tbuckley/cabot-search huggingface dataset:
BRAF mutations are associated with distinctive clinical, pathological and molecular features of colorectal cancer independently of microsatellite instability status
Authors: Wei Qi Li, Kazuyuki Kawakami, Andrew Ruszkiewicz, Graeme Bennett, James Moore, Barry Iacopetta
Journal: Molecular Cancer (2006)

Abstract Background BRAF is a member of RAF family of serine/threonine kinases and mediates cellular responses to growth signals through the RAS-RAF-MAP kinase pathway. Activating mutations in BRAF have recently been found in about 10% of colorectal cancers, with the vast majority being a V600E hotspot mutation. The aim of the present study was to evaluate the clinical, pathological and molecular phenotype of colorectal tumors with BRAF mutations. Results Mutations in BRAF were identified in 8% (23/275) of colorectal cancers. They were 5–10-fold more frequent in tumors with infiltrating lymphocytes, location in the proximal colon, poor histological grade and mucinous appearance ( P &lt; 0.002 for each). Tumors with BRAF mutation were also 10-fold more likely to show microsatellite instability and frequent DNA methylation ( P &lt; 0.0001) compared to tumors without this mutation. The characteristic morphological features of tumors with BRAF mutation (infiltrating lymphocytes, poor grade, mucinous) remained after stratification according to microsatellite instability and methylator phenotypes. Mutations in BRAF were mutually exclusive with mutations in KRAS but showed no clear association with the presence of TP53 mutation. Conclusion BRAF mutation identifies a colorectal cancer subgroup with distinctive phenotypic properties independent of microsatellite instability status and thus could be a valuable marker for studies into the clinical properties of these tumors.
Array-CGH Analysis of T-ALL Patients and Cell Lines.
Authors: Idoya Lahortiga, Carlos Graux, Nicole Mentens, Katrien Van Roosbroeck, Kim De Keersmaecker, Frederic Lambert, Peter Vandenberghe, Iwona Wlodarska, Guy Froyen, Maria D. Odero, Peter Marynen, Jan Cools
Journal: Blood (2006)
aTTom (adjuvant Tamoxifen—To offer more?): Randomized trial of 10 versus 5 years of adjuvant tamoxifen among 6,934 women with estrogen receptor-positive (ER+) or ER untested breast cancer—Preliminary results
Authors: R. G. Gray, D. W. Rea, K. Handley, A. Marshall, M. G. Pritchard, P. Perry, H. M. Earl, C. J. Poole, A. Salman, M. Lee
Journal: Journal of Clinical Oncology (2008)

513 Background: In ER+ early breast cancer, 5 years of tamoxifen substantially reduces the annual recurrence rate throughout the first decade (years 0–9). Despite this, appreciable risks of recurrence remain, with similar annual recurrence risks for ER+ disease during years 0–4, 5–9 and 10–14 following surgery. It is not reliably known how 10 years duration of adjuvant tamoxifen compares with the current standard of 5 years. Methods: Between 1991 and 2005, 6,934 women with ER+ (39%), or ER untested (61%) invasive breast cancer (53% node negative, 31% node positive, 16% node status unspecified) from 176 UK centers, who had completed 4+ years of adjuvant tamoxifen, were randomized between continuing for another 5 years and stopping. Information on compliance, hospital admission(s), breast cancer recurrence (including new contralateral disease), other new primary cancer, death and cause of death was sought annually. Results: 78% of those allocated to continue and 3% of those allocated to stop were taking adjuvant tamoxifen at 3 years following randomization; fewer than 1% switched to any other adjuvant hormone treatment. With a median follow-up of 4.2 years, there were fewer recurrences (415 vs 442; RR=0.94, 95% CI 0.81–1.09; p=0.4) among those allocated to 10yrs than 5yrs tamoxifen. Although breast cancer mortality was lower among those allocated 10yrs, with just 374 deaths from breast cancer recorded, data remain immature. Despite a doubling in the risk of endometrial cancer (76 vs 35) with 10yrs tamoxifen, there was no increase in deaths from endometrial cancer (10 vs 12) or from any other non-breast cancer cause. Conclusions: Although no significant reduction in recurrence has yet been seen in aTTom, the results are consistent with preliminary findings from the ATLAS trial, which reported a DFS but not overall survival advantage to longer tamoxifen (Peto et al SABCS 2007). Combining results from these two large studies indicate that continuation of tamoxifen beyond the first 5 years reduces recurrence over the next few years, but further follow-up is needed to assess reliably the longer-term effects on recurrence and the net effects, if any, on mortality. No significant financial relationships to disclose.
Iodine subsidy as a factor in prevention of bronchial asthma (BA) in infants
Authors: Evgeniya Truntsova, Dina Bezrukova
Journal: European Respiratory Journal (2011)

Object: to evaluate the effectiveness of the prevention of the atopic diseases and BA in babies with the use of the iodine drugs.   Methods:  Evaluation of the health state of the babies having got the iodine with maternal milk in the lactation period from 3 to 6 months (n=117) were studied. 118 babies without iodine donation was the control group. Evaluation of the health state according to the anamnesis, examination, laboratory data and hereditary predisposition to allergic diseases was carried. The indices of median iodurea in babies were studied.   Results:  Breast feeding mothers got the potassium iodide at a dose of 200 mcg per day. This dose corresponds with the norms recommended by the WHO for the groups with higher risk of iodine deficiency. Excretion of iodine with urine in babies getting additional iodine in maternal milk was much higher in comparison with the control group (94.6 mcg/L and 38.8 mcg/L respectively; p   Conclusions:  The iodine drugs can be recommended to breast feeding mothers during the lactation period for the prevention atopic diseases and BA in infants.
In the Wake of Tragedy
Authors: Lynne Lamberg
Journal: JAMA (2003)

SAN FRANCISCO—Epidemiological assessment of the mental health consequences of terrorist attacks, wars, and torture holds practical implications for treatment of those exposed to such events. Findings also may spur development of better ways to minimize adverse effects of future episodes of violence on both individuals and society at large. Researchers from several countries reviewed studies and provided perspectives derived from experience working with adults and children exposed to mass violence in a symposium held at the annual meeting of the American Psychiatric Association here in May, and in subsequent interviews.
Vascular endothelial growth factor receptor 2 (VEGFr2) expression and recurrence of hepatocellular carcinoma following liver transplantation: The Cleveland Clinic experience
Authors: R. D. Kim, A. Lazaryan, F. Aucejo, B. Eghtesad, R. Pelley, J. Fung, C. Miller, L. Yerian
Journal: Journal of Clinical Oncology (2008)

4594 Background: The optimal treatment for hepatocellular carcinoma (HCC) for advanced cirrhosis is deceased donor liver transplantation (LT). However, tumor reoccurrence represents major limitation of long term survival. It is, therefore, important to recognize markers which portend poor prognosis including VEGFr2 expression. We examined the association between VEGFr2 expression and tumor recurrence, following liver transplantation in MELD era. Methods: Of 361 consecutive patients who underwent LT at the Cleveland Clinic between June 2002 and August 2006, 126 patients were diagnosed with HCC. Immunohistochemical staining for VEGFr2 was performed in HCC and corresponding adjacent cirrhotic liver from 79 patients out of 126 patients. Stains were scored by estimating percent of positive surface area in veins, arteries, and sinusoidal lining cells of tumor and adjacent tissues. Binary staining variables were created based on median values. Kaplan-Meier survival analysis was used to assess the association between VEGFr2 staining and either recurrence-free survival (RFS) or overall survival (OS). Analysis was only done on 79 patients who had VEGFr2 staining. Results: 87% of the study patients were males. The mean age was 57 (range, 35–76). 1-year and 2-year RFS was 94% and 78%, respectively, as compared to 89% and 79% for the OS. Patients’ death secondary to complication of liver transplant was not censored. Vascular invasion was consistently associated with HCC recurrence (p<0.01) and overall mortality (p<0.05). Subjects with VEGFr2 overexpression in tumor arterioles (p<0.01), venules (p<0.05), or sinusoids (p<0.05) had worse overall survival. In the RFS analysis, similar trends were detected for VEGFr2 overexpression in all three HCC vascular tissues. Higher expression of VEGFr2 in the sinusoids of adjacent non-tumorous liver portended poorer recurrence-free survival (p<0.05). Conclusions: Elevated VEGFr2 expression in HCC was correlated with worse outcome. VEGFr2 inhibitors such as sorafenib may play a role in preventing tumor reoccurrence. No significant financial relationships to disclose.
Discovery of prognostic and predictive tissue biomarkers in patients with resectable esophageal cancer.
Authors: Thomas P. MacGregor, Richard S. Gillies, Natasha Sahgal, Runjan Chetty, Lai-Mun Wang, Richard Calvin Turkington, Nicholas D. Maynard, Peter J. McHUGH, Richard D. Kennedy, Mark R. Middleton, Ricky A. Sharma
Journal: Journal of Clinical Oncology (2014)

45 Background: Patients with operable esophageal adenocarcinoma have a poor prognosis (median survival &lt;2 years). We aimed to discover novel prognostic and predictive biomarkers to be validated as tools for patient selection for optimal neo-adjuvant therapy. Methods: Protein levels of XPF, MUS81, Cyclins A, B1, D1 and E, and Ki67 were assessed by retrospective immunohistochemical analysis of baseline tumor biopsy samples from 3 groups of patients with operable esophageal adenocarcinoma: surgery alone (N=54), 2 cycles of cisplatin-fluorouracil chemotherapy followed by surgery (N=46), and 2 cycles of oxaliplatin-fluorouracil chemotherapy (N=38). Expression of 48,803 genes was studied by Illumina HT-12 chip array followed by functional pathway analysis in oxaliplatin-treated patients before and after chemotherapy (N=38). Results were tested for association with pathological response (Mandard regression grading) (Chi-square test), disease free survival (DFS) and overall survival (OS) (Wilcoxon test). Results: High Ki67 protein levels were associated with worse OS (P=0.034; N=93). None of the markers were predictive of clinical endpoints following cisplatin chemotherapy. In oxaliplatin-treated patients (N=38), functional pathway analysis revealed associations between overexpression of cell cycle/DNA repair genes at baseline and worse clinical outcomes. Expression of 15 DNA repair (DNAR) genes was associated with DFS, and 16 DNAR genes with OS. Expression of 21 DNAR genes significantly increased after chemotherapy. Gene expression associations were validated at the protein level: high MUS81 at baseline predicted poor DFS (P=0.036) and poor OS (P=0.015) following oxaliplatin therapy; high XPF expression was associated with lack of pathological response (P=0.032); high Cyclin B1 predicted poor DFS (P=0.017). XPF protein levels increased following oxaliplatin (P=0.001, paired t-test). Conclusions: By confirmation of mRNA findings at the protein level, XPF, MUS81, and Cyclin B1 have been discovered as predictive biomarkers for response to oxaliplatin chemotherapy that merit prospective validation as tools for patient selection. Funded by Oxford NIHR Biomedical Research Centre and ECMC.
Frequency of depression in patients with chronic obstructive pulmonary disease
Authors: Muqarrab Hussain Kamran, Mohammad Azam Mushtaq, Homayoun Ghulam Murtaza, Mohammad Imran Shehzad, Mohammad Zubair Shaheen, Shazib Shamim, Fasiha Bukhari
Journal: European Respiratory Journal (2014)

Introduction: COPD is chronic respiratory illnesses which is usually progressive and irreversible. Depression is a common co -morbidity in patients with COPD. Early diagnosis and treatment of depression is an important aspect for COPD management.Depressed mood lowers the force needed to cope with the chronic disease and the physical symptoms become less tolerable.  Objective: To find out the frequency of depression in COPD patients.  Material and Methods:100 consecutive patients with diagnosed COPD and fulfilling the inclusion and exclusion criteria were included in the study. All the patients were asked questions from BDI Questionnaire and were classified into those with either no depression, mild to moderate depression, moderate to severe depression or severe depression.  Results: N=100 patients with COPD, 85% males and 15% females. Mean duration of disease was 5.35+3.24. Mean for duration of treatment was 5.34+3.24 years. Mean number of smoking pack years was 23.24+8.9. Overall 47 patients (47%) were found to have depression. There were only 15 (31.9%) patients with mild to moderate depression, 14 (29.7%) with moderate to severe depression and 18 (38.2%) with severe depression. Depression was seen in 41.3% patients with smoking 20 pack years.Depression was seen in 6.67% patient with mild COPD, 44.6% with moderate COPD, 58.6% with severe COPD and 80% with very severe COPD.  Conclusion: There is a high frequency of depression in patients with COPD. Depression was found to be associated with longer duration of disease, higher number of smoking pack years and with increasing severity of COPD.  Key words:Chronic Obstructive Pulmonary Disease, Beck Depression Inventory.
Hepatitis A antibody prevalence among people with an intellectual disability in Ireland
Authors: G Sayers, S Dooley, A Staines, J Lane, L Thornton, M Staines, S Brennan, P Kelly, F Finlay
Journal: Eurosurveillance (2007)

This manuscript aims to determine the prevalence of antibody to and risk factors for hepatitis A virus (HAV) in individuals attending three intellectual disability services through a cross-sectional survey held in Dublin, Ireland. Participants were 636 individuals aged four to 78 years attending three intellectual disability services. The main outcome measure was the measurement of anti-HAV (IgG antibody) in oral fluid swabs using an antibody capture enzyme immunoassay (EIA) technique. Risk factor information was obtained by questionnaire from the individual’s medical record.
Stabilization of cysteine-linked antibody drug conjugates with N-aryl maleimides
Authors: R. James Christie, Ryan Fleming, Binyam Bezabeh, Rob Woods, Shenlan Mao, Jay Harper, Augustine Joseph, Qianli Wang, Ze-Qi Xu, Herren Wu, Changshou Gao, Nazzareno Dimasi
Journal: Journal of Controlled Release (2015)
A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis
Authors: Ariella Weinberg-Shukron, Paul Renbaum, Rachel Kalifa, Sharon Zeligson, Ziva Ben-Neriah, Amatzia Dreifuss, Amal Abu-Rayyan, Noa Maatuk, Nilly Fardian, Dina Rekler, Moien Kanaan, Abraham O. Samson, Ephrat Levy-Lahad, Offer Gerlitz, David Zangen
Journal: Journal of Clinical Investigation (2015)

Ovarian development and maintenance are poorly understood; however, diseases that affect these processes can offer insights into the underlying mechanisms. XX female gonadal dysgenesis (XX-GD) is a rare, genetically heterogeneous disorder that is characterized by underdeveloped, dysfunctional ovaries, with subsequent lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism. Here, we report an extended consanguineous family of Palestinian origin, in which 4 females exhibited XX-GD. Using homozygosity mapping and whole-exome sequencing, we identified a recessive missense mutation in nucleoporin-107 (NUP107, c.1339G>A, p.D447N). This mutation segregated with the XX-GD phenotype and was not present in available databases or in 150 healthy ethnically matched controls. NUP107 is a component of the nuclear pore complex, and the NUP107-associated protein SEH1 is required for oogenesis in Drosophila. In Drosophila, Nup107 knockdown in somatic gonadal cells resulted in female sterility, whereas males were fully fertile. Transgenic rescue of Drosophila females bearing the Nup107D364N mutation, which corresponds to the human NUP107 (p.D447N), resulted in almost complete sterility, with a marked reduction in progeny, morphologically aberrant eggshells, and disintegrating egg chambers, indicating defective oogenesis. These results indicate a pivotal role for NUP107 in ovarian development and suggest that nucleoporin defects may play a role in milder and more common conditions such as premature ovarian failure.
Abstract 17258: Incremental Value of Coronary CT Angiography over Calcium Score in Predicting Intermediate-Term Outcomes and Resource Utilization
Authors: Kavitha M Chinnaiyan, Michael J Gallagher, Amr E Abbas, Gilbert L Raff
Journal: Circulation (2011)

Background: Prognostic utility of coronary artery calcium (CAC) is well-established. The incremental value of CAD severity assessed by coronary CT angiography (CCTA) over CAC is not well known. Methods: This retrospective analysis included patients who underwent CAC + CCTA at our institution and had complete 2-year follow-up. The study group was divided into four: CAC ≤400 + stenosis ≤50% (Group I), CAC ≤400 + stenosis &gt;50% (Group II), CAC &gt;400 + stenosis ≤50% (Group III) and CAC &gt;400 + stenosis &gt;50% (Group IV). Baseline demographics and 2-year follow-up data were compared among the groups for downstream major adverse cardiac events (MACE) (death, acute coronary syndromes and revascularization) and total resource utilization (CAD-related hospitalizations and emergency department (ED) evaluations, stress testing, invasive coronary angiography (ICA) and surgical or percutaneous revascularization). Results: The study group included 1496 patients (mean age 56 ± 12 years, 54% males) who underwent CAC and CCTA. Distribution among the four groups were: Group I = 1092 (73%), Group II = 236 (15.7%), Group III = 102 (6.8%) and Group IV = 66 (4.4%). Patients in Groups II and IV (stenosis &gt;50%) were more frequently male, older, diabetic, hypertensive and dyslipidemic (all p&lt;0.0001). At 2 years, patients in Groups II and IV had higher rates of MACE as well as resource utilization (p&lt;0.0001). On stepwise multivariable analysis of Framingham Risk Score, additional risk factors (peripheral, cerebrovascular and chronic obstructive lung disease), symptoms, CAC and CCTA findings, stenosis &gt;50% on CCTA alone was the strongest predictor of MACE and resource utilization, with significant incremental value over the combined effect of all clinical variables and CAC (Figure). Conclusions: CAD severity assessed by CCTA provides significant and incremental value over clinical risk scoring and CAC for predicting MACE and resource utilization at intermediate-term follow-up.
microRNA-mediated inhibition of IL-8 production from cystic fibrosis bronchial epithelial cells
Authors: Kevin Gaughan, Tidi Hassan, Raman Agarwal, Marcus Mall, Noel McElvaney, Catherine Greene
Journal: European Respiratory Journal (2013)

The pulmonary manifestations of cystic fibrosis (CF) are characterized by abnormally high levels of infiltrating neutrophils largely due to aberrant expression of interleukin-8 (IL-8) by airway epithelial cells. Thus inhibiting IL-8 expression within the CF lung represents an anti-inflammatory strategy. MicroRNAs (miRs) are post-transcriptional negative regulators. Overexpression of miRs is possible by the use of premiR mimetics. Here we profiled miRNA expression in CF vs. non CF endobronchial brushings (n=5 each) and CFBE41o- vs. 16HBE14o- bronchial epithelial cells lines. We identified a selection of lead miRs that are predicted to regulate IL-8 in silico and are under expressed in CF bronchial epithelium in vitro and in vivo. Based on further bioinformatic analysis and validation studies using an IL-8 3’UTR luciferase reporter we focused on four specific miRs. Levels of these miRs were quantified in whole lung homogenates from wild type (WT) and betaENaC-overexpressing (betaENaC-Tg) mice. All miRs were marginally decreased in the betaENaC-Tg compared to WT mice at 2 and 6 weeks of age, with miR-200b significantly lower at 6 weeks (*p
Positive expiratory pressure therapy improves inspiratory capacity and physical activity in patients with chronic obstructive pulmonary disease
Authors: Te-Fang Sheng, Wen-Ching Jao, Shu-Chuan Ho, Li-Fei Chen, Chun-Hua Wang, Han-Pin Kuo, Horng-Chyuan Lin
Journal: European Respiratory Journal (2013)

Background:  Dynamic hyperinflation results in exercise limitation in chronic obstructive pulmonary disease (COPD). Breathing techniques with a positive expiratory pressure (PEP) may be used to improve pulmonary function.   Objectives:  A study was undertaken to investigate whether PEP device could improve lung function, exercise tolerance and quality of life in COPD patients.   Methods:  Eight COPD patients received the 20-minute breathing training with a PEP device twice daily (PEP group) and 8 COPD patients did not take any breathing training as a control group. The pulmonary function, including inspiratory capacity (IC), exercise capacity (6 minute walk test), limb muscle strength and the quality of life (SF-12 test) were measured for each patient before and following 2-month study period.   Results:  The IC of COPD patients receiving PEP training was significantly increased from 1.2±0.3 to 1.3±0.3L (n=8, p   Conclusions:  Breathing control with a PEP device will not only improve the lung function, especially inspiratory capacity, but also better exercise capacity and physical activity of daily life in COPD patients.
Male and female psychiatrists and their patients
Authors: W. S. Fenton, C. B. Robinowitz, P. J. Leaf
Journal: American Journal of Psychiatry (1987)

Data from a national survey were used to explore whether the patients of male and female psychiatrists differed substantially in demographic or clinical characteristics and whether there were any differences in psychiatrists' treatment of same-gender versus opposite-gender patients. Women constituted about two-thirds of the female but only one-half of the male psychiatrists' patient loads. Female psychiatrists tended to see all of their patients more frequently, but few other differences were found. Better educated patients of both genders tended to have same-gender therapists; patients experiencing marital disruption tended to be seen by therapists of the opposite gender. Implications of these differences for training and manpower development are discussed.
Mechanisms of Cancer Cell Dormancy—Another Hallmark of Cancer?
Authors: Albert C. Yeh, Sridhar Ramaswamy
Journal: Cancer Research (2015)

Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biologic level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biologic insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately downregulate the RAS/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance.