bluuebunny/crossref_metadata_2025_split huggingface dataset:
The neonatal CNS is not conducive for encephalitogenic Th1 T cells and B cells during experimental autoimmune encephalomyelitis
Authors: Cravens Petra D , Kieseier Bernd C , Hussain Rehana , Herndon Emily , Arellano Benjamine , Ben Li-Hong , Timmons Brenda C , Castro-Rojas Cyd , Hartung Hans-Peter , Hemmer Bernhard , Weber Martin S , Zamvil Scott S , Stüve Olaf 
Published: May 2013

AbstractMultiple sclerosis (MS) is thought to be a CD4+T cell mediated autoimmune demyelinating disease of the central nervous system (CNS) that is rarely diagnosed during infancy. Cellular and molecular mechanisms that confer disease resistance in this age group are unknown. We tested the hypothesis that a differential composition of immune cells within the CNS modulates age-associated susceptibility to CNS autoimmune disease. C57BL/6 mice younger than eight weeks were resistant to experimental autoimmune encephalomyelitis (EAE) following active immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (p) 35–55. Neonates also developed milder EAE after transfer of adult encephalitogenic T cells primed by adult or neonate antigen presenting cells (APC). There was a significant increase in CD45+hematopoietic immune cells and CD45+high side scatter granulocytes in the CNS of adults, but not in neonates. Within the CD45+immune cell compartment of adults, the accumulation of CD4+T cells, Gr-1+and Gr-1-monocytes and CD11c+dendritic cells (DC) was identified. A significantly greater percentage of CD19+B cells in the adult CNS expressed MHC II than neonate CNS B cells. Only in the adult CNS could IFNγ transcripts be detected 10 days post immunization for EAE. IFNγ is highly expressed by adult donor CD4+T cells that are adoptively transferred but not by transferred neonate donor cells. In contrast, IL-17 transcripts could not be detected in adult or neonate CNS in this EAE model, and neither adult nor neonate donor CD4+T cells expressed IL-17 at the time of adoptive transfer.
The design of a new truncated and engineered alpha1-antitrypsin based on theoretical studies: an antiprotease therapeutics for pulmonary diseases
Authors: Pirooznia Nazanin , Hasannia Sadegh , Arab Seyed Shahriar , Lotfi Abbas Sahebghadam , Ghanei Mostafa , Shali Abbas 
Published: May 2013

Abstract
Alpha 1- antitrypsin (α1AT) a 54 kDa glycoprotein is a protease inhibitor. In the absence of α1AT, elastase released by lung macrophages, was not inhibited and lead to elastin breakdown and pulmonary problems such as emphysema or COPD. α1AT has three site of N-glycosylation and a characteristic reactive central loop (RCL). As small-scale medicines are preferred for pulmonary drug delivery, in this study α1ATs (1, 2, 3, 4 and 5) were engineered and shortened from the N-terminal region. In order to investigate the effect of different mutations and the deletion of 46 amino acids theoretical studies were performed. Homology modeling was performed to generate the 3D structure of α1ATs. The 10 ns Molecular Dynamic (MD) simulations were carried out to refine the models. Results from MD and protein docking showed that α1AT2 has the highest binding affinity for neutrophil elastase, provided the basis for the experimental phase in which sequences from the five α1AT constructs were inserted into the expression vector pGAPZα and expressed in the yeast Pichia pastoris. Although, the α1AT2 construct has the highest inhibitory activity even more that the native construct (α1AT5), results indicated the presence of protease inhibitory function of all the proteins' construct against elastase.
Postoperative radiotherapy improves local control and survival in patients with uterine leiomyosarcoma
Authors: Wong Philip , Han Kathy , Sykes Jenna , Catton Charles , Laframboise Stephane , Fyles Anthony , Manchul Lee , Levin Wilfred , Milosevic Michael 
Published: May 2013

Abstract

Background
To examine the role of radiotherapy (RT) in uterine leiomyosarcomas (LMS) and to determine the patient population who may benefit from RT.

Methods
From 1998–2008, 69 patients with primary uterine LMS underwent hysterectomy with or without pelvic radiotherapy to a median dose of 45 Gy. Univariate analysis was performed using the Kaplan-Meier method and cumulative-incidence function, and multivariate analyses using Fine and Gray or Cox proportional hazard models.

Results
Following surgery, 32 out of 69 patients received RT. There was no evidence of any correlation between patient, disease and treatment characteristics and the use of RT. Median follow-up was 57 months. RT was associated with reduced local recurrence (3y LR 19% vs. 39%; Gray’s p = 0.019) and improved overall survival (3y OS 69% vs. 35%; log-rank p = 0.025) on univariate analysis. Multivariate analysis demonstrated that RT reduced LR (HR: 0.28, CI: 0.11-0.69, p = 0.006) and increased OS (HR: 0.44, CI: 0.23-0.85, p = 0.014) independent of other clinical and pathologic factors. Positive surgical margins increased the odds of LR (HR: 5.6, CI: 2.3-13.4, p = 0.00012). Large tumor size and advanced stage (II-IV) were associated with the development of distant metastases and inferior OS.

Conclusions
Postoperative pelvic RT reduces LR and improves OS of patients with uterine LMS.
Identification of novel arthropod vector G protein-coupled receptors
Authors: Nowling Ronald J , Abrudan Jenica L , Shoue Douglas A , Abdul-Wahid Badi’ , Wadsworth Mariha , Stayback Gwen , Collins Frank H , McDowell Mary Ann , Izaguirre Jesús A 
Published: May 2013

Abstract

Background
The control of vector-borne diseases, such as malaria, dengue fever, and typhus fever is often achieved with the use of insecticides. Unfortunately, insecticide resistance is becoming common among different vector species. There are currently no chemical alternatives to these insecticides because new human-safe classes of molecules have yet to be brought to the vector-control market. The identification of novel targets offer opportunities for rational design of new chemistries to control vector populations. One target family, G protein-coupled receptors (GPCRs), has remained relatively under explored in terms of insecticide development.

Methods
A novel classifier, Ensemble*, for vector GPCRs was developed. Ensemble* was validated and compared to existing classifiers using a set of all known GPCRs from Aedes aegypti, Anopheles gambiae, Apis Mellifera, Drosophila melanogaster, Homo sapiens, and Pediculus humanus. Predictions for unidentified sequences from Ae. aegypti, An. gambiae, and Pe. humanus were validated. Quantitative RT-PCR expression analysis was performed on previously-known and newly discovered Ae. aegypti GPCR genes.

Results
We present a new analysis of GPCRs in the genomes of Ae, aegypti, a vector of dengue fever, An. gambiae, a primary vector of Plasmodium falciparum that causes malaria, and Pe. humanus, a vector of epidemic typhus fever, using a novel GPCR classifier, Ensemble*, designed for insect vector species. We identified 30 additional putative GPCRs, 19 of which we validated. Expression of the newly discovered Ae. aegypti GPCR genes was confirmed via quantitative RT-PCR.

Conclusion
A novel GPCR classifier for insect vectors, Ensemble*, was developed and GPCR predictions were validated. Ensemble* and the validation pipeline were applied to the genomes of three insect vectors (Ae. aegypti, An. gambiae, and Pe. humanus), resulting in the identification of 52 GPCRs not previously identified, of which 11 are predicted GPCRs, and 19 are predicted and confirmed GPCRs.
Modelling the geographical distribution of soil-transmitted helminth infections in Bolivia
Authors: Chammartin Frédérique , Scholte Ronaldo GC , Malone John B , Bavia Mara E , Nieto Prixia , Utzinger Jürg , Vounatsou Penelope 
Published: May 2013

Abstract

Background
The prevalence of infection with the three common soil-transmitted helminths (i.e. Ascaris lumbricoides, Trichuris trichiura, and hookworm) in Bolivia is among the highest in Latin America. However, the spatial distribution and burden of soil-transmitted helminthiasis are poorly documented.

Methods
We analysed historical survey data using Bayesian geostatistical models to identify determinants of the distribution of soil-transmitted helminth infections, predict the geographical distribution of infection risk, and assess treatment needs and costs in the frame of preventive chemotherapy. Rigorous geostatistical variable selection identified the most important predictors of A. lumbricoides, T. trichiura, and hookworm transmission.

Results
Results show that precipitation during the wettest quarter above 400 mm favours the distribution of A. lumbricoides. Altitude has a negative effect on T. trichiura. Hookworm is sensitive to temperature during the coldest month. We estimate that 38.0%, 19.3%, and 11.4% of the Bolivian population is infected with A. lumbricoides, T. trichiura, and hookworm, respectively. Assuming independence of the three infections, 48.4% of the population is infected with any soil-transmitted helminth. Empirical-based estimates, according to treatment recommendations by the World Health Organization, suggest a total of 2.9 million annualised treatments for the control of soil-transmitted helminthiasis in Bolivia.

Conclusions
We provide estimates of soil-transmitted helminth infections in Bolivia based on high-resolution spatial prediction and an innovative variable selection approach. However, the scarcity of the data suggests that a national survey is required for more accurate mapping that will govern spatial targeting of soil-transmitted helminthiasis control.
Quantitative medical cost-effectiveness analysis of molecular-targeting cancer drugs in Japan
Authors: Ebara Takeshi , Ohno Tatsuya , Nakano Takashi 
Published: May 2013

Abstract

Background
In Japan, both incidence and mortality rates of cancers have continuously increased and medical costs are growing more rapidly than the overall economy of Japan. However, there is no consensus threshold for cost-effectiveness in medical care, and few studies have investigated cost-effectiveness of medical care in Japan. The present study was to determine the direct costs of molecular-targeting drugs that were recently approved in Japan through simple and quantitative calculations. Thus, we calculated an incremental cost-effectiveness ratio (ICER) and the cost per life-year gained (LYG) by using reported data from randomized clinical trials for various cancers.

Methods
Between 2008 and 2011, we reviewed seven molecular-targeting drugs that were approved for treatment of five cancers in Japan. These drugs included Bevacizumab, sorafenib, sunitinib, temsirolimus, Lapatinib, and panitumumab. Direct cost, ICER, and LYG of the drugs were estimated from the randomized phase III clinical trial data referred to in package leaflets. Effectiveness was defined as the prolongation of both median overall survival (OS) and progression-free survival (PFS). Costs were calculated as those of molecular-targeting drugs. Subsequently, ICER was based on 1-month increases in both OS and PFS periods and 1% increases in OS, and LYG was determined.

Results
Direct costs ranged from ¥724,804 ($9,060) to ¥1,506,628 ($18,833). ICERs of the drugs ranged from ¥724,804 ($9,060) to ¥1,506,628 ($18,833) for a 1-month increase in OS. For each month of PFS, ICERs ranged from ¥372,243 ($4,653) to ¥7,399,877 ($92,498). The costs of Bevacizumab and sorafenib for treatment of HCC per 1% increase in OS were ¥376,657 ($4,708) and ¥313,733 ($3,922), respectively. LYG ranged from ¥8,697,650 ($108,721) to ¥18,079,530 ($225,994).

Conclusions
Some molecular-targeting drugs are not cost-effective. Considering ethical and moral issues, we should establish economic endpoints to approve new drugs in Japan.
Converting non-metallic printed circuit boards waste into a value added product
Authors: Muniyandi Shantha Kumari , Sohaili Johan , Hassan Azman , Mohamad Siti Suhaila 
Published: May 2013

Abstract
The aim of this study was to investigate the feasibility of using nonmetallic printed circuit board (PCB) waste as filler in recycled HDPE (rHDPE) in production of rHDPE/PCB composites. Maleic anhydride modified linear low-density polyethylene (MAPE) was used as compatibilizer. In particular, the effects of nonmetallic PCB and MAPE on mechanical properties of the composites were assessed through tensile, flexural and impact testing. Scanning electron microscope (SEM) was used to study the dispersion of nonmetallic PCB and MAPE in the matrix. Nonmetallic PCB was blended with rHDPE from 0–30 wt% and prepared by counter-rotating twin screw extruder followed by molding into test samples via hot press for analysis. A good balance between stiffness, strength and toughness was achieved for the system containing 30 wt% PCB. Thus, this system was chosen in order to investigate the effect of the compatibilizer on the mechanical properties of the composites. The results indicate that MAPE as a compatiblizer can effectively promote the interfacial adhesion between nonmetallic PCB and rHDPE. The addition of 6 phr MAPE increased the flexural strength, tensile strength and impact strength by 71%, 98% and 44% respectively compared to the uncompatibilized composites.
Biological degradation of catechol in wastewater using the sequencing continuous-inflow reactor (SCR)
Authors: Aghapour Ali Ahmad , Moussavi Gholamreza , Yaghmaeian Kamyar 
Published: May 2013

Abstract
Catechol is used in many industries. It can be removed from wastewater by various methods but biological processes are the most superior and commonly used technology. The SCR is a modified form of SBR used to degrade catechol. The objective of this study was to investigate the performance of SCR for biodegradation and mineralization of catechol under various inlet concentrations (630–1500 mg/L) and hydraulic retention times (HRT) (18–9 h). This study used a bench scale SCR setup to test catechol degradation. The acclimation time of biomass for catechol at degradation at 630 mg/L was 41 d. The SCR operating cycle time was 6 h and the consecutive times taken for aerating, settling and decanting were 4, 1.5 and 0.5 h, respectively. This study investigated the effects of inlet catechol concentration (630–1560 mg/L) and HRT (18–9 h). The average catechol removal efficiencies in steady-state conditions of 630, 930, 12954 and 1559 mg/L of catechol were 98.5%, 98.5%, 98.2% and 96.9% in terms catechol and 97.8%, 97.7%, 96.4% and 94.3% for COD, respectively. SCR with acclimated biomasses could effectively remove the catechol and the corresponding COD from wastewater with concentrations of up to 1560, at the loading rate of 5.38 kg COD/m3.d and at a HRT of up to 13 h. The HRT was determined as an important variable affecting catechol removal from wastewater. Reducing the HRT to below 13 h led to reduced removal of catechol and COD.
Growth differentiation factor-15 and prognosis in acute respiratory distress syndrome: a retrospective cohort study
Authors: Clark Brendan J , Bull Todd M , Benson Alexander B , Stream Amanda R , Macht Madison , Gaydos Jeanette , Meadows Christina , Burnham Ellen L , Moss Marc ,   the ARDS Network Investigators
Published: May 2013

Abstract
Introduction
We sought to determine whether higher levels of the novel biomarker growth differentiation factor-15 (GDF-15) are associated with poor outcomes and the presence of pulmonary vascular dysfunction (PVD) in patients with acute respiratory distress syndrome (ARDS).

Methods
We conducted a retrospective cohort study in patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment (FACT) Trial. Patients enrolled in the FACT Trial who received a pulmonary artery catheter (PAC), had plasma available from the same study day and sufficient hemodynamic data to determine the presence of PVD were included. Logistic regression was used to determine the association between GDF-15 level and 60-day mortality.

Results
Of the 513 patients enrolled in the FACT Trial assigned to receive a PAC, 400 were included in this analysis. Mortality at 60 days was significantly higher in patients whose GDF-15 levels were in the third (28%) or fourth (49%) quartile when compared to patients with GDF-15 levels in the first quartile (12%) (P <0.001). Adjusting for severity of illness measured by APACHE III score, the odds of death for patients with GDF-15 levels in the fourth quartile when compared to the first quartile was 4.26 (95% CI 2.18, 10.92, P <0.001). When added to APACHE III alone for prediction of 60-day mortality, GDF-15 levels increased the area under the receiver operating characteristic curve from 0.72 to 0.77. At an optimal cutoff of 8,103 pg/mL, the sensitivity and specificity of GDF-15 for predicting 60-day mortality were 62% (95% CI 53%, 71%) and 76% (95% CI 71%, 81%), respectively. Levels of GDF-15 were not useful in identifying the presence of PVD, as defined by hemodynamic measurements obtained by a PAC.

Conclusions
In patients with ARDS, higher levels of GDF-15 are significantly associated with poor outcome but not PVD.
The 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsis
Authors: Lorente Leonardo , Martín Mar , Plasencia Fátima , Solé-Violán Jordi , Blanquer José , Labarta Lorenzo , Díaz César , Borreguero-León Juan María , Jiménez Alejandro , Páramo José Antonio , Orbe Josune , Rodríguez José A , Salido Eduardo 
Published: May 2013

Abstract
Introduction
Previous studies have found higher circulating levels of tissue inhibitor of matrix metalloproteinase (TIMP)-1 in nonsurviving septic patients than in surviving septic patients, and an association between the 372 T/C genetic polymorphism of TIMP-1 and the risk of developing certain diseases. However, the relationship between genetic polymorphisms of TIMP-1, circulating TIMP-1 levels and survival in patients with severe sepsis has not been examined, and this was the objective of the study.

Methods
This multicentre, prospective, observational study was carried out in six Spanish ICUs. We determined the 372 T/C genetic polymorphism of TIMP-1 (rs4898), serum levels of TIMP-1, matrix metalloproteinase (MMP)-9, MMP-10, TNFα, IL-10 and plasma plasminogen activator inhibitor-1 (PAI-1). Survival at 30 days from ICU admission was the endpoint assessed. The association between continuous variables was carried out using Spearman's rank correlation coefficient or Spearman's rho coefficient. Multivariate logistic regression analysis was applied to determine the association between the 372 T/C genetic polymorphism and survival 30 days from ICU admission.

Results
Of 275 patients with severe sepsis, 80 had genotype CC, 55 had genotype CT and 140 had genotype TT of the 372 T/C genetic polymorphism of TIMP-1. Patients with the T allele showed higher serum levels of TIMP-1 than patients without the T allele (P = 0.004). Multiple logistic regression analysis showed that the T allele was associated with higher mortality at 30 days (odds ratio = 2.08; 95% confidence interval = 1.06 to 4.09; P = 0.03). Survival analysis showed that patients with the T allele presented lower 30-day survival than patients without the T allele (χ2 = 5.77; P = 0.016). We found an association between TIMP-1 levels and levels of MMP-9 (ρ = -0.19; P = 0.002), MMP-10 (ρ = 0.55; P <0.001), TNFα (ρ = 0.56; P <0.001), IL-10 (ρ = 0.48; P <0.001) and PAI-1 (ρ = 0.49; P <0.001).

Conclusion
The novel findings of our study are that septic patients with the T allele in the 372 T/C genetic polymorphism of TIMP-1 showed higher serum TIMP-1 levels and lower survival rate. The determination of the 372 T/C genetic polymorphism of TIMP-1 thus has prognostic implications and could help in the selection of patients who may benefit from modulation of the MMP/TIMP balance.
Cognitive dysfunctions in recreational and dependent cocaine users: role of attention-deficit hyperactivity disorder, craving and early age at onset
Authors: Vonmoos Matthias , Hulka Lea M. , Preller Katrin H. , Jenni Daniela , Baumgartner Markus R. , Stohler Rudolf , Bolla Karen I. , Quednow Boris B. 
Published: May 2013

BackgroundDependent cocaine users consistently display cognitive deficits but cognitive performance of recreational cocaine users has rarely been investigated.AimsTo examine whether cognitive performance is impaired in relatively pure recreational and dependent cocaine users.MethodThe cognitive performance of recreational (n = 68) and dependent cocaine users (n = 30) was compared with the performance of stimulant-naive controls (n = 68) employing an extensive neuropsychological test battery. Moreover, the impact of attention-deficit hyperactivity disorder (ADHD) symptoms, craving and early age at onset was analysed.ResultsDependent cocaine users display broad cognitive impairments in the domains of attention, working memory, declarative memory and executive functions. The performance of recreational cocaine users in all four domains was intermediate between that of controls and dependent users and they displayed significant deficits foremost in the domains of attention and working memory. In addition, ADHD symptoms, craving and age at onset were important modulators of cognitive function in cocaine users.ConclusionsCognitive deficits occur at a recreational and non-dependent level of cocaine use. Cocaine use and ADHD seem to have mutually aggravating effects on cognitive impairment.
Risk of bipolar disorder and schizophrenia in relatives of people with attention-deficit hyperactivity disorder
Authors: Larsson Henrik , Rydén Eleonore , Boman Marcus , Långström Niklas , Lichtenstein Paul , Landén Mikael 
Published: May 2013

BackgroundAttention-deficit hyperactivity disorder (ADHD) is associated with bipolar disorder and schizophrenia, and it has been suggested that combined bipolar disorder and ADHD is aetiologically distinct from the pure disorders.AimsTo clarify whether ADHD shares genetic and environmental factors with bipolar disorder and schizophrenia.MethodBy linking longitudinal Swedish national registers, we identified 61 187 persons with ADHD (the proband group) and their first- and second-degree relatives, and matched them with a control group of people without ADHD and their corresponding relatives. Conditional logistic regression was used to determine the risks of bipolar disorder and schizophrenia in the relatives of the two groups.ResultsFirst-degree relatives of the ADHD proband group were at increased risk of both bipolar disorder (odds ratio (OR) = 1.84−2.54 for parents, offspring and full siblings) and schizophrenia (OR = 1.71−2.22 for parents, offspring and full siblings). The risks of bipolar disorder and schizophrenia among second-degree relatives were substantially lower than among full siblings.ConclusionsThese findings suggest that the co-occurrence of ADHD and bipolar disorder as well as ADHD and schizophrenia is due to shared genetic factors, rather than representing completely aetiologically distinct subsyndromes.