bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Higher Plasma Vitamin D Binding Protein and Lower Free Calcitriol Levels with Tenofovir Disoproxil Fumarate Use and Plasma and Intracellular Tenofovir Pharmacokinetics: Cause of a Functional Vitamin D Deficiency?
Authors: Havens Peter L. , Kiser Jennifer J. , Stephensen Charles B. , Hazra Rohan , Flynn Patricia M. , Wilson Craig M. , Rutledge Brandy , Bethel James , Pan Cynthia G. , Woodhouse Leslie R. , Van Loan Marta D. , Liu Nancy , Lujan-Zilbermann Jorge , Baker Alyne , Kapogiannis Bill G. , Gordon Catherine M. , Mulligan Kathleen 
Published: September 2013

ABSTRACTTenofovir disoproxil fumarate (TDF) causes bone, endocrine, and renal changes by an unknown mechanism(s). Data are limited on tenofovir pharmacokinetics and these effects. Using baseline data from a multicenter study of HIV-infected youth on stable treatment with regimens containing TDF (n= 118) or lacking TDF (n= 85), we measured cross-sectional associations of TDF use with markers of renal function, vitamin D-calcium-parathyroid hormone balance, phosphate metabolism (tubular reabsorption of phosphate and fibroblast growth factor 23 [FGF23]), and bone turnover. Pharmacokinetic-pharmacodynamic associations with plasma tenofovir and intracellular tenofovir diphosphate concentrations were explored among those receiving TDF. The mean age was 20.9 (standard deviation [SD], 2.0) years; 63% were male; and 52% were African American. Compared to the no-TDF group, the TDF group showed lower mean estimated glomerular filtration rates and tubular reabsorption of phosphate, as well as higher parathyroid hormone and 1,25-dihydroxy vitamin D [1,25-OH(2)D] levels. The highest quintile of plasma tenofovir concentrations was associated with higher vitamin D binding protein, lower free 1,25-OH(2)D, higher 25-OH vitamin D, and higher serum calcium. The highest quintile of intracellular tenofovir diphosphate concentration was associated with lower FGF23. Higher plasma tenofovir concentrations were associated with higher vitamin D binding protein and lower free 1,25-OH(2)D, suggesting a functional vitamin D deficiency explaining TDF-associated increased parathyroid hormone. The finding of lower FGF23 accompanying higher intracellular tenofovir diphosphate suggests that different mechanisms mediate TDF-associated changes in phosphate handling. Separate pharmacokinetic properties may be associated with distinct TDF toxicities: tenofovir with parathyroid hormone and altered calcium balance and tenofovir diphosphate with hypophosphatemia and FGF23 regulation.IMPORTANCE(The clinical trial registration number for this study is NCT00490412 and is available online athttp://clinicaltrials.gov/ct2/show/NCT00490412.)
RALP1 Is a Rhoptry Neck Erythrocyte-Binding Protein of Plasmodium falciparum Merozoites and a Potential Blood-Stage Vaccine Candidate Antigen
Authors: Ito Daisuke , Hasegawa Tomoyuki , Miura Kazutoyo , Yamasaki Tsutomu , Arumugam Thangavelu U. , Thongkukiatkul Amporn , Takeo Satoru , Takashima Eizo , Sattabongkot Jetsumon , Han Eun-Taek , Long Carole A. , Torii Motomi , Tsuboi Takafumi 
Published: September 2013

ABSTRACT

Erythrocyte invasion by merozoites is an obligatory stage of
Plasmodium
infection and is essential to disease progression. Proteins in the apical organelles of merozoites mediate the invasion of erythrocytes and are potential malaria vaccine candidates. Rhoptry-associated, leucine zipper-like protein 1 (RALP1) of
Plasmodium falciparum
was previously found to be specifically expressed in schizont stages and localized to the rhoptries of merozoites by immunofluorescence assay (IFA). Also, RALP1 has been refractory to gene knockout attempts, suggesting that it is essential for blood-stage parasite survival. These characteristics suggest that RALP1 can be a potential blood-stage vaccine candidate antigen, and here we assessed its potential in this regard. Antibodies were raised against recombinant RALP1 proteins synthesized by using the wheat germ cell-free system. Immunoelectron microscopy demonstrated for the first time that RALP1 is a rhoptry neck protein of merozoites. Moreover, our IFA data showed that RALP1 translocates from the rhoptry neck to the moving junction during merozoite invasion. Growth and invasion inhibition assays revealed that anti-RALP1 antibodies inhibit the invasion of erythrocytes by merozoites. The findings that RALP1 possesses an erythrocyte-binding epitope in the C-terminal region and that anti-RALP1 antibodies disrupt tight-junction formation, are evidence that RALP1 plays an important role during merozoite invasion of erythrocytes. In addition, human sera collected from areas in Thailand and Mali where malaria is endemic recognized this protein. Overall, our findings indicate that RALP1 is a rhoptry neck erythrocyte-binding protein and that it qualifies as a potential blood-stage vaccine candidate.
Small-Molecule Inhibitor of the Shigella flexneri Master Virulence Regulator VirF
Authors: Koppolu Veerendra , Osaka Ichie , Skredenske Jeff M. , Kettle Bria , Hefty P. Scott , Li Jiaqin , Egan Susan M. 
Published: September 2013

ABSTRACTVirF is an AraC family transcriptional activator that is required for the expression of virulence genes associated with invasion and cell-to-cell spread byShigella flexneri, including multiple components of the type three secretion system (T3SS) machinery and effectors. We tested a small-molecule compound, SE-1 (formerly designated OSSL_051168), which we had identified as an effective inhibitor of the AraC family proteins RhaS and RhaR, for its ability to inhibit VirF. Cell-based reporter gene assays withEscherichia coliandShigella, as well asin vitroDNA binding assays with purified VirF, demonstrated that SE-1 inhibited DNA binding and transcription activation (likely by blocking DNA binding) by VirF. Analysis of mRNA levels using real-time quantitative reverse transcription-PCR (qRT-PCR) further demonstrated that SE-1 reduced the expression of the VirF-dependent virulence genesicsA,virB,icsB, andipaBinShigella. We also performed eukaryotic cell invasion assays and found that SE-1 reduced invasion byShigella. The effect of SE-1 on invasion required preincubation ofShigellawith SE-1, in agreement with the hypothesis that SE-1 inhibited the expression of VirF-activated genes required for the formation of the T3SS apparatus and invasion. We found that the same concentrations of SE-1 had no detectable effects on the growth or metabolism of the bacterial cells or the eukaryotic host cells, respectively, indicating that the inhibition of invasion was not due to general toxicity. Overall, SE-1 appears to inhibit transcription activation by VirF, exhibits selectivity toward AraC family proteins, and has the potential to be developed into a novel antibacterial agent.
Mechanism of Homologous Recombination and Implications for Aging-Related Deletions in Mitochondrial DNA
Authors: Chen Xin Jie 
Published: September 2013

SUMMARY
Homologous recombination is a universal process, conserved from bacteriophage to human, which is important for the repair of double-strand DNA breaks. Recombination in mitochondrial DNA (mtDNA) was documented more than 4 decades ago, but the underlying molecular mechanism has remained elusive. Recent studies have revealed the presence of a Rad52-type recombination system of bacteriophage origin in mitochondria, which operates by a single-strand annealing mechanism independent of the canonical RecA/Rad51-type recombinases. Increasing evidence supports the notion that, like in bacteriophages, mtDNA inheritance is a coordinated interplay between recombination, repair, and replication. These findings could have profound implications for understanding the mechanism of mtDNA inheritance and the generation of mtDNA deletions in aging cells.
Cognitive screening improves the predictive value of stroke severity scores for functional outcome 3–6 months after mild stroke and transient ischaemic attack: an observational study
Authors: Dong YanHong , Slavin Melissa Jane , Chan Bernard Poon-Lap , Venketasubramanian Narayanaswamy , Sharma Vijay Kumar , Crawford John D , Collinson Simon Lowes , Sachdev Perminder , Chen Christopher Li-Hsian 
Published: September 2013

ObjectivesTo investigate the prognostic value of the neurocognitive status measured by screening instruments, the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), individually and in combination with the stroke severity scale, the National Institute of Health Stroke Scale (NIHSS), obtained at the subacute stroke phase or the baseline (≤2 weeks), for functional outcome 3–6 months later.DesignProspective observational study.SettingTertiary stroke neurology service.Participants400 patients with a recent ischaemic stroke or transient ischaemic attack (TIA) received NIHSS, MoCA and MMSE at baseline and were followed up 3–6 months later.Primary outcome measuresAt 3–6 months following the index event, functional outcome was measured by the modified Rankin Scale (mRS) scores.ResultsMost patients (79.8%) had a mild ischaemic stroke and less disability (median NIHSS=2, median mRS=2 and median premorbid mRS=0), while a minority of patients had TIA (20.3%). Baseline NIHSS, MMSE and MoCA scores individually predicted mRS scores at 3–6 months, with NIHSS being the strongest predictor (NIHSS: R2change=0.043, p<0.001). Moreover, baseline MMSE scores had a small but statistically significant incremental predictive value to the baseline NIHSS for mRS scores at 3–6 months, while baseline MoCA scores did not (MMSE: R2changes=0.006, p=0.03; MoCA: R2changes=0.004, p=0.083). However, in patients with more severe stroke at baseline (defined as NIHSS>2), baseline MoCA and MMSE had a significant and moderately large incremental predictive value to the baseline NIHSS for mRS scores at 3–6 months (MMSE: R2changes=0.021, p=0.010; MoCA: R2changes=0.017, p=0.021).ConclusionsCognitive screening at the subacute stroke phase can predict functional outcome independently and improve the predictive value of stroke severity scores for functional outcome 3–6 months later, particularly in patients with more severe stroke.
Comprehensive screening for PRSS1, SPINK1, CFTR, CTRC and CLDN2 gene mutations in Chinese paediatric patients with idiopathic chronic pancreatitis: a cohort study
Authors: Wang Wei , Sun Xiao-Tian , Weng Xiao-Ling , Zhou Dai-Zhan , Sun Chang , Xia Tian , Hu Liang-Hao , Lai Xiao-Wei , Ye Bo , Liu Mu-Yun , Jiang Fei , Gao Jun , Bo Lu-Min , Liu Yun , Liao Zhuan , Li Zhao-Shen 
Published: September 2013

ObjectiveGenetic alterations may contribute to chronic pancreatitis (CP) in Chinese young patients. This study was designed to investigate mutations of cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor or serine protease inhibitor Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator(CFTR), chymotrypsin C(CTRC)andCLDN2genes and the copy number variations (CNVs) ofPRSS1and asses associations with the development of idiopathic CP (ICP) in Chinese children.DesignRetrospective.SettingA single center.Participants75 ICP Chinese children (40 boys and 35 girls).Primary and secondary outcome measuresMutations ofPRSS1,SPINK1,CFTR,CTRCandCLDN2genes and CNVs.Results7 patients had heterozygous mutations inPRSS1, that is, N29I (n=1), R122H or R122C (n=6). The CNVs of PRSS1 in five patients had abnormal copies (1 copy (n=4), five copies (n=1)). 43 patients had IVS3+2T>C (rs148954387) (10 homozygous and 33 heterozygous) inSPINK1. None of thePRSS1mutation patients carried aSPINK1mutation. Frequency ofPRSS1andSPINK1mutations was 9.3% and 57.3%, respectively, with an overall frequency of 66.6% (50/75). In addition, one patient had a novel deletion ofCFTR(GCTTCCTA from c.500 to c.508 leading to the shortened polypeptide molecule via a stop codon). Another patient had a novel missense inCLDN2exon 2 (c.592A>C mutation). Clinically, patients withSPINK1mutations had a higher rate of pancreatic duct stones, pancreatic pseudocyst and pancreatic calcification than those withoutSPINK1mutations (p<0.05).ConclusionsSPINK1mutations were more commonly associated with Chinese children with ICP.SPINK1IVS3+2T>C mutation may play an important role in the pathogenesis of Chinese paediatric ICP. However, further study is needed to confirm and to investigate the role of these genes in the development of Chinese ICP.
UK wide survey on the prevention of post-ERCP pancreatitis
Authors: Hanna Mina S , Portal Andrew J , Dhanda Ashwin D , Przemioslo Robert 
Published: September 2013

ObjectiveIn 2010, the European Society of Gastrointestinal Endoscopy delivered guidelines on the prophylaxis of postendoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis (PEP). These included Grade A recommendations advising the use of prophylactic pancreatic stent (PPS) and non-steroidal anti-inflammatory drugs (NSAIDs) in high-risk cases. Our study aim was to capture the current practice of UK biliary endoscopists in the prevention of PEP.DesignIn summer 2012, an anonymous online 15-item survey was emailed to 373 UK consultant gastroenterologists, gastrointestinal surgeons and radiologists identified to perform ERCP.ResultsThe response rate was 59.5% (222/373). Of the respondents, 52.5% considered ever using PPS for the prevention of PEP. PPS users always attempted insertion for the following procedural risk factors: pancreatic sphincterotomy (48.9%), suspected sphincter of Oddi dysfunction (46.5%), pancreatic duct instrumentation (35.9%), previous PEP (25.2%), precut sphincterotomy (8.5%) and pancreatic duct injection (7.8%). Prophylactic NSAID use was significantly associated with attempts at PPS placement (p<0.001). 64.1% of non-PPS users cited a lack of conviction in their benefit as the main reason for their decision. Self-reported pharmacological use rates for PEP prevention were: NSAIDs (34.6%), antibiotics (20.6%), rapid intravenous fluids (13.2%) and octreotide (1.6%). 6% routinely measured amylase post-ERCP.ConclusionsDespite strong evidence-based guidelines for prevention of PEP, less than 53% of ERCP practitioners use pancreatic stenting or NSAIDs. This suggests a need for the development of British Society of Gastroenterology guidelines to increase awareness in the UK. Even among stent users, PPS are being underused for most high-risk cases. Prophylactic pharmacological measures were rarely used as was routine post-ERCP serum amylase measurement.
‘Heavier the interval than the consummation’: bronchial disease in Seán Ó Ríordáin's diaries
Authors: Breathnach Ciara 
Published: September 2013

AbstractNarratives of the experience of pulmonary tuberculosis (TB) are relatively rare in the Irish context. A scourge of the early twentieth century, TB was as much a social as a physically debilitating disease that rendered sufferers silent about their experience. Thus, the personal diaries and letters of Irish poet, Seán Ó Ríordáin, (1916–1977) are rare. This article presents translations of his personal papers in a historico-medical context to chronicle Ó Ríordáin’s experience of a life marred by respiratory disease. Familiar to generations of schoolchildren are his imaginative poems, whose lively metre punctuated the Irish language curriculum from primary through to secondary schooling; for most they leave an indelible mark. Such buoyant poems however belie the reality of his existence, lived in the shadow of chronic illness, and punctuated with despair over his condition and anxiety about the periods of extended sick leave his illness necessitated. Although despair dominated his diaries and he routinely begged God, Mary, the Saints and the devil for death, they were also the locus where his creativity developed. In his diaries, caricatures of friends and sketches of everyday things nestle among the first lines of some of his most influential poems and quotes from distinguished philosophers and writers. Evocative and tragic, his diaries offer a unique prism to the experience of respiratory disease in Ireland.
MOLECULAR STRUCTURE, VIBRATIONAL ASSIGNMENTS, CONFORMATIONAL STABILITY, GROUND AND EXCITED STATE HYDROGEN-BONDING ANALYSIS OF 2-NITROSO VINYL AMINE
Authors: MOLLANIA FARIBA , RAISSI HEIDAR 
Published: September 2013

In the present work, a detailed conformational study is performed using several computational methods, including density functional theory (DFT) (B3LYP), MP2 and G2MP2 on 2-Nitroso vinyl amine (NVA) in order to determine the stability order of conformers and the various possibilities of intramolecular hydrogen bonding (HB) formation. Four conformers exhibit HB . This feature, although not being the dominant factor in energetic terms, appears to be of foremost importance to define the geometry of the molecule. According to our theoretical results, oximimine conformers are more stable than the corresponding nitrosoamine and nitrosoimine analogues. Theoretical calculations show the following order for intramolecular HB strength in the conformers of title compound: [Formula: see text]The nature of intramolecular HB has been investigated by means of the Bader theory of atoms in molecules (AIM) and natural bond orbital (NBO) analysis. Also, Harmonic Oscillator Model of Aromaticity (HOMA) index as a geometrical indicator of a local aromaticity are investigated. The influence of the solvent on the stability order of conformers and the strength of intramolecular HB is considered using the Onsager reaction field model. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies confirm that charge transfer occur within the molecule. Further verification of the obtained transition state structures were implemented via intrinsic reaction coordinate (IRC) analysis. Calculations of the1H NMR chemical shift at GIAO/B3LYP/6–311++G** levels of theory are also presented. The excited-state properties of intramolecular HB in H -bonded systems have been investigated theoretically using the time-dependent density functional theory (TD-DFT) method. The complete vibrational assignment for three H -bonded conformers has been made on the basis of the calculated potential energy distribution (PED).
Paclitaxel–Hyaluronic NanoConjugates Prolong Overall Survival in a Preclinical Brain Metastases of Breast Cancer Model
Authors: Mittapalli Rajendar K. , Liu Xinli , Adkins Chris E. , Nounou Mohamed I. , Bohn Kaci A. , Terrell Tori B. , Qhattal Hussaini S. , Geldenhuys Werner J. , Palmieri Diane , Steeg Patricia S. , Smith Quentin R. , Lockman Paul R. 
Published: September 2013

Abstract
Brain (central nervous system; CNS) metastases pose a life-threatening problem for women with advanced metastatic breast cancer. It has recently been shown that the vasculature within preclinical brain metastasis model markedly restricts paclitaxel delivery in approximately 90% of CNS lesions. Therefore to improve efficacy, we have developed an ultra-small hyaluronic acid (HA) paclitaxel nanoconjugate (∼5 kDa) that can passively diffuse across the leaky blood–tumor barrier and then be taken up into cancer cells (MDA–MB–231Br) via CD44 receptor–mediated endocytocis. Using CD44 receptor–mediated endocytosis as an uptake mechanism, HA-paclitaxel was able to bypass p-glycoprotein–mediated efflux on the surface of the cancer cells. In vitro cytoxicity of the conjugate and free paclitaxel were similar in that they (i) both caused cell-cycle arrest in the G2–M phase, (ii) showed similar degrees of apoptosis induction (cleaved caspase), and (iii) had similar IC50 values when compared with paclitaxel in MTT assay. A preclinical model of brain metastases of breast cancer using intracardiac injections of Luc-2 transfected MDA–MB–231Br cells was used to evaluate in vivo efficacy of the nanoconjugate. The animals administered with HA–paclitaxel nanoconjugate had significantly longer overall survival compared with the control and the paclitaxel-treated group (P &lt; 0.05). This study suggests that the small molecular weight HA–paclitaxel nanoconjugates can improve standard chemotherapeutic drug efficacy in a preclinical model of brain metastases of breast cancer. Mol Cancer Ther; 12(11); 2389–99. ©2013 AACR.
Marx as the Historical Materialist: Re-reading The Eighteenth Brumaire
Authors: Tomba Massimiliano 
Published: September 2013

AbstractThe purpose of this paper is to re-read Marx’sEighteenth Brumaireby highlighting the political meaning of a materialist historiography. In the first part, I consider Marx’s historiographical and political intention to represent the history of the aftermath of the revolution of ’48 as a farce in order to liquidate ‘any faith in the superstitious past’. In the second part I analyse the theatrical register chosen by Marx in order to represent the Second Empire as a society without a body, a phantasmagoria in which the Constitution, the National Assembly and law – in short, everything that the middle class had put up as essential principles of modern democracy – disappear. In the third part I argue that Marx does not elaborate a theory of revolution that is good for every occasion. What interests him is a historiography capable of grasping, in the various temporalities of the revolution, the chance for a true liberation.
Imperialism and Capitalist Development in Marx’s Capital
Authors: Pradella Lucia 
Published: September 2013

AbstractThis article aims at contributing to current debates on the ‘new imperialism’ by presenting the main results of a reading of Marx’sCapitalin light of his writings on colonialism, which were unknown in the early Marxist debate on imperialism. It aims to prove that, in his main work, Marx does not analyse a national economy or – correspondingly – an abstract model of capitalist society, but a world-polarising and ever-expanding system. This abstraction allows the identification of the laws of development of capitalism and its antagonisms, and reflects the tendency of the capital of the dominant states, by making permanent recourse also to methods of so-called ‘primitive accumulation’, to expand and increase the exploitation of workers worldwide, and, at the same time, the cooperation between them. What, for Marx, was later defined as imperialism is the concrete form of the process of ‘globalisation’ of the capital of the dominant states. With the development of his analysis, Marx became increasingly aware of the economic and political consequences of imperialism. In his activity within the First International, with regard to the question of Irish independence, he affirmed the fundamental importance of building a real solidarity between class struggles in imperialist countries and anti-colonial resistance in colonised and dependent countries. His examination of imperialism and internationalist perspective were downplayed, denied, if not completely reversed in the interpretation and systematisation of his thought by reformist leaders within the Second International. In their attempt to react against this tendency and develop an analysis and a political strategy adequate to the new phase of generalised imperialist expansion, increased inter-imperialist rivalries and rising anti-colonial resistance, Rosa Luxemburg and Lenin reaffirmed the centrality of the critique of imperialism at the economic and at the political levels. Even if they were partially unaware of this, they thus developed and expanded on some aspects already present in Marx’s work.