bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda
Authors: Prasher Bhavana , Negi Sapna , Aggarwal Shilpi , Mandal Amit K , Sethi Tav P , Deshmukh Shailaja R , Purohit Sudha G , Sengupta Shantanu , Khanna Sangeeta , Mohammad Farhan , Garg Gaurav , Brahmachari Samir K ,   Indian Genome Variation Consortium, Mukerji Mitali 
Published: September 2008

Abstract

Background
Ayurveda is an ancient system of personalized medicine documented and practiced in India since 1500 B.C. According to this system an individual's basic constitution to a large extent determines predisposition and prognosis to diseases as well as therapy and life-style regime. Ayurveda describes seven broad constitution types (Prakriti s) each with a varying degree of predisposition to different diseases. Amongst these, three most contrasting types, Vata, Pitta, Kapha, are the most vulnerable to diseases. In the realm of modern predictive medicine, efforts are being directed towards capturing disease phenotypes with greater precision for successful identification of markers for prospective disease conditions. In this study, we explore whether the different constitution types as described in Ayurveda has molecular correlates.

Methods
Normal individuals of the three most contrasting constitutional types were identified following phenotyping criteria described in Ayurveda in Indian population of Indo-European origin. The peripheral blood samples of these individuals were analysed for genome wide expression levels, biochemical and hematological parameters. Gene Ontology (GO) and pathway based analysis was carried out on differentially expressed genes to explore if there were significant enrichments of functional categories among Prakriti types.

Results
Individuals from the three most contrasting constitutional types exhibit striking differences with respect to biochemical and hematological parameters and at genome wide expression levels. Biochemical profiles like liver function tests, lipid profiles, and hematological parameters like haemoglobin exhibited differences between Prakriti types. Functional categories of genes showing differential expression among Prakriti types were significantly enriched in core biological processes like transport, regulation of cyclin dependent protein kinase activity, immune response and regulation of blood coagulation. A significant enrichment of housekeeping, disease related and hub genes were observed in these extreme constitution types.

Conclusion
Ayurveda based method of phenotypic classification of extreme constitutional types allows us to uncover genes that may contribute to system level differences in normal individuals which could lead to differential disease predisposition. This is a first attempt towards unraveling the clinical phenotyping principle of a traditional system of medicine in terms of modern biology. An integration of Ayurveda with genomics holds potential and promise for future predictive medicine.
The role of the humoral immune response in the molecular evolution of the envelope C2, V3 and C3 regions in chronically HIV-2 infected patients
Authors: Borrego Pedro , Marcelino José Maria , Rocha Cheila , Doroana Manuela , Antunes Francisco , Maltez Fernando , Gomes Perpétua , Novo Carlos , Barroso Helena , Taveira Nuno 
Published: September 2008

AbstractBackgroundThis study was designed to investigate, for the first time, the short-term molecular evolution of the HIV-2 C2, V3 and C3 envelope regions and its association with the immune response. Clonal sequences of theenvC2V3C3 region were obtained from a cohort of eighteen HIV-2 chronically infected patients followed prospectively during 2–4 years. Genetic diversity, divergence, positive selection and glycosylation in the C2V3C3 region were analysed as a function of the number of CD4+ T cells and the anti-C2V3C3 IgG and IgA antibody reactivityResultsThe mean intra-host nucleotide diversity was 2.1% (SD, 1.1%), increasing along the course of infection in most patients. Diversity at the amino acid level was significantly lower for the V3 region and higher for the C2 region. The average divergence rate was 0.014 substitutions/site/year, which is similar to that reported in chronic HIV-1 infection. The number and position of positively selected sites was highly variable, except for codons 267 and 270 in C2 that were under strong and persistent positive selection in most patients. N-glycosylation sites located in C2 and V3 were conserved in all patients along the course of infection. Intra-host variation of C2V3C3-specific IgG response over time was inversely associated with the variation in nucleotide and amino acid diversity of the C2V3C3 region. Variation of the C2V3C3-specific IgA response was inversely associated with variation in the number of N-glycosylation sites.ConclusionThe evolutionary dynamics of HIV-2 envelope during chronic aviremic infection is similar to HIV-1 implying that the virus should be actively replicating in cellular compartments. Convergent evolution of N-glycosylation in C2 and V3, and the limited diversification of V3, indicates that there are important functional constraints to the potential diversity of the HIV-2 envelope. C2V3C3-specific IgG antibodies are effective at reducing viral population size limiting the number of virus escape mutants. The C3 region seems to be a target for IgA antibodies and increasing N-linked glycosylation may prevent HIV-2 envelope recognition by these antibodies. Our results provide new insights into the biology of HIV-2 and its relation with the human host and may have important implications for vaccine design.
Surgery vs. radiotherapy in localized prostate cancer. Which is best?
Authors: Welz Stefan , Nyazi Maximilian , Belka Claus , Ganswindt Ute 
Published: September 2008

Abstract
Surgery and radiotherapy are currently accepted alternatives for the treatment of localized prostate cancer. In the absence of relevant randomized trials no decision regarding the superiority of any of the given approaches can be made. Up to now several cohort-based approaches indicate similar outcomes for both treatments. Based on a new population based approach, Merglen and co-workers recently concluded that surgery would offer the best chance of long-term control in terms of 10-year survival for T1–T3 prostate cancer patients. Unfortunately the strength of this trial is limited by several shortcomings. Most importantly, issues of radiation dosage have not been taken into account. In addition, several relevant parameters including Gleason score and PSA are not well balanced between the arms and the assignment to arbitrary risk groups does not reflect the real biological behaviour. Thus, the data provided do not support the strong conclusion issued by the authors. Based on the data available, surgery and radiotherapy still have to be considered as equally effective.
The GLAaS algorithm for portal dosimetry and quality assurance of RapidArc, an intensity modulated rotational therapy
Authors: Nicolini Giorgia , Vanetti Eugenio , Clivio Alessandro , Fogliata Antonella , Korreman Stine , Bocanek Jiri , Cozzi Luca 
Published: September 2008

Abstract

Background
To expand and test the dosimetric procedure, known as GLAaS, for amorphous silicon detectors to the RapidArc intensity modulated arc delivery with Varian infrastructures and to test the RapidArc dosimetric reliability between calculation and delivery.

Methods
The GLAaS algorithm was applied and tested on a set of RapidArc fields at both low (6 MV) and high (18 MV) beam energies with a PV-aS1000 detector. Pilot tests for short arcs were performed on a 6 MV beam associated to a PV-aS500. RapidArc is a novel planning and delivery method in the category of intensity modulated arc therapies aiming to deliver highly modulated plans with variable MLC shapes, dose rate and gantry speed during rotation. Tests were repeated for entire (360 degrees) gantry rotations on composite dose plans and for short partial arcs (of ~6 or 12 degrees) to assess GLAaS and RapidArc mutual relationships on global and fine delivery scales. The gamma index concept of Low and the Modulation Index concept of Webb were applied to compare quantitatively TPS dose matrices and dose converted PV images.

Results
The Gamma Agreement Index computed for a Distance to Agreement of 3 mm and a Dose Difference (ΔD) of 3% was, as mean ± 1 SD, 96.7 ± 1.2% at 6 MV and 94.9 ± 1.3% at 18 MV, over the field area. These findings deteriorated slightly is ΔD was reduced to 2% (93.4 ± 3.2% and 90.1 ± 3.1%, respectively) and improved with ΔD = 4% (98.3 ± 0.8% and 97.3 ± 0.9%, respectively). For all tests a grid of 1 mm and the AAA photon dose calculation algorithm were applied. The spatial resolution of the PV-aS1000 is 0.392 mm/pxl. The Modulation Index for calculations resulted 17.0 ± 3.2 at 6 MV and 15.3 ± 2.7 at 18 MV while the corresponding data for measurements were: 18.5 ± 3.7 and 17.5 ± 3.7. Partial arcs findings were (for ΔD = 3%): GAI = 96.7 ± 0.9% for 6° rotations and 98.0 ± 1.1% for 12° rotations.

Conclusion
The GLAaS method can be considered as a valid Quality Assurance tool for the verification of RapidArc fields. The two implementations (composite rotation or short arcs) allow the verification of either the entire delivery or of short partial segments to possibly identify local discrepancies between delivery and calculations. RapidArc, according to the findings, appears to be a safe delivery method in terms of dosimetric accuracy allowing its clinical application.
Retention of foreign body in the gut can be a sign of congenital obstructive anomaly: a case report
Authors: Subudhi Pravas Chandra , Singh Shivaram Prasad , Meher Chudamani , Agrawal Omprakash 
Published: September 2008

AbstractIntroductionSmall smooth objects that enter the gut nearly always pass uneventfully through the gastrointestinal tract. Retention of foreign objects may occur due to congenital obstructive anomaly of the gut.Case presentationWe report here a child who presented with features of small gut obstruction which were attributed to a foreign body impacted in the intestine. At surgery, an annular pancreas was detected and the foreign body was found to be lodged in the distended proximal duodenum.ConclusionThe reported case highlights the fact that an impacted radio-opaque foreign body in a child should warn the pediatrician to the possibility of an obstructive congenital anomaly.
In GFP with high risk HPV-18E6 fusion protein expressed 293T and MCF-7 cells, the endogenous wild-type p53 could be transiently phosphorylated at multiple sites
Authors: Sun Lina , Zhang Ge , Li Zongfang , Song Tusheng , Huang Chen , Si Lusheng 
Published: September 2008

Abstract

Background
Infected cells recognize viral replication as a DNA damage stress and elicit the host surveillance mechanism to anti-virus infection. Modulation of the activity of tumor suppressor p53 is a key event in the replication of many viruses. They could manipulate p53 function through phosphorylation modification for their own purpose. But there is rarely research about p53 phosphorylation status in the context of HPV-E6. Therefore, we investigated whether p53 could be phosphorylated by HPV-E6.

Methods
We used a mammalian green fluorescence protein (GFP) expression system to express HPV-18E6 with GFP fusion proteins (GFP-18E6) in wild-type (wt) p53 cell lines, such as 293T and MCF-7 cells to trace the traffic and subcellular location of E6 protein. By immunofluorescence technique and immunoblotting, we determined the positive phosphorylated sites of p53 and observed the distribution of phosphorylated p53 in the context of GFP-18E6.

Results
GFP-18E6 was predominantly located in nuclei of wt p53 cell lines, and it could induce transient phosphorylation of p53 at multiple sites, such as Ser15, Ser20, and Ser392. All the three sites of phosphorylated p53s were localized in nuclei together with GFP-18E6.

Conclusion
In GFP with high risk HPV-18E6 fusion protein expressed 293T and MCF-7 cells, the endogenous wt p53 could be transiently phosphorylated at multiple sites.
Induction of HLA-B27 heavy chain homodimer formation after activation in dendritic cells
Authors: Santos Susana G , Lynch Sarah , Campbell Elaine C , Antoniou Antony N , Powis Simon J 
Published: September 2008

Abstract
Introduction
Ankylosing spondylitis (AS) is a severe, chronic inflammatory arthritis, with a strong association to the human major histocompatibilty complex (MHC) class I allele human leucocyte antigen (HLA) B27. Disulfide-linked HLA-B27 heavy-chain homodimers have been implicated as novel structures involved in the aetiology of AS. We have studied the formation of HLA-B27 heavy-chain homodimers in human dendritic cells, which are key antigen-presenting cells and regulators of mammalian immune responses.

Method
Both an in vitro dendritic-like cell line and monocyte-derived dendritic cells from peripheral blood were studied. The KG-1 dendritic-like cell line was transfected with HLA-B27 cDNA constructs, and the cellular distribution, intracellular assembly and ability of HLA-B27 to form heavy-chain homodimers was compared with human monocyte-derived dendritic cells after stimulation with bacterial lipopolysaccharide (LPS).

Results
Immature KG-1 cells expressing HLA-B27 display an intracellular source of MHC class I heavy-chain homodimers partially overlapping with the Golgi bodies, but not the endoplasmic reticulum, which is lost at cell maturation with phorbyl-12-myristate-13-acetate (PMA) and ionomycin. Significantly, the formation of HLA-B27 homodimers in transfected KG-1 cells is induced by maturation, with a transient induction also seen in LPS-stimulated human monocyte-derived dendritic cells expressing HLA-B27. The weak association of wildtype HLA-B*2705 with the transporter associated with antigen processing could also be enhanced by mutation of residues at position 114 and 116 in the peptide-binding groove to those present in the HLA-B*2706 allele.

Conclusion
We have demonstrated that HLA-B27 heavy-chain homodimer formation can be induced by dendritic cell activation, implying that these novel structures may not be displayed to the immune system at all times. Our data suggests that the behaviour of HLA-B27 on dendritic cells may be important in the study of inflammatory arthritis.
4-Hydroxynonenal induces apoptosis in human osteoarthritic chondrocytes: the protective role of glutathione-S-transferase
Authors: Vaillancourt France , Fahmi Hassan , Shi Qin , Lavigne Patrick , Ranger Pierre , Fernandes Julio C , Benderdour Mohamed 
Published: September 2008

Abstract
Introduction
4-Hydroxynonenal (HNE) is one of the most abundant and reactive aldehydes of lipid peroxidation products and exerts various effects on intracellular and extracellular signalling cascades. We have previously shown that HNE at low concentrations could be considered as an important mediator of catabolic and inflammatory processes in osteoarthritis (OA). In the present study, we focused on characterizing the signalling cascade induced by high HNE concentration involved in cell death in human OA chondrocytes.

Methods
Markers of apoptosis were quantified with commercial kits. Protein levels were evaluated by Western blotting. Glutathione (GSH) and ATP levels were measured with commercial kits. Glucose uptake was assessed by 2-deoxy-D-[3H]-glucose. The role of GSH-S-transferase A4-4 (GSTA4-4) in controlling HNE-induced chondrocyte apoptosis was investigated by chondrocyte transfection with small interfering RNA (siRNA) or with the expression vector of GSTA4-4.

Results
Our data showed that HNE at concentrations of up to 10 μM did not alter cell viability but was cytotoxic at concentrations of greater than or equal to 20 μM. HNE-induced chondrocyte death exhibited several classical hallmarks of apoptosis, including caspase activation, cytochrome c and apoptosis-induced factor release from mitochondria, poly (ADP-ribose) polymerase cleavage, Bcl-2 downregulation, Bax upregulation, and DNA fragmentation. Our study of signalling pathways revealed that HNE suppressed pro-survival Akt kinase activity but, in contrast, induced Fas/CD95 and p53 expression in chondrocytes. All of these effects were inhibited by an antioxidant, N-acetyl-cysteine. Analysis of cellular energy and redox status showed that HNE induced ATP, NADPH, and GSH depletion and inhibited glucose uptake and citric acid cycle activity. GSTA4-4 ablation by the siRNA method augmented HNE cytotoxicity, but, conversely, its overexpression efficiently protected chondrocytes from HNE-induced cell death.

Conclusion
Our study provides novel insights into the potential mechanisms of cell death in OA cartilage and suggests the potential role of HNE in OA pathophysiology. GSTA4-4 expression is critically important for cellular defence against oxidative stress-induced cell death in OA cartilage, possibly by HNE elimination.
Tirofiban preserves platelet loss during continuous renal replacement therapy in a randomised prospective open-blinded pilot study
Authors: Link Andreas , Girndt Matthias , Selejan Simina , Rbah Ranja , Böhm Michael 
Published: September 2008

Abstract
Introduction
Approximately one third of all patients with cardiogenic shock suffer from acute kidney injury. Percutaneous coronary intervention, intra-aortic balloon pump, and continuous renal replacement therapy (CRRT) require effective antiplatelet therapy and anticoagulation, resulting in a high risk for platelet loss and bleeding events. The reversible platelet glycoprotein IIb/IIIa receptor inhibitor tirofiban was investigated to preserve platelet number and activation in a prospective open-blinded endpoint evaluation study.

Methods
Forty patients with cardiogenic shock and acute kidney injury requiring CRRT were randomly assigned to two groups receiving unfractioned heparin (UFH) (n = 20) or a combined anticoagulation with UFH and tirofiban (n = 20). The primary endpoint was platelet loss during CRRT. Secondary endpoints were urea reduction, haemofilter life span, bleeding events, and necessity for platelet transfusions.

Results
In UFH-treated patients, the percentage of platelet-monocyte aggregates significantly increased (P < 0.001) and consecutively platelet cell count significantly decreased (P < 0.001). In contrast, combined treatment with UFH and tirofiban significantly decreased platelet-monocyte aggregates and platelet numbers (P < 0.001).

Conclusions
This pilot study provides evidence that the use of tirofiban in addition to UFH prevents platelet loss and preserves platelet function in patients with cardiogenic shock and acute kidney injury requiring CRRT. The pathophysiological inhibition of platelet aggregation and platelet-monocyte interaction appears to be causally involved.
Embryonic implantation: cytokines, adhesion molecules, and immune cells in establishing an implantation environment
Authors: van Mourik Maaike S M , Macklon Nick S , Heijnen Cobi J 
Published: September 2008

AbstractSuccessful implantation is an absolute requirement for the reproduction of species, including humans. The process by which a foreign blastocyst is accepted by the maternal endometrium is complex and requires interplay of many systems. Implantation occurs during the putative implantation window, in which the maternal endometrium is ready to accept the blastocyst, which on the other hand, also plays a specific role. It produces cytokines and chemokines and expresses adhesion molecules and certain classes of MHC molecules. We review the most important players in implantation. Concerning the cytokines, the establishment of controlled aggression is key; an excess of pro- or anti-inflammation is detrimental to pregnancy outcome. Chemokines control the orientation of the embryo. The adhesion molecules are necessary to establish the required physical interaction between mother and blastocyst. Finally, immune cells and in particular, uterine NK and regulatory T cells are pivotal in inducing tolerance to the blastocyst. The aim of this review is to discuss mechanisms at play and their relative importance to the establishment of pregnancy.
Performance ofBRCA1/2Mutation Prediction Models in Asian Americans
Authors: Kurian Allison W. , Gong Gail D. , Chun Nicolette M. , Mills Meredith A. , Staton Ashley D. , Kingham Kerry E. , Crawford Beth B. , Lee Robin , Chan Salina , Donlon Susan S. , Ridge Yolanda , Panabaker Karen , West Dee W. , Whittemore Alice S. , Ford James M. 
Published: September 2008

PurposeThere are established differences in breast cancer epidemiology between Asian and white individuals, but little is known about hereditary breast cancer in Asian populations. Although increasing numbers of Asian individuals are clinically tested for BRCA1/2 mutations, it is not known whether computer models that predict mutations work accurately in Asian individuals. We compared the performance in Asian and white individuals of two widely used BRCA1/2 mutation prediction models, BRCAPRO and Myriad II.Patients and MethodsWe evaluated BRCAPRO and Myriad II in 200 Asian individuals and a matched control group of 200 white individuals who were tested for BRCA1/2 mutations at four cancer genetics clinics, by comparing numbers of observed versus predicted mutation carriers and by evaluating area under the receiver operating characteristic curve (AUC) for each model.ResultsBRCAPRO and Myriad II accurately predicted the number of white BRCA1/2 mutation carriers (25 observed v 24 predicted by BRCAPRO; 25 predicted by Myriad II, P ≥ .69), but underpredicted Asian carriers by two-fold (49 observed v 25 predicted by BRCAPRO; 26 predicted by Myriad II; P ≤ 3 × 10−7). For BRCAPRO, this racial difference reflects substantial underprediction of Asian BRCA2 mutation carriers (26 observed v 4 predicted; P = 1 × 10−30); for Myriad II, separate mutation predictions were not available. For both models, AUCs were nonsignificantly lower in Asian than white individuals, suggesting less accurate discrimination between Asian carriers and noncarriers.ConclusionBoth BRCAPRO and Myriad II underestimated the proportion of BRCA1/2 mutation carriers, and discriminated carriers from noncarriers less well, in Asian compared with white individuals.
Cognitive and Adaptive Outcome in Extracerebellar Low-Grade Brain Tumors in Children: A Report From the Children's Oncology Group
Authors: Ris M. Douglas , Beebe Dean W. , Armstrong F. Daniel , Fontanesi John , Holmes Emi , Sanford Robert A. , Wisoff Jeffrey H. 
Published: September 2008

Purpose To determine whether pediatric patients treated with surgery only for low-grade tumors in the cerebral hemispheres, supratentorial midline, and exophytic brainstem evidence neurocognitive, academic, adaptive, or emotional/behavioral sequelae. Patients and Methods Ninety-three patients from a natural history study of low-grade astrocytomas were tested an average of 111 days after surgery. Rates of below average (≤ 25th percentile) scores in this sample were compared with test norms, and performances were compared across anatomic sites. Finally, the relationships of pre-, peri-, and postsurgical complications to outcome were investigated. Results For the entire sample, there was a significantly elevated rate of below average scores across intelligence quotient, achievement, and adaptive behavior, but not behavioral/emotional adjustment measures. Patients with hemispheric, midline, and brainstem tumors did not differ significantly. Patients with left hemisphere tumors generally performed worse than those with right hemisphere tumors. Finally, neurobehavioral outcome was unrelated to pre-, peri-, or postsurgery complications. Conclusion After surgery for low-grade brain tumors, a significant number of patients was found to function below average, by as much as 55% compared with 25% in the normative population. Moreover, these results suggest greater risk for patients with lesions situated in the left cerebral hemisphere. Routine neuropsychological follow-up of children after treatment for low-grade tumors is recommended.