteban, I. Lehmann, I. Kull, A. Reich, S. Lau, A. Wijga, J. M. Antó, T. S. Nawrot, J. Heinrich, T. Keil, M. Torrent
Journal: Allergy (2015)
Abstract B17: Type 2 diabetes, metformin, and ovarian cancer survival: An analysis of tumor registry and electronic medical record data.
Authors: Spencer Keene, Samantha P. Stansel, Leshaun Clayton, Min Jiang, Melinda Aldrich, Hua Xu, Jeremy Warner, Joshua Denny, Dineo Khabele, Alicia Beeghly-Fadiel
Journal: Clinical Cancer Research (2016)

Abstract Background: Type 2 Diabetes Mellitus (T2D) is associated with increased cancer risk and higher cancer mortality. Metformin, a common T2D treatment, is associated with improved survival for several cancers. With a five year survival of 42%, repurposing metformin to improve ovarian cancer prognosis is attractive. However, only a few studies to date have evaluated associations between T2D, metformin use, and ovarian cancer survival. Methods: We evaluated tumor registry confirmed ovarian and fallopian tube cancer cases from the Vanderbilt University Medical Center. Metformin use was determined from electronic medical records (EMR) using MedEx. For validation, natural language processing EMR review was conducted for 50 subjects. Cox proportional hazards regression was used to evaluate associations with overall survival and calculate Hazard Ratios (HR) and corresponding 95% Confidence Intervals (CI); models included adjustment for age, stage, histologic subtype, and body-mass index (BMI). Results: Tumor registry data and EMR was available for 372 invasive epithelial ovarian cancer cases. Forty (10.8%) had T2D, and 20 had metformin use (5.4%). MedEx and EMR reviewed metformin use was highly concordant (Kappa=0.96). Associations with overall survival were suggestive but non-significant for T2D (HR: 0.80, 95% CI: 0.51-1.25) and metformin use, either among only T2D cases (HR: 0.73, 95% CI: 0.29-1.84) or among all ovarian cancer cases (HR: 0.61, 95% CI: 0.31-1.21). Two or more years of metformin use was significantly associated with better survival compared to cases without metformin use (HR: 0.28, 95% CI: 0.09-0.89). Exploratory analyses suggested better survival among serous cases and worse survival among non-serous cases for both T2D and metformin, but associations were not significant. Analyses to address survival time bias yielded results comparable to our primary findings. Conclusions: Ovarian cancer cases with metformin use had marginally better overall survival. While not significant, these associations indicate that metformin may have utility repurposed as a treatment for ovarian cancer. Larger studies are needed to determine if associations differ by histology, and if metformin may be beneficial to all ovarian cancer subtypes. Citation Format: Spencer Keene, Samantha P. Stansel, Leshaun Clayton, Min Jiang, Melinda Aldrich, Hua Xu, Jeremy Warner, Joshua Denny, Dineo Khabele, Alicia Beeghly-Fadiel. Type 2 diabetes, metformin, and ovarian cancer survival: An analysis of tumor registry and electronic medical record data. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B17.
Thomas Young
Authors: Renwick K. Caldwell
Journal: New England Journal of Medicine (1957)

THE life of the physician before and during the American Revolution was usually a busy one. In addition to his professional responsibilities, he was often, because of his respected position in the community, a leader in the struggle for independence. In fulfilling these tasks several physicians attained considerable renown; others, of lesser fame, also made substantial contributions. Dr. Thomas Young was one of the less well known. A contemporary of Joseph Warren and Benjamin Rush and a colleague of Benjamin Franklin, Samuel Adams and Ethan Allen, Young deserves wider recognition for his contributions to the struggle for freedom.Thomas Young . . .
Colon Cancer
Authors: John L. Zeller, Cassio Lynm, Richard M. Glass
Journal: JAMA (2006)

Colon Cancer Colorectal cancer (cancer of the colon [large intestine] or rectum) is the third most common cancer in men and women.When it is discovered in its early stages, colon cancer is treated with surgery and often cured.However, many individuals with colon cancer have no symptoms until the disease reaches an advanced stage, such as metastasizing (spreading) to other organs.Colorectal cancer is the second leading cause of cancer deaths (after lung cancer) in the United States.Testing persons without signs or symptoms of colon cancer is called screening.Screening for colon cancer is recommended for everyone older than 50 years and especially for individuals who have significant risk factors.Several articles in the September 27, 2006, issue of JAMA discuss the importance of screening tests for early detection of this disease.
Human immunodeficiency virus-associated neoplasia: changing spectrum?
Authors: L D Kaplan
Journal: Journal of Clinical Oncology (1995)

AbstractNovember 01, 1995 Share on Human immunodeficiency virus-associated neoplasia: changing spectrum?Author: L D KaplanAuthors Info & AffiliationsPublication: Journal of Clinical OncologyVolume 13, Number 11https://doi.org/10.1200/JCO.1995.13.11.2684 Get Access
Hypofractionated Radiotherapy Reduces Acute Skin Toxicity in Small and Large Breasted Patients Receiving Whole-Breast Irradiation
Authors: L. Veldeman, S. De Langhe, V. Remouchamps, A. van Greveling, M. Gilsoul, B. Speleers, W. De Neve, R. van den Broecke, T. Mulliez
Journal: Annals of Oncology (2014)
Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis
Authors: Michael Frisk, Marianne Ruud, Emil K. S. Espe, Jan Magnus Aronsen, Åsmund T. Røe, Lili Zhang, Per Andreas Norseng, Ole M. Sejersted, Geir A. Christensen, Ivar Sjaastad, William E. Louch
Journal: Cardiovascular Research (2016)

Invaginations of the cellular membrane called t-tubules are essential for maintaining efficient excitation–contraction coupling in ventricular cardiomyocytes. Disruption of t-tubule structure during heart failure has been linked to dyssynchronous, slowed Ca2+ release and reduced power of the heartbeat. The underlying mechanism is, however, unknown. We presently investigated whether elevated ventricular wall stress triggers remodelling of t-tubule structure and function. MRI and blood pressure measurements were employed to examine regional wall stress across the left ventricle of sham-operated and failing, post-infarction rat hearts. In failing hearts, elevated left ventricular diastolic pressure and ventricular dilation resulted in markedly increased wall stress, particularly in the thin-walled region proximal to the infarct. High wall stress in this proximal zone was associated with reduced expression of the dyadic anchor junctophilin-2 and disrupted cardiomyocyte t-tubular structure. Indeed, local wall stress measurements predicted t-tubule density across sham and failing hearts. Elevated wall stress and disrupted cardiomyocyte structure in the proximal zone were also associated with desynchronized Ca2+ release in cardiomyocytes and markedly reduced local contractility in vivo. A causative role of wall stress in promoting t-tubule remodelling was established by applying stretch to papillary muscles ex vivo under culture conditions. Loads comparable to wall stress levels observed in vivo in the proximal zone reduced expression of junctophilin-2 and promoted t-tubule loss. Elevated wall stress reduces junctophilin-2 expression and disrupts t-tubule integrity, Ca2+ release, and contractile function. These findings provide new insight into the role of wall stress in promoting heart failure progression.
Novel Intracranial Xenografts Of CNS Lymphoma Implicate a Role For Cereblon As a Mediator Of Lenalidomide Efficacy
Authors: Hua-Xin Gao, Shawn Anderson, Cigall Kadoch, Mekhala Maiti, Lingjing Chen, Dong-Han Yao, Gerd Melkus, Maria Wang, Yan Ren, Michael Breider, Carla Heise, Clifford A. Lowell, Colin Collins, James L. Rubenstein
Journal: Blood (2013)
Abstract A32: The role of microRNA in the regulation of DUSP16 gene and JNK family in hepatocellular carcinoma patients
Authors: Marwa Tantawy, Nagwa Hassan, Mohamed Kobaisi, Abdel Hady Abdel Wahab
Journal: Cancer Research (2016)

Abstract Introduction: Human hepatocellular carcinoma (HCC) is consider one of the most common and lethal tumors worldwide, HCC is currently the fifth most common solid tumor worldwide and the fourth important cause of cancer-related death. Eighty percent of new cases found in developing countries as Egypt, but the incidence is increasing in economically developed regions, including Japan, Western Europe, and the United States. It has shown that expression level of different miRNAs was correlated with cellular liver processes such as inflammation, hepatocyte regeneration and apoptosis which indicate their important role in many liver diseases including hepatocellular carcinoma. The main objective of the present study is to correlate between the expression levels of liver specific miRNAs with different mitogen activated protein kinase (MAPK) pathway in primary HCC patients. Patients and Methods: The expression level of miRNA targeting MAPK pathway, Dual-Specificity Phosphatase 16 (DUSP16), c-Jun N-terminal kinases (JNK) family (JNK1, JNK2 and JNK3) were detected in tissue biopsy of 38 primary HCC patients as well as 6 healthy controls using qRT-PCR technique. Detection of the protein levels for DUSP16, JNK1 and JNK2 was done using immunohistochemistry (IHC) assay. Results: The correlation between different expressions was done using (statistical method). Significant correlation was observed between 10 miRNAs with mRNA for DUSP16, JNK1, JNK2 and JNK3 (miR-18b; miR-30c; miR-30e; miR-99a; miR-126; miR-194; miR-198; miR-215; miR-455 and miR-455-3p). Highly significant down regulation was detected in JNK2 and JNK3 gene expression in HCC patients as compared to controls with (P value = 0.016, 0.000) respectively. Using IHC assay, 34% (13 out 38) showed DUSP16 (P value &amp;lt;0.0001), 82% (31 out 38) for JNK1 (P value &amp;lt;0.0001) and 71% (27 out 38) for JNK2. All control samples didn't show any protein expression of genes analyzed. Conclusion: Understanding the role of miRNA in MAPK pathway may open new avenue for development novel treatment strategy in primary hepatocellular carcinoma. Citation Format: Marwa Tantawy, Nagwa Hassan, Mohamed Kobaisi, Abdel Hady Abdel Wahab. The role of microRNA in the regulation of DUSP16 gene and JNK family in hepatocellular carcinoma patients. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr A32.
Abstract 355: Post-translational Modification of Histone Variants in Cardiac Hypertrophy
Authors: Mickey Miller, Aman Makaju, Li Wang, Sarah Franklin
Journal: Circulation Research (2014)

While global changes in gene expression are a hallmark of cardiac hypertrophy, much less is known regarding the epigenetic factors driving these changes. Local chromatin packing and gene accessibility, which governs transcriptional status, has been correlated with specific post-translational modifications on the histone tails of nucleosomes occupying these regions. However, the specific alterations in histone post-translational modifications driving gene expression changes during cardiac hypertrophy are largely unknown. To identify myocyte specific changes in histone post-translational modifications during cardiac hypertrophy we performed label-free quantitation of nuclear proteins from isolated neonatal rat ventricular myocytes exposed to the hypertrophic agonists, phenylephrine and isoproterenol. Peptide samples were analyzed on a Thermo Orbitrap Velos Pro mass spectrometer using CID &amp; HCD fragmentation. Differential expression analysis was performed using the Progenesis LC-MS software where modified histone peptides were normalized against total protein expression. We observed multiple known and novel post-translational modifications on each of the four core histones, many of which changed in the setting of hypertrophy. To validate these findings in an animal model we performed the same analysis of histone post-translational modifications from cardiac tissue of mice under basal conditions or after pressure-overload induced hypertrophy. This study provides the first global characterization of myocyte specific changes in histone post-translational modifications in cardiac hypertrophy and highlight basic mechanisms of genomic reprogramming operative in disease.
Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program
Authors: Mengle Shao, Jeff Ishibashi, Christine M. Kusminski, Qiong A. Wang, Chelsea Hepler, Lavanya Vishvanath, Karen A. MacPherson, Stephen B. Spurgin, Kai Sun, William L. Holland, Patrick Seale, Rana K. Gupta
Journal: Cell Metabolism (2016)
Relationship between the Tridimensional Personality Questionnaire and DSM-III-R personality traits
Authors: R G Goldman, A E Skodol, P J McGrath, J M Oldham
Journal: American Journal of Psychiatry (1994)

The authors investigated the relationship between Cloninger's personality dimensions and DSM-III-R personality traits by comparison of scores on the Tridimensional Personality Questionnaire with axis II traits found in structured interviews with 99 patients. Consistent with theoretical predictions, axis II pathology was significantly related to personality dimensions after the effects of axis I disorders were controlled for.
Studies on the Myocardial Metabolism of Diabetes Mellitus and the Effects of Insulin, Glucocorticoid and Epinephrine on the Metabolism of the Heart
Authors: Yoshio Ito
Journal: Circulation (1962)

The myocardial carbohydrate and non-esterified fatty acid metabolism in the human diabetic heart along with the effect of insulin and the changes of myocardial metabolism induced by the intravenous administration of glucocorticoid and epinephrine were studied by coronary sinus catheterization. In the diabetic heart, there was an unbalance of the supply and demand of oxygen, and disturbances in glucose, lactate, pyruvate and citrate metabolism. The insulin improved the disturbed glucose and citrate metabolism and in some cases the unbalance of the oxygen supply and demand in the myocardium. The myocardial fuel tended to shift from carbohydrate to lipid by the administration of glucocorticoid. The epinephrine also increased the myocardial lipid utilization and at the same time brought about slight myocardial hypoxia. It was proven in another experiment using C14 labelled substrates in the rat heart slice that the pentose phosphate pathway existed in a fairly large percentage and insulin, epinephrine and glucocorticoid influenced it. Part of the glucose extracted by the myocardium was stored as glycogen and lipid, though this might be temporary.
Biased Expression of the FOXP3Δ3 Isoform in Aggressive Bladder Cancer Mediates Differentiation and Cisplatin Chemotherapy Resistance
Authors: Hanwei Zhang, Kris Prado, Kelvin X. Zhang, Elizabeth M. Peek, Jane Lee, Xiaoyan Wang, Jiaoti Huang, Gang Li, Matteo Pellegrini, Arnold I. Chin
Journal: Clinical Cancer Research (2016)

The transcriptional regulation mediating cancer cell differentiation into distinct molecular subtypes and modulating sensitivity to existing treatments is an enticing therapeutic target. Our objective was to characterize the ability of the forkhead/winged transcription factor FOXP3 to modulate the differentiation of bladder cancer.Expression of FOXP3 was analyzed by immunohistochemistry in a tumor microarray of 587 samples and overall survival in a subset of 187 patients following radical cystectomy. Functional assays were performed in SW780 and HT1376 cell lines in vitro and in vivo and gene expression profiling performed by RNA-Seq. Validation was undertaken using gene expression profiles of 131 patients from The Cancer Genome Atlas (TCGA) consortium in bladder cancer.FOXP3 expression correlates with bladder cancer stage and inversely with overall survival, with biased expression of the FOXP3Δ3 isoform. Functional assays of FOXP3Δ3 demonstrated resistance to chemotherapy in vitro, whereas subcutaneous xenografts overexpressing FOXP3Δ3 developed larger and more poorly differentiated bladder cancers. RNA expression profiling revealed a unique FOXP3Δ3 gene signature supporting a role in chemotherapy resistance. Accordingly, knockdown of Foxp3 by siRNA in HT1376 cells conferred sensitivity to cisplatin- and gemcitabine-induced cytotoxicity. Validation in TCGA dataset demonstrated increased expression of FOXP3 in subtypes II to IV and skewing of molecular subtypes based on FOXP3Δ3-specific gene expression.(i) Biased expression of the FOXP3Δ3 isoform in bladder cancer inversely correlates with overall survival, (ii) FOXP3Δ3 induces a unique gene program that mediates cancer differentiation, and (iii) FOXP3Δ3 may augment chemotherapy resistance. Clin Cancer Res; 22(21); 5349-61. ©2016 AACR.
Effect of Castration on Histochemistry and Biochemistry of Acid Hydrolases in Rat Prostate Gland2
Authors: Joseph E. Paris, David Brandes, Elsa B. Anton, Sandra Barnard
Journal: JNCI Journal of the National Cancer Institute (1972)

The rat ventral prostate has been used as a model of an androgen-dependent tissue. Organ weight and protein content decreased markedly after castration to less than one-fifth of their initial values by day 4. The loss of lysosomal hydrolases was slower and, by day 4, 30–40% of the initial enzyme amounts could be found in the atrophic prostates. The lysosomal enzymes, therefore, either possessed a slower turnover or were degraded more slowly than other tissue proteins. After castration histochemically detectable enzymes increased, possibly due to selective retention of the hydro lases by the regressing prostate. The observed rise in percent unsedimentable absolute activities of various lysosomal enzymes in this organ after castration was attributable to intracellular release of hydro lases toward the cell soluble phase. Electron histochemical preparations showed that prostate cells cannot sustain the integrity of their cytoplasms after androgen deprivation. Cell organelles became obsolete, were enclosed within autophagic vacuoles, and subsequently were degraded by lysosomal enzymes.
Combination immunotherapy with oncolytic adenovirus and adoptive T-cell transfer leads to systemic anti-tumor immunity and enhanced therapeutic efficacy in a preclinical melanoma model
Authors: S. Tähtinen, S. Grönberg-Vähä-Koskela, D. Lumen, M. Merisalo-Soikkeli, M. Siurala, A.J. Airaksinen, M. Vähä-Koskela, A. Hemminki
Journal: Annals of Oncology (2015)
Physical rehabilitation interventions for adult patients during critical illness: an overview of systematic reviews
Authors: Bronwen Connolly, Brenda O'Neill, Lisa Salisbury, Bronagh Blackwood
Journal: Thorax (2016)

<h3>Background</h3> Physical rehabilitation interventions aim to ameliorate the effects of critical illness-associated muscle dysfunction in survivors. We conducted an overview of systematic reviews (SR) evaluating the effect of these interventions across the continuum of recovery. <h3>Methods</h3> Six electronic databases (Cochrane Library, CENTRAL, DARE, Medline, Embase, and Cinahl) were searched. Two review authors independently screened articles for eligibility and conducted data extraction and quality appraisal. Reporting quality was assessed and the Grading of Recommendations Assessment, Development and Evaluation approach applied to summarise overall quality of evidence. <h3>Results</h3> Five eligible SR were included in this overview, of which three included meta-analyses. Reporting quality of the reviews was judged as medium to high. Two reviews reported moderate-to-high quality evidence of the beneficial effects of physical therapy commencing during intensive care unit (ICU) admission in improving critical illness polyneuropathy/myopathy, quality of life, mortality and healthcare utilisation. These interventions included early mobilisation, cycle ergometry and electrical muscle stimulation. Two reviews reported very low to low quality evidence of the beneficial effects of electrical muscle stimulation delivered in the ICU for improving muscle strength, muscle structure and critical illness polyneuropathy/myopathy. One review reported that due to a lack of good quality randomised controlled trials and inconsistency in measuring outcomes, there was insufficient evidence to support beneficial effects from physical rehabilitation delivered post-ICU discharge. <h3>Conclusions</h3> Patients derive short-term benefits from physical rehabilitation delivered during ICU admission. Further robust trials of electrical muscle stimulation in the ICU and rehabilitation delivered following ICU discharge are needed to determine the long-term impact on patient care. This overview provides recommendations for design of future interventional trials and SR. <h3>Trial registration number</h3> CRD42015001068.
Abstract IA12: Open-source, crowdsourcing-capable tools for N of 1 cancer genomics
Authors: Elaine R. Mardis
Journal: Clinical Cancer Research (2016)

Abstract There are multiple challenges to implementing cancer genomics in a clinical setting to identify for individual patients and their oncologist, the potentially druggable targets in their disease. Our group has introduced several open-source informatics tools for the identification of known driver mutations, for identifying their vulnerabilities regarding small molecule- and/or antibody-based inhibitors. These are meant not only to negotiate databased information that resides in different formats and locations, but also to serve as crowdsourcing-based information intake points that permit the community of practicing cancer care physicians to participate in knowledge sharing. My talk will highlight these tools and their functionality in the context of several “N of 1” examples from our work. Citation Format: Elaine R. Mardis. Open-source, crowdsourcing-capable tools for N of 1 cancer genomics. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr IA12.