bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacodynamic Monitoring of Tacrolimus-Based Immunosuppression in CD14+ Monocytes After Kidney Transplantation
Authors: Kannegieter Nynke M. , Hesselink Dennis A. , Dieterich Marjolein , de Graav Gretchen N. , Kraaijeveld Rens , Rowshani Ajda T. , Leenen Pieter J. M. , Baan Carla C. 
Published: June 2017

Background:
Monocytes significantly contribute to ischemia-reperfusion injury and allograft rejection after kidney transplantation. However, the knowledge about the effects of immunosuppressive drugs on monocyte activation is limited. Conventional pharmacokinetic methods for immunosuppressive drug monitoring are not cell type–specific. In this study, phosphorylation of 3 signaling proteins was measured to determine the pharmacodynamic effects of immunosuppression on monocyte activation in kidney transplant patients.

Methods:
Blood samples from 20 kidney transplant recipients were monitored before and during the first year after transplantation. All patients received induction therapy with basiliximab, followed by tacrolimus (TAC), mycophenolate mofetil, and prednisolone maintenance therapy. TAC whole-blood predose concentrations were determined using an antibody-conjugated magnetic immunoassay. Samples were stimulated with phorbol 12-myristate 13-acetate (PMA)/ionomycin, and phosphorylation of p38MAPK, ERK, and Akt in CD14+ monocytes was quantified by phospho-specific flow cytometry.

Results:
Phosphorylation of p38MAPK and Akt in monocytes of immunosuppressed recipients was lower after 360 days compared with before transplantation in the unstimulated samples [mean reduction in median fluorescence intensity 36%; range −28% to 77% for p-p38MAPK and 20%; range −22% to 53% for p-Akt; P < 0.05]. P-ERK was only decreased at day 4 after transplantation (mean inhibition 23%; range −52% to 73%; P < 0.05). At day 4, when the highest whole-blood predose TAC concentrations were measured, p-p38MAPK and p-Akt, but not p-ERK, correlated inversely with TAC (rs = −0.65; P = 0.01 and rs = −0.58; P = 0.03, respectively).

Conclusions:
Immunosuppressive drug combination therapy partially inhibits monocyte activation pathways after kidney transplantation. This inhibition can be determined by phospho-specific flow cytometry, which enables the assessment of the pharmacodynamic effects of immunosuppressive drugs in a cell type–specific manner.
An Atmospheric Pressure Chemical Ionization MS/MS Assay Using Online Extraction for the Analysis of 11 Cannabinoids and Metabolites in Human Plasma and Urine
Authors: Klawitter Jelena , Sempio Cristina , Mörlein Sophie , De Bloois Erik , Klepacki Jacek , Henthorn Thomas , Leehey Maureen A. , Hoffenberg Edward J. , Knupp Kelly , Wang George S. , Hopfer Christian , Kinney Greg , Bowler Russell , Foreman Nicholas , Galinkin Jeffrey , Christians Uwe , Klawitter Jost 
Published: June 2017

Background:
Although, especially in the United States, there has been a recent surge of legalized cannabis for either recreational or medicinal purposes, surprisingly little is known about clinical dose–response relationships, pharmacodynamic and toxicodynamic effects of cannabinoids such as Δ9-tetrahydrocannabinol (THC). Even less is known about other active cannabinoids.

Methods:
To address this knowledge gap, an online extraction, high-performance liquid chromatography coupled with tandem mass spectrometry method for simultaneous quantification of 11 cannabinoids and metabolites including THC, 11-hydroxy-Δ9-tetrahydrocannabinol, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-C-gluc), cannabinol, cannabidiol, cannabigerol, cannabidivarin, Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (THCV-COOH) was developed and validated in human urine and plasma.

Results:
In contrast to atmospheric pressure chemical ionization, electrospray ionization was associated with extensive ion suppression in plasma and urine samples. Thus, the atmospheric pressure chemical ionization assay was validated showing a lower limit of quantification ranging from 0.39 to 3.91 ng/mL depending on study compound and matrix. The upper limit of quantification was 400 ng/mL except for THC-C-gluc with an upper limit of quantification of 2000 ng/mL. The linearity was r > 0.99 for all analyzed calibration curves. Acceptance criteria for intrabatch and interbatch accuracy (85%–115%) and imprecision (<15%) were met for all compounds. In plasma, the only exceptions were THCV (75.3%–121.2% interbatch accuracy) and cannabidivarin (interbatch imprecision, 15.7%–17.2%). In urine, THCV did not meet predefined acceptance criteria for intrabatch accuracy.

Conclusions:
This assay allows for monitoring not only THC and its major metabolites but also major cannabinoids that are of interest for marijuana research and clinical practice.
Augmented Renal Clearance Using Population-Based Pharmacokinetic Modeling in Critically Ill Pediatric Patients*
Authors: Avedissian Sean N. , Bradley Erin , Zhang Diana , Bradley John S. , Nazer Lama H. , Tran Tri M. , Nguyen Austin , Le Jennifer 
Published: June 2017

Objectives:
The objectives of this study were to: 1) evaluate the prevalence of augmented renal clearance in critically ill pediatric patients using vancomycin clearance; 2) derive the pharmacokinetic model that best describes vancomycin clearance in critically ill pediatric patients; and 3) correlate vancomycin clearance with creatinine clearance estimated by modified Schwartz or Cockcroft-Gault.

Design:
Retrospective, two-center, cohort study from 2003 to 2016.

Setting:
Clinical drug monitoring services in the PICUs at two tertiary care, teaching hospitals.

Patients:
Children from 1 to 21 years old.

Interventions:
None.

Measurements and Main Results:
Identify patients with augmented renal clearance (vancomycin clearance ≥ 130 mL/min/1.73 m2 used as definition of augmented renal clearance). Derive final population-based pharmacokinetic model and estimate individual patient pharmacokinetic parameters. Compare estimated glomerular filtration rate (modified Schwartz or Cockcroft-Gault depending on age < or ≥ 17 yr) with vancomycin clearance. Augmented renal clearance was identified in 12% of 250 total subjects. The final population-based pharmacokinetic model for vancomycin clearance (L/hr) was 0.118 × weight (e–1.13 × [serum creatinine (Scr) – 0.40]). Median vancomycin clearance in those with versus without augmented renal clearance were 141.3 and 91.7 mL/min/1.73 m2, respectively (p < 0.001). By classification and regression tree analysis, patients who were more than 7.9 years old were significantly more likely to experience augmented renal clearance (17% vs 4.6% in those ≤ 7.9 yr old; p = 0.002). In patients with augmented renal clearance, 79% of 29 had vancomycin trough concentrations less than 10 µg/mL, compared with 52% of 221 in those without augmented renal clearance (p < 0.001). Vancomycin clearance was weakly correlated to the glomerular filtration rate estimated by the modified Schwartz or Cockcroft-Gault method (Spearman R
2 = 0.083).

Conclusions:
Augmented renal clearance was identified in one of 10 critically ill pediatric patients using vancomycin clearance, with an increase of approximately 50 mL/min/1.73 m2 in those with augmented renal clearance. As augmented renal clearance results in subtherapeutic antibiotic concentrations, optimal dosing is essential in those exhibiting augmented renal clearance.
HIV Care Initiation Delay Among Rural Residents in the Southeastern United States, 1996 to 2012
Authors: Lopes Brettania L.W. , Eron Joseph J. , Mugavero Michael J. , Miller William C. , Napravnik Sonia 
Published: June 2017

Background:
Delaying HIV care initiation may lead to greater morbidity, mortality, and further HIV transmission. Rural residence may be associated with delayed diagnosis and linkage to care, with negative clinical outcomes.

Objective:
To examine the association between rural patient residence and CD4 cell count at HIV care initiation in a large HIV clinical cohort in the Southeastern United States.

Methods:
We included HIV-infected patients who initiated care between 1996 and 2012 with a geocodable address and no previous history of HIV clinical care. Patient residence was categorized as urban or rural using United States Department of Agriculture Rural Urban Commuting Area codes. Multivariable linear regression models were fit to estimate the association between patient residence and CD4 cell count at HIV care initiation.

Results:
Among 1396 patients who met study inclusion criteria, 988 had a geocodable address. Overall, 35% of patients resided in rural areas and presented to HIV care with a mean CD4 cell count of 351 cells/mm3 (SD, 290). Care initiation mean CD4 cell counts increased from 329 cells/mm3 (SD, 283) in 1996–2003 to 391 cells/mm3 (SD, 292) in 2008–2012 (P = 0.006). Rural in comparison with urban patients presented with lower CD4 cell counts with an unadjusted and adjusted mean difference of −48 cells/mm3 [95% confidence interval, −86 to −10) and −37 cells/mm3 (95% confidence interval: −73 to −2), respectively, consistently observed across calendar years.

Conclusions:
HIV care initiation at low CD4 cell counts was common in this Southeastern US cohort and more common among rural area residents.
Reassessing the Anatomic Origin of the Juvenile Nasopharyngeal Angiofibroma
Authors: McKnight Colin D. , Parmar Hemant A. , Watcharotone Kuanwong , Mukherji Suresh K. 
Published: June 2017

ObjectiveA modern imaging review is necessary to further define the anatomic origin of the juvenile nasopharyngeal angiofibroma.MethodsAfter institutional review board approval, a search from January 1998 to January 2013 yielded 33 male patients (aged 10–23 years) with pathologically proven juvenile nasopharyngeal angiofibroma lesions, as well as pretreatment computed tomography/magnetic resonance imaging. Juvenile nasopharyngeal angiofibroma involvement was assessed in the following regions: sphenopalatine foramen, pterygopalatine fossa, vidian canal, nasopharynx, nasal cavity, sphenoid sinus, choana, pterygomaxillary fissure/masticator space, orbit, and sphenoid bone.ResultsThe choana and nasopharynx were involved in all 33 patients. In contrast, only 22 lesions involved the pterygopalatine fossa, 24 lesions involved the sphenopalatine foramen, and 28 lesions involved the vidian canal.ConclusionsOur results suggest that the juvenile nasopharyngeal angiofibroma origin is in the region of the choana and nasopharynx rather than the sphenopalatine foramen or pterygopalatine fossa.
Acute Rejection After Kidney Transplantation Associates With Circulating MicroRNAs and Vascular Injury
Authors: Bijkerk Roel , Florijn Barend W. , Khairoun Meriem , Duijs Jacques M. G. J. , Ocak Gurbey , de Vries Aiko P.J. , Schaapherder Alexander F. , Mallat Marko J. K. , de Fijter Johan W. , Rabelink Ton J. , van Zonneveld Anton Jan , Reinders Marlies E. J. 
Published: June 2017

Background
Acute rejection (AR) of kidney transplants is associated with the loss of endothelial integrity, microvascular rarefaction and, ultimately, graft dysfunction. Circulating angiogenic microRNAs (miRNAs) may serve as markers for microvascular injury. Here, we investigated the short- and long-term effects of AR after kidney transplantation on systemic vascular injury and the associated circulating miRNA profile.

Methods
Systemic vascular injury was determined by measuring capillary tortuosity and density within the oral mucosa as well as by assessing circulating levels of angiopoietin-2/angiopoietin-1 ratio, vascular endothelial growth factor and soluble thrombomodulin. After a pilot study, we selected 48 miRNAs to assess the AR- and microvascular injury associated circulating miRNAs.

Results
In stable transplant recipients (n = 25) and patients with AR (n = 13), which were also studied longitudinally (1, 6, and 12 months post-AR), we found an AR-associated increase in markers of systemic vascular injury, of which vascular endothelial growth factor and soluble thrombomodulin normalized within 1 year after AR. Of the 48 selected miRNAs, 8 were either decreased (miR-135a, miR-199a-3p, and miR-15a) or increased (miR-17, miR-140-3p, miR-130b, miR-122 and miR-192) in AR. Of these, miR-130b, miR-199a, and miR-192 associated with markers of vascular injury, whereas miR-140-3p, miR-130b, miR-122, and miR-192 normalized within 1 year after AR.

Conclusions
AR after kidney transplantation is characterized by systemic microvascular injury and associates with specific circulating miRNA levels.
Degree of Postictal Suppression Depends on Seizure Induction Time in Magnetic Seizure Therapy and Electroconvulsive Therapy
Authors: Kayser Sarah , Bewernick Bettina H. , Soehle Martin , Switala Christina , Gippert Sabrina M. , Dreimueller Nadine , Schlaepfer Thomas E. 
Published: June 2017

Objectives
Anesthesia is required for both magnetic seizure therapy (MST) and electroconvulsive therapy (ECT), although it has anticonvulsant properties. In this case, bispectral index (BIS) monitoring, a specific electroencephalogram-derived monitoring, can be used to find the optimal seizure induction time during anesthesia to elicit adequate seizures. A measurement of seizure adequacy in electroencephalogram is the postictal suppression. The purpose of this study was to investigate the influence of seizure induction time on the degree of postictal suppression by comparing BIS versus no-BIS monitoring in MST and ECT.

Methods
Twenty patients with treatment-resistant depression were randomly assigned to either MST or ECT. Each patient underwent 3 treatments with the determination of seizure induction time by defined prestimulation BIS (BIS condition) and 3 treatments with determination of seizure induction time by controlled clinical trial protocol (no-BIS condition). Statistical analysis was calculated by repeated-measures analysis of variance.

Results
The degree of postictal suppression was more pronounced in both MST and ECT, with BIS monitoring. In this connection, no differences between MST and ECT were found. Seizure induction time was significantly later in the BIS condition (181.3 ± 6 seconds) compared with the no-BIS condition (114.3 ± 12 seconds) (P < 0.001).

Conclusions
Adequacy of seizures, in the form of the degree of postictal suppression, was superior by determining the seizure induction time with BIS in both MST and ECT. Further research is needed to investigate the correlation between the degree of postictal suppression and treatment response.
Highly multiplexed immunofluorescence imaging of human tissues and tumors using t-CyCIF and conventional optical microscopes
Authors: Lin Jia-Ren , Izar Benjamin , Wang Shu , Yapp Clarence , Mei Shaolin , Shah Parin , Santagata Sandro , Sorger Peter K 
Published: June 2017

AbstractThe architecture of normal and diseased tissues strongly influences the development and progression of disease as well as responsiveness and resistance to therapy. We describe a tissue-based cyclic immunofluorescence (t-CyCIF) method for highly multiplexed immuno-fluorescence imaging of formalin-fixed, paraffin-embedded (FFPE) specimens mounted on glass slides, the most widely used specimens for histopathological diagnosis of cancer and other diseases. t-CyCIF generates up to 60-plex images using an iterative process (a cycle) in which conventional low-plex fluorescence images are repeatedly collected from the same sample and then assembled into a high dimensional representation. t-CyCIF requires no specialized instruments or reagents and is compatible with super-resolution imaging; we demonstrate its application to quantifying signal transduction cascades, tumor antigens and immune markers in diverse tissues and tumors. The simplicity and adaptability of t-CyCIF makes it an effective method for pre-clinical and clinical research and a natural complement to single-cell genomics.
Microbial manganese(III) reduction fuelled by anaerobic acetate oxidation
Authors: Szeinbaum Nadia , Lin Hui , Brandes Jay A. , Taillefert Martial , Glass Jennifer B. , DiChristina Thomas J. 
Published: June 2017

SummarySoluble manganese in the intermediate +III oxidation state (Mn3+) is a newly identified oxidant in anoxic environments, whereas acetate is a naturally abundant substrate that fuels microbial activity. Microbial populations coupling anaerobic acetate oxidation to Mn3+ reduction, however, have yet to be identified. We isolated a Shewanella strain capable of oxidizing acetate anaerobically with Mn3+ as the electron acceptor, and confirmed this phenotype in other strains. This metabolic connection between acetate and soluble Mn3+ represents a new biogeochemical link between carbon and manganese cycles. Genomic analyses uncovered four distinct genes that allow for pathway variations in the complete dehydrogenase‐driven TCA cycle that could support anaerobic acetate oxidation coupled to metal reduction in Shewanella and other Gammaproteobacteria. An oxygen‐tolerant TCA cycle supporting anaerobic manganese reduction is thus a new connection in the manganese‐driven carbon cycle, and a new variable for models that use manganese as a proxy to infer oxygenation events on early Earth.
Urban Operating Systems: Diagramming the City
Authors: Marvin Simon , Luque‐Ayala Andrés 
Published: June 2017

AbstractA set of software/hardware packages developed by IT companies for the urban market is transforming the way in which cities are imagined and configured. These urban operating systems (Urban OS) embody important presumptions about what constitutes appropriate knowledge and forms of decision making, pointing to how novel forms of ‘smart' or ‘computational' urbanism may govern urban life. Arguing that an analysis of the interface between the urban and IT requires a broader historical and theoretical perspective, the article traces the ways in which the city has been diagrammed as a space of power since the nineteenth century and highlights the antecedents of Urban OS present across different domains of life—particularly in military and corporate enterprises. Relaying the urban as an efficient logistical enterprise, and operating as a piloting device (Deleuze and Guattari, 1987), the Urban OS appears as an emerging urban diagram introducing an informational diagrammatic of control. We focus on five archetypal framings of how Urban OS envision the city, illustrating how a new corporate rationality of control based on functional simplification and heterogeneous reintegration seeks to take hold in the city (via re‐engineering, agility, modularity, flexibility and configurability).
Molecular Detection, Typing, and Quantification of Campylobacter spp. in Foods of Animal Origin
Authors: Frasao Beatriz da Silva , Marin Victor Augustus , Conte‐Junior Carlos Adam 
Published: June 2017

AbstractThe most frequently reported zoonosis and the main bacterial foodborne disease infection in humans is caused by Campylobacter spp., and C. jejuni and C. coli are the most common types. These bacteria can be found in the intestinal tracts of cattle, dogs, cats, sheep, poultry and pigs. The isolation of this microorganism is laborious because it requires specific media and a low oxygen concentration for growth. Additionally, differentiation between species through conventional bacteriology is difficult, as there are few different biochemical characteristics among the various species. Molecular microbiological techniques have become more important and are now broadly applied to help overcome difficulties in the identification, differentiation, and quantification of this pathogen. To date, there have been advances in the development and use of molecular techniques for the identification of microorganisms in foodstuffs. Tools such as pulsed‐field gel electrophoresis and multilocus sequence typing are the most commonly used for typing. For the identification and confirmation of species, polymerase chain reaction (PCR) is crucial. Quantification by real‐time PCR has wide applicability. To identify strains and antimicrobial resistance genes, sequencing technologies have been applied. This review builds on the discussion about the main and most widely used molecular methods for Campylobacter, as well as methods showing better potential for the classification, identification, and quantification of this important pathogen.
A Univariate Approach to Sex Estimation for the Fragmentary Upper Limb
Authors: Bongiovanni Rosanne , LeGarde Carrie B. 
Published: June 2017

AbstractAlthough there are numerous reliable multivariate models for sex estimation, many scenarios, both forensic and archaeological, result in the recovery of fragmentary remains, which prevents the collection of various standard measurements. The purpose of this research was to establish metric applications for sex estimation from the distal humerus and distal radius of European/American Whites and American Blacks. Data for this research were retrieved from a sample consisting of a larger database from multiple skeletal collections. Measurements include epicondylar breadth, breadth of the capitulum‐trochlea, and distal breadth of the radius. Student's t‐test and descriptive statistics were utilized to analyze the data. Classification rates ranged from 75% to 96.4%, with the capitulum‐trochlea breadth performing best. Overall, significant metric differences exist between the sexes in the distal humerus and radius and can be utilized to estimate sex. This study offers a reliable alternative sex estimation technique applicable to fragmentary or damaged remains.
A Unique Fatal Moose Attack Mimicking Homicide
Authors: Gudmannsson Petur , Berge Johan , Druid Henrik , Ericsson Göran , Eriksson Anders 
Published: June 2017

AbstractFatalities caused by animal attacks are rare, but have the potential to mimic homicide. We present a case in which a moose attacked and killed a woman who was walking her dog in a forest. Autopsy showed widespread blunt trauma with a large laceration on one leg in which blades of grass were embedded. Flail chest was the cause of death. The case was initially conceived as homicide by means of a riding lawn mower. A review of the case by moose experts and analyses of biological trace material that proved to originate from moose, established the true source of injury. The dog probably provoked a moose, which, in response, stomped and gored the victim to death. The injuries resembled those previously reported from attacks by cattle and water buffalo. Fatal moose attacks constitute an extremely rare threat in boreal areas, but can be considered in traumatic deaths of unknown cause.
Inactivation of Bacillus cereus Spores on Red Chili Peppers Using a Combined Treatment of Aqueous Chlorine Dioxide and Hot‐Air Drying
Authors: Kim Songyi , Lee Huyong , Ryu Jee‐Hoon , Kim Hoikyung 
Published: June 2017

AbstractThe effect of a combined treatment using aqueous chlorine dioxide (ClO2) and hot‐air drying to inactivate Bacillus cereus spores on red chili peppers was evaluated. Ten washed and dried pepper samples, each comprising half of a single pepper (Capsicum annuum L.), were inoculated with B. cereus spore suspension. The inoculated samples were washed with sodium hypochlorite (NaOCl; 50, 100, or 200 μg/mL) or ClO2 (50, 100, or 200 μg/mL) solution for 1 min and then air‐dried (25 ± 1 °C, 47 ± 1% relative humidity), which was followed by drying with hot air at 55 °C for up to 48 h. The spore populations on the samples were enumerated and their aw and chromaticity values were measured. The spore numbers immediately after treatment with NaOCl and ClO2 were not significantly different. A more rapid reduction in spore numbers was observed in the samples treated with ClO2 than those treated with NaOCl during drying. A combined treatment of ClO2 and hot‐air drying significantly reduced the spore populations to below the detection limit (1.7 log CFU/sample). B. cereus spores on chili peppers were successfully inactivated by washing with ClO2 solution followed by hot‐air drying whereas the pepper color was maintained.