bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multi-center, Dose-escalation Study of Human type I Pancreatic Elastase (PRT-201) Administered after Arteriovenous Fistula Creation
Authors: Peden Eric K. , Leeser David B. , Dixon Bradley S. , El-Khatib Mahmoud T. , Roy-Chaudhury Prabir , Lawson Jeffrey H. , Menard Matthew T. , Dember Laura M. , Glickman Marc H. , Gustafson Pamela N. , Blair Andrew T. , Magill Marianne , Franano F. Nicholas , Burke Steven K. 
Published: November 2012

Purpose To explore the safety and efficacy of PRT-201. Methods Randomized, double-blind, placebo-controlled, single-dose escalation study of PRT-201 (0.0033 to 9 mg) applied after arteriovenous fistula (AVF) creation. Participants were followed for one year. The primary outcome measure was safety. Efficacy measures were the proportion with intra-operative increases in AVF outflow vein diameter or blood flow ≥25% (primary), changes in outflow vein diameter and blood flow, AVF maturation and lumen stenosis by ultrasound criteria and AVF patency. Results The adverse events in the PRT-201 group (n=45) were similar to those in the placebo group (n=21). There were no differences in the proportion with ≥25% increase in vein diameter or blood flow, successful maturation or lumen stenosis. There was no statistically significant difference in primary patency between the dose groups (placebo n=21, Low Dose n=16, Medium Dose n=17 and High Dose n=12). In a subgroup analysis that excluded three participants with early surgical failures, the hazard ratio (HR) for primary patency loss of Low Dose compared with placebo was 0.38 (95% CI 0.10-1.41, P=0.15). In a Cox model, Low Dose (HR 0.27, 95% CI 0.04-0.79, P=0.09), white race (HR 0.17, 95% CI 0.03-0.79, P=0.02), and age <65 years (HR 0.25, CI 0.05-1.15, P=0.08) were associated (P<0.10) with a decreased risk of primary patency loss. Conclusions PRT-201 was not different from placebo for safety or efficacy measures. There was a suggestion for improved AVF primary patency with Low Dose PRT-201 that is now being studied in a larger clinical trial.
NGAL as a Renai Injury Marker: A Prospective Randomized Trial using Wolf Piezolith 3000
Authors: Varisco Daniela , Gelosa Marco , Grasso Angelica , Rastaldi Maria Pia , Croci Daniela , Messa Piergiorgio , Zanetti Giampaolo , Ferruti Mario , Rocco Francesco 
Published: November 2012

Background Shock wave lithotripsy (SWL) has proven to be safe and effective for renal stone treatment. The shock wave rate used during the SWL procedure causes cavitation, which is the phenomenon responsible for stone fragmentation and may be responsible for tissue and vascular damages ascribed to lithotripsy. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has been shown to be one of the earliest and most overexpressed markers in case of cellular damage in the kidney. Objective Using a new generation piezoelectric lithotripter, we evaluated the relation between renal damage, stone fragmentation rate, pain and shock wave rate delivered during SWL. Materials and Methods 80 patients suffering from a single renal stone were included in our clinical trial and underwent SWL with Wolf PiezoLith 300 lithotripter. A urine sample was collected in 54 patients (30 belonging to Group A, 24 to Group B) before treatment, within 2 hours and 72 hours after SWL, for NGAL measurement. Results The stone fragmentation rate obtained in the 2 groups was practically the same 30 days after SWL, with an efficacy rate of 72.7% in Group A and of 73.3% in Group B. NGAL increased after treatment, but was not statistically different in the two groups, and returned to the baseline value after 72 h. Furthermore, NGAL was always well below the threshold value of 350 ng/mL, indicative of acute renal failure. Conclusions The best stone fragmentation rate achievable with a piezoelectric lithotripter can be reached with a higher shock wave rate without significant renal damage, thus optimizing the treatment time.
Quantifying and addressing losses along the continuum of care for people living with HIV infection in sub‐Saharan Africa: a systematic review
Authors: Kranzer Katharina , Govindasamy Darshini , Ford Nathan , Johnston Victoria , Lawn Stephen D 
Published: November 2012

IntroductionRecent years have seen an increasing recognition of the need to improve access and retention in care for people living with HIV/AIDS. This review aims to quantify patients along the continuum of care in sub‐Saharan Africa and review possible interventions.MethodsWe defined the different steps making up the care pathway and quantified losses at each step between acquisition of HIV infection and retention in care on antiretroviral therapy (ART). We conducted a systematic review of data from studies conducted in sub‐Saharan Africa and published between 2000 and June 2011 for four of these steps and performed a meta‐analysis when indicated; existing data syntheses were used for the remaining two steps.ResultsThe World Health Organization estimates that only 39% of HIV‐positive individuals are aware of their status. Among patients who know their HIV‐positive status, just 57% (95% CI, 48 to 66%) completed assessment of ART eligibility. Of eight studies using an ART eligibility threshold of≤200 cells/µL, 41% of patients (95% CI, 27% to 55%) were eligible for treatment, while of six studies using an ART eligibility threshold of≤350 cells/µL, 57% of patients (95% CI, 50 to 63%) were eligible. Of those not yet eligible for ART, the median proportion remaining in pre‐ART care was 45%. Of eligible individuals, just 66% (95% CI, 58 to 73%) started ART and the proportion remaining on therapy after three years has previously been estimated as 65%. However, recent studies highlight that this is not a simple linear pathway, as patients cycle in and out of care. Published studies of interventions have mainly focused on reducing losses at HIV testing and during ART care, whereas few have addressed linkage and retention during the pre‐ART period.ConclusionsLosses occur throughout the care pathway, especially prior to ART initiation, and for some patients this is a transient event, as they may re‐engage in care at a later time. However, data regarding interventions to address this issue are scarce. Research is urgently needed to identify effective solutions so that a far greater proportion of infected individuals can benefit from long‐term ART.
Cost‐effectiveness evaluation of initial HAART regimens for managing HIV‐infected patients according to real clinical practice
Authors: Castagna A , Colombo G , Salpietro S , Galli L , Poli A , Lazzarin A 
Published: November 2012

We evaluated the single‐tablet regimen (STR) versus multiple‐tablet regimen (MTR) strategies through an incremental cost‐effectiveness analysis in a large cohort of patients starting their first HAART. Adult HIV‐1‐naïve patients, followed at the San Raffaele Hospital, starting their first‐line regimen from June 2008 to April 2012, were included in the analysis. First‐line HAART regimens more frequently used (>10%) were grouped into two classes as follows: a) single‐tablet regimen (STR) of TDF + FTC + EFV; b) multiple‐tablet regimen (MTR) including TDF + FTC + EFV, TDF + FTC + ATV/r, TDF + FTC + DRV/r TDF + FTC + LPV/r. The incremental cost‐effectiveness analysis was carried out by means of a Markov model calculating quality of life and costs for each patient, according to the given regimen (including any subsequent switch if occurred), through 1‐year cycles. The outcome measure was quality‐adjusted life‐years (QALYs). Data were analysed from the point of view of the Lombardy Regional Health Service (RHS): HAART, hospitalisations, visits, examinations and other concomitant non‐HAART drugs costs were evaluated, price variations included. 474 naïve patients: 90% males, mean age 42.2 years, mean baseline HIV‐RNA 4.50 log10copies/ml and CD4+ count of 310 cells/µL with a mean follow‐up of 28 months. Patients starting with an STR treatment were less frequently HCVAb positive (4% vs 11%, P=0.040), had higher mean CD4+ values [351 vs 297, P=0.004] as compared to MTR patients. The mean year cost/patient was €9,213 (range: €6,574.71–€33,570.00) with a mean per patient QALYs of 0.986 (range: 0.878–0.999) among STR patients; the mean year cost/patient was €14,277 (range: €5,908.89–€82,310.30) with a mean QALY of 0.933 (0.830–0.976) among MTR patients. STR dominates (i.e. is more effective and less costly) compared to MTR. (Fig. 1) At multivariable analysis, after adjustment for age, gender, HCVAb status, HIV risk factor, baseline CD4+ and HIV‐RNA, the cost‐effectiveness ratio was significantly lower among patients starting an STR treatment as compared to a MTR regimen (adjusted mean: €12,096 vs. €16,106; P=0.0001). The incremental cost‐effectiveness ratio (ICER) values comparing the two treatment strategies reported in the table. Starting with a first‐line STR regimen compared to multiple‐tablet regimens resulted cost‐effective showing lower costs and better efficacy as measured by QALYs.Incremental Cost Effectiveness Ratio of HAART Regimens.image
Raltegravir switch improves hepatitis C transaminitis in HIV‐1 and hepatitis C (HCV) co‐infected individuals
Authors: Cevik M , Jagjit Singh G , Dickinson L , Nelson M 
Published: November 2012

Purpose of the studyHCV is one of the most relevant co‐morbidities seen in HIV‐infected individuals as evidenced by the negative impact that HIV exerts on the course of HCV infection. Despite remarkable results on HIV infection alone, the impact of highly active antiretroviral therapy (HAART) on liver disease in co‐infection remains unknown. We sought to explore the impact of raltegravir (RAL) on amino transferase (ALT) in HIV/HCV co‐infected individuals.MethodsHIV‐infected individuals co‐infected with HCV within the last 5 years receiving non‐integrase inhibitor containing HAART with a subsequent switch to RAL‐containing HAART were identified from a retrospectively maintained outpatient database. Patient demographics were extracted. Biochemical, virological and immunological parameters were collated and individuals received pegylated interferon with ribavirin were excluded. ALT levels at switch and post switch were compared using Kruskal‐Wallis test. Spearman's Rank correlation was used to assess the relationship between ALT and HCV‐RNA.Summary of resultsTwenty‐seven HIV‐HCV co‐infected individuals were identified between January 2007 and January 2012 and seven individuals were excluded. Median age was 44 years (range: 31–68). Five had acute and fifteen had chronic HCV infection during the switch. Twenty (100%) had HIV‐RNA‐1<40 copies/mL at time of RAL switch. In chronic HCV infected individuals, median ALT levels at the time of switch were 465 IU/L, decreased significantly to 179 IU/L 1 month following switch (p=0.0261) and to 140 IU/L 6 months later (p=0.0225). On the other hand, in acute HCV infected individuals median ALT levels were 1005 IU/L at time of switch but decreased significantly to 220 IU/L 1 month later (p=0.0034) and to 35 IU/L 6 month later (p=0.0026). Sustained improvement in ALT levels from baseline to 1 month and up to 24 weeks after switch to RAL was observed in both groups but the reduction in ALT levels was statistically more significant in acutely infected individuals. ALT and HCV‐RNA levels showed a positive correlation at 6 months pre, post and at time of switch both in acute and chronic HCV‐infected individuals (Spearman's Rank correlation).ConclusionIn our study, RAL had a favourable effect on the liver up to 24 weeks after switch in HIV/HCV infected individuals.image
Hepatitis B virus infection in adolescents and young adults with human immunodeficiency virus infection in an urban clinic in a resource‐limited setting
Authors: Katusiime C , Kambugu A 
Published: November 2012

Purpose of the studyPatients with HBV/HIV co‐infection are at an increased risk of progression to hepatic cirrhosis and eventual liver‐related death. There is limited data on HBV/HIV co‐infection prevalence in adolescents and young adults in developing countries. The objective of the study was to estimate the prevalence of hepatitis B virus co‐infection among HIV‐positive adolescents and young adults attending an urban clinic in Kampala, Uganda.MethodsProspective study in HIV‐infected adolescents and young adults aged from 15–24 years.Summary of resultsFrom the adolescent/young adult HIV clinic, we purposively selected a sample of 148 adolescents and young adults who had been diagnosed with sexually transmitted infections between April 2011 and March 2012. A total of 148 HIV‐positive adolescents and young adults, 10 males and 138 females, aged between 15 and 24 years, were examined. Nine participants (6.1%) were HBsAg‐positive and were diagnosed with hepatitis B. Hepatitis B was predominant amongst the female participants compared to the male participants: 6.1% vs 0%. The median age of the participants diagnosed with hepatitis B was 22 years (IQR: 18.5–24.0). Of the 9 HBV/HIV co‐infected participants, 7 (77.8%) had CD4+counts of>250 cells/µl while 2 (22.2%) had CD4+counts<250 cells/µl (p<0.001). The median CD4+counts for the HBV/HIV co‐infected participants whose CD4+counts>250 cells/µl was 434 cells/µl (IQR: 289–577). On the other hand, the participants whose CD4+counts<250 cells/µl had a median CD4+count of 120 cells/µl. There was very strong evidence to show that the 8 (88.9%) HBV/HIV co‐infected participants who were in WHO stage I and II were more as compared to 1 (11.1%) HBV/HIV co‐infected patients who was in WHO stage III and IV (p<0.001).ConclusionOnly 6.1% of the HIV‐positive adolescents/young adults had hepatitis B co‐infection. HIV/HBV co‐infection was predominant among female adolescents/young adults and there was very strong evidence to show that HIV/HBV co‐infection was largely associated with WHO stage I and II disease.
The Vesicular Transport Assay: Validated In Vitro Methods to Study Drug‐Mediated Inhibition of Canalicular Efflux Transporters ABCB11/BSEP and ABCC2/MRP2
Authors: Herédi‐Szabó Krisztina , Kis Emese , Krajcsi Peter 
Published: November 2012

AbstractThe canalicular membrane of hepatocytes contains several transport proteins that use the energy of ATP to efflux potentially toxic molecules to the bile. Probably the two most important proteins at this location are MRP2 and BSEP, which transport phase II conjugates of xenobiotics and endobiotics and conjugated bile salts, respectively. The impaired function of either of these transporter proteins reduces the clearance of the toxic conjugates, resulting in their accumulation in the hepatocytes and eventually the plasma. Conjugated bile salts and phase II metabolites are compounds with low passive permeability; therefore, the most commonly used test system to investigate MRP2‐ and BSEP‐mediated transport processes is the vesicular transport assay. The concentration of probe substrates and inhibitors used in the experiment is close to their free concentration in the hepatocytes, providing an advantage when calculating kinetic parameters (Km, Ki, Vmax). The protocols aim to assist scientists to set up a transport assay for a known or potential substrate and test small molecule inhibition of the transporters. Curr. Protoc. Toxicol. 54:23.4.1‐23.4.16. © 2012 by John Wiley & Sons, Inc.
Efficacy of a multidisciplinary fibromyalgia treatment adapted for women with low educational levels: A randomized controlled trial
Authors: Castel Antoni , Fontova Ramon , Montull Salvador , Periñán Rocío , Poveda Maria José , Miralles Iris , Cascón‐Pereira Rosalia , Hernández Pilar , Aragonés Natalia , Salvat Isabel , Castro Sonia , Monterde Sonia , Padrol Anna , Sala José , Añez Cristóbal , Rull Maria 
Published: November 2012

AbstractObjectiveMultidisciplinary treatments of fibromyalgia (FM) have demonstrated efficacy. Nevertheless, they have been criticized for not maintaining their benefits and for not being studied for specific populations. Our objectives were to determine the efficacy of a multidisciplinary treatment for FM adapted for patients with low educational levels and to determine the maintenance of its therapeutic benefits during a long‐term followup period.MethodsInclusion criteria consisted of female sex, a diagnosis of FM (using American College of Rheumatology criteria), age between 18 and 60 years, and between 3 and 8 years of schooling. Patients were randomly assigned to 1 of the 2 treatment conditions: conventional pharmacologic treatment or multidisciplinary treatment. Outcome measures were functionality, sleep disturbances, pain intensity, catastrophizing, and psychological distress. Analysis was by intent‐to‐treat and missing data were replaced following the baseline observation carried forward method.ResultsOne hundred fifty‐five participants were recruited. No statistically significant differences regarding pretreatment measures were found between the 2 experimental groups. Overall statistics comparison showed a significant difference between the 2 groups in all of the variables studied (P < 0.0001). Mixed linear model analysis demonstrated the superiority of the multidisciplinary treatment in all of the studied variables at posttreatment. The differences were maintained at 12‐month followup in sleep disturbances (P < 0.0001), catastrophizing (P < 0.0001), and psychological distress (P < 0.01).ConclusionMultidisciplinary treatment adapted for individuals with low educational levels is effective in reducing key symptoms of FM. Some improvements were maintained 1 year after completing the multidisciplinary treatment.
Steric and Electronic Effects on the Configurational Stability of Residual Chiral Phosphorus‐Centered Three‐Bladed Propellers: Tris‐aryl Phosphanes
Authors: Rizzo Simona , Benincori Tiziana , Bonometti Valentina , Cirilli Roberto , Mussini Patrizia R. , Pierini Marco , Pilati Tullio , Sannicolò Francesco 
Published: November 2012

AbstractA series of tris‐aryl phosphanes, structurally designed to exist as residual enantiomers or diastereoisomers, bearing substituents differing in size and electronic properties on the aryl rings, were synthesized and characterized. Their electronic properties were evaluated on the basis of their electrochemical oxidation potential determined by voltammetry. The configurational stability of residual phosphanes, evaluated by dynamic HPLC on a chiral stationary phase or/and by dynamic 1H and 31P NMR spectroscopy, was found to be rather modest (barriers of about 18–20 kcal mol−1), much lower than that shown by the corresponding phosphane oxides (barriers of about 25–29 kcal mol−1). For the first time, the residual antipodes of a tris‐aryl phosphane were isolated in enantiopure state and the absolute configuration assigned to them by single‐crystal anomalous X‐ray diffraction analysis. In this case, the racemization barrier could be calculated also by CD signal decay kinetics. A detailed computational investigation was carried out to clarify the helix reversal mechanism. Calculations indicated that the low configurational stability of tris‐aryl phosphanes can be attributed to an unexpectedly easy phosphorus pyramidal inversion which, depending upon the substituents present on the blades, can occur even on the most stable of the four conformers constituting a single residual stereoisomer.
Guest Covalent Capture by a Host: A Biomimetic Strategy for the Selective Functionalization of a Cavity
Authors: Menard Nicolas , Reinaud Olivia , Colasson Benoit 
Published: November 2012

AbstractA biomimetic strategy for the monofunctionalization of a calix[6]arene core is described. It is based on host–guest chemistry (mimicking the Michaelis–Menten adduct in enzymes) and allows the finely tuned pre‐organization of the substrate (an alkyne) with respect to the reactant (three azido groups introduced at the calixarene large rim). It is shown that the thermal Huisgen reaction implemented in this work proceeds under very mild conditions with total regioselectivity of the cycloaddition process. The scope of the reaction was explored and the results suggest that such a supramolecular strategy is quite versatile and could be applied to the selective functionalization of other cavitands bearing different recognition patterns. A detailed structural, thermodynamic, and kinetic study is also reported, highlighting interesting biomimetic features: The importance of the host–guest adduct strength, the high sensitivity of the reaction to the pre‐organization of the reactive partners (alkyne vs. azide), and a significant impact of the embedment on the transition state. The self‐coordination of the monofunctionalized products was also studied and an “endo/exo” switch of the internal side‐chain could be triggered by adding competitive ligands.
Light‐Harvesting Ytterbium(III)–Porphyrinate–BODIPY Conjugates: Synthesis, Excitation‐Energy Transfer, and Two‐Photon‐Induced Near‐Infrared‐Emission Studies
Authors: Zhang Tao , Zhu Xunjin , Wong Wai‐Kwok , Tam Hoi‐Lam , Wong Wai‐Yeung 
Published: November 2012

AbstractBased on a donor–acceptor framework, several conjugates have been designed and prepared in which an electron‐donor moiety, ytterbium(III) porphyrinate (YbPor), was linked through an ethynyl bridge to an electron‐acceptor moiety, boron dipyrromethene (BODIPY). Photoluminescence studies demonstrated efficient energy transfer from the BODIPY moiety to the YbPor counterpart. When conjugated with the YbPor moiety, the BODIPY moiety served as an antenna to harvest the lower‐energy visible light, subsequently transferring its energy to the YbPor counterpart, and, consequently, sensitizing the YbIII emission in the near‐infrared (NIR) region with a quantum efficiency of up to 0.73 % and a lifetime of around 40 μs. Moreover, these conjugates exhibited large two‐photon‐absorption cross‐sections that ranged from 1048–2226 GM and strong two‐photon‐induced NIR emission.
Evidence of stable genetic structure across a remote island archipelago through self‐recruitment in a widely dispersed coral reef fish
Authors: Priest Mark A. , Halford Andrew R. , McIlwain Jennifer L. 
Published: November 2012

AbstractWe used microsatellite markers to assess the population genetic structure of the scribbled rabbitfish Siganus spinus in the western Pacific. This species is a culturally important food fish in the Mariana Archipelago and subject to high fishing pressure. Our primary hypothesis was to test whether the individuals resident in the southern Mariana Island chain were genetically distinct and hence should be managed as discrete stocks. In addition to spatial sampling of adults, newly‐settled individuals were sampled on Guam over four recruitment events to assess the temporal stability of the observed spatial patterns, and evidence of self‐recruitment. We found significant genetic structure in S. spinus across the western Pacific, with Bayesian analyses revealing three genetically distinct clusters: the southern Mariana Islands, east Micronesia, and the west Pacific; with the southern Mariana Islands being more strongly differentiated from the rest of the region. Analyses of temporal samples from Guam indicated the southern Mariana cluster was stable over time, with no genetic differentiation between adults versus recruits, or between samples collected across four separate recruitment events spanning 11 months. Subsequent assignment tests indicated seven recruits had self‐recruited from within the Southern Mariana Islands population. Our results confirm the relative isolation of the southern Mariana Islands population and highlight how local processes can act to isolate populations that, by virtue of their broad‐scale distribution, have been subject to traditionally high gene flows. Our results add to a growing consensus that self‐recruitment is a highly significant influence on the population dynamics of tropical reef fish.