tbuckley/cabot-search huggingface dataset:
Phase II Study of Gemcitabine and Oxaliplatin in Combination With Bevacizumab in Patients With Advanced Hepatocellular Carcinoma
Authors: Andrew X. Zhu, Lawrence S. Blaszkowsky, David P. Ryan, Jeffrey W. Clark, Alona Muzikansky, Kerry Horgan, Susan Sheehan, Kelly E. Hale, Peter C. Enzinger, Pankaj Bhargava, Keith Stuart
Journal: Journal of Clinical Oncology (2006)

Hepatocellular carcinoma (HCC) is a vascular tumor with poor prognosis. Given the reported activity of gemcitabine and oxaliplatin (GEMOX) in HCC and the potential benefits of targeting the vascular endothelial growth factor pathway with bevacizumab (B), a phase II study of GEMOX-B was undertaken to define efficacy and toxicity profiles in HCC patients.Eligible patients had pathologically proven measurable unresectable or metastatic HCC. For cycle 1 (14 days), bevacizumab 10 mg/kg was administered alone intravenously on day 1. For cycle 2 and beyond (28 days/cycle), bevacizumab 10 mg/kg was administered on days 1 and 15, gemcitabine 1,000 mg/m2 was administered as a dose rate infusion at 10 mg/m2/min followed by oxaliplatin at 85 mg/m2 on days 2 and 16.Thirty-three patients were enrolled and 30 patients were assessable for efficacy. The objective response rate was 20%, and 27% of patients had stable disease. Median overall survival was 9.6 months (95% CI, 8.0 months to not available) and median progression-free survival (PFS) was 5.3 months (95% CI, 3.7 to 8.7 months); the PFS rate at 3 and 6 months was 70% (95% CI, 54% to 85%) and 48% (95% CI, 31% to 65%), respectively. The most common treatment-related grade 3 to 4 toxicities included leukopenia/neutropenia, transient elevation of aminotransferases, hypertension, and fatigue.GEMOX-B could be safely administered with close monitoring and had moderate antitumor activity for patients with advanced HCC. The high 6-month PFS rate is encouraging, and this regimen is worthy of further investigation.
Cadmium Exposure and All-Cause and Cardiovascular Mortality in the U.S. General Population
Authors: Maria Tellez-Plaza, Ana Navas-Acien, Andy Menke, Ciprian M. Crainiceanu, Roberto Pastor-Barriuso, Eliseo Guallar
Journal: Environmental Health Perspectives (2012)

Urine cadmium concentrations were associated with all-cause and cardiovascular mortality in men in the 1988-1994 U.S. National Health and Nutrition Examination Survey (NHANES) population. Since 1988, cadmium exposure has decreased substantially in the United States. The associations between blood and urine cadmium and cardiovascular disease (CVD) mortality at more recent levels of exposure are unknown. We evaluated the prospective association of blood and urine cadmium concentrations with all-cause and CVD mortality in the 1999-2004 U.S. population. We followed 8,989 participants who were ≥ 20 years of age for an average of 4.8 years. Hazard ratios for mortality end points comparing the 80th to the 20th percentiles of cadmium distributions were estimated using Cox regression. The multivariable adjusted hazard ratios [95% confidence intervals (CIs)] for blood and urine cadmium were 1.50 (95% CI: 1.07, 2.10) and 1.52 (95% CI: 1.00, 2.29), respectively, for all-cause mortality, 1.69 (95% CI: 1.03, 2.77) and 1.74 (95% CI: 1.07, 2.83) for CVD mortality, 1.98 (95% CI: 1.11, 3.54) and 2.53 (95% CI: 1.54, 4.16) for heart disease mortality, and 1.73 (95% CI: 0.88, 3.40) and 2.09 (95% CI: 1.06, 4.13) for coronary heart disease mortality. The population attributable risks associated with the 80th percentile of the blood (0.80 μg/L) and urine (0.57 μg/g) cadmium distributions were 7.0 and 8.8%, respectively, for all-cause mortality and 7.5 and 9.2%, respectively, for CVD mortality. We found strongly suggestive evidence that cadmium, at substantially low levels of exposure, remains an important determinant of all-cause and CVD mortality in a representative sample of U.S. adults. Efforts to further reduce cadmium exposure in the population could contribute to a substantial decrease in CVD disease burden.
Blood Monocytes: Development, Heterogeneity, and Relationship with Dendritic Cells
Authors: Cedric Auffray, Michael H. Sieweke, Frederic Geissmann
Journal: Annual Review of Immunology (2009)

Monocytes are circulating blood leukocytes that play important roles in the inflammatory response, which is essential for the innate response to pathogens. But inflammation and monocytes are also involved in the pathogenesis of inflammatory diseases, including atherosclerosis. In adult mice, monocytes originate in the bone marrow in a Csf-1R (MCSF-R, CD115)-dependent manner from a hematopoietic precursor common for monocytes and several subsets of macrophages and dendritic cells (DCs). Monocyte heterogeneity has long been recognized, but in recent years investigators have identified three functional subsets of human monocytes and two subsets of mouse monocytes that exert specific roles in homeostasis and inflammation in vivo, reminiscent of those of the previously described classically and alternatively activated macrophages. Functional characterization of monocytes is in progress in humans and rodents and will provide a better understanding of the pathophysiology of inflammation.
Stable pulmonary capillary haemangiomatosis without symptomatic pulmonary hypertension
Authors: Y Takiguchi
Journal: Thorax (2001)

Pulmonary capillary haemangiomatosis is a rare disorder characterised by multiple angiomatous lesions composed of proliferating capillary vessels in the lung parenchyma that usually progress rapidly to establish fatal pulmonary hypertension. The 29 year old man presented here, however, has been stable for 3.5 years since the diagnosis without symptoms of pulmonary hypertension. High resolution computed tomographic findings of the pulmonary lesions seemed specific to the disease.
1061 MOLECULAR PATHWAYS LEADING TO INSULIN RESISTANCE IN HEPATITIS C VIRUS INFECTION
Authors: L.C. Godoy, R.G. Fonseca, R.J. Carvalho-Filho, C.T. Emori, I.C. Melo, V.P. Lanzoni, C.P. Oliveira, J.T. Stefano, A.E.B. Silva, J.B. Pesquero, M.L.G. Ferraz
Journal: Journal of Hepatology (2010)
High Relapse Rate in Patients with MALT Lymphoma Warrants Lifelong Follow-up
Authors: Markus Raderer, Berthold Streubel, Stefan Woehrer, Andreas Puespoek, Ulrich Jaeger, Michael Formanek, Andreas Chott
Journal: Clinical Cancer Research (2005)

Abstract Background: B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is thought to be an indolent disease, with a good prognosis following various forms of treatment. Little, however, is known about the rate and pattern of relapse following successful treatment. Patients and Methods: We have analyzed time to and pattern of relapse in patients with MALT lymphoma, along with investigation of t(11;18)(q21;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21) involving IGH/MALT1, trisomy 3, and trisomy 18. Eighty-six patients achieving complete remission (CR) after initial therapy with sufficient follow-up data were available. Primary site of disease was the stomach (n = 36), salivary gland (n = 19), ocular adnexa/orbit (n = 12), lung (n = 8), thyroid (n = 5), breast (n = 3), liver (n = 2), and skin (n = 1). Results: Thirty-two patients (37%) relapsed between 14 and 307 months (median 47 months) after initial CR. Ten relapses were local, whereas the remaining patients relapsed in a distant organ. Eight of 36 gastric versus 24 of 50 nongastric MALT lymphomas (P = 0.02) relapsed. Five patients had a second recurrence 26 to 56 months after a second CR. Relapse rates were not related to forms of initial treatment. Chromosomal aberrations were detected in 14 of 28 (50%) relapsing patients, and chromosomal alterations were identical at diagnosis and relapse. No significant association of any of the genetic changes investigated with relapse was found. Interestingly, patients with t(11;18)(q21;q21) had a significantly longer median time to relapse (76 months) than patients without this translocation (29 months; P = 0.012). Conclusions: In view of the late relapses seen in our series, lifelong observation of all patients treated for MALT lymphoma seems to be required.
Variants within the<i>MMP3</i>gene are associated with Achilles tendinopathy: possible interaction with the<i>COL5A1</i>gene
Authors: S M Raleigh, L van der Merwe, W J Ribbans, R K W Smith, M P Schwellnus, M Collins
Journal: British Journal of Sports Medicine (2008)

Objectives: Sequence variation within the COL5A1 and TNC genes are known to associate with Achilles tendinopathy. The primary aim of this case-control genetic association study was to investigate whether variants within the matrix metalloproteinase 3 ( MMP3 ) gene also contributed to both Achilles tendinopathy and Achilles tendon rupture in a Caucasian population. A secondary aim was to establish whether variants within the MMP3 gene interacted with the COL5A1 rs12722 variant to raise risk of these pathologies. Methods: 114 subjects with symptoms of Achilles tendon pathology and 98 healthy controls were genotyped for MMP3 variants rs679620, rs591058 and rs650108. Results: As single markers, significant associations were found between the GG genotype of rs679620 (OR = 2.5, 95% CI 1.2 to 4.90, p = 0.010), the CC genotype of rs591058 (OR = 2.3, 95% CI 1.1 to 4.50, p = 0.023) and the AA genotype of rs650108 (OR = 4.9, 95% CI 1.0 to 24.1, p = 0.043) and risk of Achilles tendinopathy. The ATG haplotype (rs679620, rs591058, and rs650108) was under-represented in the tendinopathy group when compared to the control group (41% vs 53%, p = 0.038). Finally, the G allele of rs679620 and the T allele of COL5A1 rs12722 significantly interacted to raise risk of AT (p = 0.006). No associations were found between any of the MMP3 markers and Achilles tendon rupture. Conclusion: Variants within the MMP3 gene are associated with Achilles tendinopathy. Furthermore, the MMP3 gene variant rs679620 and the COL5A1 marker rs12722 interact to modify the risk of tendinopathy. These data further support a genetic contribution to a common sports related injury.
Wearable Medical Systems for p-Health
Authors: None Xiao-Fei Teng, None Yuan-Ting Zhang, C.C.Y. Poon, P. Bonato
Journal: IEEE Reviews in Biomedical Engineering (2008)

Driven by the growing aging population, prevalence of chronic diseases, and continuously rising healthcare costs, the healthcare system is undergoing a fundamental transformation, from the conventional hospital-centered system to an individual-centered system. Current and emerging developments in wearable medical systems will have a radical impact on this paradigm shift. Advances in wearable medical systems will enable the accessibility and affordability of healthcare, so that physiological conditions can be monitored not only at sporadic snapshots but also continuously for extended periods of time, making early disease detection and timely response to health threats possible. This paper reviews recent developments in the area of wearable medical systems for p-Health. Enabling technologies for continuous and noninvasive measurements of vital signs and biochemical variables, advances in intelligent biomedical clothing and body area networks, approaches for motion artifact reduction, strategies for wearable energy harvesting, and the establishment of standard protocols for the evaluation of wearable medical devices are presented in this paper with examples of clinical applications of these technologies.
PD-1 blockade during chronic SIV infection reduces hyperimmune activation and microbial translocation in rhesus macaques
Authors: Ravi Dyavar Shetty, Vijayakumar Velu, Kehmia Titanji, Steven E. Bosinger, Gordon J. Freeman, Guido Silvestri, Rama Rao Amara
Journal: Journal of Clinical Investigation (2012)

Hyperimmune activation is a strong predictor of disease progression during pathogenic immunodeficiency virus infections and is mediated in part by sustained type I IFN signaling in response to adventitious microbial infection. The immune inhibitory receptor programmed death–1 (PD-1) regulates functional exhaustion of virus-specific CD8+ T cells during chronic infections, and in vivo PD-1 blockade has been shown to improve viral control of SIV. Here, we show that PD-1 blockade during chronic SIV infection markedly reduced the expression of transcripts associated with type I IFN signaling in the blood and colorectal tissue of rhesus macaques (RMs). The effect of PD-1 blockade on type I IFN signaling was durable and persisted even under conditions of high viremia. Reduced type I IFN signaling was associated with enhanced expression of some of the junction-associated genes in colorectal tissue and with a profound decrease in plasma LPS levels, suggesting a possible repair of gut-associated junctions and decreased microbial translocation into the blood. PD-1 blockade enhanced immunity to gut-resident pathogenic bacteria, control of gut-associated opportunistic infections, and survival of SIV-infected RMs. Our results suggest PD-1 blockade as a potential novel therapeutic approach to enhance combination antiretroviral therapy by suppressing hyperimmune activation in HIV-infected individuals.
High Expression of IL-13 Receptor α2 in Colorectal Cancer Is Associated with Invasion, Liver Metastasis, and Poor Prognosis
Authors: Rodrigo Barderas, Rubén A. Bartolomé, María Jesús Fernandez-Aceñero, Sofia Torres, J. Ignacio Casal
Journal: Cancer Research (2012)

Autocrine secretion of cytokines by metastatic colorectal cancer cells and their role during invasion and liver homing has been poorly characterized. In this study, we used cytokine arrays to analyze the secretomes of poorly and highly metastatic colorectal cancer cells. Compared with poorly metastatic cancer cells, highly metastatic cells expressed increased levels of the immunosuppressive cytokines interleukin (IL)-4 and IL-13 in addition to increased surface expression of the high affinity IL-13 receptor IL-13Rα2, suggesting that IL-13Rα2 mediates IL-13 effects in colorectal cancer cells. Silencing of IL-13Rα2 in highly metastatic cells led to a decrease in adhesion capacity in vitro and a reduction in liver homing and increased survival in vivo, revealing a role for this receptor in cell adhesion, migration, invasion, and metastatic colonization. In support of this, IL-13 signaling activated the oncogenic signaling molecules phosphoinositide 3-kinase, AKT, and SRC in highly metastatic cells. Clinically, high expression of IL-13Rα2 was associated with later stages of disease progression and poor outcome in patients with colorectal cancer. Our findings therefore support a critical role for IL-13Rα2 expression in colon cancer invasion and metastasis.
Project aims to halve stillbirths and brain injuries during labour
Authors: J. Wise
Journal: BMJ (2014)

An initiative to halve the number of stillbirths, neonatal deaths, and brain injuries caused by incidents that occur during labour at term has been launched by the Royal College of Obstetricians and Gynaecologists.

Each Baby Counts is a five year project, partly funded by the Department of Health for England, which will start gathering data from all UK maternity units from …
Pressure–Volume Curve Does Not Predict Steady-State Lung Volume in Canine Lavage Lung Injury
Authors: John M. Downie, Arthur J. Nam, Brett A. Simon
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

To better understand strategies for recruiting and maintaining lung volume in acute lung injury, we examined relationships between steady-state lung volume and cumulative cyclic recruitment/derecruitment volume history and the quasi-static pressure-volume curve, in an animal saline lavage lung injury model. Small-volume tidal pressure-volume loops performed after inflation from functional residual capacity demonstrated incremental, cyclic recruitment only if the peak pressure achieved exceeded the pressure at which the compliance increased (Pflex) on the pressure-volume curve, whereas loops performed after deflation from total lung capacity remained close to the envelope deflation curve. Recruitment continued to occur up to and beyond a peak inspiratory airway pressure of 40 cm H(2)O, as demonstrated by both the tidal loops and by computed tomography-derived lung volume data. Tidal-specific compliance was relatively constant across positive end-expiratory pressure levels after inflation from functional residual capacity, but peaked at moderate positive end-expiratory pressure after deflation from total lung capacity, further demonstrating the effects of volume history and providing experimental validation of the recruitment models of Hickling (AJRCCM 2001;163:69-78). These results support the interpretation of Pflex as pressure threshold for recruitment, but otherwise do not suggest a role for the pressure-volume curve in predicting steady-state lung volume.
Epidermal Growth Factor Receptor Tyrosine Phosphorylation and Signaling Controlled by a Nuclear Receptor Coactivator, Amplified in Breast Cancer 1
Authors: Tyler Lahusen, Mark Fereshteh, Annabell Oh, Anton Wellstein, Anna T. Riegel
Journal: Cancer Research (2007)

Abstract The steroid receptor coactivator amplified in breast cancer 1 (AIB1) as well as epidermal growth factor receptor (EGFR) family members are frequently overexpressed in epithelial tumors, and their expression is associated with poor prognosis. However, a direct role of AIB1 in EGF signaling has not been determined. To address this, we reduced endogenous AIB1 levels using RNA interference in lung, breast, and pancreatic cancer cell lines. We found that a knockdown of AIB1 levels resulted in a loss of the growth response of these cell lines to EGF. Further analysis revealed that the depletion of AIB1 reduced tyrosine phosphorylation of EGFR at multiple residues both at autophosphorylation and Src kinase phosphorylation sites. AIB1 knockdown did not affect tyrosine phosphorylation of the receptor tyrosine kinases, platelet-derived growth factor receptor and HER3, or overall tyrosine phosphorylation of cellular proteins. However, EGF-dependent phosphorylation of HER2 was decreased. EGFR levels and membrane trafficking were not changed by AIB1 depletion, but there was less recruitment of Src homology 2 domain-containing proteins to the EGFR. This led to a substantial reduction in EGF-induced phosphorylation of signal transducers and activators of transcription 5 and c-Jun NH2-terminal kinase but no significant change in the activation of AKT. Vanadate treatment of cells revealed that the reduction in EGFR tyrosine phosphorylation is dependent in part on changes in cellular phosphatase activity. We propose that a portion of the oncogenic effect of AIB1 could be through control of EGFR and HER2 activity and subsequent modulation of cellular signaling pathways. [Cancer Res 2007;67(15):7256–65]
Use of Geriatric Assessment for Older Adults in the Oncology Setting: A Systematic Review
Authors: M. T. E. Puts, J. Hardt, J. Monette, V. Girre, E. Springall, S. M. H. Alibhai
Journal: JNCI Journal of the National Cancer Institute (2012)

Geriatric assessment is a multidisciplinary diagnostic process that evaluates the older adult's medical, psychological, social, and functional capacity. No systematic review of the use of geriatric assessment in oncology has been conducted. The goals of this systematic review were: 1) to provide an overview of all geriatric assessment instruments used in the oncology setting; 2) to examine the feasibility and psychometric properties of those instruments; and 3) to systematically evaluate the effectiveness of geriatric assessment in predicting or modifying outcomes (including the impact on treatment decision making, toxicity of treatment, and mortality).
Preference-Based Measures in Economic Evaluation in Health Care
Authors: Peter J. Neumann, Sue J. Goldie, Milton C. Weinstein
Journal: Annual Review of Public Health (2000)

▪ Abstract Estimating preferences for states of health has been an active area of research in recent years. Unlike psychophysical approaches, which discriminate levels of health status, preference-based approaches incorporate values or utilities for health outcomes and can be used in cost-effectiveness analyses to aid resource allocation decisions. This chapter considers issues and controversies involved in using preference-based measures in economic evaluation in health care, with a particular emphasis on cost-utility analysis and the estimation of quality-adjusted life years. Topics considered include techniques for measuring preferences, the use of preference-based classification systems, the relationship between patient and community preferences, methods for obtaining utilities from clinical trials, mapping health status from health utilities, the development of “off-the-shelf” preference weights, and proposed alternatives to quality-adjusted life years. We also consider applications of cost-utility analyses to public health interventions. Although cost-utility analyses have become more popular recently, many challenges remain for the field. Widespread acceptance of the methodology likely awaits more consensus on measurement techniques, as well as educational efforts in the public health and medical communities on the usefulness of the approach.
Asthma and atopy: endocrine or metabolic conditions?
Authors: L Forbes
Journal: Thorax (2005)

New perspectives on the relationship between asthma or allergy and female sex hormones

Female sex hormones seem to have something to do with asthma and allergy. You might think this is a bit vague, but the research on this so far doesn’t merit anything stronger. Women of reproductive age are more likely to be admitted to hospital for asthma than men.1 Intrigued by this, people have studied the link between asthma or allergy and markers of female sex hormone levels—for example, time of menstrual cycle, menopause, pregnancy, hormonal contraceptives, hormone replacement therapy, maternal parity, and age at menarche—but the overall picture remains confused. The results of the studies are inconsistent, with no unifying pattern of effects of hormones. Three recent studies in Thorax , two in this issue2,3 and one published in June this year,4 have added some new pieces to the jigsaw puzzle and a new perspective on the problem.

Brenner et al 2 looked at menstrual variation in asthma symptoms. We have recognised for a long time that some women get worse asthma symptoms at certain times of the month. Surveys of asthma outpatient clinics suggest that about a third of women experience worse symptoms just before and during their periods,5–7 although the figure would probably be lower in community based surveys. A few researchers have shown that peak expiratory flows5,6 or bronchial responsiveness8 vary over the menstrual cycle, but others have shown no such variation.9,10 As with the premenstrual syndrome, exactly what it is about the different phases of the menstrual cycle that …