bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potent Rifamycin-Sparing Regimen Cures Guinea Pig Tuberculosis as Rapidly as the Standard Regimen
Authors: Dutta Noton K. , Alsultan Abdullah , Gniadek Thomas J. , Belchis Deborah A. , Pinn Michael L. , Mdluli Khisimuzi E. , Nuermberger Eric L. , Peloquin Charles A. , Karakousis Petros C. 
Published: June 2013

ABSTRACT

Strategies involving new drug combinations, as well as new uses of existing drugs, are urgently needed to reduce the time required to cure patients with drug-sensitive or multidrug-resistant (MDR) tuberculosis (TB). We compared the sterilizing activity of the standard first-line antitubercular regimen, rifampin-isoniazid-pyrazinamide (RHZ), with that of the novel regimen PA-824–moxifloxacin–pyrazinamide (PaMZ), which is currently being studied in clinical trials (NCT01498419), in the guinea pig model of chronic TB infection, in which animals develop necrotic granulomas histologically resembling their human counterparts. Guinea pigs were aerosol infected with ∼2 log
10
bacilli of wild-type
Mycobacterium tuberculosis
H37Rv, and antibiotic treatment was initiated 6 weeks after infection. Separate groups of animals received RHZ, PaMZ, or single or two-drug components of the latter regimen administered at human-equivalent doses 5 days/week for a total of 8 weeks. Relapse rates were assessed 3 months after discontinuation of treatment to determine the sterilizing activity of each combination regimen. PaMZ given at human-equivalent doses was safe and well tolerated for the entire treatment period and rendered guinea pig lungs culture negative more rapidly than RHZ did. After 1 month of treatment, 80% and 50% of animals in the RHZ and PaMZ groups, respectively, had lung culture-positive relapse. Both combination regimens prevented microbiological relapse when administered for a total of 2 months. Our data support the use of PaMZ as a novel isoniazid- and rifamycin-sparing regimen suitable for treatment of both drug-sensitive TB and MDR-TB.
Dominant Role of Oncogene Dosage and Absence of Tumor Suppressor Activity in Nras-Driven Hematopoietic Transformation
Authors: Xu Jin , Haigis Kevin M. , Firestone Ari J. , McNerney Megan E. , Li Qing , Davis Elizabeth , Chen Shann-Ching , Nakitandwe Joy , Downing James , Jacks Tyler , Le Beau Michelle M. , Shannon Kevin 
Published: June 2013

Abstract
Biochemical properties of Ras oncoproteins and their transforming ability strongly support a dominant mechanism of action in tumorigenesis. However, genetic studies unexpectedly suggested that wild-type (WT) Ras exerts tumor suppressor activity. Expressing oncogenic NrasG12D in the hematopoietic compartment of mice induces an aggressive myeloproliferative neoplasm that is exacerbated in homozygous mutant animals. Here, we show that increased NrasG12D gene dosage, but not inactivation of WT Nras, underlies the aggressive in vivo behavior of NrasG12D/G12D hematopoietic cells. Modulating NrasG12D dosage had discrete effects on myeloid progenitor growth, signal transduction, and sensitivity to MAP-ERK kinase (MEK) inhibition. Furthermore, enforced WT N-Ras expression neither suppressed the growth of Nras-mutant cells nor inhibited myeloid transformation by exogenous NrasG12D. Importantly, NRAS expression increased in human cancer cell lines with NRAS mutations. These data have therapeutic implications and support reconsidering the proposed tumor suppressor activity of WT Ras in other cancers.
Significance: Understanding the mechanisms of Ras-induced transformation and adaptive cellular responses is fundamental. The observation that oncogenic Nras lacks tumor suppressor activity, whereas increased dosage strongly modulates cell growth and alters sensitivity to MEK inhibition, suggests new therapeutic opportunities in cancer. Cancer Discov; 3(9); 993–1001. ©2013 AACR.
This article is highlighted in the In This Issue feature, p. 953
Perturbation of the heparin/heparin-sulfate interactome of human breast cancer cells modulates pro-tumourigenic effects associated with PI3K/Akt and MAPK/ERK signalling
Authors: Chen Yunliang , Scully Michael , Dawson Gloria , Goodwin Christopher , Xia Min , Lu Xinjie , Kakkar Ajay 
Published: June 2013

SummaryHeparansulfate-proteoglycans (HSPGs) interact via their polyanionic heparansulfate (HS) side chains with a variety of proteins on the cell surface or within the extracellular matrix membrane. The large number of heparin/HS binding proteins form a highly interconnected functional network, which has been termed as the heparin/HS interactome and is functionally linked to physiological and pathological processes. The aim of this study was to investigate the global effect of these protein-HSPG interactions on the tumourigenicity of two breast cancer cell lines (MCF-7 and MDA-MB-231). Cancer cells were cultured in serum-free medium and treated with a concentration of heparin which was capable of modulating HS/ligand interaction. Microarray analysis of MCF-7 cells cultured under these conditions showed that expression of 105 of 1,357 genes potentially related to the pathogenesis of breast neoplasm was significantly altered by heparin treatment. The changes in gene expression correlated with a less tumourigenic phenotype, including reduction of cell adhesive, invasive and migratory properties. These effects were associated with an inhibition of the PI3K/Akt and Raf/MEK/ERK signalling pathways. The modulatory effect of heparin on HS-associated activity was confirmed with one example of heparin/HS interactomes, transforming growth factor β (TGFβ). The innate TGFβ activity of MCF-7 cells was reduced by heparin treatment, with specific interruption of the TGFβ–Smad signalling pathway. The pro-tumourigenic contribution of the heparin/HS interactomes was verified in cells in which HSPG synthesis was blocked using β-xyloside. In conclusion, the interaction between cell surface HPSGs and innate heparin/HS interactomes makes a significant contribution to the tumourigenicity.
Descent and Ascent from Ockham to Domingo de Soto: An Answer to Paul Spade
Authors: Ashworth E. Jennifer 
Published: June 2013

Abstract
Paul Spade has attacked the theory of the modes of personal supposition as found in Ockham and Buridan, partly on the grounds that the details of the theory are incompatible with the equivalence between propositions and their descended forms which is implied by the appeal to suppositional descent and ascent. I trace the development of the doctrines of ascent and descent from the mid-fourteenth century to the early sixteenth century, and I investigate Domingo de Soto’s elaborate account of how descent and ascent actually worked. I show that although Soto himself shared some of Spade’s doubts, including those about the use of merely confused supposition, he had a way of reducing at least some propositions containing terms with such supposition to equivalent disjunctions and conjunctions of singular propositions. Moreover, he gave explicit instructions on how to avoid the supposed problem of O-propositions.
Logic in Salamanca in the Fifteenth Century The Tractatus Suppositionum Terminorum by Master Franquera
Authors: d’Ors† Angel 
Published: June 2013

Abstract
This paper looks into the contents of the Tractatus suppositionum terminorum by Master Franquera, in the context of the teaching of logic in Salamanca (and elsewhere in Spain) in the fifteenth century. Franquera’s work is characterised by its explicit realist bias and its rejection of Ockhamist theses, i.e., by its recognition of the existence of a natura communis or a universale in re, which is evident in all discussions related to suppositio simplex and the theory of significatio. But, apart from this, Franquera’s discussion of the theory of suppositio stands out as a strange mixture of different doctrines: some of them are derived from thirteenth-century (or earlier) analyses, others from fourteenth-century developments; realist goals are reached by means of instruments that, while not being nominalist, are definitely inspired by terminism. While upholding the theses of realist schools, Franquera adopts the definitions and rules of nominalist authors.
Application of a published methodology for evaluating within-bale repeatability of measurements obtained with standardized instruments for testing cotton: Gossypium hirsutum in Eastern and Southern Africa
Authors: Lukonge Everina E , Aboé Modeste , Gozé Eric , Sinoimeri Artan , Gourlot Jean-Paul 
Published: June 2013

The possible application of conclusions from a published study concerning cottons from West and Central Africa (WCA), involving an evaluation of the within-bale variability of fiber Micronaire, Length, Uniformity, Strength, Reflectance and Yellowness in cottons from Eastern and Southern Africa (ESA) was investigated. We took eight cotton samples per bale from 240 bales produced by 32 ginning mills in six ESA countries in two crop seasons. Our representative sample comprised 1920 fiber samples that were centrally analyzed under controlled conditions using standardized instruments for testing cotton (SITC). We evaluated within-bale variability levels for both saw- and roller-ginned cottons and checked the applicability of the published conclusions to ESA. We found that (1) sampling variance levels were comparable in ESA and in WCA for saw-ginned cottons, (2) WCA recommendations for saw-ginned cottons would also apply in ESA for most fiber characteristics measured by SITC, and (3) for roller-ginned cottons, the higher within-bale variability of roller-ginned cotton fibers compared to saw-ginned cotton would require the definition of a specific sampling and testing method based on an experiment to be designed.
Clinical and Electromyographic Results of Proximal and Distal Realignment Procedures in Young Patients With Recurrent Patellar Dislocations
Authors: Kreuz Peter C. , Peterson Lars , van der Werf-Grohmann Natascha , Vohrer Michael , Schwering Ludwig 
Published: June 2013

Background: Until now, no study has been published about the electromyographic changes in the extensor apparatus after the Green procedure for proximal realignment in young patients with recurrent patellar dislocations. This electromyographic study was performed to analyze imbalances between the vastus medialis and vastus lateralis muscles after different patellar realignment procedures. Hypothesis: Surgical proximal realignment leads to electromyographic changes in the extensor apparatus of the knee and to imbalances between the vastus medialis and vastus lateralis muscles. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 28 knees of 25 patients, with a mean age of 15 years, were treated operatively for recurrent patellar dislocations. The mean follow-up was 6.3 years. Depending on the type of surgical intervention, the patients were assigned to 3 different groups: the patients of group 1 underwent only the Green vastus medialis obliquus (VMO) advancement, group 2 was treated with a combination of the Green proximal and the Roux-Goldthwait distal realignment, and group 3 was treated with a combination of the Green proximal realignment and an additional tubercle transfer. All patients underwent clinical, radiological, and electromyographic examinations. The muscle activities of a healthy control group without patellar dislocations were used for comparison. Results: A combination of the Green procedure and tubercle transfer led to significantly better clinical results and a lower number of redislocations ( P < .05) compared with patients who underwent only the Green proximal realignment. While ascending or descending stairs, the ratio between the electromyographic activities of the vastus medialis and vastus lateralis muscles in groups 1 and 2 was significantly smaller compared with the control group ( P < .02). Only the electromyograms of group 3 revealed a balanced extensor apparatus during loading with comparable activities of the vastus medialis and vastus lateralis muscles and no significant difference to the control group ( P = .37). Conclusion: Our electromyographic investigations showed the importance of the vastus medialis in the pathogenesis of malalignment of the extensor mechanism. The Green VMO advancement without tibial tubercle transfer is not able to balance the activities of the vastus medialis and vastus lateralis muscles and cannot be recommended for further use.
Stent fabric fatigue of grafts supported by Z-stents versus ringed stents: An in vitro buckling test
Authors: Lin Jing , Wang Lu , Guidoin Robert , Nutley Mark , Song Ge , Zhang Ze , Du Jia , Douville Yvan 
Published: June 2013

Stent-grafts externally fitted with a Z-shaped stents were compared to devices fitted with ringed stents in an in vitro oscillating fatigue machine at 200 cycles per minute and a pressure of 360 mmHg for scheduled durations of up to 1 week. The devices fitted with Z-stents showed a considerably lower endurance limit to buckling compared to the controls. The contact between the apexes of adjacent Z-stents resulted in significant damage to the textile scaffolds and polyester fibers due to the sharp angle of the Z-stents. The ringed stents did not cause any fraying in the textile scaffolds.
Association Between Functional Impairment, Depression, and Extrapyramidal Signs in Neuroleptic-Free Patients With Alzheimer Disease
Authors: Choi Junbae , Myung Woojae , Chung Jae Won , Kang Hyo Shin , Na Duk L. , Kim Seong Yoon , Lee Jae-Hong , Han Seol-Heui , Choi Seong Hye , Kim SangYun , Kim Seonwoo , Carroll Bernard J. , Kim Doh Kwan 
Published: June 2013

Background: Extrapyramidal signs (EPSs) are commonly observed in patients with Alzheimer disease (AD). We report here the base rate of EPS in a large cohort of patients with AD who were not receiving neuroleptic drugs, and the associations of EPS with functional outcomes and depressive symptoms. Methods: In a consortium involving 56 clinics, we recruited 2614 patients with AD. We estimated basic activities of daily living (ADL) and instrumental ADL by the Barthel index and the Seoul-Instrumental Activities of Daily Living (S-IADL) scales, respectively. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). The EPS group was defined by the presence of at least 1 EPS based on a focused neurologic examination. Results: The prevalence of EPS-positive patients was 12%. These had lower Korean version of the Mini-Mental State Examination (K-MMSE) scores than the EPS-negative cases ( P < .001). After controlling for demographic, medical, radiological, genetic, and cognitive (K-MMSE) factors, the proportion of patients with impaired ADL was significantly higher in the EPS group than in the non-EPS group ( P < .001, odds ratio = 1.90, 95% confidence interval, 1.45–2.48, and logistic regression). The S-IADL scores were significantly higher in the EPS group than this in the non-EPS group ( P < .001, regression coefficient = 3.19, and median regression). The GDS-15 scores were higher in the EPS group ( P = .04, regression coefficient = 0.89, and median regression). Conclusion: The presence of EPS in patients with AD who were not receiving neuroleptic drugs was associated with more impaired basic and instrumental ADL functioning and with greater depression symptoms.
Thermal, morphological, and conductivity profile of pyridine/thiophene-based polyesters and their miscible blends
Authors: Kausar Ayesha , Hussain Syed Tajammul 
Published: June 2013

New Schiff-base polyesters were prepared from a dihydroxy monomer ( E) -1-(5-(4-hydroxy-3-chlorobenzylidene)thiocarbamoylaminonaphthyl)-3-(4-hydroxy-3-chlorobenzylidene)thiourea. The processable pyridine or thiophene-based poly(azomethine–ester)s (PAEs) possess high molar mass of 111 × 103–127 × 103 g mol−1. The 10% weight loss (521–527°C) and glass transition temperature (287–291°C) depicted high thermal stability. Polyaniline (PAN) doped with dodecylbenzenesulfonic acid (PAN/DBSA), prepared by in situ doping polymerization, was blended in solution/melt with PAEs. Field emission scanning electron microscopy of melt blended PAEs/PAN/DBSA showed nanolevel homogeneity of microstructure accountable for superior electrical conductivity (1.9–2.8 S cm−1). The miscible nanoblends also exhibited high heat stability ( T10; 500–507°C) and mechanical strength (45.51–48.17 MPa) relative to reported azomethine/PAN-based structures.
Notch-HES1 signaling axis controls hemato-endothelial fate decisions of human embryonic and induced pluripotent stem cells
Authors: Lee Jung Bok , Werbowetski-Ogilvie Tamra E. , Lee Jong-Hee , McIntyre Brendan A. S. , Schnerch Angelique , Hong Seok-Ho , Park In-Hyun , Daley George Q. , Bernstein Irwin D. , Bhatia Mickie 
Published: June 2013

Key PointsNotch signaling controls hematopoiesis of human pluripotent stem cells.
Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study
Authors: Mukonzo Jackson K , Okwera Alphonse , Nakasujja Neoline , Luzze Henry , Sebuwufu Deogratious , Ogwal-Okeng Jasper , Waako Paul , Gustafsson Lars L , Aklillu Eleni 
Published: June 2013

AbstractBackgroundHIV infection, anti-tuberculosis and efavirenz therapy are associated with neuropsychological effects. We evaluated the influence of rifampicin cotreatment, efavirenz pharmacokinetics and pharmacogenetics on neuropsychiatric disorders in Ugandan HIV patients with or without tuberculosis coinfection.Methods197 treatment naïve Ugandan HIV patients, of whom 138 were TB co-infected, enrolled prospectively and received efavirenz based HAART. TB-HIV confected patients received concomitant rifampicin based anti-TB therapy. Genotypes forCYP2B6(*6,*11),CYP3A5(*3,*6,*7), ABCB1 (c.3435C>T and c.4036 A/G rs3842),CYP2A6(*9, *17) andNR1I3rs3003596 T/C were determined. Efavirenz plasma concentrations were serially quantified at 3rd day, 1st, 2nd, 4th, 6th, 8th and 12th weeks during therapy. Efavirenz neuropsychiatric symptoms were evaluated in terms of sleep disorders, hallucinations and cognitive effects at baseline, at two and twelve weeks of efavirenz treatment using a modified Mini Mental State Examination (MMSE) score.ResultsDuring the first twelve weeks of ART, 73.6% of the patients experienced at least one efavirenz related neuropsychiatric symptom. Commonest symptoms experienced were sleep disorders 60.5% (n=124) and hallucination 30.7% (n=63). Neuropsychiatric symptoms during HAART were significantly predicted by efavirenz plasma concentrations consistently. Rifampicin cotreatment reduced plasma efavirenz concentrations significantly only during the first week but not afterwards. There was no significant difference in the incidence of neuropsychiatric symptoms between patients receiving efavirenz with or without rifampicin cotreatment.CYP2B6*6and ABCB1 c.4036 A/G genotype significantly predicted efavirenz concentrations. The tendency ofCYP2B6*6genotype association with higher incidence of having vivid dream (p=0.05), insomnia (p=0.19) and tactile hallucination (p=0.09) was observed mainly at week-2.ConclusionsEfavirenz related neuropsychiatric symptoms are common among Ugandan HIV patients receiving ART and is mainly predicted by higher efavirenz plasma concentrations andCYP2B6genotype but not by rifampicin based anti-TB co-treatment.
Association between psychiatric disorders and iron deficiency anemia among children and adolescents: a nationwide population-based study
Authors: Chen Mu-Hong , Su Tung-Ping , Chen Ying-Sheue , Hsu Ju-Wei , Huang Kai-Lin , Chang Wen-Han , Chen Tzeng-Ji , Bai Ya-Mei 
Published: June 2013

Abstract

Background
A great deal of evidence has shown that iron is an important component in cognitive, sensorimotor, and social-emotional development and functioning, because the development of central nervous system processes is highly dependent on iron-containing enzymes and proteins. Deficiency of iron in early life may increase the risk of psychiatric morbidity.

Methods
Utilizing the National Health Insurance Database from 1996 to 2008, children and adolescents with a diagnosis of IDA were identified and compared with age and gender-matched controls (1:4) in an investigation of the increased risk of psychiatric disorders.

Results
A total of 2957 patients with IDA, with an increased risk of unipolar depressive disorder (OR = 2.34, 95% CI = 1.58 ~ 3.46), bipolar disorder (OR = 5.78, 95% CI = 2.23 ~ 15.05), anxiety disorder (OR = 2.17, 95% CI = 1.49 ~ 3.16), autism spectrum disorder (OR = 3.08, 95% CI = 1.79 ~ 5.28), attention deficit hyperactivity disorder (OR = 1.67, 95% CI = 1.29 ~ 2.17), tic disorder (OR = 1.70, 95% CI = 1.03 ~ 2.78), developmental delay (OR = 2.45, 95% CI = 2.00 ~ 3.00), and mental retardation (OR = 2.70, 95% CI = 2.00 ~ 3.65), were identified. A gender effect was noted, in that only female patients with IDA had an increased OR of bipolar disorder (OR = 5.56, 95% CI = 1.98 ~ 15.70) and tic disorder (OR = 2.95, 95% CI = 1.27 ~ 6.86).

Conclusion
Iron deficiency increased the risk of psychiatric disorders, including mood disorders, autism spectrum disorder, attention deficit hyperactivity disorder, and developmental disorders. Further study is required to clarify the mechanism in the association between IDA and psychiatric disorder.
What is different about medical students interested in non-clinical careers?
Authors: Kim Kyong-Jee , Park Jae-Hyun , Lee Young-Ho , Choi Kyusik 
Published: June 2013

AbstractBackgroundThe proportion of medical school graduates who pursue careers other than full-time clinical practice has increased in some countries as the physician’s role has evolved and diversified with the changing landscape of clinical practice and the advancement of biomedicine. Still, past studies of medical students’ career choices have focused on clinical specialties and little is known about their choice of non-clinical careers. The present study examined backgrounds, motivation and perceptions of medical students who intended non-clinical careers.MethodsA questionnaire was administered to students at six Korean medical schools distributed across all provinces in the nation. The questionnaire comprised 40 items on respondents’ backgrounds, their motivation for and interest in the study of medicine, their perceptions of medical professions, and their career intentions. Data was analyzed using various descriptive and inferential statistics.ResultsIn total, 1,388 students returned the questionnaire (60% response rate), 12.3% of whom intended non-clinical careers (i.e., basic sciences, non-clinical medical fields, and non-medical fields). Those who planned non-clinical careers were comparable with their peers in their motivation for studying medicine and in their views of medical professions, but they were less interested in the study of medicine (P < 0.01). The two groups also differed significantly on their perceptions of what was uninteresting about the study of medicine (P < 0.01). The two groups were comparable in gender and entry-level ratios but their distributions across ages and years of study differed significantly (P < 0.01). A majority of respondents agreed with the statements that “it is necessary for medical school graduates to pursue non-clinical careers” and that “medical schools need to offer programs that provide information on such careers.” Still, our finding indicates that medical school curricula do not address such needs sufficiently.ConclusionsOur study found some differences in backgrounds and perceptions of the study of medicine in medical students interested in non-clinical careers from their peers. Future studies are suggested to enhance our understanding of medical students” choice of non-clinical careers.
Some common fixed point theorems for a family of non-self mappings in cone metric spaces
Authors: Huang Xianjiu , Zhu Chuanxi , Wen Xi , Lalović Ljubica 
Published: June 2013

Abstract
Some common fixed point theorems for a family of non-self mappings defined on a closed subset of a metrically convex cone metric space (over the cone which is not necessarily normal) are obtained which generalize earlier results due to Imdad et al. and Janković et al.

MSC:47H10, 54H25.