tbuckley/cabot-search huggingface dataset:
Digital ulcers and necroses: novel manifestations of angiocentric lymphoma
Authors: T. Ohtsuka, A. Yamakage, S. Yamazaki
Journal: British Journal of Dermatology (2000)

We describe a patient with angiocentric lymphoma whose presenting features were multiple areas of digital ulceration and necrosis, including deep ulcers on both great toes. He lacked the lateral halves of both earlobes because of multiple ulcers. Skin biopsy revealed a patchy and diffuse infiltrate of lymphoid cells with nuclear atypia in the dermis and subcutaneous tissue. Angiocentric and angiodestructive features of the lymphoid cells, a prominent histiocytic infiltrate and some epithelioid cell granulomas were found. The results of immunohistochemical staining showed a T-cell phenotype, and showed positive staining for apoptosis. He died in July 1999. Peripheral vascular disturbances including Raynaud's phenomenon, digital skin ulcers and necroses are novel clinical symptoms in patients with angiocentric lymphoma, which should be added to the differential diagnosis in patients with peripheral vascular disturbances.
Psoriasis is associated with increased β-defensin genomic copy number
Authors: Edward J Hollox, Ulrike Huffmeier, Patrick L J M Zeeuwen, Raquel Palla, Jesús Lascorz, Diana Rodijk-Olthuis, Peter C M van de Kerkhof, Heiko Traupe, Gys de Jongh, Martin den Heijer, André Reis, John A L Armour, Joost Schalkwijk
Journal: Nature Genetics (2007)
Arrhythmogenesis and Contractile Dysfunction in Heart Failure
Authors: Steven M. Pogwizd, Klaus Schlotthauer, Li Li, Weilong Yuan, Donald M. Bers
Journal: Circulation Research (2001)

Abstract —Ventricular arrhythmias and contractile dysfunction are the main causes of death in human heart failure (HF). In a rabbit HF model reproducing these same aspects of human HF, we demonstrate that a 2-fold functional upregulation of Na + -Ca 2+ exchange (NaCaX) unloads sarcoplasmic reticulum (SR) Ca 2+ stores, reducing Ca 2+ transients and contractile function. Whereas β-adrenergic receptors (β-ARs) are progressively downregulated in HF, residual β-AR responsiveness at this critical HF stage allows SR Ca 2+ load to increase, causing spontaneous SR Ca 2+ release and transient inward current carried by NaCaX. A given Ca 2+ release produces greater arrhythmogenic inward current in HF (as a result of NaCaX upregulation), and ≈50% less Ca 2+ release is required to trigger an action potential in HF. The inward rectifier potassium current ( I K1 ) is reduced by 49% in HF, and this allows greater depolarization for a given NaCaX current. Partially blocking I K1 in control cells with barium mimics the greater depolarization for a given current injection seen in HF. Thus, we present data to support a novel paradigm in which changes in NaCaX and I K1 , and residual β-AR responsiveness, conspire to greatly increase the propensity for triggered arrhythmias in HF. In addition, NaCaX upregulation appears to be a critical link between contractile dysfunction and arrhythmogenesis.
Aurora kinase inhibitory VX-680 increases Bax/Bcl-2 ratio and induces apoptosis in Aurora-A-high acute myeloid leukemia
Authors: Xue-Fei Huang, Shao-Kai Luo, Jie Xu, Juan Li, Duo-Rong Xu, Li-Hui Wang, Min Yan, Xian-Ren Wang, Xiang-Bo Wan, Fei-Meng Zheng, Yi-Xin Zeng, Quentin Liu
Journal: Blood (2007)
Multivitamins, folate, and colon cancer
Authors: J LITTLE
Journal: Gut (2001)

BackgroundA low folate intake may lead to reduced DNA methylation, resulting in abnormalities in DNA synthesis and repair, which could contribute to colonic carcinogenesis.There is evidence from prospective cohort studies that folate deficiency increases the risk of colon cancer in men, but such data are lacking for women. AimTo determine whether dietary folate and folate from supplements protects against colon cancer in women. DesignA prospective cohort investigation.Subjects 88 756 registered female nurses in the United States aged 30-55 years (Nurses' Health Study). MethodsSubjects completed semiquantitative food frequency questionnaires which included information on 61 foods and beverages plus vitamin and mineral supplements.The cohort was followed up for the development of colon cancer.Cases were identified through follow up questionnaires and the United States National Death Index.Relative risks were calculated and adjusted for energy intake, age, family history of colorectal cancer, aspirin, smoking, body mass, and intake of red meat, fibre, and methionine. ResultsFollow up of the cohort was almost complete (96%) and 442 new cases of colon adenocarcinoma were identified.Higher adjusted total folate intake was related to a lower risk for colon cancer (RR=0.69,95% CI=0.52-0.93)for intake of > 400 µg/day compared with < 200 µg/day.Folate intake from dietary sources alone was related to a modest risk reduction and women who used supplements for 15 years or more had a marked reduction (RR=0.25,95% CI=0.13-0.51). ConclusionsA high dietary folate intake and long term folate supplementation may reduce the risk of colon cancer.
MicroRNA-221 overexpression accelerates hepatocyte proliferation during liver regeneration
Authors: Qinggong Yuan, Komal Loya, Bhavna Rani, Selina Möbus, Asha Balakrishnan, Jutta Lamle, Toni Cathomen, Arndt Vogel, Michael P. Manns, Michael Ott, Tobias Cantz, Amar Deep Sharma
Journal: Hepatology (2012)

The tightly controlled replication of hepatocytes in liver regeneration and uncontrolled proliferation of tumor cells in hepatocellular carcinoma (HCC) are often modulated by common regulatory pathways. Several microRNAs (miRNAs) are involved in HCC progression by modulating posttranscriptional expression of multiple target genes. miR-221, which is frequently up-regulated in HCCs, delays fulminant liver failure in mice by inhibiting apoptosis, indicating a pleiotropic role of miR-221 in hepatocytes. Here, we hypothesize that modulation of miR-221 targets in primary hepatocytes enhances proliferation, providing novel clues for enhanced liver regeneration. We demonstrate that miR-221 enhances proliferation of in vitro cultivated primary hepatocytes. Furthermore, applying two-thirds partial hepatectomy as a surgically induced liver regeneration model we show that adeno-associated virus-mediated overexpression of miR-221 in the mouse liver also accelerates hepatocyte proliferation in vivo. miR-221 overexpression leads to rapid S-phase entry of hepatocytes during liver regeneration. In addition to the known targets p27 and p57, we identify Aryl hydrocarbon nuclear translocator (Arnt) messenger RNA (mRNA) as a novel target of miR-221, which contributes to the pro-proliferative activity of miR-221.miR-221 overexpression accelerates hepatocyte proliferation. Pharmacological intervention targeting miR-221 may thus be therapeutically beneficial in liver failure by preventing apoptosis and by inducing liver regeneration.
Internet Diabetic Patient Management Using a Short Messaging Service Automatically Produced by a Knowledge Matrix System
Authors: Chulsik Kim, Haijin Kim, Jisun Nam, Minho Cho, Jongsuk Park, Eunseok Kang, Chulwoo Ahn, Bongsoo Cha, Eunjig Lee, Sungkil Lim, Kyungrae Kim, Hyunchul Lee
Journal: Diabetes Care (2007)

Lifelong strict self-care is essential in the management of diabetes, along with easy access to the health care system (1–3). However, there is an evident limitation in fulfilling these conditions in the current health care system, which is oriented toward outpatient care (4–7). Thus, various strategies have been designed to improve the quality and efficiency of treating diabetic patients.

Wireless technology is a worldwide communication system that allows a person to contact others anywhere at any time. Therefore, doctor-patient communication becomes possible anywhere with the use of this system (8). Currently, in civilized countries, nearly all adults and adolescences have their own cellular phones and use short message services (SMSs) in their daily lives. Moreover, numerous people are using ultra-fast Internet services at work or in the home. We designed an Internet-based diabetic patient management system using SMS that was automatically produced by a knowledge matrix. Subsequently, we compared biochemical profiles and clinical status between diabetic patients who used our system for 12 weeks and those who received the conventional outpatient management over the same time period.

We developed a knowledge matrix containing information on proper diet and exercise for diabetic patients based on the Korea Staged Diabetes Management Guideline (Table 1). Moreover, with the technical assistance from ISU UBCare, we created a Web site program (http://yds.healthkorea.net) that was used to formulate appropriate messages through an automated algorithm. We also designed a device that had the dual function of a glucometer and a pedometer. By connecting this device to the …
A Gene Expression–Based Predictor for Myeloma Patients at High Risk of Developing Bone Disease on Bisphosphonate Treatment
Authors: Ping Wu, Brian A. Walker, Daniel Brewer, Walter M. Gregory, John Ashcroft, Fiona M. Ross, Graham H. Jackson, Anthony J. Child, Faith E. Davies, Gareth J. Morgan
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Myeloma bone disease impairs quality of life and is associated with impaired survival. Even with effective bisphosphonate treatment, a significant proportion of patients still develop skeletal-related events (SRE). Identifying such patients at presentation would allow treatment modification. Experimental Design: To investigate the molecular basis of bone disease at presentation and to develop a predictive signature for patients at high risk of developing SREs on bisphosphonates, 261 presenting myeloma samples were analyzed by global gene expression profiling. The derived “SRE gene signature” was complemented by the integration of associated clinical parameters to generate an optimal predictor. Results: Fifty genes were significantly associated with presenting bone disease, including the WNT signaling antagonist DKK1 and genes involved in growth factor signaling and apoptosis. Higher serum calcium level and the presence of bone disease and hyperdiploidy at presentation were associated with high risk of SRE development. A gene signature derived from the fourteen genes overexpressed in the SRE group was able to identify patients at high risk of developing an SRE on treatment. These genes either belonged to the IFN-induced family or were involved in cell signaling and mitosis. Multivariate logistic model selection yielded an optimal SRE predictor comprising seven genes and calcium level, which was validated as an effective predictor in a further set of patients. Conclusions: The simple expression-based SRE predictor can effectively identify individuals at high risk of developing bone disease while being on bisphosphonates. This predictor could assist with developing future trials on novel therapies aimed at reducing myeloma bone disease. Clin Cancer Res; 17(19); 6347–55. ©2011 AACR.
Sex differences in respiratory symptoms: Fig. 1.—
Authors: R. Varraso, M.P. Oryszczyn, F. Kauffmann
Journal: European Respiratory Journal (2003)

<h3>Objectives</h3> Disclosure of a hereditary condition in the family poses notable challenges for patients who often seek the assistance of genetic health professionals (GHPs). This study aimed to investigate GHPs’ opinions about the ideal time for disclosure to offspring and their responsibility to at-risk relatives. <h3>Design</h3> Cross-sectional qualitative study. <h3>Setting</h3> Genetic familial cancer clinics related to mostly secondary and tertiary care hospitals and centres in urban, regional and rural areas across all states of Australia. <h3>Participants</h3> GHPs (N=73) including clinical geneticists, genetic counsellors, medical specialists, nurses, surgeons and mental health specialists (eg, psychiatrists, psychologists) who had worked with <i>BRCA1</i> and <i>BRCA2</i> families for an average of 9 years. <h3>Results</h3> Focus groups and interviews were transcribed and analysed thematically. GHPs perceived that life stage, maturity, parents’ knowledge and capacity to disseminate information influenced parent–offspring disclosure. In general, GHPs recommended early informal conversations with offspring about a family illness. GHPs considered that facilitation of disclosure to relatives using counselling strategies was their responsibility, yet there were limitations to their role (eg, legal and resource constraints). Variability exists in the extent to which genetic clinics overcome challenges to disclosure. <h3>Conclusions</h3> GHPs’ views on the ideal time for the disclosure of genetic risk are generally dependent on the patient’s age and relative’s ability to disclose information. A responsibility towards the patient and their at-risk relative was widely accepted as a role of a GHP but views vary depending on legislative and specialty differences. Greater uniformity is needed in genetic procedural guidelines and the role of each discipline (eg, geneticists, genetic counsellors, oncologists, nurses and mental health specialists) in genetic clinics to manage disclosure challenges.
Bioinformatics in bacterial molecular epidemiology and public health: databases, tools and the next-generation sequencing revolution
Authors: J A Carriço, A J Sabat, A W Friedrich, M Ramirez, Collective on behalf of the ESCMID Study Group
Journal: Eurosurveillance (2013)

Advances in typing methodologies have been the driving force in the field of molecular epidemiology of pathogens. The development of molecular methodologies, and more recently of DNA sequencing methods to complement and improve phenotypic identification methods, was accompanied by the generation of large amounts of data and the need to develop ways of storing and analysing them. Simultaneously, advances in computing allowed the development of specialised algorithms for image analysis, data sharing and integration, and for mining the ever larger amounts of accumulated data. In this review, we will discuss how bioinformatics accompanied the changes in bacterial molecular epidemiology. We will discuss the benefits for public health of specialised online typing databases and algorithms allowing for real-time data analysis and visualisation. The impact of the new and disruptive next-generation sequencing methodologies will be evaluated, and we will look ahead into these novel challenges.
Cutaneous hyalohyphomycosis caused by Paecilomyces lilacinus in a renal transplant patient
Authors: V. Blackwell, K. Ahmed, C. O’Docherty, R.J. Hay
Journal: British Journal of Dermatology (2000)

We describe a renal transplant recipient with cutaneous hyalohyphomycosis due to Paecilomyces lilacinus and highlight the increasing importance of such opportunistic fungal infections in immunosuppressed patients.
Fine Tuning of Sympathetic Transmitter Release via Ionotropic and Metabotropic Presynaptic Receptors
Authors: S. Boehm
Journal: Pharmacological Reviews (2002)

The release of transmitters at sympathoeffector junctions is not constant, but subject to modulation by a plethora of different mechanisms. In this respect, presynaptic receptors located on the sympathetic axon terminals are of utmost importance, because they are activated by exogenous agonists and by endogenous neurotransmitters. In the latter case, the transmitters that activate the presynaptic receptors of a nerve terminal may be released either from the very same nerve ending or from a different axon terminal, and the receptors involved are auto- and heteroreceptors, respectively. In terms of their structural and functional features, receptors of sympathetic axon terminals can be categorized as either ionotropic (transmitter-gated ion channels) or metabotropic (most commonly G protein-coupled) receptors. This review summarizes results on more than 30 different metabotropic and four different ionotropic receptors that have been found to control the amount of transmitter being released from sympathetic neurons. Each of these receptors may not only stimulate, facilitate, and reduce sympathetic transmitter release, respectively, but also interact with the functions of other receptors present on the same axonal varicosity. This provides a multitude of mechanisms that regulate the amount of sympathetic transmitter output. Accordingly, a sophisticated cross-talk within and between extra- and intracellular signals is integrated at axon terminals to adapt the strength of sympathoeffector transmission to a given situation. This will not only determine the function of the sympathetic nervous system in health and disease, but also therapeutic and untoward effects of drugs that bind to the presynaptic receptors in sympathetically innervated tissues.
Early Endothelial Dysfunction Predicts the Development of Transplant Coronary Artery Disease at 1 Year Posttransplant
Authors: Stacy F. Davis, Alan C. Yeung, Ian T. Meredith, François Charbonneau, Peter Ganz, Andrew P. Selwyn, Todd J. Anderson
Journal: Circulation (1996)

Accelerated coronary arteriosclerosis is the major obstacle to long-term survival after cardiac transplantation. Endothelial dysfunction is common early posttransplant. The relationship between early endothelial dysfunction and the development of allograft arteriosclerosis has not been analyzed serially with intravascular ultrasound in the same patients. We hypothesized that an early constrictor response to acetylcholine, indicative of endothelial dysfunction, may predict the development of transplant coronary arteriosclerosis.Endothelium-dependent vasomotion was assessed early posttransplant in 20 patients by serial intracoronary acetylcholine infusion, and the percent change in diameter was measured by quantitative angiography. The development of arteriosclerosis was studied by use of intravascular ultrasound in the same 20 patients by quantifying the changes in intimal index (delta Ii) and maximal intimal thickness [delta Mt] of 46 matched coronary segments between initial and 1-year follow-up studies. Coronary segments with endothelial dysfunction (constriction > or = 5%; n = 23) demonstrated a significantly greater increase in mean Ii and Mt by 1 year posttransplant compared with segments with normal endothelial function (n = 23) (delta Ii = 7 +/- 2% versus 2 +/- 1% [P < .05] and delta Mt = 140 +/- 40 versus 50 +/- 20 microns [P < .05]). No other parameters examined predicted the development of allograft arteriosclerosis in the initial year posttransplant.Paired studies that used intravascular ultrasound showed that early endothelial dysfunction predicts the development of allograft arteriosclerosis during the initial year posttransplant. This early pathophysiological feature is likely an important marker that could be useful in therapeutic trials.
Why Most Published Research Findings Are False
Authors: John P. A. Ioannidis
Journal: PLoS Medicine (2005)

There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.
Air pollution in Iran
Authors: C. Mawer
Journal: BMJ (2014)

Brauer and Mancini say that “nowhere are the health effects of outdoor air pollution felt more than in China.”1

But four of the top 10 air polluted cities are in Iran. Ahvaz is the most polluted city in the world, with particulate levels three times that of Beijing, and nearly 13 times that of London.2 Ahvaz struggles with micro-dust blowing in from …
Suramin and radiotherapy in newly diagnosed glioblastoma: Phase 2 NABTT CNS Consortium study
Authors: John J. Laterra, Stuart A. Grossman, Kathryn A. Carson, Glenn J. Lesser, Fred H. Hochberg, Mark R. Gilbert
Journal: Neuro-Oncology (2004)

Suramin is a polysulfonated naphthylurea that inhibits the function of growth factors and growth factor receptors implicated in glioma progression, angiogenesis, and radioresistance. The safety and benefits of combining inhibitors of angiogenesis and growth factors with cytotoxic therapies in patients with neoplasms of the central nervous system remain unclear. The objectives of this phase 2 study were to determine the safety of administering suramin with standard cranial radiotherapy (RT) and to estimate survival using this approach in patients with newly diagnosed glioblastoma multiforme (GBM). Fifty-five patients with newly diagnosed GBM (Karnofsky performance status≥ 60) were enrolled in this multicenter phase 2 study. Patients received suramin by a conventional intermittent fixed-dosing regimen for 1 week prior to and during cranial RT (60 Gy in 30 fractions, weeks 2-7). Patients with stable or responsive disease at week 18 received an additional 4 weeks of suramin (weeks 19-22). The median survival for suramin-treated patients was 11.6 months, with 1-year and 18-month survival rates of 49% (95% confidence interval [CI], 36%-62%) and 18% (95% CI, 8%-28%), respectively. Overall, 55% of the patients (30/55) had greater than grade 2 toxicity at least possibly related to suramin therapy. Two patients died of possibly related neurologic events (i.e., stroke, elevated intracranial pressure). Otherwise, toxicities were generally transient and self-limited. Administration of suramin using an intermittent fixed-dosing regimen during cranial RT was generally well tolerated. However, overall survival is not significantly improved when compared with the New Approaches to Brain Tumor Therapy GBM database or other comparable patient populations.
Androgen Receptor Content of the Normal and Hyperplastic Canine Prostate
Authors: Sydney A. Shain, Robert W. Boesel
Journal: Journal of Clinical Investigation (1978)

A procedure was developed for measurement of androgen receptors in cytoplasmic extracts of prostates from intact dogs. The protocol utilized exchange saturation analysis at 15°C employing the synthetic androgen R1881 (17β-hydroxy-17α-methylestra-4,9,11-trien-3-one) as the ligand probe and quantitatively detected total cytoplasmic androgen receptor (Rc, androgen-free receptor, and RcA, androgen-occupied receptor) present at the initiation of the assay. This protocol was employed in conjunction with a tissue mince saturation analysis procedure (for quantitation of nuclear androgen receptor) to quantitate total androgen receptor content of normal and hyperplastic prostates obtained from young (2.5- or 4.6-yr old) and aged (12.5-yr old) purebred dogs of known birth date.
Identification of functional modules that correlate with phenotypic difference: the influence of network topology
Authors: Jui-Hung Hung, Troy W Whitfield, Tun-Hsiang Yang, Zhenjun Hu, Zhiping Weng, Charles DeLisi
Journal: Genome biology (2010)

Abstract One of the important challenges to post-genomic biology is relating observed phenotypic alterations to the underlying collective alterations in genes. Current inferential methods, however, invariably omit large bodies of information on the relationships between genes. We present a method that takes account of such information - expressed in terms of the topology of a correlation network - and we apply the method in the context of current procedures for gene set enrichment analysis.