bluuebunny/crossref_metadata_2025_split huggingface dataset:
Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro
Authors: Sun Ting , Zhang Zizhu , Li Bin , Chen Guilin , Xie Xueshun , Wei Yongxin , Wu Jie , Zhou Youxin , Du Ziwei 
Published: August 2013

Abstract

Background
Glioma stem cells in the quiescent state are resistant to clinical radiation therapy. An almost inevitable glioma recurrence is due to the persistence of these cells. The high linear energy transfer associated with boron neutron capture therapy (BNCT) could kill quiescent and proliferative cells.

Methods
The present study aimed to evaluate the effects of BNCT on glioma stem/progenitor cells in vitro. The damage induced by BNCT was assessed using cell cycle progression, apoptotic cell ratio and apoptosis-associated proteins expression.

Results
The surviving fraction and cell viability of glioma stem/progenitor cells were decreased compared with differentiated glioma cells using the same boronophenylalanine pretreatment and the same dose of neutron flux. BNCT induced cell cycle arrest in the G2/M phase and cell apoptosis via the mitochondrial pathway, with changes in the expression of associated proteins.

Conclusions
Glioma stem/progenitor cells, which are resistant to current clinical radiotherapy, could be effectively killed by BNCT in vitro via cell cycle arrest and apoptosis using a prolonged neutron irradiation, although radiosensitivity of glioma stem/progenitor cells was decreased compared with differentiated glioma cells when using the same dose of thermal neutron exposure and boronophenylalanine pretreatment. Thus, BNCT could offer an appreciable therapeutic advantage to prevent tumor recurrence, and may become a promising treatment in recurrent glioma.
Fibrosis: a key feature of Fabry disease with potential therapeutic implications
Authors: Weidemann Frank , Sanchez-Niño Maria D , Politei Juan , Oliveira João-Paulo , Wanner Christoph , Warnock David G , Ortiz Alberto 
Published: August 2013

Abstract
Fabry disease is a rare X-linked hereditary disease caused by mutations in the AGAL gene encoding the lysosomal enzyme alpha-galactosidase A. Enzyme replacement therapy (ERT) is the current cornerstone of Fabry disease management. Involvement of kidney, heart and the central nervous system shortens life span, and fibrosis of these organs is a hallmark of the disease. Fibrosis was initially thought to result from tissue ischemia secondary to endothelial accumulation of glycosphingolipids in the microvasculature. However, despite ready clearance of endothelial deposits, ERT is less effective in patients who have already developed fibrosis. Several potential explanations of this clinical observation may impact on the future management of Fabry disease. Alternative molecular pathways linking glycosphingolipids and fibrosis may be operative; tissue injury may recruit secondary molecular mediators of fibrosis that are unresponsive to ERT, or fibrosis may represent irreversible tissue injury that limits the therapeutic response to ERT. We provide an overview of Fabry disease, with a focus on the assessment of fibrosis, the clinical consequences of fibrosis, and recent advances in understanding the cellular and molecular mechanisms of fibrosis that may suggest novel therapeutic approaches to Fabry disease.
Monomeric Ti(IV) homopiperazine complexes and their exploitation for the ring opening polymerisation of rac-lactide
Authors: Hancock Stuart L , Mahon Mary F , Jones Matthew D 
Published: August 2013

Abstract

Background
The area of biodegradable/sustainable polymers is one of increasing importance in the 21st Century due to their positive environmental characteristics. Lewis acidic metal centres are currently one of the most popular choices for the initiator for the polymerisation. Thus, in this paper we report the synthesis and characterisation of a series of monometallic homopiperazine Ti(IV) complexes where we have systematically varied the sterics of the phenol moieties.

Results
When the ortho substituent of the ligand is either a Me, tBu or amyl then the β-cis isomer is isolated exclusively in the solid-state. Nevertheless, in solution multiple isomers are clearly observed from analysis of the NMR spectra. However, when the ortho substituent is an H-atom then the trans-isomer is formed in the solid-state and solely in solution. The complexes have been screened for the polymerisation of rac-lactide in solution and under the industrially preferred melt conditions. Narrow molecular weight material (PDI 1.07 – 1.23) is formed under melt conditions with controlled molecular weights.

Conclusions
Six new Ti(IV) complexes are presented which are highly active for the polymerisation. In all cases atactic polymer is prepared with predictable molecular weight control. This shows the potential applicability of Ti(IV) to initiate the polymerisations.
Sero-prevalence and factors associated with Toxoplasma gondii infection among pregnant women attending antenatal care in Mwanza, Tanzania
Authors: Mwambe Berno , Mshana Stephen E , Kidenya Benson R , Massinde Anthony N , Mazigo Humphrey D , Michael Denna , Majinge Charles , Groß Uwe 
Published: August 2013

Abstract

Background
Serological screening of pregnant women for Toxoplasma gondii-specific antibodies is not practiced as an antenatal care in Tanzania; and there is a limited data about sero-prevalence of T. gondii infection in developing countries. We therefore conducted this study to determine the sero-prevalence and factors associated with T. gondii infection among pregnant women attending antenatal care clinics in Mwanza, Tanzania.

Methods
Between 1st November 2012 and 31st May 2013 a total of 350 pregnant women attending antenatal care clinics in Mwanza were enrolled and screened for IgG and IgM antibodies against T. gondii using the ELISA technique.

Results
Of 350 pregnant women, 108 (30.9%) were sero-positive for T. gondii-specific antibodies. The risk of contracting T. gondii infection increases by 7% with each yearly increase in a woman’s age (OR=1.07, 95% CI: 1.02 - 1.11, p=0.002). The sero-positivity rate of T. gondii- specific antibodies was higher among pregnant women from the urban than those from rural communities (41.5% versus 22.0%); [OR=2.2, 95% CI; 1.4 - 3.7, p=0.001]. Likewise employed/business women were more likely to get T. gondii infection than peasants (40.0% versus 25.9%) [OR=1.9, 95% CI: 1.2 - 3.0, p=0.006].

Conclusions
Sero-prevalence of T. gondii- specific antibodies is high among pregnant women in Mwanza with a significant proportion of women at risk of contracting primary T. gondii infections. Screening of T. gondii infections during antenatal care should be considered in Tanzania as the main strategy to minimize congenital toxoplasmosis.
Analysis of the genetic diversity of the nematode parasite Baylisascaris schroederi from wild giant pandas in different mountain ranges in China
Authors: Zhou Xuan , Xie Yue , Zhang Zhi-he , Wang Cheng-dong , Sun Yun , Gu Xiao-bin , Wang Shu-xian , Peng Xue-rong , Yang Guang-you 
Published: August 2013

Abstract

Background

Baylisascaris schroederi is one of the most common nematodes of the giant panda, and can cause severe baylisascarosis in both wild and captive giant pandas. Previous studies of the giant pandas indicated that this population is genetically distinct, implying the presence of a new subspecies. Based on the co-evolution between the parasite and the host, the aim of this study was to investigate the genetic differentiation in the B. schroederi population collected from giant pandas inhabiting different mountain ranges, and further to identify whether the evolution of this parasite correlates with the evolution of giant pandas.

Methods
In this study, 48 B. schroederi were collected from 28 wild giant pandas inhabiting the Qinling, Minshan and Qionglai mountain ranges in China. The complete sequence of the mitochondrial cytochrome b (mtCytb) gene was amplified by PCR, and the corresponding population genetic diversity of the three mountain populations was determined. In addition, we discussed the evolutionary relationship between B. schroederi and its host giant panda.

Results
For the DNA dataset, insignificant Fst values and a significant, high level of gene flow were detected among the three mountain populations of B. schroederi, and high genetic variation within populations and a low genetic distance were observed. Both phylogenetic analyses and network mapping of the 16 haplotypes revealed a dispersed pattern and an absence of branches strictly corresponding to the three mountain range sampling sites. Neutrality tests and mismatch analysis indicated that B. schroederi experienced a population expansion in the past.

Conclusions
Taken together, the dispersed haplotype map, extremely high gene flow among the three populations of B. schroederi, low genetic structure and rapid evolutionary rate suggest that the B. schroederi populations did not follow a pattern of isolation by distance, indicating the existence of physical connections before these populations became geographically separated.
Dose and type of crystalloid fluid therapy in adult hospitalized patients
Authors: Smorenberg Annemieke , Ince Can , Groeneveld AB Johan 
Published: August 2013

AbstractObjectiveIn this narrative review, an overview is given of the pros and cons of various crystalloid fluids used for infusion during initial resuscitation or maintenance phases in adult hospitalized patients. Special emphasis is given on dose, composition of fluids, presence of buffers (in balanced solutions) and electrolytes, according to recent literature. We also review the use of hypertonic solutions.MethodsWe extracted relevant clinical literature in English specifically examining patient-oriented outcomes related to fluid volume and type.ResultsA restrictive fluid therapy prevents complications seen with liberal, large-volume therapy, even though restrictive fluid loading with crystalloids may not demonstrate large hemodynamic effects in surgical or septic patients. Hypertonic solutions may serve the purpose of small volume resuscitation but carry the disadvantage of hypernatremia. Hypotonic solutions are contraindicated in (impending) cerebral edema, whereas hypertonic solutions are probably more helpful in ameliorating than in preventing this condition and improving outcome. Balanced solutions offer a better approach for plasma composition than unbalanced ones, and the evidence for benefits in patient morbidity and mortality is increasing, particularly by helping to prevent acute kidney injury.ConclusionsIsotonic and hypertonic crystalloid fluids are the fluids of choice for resuscitation from hypovolemia and shock. The evidence that balanced solutions are superior to unbalanced ones is increasing. Hypertonic saline is effective in mannitol-refractory intracranial hypertension, whereas hypotonic solutions are contraindicated in this condition.
Impulsivity, anxiety, and alcohol misuse in bipolar disorder comorbid with eating disorders
Authors: Jen Andrew , Saunders Erika FH , Ornstein Rollyn M , Kamali Masoud , McInnis Melvin G 
Published: August 2013

Abstract

Background
Eating disorders (ED) are noted to occur with bipolar disorder (BD), but relationships between additional comorbidities, clinical correlates, and personality factors common to both remain largely unknown.

Methods
Using data from the Prechter Longitudinal Study of Bipolar Disorder, we measured the prevalence and demographic factors of comorbid ED with BD, presence of additional comorbidity of anxiety and substance use disorders, psychosis, suicide attempts, mixed symptoms, childhood abuse, impact of NEO-Personality Inventory (NEO-PI) personality factors, and mood outcome in 354 patients with BD. We analyzed the prevalence of ED using both broad and narrow criteria.

Results and discussion
ED was more common in the Prechter BD sample than the general population, with the majority of those with ED being female. Anxiety disorders, alcohol abuse/dependence, and NEO-PI N5 impulsiveness were independently associated with ED in a multivariable linear regression analysis. BD age at onset was earlier in the ED group than that in the non-ED group and was earlier than the average onset of ED. Anxiety occurred before ED and alcohol use disorders after both BD and ED. Childhood trauma was associated with ED. Impulsivity and anxiety associated with BD may fuel ED and put patients at risk for other impulsivity-related disorders such as alcohol use disorders. ED was associated with more severe and variable moods and more frequent depression. Patients with BD should be regularly screened for ED, anxiety disorders, and alcohol use disorders, and comorbidity should be promptly addressed.
IFN-γ-rich environment programs dendritic cells toward silencing of cytotoxic immune responses
Authors: Švajger Urban , Obermajer Nataša , Jeras Matjaž 
Published: August 2013

ABSTRACTLately, there is increasing evidence that emphasizes the regulatory functions of IFN-γ, which serve as negative-feedback mechanisms after, e.g., pathogen clearance, to prevent unnecessary tissue destruction. Inflammatory processes involving Th1 and cytotoxic responses are characterized by high, local IFN-γ concentrations, followed by resolution and immune silencing. Although this is a well-known course of events, extensive attempts to address potential differential effects of IFN-γ in the manner of its availability (quantitatively) in the environment do not exist. We demonstrate that high doses of IFN-γ do not induce DC maturation and activation but instead, induce specific regulatory characteristics in DCs. Considering their phenotype, high doses of IFN-γ extensively induce the expression of ILT-4 and HLA-G inhibitory molecules. Interestingly, the well-known priming effect of IFN-γ for IL-12p70 production is lost at these conditions, and the DC cytokine profile is switched toward an increased IL-10/IL-12p70 ratio upon subsequent stimulation with CD40L. Furthermore, such DCs are capable of silencing cellular immune responses and activation of cytotoxic CD8+ T lymphocytes, resulting in reduced cell proliferation and down-regulation of granzyme B expression. Additionally, we find that in this manner, immune regulation mediated by IFN-γ is not mainly a result of increased enzymatic activity of IDO in DCs but rather, a result of HLA-G signaling, which can be reversed by blocking mAb. Altogether, our results identify a novel mechanism by which a Th1-like environment programs the functional status of DCs to silence ongoing cytotoxic responses to prevent unwanted tissue destruction and inflammation.
DNA Methylation Signatures for Prediction of Biochemical Recurrence After Radical Prostatectomy of Clinically Localized Prostate Cancer
Authors: Haldrup Christa , Mundbjerg Kamilla , Vestergaard Else Marie , Lamy Philippe , Wild Peter , Schulz Wolfgang A. , Arsov Christian , Visakorpi Tapio , Borre Michael , Høyer Søren , Ørntoft Torben F. , Sørensen Karina D. 
Published: August 2013

Purpose Diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, causing overtreatment of indolent PC and risk of delayed treatment of aggressive PC. Here, we identify six novel candidate DNA methylation markers for PC with promising diagnostic and prognostic potential. Methods Microarray-based screening and bisulfite sequencing of 20 nonmalignant and 29 PC tissue specimens were used to identify new candidate DNA hypermethylation markers for PC. Diagnostic and prognostic potential was evaluated in 35 nonmalignant prostate tissue samples, 293 radical prostatectomy (RP) samples (cohort 1, training), and 114 malignant RP samples (cohort 2, validation) collected in Denmark, Switzerland, Germany, and Finland. Sensitivity and specificity for PC were evaluated by receiver operating characteristic analyses. Correlations between DNA methylation levels and biochemical recurrence were assessed using log-rank tests and univariate and multivariate Cox regression analyses. Results Hypermethylation of AOX1, C1orf114, GAS6, HAPLN3, KLF8, and MOB3B was highly cancer specific (area under the curve, 0.89 to 0.98). Furthermore, high C1orf114 methylation was significantly (P < .05) associated with biochemical recurrence in multivariate analysis in cohort 1 (hazard ratio [HR], 3.10; 95% CI, 1.89 to 5.09) and was successfully validated in cohort 2 (HR, 3.27; 95% CI, 1.17 to 9.12). Moreover, a significant (P < .05) three-gene prognostic methylation signature (AOX1/C1orf114/HAPLN3), classifying patients into low- and high-methylation subgroups, was trained in cohort 1 (HR, 1.91; 95% CI, 1.26 to 2.90) and validated in cohort 2 (HR, 2.33; 95% CI, 1.31 to 4.13). Conclusion We identified six novel candidate DNA methylation markers for PC. C1orf114 hypermethylation and a three-gene methylation signature were independent predictors of time to biochemical recurrence after RP in two PC patient cohorts.
Tamoxifen and Risk of Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers
Authors: Phillips Kelly-Anne , Milne Roger L. , Rookus Matti A. , Daly Mary B. , Antoniou Antonis C. , Peock Susan , Frost Debra , Easton Douglas F. , Ellis Steve , Friedlander Michael L. , Buys Saundra S. , Andrieu Nadine , Noguès Catherine , Stoppa-Lyonnet Dominique , Bonadona Valérie , Pujol Pascal , McLachlan Sue Anne , John Esther M. , Hooning Maartje J. , Seynaeve Caroline , Tollenaar Rob A.E.M. , Goldgar David E. , Terry Mary Beth , Caldes Trinidad , Weideman Prue C. , Andrulis Irene L. , Singer Christian F. , Birch Kate , Simard Jacques , Southey Melissa C. , Olsson Håkan L. , Jakubowska Anna , Olah Edith , Gerdes Anne-Marie , Foretova Lenka , Hopper John L. 
Published: August 2013

Purpose To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers. Methods Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated using Cox regression, adjusting for year and age of diagnosis, country, and bilateral oophorectomy and censoring at contralateral mastectomy, death, or loss to follow-up. Results Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC diagnosis. There were 520 CBCs over 20,104 person-years of observation. The adjusted HR estimates were 0.38 (95% CI, 0.27 to 0.55) and 0.33 (95% CI, 0.22 to 0.50) for BRCA1 and BRCA2 mutation carriers, respectively. After left truncating at recruitment to the cohort, adjusted HR estimates were 0.58 (95% CI, 0.29 to 1.13) and 0.48 (95% CI, 0.22 to 1.05) based on 657 BRCA1 and 426 BRCA2 mutation carriers with 100 CBCs over 4,392 person-years of prospective follow-up. HRs did not differ by estrogen receptor status of the first BC (missing for 56% of cases). Conclusion This study provides evidence that tamoxifen use is associated with a reduction in CBC risk for BRCA1 and BRCA2 mutation carriers. Further follow-up of these cohorts will provide increased statistical power for future prospective analyses.
Apatinib for Chemotherapy-Refractory Advanced Metastatic Gastric Cancer: Results From a Randomized, Placebo-Controlled, Parallel-Arm, Phase II Trial
Authors: Li Jin , Qin Shukui , Xu Jianming , Guo Weijian , Xiong Jianping , Bai Yuxian , Sun Guoping , Yang Yan , Wang Liwei , Xu Nong , Cheng Ying , Wang Zhehai , Zheng Leizhen , Tao Min , Zhu Xiaodong , Ji Dongmei , Liu Xin , Yu Hao 
Published: August 2013

Purpose Patients with metastatic gastric cancer (mGC) who do not respond to or who experience progression with second-line chemotherapy have no treatment options that clearly confer a survival benefit. This trial investigated the safety and efficacy of apatinib, an inhibitor of vascular endothelial growth factor receptor, as a treatment option for heavily pretreated patients with mGC. Patients and Methods Patients who experienced treatment failure with at least two chemotherapeutic regimens were randomly assigned to receive placebo (group A), apatinib 850 mg once daily (group B), or apatinib 425 mg twice daily (group C). Results We enrolled 144 patients onto this study. In groups A, B, and C, the median overall survival (OS) times were 2.50 months (95% CI, 1.87 to 3.70 months), 4.83 months (95% CI, 4.03 to 5.97 months), and 4.27 months (95% CI, 3.83 to 4.77 months), respectively, and the median progression-free survival (PFS) times were 1.40 months (95% CI, 1.20 to 1.83 months), 3.67 months (95% CI, 2.17 to 6.80 months), and 3.20 months (95% CI, 2.37 to 4.53 months), respectively. There were statistically significant differences between the apatinib and placebo groups for both PFS (P < .001) and OS (P < .001 and P = .0017). Nine patients had a partial response (three patients in group B and six patients in group C). Toxicities were tolerable or could be clinically managed. The most common grade 3 to 4 adverse events were hand-foot syndrome and hypertension. Hematologic toxicities were moderate, and grade 3 to 4 hematologic toxicities were rare. Conclusion Apatinib showed improved PFS and OS in heavily pretreated patients with mGC who had experienced treatment failure with two or more chemotherapy regimens.
Adiposity and Insulin Resistance in Humans: The Role of the Different Tissue and Cellular Lipid Depots
Authors: Hocking Samantha , Samocha-Bonet Dorit , Milner Kerry-Lee , Greenfield Jerry R. , Chisholm Donald J. 
Published: August 2013

AbstractHuman adiposity has long been associated with insulin resistance and increased cardiovascular risk, and abdominal adiposity is considered particularly adverse. Intra-abdominal fat is associated with insulin resistance, possibly mediated by greater lipolytic activity, lower adiponectin levels, resistance to leptin, and increased inflammatory cytokines, although the latter contribution is less clear. Liver lipid is also closely associated with, and likely to be an important contributor to, insulin resistance, but it may also be in part the consequence of the lipogenic pathway of insulin action being up-regulated by hyperinsulinemia and unimpaired signaling. Again, intramyocellular triglyceride is associated with muscle insulin resistance, but anomalies include higher intramyocellular triglyceride in insulin-sensitive athletes and women (vs men). Such issues could be explained if the “culprits” were active lipid moieties such as diacylglycerol and ceramide species, dependent more on lipid metabolism and partitioning than triglyceride amount.Subcutaneous fat, especially gluteofemoral, appears metabolically protective, illustrated by insulin resistance and dyslipidemia in patients with lipodystrophy. However, some studies suggest that deep sc abdominal fat may have adverse properties.Pericardial and perivascular fat relate to atheromatous disease, but not clearly to insulin resistance.There has been recent interest in recognizable brown adipose tissue in adult humans and its possible augmentation by a hormone, irisin, from exercising muscle. Brown adipose tissue is metabolically active, oxidizes fatty acids, and generates heat but, because of its small and variable quantities, its metabolic importance in humans under usual living conditions is still unclear.Further understanding of specific roles of different lipid depots may help new approaches to control obesity and its metabolic sequelae.