LLukas22/scidocs huggingface dataset:
Application of CYP3A4 in vitro data to predict clinical drug-drug interactions; predictions of compounds as objects of interaction.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
Numerous retrospective analyses have shown the utility of in vitro systems for predicting potential drug-drug interactions (DDIs). Prediction of DDIs from in vitro data is commonly obtained using estimates of enzyme K(i), inhibitor and substrate concentrations and absorption rate for substrate and inhibitor.


WHAT THIS STUDY ADDS
Using a generic approach for all test compounds, the findings from the current study showed the use of recombinant P450s provide a more robust in vitro measure of P450 contribution (fraction metabolized, f(m)) than that achieved when using chemical inhibitors in combination with human liver microsomes, for the prediction of potential CYP3A4 drug-drug interactions prior to clinical investigation. The current study supported the use of SIMCYP(R), a modelling and simulation software in utilizing the in vitro measures in the prediction of potential drug-drug interactions.


AIMS
The aim of this study was to explore and optimize the in vitro and in silico approaches used for predicting clinical DDIs. A data set containing clinical information on the interaction of 20 Pfizer compounds with ketoconazole was used to assess the success of the techniques.


METHODS
The study calculated the fraction and the rate of metabolism of 20 Pfizer compounds via each cytochrome P450. Two approaches were used to determine fraction metabolized (f(m)); 1) by measuring substrate loss in human liver microsomes (HLM) in the presence and absence of specific chemical inhibitors and 2) by measuring substrate loss in individual cDNA expressed P450s (also referred to as recombinant P450s (rhCYP)) The fractions metabolized via each CYP were used to predict the drug-drug interaction due to CYP3A4 inhibition by ketoconazole using the modelling and simulation software SIMCYP.


RESULTS
When in vitro data were generated using Gentest supersomes, 85% of predictions were within two-fold of the observed clinical interaction. Using PanVera baculosomes, 70% of predictions were predicted within two-fold. In contrast using chemical inhibitors the accuracy was lower, predicting only 37% of compounds within two-fold of the clinical value. Poorly predicted compounds were found to either be metabolically stable and/or have high microsomal protein binding. The use of equilibrium dialysis to generate accurate protein binding measurements was especially important for highly bound drugs.


CONCLUSIONS
The current study demonstrated that the use of rhCYPs with SIMCYP provides a robust in vitro system for predicting the likelihood and magnitude of changes in clinical exposure of compounds as a consequence of CYP3A4 inhibition by a concomitantly administered drug.
A Millimeter-Wave Gain Enhanced Multi-Beam Antenna Based on a Coplanar Cylindrical Dielectric Lens

A planar millimeter-wave high gain multi-beam antenna with 5 beams in azimuth based on substrate integrated waveguide (SIW) fed antipodal linear tapered slot antennas (ALTSAs) and a coplanar cylindrical dielectric lens is proposed and implemented at 28 GHz. Both the antennas and the lens are fabricated on a single planar substrate covered by high permittivity substrate with a radius of 0.5λ0 . A prototype with 5 beams has been designed, fabricated and measured. The measured gain of each beam is around 20 dB which is about 6.5 dB higher than that of the ALTSA element. The gain enhanced multi-beam lens antenna is with the advantages of high gain, good beam uniformity, higher isolation between ports, low cost, and easily be integrated with other coplanar circuits etc.
Predictors of Limb Fat Gain in HIV Positive Patients Following a Change to Tenofovir-Emtricitabine or Abacavir-Lamivudine

BACKGROUND
Antiretroviral treatment (cART) in HIV causes lipoatrophy. We examined predictors of anthropometric outcomes over 96 weeks in HIV-infected, lipoatrophic adults receiving stable cART randomised to tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine (ABC-3TC) fixed dose combinations.


METHODOLOGY/PRINCIPAL FINDINGS
The STEAL study was a prospective trial of virologically suppressed participants randomised to either TDF-FTC (n = 178) or ABC-3TC (n = 179). Anthropometric assessment was conducted at baseline, weeks 48 and 96. The analysis population included those with baseline and week 96 data remaining on randomised therapy. Distribution of limb fat change was divided into four categories (≤ 0%, >0-10%, >10-20%, >20%). Baseline characteristics [demographics, medical history, metabolic and cardiovascular biomarkers] were assessed as potential predictors of change in percent subcutaneous limb fat using linear regression. 303 participants (85% of STEAL population) were included. Baseline characteristics were: mean (± SD) age 45 (± 8) years; thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI) duration 4 (± 3) years; limb fat 5.4 (± 3.0)kg; body mass index 24.7 (± 3 .5) kg/m(2). Mean (SD) limb fat gain to week 48 and 96 was 7.6% (± 22.4) and 13.2% (± 27.3), respectively, with no significant difference between groups. 51.5% of all participants had >10% gain in limb fat. Predictors of greater limb fat gain at week 96 were baseline tNRTI (10.3, p = 0.001), glucose >6 mmol/L (16.1, p = 0.04), higher interleukin 6 (IL-6) (2.8, p = 0.004) and lower baseline limb fat (3.8-6.4 kg - 11.2; >6.4 kg - 15.7, p trend<0.001).


CONCLUSIONS/SIGNIFICANCE
Modest peripheral fat gain occurred with both TDF-FTC and ABC-3TC. Baseline factors associated with more severe lipodystrophy (lipoatrophy, baseline tNRTI, raised IL6, and glucose) predicted greater limb fat recovery at 96 weeks.
Use of capillary zone electrophoresis for differentiating excessive from moderate alcohol consumption.

BACKGROUND
The poorly sialylated transferrin isoforms in serum were analyzed by capillary zone electrophoresis (CZE) to differentiate moderate from heavy alcohol consumption.


METHODS
We enrolled 614 volunteers, classified after interviews, self-reported drinking habits, and AUDIT scores as alcohol abusers (consuming >50 g/day ethanol for the previous 3 months or longer; n = 413) or moderate drinkers (<30 g/day ethanol; n = 201). Serum transferrin isoforms were separated at 28 kV and monitored at 214 nm on a P/ACE 5500 CZE with use of fused-silica capillaries and the related CEofix CDT reagent set. Immunosubtraction by anti-human transferrin and electrophoretic migration times identified the isoforms. Previous markers of alcohol abuse and an assay combining anion-exchange minicolumn chromatography with immunoturbidimetry (%CDT) were included in the study. Sensitivities and specificities were compared by ROC analysis.


RESULTS
The asialylated isoform was missing in 95% of moderate drinkers but present in 92% of alcohol misusers. Disialotransferrin had a specificity and sensitivity of 0.75 at a cutoff of 0.7% of total transferrin, whereas the sum (asialo- + disialotransferrin) at a threshold of 1.2% had a sensitivity of 0.73 and a specificity of 0.92. Trisialotransferrin values did not distinguish between the two populations. Sensitivities and specificities of %CDT averaged 0.77 and 0.74, respectively, at a 2.6% cutoff; 0.67 and 0.83 at 2.8%; and 0.63 and 0.90 at 3%. CDT data were more sensitive and specific for males. Conventional biomarkers appeared less discriminating.


CONCLUSIONS
Asialotransferrin detected by CZE in sera of alcohol abusers offers the highest discrimination between excessive and moderate drinking.
A Tabu Search Algorithm for the Location of Data Centers and Software Components in Green Cloud Computing Networks

The ubiquity of cloud applications requires the meticulous design of cloud networks with high quality of service, low costs, and low CO2 emissions. This paper presents a planning problem and an extremely efficient tabu search heuristic for optimizing the locations of cloud data centers and software components while simultaneously finding the information routing and network link capacities. The objectives are to optimize the network performance, the CO2 emissions, the capital expenditures (CAPEX), and the operational expenditures (OPEX). The problem is modeled using a mixed-integer programming model and solved with both an optimization solver and a tabu search heuristic. A case study of a web search engine is presented to explain and optimize the different aspects, showing how planners can use the model to direct the optimization and find the best solutions. The efficiency of the tabu search algorithm is presented for networks with up to 500 access nodes and 1,000 potential data center locations distributed around the globe.
Palaeobiology of angiosperm origins : problems of Mesozoic seed-plant evolution

1. Introduction and proposition Part I. Technical Situation: 2. Biology and Earth evolution 3. Palaeobotanical factors 4. Data-handling for fossils Part II. Cretaceous Earth History: 5. Cretaceous flora 6. Cretaceous land fauna 7. Cretaceous stratigraphy Part III. Critical Fossil Evidence: 8. Jurassic gymnosperms 9. Early Cretaceous gymnosperms 10. Early Cretaceous fossil evidence of angiosperm characters 11. Late Cretaceous angiosperms Part IV. Conclusion from Evidence: 12. Theory of angiosperm origin and early evolution Part V. Other Theories: 13 Pre-Cretaceous angiosperm chains 14. Contribution of studies of comparative morphology 15. Other current theories Part VI. Consequences: 16. Classification of angiosperms 17. Summary and future Glossary References Index.
Rocuronium for nonemergent intubation of term and preterm infants

Objective:The aim of this study was to analyze clinical characteristics of rocuronium as premedication for nonemergent intubation in infants.Study Design:Preterm infants requiring nonemergent intubation were randomized to receive atropine and fentanyl with or without rocuronium. Outcomes, patient characteristics and intubator's experience were noted. Onset, duration and degree of clinical paralysis were recorded for rocuronium group and for older infants receiving rocuronium per unit protocol.Result:Forty-four intubations were randomized (20 rocuronium, 24 control). Groups were similar in chronological and corrected gestational age, weight and intubator's experience. Successful intubation on first attempt was achieved in 35% of intubations under rocuronium vs 8% of controls; rocuronium was the only significant variable by logistic regression (odds ratio=0.052, P=0.029). Complete paralysis was reported in 80% of 57 rocuronium intubations; onset ranged from 14 to 178 s (65.9±43.4), and duration from 1 to 60 min (16.3±13.5).Conclusion:Rocuronium facilitated successful intubation and provided clinical paralysis quickly in most infants.
Customer-based brand equity for a destination

The paper introduces the concept of customer-based brand equity and applies it to a destination. The theoretically proposed and empirically verified model complements previous research findings on a destination’s evaluation from the tourist’s perspective. In addition to numerous studies, which have stressed the importance of image, the results of this study imply that an image plays a vital role in evaluation but is not the only brand dimension that should be considered. For a more complete evaluation, the dimensions of awareness, quality, and loyalty should also be examined. The concept of brand equity was tested on two Slovenian markets. Results reveal that brand equity differed between the markets according to their evaluation of brand dimensions.
Giant nevus sebaceus: definition, surgical techniques, and rationale for treatment.

BACKGROUND
A reduction in the reported incidence of malignant degeneration within nevus sebaceus has led many physicians to recommend serial clinical evaluation and biopsy of suspicious areas rather than prophylactic surgical excision. Unfortunately, no well-defined inclusion criteria, including lesion size and location, have been described for the management of nevus sebaceus.


METHODS
To assess whether the incidence or timing of malignant degeneration contraindicates surgical excision, the authors performed a PubMed literature search for any studies, excluding case reports, related to malignant change within nevus sebaceus since 1990. They then defined giant nevus sebaceus to consist of lesions greater than 20 cm or greater than 1 percent of the total body surface area and retrospectively examined their experience and outcomes treating giant nevus sebaceus.


RESULTS
Data were pooled from six large retrospective institutional studies (2520 patients). The cumulative incidence of benign and malignant tumors was 6.1 and 0.5 percent, respectively. Of the authors' 195 patients with giant congenital nevi, only six (3.0 percent) met the definition of giant nevus sebaceus. All patients required tissue expansion for reconstruction, and two patients required concomitant skin grafting. Two complications required operative intervention.


CONCLUSIONS
Early malignant degeneration within nevus sebaceus is rare. Management, however, must account for complex monitoring, particularly for lesions within the scalp, associated alopecia, involvement of multiple facial aesthetic subunits, and postpubertal transformation affecting both appearance and monitoring of the lesions. The latter considerations, rather than the reported incidence of malignant transformation, should form the bases for surgical intervention in giant nevus sebaceus.


CLINICAL QUESTION/LEVEL OF EVIDENCE
Therapeutic, V.
Religion in the Cartography of the Unconscious: A Discussion of Stanislav Grof's Realms of the Human Unconscious

"In my experience, everyone who has reached these levels develops convincing insights into the utmost relevance of the spiritual and religious dimensions in the universal scheme of things. Even hardcore materialists, positivistically oriented scientists, skeptics and cynics, and uncompromising atheists and antireligious crusaders such as the Marxist philosophers suddenly became interested in a spiritual search after they confronted these levels themselves.'
Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial.

PURPOSE
To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma.


PATIENTS AND METHODS
Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who were randomly assigned onto the Breast International Group (BIG) 1-98 trial and who had centrally reviewed pathology data were included (N = 2,923). HER2-negative IDC and ILC were additionally classified as hormone receptor-positive with high (luminal B [LB] -like) or low (luminal A [LA] -like) proliferative activity by Ki-67 labeling index. Survival analyses were performed with weighted Cox models that used inverse probability of censoring weighted modeling.


RESULTS
The median follow-up time was 8.1 years. In multivariable models for disease-free survival (DFS), significant interactions between treatment and histology (ILC or IDC; P = .006) and treatment and subgroup (LB like or LA like; P = .01) were observed. In the ILC subset, there was a 66% reduction in the hazard of a DFS event with letrozole for LB (hazard ratio [HR], 0.34; 95% CI, 0.21 to 0.55) and a 50% reduction for LA subtypes (HR, 0.50; 95% CI, 0.32 to 0.78). In the IDC subset, there was a significant 35% reduction in the hazard of a DFS event with letrozole for the LB subtype (HR, 0.65; 95% CI, 0.53 to 0.79), but no difference between treatments was noted for IDC and the LA subtype (HR, 0.95; 95% CI, 0.76 to 1.20).


CONCLUSION
The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma.
The Multilevel Conception of Intentionality: Implications for counselor training

Abstract Counseling training programs have failed to differentiate between and among behavioral, cognitive, and unconsciousness dimesnsions. This omission has resulted in confusion and competition in many counseling curricula in that valuable programs are competing for space rather than being integrated systematically. This article proposes a multilevel model of intentionality which integrates the several aspects of the counselor-client relationship. In turn, this integration of behavioral, cognitive, and unconscious dimensions will have important applications in counselor daily practice.
SnOx obtaining by thermal oxidation of nanoscale tin films in the air and its characterization

Abstract Nanocrystalline films of metal tin with a thickness of 30, 100 nm were annealed in the air for 1 h at constant temperatures varying from 170 to 750 °C. Transmission electron microscopy and X-ray absorption near edge structure experimental data show the dependence of phase composition not only on the temperature of treatment but also on the thickness of initial metal layer. Optical investigations of absorption show a considerable dependence of position of the fundamental edges on the thickness of the films. The observed maxima of absorption at ∼ 3.6 eV are related with the defect states, mainly, with oxygen vacancies of non-stoichiometric oxide.
Randomized trial of a lay health advisor and computer intervention to increase mammography screening in African American women.

BACKGROUND
Low-income African American women face numerous barriers to mammography screening. We tested the efficacy of a combined interactive computer program and lay health advisor intervention to increase mammography screening.


METHODS
In this randomized, single blind study, participants were 181 African American female health center patients of ages 41 to 75 years, at < or =250% of poverty level, with no breast cancer history, and with no screening mammogram in the past 15 months. They were assigned to either (a) a low-dose comparison group consisting of a culturally appropriate mammography screening pamphlet or (b) interactive, tailored computer instruction at baseline and four monthly lay health advisor counseling sessions. Self-reported screening data were collected at baseline and 6 months and verified by medical record.


RESULTS
For intent-to-treat analysis of primary outcome (medical record-verified mammography screening, available on all but two participants), the intervention group had increased screening to 51% (45 of 89) compared with 18% (16 of 90) for the comparison group at 6 months. When adjusted for employment status, disability, first-degree relatives with breast cancer, health insurance, and previous breast biopsies, the intervention group was three times more likely (adjusted relative risk, 2.7; 95% confidence interval, 1.8-3.7; P < 0.0001) to get screened than the low-dose comparison group. Similar results were found for self-reported mammography stage of screening adoption.


CONCLUSIONS
The combined intervention was efficacious in improving mammography screening in low-income African American women, with an unadjusted effect size (relative risk, 2.84) significantly higher (P < 0.05) than that in previous studies of each intervention alone.
Individual- and organizational-level consequences of organizational citizenship behaviors: A meta-analysis.

Although one of the main reasons for the interest in organizational citizenship behaviors (OCBs) is the potential consequences of these behaviors, no study has been reported that summarizes the research regarding the relationships between OCBs and their outcomes. Therefore, the purpose of this study is to provide a meta-analytic examination of the relationships between OCBs and a variety of individual- and organizational-level outcomes. Results, based on 168 independent samples (N = 51,235 individuals), indicated that OCBs are related to a number of individual-level outcomes, including managerial ratings of employee performance, reward allocation decisions, and a variety of withdrawal-related criteria (e.g., employee turnover intentions, actual turnover, and absenteeism). In addition, OCBs were found to be related (k = 38; N = 3,611 units) to a number of organizational-level outcomes (e.g., productivity, efficiency, reduced costs, customer satisfaction, and unit-level turnover). Of interest, somewhat stronger relationships were observed between OCBs and unit-level performance measures in longitudinal studies than in cross-sectional studies, providing some evidence that OCBs are causally related to these criteria. The implications of these findings for both researchers and practitioners are discussed. (PsycINFO Database Record (c) 2009 APA, all rights reserved).
Effects of chronic plus acute prolonged stress on measures of coping style, anxiety, and evoked HPA-axis reactivity

Exposure to psychological trauma is the precipitating factor for PTSD. In addition, a history of chronic or traumatic stress exposure is a predisposing risk factor. We have developed a Chronic plus Acute Prolonged Stress (CAPS) treatment for rats that models some of the characteristics of stressful events that can lead to PTSD in humans. We have previously shown that CAPS enhances acute fear responses and impairs extinction of conditioned fear. Further, CAPS reduced the expression of glucocorticoid receptors in the medial prefrontal cortex. In this study we examined the effects of CAPS exposure on behavioral stress coping style, anxiety-like behaviors, and acute stress reactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Male Sprague-Dawley rats were exposed to CAPS treatment, consisting of chronic intermittent cold stress (4 °C, 6 h/day, 14 days) followed on day 15 by a single 1-h session of sequential acute stressors (social defeat, immobilization, swim). After CAPS or control treatment, different groups were tested for shock probe defensive burying, novelty suppressed feeding, or evoked activation of adrenocorticotropic hormone (ACTH) and corticosterone release by an acute immobilization stress. CAPS resulted in a decrease in active burying behavior and an increase in immobility in the shock probe test. Further, CAPS-treated rats displayed increases in the latency to feed in the novelty suppressed feeding test, despite an increase in food intake in the home cage. CAPS treatment also reduced the HPA response to a subsequent acute immobilization stress. These results further validate CAPS treatment as a rat model of relevance to PTSD, and together with results reported previously, suggest that CAPS impairs fear extinction, shifts coping behavior from an active to a more passive strategy, increases anxiety, and alters HPA reactivity, resembling many aspects of human PTSD.