bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of a reduced dose of DARUNAVIR/RTV in a cohort of antiretroviral‐naïve and experienced HIV‐infected patients: a medium‐term follow‐up
Authors: Lanzafame Massimiliano , Lattuada Emanuela , Rigo Fabio , Hill Andrew , Vento Sandro 
Published: November 2014

BackgroundThe currently approved dose of darunavir/ritonavir is 800/100 mg once daily for PI‐naïve patients, and 600/100 mg twice daily for PI‐pretreated patients. However, in DRV‐sensitive patients at baseline in the POWER 1/2 trials, similar rates of HIV RNA suppression (1 log reduction) were achieved with doses ranging from 400/100 mg once daily to 600/100 mg twice daily. In previously virologically suppressed patients, a reduced dose of DRV (600/100 QD) is non‐inferior to the standard dose (800 mg QD)[1] and DRV concentrations in plasma and CSF are similar in patients receiving the above different doses [1, 2].MethodsTwelve treatment‐naïve patients were started on darunavir/ritonavir 600/100mg once daily, with TDF/FTC (8) or ABC/3TC (4). Seven patients were switched to darunavir/ritonavir 600/100 mg once daily, with TDF/FTC (2), ABC/3TC (2), NVP (1), AZT/3TC (1). One was on monotherapy with DRV. Seven treatment‐experienced patients were switched to darunavir/ritonavir 600/100 mg once daily, with TDF/FTC (5), ABC/3TC (1), RAL (1).ResultsOf the 12 naïve patients (mean baseline HIV RNA 134,024 log10 copies/mL, range 4,256‐397,932), 11 had HIV RNA <20 c/mL after a mean 27.4 months of follow‐up (range 12–33). Mean PK level was 2,920 ng/mL (1,268–4,562). One patient had virological failure after 14 months (HIV RNA 39,300 copies/mL); no mutations were detected and after introduction of DRV/r 600 mg b.i.d., he returned aviremic. All switched patients maintained HIV RNA suppression (<20 c/mL) for a mean of 32.8 months (range 21‐54). PK level was available for one patient only (Ctrough 3,442 ng/mL). Of the treatment‐experienced patients (mean baseline HIV RNA 24,167 log10 copies/mL, range 112–111,426), five maintained HIV RNA suppression for a mean of 46.2 months (range 31–67). One patient interrupted HAART for three months and then restarted it, the latest HIV RNA level being 628 copies/mL after five weeks of therapy. One patient failed after 42 months (HIV RNA 3,930 copies/mL); after intensification (DRV/r 600 twice daily), he returned aviremic. PK levels were available for three patients (mean 2,502 ng/mL; range 844–4,518).ConclusionsIn this pilot study of 26 patients, use of DRV/r at 600/100 mg OD dose led to sustained HIV RNA suppression in 23 patients with acceptable PK exposures to DRV. Large non‐inferiority trials are warranted to establish its efficacy.
The impact of nevirapine‐ versus protease inhibitor‐based regimens on virological markers of HIV‐1 persistence during seemingly suppressive ART
Authors: Kiselinova Maja , Anna Maria , Malatinkova Eva , Vervish Karen , Beloukas Apostolos , Messiaen Peter , Bonczkowski Pawel , Trypsteen Wim , Callens Steven , Verhofstede Chris , De Spiegelaere Ward , Vandekerckhove Linos 
Published: November 2014

IntroductionThe source and significance of residual plasma HIV‐1 RNA detection during suppressive ART remain controversial. It has been proposed that nevirapine (NVP)‐based regimens achieve a greater HIV‐1 RNA suppression than regimens containing a protease inhibitor (PI). The aim of this study was to compare the effect of receiving NVP‐ vs PI‐based ART on the virological markers of HIV persistence in peripheral blood.Material and MethodsThe study population comprised 161 HIV‐1 infected patients receiving either NVP‐based (n=81) or PI‐based (n=80) ART and showing a HIV‐1 RNA load stably suppressed <40 copies/mL for median of 5.2 years (IQR 2.2–8.0). Residual viraemia was detected by real‐time PCR with 50% and 95% detection thresholds of 1 and 3 HIV‐1 RNA copies/mL, respectively. Cell‐associated (CA) unspliced HIV‐1 RNA, total HIV‐1 DNA and 2 LTR circles were quantified in peripheral blood mononuclear cells (PBMCs) using droplet digital PCR. Groups were compared by standard non‐parametric tests; factors associated with HIV‐1 detection were analyzed by univariate regression analysis and generalized linear models (SPSS® V22 and Rstudio).ResultsPlasma HIV‐1 RNA was detected in 37/81 (45.7%) and 47/80 (58.8%) subjects on NVP‐ and PI‐based ART, with median (IQR) levels of 5 (3–6) and 5 (3–8) copies/mL, respectively. HIV‐1 RNA detection was associated with shorter duration of suppressive ART regardless of treatment arm (p=0.007), and lower CD4 nadir (p=0.015). HIV‐1 DNA levels were median 282 (120–484) and 213 (87–494) copies/106 PBMCs in the two groups respectively, and were lowest (<100 copies/106 PBMCs) in subjects with lower plasma HIV‐1 RNA (p=0.049), CA unspliced HIV‐1 RNA (p=0.0001), 2 LTR circles (p=0.005) and pre‐ART HIV‐1 RNA load (p=0.0001).ConclusionsIn this comprehensive characterization of patients on long‐term suppressive ART, we did not observe evidence for a greater suppressive activity of NVP‐based over PI‐based therapy on plasma and intracellular markers of virus persistence. Overall excellent correlation was observed between the markers, allowing the identification of a subset of treated patients with low HIV‐1 expression as an important cohort for future HIV cure studies.
Treatment discontinuation in HIV‐1‐infected individuals starting their first‐line HAART after 2008: data from the ICONA Foundation Study Cohort
Authors: Di Biagio Antonio , Cozzi‐Lepri Alessandro , Prinapori Roberta , Angarano Gioacchino , Gori Andrea , Quirino Tiziana , De Luca Andrea , Costantini Andrea , Mussini Cristina , Rizzardini Giuliano , Antinori Andrea , D'Arminio Monforte Antonella ,   on behalf of the ICONA, Foundation Study
Published: November 2014

IntroductionThe aim of this study was to analyze the likelihood and the predictors of discontinuation of first‐line regimen in the late HAART era.MethodologyAn observational multi‐center analysis of HIV‐positive patients enrolled in ICONA. Patients eligible were those starting a first‐line HAART after 1 January 2008. Discontinuation was defined as stop and/or switch of at least one drug of the regimen. All causes of discontinuation, as reported by the treating physician, were evaluated and cumulative risk of stopping was investigated according to age, gender, co‐morbidity, years since starting HAART, immuno‐virological status, third drug and backbone of the first regimen. Kaplan Meier (KM) analysis and Cox proportional hazards model were used for the outcome discontinuation of ≥1 drug regardless of the reason. For the KM estimates a competing risk approach was used to estimate the contribution of each of the reasons over time to the cumulative risk of stopping over time.ResultsData of 1759 patients who started first HAART and had at least one month of clinical follow‐up were analyzed. The overall discontinuation risk was 33% over a median follow‐up of 12 months. The likelihood of discontinuation by KM was 27% by one year (95% CI 25–29) and 41% by two years (95% CI 38–44). Main reason for stopping at least one drug in regimen was simplification (10%), followed by intolerance (7%), toxicity (5%), failure (2%) and other causes (8%). Estimates of the cumulative risk of discontinuation of ≥1 drug over time and according to reason are shown in Figure 1. In a multivariable Cox model independent predictors of discontinuation regardless of the reason were: longer time from HIV diagnosis to date of starting HAART (hazard ratio [HR] 0.96; 95% CI 0.93–1.00; p=0.039), regimens containing ZDV/3TC (HR 2.86; 95% CI 1.42–5.76; p=0.003 vs TDF/FTC) and an NNRTI‐based regimen (HR 2.47; 95% CI 0.91–6.72; p=0.07 vs regimens not NNRTI‐based).ConclusionsIn a previously reported analysis of the ICONA data [1], the overall risk of discontinuation of first‐line HAART was 36% with 21% due to intolerance/toxicity. In this updated analysis, the main reason for stopping is simplification (accounting for 32% of stops), reflecting the recent changes in recommendations aimed to minimize drug toxicity, enhancing adherence and quality of life.
Preparation of Soluble Proteins fromEscherichia coli
Authors: Wingfield Paul T. 
Published: November 2014

AbstractPurification of human IL‐1β is used in this unit as an example of the preparation of a soluble protein fromE. coli. Bacteria containing IL‐1β are lysed, and IL‐1 β in the resulting supernatant is purified by anion‐exchange chromatography, salt precipitation, and cation‐exchange chromatography, and then concentrated. Finally, the IL‐1 β protein is applied to a gel‐filtration column to separate it from remaining higher‐ and lower‐molecular‐weight contaminants, the purified protein is stored frozen or is lyophilized. The purification protocol described is typical for a protein that is expressed in fairly high abundance (i.e., >5% total protein) and accumulates in a soluble state. In addition, the purification procedure serves as an example of how to use classical protein purifications methods, which may also be used in conjunction with the affinity‐based methods now more commonly used. © 2014 by John Wiley & Sons, Inc.
Cryopreservation of Human Pluripotent Stem Cells in Defined Medium
Authors: Liu Weiwei , Chen Guokai 
Published: November 2014

AbstractThis unit describes a cryopreservation procedure using an enzyme‐free dissociation method to harvest cells and preserve cells in albumin‐free chemically defined E8 medium for human pluripotent stem cells (hPSCs). The dissociation by EDTA/PBS produces small cell aggregates that allow high survival efficiency in passaging and cryopreservation. Cryopreservation in E8 medium eliminates serum and other animal products, and is suitable for dealing with the increasing demand for high‐quality hPSCs in translational research. In combination with the special feature of EDTA/PBS dissociation, the protocols in this unit allow for efficient cryopreservation in a more time‐saving manner. © 2014 by John Wiley & Sons, Inc.
Isolation and Long‐Term Expansion of Functional, Myelinating Oligodendrocyte Progenitor Cells from Neonatal Rat Brain
Authors: Zhu Bangfu , Zhao Chao , Young Fraser I. , Franklin Robin J.M. , Song Bing 
Published: November 2014

AbstractOligodendrocytes are the myelinating cells of the central nervous system (CNS). The isolation of purified oligodendrocyte progenitor cells (OPCs) in large numbers has been sought after as a source of cells for repair following CNS‐demyelinating diseases and injuries, such as multiple sclerosis (MS) and spinal cord injury (SCI). Methods for isolation of OPCs from rodent neonatal brains are well established and have formed the basis for research in myelin repair within the CNS for many years. However, long‐term maintenance of OPCs has been a challenge owing to small cellular yields per animal and spontaneous differentiation within a short period of time. Much effort has been devoted to achieving long‐term culture and maintenance of OPCs, but little progress has been made. Here, protocols are presented for preparation of highly enriched rat OPC populations and for their long‐term maintenance as oligospheres using mixed‐glial‐conditioned medium. Functional myelinating oligodendrocytes can be achieved from such protocols, when co‐cultured with primary neurons. This approach is an extension of our normal shaking method for isolating OPCs, and incorporates some adaptations from previous OPC culture methods. © 2014 by John Wiley & Sons, Inc.
Vibrio cholerae: Measuring Natural Transformation Frequency
Authors: Watve Samit S. , Bernardy Eryn E. , Hammer Brian K. 
Published: November 2014

AbstractMany bacteria can become naturally competent to take up extracellular DNA across their outer and inner membranes by a dedicated competence apparatus. Whereas some studies show that the DNA delivered to the cytoplasm may be used for genome repair or for nutrition, it can also be recombined onto the chromosome by homologous recombination: a process called natural transformation. Along with conjugation and transduction, natural transformation represents a mechanism for horizontal transfer of genetic material, e.g., antibiotic resistance genes, which can confer new beneficial characteristics onto the recipient bacteria. Described here are protocols for quantifying the frequency of transformation for the human pathogen Vibrio cholerae, one of several Vibrio species recently shown to be capable of natural transformation. © 2014 by John Wiley & Sons, Inc.
Observer error, dental wear, and the inference of new world sundadonty
Authors: Stojanowski Christopher M. , Johnson Kent M. 
Published: November 2014

ABSTRACTDental morphology provides important information on human evolution and interpopulation relationships. Dental wear is one of the major limitations of morphological data analysis. Wear figures heavily in existing debates about patterns of New World dental variation with some scholars finding evidence for a more generalized dentition in early New World populations (Powell: Doctoral Dissertation, Texas A&M University, TX (1995)) and others questioning these findings based on the probable effects of dental wear on trait scores (Turner, The First Americans: the Pleistocene Colonization of the New World. San Francisco: California Academy of Sciences (2002) 123–158; Turner: Am J Phys Anthropol 130 (2006) 455–461; Turner and Scott, Handbook of paleoanthropology, Vol. III: Phylogeny of Hominids. New York: Springer (2007) 1901–1941). Here we evaluate these competing claims using data from the Early Archaic Windover sample. Results confirm the dental distinctiveness of Windover with respect to other Old World Asian (i.e., sinodont/sundadont) populations. However, comparison of our results to those of Powell (1995) also highlights significant interobserver error. Statistical analysis of matched wear and morphology scores suggests trait downgrading for some traits. Patterns of missing data present a more challenging (and potentially serious) problem. Use of Little's MCAR test for missing data mechanisms indicates a complex process of data collection in which incidental and opportunistic recording of both highly worn and unerupted teeth introduce a “missing not at random” mechanism into our dataset that biases dental trait frequencies. We conclude that patterns of missingness and formal research designs for “planned missingness” are needed to help mitigate this bias. Am J Phys Anthropol 156:349–362, 2015. © 2014 Wiley Periodicals, Inc.
Geographic and temporal trends in frontal sinus surgery
Authors: Svider Peter F. , Sekhsaria Vibhav , Cohen David S. , Eloy Jean Anderson , Setzen Michael , Folbe Adam J. 
Published: November 2014

BackgroundThe purpose of this study was to evaluate geographic and temporal trends in frontal sinus surgery procedures.MethodsMedicare Part B data files from 2000 to 2011 were examined for temporal trends in various frontal sinus procedures, and the most recent year containing geographic information (2010) was evaluated for Current Procedural Terminology (CPT) code use. Additionally, nationwide charges per procedure were recorded. Regional populations of individuals ≥65 years old were obtained from the 2010 U.S. Census, and surgical society websites were used to determine the number of practicing rhinologists and otolaryngologists in each region.ResultsThe use of open approaches declined by one third, while endoscopic procedures went from 6463 to 19262 annually, with the most marked increases occurring from 2006 through 2011. Geographic variation was noted, with practitioners in the South Atlantic states performing the greatest number of endoscopic procedures in 2010, whereas the East South Central states had the greatest number when controlling for population. There was an inverse relationship between endoscopic procedures performed and number of fellowship‐trained rhinologists (controlling for regional populations) (R2 = 0.66). The first year frontal sinus ballooning had a unique CPT code illustrated decreased reimbursements for non‐balloon endoscopic surgery ($609) relative to balloon approaches ($2635).ConclusionDeclines in open frontal sinus surgery and marked increases in endoscopic approaches have potential implications for residency training. Potential reasons for marked increases in endoscopic approaches include the rising popularity of balloon technologies, although this is speculative. Geographic variation exists in frontal sinus surgery patterns, including an inverse relationship between endoscopic approaches and the number of fellowship‐trained rhinologists.
Topical intranasal corticosteroids and growth velocity in children: a meta‐analysis
Authors: Mener David J. , Shargorodsky Josef , Varadhan Ravi , Lin Sandra Y. 
Published: November 2014

BackgroundThere is no consensus regarding the effects on growth velocity of intranasal topical corticosteroid (ITC) use in children. The objective of this study was to determine whether ITC use reduces growth velocity in children with allergic rhinitis (AR).MethodsA literature search of the National Center for Biotechnology Information PubMed, EMBASE, SCOPUS, and Cochrane databases from January 1, 1988 to October 7, 2013. The study selection was composed of randomized clinical trials investigating ITC for treatment of AR in children (age <18 years of age) with appropriate controls. Studies must have included interval change in growth as an outcome. Two authors independently extracted data and assessed study quality. Eligible studies were pooled using a random‐effects approach.ResultsEight studies with 755 participants from 3 countries provided data for the meta‐analysis (knemometry, n =342 participants; stadiometry, n =413 participants). Study duration ranged from 2 to 4 weeks for trials evaluating knemometry outcomes, and 12 months for trials evaluating stadiometry outcomes. Age of participants ranged from 3 to 12 years. The pooled standardized mean difference showed that among studies using knemometry, mean growth was statistically significantly lower among children using ITC vs placebo (−.223 mm/week; 95% confidence interval [CI], −0.429 to −0.017; p < 0.034).The pooled standardized mean difference showed that among studies using stadiometry, there was no significant growth difference among children using ITC vs placebo (−0.053 cm/year; 95% CI, −0.491 to 0.385; p = 0.813). The limitations of this study were the difficulty in predicting longer‐term or catch‐up growth in children.ConclusionMeta‐analytic pooling of trials suggest that short‐term ITC for the treatment of AR in children may decrease short‐term growth velocity using knemometry; however, the effect on longer‐term growth velocity as measured by stadiometry is unclear.
Quinone Diazides for Olefin Functionalization
Authors: Dao Hai T. , Baran Phil S. 
Published: November 2014

AbstractThe utility of quinone diazides in materials science is vast and well‐documented, yet this potentially useful motif has languished in the annals of organic synthesis. Herein we show that modern tools of catalysis can be employed with free or suitably masked quinone diazides to unleash the power of these classic diazo compounds in the context of both inter‐ and intramolecular olefin cyclopropanation.
Colloidal Nanocrystals of Lithiated Group 14 Elements
Authors: Cloud Jacqueline E. , Wang Yonglong , Yoder Tara S. , Taylor Lauren W. , Yang Yongan 
Published: November 2014

AbstractThe synthesis of colloidal nanocrystals (NCs) of lithiated group 14 elements (Z=Si, Ge, and Sn) is reported, which are Li4.4Si, Li3.75Si, Li4.4Ge, and Li4.4Sn. LixZ compounds are highly reactive and cannot be synthesized by existing methods. The success relied on separating the surface protection from the crystal formation and using a unique passivating ligand. Bare LixZ crystals were first produced by milling elemental Li and Z in an argon‐filled jar. Then, under the assistance of additional milling, hexyllithium was added to passivate the freshly generated LixZ NCs. This ball‐milling‐assisted surface protection method may be generalized to similar systems, such as NaxZ and KxZ. Moreover, Li4.4Si and Li4.4Ge NCs were conformally encapsulated in carbon fibers, providing great opportunities for studying the potential of using LixZ to mitigate the volume‐fluctuation‐induced poor cyclability problem confronted by Z anodes in lithium‐ion batteries.
Prüfen der Pumpbarkeit von Beton – Vom Labor in die Praxis
Authors: Secrieru Egor , Butler Marko , Mechtcherine Viktor 
Published: November 2014

AbstractFür die Beurteilung der Pumpbarkeit von Frischbeton existieren bislang keine normativen Regelungen, in denen die Anforderungen an seine rheologischen Eigenschaften festgeschrieben sind. Zur Prüfung der Pumpbarkeit von Frischbeton – vor allem auf der Baustelle – ist die Etablierung einfacher, robuster und dennoch aussagekräftiger rheologischer Messtechniken von elementarer Bedeutung. Im vorliegenden Beitrag werden die neuen prüftechnischen Ansätze für eine zielsichere Optimierung des Pumpens von Frischbeton vorgestellt. Insbesondere wird die Funktionsweise des sog. Gleitrohr‐Rheometers (Sliding Pipe Rheometer, SLIPER) erläutert, mit dem Fördermengen, Druckverhältnisse und resultierende Bewegungszustände des Frischbetons in einer Betonförderleitung in guter Näherung quantitativ abgeschätzt werden können. Im Rahmen einer Parameterstudie werden die unter Verwendung von SLIPER erzielten Ergebnisse analysiert und mit denen eines stationären Betonviskosimeters verglichen. Es werden die ermittelten Zusammenhänge zwischen Rheologie und Pumpbarkeit sowohl von Normalbetonen als auch von Sonderbetonen (selbstverdichtender Beton (SVB) und hochduktiler Beton (SHCC)) dargestellt. Schließlich wird die Vorhersagefähigkeit des Pumpverhaltens von Beton auf der Basis der SLIPER‐Untersuchungen durch Messung des Pumpdruckes unter Baustellenbedingungen validiert.Testing pumpability of concrete – From laboratory into practiceIn assessing concrete pumpability, there are still no norms or regulations providing guidelines with regard of fresh concrete's rheological properties. For testing concrete pumpability, especially on the construction site, the establishment of simple, robust but reliable testing techniques is of great importance. The paper at hand gives an overview of the new approaches in estimating pumpability of fresh concrete. In particular, the idea and working principle of the so‐called Sliding Pipe Rheometer (SLIPER) are explained. Using SLIPER, pumping pressure vs. discharge rate relationships can be reliably estimated for various pipe lengths and diameters. A parameter study on the effect of concrete composition on its pumpability is also presented. The results obtained from the SLIPER tests are analysed and compared with those obtained during tests with a stationary concrete viscometer and testing using conventional, empirical tests. The correlations between the rheological properties according to the BINGHAM model and the pumpability of four various ordinary concretes and two high performance concretes (self‐compacting concrete (SCC) and strain‐hardening cement‐based composite (SHCC)) are investigated. Finally, based on the investigations the predictive capacity of the SLIPER in respect of concrete pumpability is validated by measuring the discharge pressure under field conditions.