tbuckley/cabot-search huggingface dataset:
Prospective Multicenter Cohort Study to Refine Management Recommendations for Women at Elevated Familial Risk of Breast Cancer: The EVA Trial
Authors: Christiane Kuhl, Stefanie Weigel, Simone Schrading, Birke Arand, Heribert Bieling, Roy König, Bernd Tombach, Claudia Leutner, Andrea Rieber-Brambs, Dennis Nordhoff, Walter Heindel, Maximilian Reiser, Hans H. Schild
Journal: Journal of Clinical Oncology (2010)

We investigated the respective contribution (in terms of cancer yield and stage at diagnosis) of clinical breast examination (CBE), mammography, ultrasound, and quality-assured breast magnetic resonance imaging (MRI), used alone or in different combination, for screening women at elevated risk for breast cancer.Prospective multicenter observational cohort study. Six hundred eighty-seven asymptomatic women at elevated familial risk (> or = 20% lifetime) underwent 1,679 annual screening rounds consisting of CBE, mammography, ultrasound, and MRI, read independently and in different combinations. In a subgroup of 371 women, additional half-yearly ultrasound and CBE was performed more than 869 screening rounds. Mean and median follow-up was 29.18 and 29.09 months.Twenty-seven women were diagnosed with breast cancer: 11 ductal carcinoma in situ (41%) and 16 invasive cancers (59%). Three (11%) of 27 were node positive. All cancers were detected during annual screening; no interval cancer occurred; no cancer was identified during half-yearly ultrasound. The cancer yield of ultrasound (6.0 of 1,000) and mammography (5.4 of 1,000) was equivalent; it increased nonsignificantly (7.7 of 1,000) if both methods were combined. Cancer yield achieved by MRI alone (14.9 of 1,000) was significantly higher; it was not significantly improved by adding mammography (MRI plus mammography: 16.0 of 1,000) and did not change by adding ultrasound (MRI plus ultrasound: 14.9 of 1,000). Positive predictive value was 39% for mammography, 36% for ultrasound, and 48% for MRI.In women at elevated familial risk, quality-assured MRI screening shifts the distribution of screen-detected breast cancers toward the preinvasive stage. In women undergoing quality-assured MRI annually, neither mammography, nor annual or half-yearly ultrasound or CBE will add to the cancer yield achieved by MRI alone.
A semi-quantitative GeLC-MS analysis of temporal proteome expression in the emerging nosocomial pathogen Ochrobactrum anthropi
Authors: Robert Leslie James Graham, Mohit K Sharma, Nigel G Ternan, D Brent Weatherly, Rick L Tarleton, Geoff McMullan
Journal: Genome biology (2007)

Abstract Background The α-Proteobacteria are capable of interaction with eukaryotic cells, with some members, such as Ochrobactrum anthropi , capable of acting as human pathogens. O. anthropi has been the cause of a growing number of hospital-acquired infections; however, little is known about its growth, physiology and metabolism. We used proteomics to investigate how protein expression of this organism changes with time during growth. Results This first gel-based liquid chromatography-mass spectrometry (GeLC-MS) temporal proteomic analysis of O. anthropi led to the positive identification of 131 proteins. These were functionally classified and physiochemically characterized. Utilizing the emPAI protocol to estimate protein abundance, we assigned molar concentrations to all proteins, and thus were able to identify 19 with significant changes in their expression. Pathway reconstruction led to the identification of a variety of central metabolic pathways, including nucleotide biosynthesis, fatty acid anabolism, glycolysis, TCA cycle and amino acid metabolism. In late phase growth we identified a number of gene products under the control of the oxyR regulon, which is induced in response to oxidative stress and whose protein products have been linked with pathogen survival in response to host immunity reactions. Conclusion This study identified distinct proteomic profiles associated with specific growth points for O. anthropi , while the use of emPAI allowed semi-quantitative analyses of protein expression. It was possible to reconstruct central metabolic pathways and infer unique functional and adaptive processes associated with specific growth phases, thereby resulting in a deeper understanding of the physiology and metabolism of this emerging pathogenic bacterium.
Early versus Standard Antiretroviral Therapy for HIV-Infected Adults in Haiti
Authors: Patrice Severe, Marc Antoine Jean Juste, Alex Ambroise, Ludger Eliacin, Claudel Marchand, Sandra Apollon, Alison Edwards, Heejung Bang, Janet Nicotera, Catherine Godfrey, Roy M. Gulick, Warren D. Johnson, Jean William Pape, Daniel W. Fitzgerald
Journal: New England Journal of Medicine (2010)

For adults with human immunodeficiency virus (HIV) infection who have CD4+ T-cell counts that are greater than 200 and less than 350 per cubic millimeter and who live in areas with limited resources, the optimal time to initiate antiretroviral therapy remains uncertain.
Septum transversum-derived mesothelium gives rise to hepatic stellate cells and perivascular mesenchymal cells in developing mouse liver
Authors: Kinji Asahina, Bin Zhou, William T. Pu, Hidekazu Tsukamoto
Journal: Hepatology (2010)

Abstract The septum transversum mesenchyme (STM) signals to induce hepatogenesis from the foregut endoderm. Hepatic stellate cells (HSCs) are sinusoidal pericytes assumed to originate from the STM and participate in mesenchymal-epithelial interaction in embryonic and adult livers. However, the developmental origin of HSCs remains elusive due to the lack of markers for STM and HSCs. We previously identified submesothelial cells (SubMCs) beneath mesothelial cells (MCs) as a potential precursor for HSCs in developing livers. In the present study, we reveal that both STM in embryonic day (E) 9.5 and MC/SubMCs in E12.5 share the expression of activated leukocyte cell adhesion molecule (Alcam), desmin, and Wilms tumor 1 homolog (Wt1). A cell lineage analysis using MesP1Cre/Rosa26lacZflox mice identifies the mesodermal origin of the STM, HSCs, and perivascular mesenchymal cells (PMCs). A conditional cell lineage analysis using the Wt1CreERT2 mice demonstrates that Wt1+ STM gives rise to MCs, SubMCs, HSCs, and PMCs during liver development. Furthermore, we find that Wt1+ MC/SubMCs migrate inward from the liver surface to generate HSCs and PMCs including portal fibroblasts, smooth muscle cells, and fibroblasts around the central veins. On the other hand, the Wt1+ STM and MC/SubMCs do not contribute to sinusoidal endothelial cells, Kupffer cells, and hepatoblasts. Conclusion : our results demonstrate that HSCs and PMCs are derived from MC/SubMCs, which are traced back to mesodermal STM during liver development. (Hepatology 2011;.)
Botulinum toxin A inhibits salivary secretion of rabbit submandibular gland
Authors: Xiao-Feng Shan, Hui Xu, Zhi-Gang Cai, Li-Ling Wu, Guang-Yan Yu
Journal: International Journal of Oral Science (2013)

Botulinum toxin A (BTXA) has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor (M3 receptor) and aquaporin-5 (AQP5) mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular glands. Treatment with botulinum toxin A (BTXA) brings overactive salivary glands under control by restraining fluid secretion. Although several clinical studies have demonstrated that BTXA can inhibit glandular activity, its mechanism was poorly defined. Peking University researcher Zhi-Gang Cai and colleagues in China examined how BTXA affects production of saliva in the rabbit submandibular gland. Within a week of injection, they observed a considerably reduced saliva output and noted that the effects of BTXA persisted after 12 weeks. Some of these effects appear to be attributable to localized toxicity to secretory cells, but the researchers also observed selective inhibition of particular signaling pathways that control fluid production. As the effects of BTXA are relatively long-lasting but also reversible, the researchers conclude that it should offer effective treatment for medical conditions associated with excessive drooling.
Impact of Delay in Clinical Presentation on the Diagnostic Management and Prognosis of Patients with Suspected Pulmonary Embolism
Authors: Paul L. den Exter, Josien van Es, Petra M. G. Erkens, Mark J. G. van Roosmalen, Pim van den Hoven, Marcel M. C. Hovens, Pieter W. Kamphuisen, Frederikus A. Klok, Menno V. Huisman
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The nonspecific clinical presentation of pulmonary embolism (PE) frequently leads to delay in its diagnosis.This study aimed to assess the impact of delay in presentation on the diagnostic management and clinical outcome of patients with suspected PE.In 4,044 consecutive patients with suspected PE, patients presenting more than 7 days from the onset of symptoms were contrasted with those presenting within 7 days as regards the safety of excluding PE on the basis of a clinical decision rule combined with D-dimer testing. Patients were followed for 3 months to assess the rates of recurrent venous thromboembolism and mortality.A delayed presentation (presentation >7 d) was present in 754 (18.6%) of the patients. The failure rate of an unlikely clinical probability and normal D-dimer test was 0.5% (95% confidence interval [CI], 0.01-2.7) for patients with and 0.5% (95% CI, 0.2-1.2) for those without diagnostic delay. D-dimer testing yielded a sensitivity of 99% (95% CI, 96-99%) and 98% (95% CI, 97-99%) in these groups, respectively. Patients with PE with diagnostic delay more frequently had centrally located PE (41% vs. 26%; P < 0.001). The cumulative rates of recurrent venous thromboembolism (4.6% vs. 2.7%; P = 0.14) and mortality (7.6% vs. 6.6%; P = 0.31) were not different for patients with and without delayed presentation.PE can be safely excluded based on a clinical decision rule and D-dimer testing in patients with a delayed clinical presentation. A delayed presentation for patients who survived acute PE was associated with a more central PE location, although this did not affect the clinical outcome at 3 months.
Genetic parts to a preventive medicine whole
Authors: Nicholas J Schork
Journal: Genome Medicine (2013)

Integration of clinical evaluations and whole-genome sequence data from eight individuals in a recent study demonstrates that genetic and clinical information can be combined and applied to preventive medicine. Statistical and graphical tools were developed to assess and visualize the genetic risk of common chronic conditions and to show the changes in disease risk that result from monitoring clinical symptoms over time. This approach provides a direction to consider in the adoption of genetic information in health care, but, like all provocative scientific articles, it raises as many questions as it answers.http://genomemedicine.com/content/5/6/58.
Neural respiratory drive predicts clinical deterioration and safe discharge in exacerbations of COPD
Authors: Eui-Sik Suh, Swapna Mandal, Rachel Harding, Michelle Ramsay, Meera Kamalanathan, Katherine Henderson, Kevin O'Kane, Abdel Douiri, Nicholas S Hopkinson, Michael I Polkey, Gerrard Rafferty, Patrick B Murphy, John Moxham, Nicholas Hart
Journal: Thorax (2015)

<h3>Rationale</h3> Hospitalised patients with acute exacerbation of COPD may deteriorate despite treatment, with early readmission being common. <h3>Objectives</h3> To investigate whether neural respiratory drive, measured using second intercostal space parasternal muscle electromyography (EMG<sub>para</sub>), would identify worsening dyspnoea and physician-defined inpatient clinical deterioration, and predict early readmission. <h3>Methods</h3> Patients admitted to a single-site university hospital with exacerbation of COPD were enrolled. Spirometry, inspiratory capacity (IC), EMG<sub>para</sub>, routine physiological parameters, modified early warning score (MEWS), modified Borg scale for dyspnoea and physician-defined episodes of deterioration were recorded daily until discharge. Readmissions at 14 and 28 days post discharge were recorded. <h3>Measurements and main results</h3> 120 patients were recruited (age 70±9 years, forced expiratory volume in 1 s (FEV<sub>1</sub>) of 30.5±11.2%). Worsening dyspnoea, defined as at least one-point increase in Borg scale, was associated with increases in EMG<sub>para%max</sub> and MEWS, whereas an increase in EMG<sub>para%max</sub> alone was associated with physician-defined inpatient clinical deterioration. Admission-to-discharge change (Δ) in the normalised value of EMG<sub>para</sub> (ΔEMG<sub>para%max</sub>) was inversely correlated with ΔFEV<sub>1</sub> (r=−0.38, p&lt;0.001) and ΔIC (r=−0.44, p&lt;0.001). ΔEMG<sub>para%max</sub> predicted 14-day readmission (OR 1.13, 95% 1.03 to 1.23) in the whole cohort and 28-day readmission in patients under 85 years (OR 1.09, 95% CI 1.01 to 1.18). Age (OR 1.08, 95% CI 1.03 to 1.14) and 12-month admission frequency (OR 1.29, 1.01 to 1.66), also predicted 28-day readmission in the whole cohort. <h3>Conclusions</h3> Measurement of neural respiratory drive by EMG<sub>para</sub> represents a novel physiological biomarker that may be helpful in detecting inpatient clinical deterioration and identifying the risk of early readmission among patients with exacerbations of COPD. <h3>Trial registration</h3> NCT01361451.
Impact of a Scientific Presentation on Community Treatment Patterns for Primary Breast Cancer
Authors: Sharon H. Giordano, Zhigang Duan, Yong-Fang Kuo, Gabriel N. Hortobagyi, Jean Freeman, James S. Goodwin
Journal: JNCI Journal of the National Cancer Institute (2006)

The publication of results from randomized clinical trials can have a dramatic effect on treatment patterns, but the impact of oral presentations at national scientific meetings is unknown. We investigated the temporal association between the oral presentation of the results from the Cancer and Leukemia Group B (CALGB) Study 9344 at the May 1998 meeting of the American Society of Clinical Oncology, which showed that paclitaxel improves survival of women with lymph node-positive breast cancer, and use of taxane chemotherapy for breast cancer.We studied chemotherapy use in 3341 women identified through the Surveillance, Epidemiology, and End Results-Medicare database who were diagnosed with stage I-III breast cancer in 1994-1999 at age 65 years or older and received adjuvant chemotherapy, as identified through claims data, within 1 year of diagnosis. We assessed the temporal association between the CALBG presentation and taxane use with piecewise regression analysis. Multivariable logistic regression analysis was used to determine which patient characteristics were associated with taxane use.The use of taxanes increased substantially after the CALGB presentation, with absolute rates of taxane use of 5.2% before May 1998 and 23.6% in May 1998 and later. Initially, this increase was confined to patients with lymph node-positive disease (40% of whom were receiving taxanes by the end of 1999), but over time it extended to patients with lymph node-negative disease (15% of whom were receiving taxanes by the end of 1999). In multivariable analysis, patients who were treated in May 1998 or later were statistically significantly more likely to have received a taxane than patients treated before this date (estimated relative risk = 6.84, 95% confidence interval = 5.71 to 8.07). Younger patient age, larger number of lymph nodes involved, higher tumor grade, and larger tumor size were also independently associated with adjuvant taxane use.The oral presentation of a single study at a national conference was temporally associated with an increase in the use of taxanes for primary breast cancer, even before study publication or Food and Drug Administration approval.
Elastin fragments drive disease progression in a murine model of emphysema
Authors: A. M. Houghton
Journal: Journal of Clinical Investigation (2006)

Mice lacking macrophage elastase (matrix metalloproteinase-12, or MMP-12) were previously shown to be protected from the development of cigarette smoke-induced emphysema and from the accumulation of lung macrophages normally induced by chronic exposure to cigarette smoke. To determine the basis for macrophage accumulation in experimental emphysema, we now show that bronchoalveolar lavage fluid from WT smoke-exposed animals contained chemotactic activity for monocytes in vitro that was absent in lavage fluid from macrophage elastase-deficient mice. Fractionation of the bronchoalveolar lavage fluid demonstrated the presence of elastin fragments only in the fractions containing chemotactic activity. An mAb against elastin fragments eliminated both the in vitro chemotactic activity and cigarette smoke-induced monocyte recruitment to the lung in vivo. Porcine pancreatic elastase was used to recruit monocytes to the lung and to generate emphysema. Elastin fragment antagonism in this model abrogated both macrophage accumulation and airspace enlargement.
Slow Rates of Molecular Evolution in Birds and the Metabolic Rate and Body Temperature Hypotheses
Authors: D. P. Mindel, A. Knight, C. Baer, C. J. Huddleston
Journal: Molecular Biology and Evolution (1996)

It has long been hypothesized that the rate of molecular evolution in birds is slow relative to other tetrapods, particularly mammals, based on small genetic distances between bird taxa (e.g., Prager et al. 1974; Britten 1986). These studies rely heavily, however, on accurate dating of fossils or biogeographic events in estimating taxonomic divergence times. Adachi, Cao, and Hasegawa (1993) used a relative rate test, not dependent on dating, and found a significantly slower rate of mitochondrial amino acid substitution in chicken relative to human. Relative rate tests for birds have not yet been applied to either mitochondrial or nuclear DNAs.
Phase I–II study of irinotecan combined with mitomycin-C in patients with advanced gastric cancer
Authors: T. Yamao, K. Shirao, Y. Matsumura, K. Muro, Y. Yamada, M. Goto, K. Chin, Y. Shimada
Journal: Annals of Oncology (2001)

Irinotecan (CPT-11) shows synergism with mitomycin-C (MMC) in a preclinical setting. The goals of this study were to determine the maximum tolerated dose (MTD), the dose limiting toxicity, the recommended dose (RD), and preliminary anti-tumor activity in a combined CPT-11 and MMC treatment of advanced gastric cancer.The study was designed to evaluate escalated doses of CPT-11 and MMC administered every two weeks. Five escalating dose levels were studied (CPT-11/ MMC: 100/5; 125/5; 150/5; 150/7; 150/10 mg/m2).Thirty-one patients were enrolled. Thirty patients were assessable for toxicity and tumor response for 89 treatment cycles. The median age was 60 years (32-73 years), and most patients (90%) had a performance status of 0 to 1. Fourteen patients were previously treated and 17 were chemotherapynaive. The MTD was CPT-11 150 mg/m2 plus MMC 10 mg/m2, in which all three patients experienced grade 4 neutropenia. including one episode of prolonged and one of febrile neutropenia, and one patient experienced grade 3 diarrhea during the first cycle. Fifteen partial responses were observed.The RD based on this phase I-II study was CPT-11 150 mg/m2 plus MMC 5 mg/m2 administered every two weeks. This combination demonstrates promising activity against advanced gastric cancer and warrants further investigation in another phase II study.
A 27-Year-Old Woman With Migraine Headaches
Authors: K. M. A. Welch
Journal: JAMA (1997)

<h3>Dr Daley:</h3> Mrs D is a 27-year-old married elementary school teacher with migraine headaches. She recently moved to Boston from the Midwest and works as a substitute teacher. Her health care insurance is through a commercial managed care plan. Her doctor, Dr N, practices in the primary care unit at Beth Israel Deaconess Medical Center. Mrs D has been in good health aside from migraine headaches since the age of 10 years. Her mother, brother, and a maternal aunt also have migraines. She has had "normal" computed tomographic scans and electroencephalograms. Her headaches begin with a prodrome she describes as a "weird feeling," then a headache follows over her right eye with nausea and vomiting. She has these headaches as frequently as 4 to 5 times a month, but recently she only gets them once a month prior to her menstrual period. In the summer of 1996, she began taking
The specificity and sensitivity of transcranial ultrasound in the differential diagnosis of Parkinson's disease: a prospective blinded study
Authors: Alexandra Gaenslen, Barbara Unmuth, Jana Godau, Inga Liepelt, Adriana Di Santo, Katherine Johanna Schweitzer, Thomas Gasser, Hans-Jürgen Machulla, Matthias Reimold, Kenneth Marek, Daniela Berg
Journal: The Lancet Neurology (2008)
Regulation of Na+/H+ exchange by diadenosine polyphosphates, angiotensin II, and vasopressin in rat cortical collecting duct.
Authors: E Schlatter, S Haxelmans, I Ankorina, R Kleta
Journal: Journal of the American Society of Nephrology (1995)

In principal cells of rat cortical collecting ducts (CCD) cellular pH (pHi) is regulated by basolateral Na+/H+ exchange. The influence of various agonists on pHi and cellular Ca2+ activity ([Ca2+]i) in freshly isolated CCD cells was examined with BCECF and fura-2 fluorescence ratios. The recovery of pHi per minute (delta pH/min) after an acid load was 0.26 +/- 0.03 (N = 53) in control conditions and was increased by the diadenosine polyphosphates Ap4A, Ap5A, Ap6A, the phorbol ester phorbol 12-myristat 13-acetate (PMA) (each 5 mumol/L) and angiotensin II (100 nmol/L) by 0.05 +/- 0.02 (N = 10), 0.11 +/- 0.05 (N = 13), 0.09 +/- 0.02 (N = 24), 0.10 +/- 0.03 (N = 7), and 0.09 +/- 0.03 (N = 8), respectively. Vasopressin (10 nmol/L) decreased delta pH/min by 0.11 +/- 0.03 (N = 9); ATP and Ap3A (each 5 mumol/L) had no significant effect. The increase in delta pH/min with Ap6A was abolished in the presence of an inhibitor of protein kinase C, calphostin C (0.1 mumol/l, N = 8). Fura-2 fluorescence ratio was not significantly changed with angiotensin II, Ap3A, or Ap4A but increased with vasopressin, ATP, Ap5A, and Ap6A by 0.08 +/- 0.02 (N = 13), 0.04 +/- 0.02 (N = 13), 0.03 +/- 0.01 (N = 14), and 0.03 +/- 0.01 (N = 10), respectively. These data indicate that Na+/H+ exchange in rat CCD is activated by the stimulation of a Ca(2+)-independent protein kinase C and inhibited by protein kinase A.