tbuckley/cabot-search huggingface dataset:
Evaluation of an HIV Nucleic Acid Testing Program With Automated Internet and Voicemail Systems to Deliver Results
Authors: Sheldon R. Morris
Journal: Annals of Internal Medicine (2010)

Background: Nucleic acid testing (NAT) in routine HIV testing programs can increase the detection of infected individuals, but the most effective implementation of NAT remains unclear. Objective: To determine how many HIV cases can be identified with NAT and how many persons can be contacted, to identify predictors of acute and early HIV infection cases, and to test reporting of negative results by automated Internet and voicemail systems. Design: Prospective study. Setting: San Diego County, California. Participants: Persons seeking HIV testing. Measurements: Rates and predictors of HIV infection by stage, notification of positive NAT results, use of automated Internet or voicemail systems to access negative NAT results, and estimated HIV infections prevented. Results: Of 3151 persons tested, 79 had newly diagnosed cases of HIV: 64 had positive results from rapid HIV test, and 15 had positive results only by NAT (that is, NAT increased the HIV detection yield by 23%). Of all HIV infections, 44% (in 35 persons) were in the acute and early stages. Most participants (56%) and persons with HIV (91%) were men who have sex with men (MSM). All persons with NAT-positive results were notified within 1 week. Of all 3070 uninfected patients, 2105 (69%) retrieved their negative NAT results, with 1358 using the Internet system. After adjustment for covariates, persons reporting MSM behavior, higher incomes, younger ages, no testing at substance abuse rehabilitation centers, no recent syphilis, and no methamphetamine use were more likely to access negative NAT results by either Internet or voicemail systems. Limitation: Findings may not be generalizable to other populations and testing programs. Conclusion: Nucleic acid testing programs that include automated systems for result reporting can increase case yield, especially in settings that cater to MSM. Primary Funding Source: California HIV/AIDS Research Program and the National Institutes of Health.
Phase II Feasibility Study of Adjuvant S-1 Plus Docetaxel Repeated for 6 Months as Adjuvant Chemotherapy for Stage III Gastric Cancer After Curative D2 Gastrectomy (OGSG 1002)
Authors: Kimura Yutaka, Fujitani Kazumasa, Tamura Shigeyuki, Matsuyama Jin, Imamura Hiroshi, Fujita Junya, Iijima Shohei, Ueda Shugo, Shimokawa Toshio, Kurokawa Yukinori, Satoh Taroh, Tsujinaka Toshimasa, Furukawa Hiroshi
Journal: Annals of Oncology (2014)
THE STRUCTURAL BASIS OF T CELL ACTIVATION BY SUPERANTIGENS
Authors: Hongmin Li, Andrea Llera, Emilio L. Malchiodi, Roy A. Mariuzza
Journal: Annual Review of Immunology (1999)

Superantigens (SAGs) are a class of immunostimulatory and disease-causing proteins of bacterial or viral origin with the ability to activate large fractions (5-20%) of the T cell population. Activation requires simultaneous interaction of the SAG with the V beta domain of the T cell receptor (TCR) and with major histocompatibility complex (MHC) class II molecules on the surface of an antigen-presenting cell. Recent advances in knowledge of the three-dimensional structure of bacterial SAGs, and of their complexes with MHC class II molecules and the TCR beta chain, provide a framework for understanding the molecular basis of T cell activation by these potent mitogens. These structures along with those of TCR-peptide/MHC complexes reveal how SAGs circumvent the normal mechanism for T cell activation by peptide/MHC and how they stimulate T cells expressing TCR beta chains from a number of different families, resulting in polyclonal T cell activation. The crystal structures also provide insights into the basis for the specificity of different SAGs for particular TCR beta chains, and for the observed influence of the TCR alpha chain on SAG reactivity. These studies open the way to the design of SAG variants with altered binding properties for TCR and MHC for use as tools in dissecting structure-activity relationships in this system.
Limits of Detection of Regional Differences in Vasodilated Flow in Viable Myocardium by First-Pass Magnetic Resonance Perfusion Imaging
Authors: Francis J. Klocke, Orlando P. Simonetti, Robert M. Judd, Raymond J. Kim, Kathleen R. Harris, Sascha Hedjbeli, David S. Fieno, Stephan Miller, Vicky Chen, Michele A. Parker
Journal: Circulation (2001)

Background Perfusion imaging techniques intended to identify regional limitations in coronary flow reserve in viable myocardium need to identify 2-fold differences in regional flow during coronary vasodilation consistently. This study evaluated the suitability of current first-pass magnetic resonance approaches for evaluating such differences, which are 1 to 2 orders of magnitude less than in myocardial infarction. Methods and Results Graded regional differences in vasodilated flow were produced in chronically instrumented dogs with either left circumflex (LCx) infusion of adenosine or partial LCx occlusion during global coronary vasodilation. First-pass myocardial signal intensity-time curves were obtained after right atrial injection of gadoteridol (0.025 mmol/kg) with an MRI inversion recovery true-FISP sequence. The area under the initial portion of the LCx curve was compared with that of a curve from a remote area of the ventricle. Relative LCx and remote flows were assessed simultaneously with microspheres. The ratio of LCx and remote MRI curve areas and the ratio of LCx and remote microsphere concentrations were highly correlated and linearly related over a 5-fold range of flow differences ( y =0.96 x ±0.07, P &lt;0.0001, r 2 =0.87). The 95% confidence limits for individual MRI measurements were ±35%. Regional differences of ≥2-fold were consistently apparent in unprocessed MR images. Conclusions Clinically relevant regional reductions in vasodilated flow in viable myocardium can be detected with 95% confidence over the range of 1 to 5 times resting flow. This suggests that MRI can identify and quantify limitations in perfusion reserve that are expected to be produced by stenoses of ≥70%.
Disruption of Cortical Association Networks in Schizophrenia and Psychotic Bipolar Disorder
Authors: Justin T. Baker, Avram J. Holmes, Grace A. Masters, B. T. Thomas Yeo, Fenna Krienen, Randy L. Buckner, Dost Öngür
Journal: JAMA Psychiatry (2013)

Psychotic disorders (including schizophrenia, schizoaffective disorder, and psychotic bipolar disorder) are devastating illnesses characterized by breakdown in the integration of information processing. Recent advances in neuroimaging allow for the estimation of brain networks on the basis of intrinsic functional connectivity, but the specific network abnormalities in psychotic disorders are poorly understood.To compare intrinsic functional connectivity across the cerebral cortex in patients with schizophrenia spectrum disorders or psychotic bipolar disorder and healthy controls.We studied 100 patients from an academic psychiatric hospital (28 patients with schizophrenia, 32 patients with schizoaffective disorder, and 40 patients with bipolar disorder with psychosis) and 100 healthy controls matched for age, sex, race, handedness, and scan quality from December 2009 to October 2011.Functional connectivity profiles across 122 regions that covered the entire cerebral cortex.Relative to the healthy controls, individuals with a psychotic illness had disruption across several brain networks, with preferential reductions in functional connectivity within the frontoparietal control network (P < .05, corrected for family-wise error rate). This functionally defined network includes portions of the dorsolateral prefrontal cortex, posteromedial prefrontal cortex, lateral parietal cortex, and posterior temporal cortex. This effect was seen across diagnoses and persisted after matching patients and controls on the basis of scan quality.Our study results support the view that cortical information processing is disrupted in psychosis and provides new evidence that disruptions within the frontoparietal control network may be a shared feature across both schizophrenia and affective psychosis.
Regulation, Function, and Tissue-Specific Expression of Cytochrome P450 CYP1B1
Authors: Graeme I Murray, William T Melvin, William F Greenlee, M Danny Burke
Journal: The Annual Review of Pharmacology and Toxicology (2001)

Cytochrome P450 CYP1B1 is a relatively recently identified member of the CYP1 gene family. The purpose of this commentary is to review the regulatory mechanisms, metabolic specificity, and tissue-specific expression of this cytochrome P450 and to highlight its unique properties. The regulation of CYP1B1 involves a variety of both transcriptional and post-transcriptional mechanisms. CYP1B1 can metabolize a range of toxic and carcinogenic chemicals in vitro but in some cases with a unique stereoselectivity. Estradiol 4-hydroxylation appears to be a characteristic reaction catalyzed by human CYP1B1. However, there are considerable species differences regarding the regulation, metabolic specificity, and tissue-specific expression of this P450. In humans CYP1B1 is overexpressed in tumor cells, and this has important implications for tumor development and progression and the development of anticancer drugs specifically activated by CYP1B1.
Occurrence of Tertiary Lymphoid Tissue Is Associated with T-Cell Infiltration and Predicts Better Prognosis in Early-Stage Colorectal Cancers
Authors: Giuseppe Di Caro, Francesca Bergomas, Fabio Grizzi, Andrea Doni, Paolo Bianchi, Alberto Malesci, Luigi Laghi, Paola Allavena, Alberto Mantovani, Federica Marchesi
Journal: Clinical Cancer Research (2014)

Tumor-infiltrating T lymphocytes (TIL) play a key role in the clinical outcome of human colorectal cancer; however, the dynamics of their recruitment along colorectal cancer clinical progression have not been fully elucidated. Tertiary lymphoid tissue (TLT) is an ectopic organized lymph node-like structure that typically forms at sites of chronic inflammation and is involved in adaptive immune responses. Its occurrence in cancer is sporadically documented and its role and clinical relevance is largely unknown.The occurrence of TLT, the correlation with TILs, and the clinical relevance were evaluated retrospectively, in a cohort study involving a consecutive series of 351 patients with stage II and III colorectal cancer. The role of TLT in lymphocyte recruitment was assessed in a preclinical model of colorectal cancer.In both human colorectal cancer and in a murine model of colorectal cancer, we identified organized TLT, highly vascularized (including high endothelial venules), and correlated with the density of CD3(+) TILs. Intravenous injection in mice of GFP splenocytes resulted in homing of lymphocytes to TLT, suggesting an active role of TLT in the recruitment of lymphocytes to tumor areas. Accordingly, TLT density and TIL infiltration correlated and were coordinated in predicting better patient's outcome among patients with stage II colorectal cancer.We provide evidence that TLT is associated with lymphocyte infiltration in colorectal cancer, providing a pathway of recruitment for TILs. TLT cooperates with TILs in a coordinated antitumor immune response, when identifying patients with low-risk early-stage colorectal cancer, thus, representing a novel prognostic biomarker for colorectal cancer.
An Increase of Abdominal Pressure Increases Pulmonary Edema in Oleic Acid–induced Lung Injury
Authors: Michael Quintel, Paolo Pelosi, Pietro Caironi, Jurgen Peter Meinhardt, Thomas Luecke, Peter Herrmann, Paolo Taccone, Christian Rylander, Franco Valenza, Eleonora Carlesso, Luciano Gattinoni
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Increased abdominal pressure is common in intensive care unit patients. To investigate its impact on respiration and hemodynamics we applied intraabdominal pressure (aIAP) of 0 and 20 cm H(2)O (pneumoperitoneum) in seven pigs. The whole-lung computed tomography scan and a complete set of respiratory and hemodynamics variables were recorded both in healthy lung and after oleic acid (OA) injury. In healthy lung, aIAP 20 cm H(2)O significantly lowered the gas content, leaving the tissue content unchanged. In OA-injured lung at aIAP 0 cm H(2)O, the gas content significantly decreased compared with healthy lung. The excess tissue mass (edema) amounted to 30 +/- 24% of the original tissue weight (455 +/- 80 g). The edema was primarily distributed in the base regions and was not gravity dependent. Heart volume, central venous, pulmonary artery, wedge, and systemic arterial pressures significantly increased. At aIAP 20 cm H(2)O in OA-injured lung, the central venous and pulmonary artery pressures further increased. The gas content further decreased, and the excess tissue mass rose up to 103 +/- 37% (tissue weight 905 +/- 134 g), with homogeneous distribution along the cephalocaudal and sternovertebral axis. We conclude that in OA-injured lung, the increase of IAP increases the amount of edema.
Short-term effects of ambient particles on mortality in the elderly: results from 28 cities in the APHEA2 project
Authors: E. Aga, E. Samoli, G. Touloumi, H.R. Anderson, E. Cadum, B. Forsberg, P. Goodman, A. Goren, F. Kotesovec, B. Kriz, M. Macarol-Hiti, S. Medina, A. Paldy, C. Schindler, J. Sunyer, P. Tittanen, B. Wojtyniak, D. Zmirou, J. Schwartz, K. Katsouyanni
Journal: European Respiratory Journal (2003)

Within the framework of the APHEA2 (Air Pollution on Health: a European Approach) project, the effects of ambient particles on mortality among persons > or = 65 yrs were investigated. Daily measurements for particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) and black smoke (BS), as well as the daily number of deaths among persons > or = 65 yrs of age, from 29 European cities, have been collected. Data on other pollutants and meteorological variables, to adjust for confounding effects and data on city characteristics, to investigate potential effect modification, were also recorded. For individual city analysis, generalised additive models extending Poisson regression, using a locally weighted regression (LOESS) smoother to control for seasonal effects, were applied. To combine individual city results and explore effect modification, second stage regression models were applied. The per cent increase (95% confidence intervals), associated with a 10 microg x m(-3) increase in PM10, in the elderly daily number of deaths was 0.8%, (0.7-0.9%) and the corresponding number for BS was 0.6%, (0.5-0.8%). The effect size was modified by the long-term average levels of nitrogen dioxide (higher levels were associated with larger effects), temperature (larger effects were observed in warmer countries), and by the proportion of the elderly in each city (a larger proportion was associated with higher effects). These results indicate that ambient particles have effects on mortality among the elderly, with relative risks comparable or slightly higher than those observed for total mortality and similar effect modification patterns. The effects among the older persons are of particular importance, since the attributable number of events will be much larger, compared to the number of deaths among the younger population.
Engineered Thio-Trastuzumab-DM1 Conjugate with an Improved Therapeutic Index to Target Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: Jagath R. Junutula, Kelly M. Flagella, Richard A. Graham, Kathryn L. Parsons, Edward Ha, Helga Raab, Sunil Bhakta, Trung Nguyen, Debra L. Dugger, Guangmin Li, Elaine Mai, Gail D. Lewis Phillips, Hajime Hiraragi, Reina N. Fuji, Jay Tibbitts, Richard Vandlen, Susan D. Spencer, Richard H. Scheller, Paul Polakis, Mark X. Sliwkowski
Journal: Clinical Cancer Research (2010)

Antibody drug conjugates (ADCs) combine the ideal properties of both antibodies and cytotoxic drugs by targeting potent drugs to the antigen-expressing tumor cells, thereby enhancing their antitumor activity. Successful ADC development for a given target antigen depends on optimization of antibody selection, linker stability, cytotoxic drug potency, and mode of linker-drug conjugation to the antibody. Here, we systematically examined the in vitro potency as well as in vivo preclinical efficacy and safety profiles of a heterogeneous preparation of conventional trastuzumab-mcc-DM1 (TMAb-mcc-DM1) ADC with that of a homogeneous engineered thio-trastuzumab-mpeo-DM1 (thioTMAb-mpeo-DM1) conjugate.To generate thioTMAb-mpeo-DM1, one drug maytansinoid 1 (DM1) molecule was conjugated to an engineered cysteine residue at Ala114 (Kabat numbering) on each trastuzumab-heavy chain, resulting in two DM1 molecules per antibody. ThioTMAb-mpeo-DM1 retained similar in vitro anti-cell proliferation activity and human epidermal growth factor receptor 2 (HER2) binding properties to that of the conventional ADC. Furthermore, it showed improved efficacy over the conventional ADC at DM1-equivalent doses (μg/m(2)) and retained efficacy at equivalent antibody doses (mg/kg). An improved safety profile of >2-fold was observed in a short-term target-independent rat safety study. In cynomolgus monkey safety studies, thioTMAb-mpeo-DM1 was tolerated at higher antibody doses (up to 48 mg/kg or 6,000 μg DM1/m(2)) compared with the conventional ADC that had dose-limiting toxicity at 30 mg/kg (6,000 μg DM1/m(2)).The engineered thioTMAb-mpeo-DM1 with broadened therapeutic index represents a promising antibody drug conjugate for future clinical development of HER2-positive targeted breast cancer therapies.
Response to Comment on Guest et al. Clinical Outcomes and Cost-effectiveness of Continuous Positive Airway Pressure to Manage Obstructive Sleep Apnea in Patients With Type 2 Diabetes in the U.K. Diabetes Care 2014;37:1263–1271
Authors: Shahrad Taheri, Julian F. Guest, John R. Stradling
Journal: Diabetes Care (2014)

A potential association between obstructive sleep apnea (OSA) and diabetes is intriguing, as acknowledged in the commentary by Tahrani (1) on our article (2). OSA is prevalent among patients with diabetes and may contribute to several important aspects, including glycemic control, hypertension, cardiovascular disease, and microvascular complications (3,4). In our observational study in a clinical setting, patients with type 2 diabetes and untreated OSA developed higher HbA1c levels (and blood pressure) compared with best-matched patients treated with continuous positive airway pressure (CPAP), despite greater prescription of antidiabetes medications (2). Although data were unavailable, it is likely that the patients studied had significant symptomatic OSA given their BMI and the usual symptom-driven presentation to primary care.

Tahrani (1) suggested …
A Novel Somatic Deletion Mutation of ATP2B3 in Aldosterone-Producing Adenoma
Authors: Masanori Murakami, Takanobu Yoshimoto, Isao Minami, Ryotaro Bouchi, Kyoichiro Tsuchiya, Koshi Hashimoto, Hajime Izumiyama, Yasuhisa Fujii, Takashi Endo, Takumi Akashi, Koshiro Nishimoto, Kuniaki Mukai, Kazunori Kihara, Yoshihiro Ogawa
Journal: Endocrine Pathology (2015)
Adapalene-benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: a transatlantic, randomized, double-blind, controlled study in 1670 patients
Authors: H.P.M. Gollnick, Z. Draelos, M.J. Glenn, L.A. Rosoph, A. Kaszuba, R. Cornelison, B. Gore, Y. Liu, M. Graeber
Journal: British Journal of Dermatology (2009)

Background Combination therapy utilizing agents with complementary mechanisms of action is recommended by acne guidelines to help simultaneously target multiple pathogenic factors. A unique, topical, fixed‐dose combination gel with adapalene 0·1% and benzoyl peroxide (BPO) 2·5% has recently been developed for the once‐daily treatment of acne. Objectives To evaluate the efficacy and safety of adapalene 0·1%–BPO 2·5% fixed‐dose combination gel (adapalene–BPO) relative to adapalene 0·1% monotherapy (adapalene), BPO 2·5% monotherapy (BPO), and the gel vehicle (vehicle) in a large population for the treatment of acne vulgaris. Methods In total, 1670 subjects were randomized in a double‐blind controlled trial to receive adapalene–BPO, adapalene, BPO or vehicle for 12 weeks (1 : 1 : 1 : 1 randomization). Evaluations included success rate (subjects 'clear' or 'almost clear'), percentage change in lesion count from baseline, cutaneous tolerability and adverse events. Results Adapalene–BPO was significantly more effective than corresponding monotherapies, with significant differences in percentage lesion count change observed as early as 1 week. Cutaneous tolerability profile was similar to adapalene. Adverse events were more frequent with the combination therapy (mainly due to an increase in mild‐to‐moderate dry skin), occurred early in the study, and were transient. Conclusions Adapalene–BPO provides significantly greater and synergistic efficacy and a faster onset of action with an acceptable safety profile in the treatment of acne vulgaris when compared with the corresponding vehicle and the adapalene and BPO monotherapies.
A Functional Epidermal Growth Factor (EGF) Polymorphism, EGF Serum Levels, and Esophageal Adenocarcinoma Risk and Outcome
Authors: Michael Lanuti, Geoffrey Liu, Jonathan M. Goodwin, Rihong Zhai, Bryan C. Fuchs, Kofi Asomaning, Li Su, Norman S. Nishioka, Kenneth K. Tanabe, David C. Christiani
Journal: Clinical Cancer Research (2008)

The epidermal growth factor (EGF) pathway is important in esophageal adenocarcinoma (EAC) tumorigenesis. We hypothesized that the EGF A61G homozygous variant genotype (GG) is (a) both a risk and poor prognostic factor for EAC and (b) associated with higher EGF serum levels in individuals with gastroesophageal reflux disease (GERD).Using unconditional logistic regression, we compared EGF A61G in 312 EAC cases and 447 GERD-free controls, adjusting for age, gender, smoking history, and healthy adult body mass index. Using the method of Kaplan and Meier, log-rank tests, and Cox proportional hazard models, we correlated EGF A61G with overall and failure-free survival in the EAC cases. Serum EGF levels and EGF genotype (G/G versus others) were correlated in 144 GERD patients using Wilcoxon rank sum tests.The EGF A61G G/G genotype conferred increased EAC risk, with an adjusted odds ratio of 1.81 (95% confidence interval, 1.2-2.7), and was even higher in the subgroup of EAC patients with concurrent Barrett's esophagus (adjusted odds ratio, 2.18; 95% confidence interval, 1.3-3.7). However, EGF A61G was not associated with a more aggressive phenotype or prognosis in EAC patients. Higher serum EGF levels were found in GERD patients carrying G/G compared with A/A or A/G (P = 0.03, Wilcoxon rank sum test).The EGF A61G G/G genotype is associated with a near 2-fold greater risk of EAC. The G/G allele was also associated with higher EGF levels in tumor-free patients with GERD. EGF genotyping can potentially identify high-risk patients with GERD and Barrett's metaplasia who might benefit from increased surveillance.
Deflazacort—a safer systemic steroid for the treatment of chronic dermatoses
Authors: Margaret L. Wood, R.E.S. Gray, J.A. Kanis, Christine I. Harrington
Journal: British Journal of Dermatology (1985)

Journal Article Deflazacort—a safer systemic steroid for the treatment of chronic dermatoses Get access Margaret L. Wood, Margaret L. Wood Rupert Hallam Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar R.E.S. Gray, R.E.S. Gray Department of Human Metabolism and Clinical Biochemistry, Royal Hallamshire Hospital, Sheffield Search for other works by this author on: Oxford Academic Google Scholar J.A. Kanis, J.A. Kanis Department of Human Metabolism and Clinical Biochemistry, Royal Hallamshire Hospital, Sheffield Search for other works by this author on: Oxford Academic Google Scholar Christine I. Harrington Christine I. Harrington Rupert Hallam Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Pages 34–35, https://doi.org/10.1111/j.1365-2133.1985.tb12997.x Published: 01 July 1985