tbuckley/cabot-search huggingface dataset:
Urocanic acid isomers and photosensitivity in healthy children
Authors: None DE Fine Olivarius, None Wulf, None Crosby, None Norval
Journal: British Journal of Dermatology (1998)

Episodes of intense sun exposure, particularly in childhood, seem to carry a risk for the development of malignant melanoma in later life. However, little is known about photosensitivity and natural photoprotection in children. In adult subjects, photoprotection is provided mainly by the epidermal content of melanin and the thickness of the stratum corneum, while the amount of urocanic acid (UCA), a major ultraviolet-absorbing component of the stratum corneum, is not thought to contribute significantly to photoprotection. The minimal erythema dose (MED) was determined in 22 healthy children aged 6–13 years and in 36 healthy adults (mean age 28.1 years). Pigmentation was measured at six body sites by use of reflectance spectroscopy and the concentration of UCA isomers was measured in a sun-exposed area (upper back) and in unexposed buttock skin. No significant differences between children and adults were found, either in pigmentation at exposed and unexposed body sites, or in MED. The concentration of total UCA was significantly higher in the children than in the adults on the buttock (median 22.2 vs. 13.6 nmol/cm2), but not on the back. On exposed back skin, the children had a significantly higher percentage of cis-UCA than the adults (median 60.1 vs. 28.3%), while no difference was found on the buttock. In both groups, a significant correlation was found between pigmentation and MED (children: Spearman correlation coefficient 0.58, P = 0.006; adults: Spearman correlation coefficient 0.69, P < 0.0001), indicating that pigmentation is of major importance in determining photosensitivity in children as well as in adults. The concentration of total UCA did not correlate with the MED in either group.
Autoantigen Microarray for High-Throughput Autoantibody Profiling in Systemic Lupus Erythematosus
Authors: Honglin Zhu, Hui Luo, Mei Yan, Xiaoxia Zuo, Quan-Zhen Li
Journal: Genomics Proteomics & Bioinformatics (2015)

Abstract Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components (nucleic acids and associated proteins), cytoplasmic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epitopes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection. Proteomic microarray as a multiplexed high-throughput screening platform is playing an increasingly-important role in autoantibody diagnostics. In this article, we highlight the use of autoantigen microarrays for autoantibody exploration in SLE.
Risk of cardiovascular events with degarelix versus leuprolide after biochemical relapse of prostate cancer: Exploratory analysis of a randomized controlled trial.
Authors: Celestia S. Higano, E. David Crawford, Neal D. Shore, Zsolt Bosnyak, Anders Malmberg, Anders Neijber, Laurence Klotz
Journal: Journal of Clinical Oncology (2015)

151 Background: Androgen deprivation therapy (ADT) has been associated with increased cardiovascular (CV) risk in men. A pooled analysis of phase 3 trials comparing LHRH agonists with degarelix in PCa patients indicated a lower risk of CV events or death in those treated with degarelix. We now report the incidence of non-fatal CV events in men with PCa and pre-existing CV disease (CVD) treated with degarelix or leuprolide in the CS37 trial. Methods: CS37 was a prospective, randomized trial comparing intermittent (n=175) and continuous (n=50) degarelix with continuous leuprolide (n=178) in patients with biochemical relapse of PCa in the United States. CV events were retrospectively analyzed up to Month 12 (intermittent arm events censored at Month 7). Cox regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: 143 men (35%) had pre-existing CVD at baseline; 88 treated with degarelix and 55 treated with leuprolide. For degarelix and leuprolide treatment arms, median age (range) was 75 (51–88) and 73 (53–89) years and median BMI (range) 28.0 (17.7–40.7) and 30.1 (23.5–48.3) kg/m 2 , respectively. A slightly higher proportion of men treated with leuprolide than degarelix had a Gleason score of 7–10 (35 [64%] vs 46 [52%]) and slightly more men treated with degarelix vs leuprolide had hypertension (31 [35%] vs 15 [27%]), diabetes (70 [80%] vs 39 [71%]) and used statin medication (67 [76%] vs 36 [65%]) at baseline. The proportion of men who smoked or had hypercholesterolemia at baseline was similar between treatment arms. During the observation period, a subsequent CV event occurred in 3 (3.4%) men treated with degarelix and 8 (14.5%) treated with leuprolide (HR=0.22; 95% CI 0.05–1.03, p=0.054). Conclusions: Retrospective analysis of men with pre−existing CVD in CS37 identified a lower risk for subsequent CV events in men treated with degarelix vs leuprolide. The difference in CV event risk was seen within 12 months of treatment initiation. Our analysis adds to previous data on CV risk with ADT and supports consideration of CV risk factors when choosing a drug for androgen deprivation.
Dynamic contrast enhanced MRI (DCE MRI) for assessment of effects of anti-angiogenic therapy: Comparison of the transfer constant (Ktrans) to blood flow and permeability derived by a distributed parameters model
Authors: C. H. Thng, T. S. Koh, H. Rumpel, J. B. Khoo, A. B. Ong, N. Sukri, B. C. Tai, R. A. Soo, R. Humerickhouse, B. C. Goh
Journal: Journal of Clinical Oncology (2007)

14109 Background: Transfer constant (Ktrans) and IAUC60 normalized with arterial input function are commonly used dynamic contrast enhanced magnetic resonance imaging (DCE MRI) parameters. The distributed parameters model (DP) is a DCE MRI model that enables derivation of blood flow and capillary permeability-surface area product (PS). We aim to study the distributed parameters model as an alternative method of angiogenesis assessment and correlate the above parameters to drug exposure and patient outcome in a Phase I anti- angiogenic trial. Methods: Fifteen evaluable patients from an on-going Phase I trial (ABT 869) with 3 dose escalations formed the study population. Pharmacokinetic study was performed on Day 1 and the area under the concentration time curve extrapolated to infinity (AUCinfinity) was used as an indicator of drug exposure. All patients underwent DCE MRI at baseline, Day 3 and Day 15 with temporal resolution of 4 seconds. Gadolinium concentrations were estimated using a dual flip angle method. Patients demonstrating progressive disease in first 2 evaluation scans (cycle 2 or 4) based on RECIST criteria were considered progressors and all other patients non-progressors. Receiver operating curve (ROC) analysis was performed. Correlation with AUCinfinity was analyzed. Results: There is good correlation (Spearman’s coefficient -0.67, p = 0.008) between AUCinfinity and DP derived PS and less strong correlation with normalized IAUC60 (Spearman’s coefficient -0.57, p = 0.03). There is no correlation for Ktrans (Spearman’s coefficient 0.04). ROC analysis for predicting progressors versus non-progressors showed a higher ROC area for PS compared to Ktrans (0.83 versus 0.47, p = 0.037). Normalized IAUC60 showed a slightly lower area compared to PS (0.77 versus 0.83) but the difference is not significant (p = 0.58). Conclusions: PS derived from DP model shows better correlation with drug exposure and may predict patient outcome better than Ktrans. [Table: see text]
Indoor Ultraviolet Tanning: What the Data Do and Do Not Show Regarding Risk of Melanoma and Keratinocyte Malignancies
Authors: Martin A. Weinstock, David E. Fisher
Journal: Journal of the National Comprehensive Cancer Network (2010)

Recreational indoor tanning with ultraviolet (UV) radiation has become popular in recent decades, particularly among teenagers and young adults. The consequences for public health have become an important area of concern. The link between this form of UV exposure and both melanoma and non-melanoma skin cancers has been clarified through multiple lines of evidence from epidemiology and laboratory science reflected in recent reports by multiple prestigious bodies. Some have suggested that this form of indoor tanning has a role in vitamin D generation, but a review of existing evidence suggests that indoor tanning is neither a reliable nor advisable source. In addition, laboratory data suggest that tanning promotes a common molecular intermediate in skin carcinogenesis, DNA damage, which thus precludes the concept of a "safe tan." Finally, emerging evidence links UV signaling in skin to dependency/addiction, thus having implications for the organic (rather than cosmetic) impact of the process. This article presents the epidemiologic and mechanistic data relevant to the safety considerations for indoor tanning.
Killer combinations for cervical cancer
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Certain combinations of HLA class I genes and natural killer (NK) cell receptors increase the risk of developing cervical cancer, according to a study by Carrington and colleagues on page 1069. Women who possess HLA alleles that engage inhibitory NK cell receptors were less likely to develop cervical cancer, suggesting that NK cell activation may promote cancer development.






Figure 

KIR–HLA combinations that result in strong activation correlate with increased risk for cervical cancer.




Most cervical cancers (>95%) are associated with human papillomavirus (HPV), which establishes chronic infections in the genital tract. HPV infections that do not result in cancer may be due to effective cellular immune responses that limit HPV replication. NK cells are found in HPV-positive cervical lesions and may help protect against the virus.

NK cell activation hinges on a balance between activating and inhibitory signals generated in part by a diverse group of NK cell receptors—killer cell immunoglobulin-like receptors (KIRs)—that bind HLA class I molecules on interacting cells. Combinations of KIR and HLA genes that promote either NK cell activation or inhibition have been associated with increased susceptibility to various viral and autoimmune diseases.Carrington and colleagues found that individuals whose HLA molecules primarily bound to inhibitory KIRs had a decreased risk for cervical cancer; those with certain activating HLA-KIR combinations had increased risk. NK cell activation may contribute to local inflammation, suggests Carrington, which has been associated with the progression of other types of cancer, including gastric and prostate cancer. But how NK cell activation might promote transformation remains unknown.
Obesity, Intrapancreatic Fatty Infiltration, and Pancreatic Cancer
Authors: Hua Wang, Anirban Maitra, Huamin Wang
Journal: Clinical Cancer Research (2015)

Obesity and intrapancreatic fatty infiltration are associated with increased risk of pancreatic cancer and its precursor lesions. The interplay among obesity, inflammation, and oncogenic Kras signaling promotes pancreatic tumorigenesis. Targeting the interaction between obesity-associated inflammation and Kras signaling may provide new strategies for prevention and therapy of pancreatic cancer.
Mobile device usability to support chronic obstructive pulmonary disease management
Authors: Ane Arbillaga, Anael Barberan, Diego Agustin Rodriguez, Yolanda Torralba, Jordi Vilaro, Josep Roca
Journal: European Respiratory Journal (2011)

COPD generates a serious burden on healthcare system. Telemedicine contribute to an efficient use of healthcare resources reducing number of non-scheduled visits. Are lacking studies assessing patients and healthcare provider9s satisfaction on those new approaches. The aim of the study was determine the usability & satisfaction of COPD patients and professionals with a mobile device to support COPD management.  A mobile system was offered during two weeks to 17COPD patients (FEV1 47±19% pred; age 65±8). Patients answered the EuroQoL questionnaire every day and used pulse oximetry during any exercise session at home setting. Data was collected & checked in a technological platform. Patients and professionals accomplished a usability & satisfaction questionnaire at the end of the study.  18% of patients refused and 65% finished the program. 83% felt safer during exercise and more controlled by professionals. 61% indicated that the device makes them do more physical activity. Lack of acceptance to undergo the study and drop-outs were associated with personality disorders (p  Transfer of data between a mobile device and a digital platform is feasible for COPD patients. Remote monitoring of physical activity can enhance motivation to perform sustainable exercise and seems to show high grade of adherence. Long-term follow-up of a large number of patients will be needed to define effective home-based services to enhance management of COPD patients.  Supported by Nexes UE - FP7 (CIP-ICT) 225025; FIS-Pites.
Blood-Borne Revitalization of the Aged Brain
Authors: Joseph M. Castellano, Elizabeth D. Kirby, Tony Wyss-Coray
Journal: JAMA Neurology (2015)

In the modern medical era, more diverse and effective treatment options have translated to increased life expectancy. With this increased life span comes increased age-associated disease and the dire need to understand underlying causes so that therapies can be designed to mitigate the burden to health and the economy. Aging exacts a seemingly inevitable multisystem deterioration of function that acts as a risk factor for a variety of age-related disorders, including those that devastate organs of limited regenerative potential, such as the brain. Rather than studying the brain and mechanisms that govern its aging in isolation from other organ systems, an emerging approach is to understand the relatively unappreciated communication that exists between the brain and systemic environment. Revisiting classical methods of experimental physiology in animal models has uncovered surprising regenerative activity in young blood with translational implications for the aging liver, muscle, brain, and other organs. Soluble factors present in young or aged blood are sufficient to improve or impair cognitive function, respectively, suggesting an aging continuum of brain-relevant systemic factors. The age-associated plasma chemokine CCL11 has been shown to impair young brain function while GDF11 has been reported to increase the generation of neurons in aged mice. However, the identities of specific factors mediating memory-enhancing effects of young blood and their mechanisms of action are enigmatic. Here we review brain rejuvenation studies in the broader context of systemic rejuvenation research. We discuss putative mechanisms for blood-borne brain rejuvenation and suggest promising avenues for future research and development of therapies.
Randomized phase II study of FOLFOX +/- MET inhibitor, onartuzumab (O), in advanced gastroesophageal adenocarcinoma (GEC).
Authors: Manish A. Shah, Jae Yong Cho, Iain Tan Bee Huat, Niall C. Tebbutt, Chia-Jui Yen, Alice Kang, David S. Shames, Lilian Bu, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2015)

2 Background: Aberrant up-regulation of the MET/HGF pathway is associated with poor prognosis in multiple malignancies, including GEC. Onartuzumab (O) is a fully humanized, monovalent anti-MET antibody that inhibits HGF binding and receptor activation. We examined the efficacy and safety of mFOLFOX6 and O in the first-line setting for metastatic, HER2-negative GEC. Methods: This was a double-blind, placebo controlled phase II study in which patients were randomized 1:1 to mFOLFOX6 + O 10 mg/kg. Eligibility included no prior treatment for metastatic disease, age &gt;18, ECOG 0-1, retained organ function, HER2-negative, and evaluable disease. The primary objectives were to detect a meaningful improvement in progression free survival (PFS) in the ITT population or the MET-positive (≥ 50% of tumor with moderate-strong intensity staining by IHC based on central review) subgroup. With 120 patients enrolled and 84 PFS events observed, the target HR was 0.7 in the ITT population, and 0.6 in the MET-positive subgroup (estimated 50% of total). Results: 123 patients (83 Asia/Pacific, 40 US) from 25 sites were from 7/2012-5/2013. The treatment arms were well balanced: median age (57 placebo (P), 58.5 O), male (n=36 (59%) P, n=40 (65%) O), and MET-positive (n=19 (33%) P, n=16 (28%) O). Serious adverse events were more frequent with O (55%) vs placebo (40%). Selected grade 3-5 adverse events observed at least 5% more commonly with O included neutropenia (58% vs 45%), thrombocytopenia (10% vs 3%), peripheral edema (10% vs 0), and pulmonary embolism (7% vs 2%). At data cutoff (29 Jan 2014), 96 patients had PFS events (n=46 (74%) O, n=50 (82%) P), with median PFS of 6.77 and 6.97 months, respectively (HR 1.08, 95% CI 0.71-1.63). In the MET-positive subgroup, median PFS was 5.95 months for O and 6.8 months for placebo (HR 1.38 [0.60-3.20]). No difference in efficacy was noted with alternate MET-positive definitions (50% vs 90% MET staining, and 1, 2, or 3+ intensity). Conclusions: The addition of O to mFOLFOX6 in metastatic GEC did not improve PFS in either an unselected population or in MET-positive patients as defined by IHC. Additional biomarker analyses are ongoing to identify patients that may benefit from MET inhibition. Clinical trial information: NCT01662869.
Oscillating positive airway pressure (O-PAP) vs CPAP treatment in patients with obstructive sleep apneas
Authors: Nicolas Petitpierre, José Haba Rubio, Françoise Cornette, Ahmed Al-Jumaily, Raphaël Heinzer
Journal: European Respiratory Journal (2014)

Introduction   Although CPAP is the most effective therapy for obstructive sleep apnea syndrome (OSAS), the pressure needed to keep the upper airway open is not always tolerated.   Aims and objectives   We tested O-PAP, a new device delivering high frequency pressure oscillations (±1cmH2O) during CPAP therapy. We hypothesized that O-PAP, by triggering the pharyngeal dilator reflex, could control sleep respiratory events better than CPAP.   Methods   14 OSAS patients (59.9±10.1 yo, BMI 34.8±7.2 kg/m2, AHI 58.7±25.2/h) were treated with O-PAP and CPAP on two consecutive nights under polysomnography in a randomized crossover study using a subtherapeutic pressure (70% of the optimal titrated pressure). Polysomnographies were scored by a blinded investigator. The main study endpoints were residual AHI and sleep quality.   Conclusions   In this pilot study, O-PAP was well tolerated and showed a non significant trend towards a decrease in residual AHI compared to CPAP, under suboptimal pressure. Larger studies are required to evaluate if this technique allows treating OSAS patients with lower pressures than CPAP and to identify which patients could benefit from it.
Baseline MUGA scans for patients with early-stage breast cancer receiving adjuvant chemotherapy.
Authors: A. S. Jeyakumar, J. Dipenta, S. L. Snow, D. Rayson, K. Thompson, C. Theriault, T. Younis
Journal: Journal of Clinical Oncology (2010)

6087 Background: Multigated acquisition (MUGA) scans are commonly employed to assess baseline cardiac function prior to adjuvant anthracycline-based chemotherapy and/or trastuzumab treatment in view of their potential cardiac toxicity. The aims of this population based study of Nova Scotia (NS) women with early-stage BC were: (1) determine current utilization patterns of MUGA scans in women with early-stage breast cancer and (2) examine impact of MUGA scans on choice of adjuvant chemotherapy (AdjC) regimen. Methods: All women diagnosed In NS, Canada with stage I-III BC between 10/2005- 09/2006 were identified through the provincial cancer registry. A retrospective chart review was performed to abstract all relevant clinical-pathological variables. The association between MUGA scan receipt and clinical-pathologic variables was examined through standard univariate and multivariate analyses. The influence of MUGA scan on AdjC regimen choice was examined through 2x2 tables and odds ratios. Results: The study included 593 women, of whom 238 received AdjC (94% anthracycline vs. 6% nonanthracycline). Overall, 198 women underwent baseline MUGA scans. Baseline MUGA scan receipt was associated with AdjC treatment (yes vs. no; p < 0.0001), HER2/neu status (positive vs. negative vs. not tested; p < 0.0001) and choice of AdjC regimen (anthracycline vs. nonanthracycline; p < 0.0001). All patients treated with adjuvant trastuzumab underwent serial MUGA scan testing. Abnormal MUGA defined as a left ventricular ejection fraction of < 50% was observed in 5/198 (2.5%). All 5 patients were smokers and 4 of these were > 50 years of age. In the one patient < 50 years with abnormal MUGA, subsequent echocardiograms indicated normal cardiac function. Conclusions: In this population-based study of women with early-stage BC, although the majority of patients considered for AdjC underwent baseline MUGA scan testing, the incidence of abnormal scans was low. Our results suggest that routine baseline MUGAs prior to finalizing a decision regarding AdjC is likely not required for the majority of asymptomatic patients not considered for trastuzumab therapy, particularly for those under the age of 50 who are nonsmokers. No significant financial relationships to disclose.