bluuebunny/crossref_metadata_2025_split huggingface dataset:
Location-specific expression of chemokines, TNF-α and S100 proteins in a teat explant model
Authors: Lind Monique , Sipka Anja S , Schuberth Hans-Joachim , Blutke Andreas , Wanke Rüdiger , Sauter-Louis Carola , Duda Katarzyna A , Holst Otto , Rainard Pascal , Germon Pierre , Zerbe Holm , Petzl Wolfram 
Published: August 2014

The distal compartments of the udder are the first to interact with invading pathogens. The regulatory and effector functions of two major teat regions [Fürstenberg's rosette (FR); teat cistern (TC)] are largely unknown. The objective of this study was to establish an in vitro model with explants of the FR and the TC to analyse their response towards Escherichia coli LPS and Staphylococcus aureus lipoteichoic acid (LTA). Quantitative stereological analysis confirmed differences in the cellular composition of FR and TC explants. Chemokine (CXCL8, CCL5, CCL20) and TNF-α mRNA were expressed at low levels in both locations. Explant stimulation with LPS increased the mRNA abundance of all tested chemokines and TNF-α. Stimulation with LTA only induced CCL20 and CXCL8. LPS- and LTA-stimulated explant supernatants contained CXCL8 and CXCL3. Supernatants significantly attracted neutrophils in vitro. Compared with TC, the FR showed high constitutive mRNA expression of S100 proteins (A8, A9, A12). In the TC, both LPS and LTA significantly induced S100A8, whereas S100A9 and S100A12 expression was only induced by LPS. The novel model system underpins the role of the teat for recognising pathogens and shaping a pathogen- and location-specific immune response.
Intravenous thrombolysis in acute ischemic stroke patients with negative CT perfusion: a case series
Authors: Mehra Ratnesh , To Chiu Yuen , Qahwash Omar , Richards Boyd , Fessler Richard D 
Published: August 2014

Background Computed tomography perfusion (CTP) is a commonly used modality of neurophysiologic imaging to aid the selection of acute ischemic stroke patients for neuroendovascular intervention by identifying the presence of penumbra versus infarcted brain tissue. However many patients present with evidence of cerebral ischemia with normal CTP, and in that case, should intravenous thrombolytics be given? Purpose To demonstrate if tissue-type plasminogen activator (tPA)-eligible stroke patients without perfusion defects demonstrated on CTP would benefit from administration of intravenous thrombolytics. Material and Methods We retrospectively identified patients presenting with acute ischemic symptoms who received intravenous tPA (IV-tPA) from January to June 2012 without a perfusion defect on CTP. Clinical and radiographic findings including the NIHSS at presentation, 24 h, and at discharge, symptomatic and asymptomatic hemorrhagic transformation, and the modified Rankin score at 30 days were collected. A reduction of NIHSS of greater than 4 points or resolution of symptoms was considered significant. Results Seventeen patients were identified with a mean NIHSS of 8.2 prior to administration of intravenous thrombolytics, 3.5 after 24 h, and 2.5 at discharge. Among them, 13 patients had significant improvement of NIHSS with a mean reduction of 6.15 points at 24 h. One patient initially improved but had delayed hemorrhagic transformation and died. Two patients had improvement in NIHSS but were not significant and two patients had increased in NIHSS at 24 h, although one eventually improved at discharge. There was no asymptomatic hemorrhagic transformation. Mean mRS at 3 months is 1.76. Conclusion The failure to identify a perfusion deficit by CTP should not be used as a contraindication for intravenous thrombolytics. Criteria for administration of intravenous thrombolytics should still be based on time from symptom onset as previously published by NINDS.
Faecal calprotectin levels differentiate intestinal from pulmonary tuberculosis: An observational study from Southern India
Authors: Larsson Geir , Shenoy Koticherry Thrivikrama , Ramasubramanian Ramalingom , Thayumanavan Lakshmikanthan , Balakumaran Leena Kondarappassery , Bjune Gunnar A , Moum Bjørn A 
Published: August 2014

BackgroundCurrent methods to establish the diagnosis of intestinal tuberculosis are inadequate.ObjectivesWe aimed to determine the clinical features of intestinal tuberculosis and evaluate inflammatory biomarkers in intestinal as well as pulmonary tuberculosis.MethodsWe recruited 38 intestinal tuberculosis patients, 119 pulmonary tuberculosis patients and 91 controls with functional gastrointestinal disorders between October 2009 and July 2012 for the investigation of clinical features, C‐reactive protein (CRP), faecal and serum calprotectin. Faecal calprotectin ≥200 µg/g was used as a cut‐off to determine intestinal inflammation of clinical significance. Three patient categories were established: (a) pulmonary tuberculosis and faecal calprotectin <200 µg/g (isolated pulmonary tuberculosis); (b) pulmonary tuberculosis and faecal calprotectin ≥200 µg/g (combined pulmonary and intestinal tuberculosis); (c) isolated intestinal tuberculosis.ResultsCommon clinical features of intestinal tuberculosis were abdominal pain, fatigue, weight loss and watery diarrhoea. Intestinal tuberculosis patients had elevated median CRP (10.7 mg/l), faecal calprotectin (320 µg/g) and serum calprotectin (5.7 µg/ml). Complete normalisation of CRP (1.0 mg/L), faecal calprotectin (16 µg/g) and serum calprotectin (1.4 µg/ml)) was seen upon clinical remission. Patients with combined pulmonary and intestinal tuberculosis had the highest levels of CRP (53.8 mg/l) and serum calprotectin (6.5 µg/ml) and presented with signs of more severe disease.ConclusionCalprotectin analysis reveals intestinal tuberculosis in patients with pulmonary tuberculosis and pinpoints those in need of rigorous follow‐up.
Regional Backwardness and Public Spending on Development of Rural Physical and Social Infrastructure in Karnataka
Authors: H.M. Siddaram 
Published: August 2014

The word infrastructure has been derived from the different two independent words ‘Infra’ means which lies beneath or comes before and similarly ‘Structure’ which means well planned or organised. Infrastructure could serve as a true engine of growth and can provide the much needed momentum to the economic in the time of economic slowdown. The Indian economy has grown at an average 8 per cent in the recent past years, and a 10 per cent annual GDP growth is difficult to achieve unless the county improves its rural infrastructure. If India is to sustain its high growth much of the required investment is of a public goods nature and thus most of the infrastructure investments must come from public sources. Karnataka is a pioneer State in the transformation of the ‘Gram Swaraj’ concept into reality and enacting the PRI Act to bring the practice of decentralised administration and development in line with the 73rd Amendment to the Constitution. A three-tier structure was created with the Zilla Panchayath at district, Taluka Panchayath at taluks and Gram Panchayath at the village level. 73rd amendment of constitution gives more power to Gram Panchayath in context to local self governance. A high power committee for the redressal of regional imbalance was constituted by the government in 2000. It identified 35 indicators encompassing agriculture, industry, and social-economic infrastructure and population characteristics to index of development. Gram Swaraj Project implemented in Karnataka State from the year 2006–2007 was based on Prof. Nanjundappa committee to address the issue of regional imbalances in his report. With this background the State Government has intend to strengthening the 1,341 Gram Panchayats comes under ‘most backward taluks’ with the collaboration of World bank aid.
Non-HLA genes PTPN22, CDK6 and PADI4 are associated with specific autoantibodies in HLA-defined subgroups of rheumatoid arthritis
Authors: Snir Omri , Gomez-Cabrero David , Montes Ariana , Perez-Pampin Eva , Gómez-Reino Juan J , Seddighzadeh Maria , Klich Katharina U , Israelsson Lena , Ding Bo , Catrina Anca I , Holmdahl Rikard , Alfredsson Lars , Klareskog Lars , Tegnér Jesper , Gonzalez Antonio , Malmström Vivianne , Padyukov Leonid 
Published: August 2014

Abstract
Introduction
Genetic susceptibility to complex diseases has been intensively studied during the last decade, yet only signals with small effect have been found leaving open the possibility that subgroups within complex traits show stronger association signals. In rheumatoid arthritis (RA), autoantibody production serves as a helpful discriminator in genetic studies and today anti-citrullinated cyclic peptide (anti-CCP) antibody positivity is employed for diagnosis of disease. The HLA-DRB1 locus is known as the most important genetic contributor for the risk of RA, but is not sufficient to drive autoimmunity and additional genetic and environmental factors are involved. Hence, we addressed the association of previously discovered RA loci with disease-specific autoantibody responses in RA patients stratified by HLA-DRB1*04.

Methods
We investigated 2178 patients from three RA cohorts from Sweden and Spain for 41 genetic variants and four autoantibodies, including the generic anti-CCP as well as specific responses towards citrullinated peptides from vimentin, alpha-enolase and type II collagen.

Results
Our data demonstrated different genetic associations of autoantibody-positive disease subgroups in relation to the presence of DRB1*04. Two specific subgroups of autoantibody-positive RA were identified. The SNP in PTPN22 was associated with presence of anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Cochran-Mantel-Haenszel test P = 0.0001, Pcorrected <0.05), whereas SNPs in CDK6 and PADI4 were associated with anti-CCP status in DRB1*04 negative patients (Cochran-Mantel-Haenszel test P = 0.0004, Pcorrected <0.05 for both markers). Additionally we see allelic correlation with autoantibody titers for PTPN22 SNP rs2476601 and anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Mann Whitney test P = 0.02) and between CDK6 SNP rs42041 and anti-CCP in non-carriers of HLA-DRB1*04 (Mann Whitney test P = 0.02).

Conclusion
These data point to alternative pathways for disease development in clinically similar RA subgroups and suggest an approach for study of genetic complexity of disease with strong contribution of HLA.
Weakly periodic boundary conditions for the homogenization of flow in porous media
Authors: Sandstöm Carl , Larsson Fredrik , Runesson Kenneth 
Published: August 2014

AbstractBackgroundSeepage in porous media is modeled as a Stokes flow in an open pore system contained in a rigid, impermeable and spatially periodic matrix. By homogenization, the problem is turned into a two-scale problem consisting of a Darcy type problem on the macroscale and a Stokes flow on the subscale.MethodsThe pertinent equations are derived by minimization of a potential and in order to satisfy the Variationally Consistent Macrohomogeneity Condition, Lagrange multipliers are used to impose periodicity on the subscale RVE. Special attention is given to the bounds produced by confining the solutions spaces of the subscale problem.ResultsIn the numerical section, we choose to discretize the Lagrange multipliers as global polynomials along the boundary of the computational domain and investigate how the order of the polynomial influence the permeability of the RVE. Furthermore, we investigate how the size of the RVE affect its permeability for two types of domains.ConclusionsThe permeability of the RVE depends highly on the discretization of the Lagrange multipliers. However, the flow quickly converges towards strong periodicity as the multipliers are refined.
Fluid Balance, Change in Serum Creatinine and Urine Output as Markers of Acute Kidney Injury Post Cardiac Surgery: An Observational Study
Authors: Chau Katrina , Schisler Travis , Er Lee , Jaswal Dharmvir , Cheung Christopher , Israel Amanda , Bowering John , Levin Adeera 
Published: August 2014

Background: Acute kidney injury (AKI) is defined as oliguria or rise in serum creatinine but oliguria alone as a diagnostic criterion may over-diagnose AKI. Objectives: Given the association between fluid overload and AKI, we aimed to determine if positive fluid balance can complement the known parameters in assessing outcomes of AKI. Design: Prospective observational study. Setting: Teaching hospital in Vancouver, Canada. Patients: 111 consecutive patients undergoing elective cardiac surgery from January to April 2012. Measurements: Outcomes of cardiac surgery intensive care unit (CSICU) and hospital length of stay (LOS) in relation to fluid balance, urine output and serum creatinine. Methods: All fluid input and output was recorded for 72 hours post-operatively. Positive fluid balance was defined as >6.5 cc/kg. Daily serum creatinine and hourly urine output were recorded and patients were defined as having AKI according to the AKIN criteria. Results: Of the patients who were oliguric, those with fluid overload trended towards longer LOS than those without fluid overload [CSICU LOS: 62 and 39 hours (unadjusted p-value 0.02, adjusted p-value 0.58); hospital LOS: 13 and 9 days (unadjusted p-value: 0.05, adjusted p-value: 0.16)]. Patients with oliguria who were fluid overloaded had similar LOS to patients with overt AKI (change in serum creatinine ≥ 26.5 μmol/L), [CSICU LOS: 62 and 69 hours (adjusted p value: 0.32) and hospital LOS: 13 and 14 days (adjusted p value: 0.19)]. Patients with oliguria regardless of fluid balance had longer CSICU LOS (adjusted p value: 0.001) and patients who were fluid overloaded in the absence of AKI had longer hospital LOS (adjusted p value: 0.02). Limitations: Single centre, small sample, LOS as outcome. Conclusions: Oliguria and positive fluid balance is associated with a trend towards longer LOS as compared to oliguria alone. Fluid balance may therefore be a useful marker of AKI, in addition to urine output and serum creatinine.
Estimation of pressure-saturation changes for unconsolidated reservoir rocks with highVP/VSratio
Authors: Bhakta Tuhin , Landrø Martin 
Published: August 2014

We find that conventional time-lapse seismic pressure-saturation discrimination methods become unstable for high [Formula: see text] ratios. Using first-order approximations in the amplitude variation with offset (AVO) gradient and intercept changes and in the rock-physics models increase the inaccuracy in pressure-saturation changes estimates. We propose a new method, based on a stepwise linear approximation to the intercept and gradient reflectivity changes, to estimate pressure and saturation changes. The applicability of the new method is tested on synthetic data over a range of 0%–50% gas saturation and 0–3.5 MPa pore-pressure changes. The new method is more consistent and provides better estimates compared with conventional methods. In the presence of random noise (up to 15%), the estimates are reasonably better for the new method. We use this new method to investigate the feasibility of pressure-saturation discrimination for a shallow unconsolidated sand reservoir in which an underground blowout occurred in 1989. We analyze a sand layer at 490-m depth that was charged by gas due to the blowout. Because of the shallow depth, the [Formula: see text] is expected to be higher than 2 before the blowout. Near- and far-offset time-lapse seismic data sets from 1988 and 1990 are used as input to estimate changes in AVO intercept and gradient and then changes in pressure and saturation. We find that the new method estimates more realistic pressure-saturation changes compared to the conventional one.
Brentuximab Vedotin in the Front-Line Treatment of Patients With CD30+ Peripheral T-Cell Lymphomas: Results of a Phase I Study
Authors: Fanale Michelle A. , Horwitz Steven M. , Forero-Torres Andres , Bartlett Nancy L. , Advani Ranjana H. , Pro Barbara , Chen Robert W. , Davies Andrew , Illidge Tim , Huebner Dirk , Kennedy Dana A. , Shustov Andrei R. 
Published: August 2014

Purpose Front-line treatment of peripheral T-cell lymphomas (PTCL) involves regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and results in a 5-year overall survival (OS) rate of less than 50%. This phase I open-label study evaluated the safety and activity of brentuximab vedotin administered sequentially with CHOP or in combination with CHP (CHOP without vincristine) as front-line treatment in patients with CD30+ PTCL. Patients and Methods Patients received sequential treatment (once every 3 weeks) with brentuximab vedotin 1.8 mg/kg (two cycles) followed by CHOP (six cycles) or brentuximab vedotin 1.8 mg/kg plus CHP (BV+CHP) for six cycles (once every 3 weeks). Responders received single-agent brentuximab vedotin for eight to 10 additional cycles (for a total of 16 cycles). The primary objective was assessment of safety; secondary end points included objective response rate, complete remission (CR) rate, progression-free survival rate (PFS), and OS. There were no prespecified comparisons of the two treatment approaches. Results After sequential treatment, 11 (85%) of 13 patients achieved an objective response (CR rate, 62%; estimated 1-year PFS rate, 77%). Grade 3/4 adverse events occurred in eight (62%) of 13 patients. At the end of combination treatment, all patients (n = 26) achieved an objective response (CR rate, 88%; estimated 1-year PFS rate, 71%). All seven patients without anaplastic large-cell lymphoma achieved CR. Grade 3/4 adverse events (≥ 10%) in the combination-treatment group were febrile neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%). Conclusion Brentuximab vedotin, administered sequentially with CHOP or in combination with CHP, had a manageable safety profile and exhibited substantial antitumor activity in newly diagnosed patients with CD30+ PTCL. A randomized phase III trial is under way, comparing BV+CHP with CHOP (clinical trial No. NCT01777152).
Radiation Field Design in the ACOSOG Z0011 (Alliance) Trial
Authors: Jagsi Reshma , Chadha Manjeet , Moni Janaki , Ballman Karla , Laurie Fran , Buchholz Thomas A. , Giuliano Armando , Haffty Bruce G. 
Published: August 2014

Purpose ACOSOG Z0011 established that axillary lymph node dissection (ALND) is unnecessary in patients with breast cancer with one to two positive sentinel lymph nodes (SLNs) who undergo lumpectomy, radiotherapy (RT), and systemic therapy. We sought to ascertain RT coverage of the regional nodes in that trial. Methods We evaluated case report forms completed 18 months after enrollment. From 2012 to 2013, we collected all available detailed RT records for central review. Results Among 605 patients with completed case report forms, 89% received whole-breast RT. Of these, 89 (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were obtained for 228 patients, of whom 185 (81.1%) received tangent-only treatment. Among 142 with sufficient records to evaluate tangent height, high tangents (cranial tangent border ≤ 2 cm from humeral head) were used in 50% of patients (33 of 66) randomly assigned to ALND and 52.6% (40 of 76) randomly assigned to SLND. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥ three fields: 22 in the ALND arm and 21 in the SLND arm. Those receiving directed nodal RT had greater nodal involvement (P < .001) than those who did not. Overall, there was no significant difference between treatment arms in the use of protocol-prohibited nodal fields. Conclusion Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone.
Somatotropinomas, But Not Nonfunctioning Pituitary Adenomas, Maintain a Functional Apoptotic RET/Pit1/ARF/p53 Pathway That Is Blocked by Excess GDNF
Authors: Diaz-Rodriguez Esther , Garcia-Rendueles Angela R. , Ibáñez-Costa Alejandro , Gutierrez-Pascual Ester , Garcia-Lavandeira Montserrat , Leal Alfonso , Japon Miguel A. , Soto Alfonso , Venegas Eva , Tinahones Francisco J. , Garcia-Arnes Juan A. , Benito Pedro , Angeles Galvez Maria , Jimenez-Reina Luis , Bernabeu Ignacio , Dieguez Carlos , Luque Raul M. , Castaño Justo P. , Alvarez Clara V. 
Published: August 2014

AbstractAcromegaly is caused by somatotroph cell adenomas (somatotropinomas [ACROs]), which secrete GH. Human and rodent somatotroph cells express the RET receptor. In rodents, when normal somatotrophs are deprived of the RET ligand, GDNF (Glial Cell Derived Neurotrophic Factor), RET is processed intracellularly to induce overexpression of Pit1 [Transcription factor (gene : POUF1) essential for transcription of Pituitary hormones GH, PRL and TSHb], which in turn leads to p19Arf/p53-dependent apoptosis. Our purpose was to ascertain whether human ACROs maintain the RET/Pit1/p14ARF/p53/apoptosis pathway, relative to nonfunctioning pituitary adenomas (NFPAs). Apoptosis in the absence and presence of GDNF was studied in primary cultures of 8 ACROs and 3 NFPAs. Parallel protein extracts were analyzed for expression of RET, Pit1, p19Arf, p53, and phospho-Akt. When GDNF deprived, ACRO cells, but not NFPAs, presented marked level of apoptosis that was prevented in the presence of GDNF. Apoptosis was accompanied by RET processing, Pit1 accumulation, and p14ARF and p53 induction. GDNF prevented all these effects via activation of phospho-AKT. Overexpression of human Pit1 (hPit1) directly induced p19Arf/p53 and apoptosis in a pituitary cell line. Using in silico studies, 2 CCAAT/enhancer binding protein alpha (cEBPα) consensus-binding sites were found to be 100% conserved in mouse, rat, and hPit1 promoters. Deletion of 1 cEBPα site prevented the RET-induced increase in hPit1 promoter expression. TaqMan qRT-PCR (real time RT-PCR) for RET, Pit1, Arf, TP53, GDNF, steroidogenic factor 1, and GH was performed in RNA from whole ACRO and NFPA tumors. ACRO but not NFPA adenomas express RET and Pit1. GDNF expression in the tumors was positively correlated with RET and negatively correlated with p53. In conclusion, ACROs maintain an active RET/Pit1/p14Arf/p53/apoptosis pathway that is inhibited by GDNF. Disruption of GDNF's survival function might constitute a new therapeutic route in acromegaly.