tbuckley/cabot-search huggingface dataset:
Smad3-Mediated Upregulation of miR-21 Promotes Renal Fibrosis
Authors: Xiang Zhong, Arthur C.K. Chung, Hai-Yong Chen, Xiao-Ming Meng, Hui Y. Lan
Journal: Journal of the American Society of Nephrology (2011)

TGF-β/Smad signaling plays a role in fibrogenesis, but therapies targeting TGF-β are ineffective in treating renal fibrosis. Here, we explored the therapeutic potential of targeting TGF-β-induced microRNA in the progression of renal fibrosis. Microarray analysis and real-time PCR revealed upregulation of miR-21 in tubular epithelial cells (TECs) in response to TGF-β. Lack of Smad3, but not lack of Smad2, prevented cells from upregulating miR-21 in response to TGF-β. In addition, Smad3-deficient mice were protected from upregulation of miR-21 and fibrosis in the unilateral ureteral obstruction model. In contrast, conditional knockout of Smad2 enhanced miR-21 expression and renal fibrosis. Furthermore, ultrasound-microbubble-mediated gene transfer of a miR-21-knockdown plasmid halted the progression of renal fibrosis in established obstructive nephropathy. In conclusion, these data demonstrate that Smad3, but not Smad2, signaling increases expression of miR-21, which promotes renal fibrosis. Inhibition of miR-21 may be a therapeutic approach to suppress renal fibrosis.
Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three
Authors: Philippa Ellwood, M Innes Asher, Luis García-Marcos, Hywel Williams, Ulrich Keil, Colin Robertson, Gabriele Nagel
Journal: Thorax (2013)

<h3>Background</h3> Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. <h3>Methods</h3> Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13–14-year-old adolescents and by the parents/guardians of 6–7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. <h3>Results</h3> For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. <h3>Conclusions</h3> If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.
Randomized Phase II Study Comparing Gemcitabine Plus Dacarbazine Versus Dacarbazine Alone in Patients With Previously Treated Soft Tissue Sarcoma: A Spanish Group for Research on Sarcomas Study
Authors: Xavier García-del-Muro, Antonio López-Pousa, Joan Maurel, Javier Martín, Javier Martínez-Trufero, Antonio Casado, Auxiliadora Gómez-España, Joaquín Fra, Josefina Cruz, Andrés Poveda, Andrés Meana, Carlos Pericay, Ricardo Cubedo, Jordi Rubió, Ana De Juan, Nuria Laínez, Juan Antonio Carrasco, Raquel de Andrés, José M. Buesa
Journal: Journal of Clinical Oncology (2011)

To assess the activity and toxicity of the combination of gemcitabine plus dacarbazine (DTIC) in patients with advanced soft tissue sarcoma (STS) in a randomized, multicenter, phase II study using DTIC alone as a control arm.Patients with previously treated advanced STS were randomly assigned to receive either fixed-dose rate gemcitabine (10 mg/m2/min) at 1800 mg/m2 followed by DTIC at 500 mg/m2 every 2 weeks, or DTIC alone at 1200 mg/m2 every 3 weeks. The primary end point of the study was progression-free rate (PFR) at 3 months.From November 2005 to September 2008, 113 patients were included. PFR at 3 months was 56% for gemcitabine plus DTIC versus 37% for DTIC alone (P = .001). Median progression-free survival was 4.2 months versus 2 months (hazard ratio [HR], 0.58; 95% CI, 0.39 to 0.86; P = .005), and median overall survival was 16.8 months versus 8.2 months (HR, 0.56; 95% CI, 0.36 to 0.90; P = .014); both favored the arm of gemcitabine plus DTIC. Gemcitabine plus DTIC was also associated with a higher objective response or higher stable disease rate than was DTIC alone (49% v 25%; P = .009). Severe toxicities were uncommon, and treatment discontinuation for toxicity was rare. Granulocytopenia was the more common serious adverse event, but febrile neutropenia was uncommon. Asthenia, emesis, and stomatitis were the most frequent nonhematologic effects.The combination of gemcitabine and DTIC is active and well tolerated in patients with STS, providing in this phase II randomized trial superior progression-free survival and overall survival than DTIC alone. This regimen constitutes a valuable therapeutic alternative for these patients.
Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study
Authors: Christopher M Clark, Michael J Pontecorvo, Thomas G Beach, Barry J Bedell, R Edward Coleman, P Murali Doraiswamy, Adam S Fleisher, Eric M Reiman, Marwan N Sabbagh, Carl H Sadowsky, Julie A Schneider, Anupa Arora, Alan P Carpenter, Matthew L Flitter, Abhinay D Joshi, Michael J Krautkramer, Ming Lu, Mark A Mintun, Daniel M Skovronsky
Journal: The Lancet Neurology (2012)
Screening Uptake in a Well-Established Diabetic Retinopathy Screening Program
Authors: Graham P. Leese, Paul Boyle, Zhiqiang Feng, Alistair Emslie-Smith, John D. Ellis
Journal: Diabetes Care (2008)

To identify criteria that affect uptake of diabetes retinal screening in a community screening program using mobile retinal digital photography units.Data from the regional diabetes population-based retinal screening program and regional ophthalmology laser database were linked to patient postal code (zip code) data. We used distance from retinal screening event, social deprivation scores, and demographic information to identify risk factors for nonattendance at a diabetes retinal screening event. Patients were subdivided into urban (>125,000 population), other urban (3,000-125,000 population), or rural (<3,000 population) depending on where they lived. Data were collected from 2004 to 2006 inclusive and included 15,150 patients and 32,621 eye screening records.The mean +/- SD age of patients was 63 +/- 15 years, and 54% were male. Mean travel time to retinal screening event varied from 7.1 to 17.0 min. For 12% of missed appointments, patients were more likely to be younger, to have longer diabetes duration, to have poor A1C and blood pressure control, to be smokers, and to live in deprived areas. Poor attendance was not associated with sex or distance to retinal screening event.Social deprivation is strongly associated with poor attendance at retinal screening events. Time traveled to screening event was not associated with attendance in this study of a mobile retinal screening service, which visited general practitioner surgeries. This data can help inform population-based diabetes retinal screening programs about improving patient uptake.
Brief Report: Identification of <i>MTMR3</i> as a Novel Susceptibility Gene for Lupus Nephritis in Northern Han Chinese by Shared‐Gene Analysis With IgA Nephropathy
Authors: Xu‐jie Zhou, Swapan K. Nath, Yuan‐yuan Qi, Fa‐juan Cheng, Hai‐zhen Yang, Yan Zhang, Wanling Yang, Jian‐yang Ma, Ming‐hui Zhao, Nan Shen, Hong Zhang
Journal: Arthritis & Rheumatology (2014)

Several novel susceptibility genes for systemic lupus erythematosus (SLE) and IgA nephropathy have been identified in recent genome-wide association studies. Since both lupus nephritis and IgA nephropathy are autoimmune diseases of the kidney, they may share common disease mechanisms that overlap with genetic susceptibility. To test this hypothesis, we sought to identify genetic variants associated with IgA nephropathy in lupus nephritis. In the first stage, 500 patients with lupus nephritis, 240 SLE patients without nephritis, and 500 healthy controls were enrolled. Fifteen single-nucleotide polymorphisms (SNPs) that had the topmost association signals with IgA nephropathy were selected for further testing in patients with lupus nephritis. Three independent cohorts from Beijing, Shanghai, and Hong Kong were included as replicates. We also analyzed the functional significance of identified noncoding variants on regulatory motifs and gene expression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. In addition to associations with HLA gene polymorphisms, genetic variants of MTMR3 in 22q12 showed associations with lupus nephritis (for rs9983A, OR 1.61 [95% CI 1.19-2.19], P = 2.07 × 10(-3) ) compared to healthy controls in the first stage. Associations were replicated and reinforced among northern Han Chinese (for lupus nephritis patients versus SLE patients without nephritis, P = 0.01) but not southern Han Chinese, although significant genetic heterogeneity was observed. Conservative and regulatory features of rs9983 were predicted in in silico analyses. In expression analysis, we observed lower MTMR3 transcription levels in samples of blood with rs9983A and in renal biopsy samples from lupus nephritis and IgA nephropathy patients. Our results suggest that the MTMR3 gene is shared between IgA nephropathy and lupus nephritis in the northern Chinese population, further highlighting the role of autophagy in SLE. However, widespread replication of these experiments, fine mapping, and functional assays are required to establish this connection.
Keeping the family in family planning
Authors: Jenny Trinitapoli, Janneke Verheijen, Susan Watkins, Sara Yeatman
Journal: The Lancet Global Health (2014)

1posit that the term family planning is too antiquated and euphemistic to be useful and argue that it should be replaced with the more precise and scientific term contraception. We disagree that contraception is a better term and off er two simple insights to support this view. First, the anthropological and demographic literature on fertility in Africa shows that the desire for a family factors heavily in young women’s contraceptive choices. 2,3 Our own work in Kenya and Malawi provides robust evidence that sexually active young adults use contraception to plan their families. 4,5
New Mechanisms and Pathways for Monocyte Recruitment
Authors: William A. Muller
Journal: The Journal of Experimental Medicine (2001)

A great deal of recent research has identified chemoattractants and cellular activators responsible for neutrophil trafficking into inflamed tissues, as well as for lymphocyte homing to secondary lymphoid organs in the steady state and into foci of chronic inflammation ([1][1]–[5][2]).
Aldehyde Dehydrogenase 1 Is a Marker for Normal and Malignant Human Colonic Stem Cells (SC) and Tracks SC Overpopulation during Colon Tumorigenesis
Authors: Emina H. Huang, Mark J. Hynes, Tao Zhang, Christophe Ginestier, Gabriela Dontu, Henry Appelman, Jeremy Z. Fields, Max S. Wicha, Bruce M. Boman
Journal: Cancer Research (2009)

Although the concept that cancers originate from stem cells (SC) is becoming scientifically accepted, mechanisms by which SC contribute to tumor initiation and progression are largely unknown. For colorectal cancer (CRC), investigation of this problem has been hindered by a paucity of specific markers for identification and isolation of SC from normal and malignant colon. Accordingly, aldehyde dehydrogenase 1 (ALDH1) was investigated as a possible marker for identifying colonic SC and for tracking them during cancer progression. Immunostaining showed that ALDH1(+) cells are sparse and limited to the normal crypt bottom, where SCs reside. During progression from normal epithelium to mutant (APC) epithelium to adenoma, ALDH1(+) cells increased in number and became distributed farther up the crypt. CD133(+) and CD44(+) cells, which are more numerous and broadly distributed in normal crypts, showed similar changes during tumorigenesis. Flow cytometric isolation of cancer cells based on enzymatic activity of ALDH (Aldefluor assay) and implantation of these cells in nonobese diabetic-severe combined immunodeficient mice (a) generated xenograft tumors (Aldefluor(-) cells did not), (b) generated them after implanting as few as 25 cells, and (c) generated them dose dependently. Further isolation of cancer cells using a second marker (CD44(+) or CD133(+) serially) only modestly increased enrichment based on tumor-initiating ability. Thus, ALDH1 seems to be a specific marker for identifying, isolating, and tracking human colonic SC during CRC development. These findings also support our original hypothesis, derived previously from mathematical modeling of crypt dynamics, that progressive colonic SC overpopulation occurs during colon tumorigenesis and drives CRC development.
Phase I and subsequent phase II study of filgrastim (r-met-HuG-CSF) and dose intensified cyclophosphamide plus epirubicin in patients with non-Hodgkin's lymphoma and advanced solid tumors
Authors: S.M. Talbot, D.A. Westerman, A.P. Grigg, G.C. Toner, M. Wolf, J. Bishop, J. McKendrick, J. Zalcberg, J. Levi, R.M. Fox, M.D. Green
Journal: Annals of Oncology (1999)
Diabetes Is the Main Factor Accounting for the High Ferritin Levels Detected in Chronic Hepatitis C Virus Infection
Authors: Albert Lecube, Cristina Hernández, Joan Genescà, Joan I. Esteban, Rosend Jardí, Lydia García, Rafael Simó
Journal: Diabetes Care (2004)

OBJECTIVE—A high prevalence of diabetes has been reported in patients with hepatitis C virus (HCV) infection. Both diabetes and HCV infection are associated with high serum ferritin levels. Although HCV infection could be the main factor responsible for the high ferritin levels, it is also possible that diabetes rather than HCV infection might be a major contributor to the high ferritin levels observed in patients with HCV infection. The aim of this study was to investigate the contribution of diabetes to the high ferritin levels observed in HCV-infected patients with chronic hepatitis. RESEARCH DESIGN AND METHODS—A total of 634 noncirrhotic individuals were prospectively recruited at a university hospital. According to the HCV antibody status and the presence of diabetes, the subjects were divided into four groups: group A (anti–HCV-positive diabetic patients, n = 53), group B (anti–HCV-negative diabetic patients, n = 242), group C (anti–HCV-positive nondiabetic patients, n = 191), and group D (anti–HCV-negative nondiabetic control subjects, n = 148). Multiple regression analyses were used to explore the variables independently related to ferritin levels. RESULTS—Serum ferritin levels in group A were significantly higher than in the other groups (A &amp;gt; B, P &amp;lt; 0.01; A &amp;gt; C, P &amp;lt; 0.001; A &amp;gt; D, P &amp;lt; 0.001). Ferritin levels were higher in group B than in group D (P = 0.001). However, group C has ferritin values similar to those of group D. In multivariate analyses, diabetes but not HCV infection was independently related to serum ferritin concentrations. CONCLUSIONS—Diabetes rather than HCV infection itself is the main factor associated with the increased ferritin levels detected in patients with HCV infection. Therefore, the presence of diabetes should be taken into account when iron metabolism is evaluated in HCV-infected patients.
Ménétrier disease and gastrointestinal stromal tumors: hyperproliferative disorders of the stomach
Authors: Robert J. Coffey, Mary Kay Washington, Christopher L. Corless, Michael C. Heinrich
Journal: Journal of Clinical Investigation (2007)

Ménétrier disease and gastrointestinal stromal tumors (GISTs) are hyperproliferative disorders of the stomach caused by dysregulated receptor tyrosine kinases (RTKs). In Ménétrier disease, overexpression of TGF-α, a ligand for the RTK EGFR, results in selective expansion of surface mucous cells in the body and fundus of the stomach. In GISTs, somatic mutations of the genes encoding the RTK KIT (or PDGFRA in a minority of cases) result in constitutive kinase activity and neoplastic transformation of gut pacemaker cells (interstitial cells of Cajal). On the basis of the involvement of these RTKs in the pathogenesis of these disorders, Ménétrier disease patients have been effectively treated with a blocking monoclonal antibody specific for EGFR and GIST patients with KIT and PDGFRA tyrosine kinase inhibitors.
Poor adherence to ICS treatment in patients with chronic respiratory diseases
Authors: Marijke Amelink, Reinier Wener, Lucia Rijssenbeek-Nouwens, Martine Kruijtbosch, Marcel Bouvy, Elisabeth Bel
Journal: European Respiratory Journal (2013)

Rationale  One of the major causes of treatment failure in respiratory diseases is non-adherence to treatment. Adherence rates in patients with severe airway disease are scarce  Aim  To assess non-adherence to inhaled corticosteroids (ICS) in patients with severe airway disease in a large cohort of primary and secondary care patients and to assess factors associated with very poor adherence  Methods  All patients (>18yr) prescribed ICS 1000ug fluticason eq. or 500ug plus chronic oral corticosteroids were selected from 47 community pharmacies. Data contained all prescription drugs dispensed in 2011. Patients were asked to complete questionnaires on demographics and the Asthma Control Questionnaire (ACQ). Adherence was defined as very poor ( 100%)  Results  1850 out of 5002 patients completed the questionnaires. After exclusion of 664 patients with controlled disease (ACQ≤1.5), 38% were labelled as difficult-to-treat asthma, 33% as mixed asthma/COPD, 24% as COPD and 5% as other respiratory disease. Adherence rates are given in table1. Factors associated with very poor adherence were: being treated by primary care, younger age and a diagnosis of other respiratory disease. In asthma, very poor adherence was associated with being treated by primary care, and in mixed asthma/COPD with current smoking. In COPD and other respiratory diseases no associations were found  Conclusion  Poor adherence is a significant problem in chronic severe airway disease. Therefore, adherence rates should be thoroughly checked and addressed.
De novo homozygous mutation of the C1 inhibitor gene in a patient with hereditary angioedema
Authors: Valeria Bafunno, Chiara Divella, Francesco Sessa, Giovanni Luca Tiscia, Giuseppe Castellano, Loreto Gesualdo, Maurizio Margaglione, Vincenzo Montinaro
Journal: Journal of Allergy and Clinical Immunology (2013)
The instrument that determined my practice
Authors: S A. Hannan
Journal: BMJ (2003)

We all have our reasons as to why we eventually settle in our specialties. Some reasons are short and straightforward; others are multiple and meandering. Some reasons are honest and honourable; others I daresay are false and forced. I have only one real (and ridiculous) reason—the reflection of my awestruck 5 year old face in a head mirror.

Twenty five years ago, I sat high on a red swivel chair, swinging my legs nervously and staring at a selection of shiny but scary instruments sprawled across a long wooden desk. I gripped my mother's hand while she spoke to a big voice from a big face from a big man in a big white coat. He suddenly stopped and turned his big eyes on me. I dug my nails into my mother's …
CALCIUM IN CELL INJURY AND DEATH
Authors: Zheng Dong, Pothana Saikumar, Joel M. Weinberg, Manjeri A. Venkatachalam
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

Loss of Ca 2+ homeostasis, often in the form of cytoplasmic increases, leads to cell injury. Depending upon cell type and the intensity of Ca 2+ toxicity, the ensuing pathology can be reversible or irreversible. Although multiple destructive processes are activated by Ca 2+ , lethal outcomes are determined largely by Ca 2+ -induced mitochondrial permeability transition. This form of damage is primarily dependent upon mitochondrial Ca 2+ accumulation, which is regulated by the mitochondrial membrane potential. Retention of the mitochondrial membrane potential during Ca 2+ increases favors mitochondrial Ca 2+ uptake and overload, resulting in mitochondrial permeability transition and cell death. In contrast, dissipation of mitochondrial membrane potential reduces mitochondrial Ca 2+ uptake, retards mitochondrial permeability transition, and delays death, even in cells with large Ca 2+ increases. The rates of mitochondrial membrane potential dissipation and mitochondrial Ca 2+ uptake may determine cellular sensitivity to Ca 2+ toxicity under pathological conditions, including ischemic injury.
Reliability among central readers in the evaluation of endoscopic findings from patients with Crohn's disease
Authors: Reena Khanna, Guangyong Zou, Geert D'Haens, Paul Rutgeerts, J W D McDonald, Marco Daperno, Brian G Feagan, William J Sandborn, Elena Dubcenco, Larry Stitt, Margaret K Vandervoort, Allan Donner, Allison Luo, Barrett G Levesque
Journal: Gut (2015)

<h3>Objective</h3> The Crohn9s Disease Endoscopic Index of Severity (CDEIS) and Simple Endoscopic Score for Crohn9s Disease (SES-CD) are commonly used to assess Crohn9s disease (CD) activity; however, neither instrument has been fully validated. We assessed intra-rater and inter-rater reliability of these indices. <h3>Design</h3> Video recordings of colonoscopies obtained from 50 patients with CD who participated in an induction trial of a biological therapy were triplicated and reviewed in random order by four central readers. Data were used to assess intra-rater and inter-rater reliability for CDEIS, SES-CD and a global evaluation of lesion severity (GELS). Subsequently, readers participated in a consensus process that identified common sources of disagreement. <h3>Results</h3> Intraclass correlation coefficients (ICCs) for intra-rater reliability for CDEIS, SES-CD and GELS (95% CIs) were 0.89 (0.86 to 0.93), 0.91 (0.89 to 0.95) and 0.81 (0.77 to 0.89), respectively, with standard error of measurement (SEM) of 2.10, 2.42 and 1.15. The corresponding ICCs for inter-rater reliability were 0.71 (0.63 to 0.76), 0.83 (0.75 to 0.88) and 0.62 (0.52 to 0.70), with SEM of 3.42, 3.07 and 1.63, respectively. Correlation between CDEIS and GELS was 0.75, between SES-CD and GELS was 0.74 and between CDEIS and SES-CD was 0.92. The most common sources of disagreement were interpretation of superficial ulceration, definition of disease site at the ileocolonic anastomosis, assessment of anorectal lesions and grading severity of stenosis. <h3>Conclusions</h3> Central reading of CDEIS and SES-CD had ‘substantial’ to ‘almost perfect’ intra-rater and inter-rater reliability; however, the responsiveness of these instruments is yet to be determined. <h3>Trial registration number</h3> Clinicaltrials.gov NCT01466374.