tbuckley/cabot-search huggingface dataset:
Reassessing the Link between Airborne Arsenic Exposure among Anaconda Copper Smelter Workers and Multiple Causes of Death Using the Parametric g-Formula
Authors: Alexander P. Keil, David B. Richardson
Journal: Environmental Health Perspectives (2016)

Prior studies have indicated associations between ingestion of inorganic arsenic and ischemic heart disease, nonmalignant respiratory disease, and lung, skin, bladder, and kidney cancers. In contrast, inhaled arsenic has been consistently associated only with lung cancer. Evidence for health effects of inhaled arsenic derives mainly from occupational studies that are subject to unique biases that may attenuate or obscure such associations.
Identification of<i>LCK</i>mutation in a family with atypical epidermodysplasia verruciformis with T-cell defects and virus-induced squamous cell carcinoma
Authors: S.-L. Li, L.-N. Duo, H.-J. Wang, W. Dai, E.-Y.H. Zhou, Y.-N. Xu, T. Zhao, Y.-Y. Xiao, L. Xia, Z.-H. Yang, L.-T. Zheng, Y.-Y. Hu, Z.-M. Lin, H.-N. Wang, T.-W. Gao, C.-L. Ma, Y. Yang, C.-Y. Li
Journal: British Journal of Dermatology (2016)

Inherited epidermodysplasia verruciformis (EV) is a rare skin disorder characterized by susceptibility to specific types of human papilloma virus (HPV) and is strongly associated with skin carcinomas. Inactivating mutations in EVER1/EVER2 account for most cases of EV. However, more phenotypes related to but distinct from EV have been reported with an immunodeficiency state but without EVER1/EVER2 mutation, and the genetic basis for these atypical EV cases is poorly understood.To identify the causative gene responsible for three siblings affected by atypical EV but without EVER1/EVER2 mutation.Whole-exome sequencing followed by Sanger sequencing was performed to identify the gene responsible for the patients with atypical EV enrolled in our study.A homozygous splicing mutation was detected in LCK (c.188-2A>G). This mutation resulted in an exon 3 deletion T lymphocyte-specific protein tyrosine kinase isoform, which further led to frameshift mutation and subsequent mRNA decay.We demonstrate a novel mutation in LCK in a family affected by atypical EV with T-cell defects, HPV infection and virus-induced malignancy, providing new clues in the understanding of host defences against HPV and better genetic counselling of patients with the EV phenotype.
First-line gefitinib for elderly patients harboring EGFR mutations.
Authors: K. Asami, T. Koizumi, S. Amejima, A. Morikawa, N. Morozumi, K. Hirai
Journal: Journal of Clinical Oncology (2010)

e18094 Background: Potential treatment strategies for elderly patients (pts) with advanced non-small cell lung cancer (NSCLC) have not been well investigated. Gefitinib has demonstrated clinical benefit in pts with NSCLC harboring mutations of the epidermal growth factor receptor (EGFR). This phase II study aimed to investigate the efficacy and tolerability of gefitinib as first-line treatment for elderly pts with advanced lung adenocarcinoma harboring EGFR mutations. Methods: Chemotherapy-naïve advanced lung adenocarcinoma pts aged 75 years or older who had EGFR mutations (exon 19 del or L858R) were enrolled and received daily doses of 250mg of gefitinib. The primary endpoint was response rate (RR). Secondary endpoints were toxicity, disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). This study required 12 cases as sample size to show its efficacy exceeding the lower limit of interest 30% with alpha = 0.05 (one side) and beta = 0.1. Results: From April 2008 to November 2009, 15 lung adenocarcinoma pts were enrolled (median age: 79, female/male: 10/5, PS 0/1/2: 4/8/3, stage IIIB/IV: 2/13, never smoker/smoker: 9/6, exon 19 del/L858R: 6/9). Overall response rate was 60% (95%CI: 36.0-80.9%) and DCR was 87% (95%CI: 63.7-97.6%) (CR/PR/SD/PD: 2/7/4/2). Grade 3 skin rash and liver toxicity occurred in 2 patients, respectively, but none experienced lung toxicities. Median PFS was 10.4 months (95% CI: 7.2-13.6) and median OS has not been attained yet. Conclusions: First-line gefitinib was effective for and tolerated by elderly patients with EGFR mutations. Gefitinib can be recommended for this population as a standard treatment. No significant financial relationships to disclose.
The effect of hypoxia and re-oxygenation on adipose tissue lipolysis in COPD patients
Authors: Andrea Plihalova, Hana Bartakova, Martina Vasakova, Sumeet Gulati, Isabelle deGlisezinski, Vladimir Stich, Jan Polak
Journal: European Respiratory Journal (2016)

Severe chronic obstructive pulmonary disease (COPD) is a progressive disease associated with excessive mortality; however, mechanisms driving disease progression remain unclear [1]. A pro-inflammatory state, metabolic impairments and respiratory muscle weakness contribute to deterioration of lung function [1, 2]. Furthermore, a poor COPD prognosis appears to be associated with unintentional weight loss [3, 4], which has been observed in ∼50% of severe COPD patients [5]. Oxygen administration inhibits spontaneous and ANP-stimulated lipolysis in adipose tissue in severe COPD <http://ow.ly/ZVg53022Yah>
MicroRNAs 15a and 16–1 regulates tumor proliferation in multiple myeloma
Authors: A. M. Roccaro, A. Sacco, X. Leleu, B. Thompson, A. Azab, J. Runnels, C. Lin, T. Witzig, K. Anderson, I. Ghobrial
Journal: Journal of Clinical Oncology (2009)

e14640 Background: MicroRNAs (miRNAs) are non-coding RNAs that act as negative regulators of gene expression. They have been described to play roles in solid tumors and hematologic malignancies. However the role of miRNAs in multiple myeloma (MM) has not been yet fully described. Methods: We performed miRNA-profiling of primary bone marrow-derived CD138+ MM cells, compared to their normal cellular counterparts and validated data by qRT-PCR. In vitro and in vivo functional studies were performed on miRNA-15a- and -16–1-precursors-transfected MM cells. Effect of miRNA-15a and -16–1 on signaling cascades have been evaluated by western blot and immunofluorescence. NF-kB activity has been studied using the Active Motif TransAM kit. In vivo MM cell growth has been evaluated by either using an in vivo imaging model or bioluminescence. Angiogenesis has been studied both in vitro and in vivo using the chorioallantoic membrane model. Results: We identified a MM-specific miRNA signature characterized by down-expression of miRNA-15a, -16–1 and over-expression of miRNA-222/-221/-382/-181a/-181b (P&lt;0.01). Data were confirmed by qRT-PCR on matched samples. Predicted targets for the decreased miRNAs in MM patients included pro-angiogenic cytokines, oncogenes, cell cycle regulators, NFkB activators. Conversely, predicted targets for the increased miRNAs included cell cycle inhibitors, suppressors of cytokine signaling, and pro-apoptotic factors. We demonstrated that miRNA-15a and - 16–1 regulate proliferation and growth of MM cells. Indeed, transfected cells showed decreased DNA synthesis; decreased cyclinD1/cyclinD3/CDC25a/pRb protein expression; phase G1 cell cycle arrest. Moreover, transfected cells showed inhibition of NFkB pathway as shown by reduced p65-/p50-/p52-NFkB activities; downregulation of p-p65/p50/p52 nuclear protein level; upregulation of cttosolic phospho-IkB; and inhibited translocation of p-p65 from the cytolplasm to the nucleus. Similarly, inhibition of MM cell growth was confirmed in vivo; and anti-angiogenic properties of miRNA-15a and -16–1 were demonstrated both in vitro and in vivo. Conclusions: These data indicate that miRNAs play a pivotal role in the biology of MM; providing the basis for the development of new miRNA-based targeted therapies in this disease. No significant financial relationships to disclose.
CCGs vary widely in how well they deliver healthcare, new measure shows: Table 1
Authors: Nigel Hawkes
Journal: BMJ (2016)

New indicators show that primary care clinical commissioning groups (CCGs) in England vary widely in their ability to deliver healthcare equitably to rich and poor people.

Some inner city areas, such as Tower Hamlets in east London, have done well on the new measure, while others, such as central Manchester, did poorly. A large gap could also be seen in affluent areas, with south Cheshire performing relatively badly while east Surrey did well.

The Centre for Health Economics at York University devised the measure, which has now been adopted by the NHS in England as one of the tools it uses to assess and improve the performance of CCGs.

To make the comparison the York team needed a marker that enabled CCGs to be compared on how well they delivered healthcare to their populations, regardless of how large the underlying discrepancies in overall health were. This was …
The Mystery of FDG-PET Avidity In Follicular Lymphoma. Does Microenvironment Play the Key Role?
Authors: Andrea Janikova, Boris Tichy, Jana Supikova, Pavel Fabian, Leos Kren, Karol Bolcak, David Salek, Jozef Michalka, Sarka Pospisilova, Jiri Mayer
Journal: Blood (2010)
Potentiation of the Antileukemic Effects of Imatinib through the Modulation of BCRP/ABCG2 Activity.
Authors: Eliza Glodkowska-Mrowka, Magda Winiarska, Piotr Mrowka, Grzegorz Basak, Joanna Niesiobedzka-Krezel, Ilona Seferynska, Tomasz Stoklosa
Journal: Blood (2010)
Three quarters of patients with diabetes in England and Wales meet blood pressure targets
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Three quarters of patients with diabetes in England and Wales are now meeting target blood pressure levels, figures have shown.

Achieving blood pressure levels of ≤140/80 is one of three treatment targets for patients with diabetes recommended by the National Institute for Health and Care Excellence (NICE). The latest findings from the National Diabetes Audit showed a steady improvement against this target in patients with type 1 or type 2 diabetes.1

In 2014-15, 76.4% of patients with type 1 diabetes and 74.2% with type 2 diabetes achieved the target. This compares with 68.5% of patients …
KIT Inhibitor Midostaurin in Patients with Advanced Systemic Mastocytosis: Results of a Planned Interim Analysis of the Global CPKC412D2201 Trial
Authors: Jason Gotlib, Hanneke C. Kluin-Nelemans, Tracy I. George, Cem Akin, Karl Sotlar, Olivier Hermine, Farrukh Awan, Elizabeth Hexner, Michael J. Mauro, Rodica Morariu, Margaret Squier, Matthieu Villeneuve, Fabienne Emery-Salbert, Karin Hartmann, Hans-Peter Horny, Peter Valent, Andreas Reiter
Journal: Blood (2012)
Endoscopic Ultrasound Fine-Needle Aspiration Diagnosis of Synchronous Primary Pancreatic Adenocarcinoma and Effects on Staging and Resectability
Authors: Tarun Rustagi, Ferga C. Gleeson, Suresh T. Chari, Barham K. Abu Dayyeh, Michael B. Farnell, Prasad G. Iyer, Michael L. Kendrick, Randall K. Pearson, Bret T. Petersen, Elizabeth Rajan, Mark D. Topazian, Mark J. Truty, Santhi S. Vege, Kenneth K. Wang, Michael J. Levy
Journal: Clinical Gastroenterology and Hepatology (2016)
Applications of Polymers as Pharmaceutical Excipients in Solid Oral Dosage Forms
Authors: Nir Debotton, Arik Dahan
Journal: Medicinal Research Reviews (2016)

Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the “magic bullets” concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration. When formulating challenging molecules into solid oral dosage forms, polymeric pharmaceutical excipients permit masking undesired physicochemical properties of drugs and consequently, altering their pharmacokinetic profiles to improve the therapeutic effect. As a result, the number of synthetic and natural polymers available commercially as pharmaceutical excipients has increased dramatically, offering potential solutions to various difficulties. For instance, the different polymers may allow increased solubility, swellability, viscosity, biodegradability, advanced coatings, pH dependency, mucodhesion, and inhibition of crystallization. The aim of this article is to provide a wide angle prospect of the different uses of pharmaceutical polymers in solid oral dosage forms. The various types of polymeric excipients are presented, and their distinctive role in oral drug delivery is emphasized. The comprehensive know-how provided in this article may allow scientists to use these polymeric excipients rationally, to fully exploit their different features and potential influence on drug delivery, with the overall aim of making better drug products.
Futility and Avoidance: Medical Professionals in the Treatment of Obesity
Authors: Robert J. Yaes
Journal: JAMA (1993)

To the Editor.  — As a physician who is not involved in the treatment of obesity, but who himself is obese, I have often pondered the same questions as Dr Frank. 1 Certainly, at a time when it is fashionable to claim that alcoholism and drug abuse are illnesses whose treatment should be covered by health insurance, it is inconsistent to blame fat people for their own condition. Attributing obesity to poor self-control and overindulgence makes as much sense as the reasoning of patients with diabetes insipidus who believe that the cause of their frequent urination is the fact that they drink so much water.  There can be no question of the genetic origin of obesity. Fat parents tend to have fat children. Subjectively, obesity seems to be unevenly distributed among different ethnic groups, although I know of no conclusive studies on the subject. It is my impression, for example,
Mood, the Circadian System, and Melanopsin Retinal Ganglion Cells
Authors: Lorenzo Lazzerini Ospri, Glen Prusky, Samer Hattar
Journal: Annual Review of Neuroscience (2017)

The discovery of a third type of photoreceptors in the mammalian retina, intrinsically photosensitive retinal ganglion cells (ipRGCs), has had a revolutionary impact on chronobiology. We can now properly account for numerous non-vision-related functions of light, including its effect on the circadian system. Here, we give an overview of ipRGCs and their function as it relates specifically to mood and biological rhythms. Although circadian disruptions have been traditionally hypothesized to be the mediators of light's effects on mood, here we present an alternative model that dispenses with assumptions of causality between the two phenomena and explains mood regulation by light via another ipRGC-dependent mechanism.
In Between the Intensive Care Unit and the Ward
Authors: Neil A. Halpern
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine 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 Internal Medicine journal
Epigenetic changes in nucleoside transporter hENT1 and dCK, as mechanism for gemcitabine-aquired resistance in cervical cancer cell lines.
Authors: M. Candelaria, E. de la Cruz-Hernandez, A. Gonzalez-Fierro, E. Perez-Cardenas, C. Trejo-Becerril, L. Taja-Chayeb, A. Duenas- Gonzalez
Journal: Journal of Clinical Oncology (2010)

e13633 Background: Gemcitabine has activity in cervical cancer, since it increases pathological response rate, as well as overall survival. Nevertheless, a proportion of patients fail to this regimen, hence the identification of the mecanisms leading this resistance is important in order increase the efficacy of the treatment. Methods: Gemcitabine chemoresistance was induced in cervical cancer cell lines (HeLa, CaLo) after exposure to increasing concentrations. Expression of the following genes was evaluated by RT-PCR: hENT1, dCK, RRM1, RRM2, CDA before and after induction of resistance. Epigenetic changes were evaluated in the genes that were downregulated after induction of resistance: Promoter methylation was evaluated by Methylation Specific PCR (MSP) and sequencing after bisulfate DNA modification; histone methylation, as well as histone acetylation changes were evaluated by chromatin immunoprecipitation (ChIP). After resistance acquirement, CaLo cells were treated with the demethylating agent Hydralazine, and the HDAC inhibitor Valproate to revert gene downregulation and restore gemcitabine sensitivity. Results: Gemcitabine resistance was generated after exposure to increasing concentrations of gemcitabine: Inhibitory 50 concentration (IC50) in CaLo cell line increased from 3.3 uM to 927 uM and in HeLa cell line from 0.37 uM to 1000 uM. After acquired resistance, an increase on RRM2 and CDA expression was observed in HeLa cell line, but a decrease on hENT1, dCK expression was documented in Calo cell line. Downregulation of both genes was associated with promoter methylation, with an increase on repressive marks H3K9 me2 and H3K27me3, as evaluated by ChIP analysis. No changes in promoter H3 and H4 acetylation was observed. Treatment with hydralazine up-regulated the expression of hENT1 and dCK and restored gemcitabine sensitivity. Conclusions: Epigenetic changes (promoter methylation and histone methylation) are associated with downregulation of hENT1 and dCK which led to gemcitabine resistance. Hydralazine effectively reverts gemcitabine resistance in this model. No significant financial relationships to disclose.
Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial
Authors: Jan Sperl, Gabor Horvath, Waldemar Halota, Juan Arenas Ruiz-Tapiador, Anca Streinu-Cercel, Ligita Jancoriene, Klara Werling, Hege Kileng, Seyfettin Koklu, Jan Gerstoft, Petr Urbanek, Robert Flisiak, Rafael Leiva, Edita Kazenaite, Renate Prinzing, Sushma Patel, Jingjun Qiu, Ernest Asante-Appiah, Janice Wahl, Bach-Yen Nguyen, Eliav Barr, Heather L. Platt
Journal: Journal of Hepatology (2016)
Abstract 979: Dynamic epigenetic regulation of glioblastoma tumorigenicity through LSD1 modulation of MYC expression
Authors: Jie Li, David Kozono, Masayuki Nitta, Oltea Sampetrean, David Gonda, Deepa S. Kushwaha, Dmitry Merzon, Valya Ramakrishnan, Shan Zhu, Kaya Zhu, Hiroko Matsui, Olivier Harismendy, Wei Hua, Ying Mao, Chang-Hyuk Kwon, Hideyuki Saya, Bob S. Carter, Donald P. Pizzo, Scott R. VandenBerg, Clark C. Chen
Journal: Cancer Research (2015)

Abstract Glioblastoma is the most common form of primary brain cancer and remains one of the deadliest of human cancers with near-uniform fatality. Increasing evidence suggests that the lethality of glioblastoma is driven by small subpopulations of cells with self-renew ability and tumorigenicity, termed as tumor initiating cells. The mechanism how the tumor initiating cells maintain and gain tumorigenicity in glioblastoma still remains unclear. Here, we used sphere formation and tumor propagating potential to measure the tumorigenicity in established cell line and primary glioblastoma cells. The results indicated that glioblastoma tumorigenicity appears largely deterministic, though spontaneous gain and loss of this property occur at low frequency. Mechanically, this dynamic transition in tumorigenicity was governed by MYC level which was modulated epigenetically by the lysine-specific demethylase 1 (LSD1). Elevated MYC expression, in turn, regulates OLIG2, SOX2 and POU3F2, a core set of transcription factors required for reprogramming glioblastoma cells into stem-like states. Our model suggests epigenetic regulation of key transcription factors facilitates transitions between tumorigenic states and provides a framework for glioblastoma therapeutic development. Importantly, the effect of LSD1 on tumorigenity is “Janus”-like; partial depletion of LSD1 caused increased MYC expression and a pro-tumorigenic state. In contrast, complete suppression of LSD1 induced cell death. As such, therapeutic strategies targeting LSD1 and other targets manifesting similar “Janus” effect should be designed to prevent unintended induction of tumorigenesis during treatment. Citation Format: Jie Li, David Kozono, Masayuki Nitta, Oltea Sampetrean, David Gonda, Deepa S. Kushwaha, Dmitry Merzon, Valya Ramakrishnan, Shan Zhu, Kaya Zhu, Hiroko Matsui, Olivier Harismendy, Wei Hua, Ying Mao, Chang-Hyuk Kwon, Hideyuki Saya, Bob S. Carter, Donald P. Pizzo, Scott R. VandenBerg, Clark C. Chen. Dynamic epigenetic regulation of glioblastoma tumorigenicity through LSD1 modulation of MYC expression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 979. doi:10.1158/1538-7445.AM2015-979