bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and patterns of antifolate and chloroquine drug resistance markers in Plasmodium vivax across Pakistan
Authors: Khattak Aamer A , Venkatesan Meera , Khatoon Lubna , Ouattara Amed , Kenefic Leo J , Nadeem Muhammad F , Nighat Farida , Malik Salman A , Plowe Christopher V 
Published: September 2013

Abstract

Background

Plasmodium vivax is the most prevalent malaria species in Pakistan, with a distribution that coincides with Plasmodium falciparum in many parts of the country. Both species are likely exposed to drug pressure from a number of anti-malarials including chloroquine, sulphadoxine-pyrimethamine (SP), and artemisinin combination therapy, yet little is known regarding the effects of drug pressure on parasite genes associated with drug resistance. The aims of this study were to determine the prevalence of polymorphisms in the SP resistance-associated genes pvdhfr, pvdhps and chloroquine resistance-associated gene pvmdr1 in P. vivax isolates collected from across the country.

Methods
In 2011, 801 microscopically confirmed malaria-parasite positive filter paper blood samples were collected at 14 sites representing four provinces and the capital city of Islamabad. Species-specific polymerase chain reaction (PCR) was used to identify human Plasmodium species infection. PCR-positive P. vivax isolates were subjected to sequencing of pvdhfr, pvdhps and pvmdr1 and to real-time PCR analysis to assess pvmdr1 copy number variation.

Results
Of the 801 samples, 536 were determined to be P. vivax, 128 were P. falciparum, 43 were mixed vivax/falciparum infections and 94 were PCR-negative for Plasmodium infection. Of PCR-positive P. vivax samples, 372 were selected for sequence analysis. Seventy-six of the isolates (23%) were double mutant at positions S58R and S117N in pvdhfr. Additionally, two mutations at positions N50I and S93H were observed in 55 (15%) and 24 (7%) of samples, respectively. Three 18 base pair insertion-deletions (indels) were observed in pvdhfr, with two insertions at different nucleotide positions in 36 isolates and deletions in 10. Ninety-two percent of samples contained the pvdhps (S382/A383G/K512/A553/V585) SAKAV wild type haplotype. For pvmdr1, all isolates were wild type at position Y976F and 335 (98%) carried the mutation at codon F1076L. All isolates harboured single copies of the pvmdr1 gene.

Conclusions
The prevalence of mutations associated with SP resistance in P. vivax is low in Pakistan. The high prevalence of P. vivax mutant pvmdr1 codon F1076L indicates that efficacy of chloroquine plus primaquine could be in danger of being compromised, but further studies are required to assess the clinical relevance of this observation. These findings will serve as a baseline for further monitoring of drug-resistant P. vivax malaria in Pakistan.
Inactivated Sendai virus strain Tianjin, a novel genotype of Sendai virus, inhibits growth of murine colon carcinoma through inducing immune responses and apoptosis
Authors: Shi Liying , Chen Jun , Zhong Qiping , Li Mei , Geng Peng , He Jianmin , Han Zhe , Sheng Mingwei , Tang Hua 
Published: September 2013

Abstract

Background
Ultraviolet-inactivated, replication-defective Sendai virus particles (Z strain) have displayed antitumor effect through enhancing the immune responses or inducing apoptosis in a variety of carcinomas. Sendai virus strain Tianjin was isolated from the lungs of marmoset and proved to be a novel genotype of Sendai virus. In this study, we explored the antitumor effect and its mechanism of ultraviolet-inactivated, replication-defective Sendai virus strain Tianjin (UV-Tianjin) in mice bearing CT26 colon carcinoma.

Methods
Three injections of UV-Tianjin were delivered into CT26 tumors growing on the back of BALB/c mice. Tumor size was measured in a blinded manner and survival rate of mice was calculated. In order to make clear antitumor mechanism of UV-Tianjin, the maturation and interleukin-6 (IL-6) release from murine myeloid dendritic cells (DCs) was examined by flow cytometry or ELISA assay after induced by UV-Tianjin and compared with those of live virus. Moreover, real-time RT-PCR and immunohistochemistry was performed to identify whether UV-Tianjin could induce infiltration of DCs, CD4+ and CD8+ T cells into tumors. The TUNEL assay was done to observe the apoptosis of CT26 tumor cells after UV-Tianjin injection.

Results
In animal model, UV-Tianjin could obviously inhibit the growth of CT26 tumors and prolong the survival of the tumor-bearing mice compared with control group (P < 0.01). In vitro murine DCs stimulated by UV-Tianjin underwent dose-dependent maturation, similar to that elicited by live virus. And the secretion amount of IL-6 from DCs induced by UV-Tianjin was a little lower than that released in the presence of live virus. Real-time RT-PCR and immunohistochemistry revealed that UV-Tianjin induced a remarkable infiltration of DCs, CD4+ and CD8+ T cells into tumors. The TUNEL assay showed that the apoptosis index of tumor tissues injected with UV-Tianjin was significantly higher than that of control group (P < 0.01).

Conclusions
Our results have demonstrated that UV-Tianjin alone could inhibit the growth of CT26 tumor in mice through enhancing host antitumor immunity and inducing apoptosis of tumor cells. Therefore, UV-Tianjin shows its prospect as a novel drug for carcinoma therapy.
Multiplicity of solutions for nonlinear impulsive differential equations with Dirichlet boundary conditions
Authors: Zhou Chenxing , Miao Fenghua , Liang Sihua 
Published: September 2013

Abstract
In this paper, we consider the existence of solutions for nonlinear impulsive differential equations with Dirichlet boundary conditions. Infinitely many solutions are obtained by using a version of the symmetric mountain-pass theorem, and this sequence of solutions converge to zero. Some recent results are extended.

MSC:34B37, 35B38.
A time-responsive tool for informing policy making: rapid realist review
Authors: Saul Jessie E , Willis Cameron D , Bitz Jennifer , Best Allan 
Published: September 2013

AbstractBackgroundA realist synthesis attempts to provide policy makers with a transferable theory that suggests a certain program is more or less likely to work in certain respects, for particular subjects, in specific kinds of situations. Yet realist reviews can require considerable and sustained investment over time, which does not always suit the time-sensitive demands of many policy decisions. ‘Rapid Realist Review’ methodology (RRR) has been developed as a tool for applying a realist approach to a knowledge synthesis process in order to produce a product that is useful to policy makers in responding to time-sensitive and/or emerging issues, while preserving the core elements of realist methodology.MethodsUsing examples from completed RRRs, we describe key features of the RRR methodology, the resources required, and the strengths and limitations of the process. All aspects of an RRR are guided by both a local reference group, and a group of content experts. Involvement of knowledge users and external experts ensures both the usability of the review products, as well as their links to current practice.ResultsRRRs have proven useful in providing evidence for and making explicit what is known on a given topic, as well as articulating where knowledge gaps may exist. From the RRRs completed to date, findings broadly adhere to four (often overlapping) classifications: guiding rules for policy-making; knowledge quantification (i.e., the amount of literature available that identifies context, mechanisms, and outcomes for a given topic); understanding tensions/paradoxes in the evidence base; and, reinforcing or refuting beliefs and decisions taken.Conclusions‘Traditional’ realist reviews and RRRs have some key differences, which allow policy makers to apply each type of methodology strategically to maximize its utility within a particular local constellation of history, goals, resources, politics and environment. In particular, the RRR methodology is explicitly designed to engage knowledge users and review stakeholders to define the research questions, and to streamline the review process. In addition, results are presented with a focus on context-specific explanations for what works within a particular set of parameters rather than producing explanations that are potentially transferrable across contexts and populations. For policy makers faced with making difficult decisions in short time frames for which there is sufficient (if limited) published/research and practice-based evidence available, RRR provides a practical, outcomes-focused knowledge synthesis method.
Activation of NF-κB by the RANKL/RANK system up-regulates snail and twist expressions and induces epithelial-to-mesenchymal transition in mammary tumor cell lines
Authors: Tsubaki Masanobu , Komai Makiko , Fujimoto Shin-ichiro , Itoh Tatsuki , Imano Motohiro , Sakamoto Kotaro , Shimaoka Hirotaka , Takeda Tomoya , Ogawa Naoki , Mashimo Kenji , Fujiwara Daiichiro , Mukai Junji , Sakaguchi Katsuhiko , Satou Takao , Nishida Shozo 
Published: September 2013

Abstract

Background
Increased motility and invasiveness of cancer cells are reminiscent of the epithelial-mesenchymal transition (EMT), which occurs during cancer progression and metastasis. Recent studies have indicated the expression of receptor activator of nuclear factor-κB (RANK) in various solid tumors, including breast cancer. Although activation of the RANK ligand (RANKL)/RANK system promotes cell migration, metastasis, and anchorage-independent growth of tumor-initiating cells, it remains to be investigated if RANKL induces EMT in breast cancer cells. In this study, we investigated whether RANKL induces EMT in normal breast mammary epithelial cells and breast cancer cells, and the mechanism underlying such induction.

Methods
Expression levels of vimentin, N-cadherin, E-cadherin, Snail, Slug, and Twist were examined by real-time polymerase chain reaction. Cell migration and invasion were assessed using Boyden chamber and invasion assays, respectively. The effects of RANKL on signal transduction molecules were determined by western blot analyses.

Results
We found that stimulation by RANKL altered the cell morphology to the mesenchymal phenotype in normal breast epithelial and breast cancer cells. In addition, RANKL increased the expression levels of vimentin, N-cadherin, Snail, and Twist and decreased the expression of E-cadherin. We also found that RANKL activated nuclear factor-κB (NF-κB), but not extracellular signal-regulated kinase 1/2, Akt, mammalian target of rapamycin, c-Jun N-terminal kinase, and signal transducer and activator of transcription 3. Moreover, dimethyl fumarate, a NF-κB inhibitor, inhibited RANKL-induced EMT, cell migration, and invasion, and upregulated the expressions of Snail, Twist, vimentin, and N-cadherin.

Conclusions
The results indicate that RANKL induces EMT by activating the NF-κB pathway and enhancing Snail and Twist expression. These findings suggest that the RANKL/RANK system promotes tumor cell migration, invasion, and metastasis via the induction of EMT.
Analysis on genetic diversification and heterosis in autotetraploid rice
Authors: Wu Jin-Wen , Hu Chao-Yue , Shahid Muhammad Qasim , Guo Hai-Bin , Zeng Yu-Xiang , Liu Xiang-Dong , Lu Yong-Gen 
Published: September 2013

Abstract
Polyploidization has played an important role in plant evolution and is a pathway for plants to increase genetic diversification and to get higher heterosis comparing with that of diploid does. This study was undertaken to assess the genetic variation and relationships among 40 autotetraploid rice genotypes and their counterpart diploid cultivars with 99 SSR markers screened from published rice genome. The 99 SSR markers detected polymorphism among autotetraploid genotypes and revealed a total of 291 alleles with an average of 2.949 alleles per locus. Autotetraploid lines showed higher genetic diversity and significant variation in agronomic traits than diploid cultivars. Phylogenetic analysis revealed that most of autotetraploid lines were genetically different from their diploid parents, and inter-subspecific hybrids were prepared on the basis of genetic distance between parents. Inter-subspecific autotetraploid hybrids showed a higher and positive heterobeltiosis and competitive heterosis than diploid hybrids, especially for grain yield. Genetic distance appeared not to predict heterosis in diploid rice for all traits; however, it showed a significant correlation with grain yield, grain length and grain length to width ratio in autotetraploid rice. This extensive research on autotetraploid heterosis and genetic diversity will be useful for the development of autotetraploid rice hybrids.
IL-4 reduces the proangiogenic capacity of macrophages by down-regulating HIF-1α translation
Authors: Dehne Nathalie , Tausendschön Michaela , Essler Silke , Geis Theresa , Schmid Tobias , Brüne Bernhard 
Published: September 2013

ABSTRACTMΦ show a highly versatile phenotype depending on the receiving microenvironmental stimuli. MΦ phenotypes are grouped in three subcategories. One is classically activated MΦ (after stimulation with LPS or IFN-γ), and two are alternatively activated forms, known as wound-healing MΦ (induced by IL-4/IL-13) and regulatory MΦ (induced by IL-10/TGF-β). Besides cytokines, hypoxia defines MΦ functions, as shown for classically activated cells. Yet, little is known about the role of hypoxia and HIF-1 and -2 in wound-healing or regulatory MΦ. HIF target genes (such as ADM), analyzed in alternatively activated MΦ from WT and HIF−/− mice, were regulated predominantly by HIF-1 and consistently showed reduced hypoxic induction in MΦ stimulated with IL-4. To gain mechanistic insights, we analyzed HIF expression in polarized MΦ. Classically activated MΦ are characterized by the induction of HIF-1α but reduction of HIF-2α mRNA and protein, whereas wound-healing MΦ decreased HIF-1α protein expression without altering mRNA levels. Analysis of protein stability and expression after proteasomal inhibition pointed to translational regulation of HIF-1α in wound-healing MΦ. Following angiogenic-sprouting using embryonic stem cells exposed to supernatants of MΦ incubated with IL-4 under hypoxia, shorter sprouts were revealed compared with supernatants of hypoxic MΦ without IL-4. Conclusively, IL-4 reduces HIF-1α translation and thus, its activity in MΦ and concomitantly, attenuates their ability to promote angiogenesis under hypoxic conditions.
Lung-resident memory CD8 T cells (TRM) are indispensable for optimal cross-protection against pulmonary virus infection
Authors: Wu Tao , Hu Yinghong , Lee Young-Tae , Bouchard Keith R , Benechet Alexandre , Khanna Kamal , Cauley Linda S 
Published: September 2013

ABSTRACT
Previous studies have shown that some respiratory virus infections leave local populations of tissue TRM cells in the lungs which disappear as heterosubtypic immunity declines. The location of these TRM cells and their contribution to the protective CTL response have not been clearly defined. Here, fluorescence microscopy is used to show that some CD103+ TRM cells remain embedded in the walls of the large airways long after pulmonary immunization but are absent from systemically primed mice. Viral clearance from the lungs of the locally immunized mice precedes the development of a robust Teff response in the lungs. Whereas large numbers of virus-specific CTLs collect around the bronchial tree during viral clearance, there is little involvement of the remaining lung tissue. Much larger numbers of TEM cells enter the lungs of the systemically immunized animals but do not prevent extensive viral replication or damage to the alveoli. Together, these experiments show that virus-specific antibodies and TRM cells are both required for optimal heterosubtypic immunity, whereas circulating memory CD8 T cells do not substantially alter the course of disease.
Technical Advance: Novel ex vivo culture method for human monocytes uses shear flow to prevent total loss of transendothelial diapedesis function
Authors: Tsubota Yoshiaki , Frey Jeremy M , Raines Elaine W 
Published: September 2013

ABSTRACTMonocyte recruitment to inflammatory sites and their transendothelial migration into tissues are critical to homeostasis and pathogenesis of chronic inflammatory diseases. However, even short-term suspension culture of primary human monocytes leads to phenotypic changes. In this study, we characterize the functional effects of ex vivo monocyte culture on the steps involved in monocyte transendothelial migration. Our data demonstrate that monocyte diapedesis is impaired by as little as 4 h culture, and the locomotion step is subsequently compromised. After 16 h in culture, monocyte diapedesis is irreversibly reduced by ∼90%. However, maintenance of monocytes under conditions mimicking physiological flow (5–7.5 dyn/cm2) is sufficient to reduce diapedesis impairment significantly. Thus, through the application of shear during ex vivo culture of monocytes, our study establishes a novel protocol, allowing functional analyses of monocytes not currently possible under static culture conditions. These data further suggest that monocyte-based therapeutic applications may be measurably improved by alteration of ex vivo conditions before their use in patients.
Triangulation of the map of a G-manifold to its orbit space
Authors: Murayama Mitsutaka , Shiota Masahiro 
Published: September 2013

AbstractLet G be a Lie group, and let M be a smooth proper G-manifold. Let M/G denote the orbit space, and let π : M → M/G be the natural map. It is known that M/G is homeomorphic to a polyhedron. In the present paper we show that there exist a piecewise linear (PL) manifold P, a polyhedron L, and homeomorphisms τ : P → M and σ : M/G → L such that σ o π o τ is PL. This is an application of the theory of subanalytic sets and subanalytic maps of Shiota. If M and the G-action are, moreover, subanalytic, then we can choose τ and σ subanalytic and P and L unique up to PL homeomorphisms.
Structure and content of 400 CT reports in four teaching hospitals using a new, Windows-based software tool
Authors: Heikkinen K. , Löyttyniemi M. , Kormano M. 
Published: September 2013

Purpose: To test a new software tool developed for analysis of radiology reports and to compare CT reports from four different teaching hospitals. Material and Methods: Four hundred CT reports were randomly collected from four Finnish university hospitals. A Windows 3.1-based software tool was developed to make a comparative analysis of the information content of CT reports. The structure of the reports was partly analyzed manually. Results: The new software tool greatly facilitated semiquantitative analysis of the information content of residents' and radiologists' reports. There were some local differences in the length and structure of the reports, the choice of vocabulary and the number of differential diagnoses given, and large differences in the use of an “impression” section. Thorough description of focal lesions was included in less than 50% of the reports from each of the four institutions. Conclusion: The variation in well-structured CT reports indicates considerable geographic differences in radiology reporting, which may reflect the long-term influences of a few teachers. Rational application of the communication standards should improve the quality of written radiology reports. Such standards should be emphasized, particularly in teaching hospitals.
Abnormalities on brain MR images during the course of Familial Haemophagocytic lymphohistocytosis in a child: A case report
Authors: Sundgren P. C. , Geijer B. , Békássy A. N. , Dictor M. 
Published: September 2013

Purpose: To describe and report the neuroradiological findings and clinical features in a patient with familial haemophagocytic lymphohistocytosis (FHL), a rare hereditary immune dysregulation in early childhood characterised by multisystem involvement, including in approximately 30% of cases also the central nervous system (CNS). Material and Methods: Serial brain MR examinations were carried out in a 4.5-year-old boy with FHL, finally complicated with Epstein-Barr virus (EBV)-driven posttransplantation lymphoma. Results: Multiple brain MR examinations before and after contrast enhancement showed discrete perivascular non-enhancing areas of high signal intensity on T2 images, and later also an enhancing lesion in the right caudate nucleus. Conclusion: FHL should be included in the differential diagnosis of patchy white matter abnormalities in young patients. EBV-driven post-transplantation lymphoma, which may present as meningial and/or parenchymal CNS infiltration, is a differential diagnostic problem.
Association between joint bleeds and pettersson scores in severe haemophilia
Authors: Fischer K. , van Hout B. A. , van der Bom J. G. , Grobbee D. E. , van den Berg H. M. 
Published: September 2013

Purpose: To assess and quantify the association of haemophilic arthropathy, measured by the radiological Pettersson score, with the number of joint bleeds suffered by the patient. Material and Methods: In order to quantify the effect of the cumulative number of joint bleeds on the Pettersson score, a study was performed using 295 Pettersson scores obtained in 117 patients with severe haemophilia. The patients were born between 1965 and 1994, and had no history of inhibitors. The number of joint bleeds was determined annually from the entry in the clinic and onwards. The localization of bleeds was not assessed. The patients entered the clinic at a median age of 3.6 years, and received intermediate dose prophylaxis, starting at a median age of 5.3 years. Evaluation of 1643 treatment years showed a mean of 6.8 joint bleeds/year. Pettersson scores were obtained at a mean age of 15.9 years (range 1.7–32.9) and had a median value of 4 points (range 0–50). Results and Conclusion: The Pettersson scores began to rise after the age of 5 years and increased with one point for every 13 joint bleeds (95% confidence interval 11–15). No evidence was found of ‘autonomous’ progression of Pettersson scores, independent of bleeds.
Contrast-enhanced transabdominal ultrasonography in the diagnosis of pancreatic mass lesions
Authors: Takeda K. , Goto H. , Hirooka Y. , Itoh A. , Hashimoto S. , Niwa K. , Hayakawa T. 
Published: September 2013

Purpose: In this study, we evaluated the diagnostic usefulness of contrast-enhanced transabdominal ultrasonography (CE-US) in pancreatic mass lesions that could be detected by US. Material and Methods: CE-US was performed in 37 patients with various pancreatic mass lesions to evaluate the characteristic vascular findings. Results: Pancreatic tubular adenocarcinoma showed negative enhancement pattern in 16 cases and a slight spotty enhancement pattern in 5 cases. Poorly differentiated adenocarcinoma showed slight homogeneous enhancement pattern in 1 case and acinar cell carcinoma was expressed as a heterogeneous enhancement pattern in 3 cases on CE-US. Endocrine cell tumor had a strong homogeneous enhancement pattern in 3 cases, a strong central enhancement in 1 case and a strong peripheral enhancement in 2 cases. Pseudotumorous pancreatitis showed an iso-enhancement pattern in 6 cases. Conclusion: CE-US is useful in evaluating the vascularity of the lesions in various pancreatic mass lesions in real-time images, and may be useful for the differential diagnosis of pancreatic mass lesions.