Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of grapefruit juice on cyclosporin A pharmacokinetics in pediatric renal transplant patients

Abstract: Cyclosporin A (CsA) is an important immunosuppressant that is prone to numerous drug interactions. Grapefruit juice has been investigated, as a possible adjunct to CsA dosing in adult renal transplant recipients, to decrease CsA metabolism and reduce dosages. This study investigated this combination in pediatric renal transplant patients. Six stable pediatric renal transplant patients were entered into an open‐label, four‐period cross‐over study in which patients were given their current CsA dose as either an oral solution (CsA‐Sol) or a microemulsion (CsA‐ME). In addition, drugs were administered concurrently with water or grapefruit juice. Steady‐state pharmacokinetic profiles were taken during each of the four periods. Following the concurrent administration of grapefruit juice, CsA whole‐blood 12‐h trough levels were significantly increased during CsA‐Sol dosing. Furthermore, the CsA elimination rate constant was significantly reduced during the same period. After CsA‐ME dosing, no differences in CsA pharmacokinetics were found between concurrent water or grapefruit ingestion. Grapefruit juice co‐administration reduced the production of CsA metabolites, AM1 and AM9, during CsA‐Sol dosing. No changes in CsA metabolite production were found when patients were given CsA‐ME with grapefruit juice as compared with water. Hence, alterations in CsA absorption and elimination occur with concurrent grapefruit juice ingestion when stable pediatric renal transplant patients are taking the oral CsA solution, but not the microemulsion formulation. These changes may be mediated by alterations in intestinal or hepatic metabolism, or drug absorption. The effect of grapefruit juice on CsA absorption is not readily predictable in these patients.
When Does Guanxi Matter? Issues of Capitalization and Its Dark Sides:

Abstract Guanxi refers to the durable social connections and networks a firm uses to exchange favors for organizational purposes. This study examines how and when guanxi operates as a governance mechanism that influences firm marketing competence and performance in the transitional economy of China. Drawing on social capital theory, the authors propose an integrative framework that unbundles the benefits and risks of guanxi and delineates the organizational processes to internalize guanxi as a corporate core competence. The authors surveyed senior executives in 282 firms in China's consumer products industries. The findings confirm guanxi's direct effects on market performance and its indirect effects mediated through channel capability and responsive capability. The authors also confirm that technological turbulence and competition intensity can be effective structure-loosening forces, thus reducing the governance effects of guanxi. The findings suggest that firms can improve market access and growth thr.
CCL20, γδ T cells, and IL‐22 in corneal epithelial healing

After corneal epithelial abrasion, leukocytes and platelets rapidly enter the corneal stroma, and CCR6+ IL‐17+ γδ T cells migrate into the epithelium. γδ T‐cell‐deficient (TCRδ–/–) mice have significantly reduced inflammation and epithelial wound healing. Epithelial CCL20 mRNA increased 19‐fold at 3 h, and protein increased ~ 16‐fold at 6 h after injury. Systemic or topical treatment of wild‐type C57BL/6 mice with anti‐CCL20 reduced γδ T‐cell accumulation in the cornea by >50% with a concomitant decrease in epithelial healing and stromal inflammation. In addition to CCR6 and IL‐17, corneal γδ T cells stained positively for RORγt, IL‐23R, and IL‐22. Anti‐IL‐22 reduced peak cell division of the healing epithelium by 52%. Treatment of TCRδ–/– mice with rIL‐22 significantly promoted wound closure, with peak epithelial cell division increased > 3‐fold. In addition, rIL‐22 restored neutrophil and platelet influx in the TCRδ–/– mice to wild‐type levels and increased CXCL1 production by wounded corneal explants > 2‐fold. These results indicate that an important aspect of the healing response to corneal epithelial abrasion includes CCL20‐dependent influx of CCR6+ IL‐17+ IL‐22+ γδ T cells and that IL‐22 contributes to the inflammatory response and promotes epithelial healing. —Li, Z. , Burns, A. R. , Byeseda Miller, S. , Smith, C. W. CCL20, γδ T cells, and IL‐22 in corneal epithelial healing. FASEB J. 25, 2659–2668 (2011). www.fasebj. org
Personalized Top-N Sequential Recommendation via Convolutional Sequence Embedding

Top-N sequential recommendation models each user as a sequence of items interacted in the past and aims to predict top-N ranked items that a user will likely interact in a »near future». The order of interaction implies that sequential patterns play an important role where more recent items in a sequence have a larger impact on the next item. In this paper, we propose a Convolutional Sequence Embedding Recommendation Model »Caser» as a solution to address this requirement. The idea is to embed a sequence of recent items into an »image» in the time and latent spaces and learn sequential patterns as local features of the image using convolutional filters. This approach provides a unified and flexible network structure for capturing both general preferences and sequential patterns. The experiments on public data sets demonstrated that Caser consistently outperforms state-of-the-art sequential recommendation methods on a variety of common evaluation metrics.
Reply to Dr. Cornish

To the Editor: W e write with reference to an article by Fredrickson et al, which claims an advantage for continuous peripheral nerve catheter management of pain relief versus single-shot blocks after a range of more Bminor[ shoulder surgeries. We, too, have had a large experience in this area and wish to query certain aspects of their study. We are puzzled that no pain scores have been included for the period within the first 24 hours after surgery. Presumably, both groups had no pain initially. It would be interesting to know when the single-shot blocks wore off and what strategies were used to counter its effect? There seems to have been more difficulty siting the single-shot blocks, and how this may or may not have affected the duration of the block is uncertain. From the data presented, it is difficult to judge the extent of the separation between the 2 groups. There was some mixing of surgical groups, which has the potential to confound results. For example, our experience has been that lateral clavicular surgeries do not warrant continuous catheter management. Elastomeric pumps require a large volume (400 mL) to fill. Given that there is no advantage to running a catheter longer than a day and a half according to their data, a large volume of local anesthetic (È200 mL) is likely to be wasted with this approach. The authors have rightly commented on other costsVsurely, this is another one to consider. We do agree, however, with the authors’ comment that the first 36 hours after surgery seems to be the time of greatest advantage for running peripheral nerve catheters in these situations.
Defining the Roles of Actigraphy and Parent Logs for Assessing Sleep Variables in Preschool Children

Actigraphy provides a non-invasive objective means to assess sleep–wake cycles. In young children, parent logs can also be useful for obtaining sleep–wake information. The authors hypothesized that actigraphy and parent logs were both equally valid instruments in healthy preschool-aged children. The authors studied 59 children aged 3 to 5 years in full-time day care. Each child was screened for medical problems and developmental delays before being fitted with an actigraphy watch, which was worn for 1 week. Parents maintained logs of sleep and wakefulness during the same period, with input from day care workers. In general, parents overestimated the amount of nighttime sleep measured by actigraphy by 13% to 22% (all significant). Although there was no difference in sleep onset times, parents reported later rise times on the weekend and fewer nighttime awakenings. There was no significant difference between parent logs and actigraphy with regard to daytime napping. The authors conclude that parent logs are best utilized in assessing daytime sleep and sleep onset, whereas actigraphy should be used to assess nighttime sleep and sleep offset time.
A role for nuclear envelope–bridging complexes in homology-directed repair

Persistent double-strand DNA breaks (DSBs) are recruited to the nuclear periphery, where they induce formation of associated nuclear envelope–spanning LINC complexes made up of the SUN protein Sad1 and the KASH protein Kms1. The LINC complex couples DSBs within the nucleus to cytoplasmic microtubules, which alters DSB repair pathway choice.
Development of an Integrated, Personalized Comfort Methodology for Office Buildings

Despite the significant progress observed over the last decades, the European building stock still consumes significant amounts of energy (39% of the total final energy), whilst it does not always provide the conditions required for occupants’ well-being and thermal comfort sensation. In order to achieve the goal of nearly or even zero energy buildings, a deep refurbishment of the building stock is imperative. As the literature indicates, a firm evaluation of indoor conditions is essential, while having at the epicenter the occupants’ comfort perception, with emphasis on their individual characteristics. In this respect, a methodological framework is developed and a preliminary implementation is performed. The main goal of the methodological approach is the consideration of both the classical comfort parameters along with the occupants’ socioeconomic and personalized characteristics that affect their perception and can differentiate their needs even under the same conditions. Among other important findings this preliminary implementation achieved some very promising results, highlighting that occupants’ individual characteristics such as recycling and exercising can affect the occupants’ comfort perception.
Essential role of the persistent sodium current in spike initiation during slowly rising inputs in mouse spinal neurones

Spinal motoneurons, like many neurons, respond with repetitive spiking to sustained inputs. The afterhyperpolarization (AHP) that follows each spike, however, decays relatively slowly in motoneurons. The slow depolarization during this decay should allow sodium (Na+) channel inactivation to keep up with its activation and thus should prevent initiation of the next spike. We hypothesized that the persistent component of the total Na+ current provides the mechanism that generates a rate of rise sufficiently rapid to generate a spike. In large cultured spinal neurons, presumed to be primarily motoneurons, inhibition of persistent sodium current (NaP) by the drug riluzole at low concentrations resulted in a loss of repetitive firing. However, cells remained fully capable of producing spikes to transient inputs. These effects of riluzole were not due to insufficient depolarization, enhancement of the AHP, or sustained Na+ channel inactivation. To further test this hypothesis, computer simulations were performed with a kinetic Na+ channel model that provided greater independent control of NaP relative to transient Na+ current (NaT) than that provided by riluzole administration. The model was tuned to generate substantial NaP and exhibited good repetitive firing to slowly rising inputs. When NaP was sharply reduced without significantly altering NaT, the model reproduced the effects of riluzole administration, inducing failure of repetitive firing but allowing single spikes in response to sharp transients. These results strongly support the essential role of NaP in spike initiation to slow inputs in spinal neurons. NaP may play a fundamental role in determining how a neuron responds to sustained inputs.
Functioning and Mental Health in Adolescence : Patterns , Progressions , and Routes from

can be found at: Journal of Adolescent Research Additional services and information for http://jar.sagepub. com/cgi/alerts Email Alerts: http://jar.sagepub. com/subscriptions Subscriptions: http://www.sagepub. com/journalsReprints.nav Reprints: http://www.sagepub. com/journalsPermissions.nav Permissions: http://jar.sagepub. com/cgi/content/abstract/14/2/135#BIBL SAGE Journals Online and HighWire Press platforms): (this article cites 31 articles hosted on the Citations
Eggs Ultrastructure and Early Development of Franciscodoras marmoratus (Pisces: Doradidae)

This study presents, for the first time, information on the eggs and early development of Franciscodoras marmoratus, fish of São Francisco river, Brazil. To analyse the egg ultrastructure and morphological events of embryogenesis, a total of 36 F. marmoratus specimens (18 males and 18 females) were captured and subjected to spawning induction. Gametes were collected by manual extrusion, and fertilization was conducted using the dry method. After fertilization, eggs were kept in incubators with water temperature of 24°C. The embryonic development was monitored using a stereomicroscope until hatching. There was a 67% positive response to hypophysation by the females and the fertilization rate was 73.8 ± 6.2%. The oocytes are discoid, yellow, adhesive and covered by a thick jelly coat. Under the electron scanning microscope, the oocytes presented a surface with pore canals and funnel‐shaped micropyle with a smooth vestibule. Recently extruded oocytes had a mean diameter of 1.27 ± 0.4 mm and after hydration was 1.91 ± 0.05 mm. The jelly coat was 0.34 ± 0.03 mm thickness, and the perivitelline space was 0.19 ± 0.04 mm. Eight phases of the embryonic development were identified, and embryogenesis was completed at 47 h after fertilization, at 24°C water temperature. The recently hatched larvae had 2.76 ± 0.57 mm of total length. These results provide useful information for the successful breeding and reproductive strategies of fishes.
The Influence of Pregnancy and Gender on Perivascular Innervation of Rat Posterior Cerebral Arteries

The authors investigated the influence of pregnancy and gender on the density of trigeminal and sympathetic perivascular nerves in posterior cerebral arteries (PCA) and the reactivity to norepinephrine and calcitonin gene-related peptide (CGRP). PCAs were isolated from nonpregnant, late-pregnant, postpartum, and male rats, mounted and pressurized on an arteriograph chamber to obtain concentration-response curves to norepinephrine and CGRP. Arteries were immunostained for CGRP-, tyrosine hydroxylase—, and protein gene product 9.5 (PGP 9.5)—containing perivascular nerves, and nerve density was determined morphologically. Pregnancy had a trophic effect on trigeminal perivascular innervation (P < .01 vs male); however, this was not accompanied by a change in reactivity to CGRP. Sympathetic and PGP 9.5 nerve densities were not altered by pregnancy or gender, and there were no differences in reactivity to norepinephrine. Together, these results suggest that the increase in trigeminal innervation during pregnancy is more related to nociception than in controlling resting cerebral blood flow.
Flagyl in the Treatment of Trichomoniasis*

Cosar and Julou (1959) studied this preparation in vitro and in vivo in the mouse and demonstrated very high activity against Trichomonas vaginalis. Their tests showed a low incidence of acute toxicity in mice and no evidence of chronic toxicity when they gave the drug by mouth to rats in amounts of up to 50 mg. /kg. daily for one month and to dogs in amounts of up to 100 mg. /kg. daily for the same period. The first clinical trials were those reported by Durel, Roiron, Siboulet, and Borel (1959), who gave Flagyl by mouth to a small number of men suffering from trichomonal urethritis, with excellent results. They also treated women suffering from trichomonal vaginitis, but most of them received concurrent local treatment with pessaries of Flagyl. The results with this combined treatment were again excellent. They found no response to the remedy in cases of urethritis or vaginitis in which Trichomonas vaginalis was not demonstrated. Confirmation of this work was given by Sylvestre, Gallai, and Ethier (1959) and again by Durel, Roiron, Siboulet, and Borel (1960). The latter made very modest claims for the drug used systemically in the treatment of females, suggesting that it was no more than a useful adjunct to local treatment but calling for further investigation of exclusively oral treatment.
Omeprazole absorption from a compounded transdermal formulation in healthy volunteers.

OBJECTIVE To evaluate the plasma concentration versus time profile of omeprazole following the administration of a compounded transdermal gel formulation in healthy volunteers. DESIGN Single-dose transdermal pharmacokinetic (PK) study including a comparison with historical data from an oral PK study. SETTING Academic clinical research center. PARTICIPANTS Eight healthy volunteers between 18 and 50 years of age. INTERVENTIONS Omeprazole gel 40 mg (0.8 mL) was applied to the ventral surface of the forearm covering an area of 7 x 15 cm without an occlusive dressing. Blood samples were collected just before application and then at 1, 2, 3, 4, 6, and 8 hours. Plasma concentrations of omeprazole were determined using a validated liquid chromatography tandem mass spectrometry method. MAIN OUTCOME MEASURES PK parameters (maximal plasma concentration [C(max)], the time of C(max), [T(max)], the area under the omeprazole concentration versus time curve from 0 to 8 hours, the elimination rate constant, and the half-life of the elimination phase) following transdermal administration, compared with historical controls who had received an oral omeprazole 40 mg dose during a previous study. RESULTS Of the eight volunteers, five had undetectable plasma omeprazole concentrations throughout the 8-hour study, precluding a complete PK analysis. For the three volunteers with detectable plasma omeprazole concentrations, the values ranged from 0.204 to 0.552 ng/mL. Including values of 0 for the patients with undetectable levels, the mean (+/- SD) C(max) was 0.153 +/- 0.241 ng/mL, and the T(max) in patients with detectable levels occurred at approximately 6 hours. The plasma concentrations following transdermal administration were approximately 1,000-fold lower than those observed with oral dosing. CONCLUSION Transdermal absorption from a single dose of the omeprazole gel formulation used in this study was poor. This transdermal gel formulation is clearly not bioequivalent to the oral capsule.
Spectrum Sensing by Parallel Pairs of Cross-Correlators and Comb Filters for OFDM Systems With Pilot Tones

This paper proposes a new spectrum sensing method for orthogonal frequency division multiplexing (OFDM) systems with pilot tones for equalization convenience. The time-domain signal cross-correlation (TDSC) method exploits the periodic feature of pilot signals embedded in time-domain OFDM signals, while random data signals deteriorate the detection performance. The new spectrum sensing method employs parallel pairs of cross-correlators and comb filters, reducing the effect of random data signals by comb filters. Simulation results of the proposed method demonstrate that the sensing performance for any given misdetection probability is improved by around 1.2 dB in SNR over the TDSC method.
Male breast cancer: A retrospective study from a regional cancer center in northern India

Over a 7‐year period from 1987 to 1993, 41 male breast cancer patients were seen in the breast cancer clinic of the Institute Rotary Cancer Hospital (IRCH) at the All India Institute of Medical Sciences (AIIMS). Their mean age was 54.2 years; and duration of symptoms ranged from 1 to 84 months with a mean of 15.1 months. Breast lump was the commonest presenting symptom. Fine needle aspiration cytology (FNAC) was the commonest diagnostic procedure. The TNM stage distribution was stage I, 5; stage II, 13; stage III, 17; and stage IV, 6. Radical mastectomy (25/36) was the commonest surgical procedure. Locoregional radiotherapy was given in 15 patients. Thirty patients received systemic adjuvant therapy (chemotherapy or tamoxifen, or a combination of the two). Local or distant recurrence occurred in 8 patients (8/31, 28.3%). Actuarial overall and disease‐free survival was 100% and 80.1% at 2 years and 91.7% and 66.7% at 4 years, respectively. On univariate analysis, axillary lymph node status and age were found to affect disease‐free survival significantly. Advanced stage of disease at presentation is common in Indian patients and will continue to influence treatment policies. Neoadjuvant chemotherapy needs to be evaluated for locally advanced tumors to improve outcome. Multicentric studies are necessary to define the relative roles of tamoxifen and chemotherapy for adjuvant treatment. © 1996 Wiley‐Liss, Inc.
Efficient Recovery of Fluoroquinolone-Susceptible and Fluoroquinolone-Resistant Escherichia coli Strains From Frozen Samples

We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples.
WYSIWIB: exploiting fine‐grained program structure in a scriptable API‐usage protocol‐finding process

Bug‐finding tools rely on specifications of what is correct or incorrect code. As it is difficult for a tool developer or user to anticipate all possible specifications, strategies for inferring specifications have been proposed. These strategies obtain probable specifications by observing common characteristics of code or execution traces, typically focusing on sequences of function calls. To counter the observed high rate of false positives, heuristics have been proposed for ranking or pruning the results. These heuristics, however, can result in false negatives, especially for rarely used functions. In this paper, we propose an alternate approach to specification inference, in which the user guides the inference process using patterns of code that reflect the user's understanding of the conventions and design of the targeted software project. We focus on specifications describing the correct usage of API functions, which we refer to as API protocols. Our approach builds on the Coccinelle program matching and transformation tool, which allows a user to construct patterns that reflect the structure of the code to be matched. We evaluate our approach on the source code of the Linux kernel, which defines a very large number of API functions with varying properties. Linux is also critical software, implying that fixing even bugs involving rarely used protocols is essential. In our experiments, we use our approach to find over 3000 potential API protocols, with an estimated false positive rate of under 15% and use these protocols to find over 360 bugs in the use of API functions. Copyright © 2012 John Wiley & Sons, Ltd.