tbuckley/cabot-search huggingface dataset:
Summary Report 7th Annual Targeted Therapies of the Treatment of Lung Cancer
Authors: Lawrence H. Einhorn, Philip Bonomi, Paul A. Bunn, D Ross Camidge, David Paul Carbone, Hak Choy, Steven M. Dubinett, David R. Gandara, Laurie E. Gaspar, Ramaswamy Govindan, David H. Johnson, John D. Minna, Giorgio Scagliotti, Howard J. West, Roy S. Herbst
Journal: Journal of Thoracic Oncology (2008)
Is Depression in Old Age Fatal Only When People Feel Lonely?
Authors: Max L. Stek, David J. Vinkers, Jacobijn Gussekloo, Aartjan T.F. Beekman, Roos C. van der Mast, Rudi G.J. Westendorp
Journal: American Journal of Psychiatry (2004)

The impact of depression and perceived loneliness in the oldest old is largely unknown. The authors studied the relationship between the presence of depressive symptoms and all-cause mortality in old age, especially the potential distorting effect of perceived loneliness.Within a prospective population-based study of 85-year-olds, the 15-item Geriatric Depression Scale and the Loneliness Scale were annually applied in all 476 participants with a Mini-Mental State Examination score of 18 points or more.Depression was present in 23% and associated with marital state, institutionalization, and perceived loneliness. When depression and perceived loneliness were assessed during follow-up, neither depression nor perceived loneliness had a significant effect on mortality. However, those who suffered from both depression and feelings of loneliness had a 2.1 times higher mortality risk.The data suggest that the increased mortality risk attributable to depression in the presence of perceived loneliness may result from motivational depletion.
Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial
Authors: Helena M Earl, Anne-Laure Vallier, Louise Hiller, Nicola Fenwick, Jennie Young, Mahesh Iddawela, Jean Abraham, Luke Hughes-Davies, Ioannis Gounaris, Karen McAdam, Stephen Houston, Tamas Hickish, Anthony Skene, Stephen Chan, Susan Dean, Diana Ritchie, Robert Laing, Mark Harries, Christopher Gallagher, Gordon Wishart, Janet Dunn, Elena Provenzano, Carlos Caldas
Journal: The Lancet Oncology (2013)

Anthracyclines and taxanes have been the standard neoadjuvant chemotherapies for breast cancer in the past decade. We aimed to assess safety and efficacy of the addition of gemcitabine to accelerated paclitaxel with epirubicin and cyclophosphamide, and also the effect of sequencing the blocks of epirubicin and cyclophosphamide and paclitaxel (with or without gemcitabine).
The Circulatory Regulation of TPA and UPA Secretion, Clearance, and Inhibition During Exercise and During the Infusion of Isoproterenol and Phenylephrine
Authors: Wayne L. Chandler, Wayne C. Levy, John R. Stratton
Journal: Circulation (1995)

Background Exercise to exhaustion and infusions of isoproterenol and phenylephrine were used to study interactions between plasminogen activator regulation and the control of regional blood flow in 10 healthy males. Methods and Results Experimental measurements of cardiac output, heart rate, tissue plasminogen activator (TPA), urokinase plasminogen activator (UPA), plasminogen activator inhibitor (PAI-1), C1-inhibitor, and TPA/C1-inhibitor complex during the infusions and exercise were used to develop a comprehensive fluid-phase model of the circulatory regulation of fibrinolysis. α- and β-adrenergic agonists increased TPA and UPA in plasma by different mechanisms: Phenylephrine decreased hepatic blood flow and thus clearance while isoproterenol stimulated increased secretion of TPA and UPA. Exercise to exhaustion increased TPA and UPA through a combination of increased secretion and decreased clearance. The time course of UPA and TPA release were similar, but the magnitude of their secretion responses differed. In vivo, C1-inhibitor bound to TPA at a rate of 553 mol −1 · s −1 . C1-inhibitor contributed equally with PAI-1 to TPA inhibition when active PAI-1 levels were low (20 to 50 pmol/L) but was less important when active PAI-1 levels were high. Conclusions We conclude that secretion, inhibition, clearance, and regional blood flow effects must all be taken into account when evaluating changes in plasminogen activator levels.
Oxalate Intake and the Risk for Nephrolithiasis
Authors: Eric N. Taylor, Gary C. Curhan
Journal: Journal of the American Society of Nephrology (2007)

Most kidney stones consist of calcium oxalate, and higher urinary oxalate increases the risk for calcium oxalate nephrolithiasis. However, the relation between dietary oxalate and stone risk is unclear. This study prospectively examined the relation between oxalate intake and incident nephrolithiasis in the Health Professionals Follow-up Study (n = 45,985 men), the Nurses' Health Study I (n = 92,872 older women), and the Nurses' Health Study II (n = 101,824 younger women). Food frequency questionnaires were used to assess oxalate intake every 4 yr. Cox proportional hazards regression was used to adjust for age, body mass index, thiazide use, and dietary factors. A total of 4605 incident kidney stones were documented over a combined 44 yr of follow-up. Mean oxalate intakes were 214 mg/d in men, 185 mg/d in older women, and 183 mg/d in younger women and were similar in stone formers and non-stone formers. Spinach accounted for >40% of oxalate intake. For participants in the highest compared with lowest quintile of dietary oxalate, the relative risks for stones were 1.22 (95% confidence interval [CI] 1.03 to 1.45; P = 0.01 for trend) for men and 1.21 (95% CI 1.01 to 1.44; P = 0.05 for trend) for older women. Risk was higher in men with lower dietary calcium (P = 0.08 for interaction). The relative risks for participants who ate eight or more servings of spinach per month compared with fewer than 1 serving per month were 1.30 (95% CI 1.08 to 1.58) for men and 1.34 (95% CI 1.10 to 1.64) for older women. Oxalate intake and spinach were not associated with risk in younger women. These data do not implicate dietary oxalate as a major risk factor for nephrolithiasis.
A multicentre phase II study of the efficacy and safety of docetaxel as first-line treatment of advanced breast cancer: Report of the Clinical Screening Group of the EORTC
Authors: P. Fumoleau, B. Chevallier, P. Kerbrat, Y. Krakowski, J.-L. Misset, C. Maugard-Louboutin, V. Dieras, N. Azli, N. Bougon, A. Riva, H. Roche
Journal: Annals of Oncology (1996)
Endothelial Nitric Oxide Synthase Genotype and Ischemic Heart Disease
Authors: Juan P. Casas, Leonelo E. Bautista, Steve E. Humphries, Aroon D. Hingorani
Journal: Circulation (2004)

Background— Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may influence the risk of ischemic heart disease (IHD), but data from published studies with individually low statistical power are conflicting. To evaluate the role of polymorphisms in the eNOS gene in IHD, we considered all available studies in a meta-analysis. Methods and Results— Case-control studies evaluating the association between the Glu298Asp, −786T&gt;C, and intron-4 polymorphisms and IHD were searched in MEDLINE and EMBASE up to January 2003. The principal prior hypothesis was that homozygosity for eNOS Asp298, the −786C allele in the promoter, or the intron-4 ( a allele) would be associated with an increased risk of IHD. Data were available for 9867 cases and 13 161 controls from 26 studies. Homozygosity for the Asp298 was associated with an increased risk of IHD (OR, 1.31; 95% CI, 1.13 to 1.51). Although there was significant heterogeneity among studies of Asp298 ( P Het =0.0002), which was largely accounted for by a single study, the increase in risk was still significant after exclusion of that study from analysis. Homozygosity for the intron-4 a allele was also significantly associated with higher risk of IHD (OR, 1.34; 95% CI, 1.03 to 1.75). However, no significant association was found with the −786C allele (OR, 1.06; 95% CI, 0.89, 1.25). Conclusions— Individuals homozygous for the Asp298 and intron-4 a alleles of eNOS are at moderately increased risk of IHD. These findings support the proposal that common genetic variations in the eNOS gene contribute to atherosclerosis susceptibility, presumably by effects on endothelial NO availability.
Gene Expression Profiles of Mucosal Biopsy Specimens from Children with Eosinophilic Gastritis
Authors: Tetsuo Shoda, Ichiro Nomura, Akio Matsuda, Kyoko Futamura, Kanami Orihara, Hideaki Morita, Katsuhiro Arai, Hirotaka Shimizu, Yoshiyuki Yamada, Masami Narita, Yukihiro Ohya, Hirohisa Saito, Kenji Matsumoto
Journal: Journal of Allergy and Clinical Immunology (2015)
The Pattern of Cognitive Performance in CADASIL: A Monogenic Condition Leading to Subcortical Ischemic Vascular Dementia
Authors: Nils Peters, Christian Opherk, Adrian Danek, Clive Ballard, Jürgen Herzog, Martin Dichgans
Journal: American Journal of Psychiatry (2005)

Subcortical ischemic vascular lesions, which are closely related to small vessel disease, are a common substrate of cognitive impairment and dementia. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic variant of small vessel disease resulting from mutations in NOTCH3. Mutation carriers almost invariably develop cognitive deficits and eventually dementia. The current study describes the profile of cognitive abnormalities in CADASIL subjects.A cross-sectional study of 65 mutation carriers (mean age=47.3 years, SD=10.5) and 30 matched comparison subjects (mean age=47.2 years, SD=14.0) was conducted. Participants underwent a series of assessments that included ratings of global cognition, the cognitive portion of the Vascular Dementia Assessment Scale, and specific tests of executive function and attention with measures of processing speed and error monitoring.CADASIL subjects had pronounced impairments of the timed measures (Stroop II and III, Trail Making Test, symbol digit, digit cancellation). Measures of error monitoring (Stroop III, Trail Making Test, symbol digit, maze task) were also significantly affected but to a lesser extent. Prominent deficits further included verbal fluency and ideational praxis. Recall, orientation, and receptive language skills were largely preserved. Subgroup analyses indicated a similar profile in subjects with early and advanced impairment of global cognitive performance.The findings highlight processing speed as the most substantial area of cognitive impairment in CADASIL subjects, with less pronounced yet significant deficits in other aspects of executive performance and attention. This profile of cognitive impairment is present at an early stage and enables the construction of targeted test batteries for clinical trials. It is hypothesized that the profile of dysfunction described here represents the core of the cognitive syndrome associated with small vessel disease and subcortical ischemic vascular lesions.
Racial/Ethnic Differences in Association of Fasting Glucose–Associated Genomic Loci With Fasting Glucose, HOMA-B, and Impaired Fasting Glucose in the U.S. Adult Population
Authors: Quanhe Yang, Tiebin Liu, Peter Shrader, Ajay Yesupriya, Man-huei Chang, Nicole F. Dowling, Renée M. Ned, Josée Dupuis, Jose C. Florez, Muin J. Khoury, James B. Meigs
Journal: Diabetes Care (2010)

OBJECTIVE To estimate allele frequencies and the marginal and combined effects of novel fasting glucose (FG)-associated single nucleotide polymorphisms (SNPs) on FG levels and on risk of impaired FG (IFG) among non-Hispanic white, non-Hispanic black, and Mexican Americans. RESEARCH DESIGN AND METHODS DNA samples from 3,024 adult fasting participants in the National Health and Nutrition Examination Survey (NHANES) III (1991–1994) were genotyped for 16 novel FG-associated SNPs in multiple genes. We determined the allele frequencies and influence of these SNPs alone and in a weighted genetic risk score on FG, homeostasis model assessment of β-cell function (HOMA-B), and IFG by race/ethnicity, while adjusting for age and sex. RESULTS All allele frequencies varied significantly by race/ethnicity. A weighted genetic risk score, based on 16 SNPs, was associated with a 0.022 mmol/l (95% CI 0.009–0.035), 0.036 mmol/l (0.019–0.052), and 0.033 mmol/l (0.020–0.046) increase in FG levels per risk allele among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans, respectively. Adjusted odds ratios for IFG were 1.78 for non-Hispanic whites (95% CI 1.00–3.17), 2.40 for non-Hispanic blacks (1.07–5.37), and 2.39 for Mexican Americans (1.37–4.14) when we compared the highest with the lowest quintiles of genetic risk score (P = 0.365 for testing heterogeneity of effect across race/ethnicity). CONCLUSIONS We conclude that allele frequencies of 16 novel FG-associated SNPs vary significantly by race/ethnicity, but the influence of these SNPs on FG levels, HOMA-B, and IFG were generally consistent across all racial/ethnic groups.
Epigenetics: Relevance and Implications for Public Health
Authors: Laura S. Rozek, Dana C. Dolinoy, Maureen A. Sartor, Gilbert S. Omenn
Journal: Annual Review of Public Health (2014)

Improved understanding of the multilayer regulation of the human genome has led to a greater appreciation of environmental, nutritional, and epigenetic risk factors for human disease. Chromatin remodeling, histone tail modifications, and DNA methylation are dynamic epigenetic changes responsive to external stimuli. Careful interpretation can provide insights for actionable public health through collaboration between population and basic scientists and through integration of multiple data sources. We review key findings in environmental epigenetics both in human population studies and in animal models, and discuss the implications of these results for risk assessment and public health protection. To ultimately succeed in identifying epigenetic mechanisms leading to complex phenotypes and disease, researchers must integrate the various animal models, human clinical approaches, and human population approaches while paying attention to life-stage sensitivity, to generate effective prescriptions for human health evaluation and disease prevention.
US Senate outlaws "partial birth abortion"
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

The Republican controlled US Senate passed legislation last week outlawing “partial birth abortion,” a technique used in an estimated 0.6% of abortions. Similar legislation will almost certainly be passed by the House of Representatives, also in the control of the Republicans, and soon signed into law by President Bush.

Bush has long opposed abortion. After passage of the Senate bill he issued a statement calling partial birth abortion “an abhorrent procedure that offends human dignity” and the ban a step “toward building a culture of life in America.” The Republican leader in the Senate, transplant surgeon Dr Bill Frist, called the procedure “brutal … barbarous and morally offensive to the mainstream medical community.”

Partial birth abortion is what the American College of Obstetricians and Gynecologists calls …
Age-Related Accumulation of Mutations Supports a Replication-Dependent Mechanism of Spontaneous Mutation at Tandem Repeat DNA Loci in Mice
Authors: R. J. Hardwick, M. V. Tretyakov, Y. E. Dubrova
Journal: Molecular Biology and Evolution (2009)

Expanded simple tandem repeat (ESTR) loci belong to the class of highly unstable loci in the mouse genome. The mechanisms underlying the very high spontaneous instability at these loci still remain poorly understood. Using single-molecule polymerase chain reaction, here we have compared the pattern of mutation accumulation in tissues with different proliferation capacities in male mice of age 12, 26, 48, and 96 weeks. In the nonproliferating brain, we did not observe any measurable age-related accumulation of ESTR mutations. In contrast, a highly elevated frequency of ESTR mutation was detected in the sperm samples taken from old mice; similar changes were also observed in the bone marrow tissue. The spectra of ESTR mutations accumulated in all tissues of young and old mice did not significantly differ. Taken together, these data clearly imply that spontaneous ESTR mutations occur almost exclusively in replication-proficient cells. To gain further insights into the mechanisms of ESTR mutation, we developed a stochastic model of age-related mutation accumulation. The observed spectra of ESTR mutants accumulated in the brain and sperm were fairly accurately approximated assuming the values of ESTR mutation rate, ranging from 0.01 to 0.04 per cell division. As these estimates dramatically exceed those for protein-coding genes and microsatellite loci, our data therefore suggest that ESTRs represent one of the most unstable loci in the mammalian genome. The results of our study also imply that ESTR loci can be regarded as a class of expanded microsatellites, with the mechanism of spontaneous mutation most probably attributed to replication slippage.
Lung cancer in Berlin ' Significant changes in age structure, gender ratio and histologic subtypes from 2000 to 2008
Authors: Torsten Blum, Stephan Eggeling, Christian Gogoll, Christian Grah, Christian Grohé, Christel Lauer, Gunda Leschber, Jens Neudecker, Wulf Pankow, Bernd Schicke, Paul Schneider, Nicolas Schoenfeld, Christian Witt, Anita Jagota
Journal: European Respiratory Journal (2012)

Background: The Tumorzentrum Berlin (TZB) analyses the clinical data of lung cancer pts. in Berlin in order to improve patient care by means of joint quality assurance.

Aim: to evaluate time shifts in age structure, gender ratio and the proportions of histologic subtypes in pts. with lung cancer from 2000 to 2008.

Methods: In this retrospective case study, the pooled data of the TZB of pts. with newly diagn. lung cancer during 2000 and 2008 were analyzed. Pts. were divided into three 3-year groups (G1: 2000-2, G2: 2003-5 and G3: 2006-8).

Results: The total cohort comprised 14,302 pts. (G1: 4,284 pts, G2: 5,049 pts and G3: 4,969 pts). The increase in pt. numbers in G2 and G3 is explained primarily by an absolute increase in pts. aged ≥ 70 yrs., but there was no trend for an increase of younger pts.

![Figure][1] 



The proportion of pts. with adenocarcinomas has increased over time for all age groups.

![Figure][1] 



Conclusions: 

The data of the TZB documented significant epidemiologic changes in pts. with lung cancer over time. In contrast to other regions in the world, there was no increase of younger pts. inspite of a growing proportion of pts. with adenocarcinoma.

 [1]: pending:yes
SENSORI-MOTOR INSOLES MAY INCREASE PERONEUS LONGUS ACTIVITY DURING STANCE PHASE OF HUMAN GAIT
Authors: Oliver Ludwig, Roman Quadflieg, Michael Koch
Journal: British Journal of Sports Medicine (2013)

Background Sensori-motor insoles are supposed to influence muscle activity of the ankle stabilizing muscles during stance phase of human gait by imposing pressure upon tendon structures. For this purpose, specially shaped elements are integrated in the insoles. In particular, activation of m. peroneus longus as a main pronator of the foot is supposed to prevent ankle sprains. Nevertheless, no evidence for a potential effect of sensori-motor insoles could be shown until now. The objective of this study was to examine changes in muscle activity of the peroneus longus (PL) and tibialis anterior (TA) muscle caused by sensori-motor insoles with a lateral wedge. Methods For 32 healthy subjects the activity of the peroneus longus and tibialis anterior muscle was recorded by means of surface EMG (Noraxon Telemyo). A randomized, double blinded cross-over-design was used. Subjects walked in several sub-tests both in neutral shoes with sensori-motor insoles and with dummy insoles. Sensori-motor insoles (Shore 35, Springer AG, Berlin) had a convex-formed spot that was placed above the skin of the peroneus longus tendon, 8 mm distal to the inferior retinaculum. Pressure sensors under the heel and forefoot were used to identify gait phases. In a former study changes in muscular activity peaks of the peroneus longus muscle could be found mainly in the period between 14% and 34% stance phase. 1 Therefore, integrated EMG was calculated for both PL and TA for the periods of 0–15% (loading response), 15–50% (mid stance) and 50–100% (terminal stance). Sub-tests with sensori-motor insoles and dummy insoles were compared for each subject by statistical means (paired t-test). Effect size and post hoc power were calculated using G*Power 3.1. Results PL activity in mid stance was statistically significant higher (p=.0083, post hoc power =.98) with sensori-motor insoles (18.4±12.17 uV*s) compared to dummy-insoles (10.0±7.6 uV*s). Effect size (Cohen's d) was .80, indicating a large effect. For other gait phases and for TA activity no significant effects (p&lt;.05) could be found. Discussion As changes in peroneus activity could be found only in mid stance when both the body weight is transferred to the foot and the sensori-motor spots impose pressure on the skin we conclude that increased muscular activation is due to increased afferent input. In both initial contact and terminal stance the sensori-motor spots do not influence afferent input and motor activation pattern of peroneus longus. As the ankle joint is sensitive to disturbances (supination) during mid stance an increased activity of pronator muscles might help to stabilize the foot and possibly help to prevent ankle sprains.
Spondylodiscitis and ankylosing spondylitis: HLA typing and nosological implications.
Authors: V Modena, N Migone, V Daneo, A O Carbonara, S di Vittorio, M Viara
Journal: Annals of the Rheumatic Diseases (1978)

Nine cases from among 64 patients with ankylosing spondylitis (AS) are described. In addition to bilateral sacroiliitis these cases had a peculiar type of spondylodiscitis characterised by quite diffuse and marked sclerosis of multiple vertebral bodies, with only minimal erosions of the adjacent vertebral plates while classical syndesmophytosis was absent. The antigen HLA-B27 was found only in 1 of these 9 cases. This type of spondylodiscitis could discriminate among all the patients with AS a subgroup with a peculiar clinical pattern and a probably distinctive pathological mechanism.
The Erythroid Membrane Skeleton: Expression and Assembly During Erythropoiesis
Authors: C M Woods, E Lazarides
Journal: Annual Review of Medicine (1988)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
18 Differential priming of T cells by antigens expressed in hepatocytes and cholangiocytes in animal models of autoimmune hepatitis and cholangitis
Authors: K. Derkow, S. Vierich, N. Kruse, K. Klugewitz, J. Mintern, B. Wiedenmann, T. Berg, H. Ploegh, E. Schott
Journal: Journal of Hepatology (2006)