tbuckley/cabot-search huggingface dataset:
Gene expression profiles in zinc-deficient versus zinc replenished rat esophagus
Authors: Louise Y. Fong, Liang Zhang, Chang-Gong Liu, Kay Huebner
Journal: Cancer Research (2004)

1666  Zinc replenishment (ZR) in carcinogen-treated zinc-deficient (ZD) rats rapidly reverses esophageal cell proliferation by stimulating apoptosis and thereby arrests cancer development. We used oligonucleotide-arrays to compare the expression profiles of genes in the proliferative ZD versus control zinc-sufficient (ZS) esophagi, and those in ZR esophagi at 8 h, 12 h, and 48 h after ZD rats were dosed with intragastric zinc. Twenty-four weanling rats were fed a ZD diet ad libitum and 6 ZS animals pair-fed to match the decreased food consumption of ZD rats. After 6 weeks, ZD rat esophagi developed sustained cell proliferation. Zinc gluconate (containing 1.2 mg elemental Zn) in saline was then administered intragastrically to 18 ZD rats, which were switched to ZS diet to form the ZR group. ZS rats and the remaining ZD rats were treated with saline. At 8 h, 12 h, and 48 h after replenishment, 6 rats were sacrificed, forming the ZR-8, ZR-12, and ZR-48 groups. ZS and ZD rats were sacrificed 8 h after saline treatment. Whole esophagi were excised and esophageal epithelium isolated. RNA was prepared separately from pooled ZS, ZD, and ZR rat esophageal mucosa, labeled, and hybridized to the CodeLink Uniset Rat 1 Bioarray chip (Amersham Biosciences, NJ), carrying single-stranded oligonucleotide probes from ∼10,000 rat genes. Array images and data were analyzed by GeneSpring 5.1 (Silicon Genetics, CA). After replenishment, serum Zn content (μg/100 ml ± SD) surged from a ZD level of 43 ± 14 to 524 ± 221 and 610 ± 255 at 8 h and 12 h, respectively, and reverted to 206 ± 55 at 48 h, approaching the level in ZS rats (124 ± 14). Comparing the expression profiles of ZD versus ZS, a total of 33 genes showed a > 2-fold change in expression (21 were up-, and 12 downregulated). Notably, all of these 33 genes demonstrated a return to near normalcy at 48 h after ZR as compared with ZS. For example, ultraviolet B radiation-activated gene, went from a 8.7-fold increase in the proliferative ZD esophagi to a 3.3-fold increase in the nearly restored ZR-48 esophagi. Keratin 14, an important biomarker in esophageal carcinogenesis, improved from a 7-fold increase in ZD to a 1.81-fold increase in ZR-48 esophagus. Similarly, Cyclin B was up ∼4-fold in the proliferative ZD tissue but was almost back to ZS levels by 48 h post replenishment. These data illustrate that a select number of genes in the rat esophagus are highly responsive to zinc deprivation and replenishment, are induced during rapid transition from zinc deficiency to sufficiency and may be responsible for a reversal of the precancerous environment in the ZD esophagus. Thus, the characterization of these identified genes and their products will be useful in understanding the genetic mechanism involved in esophageal tumor initiation and reversal.
Primary Agranulocytic Angina
Authors: I. M. Librach, R. G. Cronin
Journal: BMJ (1946)

In view of its comparative rarity, we feel that it is worth while reporting the following case, which was treated by continuous intramuscular drip pentose nucleotide and oral sodium n ticleinate.Case Record A married fitter aged 30 was first admitted to hospital on May 27, 1943, with a history of pains in the knees, ankles, and the left elbow, wrist, and fingers of five days' duration.He was a moderate drinker and smoker.The previous history included an attack of rheumatic fever at the age of 7.On examination his temperature was 100°F.(37.8°C.), pulse 80, espiration 22.He looked pale, but had no other gross physical signs.The urine was normal; the blood sedimentation rate was 78 mm. in one hour.He was thought to be suffering from acute rheumatism, and was given salicylates, with little or no effect.On June 1 an ulcer of the gum was noted, and three days later several more had appeared, with a lymphadenitis of the deep cervical glands.The white cell count was 2,400 per c.mm. (neutrophil polymorphs 17%, lymphocytes 69%, and monocytes 14%).Haemoglobin and red cell count were notmal.He was given
Analyzing human sleep EEG: A methodological primer with code implementation
Authors: Roy Cox, Juergen Fell
Journal: Sleep Medicine Reviews (2020)

Recent years have witnessed a surge in human sleep electroencephalography (EEG) studies, employing increasingly sophisticated analysis strategies to relate electrophysiological activity to cognition and disease. However, properly calculating and interpreting metrics used in contemporary sleep EEG requires attention to numerous theoretical and practical signal-processing details that are not always obvious. Moreover, the vast number of outcome measures that can be derived from a single dataset inflates the risk of false positives and threatens replicability. We review several methodological issues related to 1) spectral analysis, 2) montage choice, 3) extraction of phase and amplitude information, 4) surrogate construction, and 5) minimizing false positives, illustrating both the impact of methodological choices on downstream results, and the importance of checking processing steps through visualization and simplified examples. By presenting these issues in non-mathematical form, with sleep-specific examples, and with code implementation, this paper aims to instill a deeper appreciation of methodological considerations in novice and non-technical audiences, and thereby help improve the quality of future sleep EEG studies.
Deciphering and predicting CD4+ T cell immunodominance of influenza virus hemagglutinin
Authors: Antonino Cassotta, Philipp Paparoditis, Roger Geiger, Ramgopal R. Mettu, Samuel J. Landry, Alessia Donati, Marco Benevento, Mathilde Foglierini, David J.M. Lewis, Antonio Lanzavecchia, Federica Sallusto
Journal: The Journal of Experimental Medicine (2020)

The importance of CD4+ T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naive and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naive and memory CD4+ T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naive CD4+ T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry–based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naive T cells specific for cryptic H1-HA peptides and demonstrate that antigen processing represents a major constraint determining immunodominance.
Pancreatitis and Systemic Lupus Erythematosus
Journal: New England Journal of Medicine (1958)

Gastrointestinal symptoms in patients with SLE are common, specifically abdominal pain.However, the rate of pancreatic diseases is much lower and does not reach 5% according to published series in Europe and the USA.This association between SLE and pancreatic disease is basically at the expense of episodes of acute pancreatitis.An association with chronic pancreatitis is much more uncommon, and only four articles have been published showing this relationship.Three cases of SLE-associated pancreatitis are described, and disease onset, etiological factors, and clinical progression are analyzed.A review of the literature and a brief discussion about pathophysiological mechanisms and the role of corticosteroids are also included.
Rheumatic disease and COVID-19
Authors: Jean W Liew, Elizabeth R Graef
Journal: Annals of the Rheumatic Diseases (2020)

We appreciated the letter from Monti et al , which was the first dedicated report of patients with rheumatic disease who have been diagnosed with COVID-19.1 We have also reviewed the response from Joob and Wiwanitkit,2 which unfortunately perpetuates the notion that individuals with systemic lupus erythematosus (SLE) or other rheumatic disease may be protected from COVID-19 infection via hydroxychloroquine use. Although the origins of this claim are not entirely clear, they may arise from the fact that rheumatic or autoimmune diseases were not initially reported among other comorbidities in the first large Chinese case …
Will the COVID-19 pandemic worsen the obesity epidemic?
Authors: Christoffer Clemmensen, Michael Bang Petersen, Thorkild I. A. Sørensen
Journal: Nature Reviews Endocrinology (2020)

The sudden outbreak and global spread of COVID-19 represents one of the most profound societal and public health challenges in modern times. In this Comment, we call attention to the possibility that the societal strategies implemented to oppose COVID-19 might have long-term, negative effects on the obesity epidemic.
Low-Dose Metformin Reprograms the Tumor Immune Microenvironment in Human Esophageal Cancer: Results of a Phase II Clinical Trial
Authors: Shuhong Wang, Yusheng Lin, Xiao Xiong, Lu Wang, Yi Guo, Yuping Chen, Shaobin Chen, Geng Wang, Peng Lin, Hongcai Chen, Sai-Ching Jim Yeung, Edwin Bremer, Hao Zhang
Journal: Clinical Cancer Research (2020)

The tumor immune microenvironment (TIME) has an important impact on response to cancer immunotherapy using immune checkpoint inhibitors. Specifically, an "infiltrated-excluded"/"cold" TIME is predictive of poor response. The antidiabetic agent metformin may influence anticancer immunity in esophageal squamous cell carcinoma (ESCC).We analyzed matched pre- and posttreatment ESCC specimens in a phase II clinical trial of low-dose metformin treatment (250 mg/day) to evaluate direct anti-ESCC activity and TIME reprogramming. Follow-up correlative studies using a carcinogen-induced ESCC mouse model were performed with short-term (1 week) or long-term (12 weeks) low-dose metformin (50 mg/kg/day) treatment.In the clinical trial, low-dose metformin did not affect proliferation or apoptosis in ESCC tumors as assayed by Ki67 and cleaved caspase-3 immunostaining. However, metformin reprogrammed the TIME toward "infiltrated-inflamed" and increased the numbers of infiltrated CD8+ cytotoxic T lymphocyte and CD20+ B lymphocyte. Further, an increase in tumor-suppressive (CD11c+) and a decrease in tumor-promoting (CD163+) macrophages were observed. Metformin augmented macrophage-mediated phagocytosis of ESCC cells in vitro. In the ESCC mouse model, short-term metformin treatment reprogrammed the TIME in a similar fashion to humans, whereas long-term treatment further shifted the TIME toward an active state (e.g., reduction in CD4+ FoxP3+ regulatory T cells) and inhibited ESCC growth. In both humans and mice, metformin triggered AMPK activation and STAT3 inactivation, and altered the production of effector cytokines (i.e., TNFα, IFNγ, and IL10) in the immune cells.Low-dose metformin reprograms the TIME to an activated status and may be a suitable immune response modifier for further investigation in patients with ESCC.
Circadian Rhythm Is Disrupted by ZNF704 in Breast Carcinogenesis
Authors: Chao Yang, Jiajing Wu, Xinhua Liu, Yue Wang, Beibei Liu, Xing Chen, Xiaodi Wu, Dong Yan, Lulu Han, Shumeng Liu, Lin Shan, Yongfeng Shang
Journal: Cancer Research (2020)

Abstract Copy number gain in chromosome 8q21 is frequently detected in breast cancer, yet the oncogenic potential underlying this amplicon in breast carcinogenesis remains to be delineated. We report here that ZNF704, a gene mapped to 8q21, is recurrently amplified in various malignancies including breast cancer. ZNF704 acted as a transcriptional repressor and interacted with the transcriptional corepressor SIN3A complex. Genome-wide interrogation of transcriptional targets revealed that the ZNF704/SIN3A complex represses a panel of genes including PER2 that are critically involved in the function of the circadian clock. Overexpression of ZNF704 prolonged the period and dampened the amplitude of the circadian clock. ZNF704 promoted the proliferation and invasion of breast cancer cells in vitro and accelerated the growth and metastasis of breast cancer in vivo. Consistently, the level of ZNF704 expression inversely correlated with that of PER2 in breast carcinomas, and high level of ZNF704 correlated with advanced histologic grades, lymph node positivity, and poor prognosis of patients with breast cancer, especially those with HER2+ and basal-like subtypes. These results indicate that ZNF704 is an important regulator of the circadian clock and a potential driver for breast carcinogenesis. Significance: This study indicates that ZNF704 could be a potential oncogenic factor, disrupting circadian rhythm of breast cancer cells and contributing to breast carcinogenesis.
Erratum to: “Significant fibrosis predicts new-onset diabetes mellitus and arterial hypertension in patients with NASH (J Hepatol 2020; 73: 17–25)
Authors: Javier Ampuero, Rocío Aller, Rocío Gallego-Durán, Javier Crespo, José Luis Calleja, Carmelo García-Monzón, Judith Gómez-Camarero, Joan Caballería, Oreste Lo Iacono, Luis Ibañez, Javier García-Samaniego, Agustín Albillos, Rubén Francés, Conrado Fernández-Rodríguez, Moisés Diago, Germán Soriano, Raúl J. Andrade, Raquel Latorre, Francisco Jorquera, Rosa María Morillas, Desamparados Escudero, Pamela Estévez, Manuel Hernandez-Guerra, Salvador Augustín, Jesús Bañales, Patricia Aspichueta, Salvador Benlloch, José Miguel Rosales, Javier Salmerón, Juan Turnes, Manuel Romero-Gómez
Journal: Journal of Hepatology (2020)
P-18 REMARRY and PURSUIT trials: Liquid biopsy-guided re-challenge of anti-EGFR monoclonal antibody for patients with RAS/BRAF V600E wild-type metastatic colorectal cancer
Authors: H. Nakajima, D. Kotani, E. Oki, T. Kato, E. Shinozaki, Y. Sunakawa, H. Bando, K. Yamazaki, S. Yuki, T. Yoshino, T. Yamanaka, T. Ohta, H. Taniguchi, Y. Kagawa
Journal: Annals of Oncology (2020)
Bovine pestivirus is a new alternative virus for multiple myeloma oncolytic virotherapy
Authors: Valentina Marchica, Valentina Franceschi, Rosanna Vescovini, Paola Storti, Emanuela Vicario, Denise Toscani, Alessia Zorzoli, Irma Airoldi, Benedetta Dalla Palma, Nicoletta Campanini, Eugenia Martella, Cristina Mancini, Federica Costa, Gaetano Donofrio, Nicola Giuliani
Journal: Journal of Hematology & Oncology (2020)

Abstract Background The oncolytic viruses have shown promising results for the treatment of multiple myeloma. However, the use of human viruses is limited by the patients’ antiviral immune response. In this study, we investigated an alternative oncolytic strategy using non-human pathogen viruses as the bovine viral diarrhea virus (BVDV) that were able to interact with CD46. Methods We treated several human myeloma cell lines and non-myeloma cell lines with BVDV to evaluate the expression of CD46 and to study the effect on cell viability by flow cytometry. The possible synergistic effect of bortezomib in combination with BVDV was also tested. Moreover, we infected the bone marrow mononuclear cells obtained from myeloma patients and we checked the BVDV effect on different cell populations, defined by CD138, CD14, CD3, CD19, and CD56 expression evaluated by flow cytometry. Finally, the in vivo BVDV effect was tested in NOD-SCID mice injected subcutaneously with myeloma cell lines. Results Human myeloma cells were selectively sensitive to BVDV treatment with an increase of cell death and, consequently, of apoptotic markers. Consistently, bone marrow mononuclear cells isolated from myeloma patients treated with BVDV, showed a significant selective decrease of the percentage of viable CD138 + cells. Interestingly, bortezomib pre-treatment significantly increased the cytotoxic effect of BVDV in myeloma cell lines with a synergistic effect. Finally, the in vitro data were confirmed in an in vivo myeloma mouse model showing that BVDV treatment significantly reduced the tumoral burden compared to the vehicle. Conclusions Overall, our data indicate, for the first time, a direct oncolytic effect of the BVDV in human myeloma cells suggesting its possible use as novel alternative anti-myeloma virotherapy strategy.
心房細動のカテーテルアブレーションに8.5F可変シースを用いる単一穿刺三シース(single-puncture three-seath)後の医原性心房中隔欠損症の発生率
Authors: Inoue Yoshiaki, Shirota Kinya, Ishii Hiroshige, Tsunoda Fumiyo, Mimura Asao, Kondo Takehito, Morishita Takaomi, Mukai Natsuko
Journal: Circulation (2012)
Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort
Authors: Jasmohan S Bajaj, Guadalupe Garcia-Tsao, Scott W Biggins, Patrick S Kamath, Florence Wong, Sara McGeorge, Jawaid Shaw, Meredith Pearson, Micheal Chew, Andrew Fagan, Randolph de la Rosa Rodriguez, Janelle Worthington, Amy Olofson, Vanessa Weir, Calvin Trisolini, Sarah Dwyer, K Rajender Reddy
Journal: Gut (2020)

Objective Comorbid conditions are associated with poor prognosis in COVID-19. Registry data show that patients with cirrhosis may be at high risk. However, outcome comparisons among patients with cirrhosis+COVID-19 versus patients with COVID-19 alone and cirrhosis alone are lacking. The aim of this study was to perform these comparisons. Design A multicentre study of inpatients with cirrhosis+COVID-19 compared with age/gender-matched patients with COVID-19 alone and cirrhosis alone was performed. COVID-19 and cirrhosis characteristics, development of organ failures and acute-on-chronic liver failure (ACLF) and mortality (inpatient death+hospice) were compared. Results 37 patients with cirrhosis+COVID-19 were matched with 108 patients with COVID-19 and 127 patients with cirrhosis from seven sites. Race/ethnicity were similar. Patients with cirrhosis+COVID-19 had higher mortality compared with patients with COVID-19 (30% vs 13%, p=0.03) but not between patients with cirrhosis+COVID-19 and patients with cirrhosis (30% vs 20%, p=0.16). Patients with cirrhosis+COVID-19 versus patients with COVID-19 alone had equivalent respiratory symptoms, chest findings and rates of intensive care unit transfer and ventilation. However, patients with cirrhosis+COVID-19 had worse Charlson Comorbidity Index (CCI 6.5±3.1 vs 3.3±2.5, p&lt;0.001), lower presenting GI symptoms and higher lactate. Patients with cirrhosis alone had higher cirrhosis-related complications, maximum model for end-stage liver disease (MELD) score and lower BiPAP/ventilation requirement compared with patients with cirrhosis+COVID-19, but CCI and ACLF rates were similar. In the entire group, CCI (OR 1.23, 95% CI 1.11 to 1.37, p&lt;0.0001) was the only variable predictive of mortality on multivariable regression. Conclusions In this multicentre North American contemporaneously enrolled study, age/gender-matched patients with cirrhosis+COVID-19 had similar mortality compared with patients with cirrhosis alone but higher than patients with COVID-19 alone. CCI was the only independent mortality predictor in the entire matched cohort.
Non-coding RNAs: update on mechanisms and therapeutic targets from the ESC Working Groups of Myocardial Function and Cellular Biology of the Heart
Authors: Christian Bär, Shambhabi Chatterjee, Inês Falcão Pires, Patrícia Rodrigues, Joost P G Sluijter, Reinier A Boon, Rosa M Nevado, Vicente Andrés, Marida Sansonetti, Leon de Windt, Michele Ciccarelli, Nazha Hamdani, Stephane Heymans, Raquel Figuinha Videira, Carlo G Tocchetti, Mauro Giacca, Serena Zacchigna, Stefan Engelhardt, Stefanie Dimmeler, Rosalinda Madonna, Thomas Thum
Journal: Cardiovascular Research (2020)

Vast parts of mammalian genomes are actively transcribed, predominantly giving rise to non-coding RNA (ncRNA) transcripts including microRNAs, long ncRNAs, and circular RNAs among others. Contrary to previous opinions that most of these RNAs are non-functional molecules, they are now recognized as critical regulators of many physiological and pathological processes including those of the cardiovascular system. The discovery of functional ncRNAs has opened up new research avenues aiming at understanding ncRNA-related disease mechanisms as well as exploiting them as novel therapeutics in cardiovascular therapy. In this review, we give an update on the current progress in ncRNA research, particularly focusing on cardiovascular physiological and disease processes, which are under current investigation at the ESC Working Groups of Myocardial Function and Cellular Biology of the Heart. This includes a range of topics such as extracellular vesicle-mediated communication, neurohormonal regulation, inflammation, cardiac remodelling, cardio-oncology as well as cardiac development and regeneration, collectively highlighting the wide-spread involvement and importance of ncRNAs in the cardiovascular system.
Abstract 13801: Cost-Effectiveness Analysis of Implantable Cardiac Devices in Patients With Systolic Heart Failure: A US Perspective Using Real World Data
Authors: Xiaoxiao Lu, Victoria F Paly, Dhvani Shah, Stelios Tsintzos
Journal: Circulation (2019)

Introduction: A cost-effectiveness analysis (CEA) of implantable cardioverter defibrillator devices (ICD), cardio resynchronisation therapy pacemakers (CRT-P), combination therapy (CRT-D), and opti...
Identification of DNA damage-dependent checkpoint kinase 1 (Chk1) posttranslational modifications and associated proteins
Authors: Eugenia M. Yazlovitskaya, Jennifer A. Pietenpol
Journal: Cancer Research (2004)

801  DNA damage checkpoints are regulatory signal transduction pathways that allow cells to control DNA damage-induced cell cycle arrest, DNA repair, and cell death by apoptosis. Most human tumors arise from multiple genetic changes, including defective DNA damage checkpoints that provide potential targets for therapeutic use of DNA-damaging agents. One strategy to enhance the impact of these agents is to inhibit the checkpoint signaling in cancer cells. The checkpoint kinase 1 (Chk1) is one of the effector kinases that regulates cell cycle progression after DNA damage. Upon DNA damage, Chk1 is phosphorylated on Ser 345 and 317, and this phosphorylation is dependent on ATM (ataxia-telangiectasia mutated) or ATR (ATM and Rad 3-related). In addition to phosphorylation, DNA damage-dependent Chk1 activity could be modulated by other posttranslational modifications and protein-protein interaction. We have developed experimental procedures for identification of novel Chk1 posttranslational modifications and associated proteins. Using immunoprecipitation followed by mass spectroscopy analysis, we have found novel candidate Chk1-associated proteins. Potentially, interaction of these proteins with Chk1 could inhibit DNA damage-dependent Chk1 activation, leading to abrogation of checkpoint response and sensitization of cancer cells to DNA-damaging drugs.
Human milk oligosaccharide profiles and allergic disease up to 18 years
Authors: Caroline J. Lodge, Adrian J. Lowe, Elasma Milanzi, Gayan Bowatte, Michael J. Abramson, Helen Tsimiklis, Christine Axelrad, Bianca Robertson, Aaron E. Darling, Cecilie Svanes, Matthias Wjst, Shyamali C. Dharmage, Lars Bode
Journal: Journal of Allergy and Clinical Immunology (2020)
P-306 Survival and recurrence of patients operated on for stomach cancer and its determinants
Authors: B. Amal, W. Farhat, M. Ben Mabrouk, M. Said, A. Mizouni, A. Ben Ali, H. Sboui, I. Belaid, C. Imene, E. Faten, N. Ammar, H. Makram, B. Leila, B. Slim
Journal: Annals of Oncology (2020)