bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of Brugia malayi larvae and DNA in vector and non-vector mosquitoes: implications for molecular diagnostics
Authors: Erickson Sara M , Fischer Kerstin , Weil Gary J , Christensen Bruce M , Fischer Peter U 
Published: November 2009

AbstractBackgroundThe purpose of this study was to extend prior studies of molecular detection ofBrugia malayiDNA in vector (Aedes aegypti-Liverpool) and non-vector (Culex pipiens) mosquitoes at different times after ingestion of infected blood.ResultsParasite DNA was detected over a two week time course in 96% of pooled thoraces of vector mosquitoes. In contrast, parasite DNA was detected in only 24% of thorax pools from non-vectors; parasite DNA was detected in 56% of midgut pools and 47% of abdomen pools from non-vectors. Parasite DNA was detected in vectors in the head immediately after the blood meal and after 14 days. Parasite DNA was also detected in feces and excreta of the vector and non-vector mosquitoes which could potentially confound results obtained with field samples. However, co-housing experiments failed to demonstrate transfer of parasite DNA from infected to non-infected mosquitoes. Parasites were also visualized in mosquito tissues by immunohistololgy using an antibody to the recombinant filarial antigen Bm14. Parasite larvae were detected consistently after mf ingestion inAe. aegypti-Liverpool. Infectious L3s were seen in the head, thorax and abdomen of vector mosquitoes 14 days after Mf ingestion. In contrast, parasites were only detected by histology shortly after the blood meal inCx. pipiens, and these were not labeled by the antibody.ConclusionThis study provides new information on the distribution of filarial parasites and parasite DNA in vector and non-vector mosquitoes. This information should be useful for those involved in designing and interpreting molecular xenomonitoring studies.
Luteinizing hormone-induced Akt phosphorylation and androgen production are modulated by MAP Kinase in bovine theca cells
Authors: Fukuda Shin , Orisaka Makoto , Tajima Kimihisa , Hattori Katsushige , Kotsuji Fumikazu 
Published: November 2009

Abstract

Background
Theca cells play an important role in controlling ovarian steroidogenesis by providing aromatizable androgens for granulosa cell estrogen biosynthesis. Although it is well established that the steroidogenic activity of theca cells is mainly regulated by LH, the intracellular signal transduction mechanisms that regulate thecal proliferation and/or steroidogenesis remain obscure. In this study, we examined whether and how LH controls the PI3K/Akt signaling pathway and androgen production in bovine theca cells. We also explored whether this LH-induced PI3K/Akt activation is modulated with other signaling pathways (i.e. PKA and MAPK).

Methods
Ovarian theca cells were isolated from bovine small antral follicles and were incubated with LH for various durations. Phospho-Akt and total-Akt content in the cultured theca cells were examined using Western blotting. Androstenedione levels in the spent media were determined using EIA. Semi-quantitative RT-PCR analyses were conducted to analyze the mRNA levels of CYP17A1 and StAR in the theca cells. To examine whether Akt activity is involved in theca cell androgen production, the PI3K inhibitors wortmannin and LY294002 were also added to the cells.

Results
Akt is constitutively expressed, but is gradually phosphorylated in cultured bovine theca cells through exposure to LH. LH significantly increased androstenedione production in bovine theca cells, whereas addition of the wortmannin and LY294002 significantly decreased LH-induced androstenedione production. LH significantly increased CYP17A1 mRNA level in theca cells, whereas addition of LY294002 significantly decreased LH-induced CYP17A1 expression. Neither LH nor PI3K inhibitors alter the mRNA levels of StAR in theca cells. Although H89 (a selective inhibitor of PKA) does not affect LH-mediated changes in Akt, U0126 (a potent MEK inhibitor) suppressed LH-induced Akt phosphorylation, CYP17A1 expression, and androgen production in theca cells.

Conclusion
These results indicate that LH stimulates CYP17 mRNA expression and androgen production in theca cells via activation of the PI3K/Akt pathway. The LH-induced Akt phosphorylation and androgen production are modulated by the MAPK signaling in bovine theca cells.
Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial
Authors: Dünser Martin W , Ruokonen Esko , Pettilä Ville , Ulmer Hanno , Torgersen Christian , Schmittinger Christian A , Jakob Stephan , Takala Jukka 
Published: November 2009

Abstract
Introduction
It is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock.

Methods
This is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP ≥ 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles ≥ 70 mmHg and mortality or the frequency and occurrence of disease-related events.

Results
There was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.28-2.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.38-2.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01).

Conclusions
MAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. Elevating MAP >70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.
Differential binding and co-binding pattern of FOXA1 and FOXA3 and their relation to H3K4me3 in HepG2 cells revealed by ChIP-seq
Authors: Motallebipour Mehdi , Ameur Adam , Reddy Bysani Madhu Sudhan , Patra Kalicharan , Wallerman Ola , Mangion Jonathan , Barker Melissa A , McKernan Kevin J , Komorowski Jan , Wadelius Claes 
Published: November 2009

Abstract
Background
The forkhead box/winged helix family members FOXA1, FOXA2, and FOXA3 are of high importance in development and specification of the hepatic linage and the continued expression of liver-specific genes.

Results
Here, we present a genome-wide location analysis of FOXA1 and FOXA3 binding sites in HepG2 cells through chromatin immunoprecipitation with detection by sequencing (ChIP-seq) studies and compare these with our previous results on FOXA2. We found that these factors often bind close to each other in different combinations and consecutive immunoprecipitation of chromatin for one and then a second factor (ChIP-reChIP) shows that this occurs in the same cell and on the same DNA molecule, suggestive of molecular interactions. Using co-immunoprecipitation, we further show that FOXA2 interacts with both FOXA1 and FOXA3 in vivo, while FOXA1 and FOXA3 do not appear to interact. Additionally, we detected diverse patterns of trimethylation of lysine 4 on histone H3 (H3K4me3) at transcriptional start sites and directionality of this modification at FOXA binding sites. Using the sequence reads at polymorphic positions, we were able to predict allele specific binding for FOXA1, FOXA3, and H3K4me3. Finally, several SNPs associated with diseases and quantitative traits were located in the enriched regions.

Conclusions
We find that ChIP-seq can be used not only to create gene regulatory maps but also to predict molecular interactions and to inform on the mechanisms for common quantitative variation.
Discovery of microvascular miRNAs using public gene expression data: miR-145 is expressed in pericytes and is a regulator of Fli1
Authors: Larsson Erik , Fredlund Fuchs Peder , Heldin Johan , Barkefors Irmeli , Bondjers Cecilia , Genové Guillem , Arrondel Christelle , Gerwins Pär , Kurschat Christine , Schermer Bernhard , Benzing Thomas , Harvey Scott J , Kreuger Johan , Lindahl Per 
Published: November 2009

Abstract
Background
A function for the microRNA (miRNA) pathway in vascular development and angiogenesis has been firmly established. miRNAs with selective expression in the vasculature are attractive as possible targets in miRNA-based therapies. However, little is known about the expression of miRNAs in microvessels in vivo. Here, we identified candidate microvascular-selective miRNAs by screening public miRNA expression datasets.

Methods
Bioinformatics predictions of microvascular-selective expression were validated with real-time quantitative reverse transcription PCR on purified microvascular fragments from mouse. Pericyte expression was shown with in situ hybridization on tissue sections. Target sites were identified with 3' UTR luciferase assays, and migration was tested in a microfluid chemotaxis chamber.

Results
miR-145, miR-126, miR-24, and miR-23a were selectively expressed in microvascular fragments isolated from a range of tissues. In situ hybridization and analysis of Pdgfb retention motif mutant mice demonstrated predominant expression of miR-145 in pericytes. We identified the Ets transcription factor Friend leukemia virus integration 1 (Fli1) as a miR-145 target, and showed that elevated levels of miR-145 reduced migration of microvascular cells in response to growth factor gradients in vitro.

Conclusions
miR-126, miR-24 and miR-23a are selectively expressed in microvascular endothelial cells in vivo, whereas miR-145 is expressed in pericytes. miR-145 targets the hematopoietic transcription factor Fli1 and blocks migration in response to growth factor gradients. Our findings have implications for vascular disease and provide necessary information for future drug design against miRNAs with selective expression in the microvasculature.
Effectiveness of a Home Care Nursing Program in the Symptom Management of Patients With Colorectal and Breast Cancer Receiving Oral Chemotherapy: A Randomized, Controlled Trial
Authors: Molassiotis Alex , Brearley Sarah , Saunders Mark , Craven Olive , Wardley Andrew , Farrell Carole , Swindell Ric , Todd Chris , Luker Karen 
Published: November 2009

PurposeTo assess the effectiveness of a symptom-focused home care program in patients with cancer who were receiving oral chemotherapy in relation to toxicity levels, anxiety, depression, quality of life, and service utilization.Patients and MethodsA randomized, controlled trial was carried out with 164 patients with a diagnosis of colorectal (n = 110) and breast (n = 54) cancers who were receiving oral capecitabine. Patients were randomly assigned to receive either a home care program by a nurse or standard care for 18 weeks (ie, six cycles of chemotherapy). Toxicity assessments were carried out weekly for the duration of the patients' participation in the trial, and validated self-report tools assessed anxiety, depression, and quality of life.ResultsSignificant improvements were observed in the home care group in relation to the symptoms of oral mucositis, diarrhea, constipation, nausea, pain, fatigue (first four cycles), and insomnia (all P < .05). This improvement was most significant during the initial two cycles. Unplanned service utilization, particularly the number of inpatient days (57 v 167 days; P = .02), also was lower in the home care group.ConclusionA symptom-focused home care program was able to assist patients to manage their treatment adverse effects more effectively than standard care. It is imperative that patients receiving oral chemotherapy are supported with such programs, particularly during initial treatment cycles, to improve their treatment and symptom experiences.
Defining the Optimal Treatment for Clinical Stage I Nonseminomatous Germ Cell Testicular Cancer Using Decision Analysis
Authors: Nguyen Carvell T. , Fu Alex Z. , Gilligan Timothy D. , Wells Brian J. , Klein Eric A. , Kattan Michael W. , Stephenson Andrew J. 
Published: November 2009

Purpose There is equipoise regarding the optimal treatment of clinical stage (CS) I nonseminomatous germ cell testicular cancer (NSGCT). Formal mechanisms that enable patients to consider cancer outcomes, treatment-related morbidity, and personal preferences are needed to facilitate decision making between retroperitoneal lymph node dissection (RPLND), primary chemotherapy, and surveillance. Methods Decision analysis was performed using a Markov model that incorporated likelihoods of survival, treatment-related morbidity, and utilities for seven undesired post-treatment health states to estimate the quality-adjusted survival (QAS) for each treatment option. Utilities were obtained from 24 hypothetical NSGCT patients using a visual analog (rating) scale and standard gamble. Results Overall, QAS associated with each treatment was high and differences in QAS were small. Surveillance was the preferred intervention for patients with a risk of relapse less than 33% and 37% using the rating scale and standard-gamble method of utility assessment, respectively. Active treatment was favored over surveillance for patients with relapse risk on surveillance greater than 33% and 37% by the rating scale (RPLND preferred) and standard-gamble methods (primary chemotherapy preferred), respectively. Substantial differences in average utilities were seen depending on the method used. By the rating scale, patients substantially devalued life in six of seven undesired health states but they were surprisingly tolerant of treatment-related morbidity using standard gamble. Conclusion A decision model has been developed for CS I NSGCT that estimates QAS for RPLND, primary chemotherapy, and surveillance by considering cancer outcomes, morbidity, and patient preferences. Surveillance was the preferred intervention for all except those patients at high risk for relapse.
Immunochemotherapy and Autologous Stem-Cell Transplantation for Untreated Patients With Mantle-Cell Lymphoma: CALGB 59909
Authors: Damon Lloyd E. , Johnson Jeffrey L. , Niedzwiecki Donna , Cheson Bruce D. , Hurd David D. , Bartlett Nancy L. , LaCasce Ann S. , Blum Kristie A. , Byrd John C. , Kelly Michael , Stock Wendy , Linker Charles A. , Canellos George P. 
Published: November 2009

Purpose Mantle-cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin's lymphoma with a poor prognosis. We explored the feasibility, safety, and effectiveness of an aggressive immunochemotherapy treatment program that included autologous stem-cell transplantation (ASCT) for patients up to age 69 years with newly diagnosed MCL. Patients and Methods The primary end point was 2-year progression-free survival (PFS). A successful trial would yield a 2-year PFS of at least 50% and an event rate (early progression plus nonrelapse mortality) less than 20% at day +100 following ASCT. Seventy-eight patients were treated with two or three cycles of rituximab combined with methotrexate and augmented CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). This treatment was followed by intensification with high doses of cytarabine and etoposide combined with rituximab and filgrastim to mobilize autologous peripheral-blood stem cells. Patients then received high doses of carmustine, etoposide, and cyclophosphamide followed by ASCT and two doses of rituximab. Results There were two nonrelapse mortalities, neither during ASCT. With a median follow-up of 4.7 years, the 2-year PFS was 76% (95% CI, 64% to 85%), and the 5-year PFS was 56% (95% CI, 43% to 68%). The 5-year overall survival was 64% (95% CI, 50% to 75%). The event rate by day +100 of ASCT was 5.1%. Conclusion The Cancer and Leukemia Group B 59909 regimen is feasible, safe, and effective in patients with newly diagnosed MCL. The incorporation of rituximab with aggressive chemotherapy and ASCT may be responsible for the encouraging outcomes demonstrated in this study, which produced results comparable to similar treatment regimens.
Late-Occurring Neurologic Sequelae in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study
Authors: Goldsby Robert E. , Liu Qi , Nathan Paul C. , Bowers Daniel C. , Yeaton-Massey Amanda , Raber Shannon H. , Hill Daniel , Armstrong Gregory T. , Yasui Yutaka , Zeltzer Lonnie , Robison Leslie L. , Packer Roger J. 
Published: November 2009

Purpose Children with acute lymphoblastic leukemia (ALL) are often cured, but the therapies they receive may be neurotoxic. Little is known about the incidence and severity of late-occurring neurologic sequelae in ALL survivors. Data were analyzed to determine the incidence of adverse long-term neurologic outcomes and treatment-related risk factors. Patients and Methods We analyzed adverse neurologic outcomes that occurred after diagnosis in 4,151 adult survivors of childhood ALL who participated in the Childhood Cancer Survivor Study (CCSS), a retrospective cohort of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. A randomly selected cohort of the survivors' siblings served as a comparison group. Self-reported auditory-vestibular-visual sensory deficits, focal neurologic dysfunction, seizures, and serious headaches were assessed. Results The median age at outcome assessment was 20.2 years for survivors. The median follow-up time to death or last survey since ALL diagnosis was 14.1 years. Of the survivors, 64.5% received cranial radiation and 94% received intrathecal chemotherapy. Compared with the sibling cohort, survivors were at elevated risk for late-onset auditory-vestibular-visual sensory deficits (rate ratio [RR], 1.8; 95% CI, 1.5 to 2.2), coordination problems (RR, 4.1; 95% CI, 3.1 to 5.3), motor problems (RR, 5.0; 95% CI, 3.8 to 6.7), seizures (RR, 4.6; 95% CI, 3.4 to 6.2), and headaches (RR, 1.6; 95% CI, 1.4 to 1.7). In multivariable analysis, relapse was the most influential factor that increased risk of late neurologic complications. Conclusion Children treated with regimens that include cranial radiation for ALL and those who suffer a relapse are at increased risk for late-onset neurologic sequelae.
Trastuzumab for Patients With Axillary-Node–Positive Breast Cancer: Results of the FNCLCC-PACS 04 Trial
Authors: Spielmann Marc , Roché Henri , Delozier Thierry , Canon Jean-Luc , Romieu Gilles , Bourgeois Hugues , Extra Jean-Marc , Serin Daniel , Kerbrat Pierre , Machiels Jean-Pascal , Lortholary Alain , Orfeuvre Hubert , Campone Mario , Hardy-Bessard Anne-Claire , Coudert Bruno , Maerevoet Marie , Piot Gilles , Kramar Andrew , Martin Anne-Laure , Penault-Llorca Frédérique 
Published: November 2009

Purpose To evaluate the efficacy of trastuzumab in patients with node-positive breast cancer treated with surgery, adjuvant chemotherapy, radiotherapy, and hormone therapy if applicable. Patients and Methods Three thousand ten patients with operable node-positive breast cancer were randomly assigned to receive adjuvant anthracycline-based chemotherapy with or without docetaxel. Patients who presented human epidermal growth factor receptor 2 (HER2) -overexpressing tumors were secondary randomly assigned to either a sequential regimen of trastuzumab (6 mg/kg every 3 weeks) for 1 year or observation. The primary end point was disease-free survival (DFS). Results Overall 528 patients were randomly assigned between trastuzumab (n = 260) and observation (n = 268) arm. Of the 234 patients (90%) who received at least one administration of trastuzumab, 196 (84%) received at least 6 months of treatment, and 41 (18%) discontinued treatment due to cardiac events (any grade). At the date of analysis (October 2007), 129 DFS events were recorded. Random assignment to the trastuzumab arm was associated with a nonsignificant 14% reduction in the risk of relapse (hazard ratio, 0.86; 95% CI, 0.61 to 1.22; P = .41, log-rank stratified on pathologic node involvement). Three-year DFS rates were 78% (95% CI, 72.3 to 82.5) and 81% (95% CI, 75.3 to 85.4) in the observation and trastuzumab arms, respectively. Conclusion After a 47-month median follow-up, 1 year of trastuzumab given sequentially after adjuvant chemotherapy was not associated with a statistically significant decrease in the risk of relapse.
Tubular Carcinoma of the Breast: Further Evidence to Support Its Excellent Prognosis
Authors: Rakha Emad A. , Lee Andrew H.S. , Evans Andrew J. , Menon Sindhu , Assad Nancy Y. , Hodi Zsolt , Macmillan Douglas , Blamey Roger W. , Ellis Ian O. 
Published: November 2009

PurposeAlthough tubular carcinoma (TC) is known to have a favorable prognosis, it is still unknown whether this subtype represents a distinct type of breast carcinoma or whether it behaves like other low-grade luminal A–type breast carcinomas.MethodsIn this study, we performed a retrospective analysis of a large well-characterized series of breast cancers (2,608 carcinomas) to assess the clinicopathologic and molecular features and prognostic value of TC compared with grade 1 ductal carcinomas of the breast.ResultsWhen compared with grade 1 ductal carcinoma (n = 212), TC (n = 102) was more likely to be detected on mammographic screening, had smaller median size, and less frequently showed lymphovascular invasion. Compared with grade 1 ductal carcinoma, TC was associated with longer disease-free survival (χ2= 13.25, P < .001) and breast cancer–specific survival (χ2= 8.8, P = .003). In this study, none of the patients with TC developed distant metastasis or died from the disease without an intervening recurrence as invasive carcinoma of different histologic type.ConclusionWe conclude that the biologic behavior of TC is excellent and is more favorable than that of grade 1 ductal carcinoma. Patients with TC may be at risk of developing second primary carcinomas in the contralateral breast, which may be of higher grade and poorer potential prognostic outcome. In addition, patients with TC seem to have a close to normal life expectancy, and as a consequence, adjuvant systemic therapy may not be justified in their routine management.