tbuckley/cabot-search huggingface dataset:
Allan McLane Hamilton
Authors: Jonathan Davidson
Journal: American Journal of Psychiatry (2018)

a prominent alienist (psychiatrist) in a career stretching from 1870 to his death in 1919.In the first part of his career, Hamilton specialized in neurology, including electrotherapeutics, epilepsy, and tremors, and he won first prize of the American Medical Association in 1879 for an essay on diseases of the spinal cord.He invented a gas cautery instrument and "the best dynamometer ever invented," according to neurologist Charles Dana (1).Dana considered Hamilton to be the "last link to that group of men who gave distinction to American neurology."In the second phase of his career, Hamilton branched out to medicolegal and psychiatric practice.He became known as the "dean of forensic psychiatry" and was an expert witness in many prominent trials (e.g., the trial of Charles Guiteau, the assassin of President James A. Garfield) and evaluations of well-known people, including Mary Baker Eddy, the founder of Christian Science.In her old age, Eddy was evaluated for mental competency by four experts, one of whom was Hamilton, who considered her to be competent.As Dana said of Hamilton, he "enjoyed the spirit of contests."He edited an encyclopedic System of Legal Medicine and authored Railway and Other Accidents: A Book for Court Use.In the second phase of his career, Hamilton wrote other books, including Mental Jurisprudence, Types of Insanity, and Nervous Diseases.Hamilton founded and became first president of the New York Psychiatric Society.Dana observed in Hamilton a restlessness that went with "a temperamental character" and that interfered with Hamilton's clinical practice.Hamilton spent many years in Europe, practiced in London, and was elected to Fellowship of the Royal Society of Edinburgh.The last phase of Hamilton's professional life was accompanied by serious illness, which curtailed his clinical activities, and he turned his attention to writing, including
Abstract 51: Kawasaki disease in a patient with Acute Myeloid Leukemia and Candida infection
Authors: Marco Yamazaki-Nakashimada, Francisco Rivas-Larrauri, Giovanni Sorcia-Ramirez, Marta Zapata, Martín Garrido-García
Journal: Circulation (2015)

Though the causative agent of Kawasaki disese (KD) remains unclear, an infectious agent is thought to trigger the disease. KD has been described associated with immunodeficiency disorders including HIV. We report a patient with Acute Myeloid Leukemia (AML) who developed KD in an early course of the disease. A 4 year-old boy was diagnosed as AML and received treatment with daunorubicin, etoposide and Ara-C. Eleven days later he started presenting fever, diarrhea and abdominal pain. A diagnosis of neutropenic colitis was made and treatment with vancomycin and cefepime was started. He continued having fever and polymorphic eruption was added, with prominent perineal erythema. Later he presented redness of the lips, hands and feet edema, erythema in the palms and soles and conjuctival erythema. The diagnosis of KD was established and treatment with IVIG and low-dose prednisone was administered. Echocardiogram revealed left coronary aneurysm and pericardial effusion. Abdominal-ultrasound showed gallbladder hydrops. Candida grew in blood culture and treatment with amphotericin-B was started. Akita et al. reported one previous case of leukemia associated with KD. As the previous reported case, our case developed the disease in the induction therapy for the AML. Interestingly, infection with Candida was documented in our patient. Administration of Candida cell Wall-antigens induced KD-like coronary vasculitis in mice. C. abicans colonizes the intestinal tract and causes invasive deep micosis in an immune-compromised host. Beta-glucan from the fungus stimulates the host immune system inducing an inflammatory response. Sampling campaigns over Japan during the KD season detected major differences in the microbiota of the tropospheric aerosols, with the unexpected finding of the Candida species as the dominant fungus from aloft samples (54% of all fungal strains). These results, provide support for the feasibility of a windborne pathogen. A fungal toxin could be pursued as a possible etiologic agent of KD. To our knowledge this is the second case of KD associated with leukemia. Chemotherapy-induced immunosuppresion could have a role in the genesis of KD in our patient and possibly triggered by a Candida infection.
Abstract 3669: Assessing the genetic heterogeneity of localized, multifocal prostate cancer via cell-free DNA
Authors: Emmalyn Chen, Clinton L. Cario, Lancelote Leong, Karen Lopez, Jeffry P. Simko, Peter R. Carroll, Caroline Tai, John S. Witte
Journal: Cancer Research (2018)

Abstract At the time of diagnosis, it is common to find multiple spatially distinct foci within a single prostate gland in men with prostate cancer. Recent studies evaluating the genetic heterogeneity of localized, multifocal prostate cancers through whole-genome sequencing and whole-exome sequencing have only recently been described. These tumors were highly heterogeneous for single-nucleotide variants, copy number alterations, and genomic rearrangements. One exciting use of cfDNA is its potential ability to simultaneously capture all genetically distinct tumor subclones. Currently, the degree to which a cfDNA sample is representative of the entire genetic landscape of localized prostate cancer is unknown. The objective of this study is to determine if somatic mutations identified in tumor tissue are detectable in cfDNA. Tumor tissue and blood samples have been collected from twenty-nine patients undergoing radical prostatectomy. Samples from fourteen patients have already been subjected to whole-exome sequencing with a target sequencing depth of 200X (HiSeq 4000). Preliminary analyses indicate that tumor foci within a single prostate gland in an individual are genetically heterogeneous. Further analysis of mutational concordance between tumor tissue DNA and cfDNA along with clinical data will be performed. Citation Format: Emmalyn Chen, Clinton L. Cario, Lancelote Leong, Karen Lopez, Jeffry P. Simko, Peter R. Carroll, Caroline Tai, John S. Witte. Assessing the genetic heterogeneity of localized, multifocal prostate cancer via cell-free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3669.
Mutational Analysis Identifies Therapeutic Biomarkers in Inflammatory Bowel Disease–Associated Colorectal Cancers
Authors: Shahida Din, Kim Wong, Mike F. Mueller, Anca Oniscu, James Hewinson, Catherine J. Black, Martin L. Miller, Alejandro Jiménez-Sánchez, Roy Rabbie, Mamunar Rashid, Jack Satsangi, David J. Adams, Mark J. Arends
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Inflammatory bowel disease–associated colorectal cancers (IBD-CRC) are associated with a higher mortality than sporadic colorectal cancers. The poorly defined molecular pathogenesis of IBD-CRCs limits development of effective prevention, detection, and treatment strategies. We aimed to identify biomarkers using whole-exome sequencing of IBD-CRCs to guide individualized management. Experimental Design: Whole-exome sequencing was performed on 34 formalin-fixed paraffin-embedded primary IBD-CRCs and 31 matched normal lymph nodes. Computational methods were used to identify somatic point mutations, small insertions and deletions, mutational signatures, and somatic copy number alterations. Mismatch repair status was examined. Results: Hypermutation was observed in 27% of IBD-CRCs. All hypermutated cancers were from the proximal colon; all but one of the cancers with hypermutation had defective mismatch repair or somatic mutations in the proofreading domain of DNA POLE. Hypermutated IBD-CRCs had increased numbers of predicted neo-epitopes, which could be exploited using immunotherapy. We identified six distinct mutation signatures in IBD-CRCs, three of which corresponded to known mechanisms of mutagenesis. Driver genes were also identified. Conclusions: IBD-CRCs should be evaluated for hypermutation and defective mismatch repair to identify patients with a higher neo-epitope load who may benefit from immunotherapies. Prospective trials are required to determine whether IHC to detect loss of MLH1 expression in dysplastic colonic tissue could identify patients at increased risk of developing IBD-CRC. We identified mutations in genes in IBD-CRCs with hypermutation that might be targeted therapeutically. These approaches would complement and individualize surveillance and treatment programs. Clin Cancer Res; 24(20); 5133–42. ©2018 AACR.
Abstract 2042: Hypoxia induces miR-153 through the IRE1α-XBP1 pathway to fine-tune the HIF1α/VEGFA axis in breast cancer angiogenesis
Authors: Huichun Liang, Zhongmei Zhou, Ceshi Chen
Journal: Cancer Research (2018)

Abstract It is well documented that hypoxia activates the hypoxia-inducible factor (HIF1α)/vascular endothelial growth factor A (VEGFA) axis to promote angiogenesis in breast cancer. However, it is unclear how this axis is negatively regulated. A number of studies suggest that miR-153 inhibits tumor growth and metastasis by targeting SNAI1, ZEB2, MTDH, ADAM19, AKT1, HECTD3, and MCL1. We recently reported that miR-153 was induced by mifepristone and inhibited the breast cancer stem cells by down-regulating KLF5. In this study, we demonstrated that miR-153 directly inhibits expression of HIF1α by binding to the 3'UTR of HIF1A mRNA, as well as suppresses tube formation of primary human umbilical vein endothelial cells (HUVECs) and breast cancer angiogenesis by decreasing the secretion of VEGFA. Importantly, expression of miR-153 was induced by hypoxia-stimulated ER stress, which activates IRE1α and its downstream transcription factor XBP1. XBP1 directly binds to the promoter of the miR-153 host gene PTPRN and activates transcription. These results indicate that hypoxia induces miR-153 to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis and miR-153 could be used for breast cancer anti-angiogenesis therapy. Citation Format: Huichun Liang, Zhongmei Zhou, Ceshi Chen. Hypoxia induces miR-153 through the IRE1α-XBP1 pathway to fine-tune the HIF1α/VEGFA axis in breast cancer angiogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2042.
Abstract 12721: Compensatory Mechanism in HCM Patients With Preserved LV Ejection Fraction Determined by 2D Speckle Tracking Echocardiographic LV Myocardial Strain Gradient Using a Novel Multi-Layer Technique
Authors: Koya Ozawa, Nobusada Funabashi, Hiroyuki Takaoka, Yoshio Kobayashi
Journal: Circulation (2014)

Introduction: A novel multi-layer technique on speckle tracking transthoracic echocardiography (TTE) can achieve quantitative strain measurements of all, subendocardial, and subepicardial layer of left ventricle (LV), respectively. Aim: To evaluate compensatory mechanism in hypertrophic cardiomyopathy (HCM) subjects with preserved LV ejection fraction (EF), we measured myocardial strain gradient by 2D LV global longitudinal (GLS) and circumferential strain (GCS) using a multi-layer technique on speckle tracking TTE. Methods: 60 subjects (40 HCM (30 male; age 62 ± 15 years, LV EF &gt;50%, and 20 age matched controls (10 male; age 59 ± 10 years)) underwent TTE (Vivid E9, GE). Apical 4-, 2-, 3-chamber views for GLS and parasternal short-axis views at the level of mitral valve, papillary muscle, and apex for GCS were acquired. We defined myocardial strain gradient as the ratio of subendocardial strain to subepicardial strain. Results: GLS from each view were significantly smaller in HCM than controls in all, subendocardial, and subepicardial layers. GCS at all levels were significantly smaller in HCM than controls in all and subepicardial layer; however there were no significant differences in subendocardial GCS between both groups at mitral valve and papillary muscle levels. GLS gradient was significant greater in HCM than controls in GLS from 4 chamber views. GCS gradients were significantly greater in HCM than in controls at all levels. In HCM, subendocardial GCS at mitral valve and papillary muscle levels significantly positive correlated with LV EF (R=0.446, 0.34, respectively) and subendocardial GLS from 4-, and 2- chamber views, and subendocardial GCS at mitral valve and papillary muscles levels significantly negatively and GCS gradients at mitral valve and papillary muscle levels significantly positively correlated with interventricular septum thickness in end diastole (R=-0.44, -0.347, -0.335, -0.359, 0.363, and 0.373, respectively). Conclusions: In HCM subjects with preserved LV EF, GLS was significantly smaller than in controls, but GLS and GCS gradients tended to be greater than controls. We speculate that in HCM, subendocardial GCS was maintained in compensation for subendocardial GLS decrement; thus GCS gradient may increase.
The Role of Fibrinogen-Like Protein 2 on Immunosuppression and Malignant Progression in Glioma
Authors: Khatri Latha, Jun Yan, Yuhui Yang, Loyola V Gressot, Ling-Yuan Kong, Ganiraju Manyam, Ravesanker Ezhilarasan, Qianghu Wang, Erik P Sulman, R Eric Davis, Suyun Huang, Gregory N Fuller, Arvind Rao, Amy B Heimberger, Shulin Li, Ganesh Rao
Journal: JNCI Journal of the National Cancer Institute (2018)

Virtually all low-grade gliomas (LGGs) will progress to high-grade gliomas (HGGs), including glioblastoma, the most common malignant primary brain tumor in adults. A key regulator of immunosuppression, fibrinogen-like protein 2 (FGL2), may play an important role in the malignant transformation of LGG to HGG. We sought to determine the mechanism of FGL2 on tumor progression and to show that inhibiting FGL2 expression had a therapeutic effect. We analyzed human gliomas that had progressed from low- to high-grade for FGL2 expression. We modeled FGL2 overexpression in an immunocompetent genetically engineered mouse model to determine its effect on tumor progression. Tumors and their associated microenvironments were analyzed for their immune cell infiltration. Mice were treated with an FGL2 antibody to determine a therapeutic effect. Statistical tests were two-sided. We identified increased expression of FGL2 in surgically resected tumors that progressed from low to high grade (n = 10). The Cancer Genome Atlas data showed that LGG cases with overexpression of FGL2 (n = 195) had statistically significantly shorter survival (median = 62.9 months) compared with cases with low expression (n = 325, median = 94.4 months, P < .001). In a murine glioma model, HGGs induced with FGL2 exhibited a mesenchymal phenotype and increased CD4+ forkhead box P3 (FoxP3)+ Treg cells, implicating immunosuppression as a mechanism for tumor progression. Macrophages in these tumors were skewed toward the immunosuppressive M2 phenotype. Depletion of Treg cells with anti-FGL2 statistically significantly prolonged survival in mice compared with controls (n = 11 per group, median survival = 90 days vs 62 days, P = .004), shifted the phenotype from mesenchymal HGG to proneural LGG, and decreased M2 macrophage skewing. FGL2 facilitates glioma progression from low to high grade. Suppressing FGL2 expression holds therapeutic promise for halting malignant transformation in glioma.
Genomic surveillance of avian-origin influenza A viruses causing human disease
Authors: Tommy T. Lam, Oliver G. Pybus
Journal: Genome Medicine (2018)

Avian influenza A viruses (AIVs) pose a threat to global health because of their sporadic zoonotic transmission and potential to cause pandemics. Genomic surveillance of AIVs has become a powerful, cost-effective approach for studying virus transmission, evolution, and dissemination, and has the potential to inform outbreak control efforts and policies.
Allow English women to take medical abortion pill at home, say doctors
Authors: Jacqui Thornton
Journal: BMJ (2018)

Wales has joined Scotland in allowing women to take the medical abortion drug misoprostol at home, sparking calls for England to follow and “extend them the same dignity.”

Currently in England, women who have an early medical abortion take one drug, mifepristone, in the clinic then need to return to take a second drug, misoprostol, 36-48 hours later.

On 29 June, Vaughan Gething, the Welsh government’s cabinet secretary for health and social services, announced a change in the rules to …
Abstract P358: Dietary Fat Quality and Risk of CHD in the 28 Year Follow-up of a Large Prospective Study of US Women
Authors: Stephanie E Chiuve, Frank B Hu, Christine M Albert, Kathryn M Rexrode, JoAnn E Manson, Walter C Willett, Eric B Rimm
Journal: Circulation (2012)

Background: The importance of fat quality is reflected in the recent 2010 Dietary Guidelines for Americans, which recommend reducing saturated fat intake, and replacing this with polyunsaturated fat. Health effects of dietary fat are often estimated as an isocaloric substitution with carbohydrates (nutrient density models). Expressing fat intake as a % of total fat instead better quantifies fat quality, in overall diet and individual foods, and may provide an alternative approach to evaluate associated disease risk. We evaluated this novel measure of dietary fat quality, the % of fat type relative to total fat intake, on CHD risk among women in the Nurses' Health Study. Methods: We followed 84,531 women, free of chronic disease at baseline, from 1980-2008. Data on diet and other factors were ascertained every 2-4 years via questionnaires. For saturated and polyunsaturated fats, fat quality was calculated as grams of fat type / grams of total fat, and included in Cox proportional hazards models with total fat (fat density model), to estimate the association between fat intake and risk of CHD. We also estimated these associations using traditional nutrient density models, with isocaloric replacement of fat with carbohydrates. Results: Over 28 years, there were 3373 cases of CHD. A greater proportion of fat intake as saturated fat was associated with higher risk of CHD (p, trend&lt;0.001) ( Table ). Conversely, a greater proportion of fat intake as polyunsaturated fat was associated with lower risk (p, trend&lt;0.001), which was seen for both N-6 and N-3 fats. Compared with nutrient density models, RR obtained from fat density models were greater in magnitude for saturated and N-3 fats, but similar in magnitude for total and N-6 polyunsaturated fat. Conclusions: Saturated and polyunsaturated fat, quantified as a % of total fat, were significantly associated with CHD risk. This novel measure of dietary fat may aid in the translation of dietary recommendations of fat quality and may provide guidance in distinguishing foods based on fat quality.
T cell senescence and CAR-T cell exhaustion in hematological malignancies
Authors: Dimitri Kasakovski, Ling Xu, Yangqiu Li
Journal: Journal of Hematology & Oncology (2018)

T cell senescence has been recognized to play an immunosuppressive role in the aging population and cancer patients. Strategies dedicated to preventing or reversing replicative and premature T cell senescence are required to increase the lifespan of human beings and to reduce the morbidity from cancer. In addition, overcoming the T cell terminal differentiation or senescence from lymphoma and leukemia patients is a promising approach to enhance the effectiveness of adoptive cellular immunotherapy (ACT). Chimeric antigen receptor T (CAR-T) cell and T cell receptor-engineered T (TCR-T) cell therapy highly rely on functionally active T cells. However, the mechanisms which drive T cell senescence remain unclear and controversial. In this review, we describe recent progress for restoration of T cell homeostasis from age-related senescence as well as recovery of T cell activation in hematological malignancies.
The Role of Nutraceuticals in Statin Intolerant Patients
Authors: Maciej Banach, Angelo Maria Patti, Rosaria Vincenza Giglio, Arrigo F.G. Cicero, Atanas G. Atanasov, Gani Bajraktari, Eric Bruckert, Olivier Descamps, Dragan M. Djuric, Marat Ezhov, Zlatko Fras, Stephan von Haehling, Niki Katsiki, Michel Langlois, Gustavs Latkovskis, G.B. John Mancini, Dimitri P. Mikhailidis, Olena Mitchenko, Patrick M. Moriarty, Paul Muntner, Dragana Nikolic, Demosthenes B. Panagiotakos, Gyorgy Paragh, Bernhard Paulweber, Daniel Pella, Christos Pitsavos, Željko Reiner, Giuseppe M.C. Rosano, Robert S. Rosenson, Jacek Rysz, Amirhossein Sahebkar, Maria-Corina Serban, Dragos Vinereanu, Michal Vrablík, Gerald F. Watts, Nathan D. Wong, Manfredi Rizzo
Journal: Journal of the American College of Cardiology (2018)
Abstract 3536: SENP1 is a p53 deSUMOylating enzyme and its depletion induces p53 activity
Authors: Mushui Dai, Krishna Chauhan, Yingxiao Chen, Xiao-Xin Sun
Journal: Cancer Research (2018)

Abstract SUMOylation plays important roles in diverse cellular processes by regulating protein-protein interaction, protein localization, trafficking, stability and activity. p53 can by SUMOyalted at lysine (K) 384. Yet, how SUMOylation regulates p53 activity remain unclear. SUMOylation can be revered by a group of proteins called deSUMOylating enyzme including the SUMO specific protease (SENP) family proteins. How p53 is regulated by deSUMOylation is also not well understood. Here, we show that SENP1 directly interacts with and desumoylates p53 in cells and in vitro. Depletion of SENP1 by siRNA-mediated knockdown drastically increased the p53 transactivation activity without inducing p53 protein levels, resulting p53-depndent cell cycle arrast. Further, SENP1 knockdown significantly promoted p53 transactivation activity in cells following DNA damage. Additionally, we found that SENP1 binds to and deSUMOylates PML and aborageted the enhancing effect of PML on p53 SUMOylation. Thus, SNEP1 is novel p53 desumoylating enzyme that regulates p53 activity but not its stability. Citation Format: Mushui Dai, Krishna Chauhan, Yingxiao Chen, Xiao-Xin Sun. SENP1 is a p53 deSUMOylating enzyme and its depletion induces p53 activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3536.
Exploiting Viruses to Treat Diseases
Authors: Dan L. Longo, Lindsey R. Baden
Journal: New England Journal of Medicine (2018)

Viruses have evolved to cause both indolent and explosive disease outbreaks, with millions of people infected with the human immunodeficiency virus and hepatitis viruses and with the current outbreaks of Ebola, yellow fever, and Zika viruses in various parts of the world. As a result of intense study, we have learned how viruses cause disease, which genes are responsible, and how they work. The resultant discoveries have led to the development of improved vaccines1 and the development of strategies to exploit features of viruses for therapeutic purposes. For example, the ability of viruses to transfer genetic material to target cells . . .
The TWIK2 Potassium Efflux Channel in Macrophages Mediates NLRP3 Inflammasome-Induced Inflammation
Authors: Anke Di, Shiqin Xiong, Zhiming Ye, R.K. Subbarao Malireddi, Satoshi Kometani, Ming Zhong, Manish Mittal, Zhigang Hong, Thirumala-Devi Kanneganti, Jalees Rehman, Asrar B. Malik
Journal: Immunity (2018)