tbuckley/cabot-search huggingface dataset:
Pathological and molecular characteristics distinguishing contralateral metastatic from new primary breast cancer
Authors: B. Banelli, I. Casciano, A. Di Vinci, B. Gatteschi, A. Levaggi, F. Carli, C. Bighin, S. Salvi, G. Allemanni, P. Ghiorzo, P. Pronzato, M. Venturini, M. Romani, L. Del Mastro
Journal: Annals of Oncology (2009)
JAK2 germline genetic variation affects disease susceptibility in primary myelofibrosis regardless of V617F mutational status: nullizygosity for the JAK2 46/1 haplotype is associated with inferior survival
Authors: A Tefferi, T L Lasho, M M Patnaik, C M Finke, K Hussein, W J Hogan, M A Elliott, M R Litzow, C A Hanson, A Pardanani
Journal: Leukemia (2009)
Cardiovascular autonomic nerve function in patients with hypoxaemic chronic obstructive pulmonary disease
Authors: AG Stewart, JC Waterhouse, P Howard
Journal: European Respiratory Journal (1991)

Intraneural hypoxaemia is recognized as a pathogenic mechanism in diabetic neuropathy. A similar pathophysiological process may occur in chronic obstructive pulmonary disease (COPD). Autonomic neuropathy is not recognized in COPD. We compared 96 patients with hypoxaemic COPD to 22 age-matched control subjects to see whether autonomic dysfunction occurs in COPD and whether there was any correlation with the severity of hypoxaemia. The cardiovascular autonomic tests consisted of heart rate responses (mainly parasympathetic function) to a Valsalva manoeuvre, deep breathing and postural change and blood pressure responses (mainly of sympathetic origin) to postural change and sustained handgrip. Early autonomic neuropathy is defined as one abnormal test and definite autonomic neuropathy as two abnormal tests according to the normal range. These autonomic tests were reproducible in our study population. Although the symptoms and signs of autonomic neuropathy were rare, definite autonomic dysfunction was found in 35%, and early autonomic neuropathy in a further 47%, of patients whose arterial oxygen tension (PaO2) was less than 8 kPa (60 mmHg). Only 18% of the control group had evidence of an age-related early autonomic dysfunction. Parasympathetic autonomic dysfunction was significantly correlated with PaO2 whilst the sympathetic tests were relatively normal. Correction of hypoxaemia for one hour or administration of ipratropium bromide or terbutaline had no effect on autonomic function. Subclinical autonomic neuropathy is a feature of hypoxaemic COPD. Its importance in the disease process and its role in prognosis needs evaluation.
Down-regulation of interleukin-3/granulocyte-macrophage colony-stimulating factor receptor β-chain in BCR-ABL+human leukemic cells: association with loss of cytokine-mediated Stat-5 activation and protection from apoptosis after BCR-ABL inhibition
Authors: Nicholas J. Donato, Ji Y. Wu, Ling Zhang, Hagop Kantarjian, Moshe Talpaz
Journal: Blood (2001)
Individual variability in compensatory eating following acute exercise in overweight and obese women
Authors: Mark Hopkins, John E Blundell, Neil A King
Journal: British Journal of Sports Medicine (2013)

While compensatory eating following acute aerobic exercise is highly variable, little is known about the underlying mechanisms that contribute to the alterations in exercise-induced eating behaviour.Overweight and obese women (body mass index=29.6±4.0 kg/m(2)) performed a bout of cycling individually tailored to expend 400 kcal (EX) or a time-matched no exercise control condition in a randomised, counter-balanced order. 60 min after the cessation of exercise, an ad libitum test meal was provided. Substrate oxidation and subjective appetite ratings were measured during exercise/time-matched rest, and during the period between the cessation of exercise and food consumption.While ad libitum energy intake (EI) did not differ between EX and the control condition (666.0±203.9 vs 664.6±174.4 kcal, respectively; ns), there was a marked individual variability in compensatory EI. The difference in EI between EX and the control condition ranged from -234.3 to 278.5 kcal. Carbohydrate oxidation during exercise was positively associated with postexercise EI, accounting for 37% of the variance in EI (r=0.57; p=0.02).These data indicate that the capacity of acute exercise to create a short-term energy deficit in overweight and obese women is highly variable. Furthermore, exercise-induced CHO oxidation can explain a part of the variability in acute exercise-induced compensatory eating. Postexercise compensatory eating could serve as an adaptive response to facilitate the restoration of carbohydrate balance.
TrkBT1 Induces Liver Metastasis of Pancreatic Cancer Cells by Sequestering Rho GDP Dissociation Inhibitor and Promoting RhoA Activation
Authors: Zhongkui Li, Zhe Chang, Lucia J. Chiao, Ya'an Kang, Qianghua Xia, Cihui Zhu, Jason B. Fleming, Douglas B. Evans, Paul J. Chiao
Journal: Cancer Research (2009)

Abstract Many genetic and molecular alterations, such as K-ras mutation and NF-κB activation, have been identified in pancreatic cancer. However, the mechanisms by which pancreatic cancer metastasizes still remain to be determined. Although we previously showed that the tropomyosin-related kinase B (TrkB) was significantly correlated with the development of liver metastasis, its function in pancreatic cancer metastasis remained unresolved. In the present study, we showed that overexpressed TrkB is an alternatively spliced transcript variant of TrkB (TrkBT1) with a unique COOH-terminal 12–amino acid sequence and is mainly localized in the cytoplasm. Our results showed that overexpression of Flag-tagged TrkBT1 but not a Flag-tagged TrkBT1 COOH-terminal deletion mutant (Flag-TrkBT1ΔC) in nonmetastatic pancreatic cancer cells enhanced cell proliferation, promoted formation of colonies in soft agar, stimulated tumor cell invasion, and induced liver metastasis in an orthotopic xenograft mouse model of pancreatic cancer. TrkBT1 interacted with Rho GDP dissociation inhibitor (GDI) in vivo, but Flag-TrkBT1ΔC did not. Furthermore, overexpression of Flag-TrkBT1 and knockdown of RhoGDI expression by RhoGDI short hairpin RNAs promoted RhoA activation, but Flag-TrkBT1ΔC overexpression did not. Therefore, our results showed that TrkBT1 overexpression induces liver metastasis of pancreatic cancer and uncovered a unique signaling mechanism by which TrkBT1 sequesters GDI and activates RhoA signaling. [Cancer Res 2009;69(19):7851–9]
Is it necessary to delay antiviral therapy for 3-6 months to anticipate HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B in endemic areas of HBV genotype C?
Authors: Byung-Cheol Song, Yoo-Kyung Cho, Hyeyoung Jwa, Eun Kwang Choi, Heung Up Kim, Hyun Joo Song, Soo-Young Na, Sun-Jin Boo, Seung Uk Jeong
Journal: Clinical and Molecular Hepatology (2014)

Background/Aims Spontaneous HBeAg seroconversion occurs frequently in the immune reactive phase in HBeAg-positive chronic hepatitis B (CHB). Therefore, observation for 3-6 months before commencing antiviral therapy is recommended in patients with alanine aminotransferase (ALT) levels that exceed twice the upper limit of normal (ULN). However, HBeAg seroconversion occurs infrequently in patients infected with hepatitis B virus (HBV) genotype C. The aim of the present study was to determine whether the waiting policy is necessary in endemic areas of HBV genotype C infection. Methods Ninety patients with HBeAg-positive CHB were followed prospectively without administering antiviral therapy for 6 months. Antiviral therapy was initiated promptly at any time if there was any evidence of biochemical (i.e., acute exacerbation of HBV infection or aggravation of jaundice) or symptomatic deterioration. After 6 months of observation, antiviral therapy was initiated according to the patient's ALT and HBV DNA levels. Results Only one patient (1.1%) achieved spontaneous HBeAg seroconversion. Biochemical and symptomatic deterioration occurred before 6 months in 17 patients (18.9%) and 5 patients, respectively. High ALT and HBV DNA levels were both independent risk factors for biochemical deterioration. Of 15 patients with HBV DNA â¥5.1Ã107 IU/mL and ALT â¥5ÃULN, biochemical deterioration occurred in 7 (46.7%), including 1 patient receiving liver transplantation due to liver failure. Conclusions Spontaneous HBeAg seroconversion in patients with HBeAg-positive CHB is rare within 6 months. Biochemical deterioration was common and may lead to liver failure. Immediate antiviral therapy should be considered, especially in patients with high ALT and HBV DNA levels in endemic areas of genotype C infection. Keywords: Hepatitis B virus, chronic hepatitis B; acute exacerbation of hepatitis B, HBV genotype
A High-Powered View of the Filtration Barrier
Authors: János Peti-Peterdi, Arnold Sipos
Journal: Journal of the American Society of Nephrology (2010)

Multiphoton excitation fluorescence microscopy is a powerful noninvasive imaging technique for the deep optical sectioning of living tissues. Its application in several intact tissues is a significant advance in our understanding of organ function, including renal pathophysiological mechanisms. The glomerulus, the filtering unit in the kidney, is one good example of a relatively inaccessible and complex structure, with cell types that are otherwise difficult to study at high resolution in their native environment. In this article, we address the application, advantages, and limitations of this imaging technology for the study of the glomerular filtration barrier and the controversy it recently generated regarding the glomerular filtration of macromolecules. More advanced and accurate multiphoton determinations of the glomerular sieving coefficient that are presented here dismiss previous claims on the filtration of nephrotic levels of albumin. The sieving coefficient of 70-kD dextran was found to be around 0.001. Using a model of focal segmental glomerulosclerosis, increased filtration barrier permeability is restricted only to areas of podocyte damage, consistent with the generally accepted role of podocytes and the glomerular origin of albuminuria. Time-lapse imaging provides new details and important in vivo confirmation of the dynamics of podocyte movement, shedding, replacement, and the role of the parietal epithelial cells and Bowman's capsule in the pathology of glomerulosclerosis.
Antitumor Effect of NK012, a 7-Ethyl-10-Hydroxycamptothecin–Incorporating Polymeric Micelle, on U87MG Orthotopic Glioblastoma in Mice Compared with Irinotecan Hydrochloride in Combination with Bevacizumab
Authors: Jun-ichiro Kuroda, Jun-ichi Kuratsu, Masahiro Yasunaga, Yoshikatsu Koga, Hirotsugu Kenmotsu, Takashi Sugino, Yasuhiro Matsumura
Journal: Clinical Cancer Research (2010)

Abstract Purpose: To clarify the effect of bevacizumab on NK012 therapy in mice bearing U87MG glioblastoma orthotopic xenografts in comparison with the combination therapy of irinotecan hydrochloride (CPT-11) with bevacizumab. Experimental Design: NK012 at 7-ethyl-10-hydroxycamptothecin (SN-38) equivalent dose of 30 mg/kg was administered intravenously three times every 4 days with or without bevacizumab. CPT-11 at 66.7 mg/kg was administered intravenously three times every 4 days or CPT-11 at 40 mg/kg/d over 5 consecutive days with or without bevacizumab. Bevacizumab was administered intraperitoneally six times every 4 days in each experiment. In vivo antitumor effects were evaluated by bioluminescence imaging, histopathologic evaluation, and immunohistochemistry. To evaluate interaction with bevacizumab, free SN-38 concentration in tumor tissues was examined by high-performance liquid chromatography. Results: CPT-11 in combination with bevacizumab showed significantly more potent antitumor activity and longer survival than CPT-11 monotherapy (P &amp;lt; 0.05). However, there was no difference between NK012 monotherapy and NK012 in combination with bevacizumab. Concentration of free SN-38 released from NK012 in tumor tissue decreased in combination with bevacizumab (P = 0.027). NK012 monotherapy or NK012 with bevacizumab showed potent antitumor activity and longer survival than any dosing method of CPT-11 in combination with bevacizumab (P &amp;lt; 0.05). Orthotopic tumors treated with NK012 showed decreased tumor cellularity and lower Ki-67 index (P &amp;lt; 0.001) relative to those treated with CPT-11/bevacizumab. Conclusions: The present study using orthotopic glioblastoma model in mice may warrant further preclinical evaluation of NK012 before conducting the clinical trial of the drug, because the antitumor activity of NK012 monotherapy was superior to the combination therapy of CPT-11 with bevacizumab. Clin Cancer Res; 16(2); 521–9
Prophylactic mastectomy cuts breast cancer risk
Authors: S. Gottlieb
Journal: BMJ (1999)

Prophylactic bilateral mastectomy dramatically reduces the likelihood of developing breast cancer in women with a strong family history of the disease, according to the first study to clarify the value of this previously controversial approach (New England Journal of Medicine 1999;340:77-84).

The findings, from a retrospective study of 639women who had their breasts removed between 1960and 1993,are being regarded …
INJURY PROFILE OF BRAZILIAN ATHLETES IN OLYMPIC GAMES 2012
Authors: C Bolling, M Leite, JG Neto, H Barreto, F Tadiello, L Medeiros, F Rodrigues
Journal: British Journal of Sports Medicine (2014)

Background Athletes performance in Olympic Games depends on health condition. Physiotherapy staff treats injuries, relieves pain and manages symptoms to help athletes to reach the highest performance. Objetive To describe injury profile of athletes treated in Physiotherapy department in London Olympic Games 2012. Design This is a descriptive epidemiological study about injuries in Olympic Games. Setting This study was conducted by Brazilian delegation physiotherapists during the Olympic Games in London 2012. Participants All athletes (n=132) treated in physiotherapy department of Brazilian Olympic committee. Intervention All brazilian delegation athletes could request for health care in the physiotherapy department. Physiotherapists reported all injuries and interventions in a standard form. Main outcome measurements The information collected was: name, gender, modality, number of sessions; related to injuries: location, type, cause, mechanism, symptoms duration. The data analyses was descriptive. Results 132 athletes (72 men/60 women) were treated in 680 treatment sessions with a mean of 5.15 session/injury. Injuries distribution related to modality was: boxe (13.9%), volleyball (13.9%), basketball (12.2%), handball (11.4%), gymnastics (7,3%), judo (6.5%), athletics (5.7%), swimming (5.7%), sailing (5.7%), others (14.7%). Injuries occurred in lower limbs (55.3%), upper limbs (22.7%), trunk (19,6%), others (2,4%). The tendinopathies (29%) and muscular injuries (31%) were the most common type. Most frequent injury cause was overuse (73%) followed by contact injuries (14%). The majority of injuries had more than 4 months duration (33%), followed by 1–7 days duration (24%) and 8–30 days (12%). According to mechanism, 30% was traumatic injuries. Conclusion The high number of overuse, tendinopathies and long term injuries indicate that many athletes arrived injured at Olympic games. Therefore a preventive strategy for chronic conditions should be a priority in Pre-Olympic training.
Review: Vitamin D<sub>3</sub>supplementation may reduce mortality in adults; vitamin D<sub>2</sub>does not
Authors: Robert H. Fletcher
Journal: Annals of Internal Medicine (2014)

Source Citation Chowdhury R, Kunutsor S, Vitezova A, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903. 24690623
Glucocorticoid Dose Thresholds Associated With All‐Cause and Cardiovascular Mortality in Rheumatoid Arthritis
Authors: Inmaculada del Rincón, Daniel F. Battafarano, Jose F. Restrepo, John M. Erikson, Agustín Escalante
Journal: Arthritis & Rheumatology (2013)

Objective To delineate daily and cumulative glucocorticoid dose thresholds associated with increased mortality rates in rheumatoid arthritis (RA). Methods We studied RA patients recruited from rheumatology clinics. Annually, we assessed the glucocorticoid dose, demographic, socioeconomic, clinical, and laboratory features of RA, cardiovascular (CV) risk factors, and vital status. We used Cox proportional hazards regression to assess associations between the daily or cumulative glucocorticoid dose and death, adjusting for potential confounders and for the propensity to receive glucocorticoids. We tested strata of the glucocorticoid dose to delineate the threshold associated with death. Results We studied 779 RA patients with a total of 7,203 person‐years of observation, during which 237 of them died, yielding a mortality rate of 3.2 per 100 person‐years (95% confidence interval [95% CI] 2.8–3.7). One hundred twenty of the deaths were due to CV causes, yielding a CV mortality rate of 1.8 (95% CI 1.5–2.1). Exposure to glucocorticoids was associated with a dose‐dependent increase in death from all causes, with a ratio (HR) of 1.07 per mg of prednisone per day (95% CI 1.05–1.08). Compared to patients who were not receiving corticosteroids, the minimum daily prednisone dose threshold associated with an increase in all‐cause mortality was 8–15 mg, with an adjusted HR of 1.78 (95% CI 1.22–2.60). For the cumulative dose of glucocorticoids, the minimum dosage associated with all‐cause mortality was 40 gm (HR 1.74 [95% CI 1.25–2.44]). Conclusion Glucocorticoid use in RA is associated with a dose‐dependent increase in mortality rates, with a daily threshold dose of 8 mg, at which the number of deaths increased in a dose‐dependent manner. These findings may assist clinicians in selecting the appropriate glucocorticoid dosage for RA patients who require these agents.
Virmid: accurate detection of somatic mutations with sample impurity inference
Authors: Sangwoo Kim, Kyowon Jeong, Kunal Bhutani, Jeong Ho Lee, Anand Patel, Eric Scott, Hojung Nam, Hayan Lee, Joseph G Gleeson, Vineet Bafna
Journal: Genome biology (2013)

Abstract Detection of somatic variation using sequence from disease-control matched data sets is a critical first step. In many cases including cancer, however, it is hard to isolate pure disease tissue, and the impurity hinders accurate mutation analysis by disrupting overall allele frequencies. Here, we propose a new method, Virmid, that explicitly determines the level of impurity in the sample, and uses it for improved detection of somatic variation. Extensive tests on simulated and real sequencing data from breast cancer and hemimegalencephaly demonstrate the power of our model. A software implementation of our method is available at http://sourceforge.net/projects/virmid/ .
Development of the PsAQoL: a quality of life instrument specific to psoriatic arthritis
Authors: S P McKenna
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Patient reported outcome measures used in studies of psoriatic arthritis (PsA) have been found to be inadequate for determining the impact of the disease from the patient’s perspective. <b>Objective:</b> To produce the PsAQoL, a PsA-specific quality of life (QoL) instrument, employing the needs based model of QoL that would be relevant and acceptable to respondents, valid, and reliable. <b>Methods:</b> Content was derived from qualitative interviews conducted with patients with PsA. Face and content validity were assessed by field test interviews with a new sample of patients with PsA. A postal survey was conducted to improve the scaling properties of the new measure. Finally, a test-retest postal survey was used to identify the final measure and to test its scaling properties, reliability, internal consistency, and validity. <b>Results:</b> Analysis of the qualitative interview transcripts identified a 51 item questionnaire. Field test interviews confirmed the acceptability and relevance of the measure. Analysis of data from the first postal survey (n = 94) reduced the questionnaire to 35 items. Rasch analysis of data from the test-retest survey (n = 286) identified a 20 item version of the PsAQoL with good item fit. This version had excellent internal consistency (α = 0.91), test-retest reliability (0.89), and validity. <b>Conclusions:</b> The PsAQoL is a valuable tool for assessing the impact of interventions for PsA in clinical studies and trials. It is well accepted by patients, taking about three minutes to complete, is easy to administer, and has excellent scaling and psychometric properties.
Assessment of Left Atrial Pressure–Area Relation in Humans by Means of Retrograde Left Atrial Catheterization and Echocardiographic Automatic Boundary Detection: Effects of Dobutamine
Authors: Christodoulos Stefanadis, John Dernellis, Costas Stratos, Eleftherios Tsiamis, Costas Tsioufis, Konstantinos Toutouzas, Charalambos Vlachopoulos, Christos Pitsavos, Pavlos Toutouzas
Journal: Journal of the American College of Cardiology (1998)
Simultaneous Blockade of Platelet-Derived Growth Factor-Receptor and Epidermal Growth Factor-Receptor Signaling and Systemic Administration of Paclitaxel as Therapy for Human Prostate Cancer Metastasis in Bone of Nude Mice
Authors: Sun Jin Kim, Hisanori Uehara, Sertac Yazici, Robert R. Langley, Junqin He, Rachel Tsan, Dominic Fan, Jerald J. Killion, Isaiah J. Fidler
Journal: Cancer Research (2004)

Abstract Once prostate cancer metastasizes to bone, conventional chemotherapy is largely ineffective. We hypothesized that inhibition of phosphorylation of the epidermal growth factor receptor (EGF-R) and platelet-derived growth factor receptor (PDGF-R) expressed on tumor cells and tumor-associated endothelial cells, which is associated with tumor progression, in combination with paclitaxel would inhibit experimental prostate cancer bone metastasis and preserve bone structure. We tested this hypothesis in nude mice, using human PC-3MM2 prostate cancer cells. PC-3MM2 cells growing adjacent to bone tissue and endothelial cells within these lesions expressed phosphorylated EGF-R and PDGF-Rα and -β on their surfaces. The percentage of positive endothelial cells and the intensity of receptor expression directly correlated with proximity to bone tissue. Oral administration of PKI166 inhibited the phosphorylation of EGF-R but not PDGF-R, whereas oral administration of STI571 inhibited the phosphorylation of PDGF-R but not EGF-R. Combination therapy using oral PKI166 and STI571 with i.p. injections of paclitaxel induced a high level of apoptosis in tumor vascular endothelial cells and tumor cells in parallel with inhibition of tumor growth in the bone, preservation of bone structure, and reduction of lymph node metastasis. Collectively, these data demonstrate that blockade of phosphorylation of EGF-R and PDGF-R coupled with administration of paclitaxel significantly suppresses experimental human prostate cancer bone metastasis.