bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genes Upregulated in Prostate Cancer Reactive Stroma Promote Prostate Cancer Progression In Vivo
Authors: Dakhova Olga , Rowley David , Ittmann Michael 
Published: October 2013

Abstract
Purpose: Marked reactive stroma formation is associated with poor outcome in clinically localized prostate cancer. We have previously identified genes with diverse functions that are upregulated in reactive stroma. This study tests the hypothesis that expression of these genes in stromal cells enhances prostate cancer growth in vivo.
Experimental Design: The expression of reactive stroma genes in prostate stromal cell lines was evaluated by reverse transcriptase (RT)-PCR and qRT-PCR. Genes were knocked down using stable expression of short-hairpin RNAs (shRNA) and the impact on tumorigenesis assessed using the differential reactive stroma (DRS) system, in which prostate stromal cell lines are mixed with LNCaP prostate cancer cells and growth as subcutaneous xenografts assessed.
Results: Nine of 10 reactive stroma genes tested were expressed in one or more prostate stromal cell lines. Gene knockdown of c-Kit, Wnt10B, Bmi1, Gli2, or COMP all resulted in decreased tumorigenesis in the DRS model. In all tumors analyzed, angiogenesis was decreased and there were variable effects on proliferation and apoptosis in the LNCaP cells. Wnt10B has been associated with stem/progenitor cell phenotype in other tissue types. Using a RT-PCR array, we detected downregulation of multiple genes involved in stem/progenitor cell biology such as OCT4 and LIF as well as cytokines such as VEGFA, BDNF, and CSF2 in cells with Wnt10B knockdown.
Conclusions: These findings show that genes upregulated in prostate cancer–reactive stroma promote progression when expressed in prostate stromal cells. Moreover, these data indicate that the DRS model recapitulates key aspects of cancer cell/reactive stroma interactions in prostate cancer. Clin Cancer Res; 20(1); 100–9. ©2013 AACR.
Altered Microenvironment Promotes Progression of Preinvasive Breast Cancer: Myoepithelial Expression of αvβ6 Integrin in DCIS Identifies High-risk Patients and Predicts Recurrence
Authors: Allen Michael D. , Thomas Gareth J. , Clark Sarah , Dawoud Marwa M. , Vallath Sabarinath , Payne Sarah J. , Gomm Jennifer J. , Dreger Sally A. , Dickinson Sarah , Edwards Dylan R. , Pennington Caroline J. , Sestak Ivana , Cuzick Jack , Marshall John F. , Hart Ian R. , Jones J. Louise 
Published: October 2013

Abstract
Purpose: This study investigated the functional and clinical significance of integrin αvβ6 upregulation in myoepithelial cells of ductal carcinoma in situ (DCIS).
Experimental Design: Archival samples of DCIS and DCIS with associated invasion (n = 532) were analyzed for expression of αvβ6 by immunohistochemistry and ability to predict recurrence and progression assessed in an independent, unique cohort of DCIS cases with long-term follow-up. Primary myoepithelial cells and myoepithelial cell lines, with and without αvβ6 expression, were used to measure the effect of αvβ6 on growth and invasion of tumor cell lines in vitro and in a xenograft mouse model. Involvement of TGFβ signaling was established using mink lung epithelial cell (MLEC) assay and antibody inhibition, and expression and activation of matrix metalloproteinase (MMP)-9 established by Real Time-PCR and zymography.
Results: Expression of αvβ6 is significantly associated with progression to invasive cancer (P &lt; 0.006) and with recurrence over a median follow-up of 114 months in a series of matched DCIS cases treated with local excision. We show that expression of αvβ6 drives myoepithelial cells to promote tumor cell invasion in vitro and enhances mammary tumor growth in vivo. The tumor-promoting effect of αvβ6-positive myoepithelial cells is dependent on TGFβ-driven upregulation of MMP9 and can be abrogated by inhibiting this pathway.
Conclusion: These findings indicate that altered myoepithelial cells in DCIS predict disease progression and recurrence and show that upregulation of αvβ6 on myoepithelial cells generates a tumor promoter function through TGFβ upregulation of MMP-9. These data suggest that expression of αvβ6 may be used to stratify patients with DCIS. Clin Cancer Res; 20(2); 344–57. ©2013 AACR.
Isoflurane Post-Treatment Ameliorates GMH-Induced Brain Injury in Neonatal Rats
Authors: Leitzke Arthur S. , Rolland William B. , Krafft Paul R. , Lekic Tim , Klebe Damon , Flores Jerry J. , Van Allen Nicole R. , Applegate Richard L. , Zhang John H. 
Published: October 2013

Background and Purpose—
This study investigated whether isoflurane ameliorates neurological sequelae after germinal matrix hemorrhage (GMH) through activation of the cytoprotective sphingosine kinase/sphingosine-1-phosphate receptor/Akt pathway.

Methods—
GMH was induced in P7 rat pups by intraparenchymal infusion of bacterial collagenase (0.3 U) into the right hemispheric germinal matrix. GMH animals received 2% isoflurane either once 1 hour after surgery or every 12 hours for 3 days. Isoflurane treatment was then combined with sphingosine-1-phosphate receptor-1/2 antagonist VPC23019 or sphingosine kinase 1/2 antagonist N,N-dimethylsphingosine.

Results—
Brain protein expression of sphingosine kinase-1 and phosphorylated Akt were significantly increased after isoflurane post-treatment, and cleaved caspase-3 was decreased at 24 hours after surgery, which was reversed by the antagonists. Isoflurane significantly reduced posthemorrhagic ventricular dilation and improved motor, but not cognitive, functions in GMH animals 3 weeks after surgery; no improvements were observed after VPC23019 administration.

Conclusions—
Isoflurane post-treatment improved the neurological sequelae after GMH possibly by activation of the sphingosine kinase/Akt pathway.
Using Variable-Resolution Meshes to Model Tropical Cyclones in the Community Atmosphere Model
Authors: Zarzycki Colin M. , Jablonowski Christiane , Taylor Mark A. 
Published: October 2013

Abstract
A statically nested, variable-mesh option has recently been introduced into the Community Atmosphere Model’s (CAM's) Spectral Element (SE) dynamical core that has become the default in CAM version 5.3. This paper presents a series of tests of increasing complexity that highlight the use of variable-resolution grids in CAM-SE to improve tropical cyclone representation by dynamically resolving storms without requiring the computational demand of a global high-resolution grid. As a simplified initial test, a dry vortex is advected through grid transition regions in variable-resolution meshes on an irrotational planet with the CAM subgrid parameterization package turned off. Vortex structure and intensity is only affected by grid resolution and no spurious artifacts are observed. CAM-SE model simulations using an idealized tropical cyclone test case on an aquaplanet show no numerical distortion or wave reflection when the cyclone interacts with an abrupt transition region. Using the same test case, the authors demonstrate that a regionally refined mesh with significantly fewer degrees of freedom can produce the same local results as a globally uniform grid. Additionally, the authors discuss a more complex aquaplanet experiment with meridionally varying sea surface temperatures that reproduces a quasi-realistic global climate. Tropical cyclogenesis is facilitated without the need for vortex bogusing in a high-resolution patch embedded within a global grid that is otherwise too coarse to resolve realistic tropical cyclones in CAM.
The Potential for Self-Organizing Maps to Identify Model Error Structures
Authors: Kolczynski Walter C. , Hacker Joshua P. 
Published: October 2013

Abstract
An important aspect of numerical weather model improvement is the identification of deficient areas of the model, particularly deficiencies that are flow dependent or otherwise vary in time or space. Here the authors introduce the use of self-organizing maps (SOMs) and analysis increments from data assimilation to identify model deficiencies. Systematic increments reveal time- and space-dependent systematic errors, while SOMs provide a method for categorizing forecasts or increment patterns. The SOMs can be either used for direct analysis or used to produce composites of other fields. This study uses the forecasts and increments of 2-m temperature and dry column mass perturbation μ over a 4-week period to demonstrate the potential of this technique. Results demonstrate the potential of this technique for identifying spatially varying systematic model errors.
Climate Influences on Meningitis Incidence in Northwest Nigeria
Authors: Abdussalam Auwal F. , Monaghan Andrew J. , Dukić Vanja M. , Hayden Mary H. , Hopson Thomas M. , Leckebusch Gregor C. , Thornes John E. 
Published: October 2013

Abstract
Northwest Nigeria is a region with a high risk of meningitis. In this study, the influence of climate on monthly meningitis incidence was examined. Monthly counts of clinically diagnosed hospital-reported cases of meningitis were collected from three hospitals in northwest Nigeria for the 22-yr period spanning 1990–2011. Generalized additive models and generalized linear models were fitted to aggregated monthly meningitis counts. Explanatory variables included monthly time series of maximum and minimum temperature, humidity, rainfall, wind speed, sunshine, and dustiness from weather stations nearest to the hospitals, and the number of cases in the previous month. The effects of other unobserved seasonally varying climatic and nonclimatic risk factors that may be related to the disease were collectively accounted for as a flexible monthly varying smooth function of time in the generalized additive models, s(t). Results reveal that the most important explanatory climatic variables are the monthly means of daily maximum temperature, relative humidity, and sunshine with no lag; and dustiness with a 1-month lag. Accounting for s(t) in the generalized additive models explains more of the monthly variability of meningitis compared to those generalized linear models that do not account for the unobserved factors that s(t) represents. The skill score statistics of a model version with all explanatory variables lagged by 1 month suggest the potential to predict meningitis cases in northwest Nigeria up to a month in advance to aid decision makers.
Pulmonary thromboembolism in lung surgery: use of unfractionated heparin
Authors: Yoshida Junichi , Inoue Masaaki , Furugaki Koichi , Oyama Mayumi , Oozono Keigo 
Published: October 2013

Background While thoracic surgeons occasionally encounter pulmonary thromboembolism, the use of unfractionated heparin may cause adverse effects. Methods We assessed a series of 323 consecutive pulmonary operations performed during 4 years from 2008 to 2011. All patients were given elastic stockings and intermittent pneumatic compression. During the first 2 years (2008–2009), none of the 169 patients received unfractionated heparin. In the second 2-year period (2010–2011), 135/154 patients received subcutaneous unfractionated heparin, either 5000 units ( n = 37) or 2500 units ( n = 93) twice daily for 3 days, or continuous intravenous unfractionated heparin ( n = 5). The epidural catheters were withdrawn 6 h or more after unfractionated heparin use. Among patients without postoperative unfractionated heparin, 8 (42.1%) had a bleeding risk and 5 (26.3%) had limited operative time. Results One (0.6%) patient developed pulmonary thromboembolism during 2008–2009, but none had this complication during 2010–2011. The adverse outcome of intrathoracic bleeding occurred in one (2.7%) of the patients given 5000 units of unfractionated heparin, but no epidural hematomas occurred in these patients. Conclusion Patients undergoing thoracic surgery at low risk of bleeding may receive unfractionated heparin to prevent pulmonary thromboembolism while avoiding epidural complications.
Current Concepts of Articular Cartilage Restoration Techniques in the Knee
Authors: Camp Christopher L. , Stuart Michael J. , Krych Aaron J. 
Published: October 2013

Context: Articular cartilage injuries are common in patients presenting to surgeons with primary complaints of knee pain or mechanical symptoms. Treatment options include comprehensive nonoperative management, palliative surgery, joint preservation operations, and arthroplasty. Evidence Acquisition: A MEDLINE search on articular cartilage restoration techniques of the knee was conducted to identify outcome studies published from 1993 to 2013. Special emphasis was given to Level 1 and 2 published studies. Study Design: Clinical review. Level of Evidence: Level 3. Results: Current surgical options with documented outcomes in treating chondral injuries in the knee include the following: microfracture, osteochondral autograft transfer, osteochondral allograft transplant, and autologous chondrocyte transplantation. Generally, results are favorable regarding patient satisfaction and return to sport when proper treatment algorithms and surgical techniques are followed, with 52% to 96% of patients demonstrating good to excellent clinical outcomes and 66% to 91% returning to sport at preinjury levels. Conclusion: Clinical, functional, and radiographic outcomes may be improved in the majority of patients with articular cartilage restoration surgery; however, some patients may not fully return to their preinjury activity levels postoperatively. In active and athletic patient populations, biological techniques that restore the articular surface may be options that provide symptom relief and return patients to their prior levels of function.
Evaluation and Management of Wolff-Parkinson-White in Athletes
Authors: Rao Ashwin L. , Salerno Jack C. , Asif Irfan M. , Drezner Jonathan A. 
Published: October 2013

Context: Wolff-Parkinson-White (WPW) is a cardiac conduction system disorder characterized by abnormal accessory conduction pathways between the atria and the ventricles. Symptomatic patients classically present with palpitations, presyncope, or syncope that results from supraventricular tachycardia. While rare, sudden cardiac death may be the first manifestation of underlying disease and occurs more frequently in exercising individuals. Evidence Acquisition: Medline and PubMed databases were evaluated through 2012, with the following keywords: WPW, Wolff-Parkinson-White, pre-excitation, sudden cardiac death, risk stratification, and athletes. Selected articles identified through the primary search, along with relevant references from those articles, were reviewed for pertinent clinical information regarding the identification, evaluation, risk stratification, and management of WPW as they pertained to the care of athletes. Study Design: Systematic review. Level of Evidence: Level 1. Results: Diagnosis of WPW is confirmed by characteristic electrocardiogram changes, which include a delta wave, short PR interval, and widened QRS complex. Utilization of the electrocardiogram as part of the preparticipation physical evaluation may allow for early identification of asymptomatic individuals with a WPW pattern. Risk stratification techniques identify individuals at risk for malignant arrhythmias who may be candidates for curative therapy through transcatheter ablation. Conclusion: WPW accounts for at least 1% of sudden death in athletes and has a prevalence of at least 1 to 4.5 per 1000 children and adults. The risk of lethal arrhythmia appears to be higher in asymptomatic children than in adults, and sudden cardiac death is often the sentinel event. The athlete with WPW should be evaluated for symptoms and the presence of intermittent or persistent pre-excitation, which dictates further consultation, treatment, and monitoring strategies as well as return to play.
DNA prime and peptide boost immunization protocol encoding the Toxoplasma gondii GRA4 induces strong protective immunity in BALB/c mice
Authors: Meng Min , Zhou Aihua , Lu Gang , Wang Lin , Zhao Guanghui , Han Yali , Zhou Huaiyu , Cong Hua , Zhao Qunli , Zhu Xing-Quan , He Shenyi 
Published: October 2013

AbstractBackgroundToxoplasma gondiiis a widespread intracellular parasite, which infects most vertebrate animal hosts and causes zoonotic infection in humans. Vaccine strategy remains a promising method for the prevention and control of toxoplasmosis.T. gondiiGRA4 protein has been identified as a potential candidate for vaccine development. In our study, we evaluated the immune response induced by four different immunization vaccination strategies encoding TgGRA4.MethodsBALB/c mice were intramuscularly (i.m.) immunized four times according to specific immunization schedules. Generally, mice in experimental groups were immunized with polypeptide, pGRA4, peptide/DNA, or DNA/peptide, and mice in the control groups were injected with PBS or pEGFP. After immunization, the levels of IgG antibodies and cytokine productions were determined by enzyme-linked immunosorbent assays (ELISA). The survival time of mice was also evaluated after challenge infection with the highly virulentT. gondiiRH strain.ResultsThe results showed that mice vaccinated with different immunization regimens (polypeptide, pGRA4, peptide/DNA, or DNA/peptide) elicited specific humoral and cellular responses, with high levels of total IgG, IgG2a isotype and gamma interferon (IFN-γ), which suggested a specific Th1 immunity was activated. After lethal challenge, an increased survival time was observed in immunized mice (11.8 ± 4.8 days) compared to the control groups injected with PBS or pEGFP (P < 0.05). Mice injected with PBS or pEGFP died within 8 days, and there was no significant difference in the protection level in two groups (P > 0.05).ConclusionsThese results demonstrated that this DNA prime and peptide boost immunization protocol encoding the TgGRA4 can elicit the highest level of humoral and cellular immune responses compared to other immunized groups, which is a promising approach to increase the efficacy of DNA immunization.
Pulmonary fungus ball caused by Penicillium capsulatum in a patient with type 2 diabetes: a case report
Authors: Chen Min , Houbraken Jos , Pan Weihua , Zhang Chao , Peng Hao , Wu Lihui , Xu Deqiang , Xiao Yiping , Wang Zhilong , Liao Wanqing 
Published: October 2013

Abstract

Background
Following the recent transfer of all accepted species of Penicillium subgenus Biverticillium to Talaromyces (including Talaromyces marneffei, formerly Penicillium marneffei), Penicillium species are becoming increasingly rare causal agents of invasive infections. Herein, we present a report of a type 2 diabetes patient with a fungus ball in the respiratory tract caused by Penicillium capsulatum.

Case presentation
A 56-year-old Chinese female gardener with a 5-year history of type 2 diabetes presented at the Shanghai Changzheng Hospital with fever, a cough producing yellow-white sputum, and fatigue. The therapeutic effect of cefoxitin was poor. An HIV test was negative, but the β-D-glucan test was positive (459.3 pg/ml). Chest radiography revealed a cavitary lesion in the left upper lobe, and a CT scan showed globate cavities with a radiopaque, gravity-dependent ball. The histopathologic features of the tissue after haematoxylin-eosin staining showed septate hyphae. The fungus was isolated from the gravity-dependent ball and identified as Penicillium capsulatum based on the morphological analysis of microscopic and macroscopic features and on ribosomal internal transcribed spacer sequencing. After surgery, the patient was cured with a sequential treatment of fluconazole 400 mg per day for 90 days and caspofungin 70 mg per day for 14 days.

Conclusions
Although the prognosis is often satisfactory, clinicians, mycologists and epidemiologists should be aware of the possibility of infection by this uncommon fungal pathogen in diabetes patients, since it may cause severe invasive infections in immunocompromised hosts such as diabetes and AIDS patients.
Development of a quantitative rapid diagnostic test for multibacillary leprosy using smart phone technology
Authors: Paula Vaz Cardoso Ludimila , Dias Ronaldo Ferreira , Freitas Aline Araújo , Hungria Emerith Mayra , Oliveira Regiane Morillas , Collovati Marco , Reed Steven G , Duthie Malcolm S , Martins Araújo Stefani Mariane 
Published: October 2013

Abstract

Background
Despite efforts to eliminate leprosy as public health problem, delayed diagnosis and disabilities still occur in many countries. Leprosy diagnosis remains based on clinical manifestations and the number of clinicians with expertise in leprosy diagnosis is in decline. We have developed a new immunochromatographic test with the goal of producing a simple and rapid system that can be used, with a minimal amount of training, to provide an objective and consistent diagnosis of multibacillary leprosy.

Methods
The test immobilizes two antigens that have been recognized as excellent candidates for serologic diagnosis (the PGL-I mimetic, ND-O, and LID-1), on a nitrocellulose membrane. This allows the detection of specific IgM and IgG antibodies within 20 minutes of the addition of patient sera. Furthermore, we coupled the NDO-LID® rapid tests with a new cell phone-based test reader platform (Smart Reader®) to provide objective interpretation that was both quantifiable and consistent.

Results
Direct comparison of serologic responses indicated that the rapid test detected a greater proportion of leprosy patients than a lab-based PGL-I ELISA. While positive responses were detected by PGL-I ELISA in 83.3% of multibacillary patients and 15.4% of paucibacillary patients, these numbers were increased to 87% and 21.2%, respectively, when a combination of the NDO-LID® test and Smart Reader® was used. Among multibacillary leprosy the sensitivity of NDO-LID® test assessed by Smart Reader® was 87% (95% CI, 79.2-92.7%) and the specificity was 96.1% (95% CI, 91.7- 98.6%). The positive predictive value and the negative predictive value of NDO-LID® tests were 94% (95% CI, 87.4-97.8%) and 91.4% (95% CI, 85.9-95.2%), respectively.

Conclusion
The widespread provision of rapid diagnostic tests to facilitate the diagnosis or prognosis of multibacillary leprosy could impact on leprosy control programs by aiding early detection, directing appropriate treatment and potentially interrupting Mycobacterium leprae transmission.
The impact on patient health and service outcomes of introducing nurse consultants: a historically matched controlled study
Authors: Lee Diana TF , Choi Kai Chow , Chan Carmen WH , Chair Sek Ying , Chan Dominic , Fung Sylvia YK , Chan Eric LS 
Published: October 2013

Abstract

Background
The position of nurse consultant (NC) was introduced in Hong Kong by the Hospital Authority in January 2009. Seven NCs were appointed in five clinical specialties: diabetes, renal, wound and stoma care, psychiatrics, and continence. This was a pilot to explore the impact of the introduction of NCs on patient health and service outcomes.

Methods
The present paper describes a historically matched controlled study. A total of 280 patients, 140 in each cohort under NC or non-NC care, participated in the study. The patient health and service outcomes of both cohorts were evaluated and compared: accident and emergency visits, hospital admissions, length of hospital stays, number of acute complications, number of times of treatment or regimen altered by nurses according to patient’s condition, glycated haemoglobin A1c (HbA1c) levels, urea and urea-to-creatinine ratios, and number of wound dressings for patients in corresponding specialty units. A patient satisfaction instrument was also used to assess the NC cohort.

Results
The study showed that patients under NC care had favourable patient health and service outcomes compared with those under non-NC care. The NC cohort also reported a high level of patient satisfaction.

Conclusions
The study demonstrates that the introduction of NCs in specialty units may have a positive impact on patients’ health and service outcomes. The high level of patient satisfaction scores indicates that patients appreciate the care they are receiving with the introduction of NCs.