tbuckley/cabot-search huggingface dataset:
Incidental Findings on Brain MRI in the General Population
Authors: Meike W. Vernooij, M. Arfan Ikram, Hervé L. Tanghe, Arnaud J.P.E. Vincent, Albert Hofman, Gabriel P. Krestin, Wiro J. Niessen, Monique M.B. Breteler, Aad van der Lugt
Journal: New England Journal of Medicine (2007)

Magnetic resonance imaging (MRI) of the brain is increasingly used both in research and in clinical medicine, and scanner hardware and MRI sequences are continually being improved. These advances are likely to result in the detection of unexpected, asymptomatic brain abnormalities, such as brain tumors, aneurysms, and subclinical vascular pathologic changes. We conducted a study to determine the prevalence of such incidental brain findings in the general population.The subjects were 2000 persons (mean age, 63.3 years; range, 45.7 to 96.7) from the population-based Rotterdam Study in whom high-resolution, structural brain MRI (1.5 T) was performed according to a standardized protocol. Two trained reviewers recorded all brain abnormalities, including asymptomatic brain infarcts. The volume of white-matter lesions was quantified in milliliters with the use of automated postprocessing techniques. Two experienced neuroradiologists reviewed all incidental findings. All diagnoses were based on MRI findings, and additional histologic confirmation was not obtained.Asymptomatic brain infarcts were present in 145 persons (7.2%). Among findings other than infarcts, cerebral aneurysms (1.8%) and benign primary tumors (1.6%), mainly meningiomas, were the most frequent. The prevalence of asymptomatic brain infarcts and meningiomas increased with age, as did the volume of white-matter lesions, whereas aneurysms showed no age-related increase in prevalence.Incidental brain findings on MRI, including subclinical vascular pathologic changes, are common in the general population. The most frequent are brain infarcts, followed by cerebral aneurysms and benign primary tumors. Information on the natural course of these lesions is needed to inform clinical management.
Phase II Trial of Irinotecan in Children With Refractory Solid Tumors: A Children's Oncology Group Study
Authors: Lisa R. Bomgaars, Mark Bernstein, Mark Krailo, Richard Kadota, Soma Das, Zhengjia Chen, Peter C. Adamson, Susan M. Blaney
Journal: Journal of Clinical Oncology (2007)

Purpose A phase II study was performed to determine the efficacy of irinotecan (IRN) in children with refractory solid tumors. Secondary objectives were to evaluate toxicity, pharmacokinetics, pharmacodynamics, and UGT1A1 genotype. Patients and Methods A total of 181 patients were enrolled, of whom 171 were eligible. Patients received IRN 50 mg/m 2 /d for 5 days repeated every 3 weeks. Pharmacokinetic studies and UGT1A1 genotyping were performed. Results Of 161 patients assessable for response, one patient with hepatoblastoma had a complete response, with partial responses observed in patients with medulloblastoma (n = 4), rhabdomyosarcoma (n = 1), neuroblastoma (n = 1), and germinoma (n = 1), for an overall response rate of 5%. Grade 4 neutropenia and grade 3 to 4 diarrhea occurred in less than 7% of the courses administered. Pharmacokinetic studies were available for 79 patients. The mean ± standard deviation IRN plasma clearance was 374 ± 148 mL/min/m 2 , with median relative extent of conversion and relative extent of glucuronidation of 0.05 (range, 0.01 to 0.25) and 2.24 (range, 0.39 to 9.6), respectively. No association between UGT1A1 genotype (n = 61) and toxicity or pharmacokinetic parameters was observed. Conclusion IRN 50 mg/m 2 /d for 5 days every 21 days is well tolerated, but was not effective as a single agent in a spectrum of solid tumors, with the possible exception of patients with medulloblastoma (16% response rate). There was no association between UGT1A1*28 genotype and toxicity or pharmacokinetic parameters.
Gender Differences in Panic Disorder: Findings From the National Comorbidity Survey
Authors: Javaid I Sheikh, Gregory A Leskin, Donald F Klein
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Several epidemiological studies have demonstrated a higher prevalence of panic disorder in women than in men. This study explored whether the prevalence of specific panic symptoms differs by gender. METHOD: National Comorbidity Survey data from 609 respondents who met DSM-III-R criteria for panic disorder or panic attacks were analyzed to test for gender differences across 18 panic symptoms. RESULTS: Among National Comorbidity Survey respondents with panic disorder or panic attacks, female respondents were more likely than male respondents to experience respiration-related difficulties during panic attacks. CONCLUSIONS: Specific symptoms occurring during panic attacks differ by gender. The pathophysiology of these symptom differences may involve gender differences in sensitivity to CO2 and in the threshold for panic attacks during hypoxic and hypercapnic states.
A Systems Approach to Analysis of Molecular Complexity in Breast Cancer
Authors: Bryan T. Hennessy, Ana Maria Gonzalez-Angulo, Mark S. Carey, Gordon B. Mills
Journal: Clinical Cancer Research (2009)

Abstract In this issue of Clinical Cancer Research, Andre et al. apply high-resolution arrays to elucidate copy number anomalies in breast cancer. They identify distinct copy number anomaly patterns in different breast cancer subtypes that implicate a number of genes as potential therapeutic targets and as potential markers of therapy responsiveness.
Closed-Loop Insulin Therapy Improves Glycemic Control in Children Aged &amp;lt;7 Years
Authors: Andrew Dauber, Liat Corcia, Jason Safer, Michael S.D. Agus, Sara Einis, Garry M. Steil
Journal: Diabetes Care (2012)

To assess the possibility of improving nocturnal glycemic control as well as meal glycemic response using closed-loop therapy in children aged <7 years.This was a randomized controlled crossover trial comparing closed-loop with standard open-loop insulin pump therapy performed in an inpatient clinical research center. Ten subjects aged <7 years with type 1 diabetes for >6 months treated with insulin pump therapy were studied. Closed-loop therapy and standard open-loop therapy were compared from 10:00 p.m. to 12:00 p.m. on 2 consecutive days. The primary outcome was plasma glucose time in range (110-200 mg/dL) during the night (10:00 p.m.-8:00 a.m.). Secondary outcomes included peak postprandial glucose levels, incidence of hypoglycemia, degree of hyperglycemia, and prelunch glucose levels.A trend toward a higher mean nocturnal time within target range was noted for closed- versus open-loop therapy, although not reaching statistical significance (5.3 vs. 3.2 h, P = 0.12). There was no difference in peak postprandial glucose or number of episodes of hypoglycemia. There was significant improvement in time spent >300 mg/dL overnight with closed-loop therapy (0.18 vs. 1.3 h, P = 0.035) and the total area under the curve of glucose >200 mg/dL (P = 0.049). Closed-loop therapy returned prelunch blood glucose closer to target (189 vs. 273 mg/dL on open loop, P = 0.009).Closed-loop insulin delivery decreases the severity of overnight hyperglycemia without increasing the incidence of hypoglycemia. The therapy is better able to reestablish target glucose levels in advance of a subsequent meal. Younger children with type 1 diabetes may reap significant benefits from closed-loop therapy.
Morning serum cortisol concentrations after 2 mg inhaled beclomethasone dipropionate in normal subjects: effect of a 750 ml spacing device.
Authors: M Farrer, A J Francis, S J Pearce
Journal: Thorax (1990)

Large spacing devices have been shown to provide more selective delivery of an inhaled steroid to the lung but the effect on the hypothalamo-pituitary-adrenal suppression associated with high dose inhaled corticosteroids has been little studied. The effect of a large spacing device (Volumatic; 750 ml) on suppression of 0900 h cortisol after 2 mg inhaled beclomethasone dipropionate was therefore investigated in normal, healthy volunteers. Twenty four subjects (12 male, 12 female) took part in a randomised, double blind, placebo controlled cross over study in which a single dose of 2 mg beclomethasone dipropionate was taken at 2300 h on two occasions seven days apart, once from a metered dose inhaler alone and once from a metered dose inhaler attached to a 750 ml spacing device. The 0900 h serum cortisol concentration was the same on the morning before each administration (468 nmol/l, 95% confidence interval (CI) 390-561 nmol/l, day 1 v 479 nmol/l, 95% CI 463-494 nmol/l, day 8). The 0900 h serum cortisol concentration the following morning, however, was lower when 2 mg beclomethasone dipropionate was given by metered dose inhaler alone (182 (95% CI 128-264) nmol/l) than when it was given by a spacing device (363 (95% CI 281-475) nmol/l). These results suggest that a large spacing device attached to a metered dose inhaler may decrease the risk of hypothalamo-pituitary-adrenal suppression by high dose inhaled steroid treatment.
CNS disease in younger patients with aggressive B-cell lymphoma: an analysis of patients treated on the Mabthera International Trial and trials of the German High-Grade Non-Hodgkin Lymphoma Study Group
Authors: N. Schmitz, S. Zeynalova, B. Glass, U. Kaiser, E. Cavallin-Stahl, M. Wolf, M. Haenel, M. Loeffler, L. Truemper, M. Pfreundschuh
Journal: Annals of Oncology (2011)
MB-13 * HDAC AND PI3K ANTAGONISTS COOPERATE TO INHIBIT GROWTH OF MYC-DRIVEN MEDULLOBLASTOMA
Authors: K.-W. Liu, Y. Pei, R. Wechsler-Reya
Journal: Neuro-Oncology (2015)

Medulloblastoma (MB) is a highly malignant pediatric brain tumor. Despite aggressive therapy, many patients succumb to the disease, and survivors experience severe side effects from treatment. MYC-driven MB has a particularly poor prognosis, and would greatly benefit from novel therapies. We used an animal model of MYC-driven MB to screen for drugs that decrease viability of tumor cells. Among the most effective compounds were histone deacetylase inhibitors (HDACI). HDACI potently inhibit survival of MYC-driven MB cells in vitro, in part by inducing expression of the Foxo1 tumor suppressor gene. HDACI also synergize with phosphatidylinositol 3-kinase inhibitors (PI3KI) to inhibit tumor growth in vivo. These studies identify a novel and effective combination therapy for the most aggressive form of MB.
Plasma concentrations of dietary and nondietary antioxidants are low in severe asthma
Authors: N. L. A. Misso, J. Brooks-Wildhaber, S. Ray, H. Vally, P. J. Thompson
Journal: European Respiratory Journal (2005)

Low antioxidant levels and oxidative stress due to airway inflammation may be important determinants of asthma severity. The objective of the present study was to determine whether lower antioxidant intake and plasma antioxidant concentrations are associated with more severe asthma. Dietary antioxidant intakes and asthma severity were assessed using questionnaires, and plasma concentrations of ascorbic acid, vitamin E, carotenoids, bilirubin, albumin, uric acid and total antioxidant status were measured in 53 mild-to-moderate and 28 severe asthmatic patients and in 43 nonasthmatic subjects. Vitamin C and carotene intakes were lower in males than females and were particularly low in males with severe asthma. Plasma ascorbic acid was lower in severe (31.9+/-3.6 microM) compared with mild-to-moderate asthmatic (52.3+/-2.6) or control subjects (52.7+/-2.9). Low plasma ascorbic acid (odds ratio (OR) 0.93; 95% confidence interval (CI) 0.9-0.97), bilirubin (OR 0.69; 95% CI 0.51-0.93) and increased plasma cholesterol (OR 1.98; 95% CI 1.05-3.73) were independently associated with severe asthma. Albumin was positively and cholesterol negatively correlated with lung function. Low plasma concentrations of specific antioxidants are associated with more severe asthma. Increased antioxidant intake may help reduce the burden of severe asthma, particularly in males.
Non-traumatic chylothorax - A retrospective analysis
Authors: Hans Dabó, Inês Neves, Fernando Coelho, Maria Teles, Anabela Marinho
Journal: European Respiratory Journal (2012)

Introduction : Chylotorax (CL) is the presence of lymph in the pleural space. Diagnosis is based on lipoprotein profile of the pleural fluid (PF). The etiology is variable.   Aims : To characterize presentation and causes of non-traumatic CL.   Methods : Retrospective analysis of adults with CL (triglycerides ≥ 110 mg/dl) hospitalized in a central hospital between Jan/04 and Jun/11. A review, after computer supported search of hospital files of patients diagnosed with CL was made. Clinical, laboratory and image presentation, as well as treatment and outcome were analysed.   Results : We identified 27 (43,5%) patients (pts)with non-traumatic CL: 19 (70,4%) were women. The median age was 62 years (33 – 96 years old). Dyspnea was present in 22 (81,5%), cough in 7 (25,9%) and chest pain in 6 (22,2%). Effusion was unilateral in 22 (81,5%), with milky appearance in 16 (59,3%); exudate in 26 (96,3%) and transudate in 1 (3,7%). Mean ± sd of the triglycerides was 477.4± 456.7 mg/dl. Etiologies: lymphoma in 14 (51,8%), metastatic cancer in 4 (14,8%), pulmonary tuberculosis in 2 (7,4%), liver cirrhosis in 2 (7,4%), lymphangioleyomiomatosis in 2 (7,4%), inconclusive in 3 (11,1%). Chest drain was needed in 11 (40,7%) pts, pleurodesis in 3 (11,1%). Infectious complications were seen in 13 (48,1%). Effusions solved in 6 (22,2%), persisted in 16 (59,3%) and 5 pts (18,5%) died. After discharge 6 (22,2%) remained without recurrence, 1 (6,3%) resolved, 12 (75%) persisted and the evolution is unknown in 3 (18,7%). Median follow up was 2,4 years (1,2 – 7,4 years).   Conclusion:  Our findings mirror those in the literature - CL may have no classic milky appearance, can be transudate, infectious complications are common and the most frequent cause was lymphoma.
Transdifferentiation of Human Peripheral Blood CD34 <sup>+</sup> -Enriched Cell Population Into Cardiomyocytes, Endothelial Cells, and Smooth Muscle Cells In Vivo
Authors: Edward T.H. Yeh, Sui Zhang, Henry D. Wu, Martin Körbling, James T. Willerson, Zeev Estrov
Journal: Circulation (2003)

Adult human peripheral blood cells have been shown to differentiate into mature cells of nonhematopoietic tissues, such as hepatocytes and epithelial cells of the skin and gastrointestinal track. We investigated whether these cells could also transdifferentiate into human cardiomyocytes, mature endothelial cells, and smooth muscle cells in vivo.Myocardial infarction was created in SCID mice by occluding the left anterior descending coronary artery, after which adult peripheral blood CD34+ cells were injected into the tail vein. Hearts were harvested 2 months after injection and stained for human leukocyte antigen (HLA) and markers for cardiomyocytes, endothelial cells, and smooth muscle cells. Cardiomyocytes, endothelial cells, and smooth muscle cells that bear HLA were identified in the infarct and peri-infarct regions of the mouse hearts. In a separate experiment, CD34+ cells were injected intraventricularly into mice without experimental myocardial infarction. HLA-positive myocytes and smooth muscle cells could only be identified in 1 of these mice killed at different time points.Adult peripheral blood CD34+ cells can transdifferentiate into cardiomyocytes, mature endothelial cells, and smooth muscle cells in vivo. However, transdifferentiation is augmented significantly by local tissue injury. The use of peripheral blood CD34+ cells for cell-based therapy should greatly simplify the procurement of cells for the regeneration of damaged myocardium.
Short term effects of temperature on risk of myocardial infarction in England and Wales: time series regression analysis of the Myocardial Ischaemia National Audit Project (MINAP) registry
Authors: K. Bhaskaran, S. Hajat, A. Haines, E. Herrett, P. Wilkinson, L. Smeeth
Journal: BMJ (2010)

Objective To examine the short term relation between ambient temperature and risk of myocardial infarction. Design Daily time series regression analysis. Setting 15 conurbations in England and Wales. Participants 84 010 hospital admissions for myocardial infarction recorded in the Myocardial Ischaemia National Audit Project during 2003-6 (median 57 events a day). Main outcome measures Change in risk of myocardial infarction associated with a 1°C difference in temperature, including effects delayed by up to 28 days. Results Smoothed graphs revealed a broadly linear relation between temperature and myocardial infarction, which was well characterised by log-linear models without a temperature threshold: each 1°C reduction in daily mean temperature was associated with a 2.0% (95% confidence interval 1.1% to 2.9%) cumulative increase in risk of myocardial infarction over the current and following 28 days, the strongest effects being estimated at intermediate lags of 2-7 and 8-14 days: increase per 1°C reduction 0.6% (95% confidence interval 0.2% to 1.1%) and 0.7% (0.3% to 1.1%), respectively. Heat had no detrimental effect. Adults aged 75-84 and those with previous coronary heart disease seemed more vulnerable to the effects of cold than other age groups (P for interaction 0.001 or less in each case), whereas those taking aspirin were less vulnerable (P for interaction 0.007). Conclusions Increases in risk of myocardial infarction at colder ambient temperatures may be one driver of cold related increases in overall mortality, but an increased risk of myocardial infarction at higher temperatures was not detected. The risk of myocardial infarction in vulnerable people might be reduced by the provision of targeted advice or other interventions, triggered by forecasts of lower temperature.
Regulation of mammalian siderophore 2,5-DHBA in the innate immune response to infection
Authors: Zhuoming Liu, Scott Reba, Wei-Dong Chen, Suheel Kumar Porwal, W. Henry Boom, Robert B. Petersen, Roxana Rojas, Rajesh Viswanathan, L. Devireddy
Journal: The Journal of Experimental Medicine (2014)

Competition for iron influences host–pathogen interactions. Pathogens secrete small iron-binding moieties, siderophores, to acquire host iron. In response, the host secretes siderophore-binding proteins, such as lipocalin 24p3, which limit siderophore-mediated iron import into bacteria. Mammals produce 2,5-dihydroxy benzoic acid, a compound that resembles a bacterial siderophore. Our data suggest that bacteria use both mammalian and bacterial siderophores. In support of this idea, supplementation with mammalian siderophore enhances bacterial growth in vitro. In addition, mice lacking the mammalian siderophore resist E. coli infection. Finally, we show that the host responds to infection by suppressing siderophore synthesis while up-regulating lipocalin 24p3 expression via TLR signaling. Thus, reciprocal regulation of 24p3 and mammalian siderophore is a protective mechanism limiting microbial access to iron.
Brain damage in American Football
Authors: Chad A Asplund, Thomas M Best
Journal: BMJ (2015)

Inevitable consequence or avoidable risk? 

The subject of brain injury in American football has never been more controversial. For 15 years, the National Football League (NFL) denied any link between football and brain injury or chronic traumatic encephalopathy. It supported this claim with research performed by an NFL appointed committee, which contradicted that of independent researchers. Despite this long history of denial, the NFL recently settled (for $870m (£578m; €822m)) a legal case filed by former players who claimed their neurological deficits were from playing football.1 It remains unclear whether this was an admission by NFL that football can lead to chronic traumatic encephalopathy or other brain injury or a public relations response to an overwhelming media reaction to deaths of prominent retired football players and a perceived lack of concern for retired NFL players and their families. What is clear is that more research is needed to determine how athletes develop brain injury and whether strategies could protect them.

Chronic traumatic encephalopathy (CTE) was first described in American football players as a progressive neurodegenerative syndrome leading to neuronal loss coupled with protein and plaque deposits in the brain as a …
Insulin like growth factor binding protein 7 (IGFBP7) expression is linked to poor prognosis but may protect from bone disease in multiple myeloma
Authors: Arnold Bolomsky, Dirk Hose, Martin Schreder, Anja Seckinger, Susanne Lipp, Bernard Klein, Daniel Heintel, Heinz Ludwig, Niklas Zojer
Journal: Journal of Hematology & Oncology (2015)

Insulin like growth factor binding protein 7 (IGFBP7) is a secreted protein binding insulin like growth factor 1 (IGF-1), insulin, vascular endothelial growth factor A (VEGFA), and activin A. It antagonizes bone morphogenetic proteins and is involved in the tumour propagation of solid as well as haematological malignancies. Its role in multiple myeloma (MM) is not defined so far. We therefore aim here to investigate its prognostic and pathophysiological role in MM.The clinical significance of IGFBP7 gene expression was investigated by gene expression profiling in two independent cohorts (n = 948) of newly-diagnosed MM patients. Methylation of the IGFBP7 promoter was analysed by pyrosequencing and treatment of MM cell lines with 5-aza-2-deoxycytidine. The impact of IGFBP7 on MM cells was studied by CCK-8 assay, BrdU assay and flow cytometry, respectively. IGFBP7 expression in bone marrow stromal cells (BMSCs) was studied by quantitative RT-PCR. For osteoblast development, immortalized and primary human BMSCs were cultured in osteogenic differentiation medium for 7-14 days in the presence of recombinant human IGFBP7 and/or activin A.Median IGFBP7 expression is significantly lower in CD138-purified plasma cells from individuals with MGUS and MM, compared to normal bone marrow plasma cells. IGFBP7 gene expression in MM cells is regulated by methylation, shown by pyrosequencing and exposure to demethylating agents (5-aza-2-deoxycytidine). High expression of IGFBP7 in MM cells is associated with adverse survival in two independent cohorts of 247 and 701 newly-diagnosed MM patients treated with high-dose therapy and autologous stem cell transplantation. IGFBP7 is associated with prognostically adverse chromosomal aberrations (t(4;14) and gain of 1q21), MMSET expression, and higher myeloma cell proliferation. In vitro, IGFBP7 overcomes activin A induced osteoblast suppression and promotes osteogenesis. MM cells downregulate IGFBP7 in stromal cells, possibly contributing to the osteoblast suppression found in MM. Conversely, higher IGFBP7 expression is associated with a lower probability of myeloma bone disease.Our data indicate that IGFBP7 expression is a marker for a specific methylation pattern in myeloma, linked to translocation t(4;14) associated MMSET expression, showing clinical features of adverse prognosis with absence of myeloma bone disease.