bluuebunny/crossref_metadata_2025_split huggingface dataset:
Switching from an EFV‐based STR to a RPV‐based STR is effective, safe and improves HIV patients health status
Authors: Maggiolo Franco , Di Matteo Sergio , Bruno Giacomo , Astuti Noemi , Di Filippo Elisa , Valenti Daniela , Colombo Giorgio 
Published: November 2014

IntroductionTDF/FTC/RPV has been shown effective in both naïve and PI‐pre‐treated patients. Less is known about a switch strategy in subjects receiving EFV.Materials and MethodsWe evaluated viro‐immunologic outcomes, Quality of Life (QoL) and costs of an unselected cohort of patients switching from a TDF/FTC/EFV STR (≥6 months duration) to a TDF/FTC/RPV STR. The considered outcome measures were quality‐adjusted life years (QALYs) as measured with the EQ5D questionnaire and the overall direct health costs. 64 patients with a baseline viral load<50 copies/mL were randomized to immediately switch therapy or to continue TDF/FTC/EFV for four months and then switch to TDF/FTC/RPV. Six patients in the deferred switch group did not actually change cART.ResultsPatients were mostly males (73.4%) with a mean age of 46 years, a baseline mean HIV‐RNA of 6.4 copies/mL and a mean baseline CD4 count of 588 cells/µL. For the considered follow‐up period, the mean cost per patient resulted 2,563 for TDF/FTC/RPV and 2,572 for TDF/FTC/EFV. Viremia remained undetectable and CD4 stable in all patients. Over time the mean QoL increased in the RPV arm ad slightly decreased in the EFV arm, after four months the mean per patient QALYs was 0.849 for RPV and 0.841 for EFV, respectively (Figure 1). A sharp increment of QoL was observed in the deferred‐switch arm after switch, too. VAS analysis of health status perception also increased overall from 82.78 to 83.79 due to the improvement in the RPV arm. Mean cholesterol levels improved in the RPV arm from 203 to 170 mg/dL, while an increment from 190 to 207 mg/dL was observed in the EFV arm. HDL levels lowered from 49 to 45 and rose from 53 to 54 mg/dL in the RPV and EFV arms, respectively. Triglycerides levels improved both in the RPV arm (from 138 to 112 mg/dL) and in the EFV arm (from 110 to 103 mg/dL).ConclusionsSwitching from TDF/FTC/EFV to TDF/FTC/RPV is a safe, well tolerated strategy that improves the overall health status of HIV‐treated patients. The switch does not expose patients to a risk of virologic failure due to possible PK interactions of the drugs. RPV compared to EFV proved to be cost‐effective showing lower cost and higher outcome measure values.
A clinical and pharmacokinetic study of the combination of etravirine plus raltegravir in HIV patients with expanded intolerance or resistance
Authors: Bañón Sara , Moreno Ana , Quereda Carmen , Gomez Cristina , Diaz de Santiago Alberto , Perez‐Elías María J , Moreno Santiago , Luis Casado Jose 
Published: November 2014

IntroductionThe combination of etravirine (ETR) plus raltegravir (RAL) could be an option for HIV patients with resistance, intolerance or important interactions with other drugs. However, there are few data on the efficacy, safety and pharmacokinetics of this dual therapy, taking into account the effect of HCV co‐infection or the possible induction of ETR in the drug metabolism of RAL.Material and MethodsCohort study of HIV patients initiating ETR plus RAL as dual therapy. Plasma trough levels of RAL were measured by LC/MS after at least one month on therapy.ResultsA total of 25 patients have been included in this combination since 2009. Mean age was 46 years, 72% were male, and 20 patients (80%) had HCV co‐infection (seven patients with fibrosis 3–4). Median nadir CD4+ count was 109 (60–209), and 21 patients had an HIV RNA level below 50 copies/mL. Median time on previous therapy was 473 months (IQR, 395–570), and reasons for this dual therapy was toxicity/intolerance in 19, and interactions in nine (two chemotherapy, three DAAs, two methadone, two other). After a median follow up of 722 days (473–1088: 53.3 patients‐year), there were no cases of blips or virological failure. Six patients (24%) discontinued therapy after more than 1.5 year on therapy, in four cases due to lost follow up and in two due to simplification after finishing the reason for interaction. There were no cases of liver toxicity, and only two patients increased slightly transaminases values (grade 1 and 2). Total cholesterol and triglycerides levels decrease significantly after initiation (TC, from 182 to 165 at one year; p=0.01; TG from 185 to 143 mg/dL; p=0.01). CT/HDL ratio decreases from 4.35 to 4.28 after six months. Geometric mean plasma trough level of RAL was 166 ng/mL (IQR, 40–249) and only one patient (6%) was below the in vitro IC50 of the wild type.ConclusionsThe combination of ETR plus RAL as dual therapy is effective and safe in patients with expanded intolerance or interactions. There are no significant pharmacokinetic interactions between both drugs.
Atazanavir/ritonavir monotherapy as maintenance strategy in HIV‐1 treated subjects with viral suppression: 96‐week analysis results of the MODAT study
Authors: Spagnuolo Vincenzo , Galli Laura , Bigoloni Alba , Nozza Silvia , d'Arminio Monforte Antonella , Antinori Andrea , Di Biagio Antonio , Rusconi Stefano , Guaraldi Giovanni , Di Giambenedetto Simona , Lazzarin Adriano , Castagna Antonella 
Published: November 2014

IntroductionThe 48‐week interim analysis of the MODAT study showed that confirmed virologic failure (CVF) was more frequent in patients simplifying to ATV/r monotherapy compared to maintaining ATV/r‐based triple therapy. The DSMB recommended stopping study enrollment but continuing follow‐up of enrolled patients. We present the 96‐week efficacy analysis.Material and MethodsMulticentre, randomized, open‐label, non‐inferiority trial (non‐inferiority margin −10%). Treatment failure (TF) was defined as CVF (two consecutive HIV‐RNA >50 cp/mL) or discontinuation for any cause. In the monotherapy arm, patients with CVF re‐introduced their previous NRTIs and remained in the study if HIV‐RNA <50 copies/mL within 12 weeks of re‐intensification.Results101 patients evaluated (Figure 1): 85% males, 21% HCV‐positive, median (IQR) age of 42 (36–48) years, baseline CD4+ 576 (447–743) cells/µL. In the 96‐week analysis (ITT; TF=failure), efficacy was 64% (32/50) in the monotherapy arm and 63% (32/51) in the triple‐therapy arm (difference +1.3%, 95% CI −17.5–20.1). Fourteen patients in monotherapy and two in triple‐therapy arm had CVF; median HIV‐RNA was 136 (72–376) copies/mL. In monotherapy arm, no PI or NRTI associated resistance mutations were observed at CVF. All patients who re‐intensified re‐suppressed. In monotherapy arm, TF was more frequent in HCV‐co‐infected patients (64% vs 28%; p=0.041). In the secondary analysis (ITT; re‐intensification=success), 82% (41/50) in monotherapy arm and 63% (32/51) in triple‐therapy arm were on study at week 96 (difference +19.3%, 95% CI 2.2–36.3). SAEs occurred in four (8%) patients in the monotherapy arm (one left basal pneumonia, one acute coronary stenosis, one traumatic lesion, one nephrolithiasis) and two (4%) in the triple therapy arm (one sepsis, one renal failure). Drug‐related adverse events (AEs) leading to discontinuation were three (6%) in the monotherapy arm (two AEs occurred in patients after successful re‐intensification) and 12 (23.5%) in the triple‐therapy (p=0.023).ConclusionsDespite the small sample size, the primary 96‐week analysis showed that simplification to ATV/r monotherapy showed inferior efficacy to maintaining ATV/r triple‐therapy but appeared to be superior when re‐intensification was considered success.
Factors involved in treatment durability and immunological recovery in a cohort of HIV‐positive patients receiving atazanavir‐based regimens
Authors: Giacomelli Andrea , Oreni Letizia , Franzetti Marco , Di Cristo Valentina , Vergani Barbara , Morosi Manuela , Colella Elisa , Galli Massimo , Rusconi Stefano 
Published: November 2014

IntroductionSince antiretroviral therapy must be taken lifelong, persistence and safety have become the goals to achieve. Protease inhibitors, in particular atazanavir (ATV) with or without ritonavir (r), represent a highly prescribed class in real life long‐term treatment.MethodsWe conducted a retrospective cohort study in HIV‐1‐positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan. Data regarding viral load, CD4 lymphocytes and the mean blood chemistry parameters were collected at baseline, first, third, sixth months from the beginning of therapy and then every six months. Factors related to persistence of therapy with ATV and time‐dependent probability to reach a CD4 cells count >500 cells/µL were evaluated with Kaplan‐Meier curve and Cox model.ResultsA total of 1030 patients were evaluated: 183 received therapy with ATV/r as naïve, 653 switched to ATV/r as a second or following line and 194 switched to unboosted ATV from previous ATV‐free regimens. A total of 138 patients shifted to unboosted ATV from a previous ATV/r regimen (17 from naïve ATV/r and 121 from experienced ATV/r). The median duration of therapy was 38 months (95% CI 29–73) in ATV/r naïve patients, 36 months (95% CI 23–53) in unboosted ATV group and 35 months (95% CI 31–43) in patients switched to ATV/r. We observed no significant difference in the persistence of the three regimens (p=0.149). Female (HR=1.317; 95% CI 1.073–1.616 p=0.008) and patients with CD4<200 cells/µL at baseline (HR=1.433 95% CI 1.086–1.892 p=0.011) were at increased risk of regimen interruption, whereas starting therapy with a backbone containing abacavir (HR=0.725; 95% CI 0.533–0.987 p=0.041) resulted protective. In multivariate analysis no significant difference between the three regimens was observed regarding reaching a count of CD4 cells >500 cells/µL. Factors associated to a poor CD4 gain were each extra Log of viral load at baseline (HR=0.915; 95% CI 0.852–0.982 p=0.014) and CD4<200 cells/µL at ATV start (HR=0.197; 95%CI 0.138–0.281 p<0.0001); conversely, females (HR=1.262; 95%CI 1.032–1.543 p=0.023) had a higher probability of CD4 recovery.ConclusionsAntiretroviral regimens containing atazanavir with or without ritonavir were durable and well tolerated, an elevated viral load and CD4 <200 cells/µL at baseline resulted related to regimen discontinuation and reduced CD4 recovery.
Proteomic Analysis of Protein Deamidation
Authors: Hao Piliang , Sze Siu Kwan 
Published: November 2014

AbstractDeamidation of asparagines and glutamines occurs spontaneously in proteins and results in protein degradation. Deamidation of asparaginyl residues in proteins produces a mixture of asparaginyl, n‐aspartyl, and isoaspartyl residues, which has been linked to the pathology of some neurodegenerative diseases. However, accurate proteomic analysis of deamidation is challenging since it occurs quickly during conventional proteomic sample preparation, and the co‐elution of the two resulting isomeric deamidated peptides in reversed‐phase liquid chromatography (RPLC) compromises their identification and quantification using RPLC‐MS/MS. To overcome these difficulties, a novel sample preparation protocol to minimize artificial deamidation has been developed alongside an offline RP‐ERLIC‐MS/MS (reversed‐phase chromatography fractionation followed by electrostatic repulsion‐hydrophilic interaction chromatography coupled with MS/MS) strategy to separate and quantify the three deamidation products from the same peptide on a proteome‐wide scale. These protocols are detailed in this unit. © 2014 by John Wiley & Sons, Inc.
T Cell Mediated Autoimmune Glomerular Disease in Mice
Authors: Ooi Joshua D. , Gan Poh‐Yi , Odobasic Dragana , Holdsworth Stephen R. , Kitching A. Richard 
Published: November 2014

AbstractMany forms of glomerulonephritis are mediated by autoimmunity. While autoantibodies are often pathogenic, cell‐mediated immunity plays an important role in a number of forms of rapidly progressive glomerulonephritis. This unit describes the induction of cell‐mediated autoimmune glomerular disease in mice. One disease model, experimental anti‐glomerular basement membrane (GBM) disease, features autoreactivity to a well‐defined component of type IV collagen found in the GBM, α3(IV)NC1. The other models the cell‐mediated effector response in forms of renal vasculitis, where autoantibodies to myeloperoxidase result in systemic neutrophil activation, resulting in their localization to the glomerulus and the subsequent deposition of myeloperoxidase within glomerular capillaries. There, myeloperoxidase acts as a “planted” autoantigen and is recognized by effector autoreactive myeloperoxidase‐specific T cells. These models are useful both in defining mechanisms germane to the development of autoimmunity to α3(IV)NC1 and myeloperoxidase, and in dissecting the role of cell‐mediated responses in effecting glomerular injury. © 2014 by John Wiley & Sons, Inc.
Laser‐Assisted Generation of Human Induced Pluripotent Stem Cells
Authors: Liu Yang , Wu Dongmei , Lao Donglin , Peterson Cory , Hohenstein Elliott Kristi A. , Snyder Evan Y. 
Published: November 2014

AbstractThis unit describes a procedure for generating human induced pluripotent stem cells (hiPSCs) using the Laser‐Enabled Analysis and Processing (LEAP®) system, which combines high‐throughput cell imaging with laser‐mediated cell manipulation. Use of this system should not only improve the quality and uniformity of hiPSCs produced, but ultimately enable a more rapid, efficient, high‐throughput, and automated production process. © 2014 by John Wiley & Sons, Inc.
Laboratory Maintenance of Acinetobacter baumannii
Authors: Jacobs Anna C. , Zurawski Daniel V. 
Published: November 2014

Abstract
Acinetobacter baumannii has recently drawn great interest in the microbiology research community due to the increase in clinical antibiotic resistance of this organism, and persistence of this bacterial species in the hospital environment. This unit outlines protocols for the growth and maintenance of A. baumannii in the laboratory. © 2014 by John Wiley & Sons, Inc.
Induktion axialer Chiralität in einem Geländer‐Oligomer durch Längendiskrepanz der Oligomerstränge
Authors: Rickhaus Michel , Bannwart Linda Maria , Neuburger Markus , Gsellinger Heiko , Zimmermann Kaspar , Häussinger Daniel , Mayor Marcel 
Published: November 2014

AbstractHelikale Moleküle zeigen einzigartige physikalische Eigenschaften, die auf ihre Chiralität zurückgehen. Wir beschreiben hier einen neuen Ansatz zum Aufbau von “Geländer”‐Oligomeren durch Verbindung zweier unterschiedlich langer Oligomerstränge. Dabei windet sich ein längerer Oligobenzylether‐Strang um ein kürzeres Oligophenyl‐Rückgrat, um die Längendiskrepanz auszugleichen. Das neue Geländer‐Oligomer (1) wurde durch Umwandlungen funktioneller Gruppen und Kreuzkupplungsschritte sowie interne nukleophile Cyclisierungen aufgebaut und vollständig charakterisiert, darunter durch Röntgenstrukturanalyse. Die Isolierung der reinen Enantiomere ermöglichte die Verfolgung des Racemisierungsprozesses mittels CD‐Spektroskopie.
Amine–Boranes: Green Hypergolic Fuels with Consistently Low Ignition Delays
Authors: Ramachandran P. Veeraraghavan , Kulkarni Ameya S. , Pfeil Mark A. , Dennis Jacob D. , Willits Jared D. , Heister Stephen D. , Son Steven F. , Pourpoint Timothée L. 
Published: November 2014

AbstractComplexation of amines with borane converts them to hypergols or decreases their ignition delays (IDs) multifold (with white fuming nitric acid as the oxidant). With consistently low IDs, amine–boranes represent a class of compounds that can be promising alternatives to toxic hydrazine and its derivatives as propellants. A structure–hypergolicity relationship study reveals the necessary features for the low ID.
Synthesis, Crystal Structure of the Receptor Derived from Diethoxycarbonyl Glycoluril for Aromatic Amide Guest
Authors: Zhou Baohan , Xu Baoming , Ma Li , Wang Meixi , Chen Kun , Chen Yanguo 
Published: November 2014

AbstractThe receptor derived from the diethoxycarbonyl glycoluril was synthesized and characterized by IR, 1H NMR, MS techniques and X‐ray single crystal analysis. Single crystal X‐ray diffraction reveals that the receptor remains monomeric because of its bulky t‐Bu groups on the side walls. Its unique binding properties for aromatic amides were studied through 1H NMR and IR techniques.
Targeting a Dynamic Protein–Protein Interaction: Fragment Screening against the Malaria Myosin A Motor Complex
Authors: Douse Christopher H. , Vrielink Nina , Wenlin Zhang , Cota Ernesto , Tate Edward W. 
Published: November 2014

AbstractMotility is a vital feature of the complex life cycle of Plasmodium falciparum, the apicomplexan parasite that causes human malaria. Processes such as host cell invasion are thought to be powered by a conserved actomyosin motor (containing myosin A or myoA), correct localization of which is dependent on a tight interaction with myosin A tail domain interacting protein (MTIP) at the inner membrane of the parasite. Although disruption of this protein–protein interaction represents an attractive means to investigate the putative roles of myoA‐based motility and to inhibit the parasitic life cycle, no small molecules have been identified that bind to MTIP. Furthermore, it has not been possible to obtain a crystal structure of the free protein, which is highly dynamic and unstable in the absence of its natural myoA tail partner. Herein we report the de novo identification of the first molecules that bind to and stabilize MTIP via a fragment‐based, integrated biophysical approach and structural investigations to examine the binding modes of hit compounds. The challenges of targeting such a dynamic system with traditional fragment screening workflows are addressed throughout.
Biomechanical model of the thorax under blast loading: a three dimensional numerical study
Authors: Goumtcha Aristide Awoukeng , Thoral‐Pierre Karine , Roth Sébastien 
Published: November 2014

SUMMARYInjury mechanisms due to high speed dynamic loads, such as blasts, are not well understood. These research fields are widely investigated in the literature, both at the experimental and numerical levels, and try to answer questions about the safety and efficiency of protection devices or biomechanical traumas. At a numerical level, the development of powerful mathematical models tends to study tolerance limits and injury mechanisms in order to avoid experimental tests which cannot be easily conducted. In a military framework, developing a fighter/soldier numerical model can help to the understanding of many traumas which are specific to soldier injuries, like mines, ballistic impacts or blast traumas. The aim of this study is to investigate the consequences of violent loads in terms of human body response, submitting a developed and validated three‐dimensional thorax finite element (FE) model to blast loadings. Specific formulations of FE methods are used to simulate this loading, and its consequence on the biomechanical model. Mechanical parameters such as pressure in the air field and also in internal organs are observed, and these values are compared to the experimental data in the literature. This study gives encouraging results and allows going further in soldier trauma investigations. Copyright © 2014 John Wiley & Sons, Ltd.
Diabetes mellitus with poor glycemic control increases bladder cancer recurrence risk in patients with upper urinary tract urothelial carcinoma
Authors: Tai Yi‐Sheng , Chen Chung‐Hsin , Huang Chao‐Yuan , Tai Huai‐Chin , Wang Sho‐Mon , Pu Yeong‐Shiau 
Published: November 2014

AbstractBackgroundThe association of diabetes mellitus and bladder cancer recurrence following radical nephroureterectomies (RNUs) in patients with upper urinary tract urothelial carcinoma (UTUC) was investigated.MethodsBetween January 1996 and March 2009, 538 patients with UTUC who received RNU and had no previous bladder cancer histories were enrolled. The clinicopathological characteristics were obtained and used for the analysis of metachronous bladder recurrence by using Cox proportional hazard model.ResultsThe diabetic patients (N = 104, 19.3%) were elderly (72 vs 67 years, p < 0.001) and had more hypertension (56.7 vs 34.5%, p < 0.001) as compared with non‐diabetic patients. There was no significant difference in the rest of clinicopathological characteristics between patient groups. During the median follow‐up duration of 51 months, bladder recurrences were discovered in 47.1 and 33.1% of diabetic and non‐diabetic patients with UTUC, respectively. Poorly controlled diabetic patients (HbA1c ≥ 7.0%) exhibited a shorter duration of bladder cancer recurrence‐free survival as compared with those with good glycemic controlled diabetes mellitus and without diabetes mellitus (log‐rank test, p < 0.001 and <0.001, respectively). In the multivariate analysis, male gender [hazard ratio (HR) = 1.67, p = 0.017], ureteral tumour (HR = 1.61, p = 0.020), end‐stage renal disease (HR = 2.09, p = 0.030) and diabetes mellitus with poor glycemic control (HR = 2.10, p < 0.018) independently predicted bladder recurrence after RNU.ConclusionsDiabetes mellitus with poor glycemic control (HbA1c ≥ 7.0%) increases the risk of subsequent bladder cancer recurrence. These results underscore the need for intensive glycemic control and close follow‐up for diabetic patients. Copyright © 2014 John Wiley & Sons, Ltd.
Dementia diagnostic criteria in Down syndrome
Authors: Sheehan Rory , Sinai Amanda , Bass Nick , Blatchford Pippa , Bohnen Ingrid , Bonell Simon , Courtenay Ken , Hassiotis Angela , Markar Therese , McCarthy Jane , Mukherji Kamalika , Naeem Asim , Paschos Dimitrios , Perez‐Achiaga Natalia , Sharma Vijaya , Thomas David , Walker Zuzana , Strydom Andre 
Published: November 2014

ObjectiveDementia is a common clinical presentation among older adults with Down syndrome. The presentation of dementia in Down syndrome differs compared with typical Alzheimer's disease. The performance of manualised dementia criteria in the International Classification of Diseases (ICD)‐10 and Diagnostic and Statistical Manual of Mental Disorders‐IV‐Text Revision (DSM‐IV‐TR) is uncertain in this population.We aimed to determine the concurrent validity and reliability of clinicians' diagnoses of dementia against ICD‐10 and DSM‐IV‐TR diagnoses. Validity of clinical diagnoses were also explored by establishing the stability of diagnoses over time.MethodsWe used clinical data from memory assessments of 85 people with Down syndrome, of whom 64 (75.3%) had a diagnosis of dementia. The cases of dementia were presented to expert raters who rated the case as dementia or no dementia using ICD‐10 and DSM‐IV‐TR criteria and their own clinical judgement.ResultsWe found that clinician's judgement corresponded best with clinically diagnosed cases of dementia, identifying 84.4% cases of clinically diagnosed dementia at the time of diagnosis. ICD‐10 criteria identified 70.3% cases, and DSM‐IV‐TR criteria identified 56.3% cases at the time of clinically diagnosed dementia. Over time, the proportion of cases meeting ICD‐10 or DSM‐IV‐TR diagnoses increased, suggesting that experienced clinicians used their clinical knowledge of dementia presentation in Down syndrome to diagnose the disorder at an earlier stage than would have been possible had they relied on the classic description contained in the diagnostic systems.ConclusionsClinical diagnosis of dementia in Down syndrome is valid and reliable and can be used as the standard against which new criteria such as the DSM‐5 are measured. Copyright © 2014 John Wiley & Sons, Ltd.