bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classical swine fever virus triggers RIG-I and MDA5-dependent signaling pathway to IRF-3 and NF-κB activation to promote secretion of interferon and inflammatory cytokines in porcine alveolar macrophages
Authors: Dong Xiao-Ying , Liu Wen-Jun , Zhao Ming-Qiu , Wang Jia-Ying , Pei Jing-Jing , Luo Yong-Wen , Ju Chun-Mei , Chen Jin-Ding 
Published: September 2013

Abstract
Background
Classical swine fever (CSF) caused by CSF virus (CSFV) is a highly contagious disease of pigs. The RNA helicases retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA-5) are differentially involved in the detection of various RNA viruses. In present study, we investigated the roles of RIG-I and MDA-5 in eliciting antiviral and inflammatory responses to CSFV shimen strain in Porcine alveolar macrophages (PAMs).

Methods
CSFV Shimen strain was used as challenge virus in this study and PAMs were cultured in vitro. Interferon regulatory factor (IRF)-3 and nuclear factor-kappa B (NF-κB) translocation was detected using immunofluorescent staining; RIG-I, MDA5, interferon promoter-stimulating factor 1 (IPS-1), IRF-3 and NF-κB expression was measured by Western Blotting; Interferon beta (IFN-β), IFN-α, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor (TNF-α) expression was tested by Enzyme-linked immunosorbent assays (ELISA) and shRNA-mediated knockdown of MDA5 or RIG-I was performed.

Results
The findings suggested that the initial response to CSFV infection resulted in the higher expression of RIG-I and MDA5 leading to the activation of IPS-1, IRF-3 and NF-κB in a dose-dependent manner. Evaluation of IFN-α, IFN-β, IL-1β, IL-6 or TNF-α expressed by PAMs showed significant differences between infected and uninfected cells. CSFV infected cells induced to express high levels of IFN-α, IFN-β, IL-1β, IL-6 and TNF-α in a dose-dependent way within 24 h post-infection (hpi). At the same time, CSFV improved the nuclear translocation of IRF-3 and NF-κB. We also directly compared and assessed the roles of RIG-I and MDA5 in triggering innate immune actions during CSFV infection through shRNA-mediated knockdown of MDA5 or RIG-I. We found that, compared to the control, the production of IFN-α, IFN-β, IL-1β, IL-6 and TNF-α in response to CSFV infection was heavily reduced in RIG-I knockdown cells while it was moderately decreased in MDA5 knockdown cells. PAMs derived from knockdown of both RIG-I and MDA5 almost failed to produce IFNs and inflammatory cytokines.

Conclusions
It indicates that CSFV can be recognized by both RIG-I and MDA5 to initiate the RIG-I signaling pathway to trigger innate defenses against infection.
Inflammatory myofibroblastic tumor with RANBP2 and ALKgene rearrangement: a report of two cases and literature review
Authors: Li Jian , Yin Wei-hua , Takeuchi Kengo , Guan Hong , Huang Yu-hua , Chan John KC 
Published: September 2013

Abstract
Inflammatory myofibroblastic tumors (IMTs) are categorized as intermediate biologic neoplasms, whereas IMTs with genetic features of ran-binding protein 2 (RANBP2) and anaplastic lymphoma kinase (ALK) rearrangement (IMT-RAs) are possibly related to a more aggressive clinical course. However, fewer than 10 cases of IMT-RA have been reported to date. Herein, we present 2 new cases of IMT-RA in which both tumors recurred quickly after primary surgery; one patient died 3 months later from the disease, and the other patient has been living with the disease for 12 months. IMT-RAs are characterized by noncohesive epithelioid and rounded tumoral cell morphology, commonly derived from pelvic and peritoneal cavities, and frequently show larger tumor sizes. The relation between the clinicopathologic features and poor prognosis of IMT-RA is discussed.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3314123381007714
Hepatic pseudocystic metastasis of well-differentiated ileal neuroendocrine tumor: a case report with review of the literature
Authors: Fiori Stefano , Del Gobbo Alessandro , Gaudioso Gabriella , Caccamo Lucio , Massironi Sara , Cavalcoli Federica , Bosari Silvano , Ferrero Stefano 
Published: September 2013

Abstract

Abstract
Imaging appearance of cyst-like changes is most frequently described in primary neuroendocrine lesions, especially pancreatic NETs.
The imaging finding of a pseudocystic lesion of the liver puts in differential diagnosis many pathologies such as infectious diseases, simple biliary cysts up to biliary cystadenomas and eventually to primary or metastatic malignancies.
Primary or metastatic hepatic malignancies with pseudocystic aspects are rare, and a pseudocystic aspect is reported only after neo-adjuvant treatment.
Liver metastasis of untreated neuroendocrine tumors are usually solid and, to our knowledge, only two cases of neuroendocrine cystic hepatic metastases of ileal atypical carcinoids have been reported so far.
We present a case of a 67 years old man with synchronous finding of an untreated hepatic pseudocystic lesion and an ileal mass histologically diagnosed as a well differentiated (G1) neuroendocrine tumor.

Virtual slides
The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1443883503102967.
Using corrected Cone-Beam CT image for accelerated partial breast irradiation treatment dose verification: the preliminary experience
Authors: Wang Jiazhou , Hu Weigang , Cai Gang , Peng Jiayuan , Pan Ziqiang , Guo Xiaomao , Chen Jiayi 
Published: September 2013

Abstract

Background
Accurate target localization is mandatory in the accelerated partial breast irradiation (APBI) delivery. Dosimetric verification for positional error will further guarantee the accuracy of treatment delivery. The purpose of this study is to evaluate the clinical feasibility of a cone beam computer tomographic (CBCT) image correction method in APBI.

Methods
A CBCT image correction method was developed. First, rigid image registration was proceeded for CTs and CBCTs; second, these images were separated into four parts; then, ratio images for each of the four parts of planning CTs/CBCTs were calculated and filtered to reduce the high spatial frequency; finally, the enhanced CBCT images were generated combing the four parts. An anthropomorphic thorax rando phantom was used to evaluate the feasibility and accuracy of the CBCT correction method. The CBCT images of consecutive 10 patients receiving APBI were corrected using the above method and dosimetric variations were evaluated. Each set of CBCT is composed of three images: one acquired after skin-marker setup, one after online setup correction and one after treatment delivery.

Results
The phantom study showed the improved accuracy of dose calculation with corrected CBCT. The Dose Volume Histogram (DVH) difference between the planning CT and corrected CBCT is less than the difference between the planning CT and original CBCT. The maximum dose difference between the corrected CBCT and planning CT is 0.8% in PTV_EVAL V100, which is 3.8% between original CBCT and planning. In the patient study, 67.4% of fractions benefit from CBCT setup corrections in PTV_EVAL D95, while in 47.4% of the fractions, reduced dose coverage was found on the post-treatment CBCT. Overall, the CBCT based initial setup correction guaranteed target dose coverage in 9 patients.

Conclusions
A generic CBCT image correction algorithm was created and proved to be easily implemented in clinic. Compared to the original CBCT, the corrected CBCT has more accuracy in dose calculation. The CBCT guided APBI based on initial skin setup is not sufficient to guarantee the accurate dose delivery throughout each fraction. The long treatment delivery time may compromise the target coverage benefits in some patients.
Global insights into energetic and metabolic networks in Rhodobacter sphaeroides
Authors: Imam Saheed , Noguera Daniel R , Donohue Timothy J 
Published: September 2013

Abstract

Background
Improving our understanding of processes at the core of cellular lifestyles can be aided by combining information from genetic analyses, high-throughput experiments and computational predictions.

Results
We combined data and predictions derived from phenotypic, physiological, genetic and computational analyses to dissect the metabolic and energetic networks of the facultative photosynthetic bacterium Rhodobacter sphaeroides. We focused our analysis on pathways crucial to the production and recycling of pyridine nucleotides during aerobic respiratory and anaerobic photosynthetic growth in the presence of an organic electron donor. In particular, we assessed the requirement for NADH/NADPH transhydrogenase enzyme, PntAB during respiratory and photosynthetic growth. Using high-throughput phenotype microarrays (PMs), we found that PntAB is essential for photosynthetic growth in the presence of many organic electron donors, particularly those predicted to require its activity to produce NADPH. Utilizing the genome-scale metabolic model iRsp1095, we predicted alternative routes of NADPH synthesis and used gene expression analyses to show that transcripts from a subset of the corresponding genes were conditionally increased in a ΔpntAB mutant. We then used a combination of metabolic flux predictions and mutational analysis to identify flux redistribution patterns utilized in the ΔpntAB mutant to compensate for the loss of this enzyme. Data generated from metabolic and phenotypic analyses of wild type and mutant cells were used to develop iRsp1140, an expanded genome-scale metabolic reconstruction for R. sphaeroides with improved ability to analyze and predict pathways associated with photosynthesis and other metabolic processes.

Conclusions
These analyses increased our understanding of key aspects of the photosynthetic lifestyle, highlighting the added importance of NADPH production under these conditions. It also led to a significant improvement in the predictive capabilities of a metabolic model for the different energetic lifestyles of a facultative organism.
Methylation profiling and evaluation of demethylating therapy in renal cell carcinoma
Authors: Ricketts Christopher J , Morris Mark R , Gentle Dean , Shuib Salwati , Brown Michael , Clarke Noel , Wei Wenbin , Nathan Paul , Latif Farida , Maher Eamonn R 
Published: September 2013

Abstract

Background
Despite therapeutic advances in targeted therapy, metastatic renal cell carcinoma (RCC) remains incurable for the vast majority of patients. Key molecular events in the pathogenesis of RCC include inactivation of the VHL tumour suppressor gene (TSG), inactivation of chromosome 3p TSGs implicated in chromatin modification and remodelling and de novo tumour-specific promoter methylation of renal TSGs. In the light of these observations it can be proposed that, as in some haematological malignancies, demethylating agents such as azacitidine might be beneficial for the treatment of advanced RCC.

Results
Here we report that the treatment of RCC cell lines with azacitidine suppressed cell proliferation in all 15 lines tested. A marked response to azacitidine therapy (>50% reduction in colony formation assay) was detected in the three cell lines with VHL promoter methylation but some RCC cell lines without VHL TSG methylation also demonstrated a similar response suggesting that multiple methylated TSGs might determine the response to demethylating therapies. To identify novel candidate methylated TSGs implicated in RCC we undertook a combined analysis of copy number and CpG methylation array data. Candidate novel epigenetically inactivated TSGs were further prioritised by expression analysis of RCC cell lines pre and post-azacitidine therapy and comparative expression analysis of tumour/normal pairs. Thus, with subsequent investigation two candidate genes were found to be methylated in more than 25% of our series and in the TCGA methylation dataset for 199 RCC samples: RGS7 (25.6% and 35.2% of tumours respectively) and NEFM in (25.6% and 30.2%). In addition three candidate genes were methylated in >10% of both datasets (TMEM74 (15.4% and 14.6%), GCM2 (41.0% and 14.6%) and AEBP1 (30.8% and 13.1%)). Methylation of GCM2 (P = 0.0324), NEFM (P = 0.0024) and RGS7 (P = 0.0067) was associated with prognosis.

Conclusions
These findings provide preclinical evidence that treatment with demethylating agents such as azacitidine might be useful for the treatment of advanced RCC and further insights into the role of epigenetic changes in the pathogenesis of RCC.
The effect of quitting smoking on HDL-cholesterol - a review based on within-subject changes
Authors: Forey Barbara A , Fry John S , Lee Peter N , Thornton Alison J , Coombs Katharine J 
Published: September 2013

AbstractA higher concentration of high density lipoprotein cholesterol (HDL-C) in ex-smokers than smokers has consistently been observed. Better evidence of quitting effects comes from within-subject changes. We extend an earlier meta-analysis to quantify the reduction, and investigate variation by time quit and other factors. We conducted Medline and Cochrane searches for studies measuring HDL-C in subjects while still smoking and later having quit. Using unweighted and inverse-variance weighted regression analysis, we related changes (in mmol/l) to intra-measurement period, and estimated time quit, and to study type, location and start year, age, sex, product smoked, validation of quitting, baseline HDL-C, baseline and change in weight/BMI, and any study constraints on diet or exercise. Forty-five studies were identified (17 Europe, 16 North America, 11 Asia, 1 Australia). Thirteen were observational, giving changes over at least 12 months, with most involving >1000 subjects. Others were smoking cessation trials, 12 randomized and 20 non-randomized. These were often small (18 of <100 subjects) and short (14 of <10 weeks, the longest a year). Thirty studies provided results for only one time interval. From 94 estimates of HDL-C change, the unweighted mean was 0.107 (95% CI 0.085-0.128). The weighted mean 0.060 (0.044 to 0.075) was lower, due to smaller estimates in longer term studies. Weighted means varied by time quit (0.083, 0.112, 0.111, 0.072, 0.058 and 0.040 for <3, 3 to <6, 6 to <13, 13 to <27, 27 to <52 and 52+ weeks, p=0.006). After adjustment for time quit, estimates varied by study constraint on diet/exercise (p=0.003), being higher in studies requiring subjects to maintain their pre-quitting habits, but no other clear differences were seen, with significant (p<0.05) increases following quitting being evident in all subgroups studied, except where data were very limited. For both continuing and never smokers, the data are (except for two large studies atypically showing significant HDL-C declines in both groups, and a smaller decline in quitters) consistent with no change, and contrast markedly with the data for quitters. We conclude that quitting smoking increases HDL-C, and that this increase occurs rapidly after quitting, with no clear pattern of change thereafter.
Immunohistochemical study of pituitary cells in wild and captive Salminus hilarii (Characiformes: Characidae) females during the annual reproductive cycle
Authors: Honji Renato Massaaki , Nóbrega Rafael Henrique , Pandolfi Matias , Shimizu Akio , Borella Maria Inês , Moreira Renata Guimarães 
Published: September 2013

Abstract
Freshwater fish that live exclusively in rivers are at particular risk from fragmentation of the aquatic system, mainly the species that migrate upriver for reproduction. That is the case of Salminus hilarii, an important migratory species currently classified as “almost threatened” in the São Paulo State (Brazil), facing water pollution, dam construction, riparian habitat destruction and environmental changes that are even more serious in this State. Additionally, this species show ovulation dysfunction in captivity. Our studies focused on the identification and distribution of the pituitary cell types in the adenohypophysis of S. hilarii females, including a morphometric analysis that compares pituitary cells from wild and captive broodstocks during the reproductive annual cycle. The morphology of adenohypophysial cells showed differences following the reproductive cycle and the environment. In general, optical density suggested a higher cellular activity during the previtellogenic (growth hormone) and vitellogenic (somatolactin) stages in both environments. Additionally, the nucleus/cell ratio analysis suggested that growth hormone and somatolactin cells were larger in wild than in captive females in most reproductive stages of the annual cycle. In contrast, prolactin hormone showed no variation throughout the reproductive cycle (in both environments). Morphometrical analyses related to reproduction of S. hilarii in different environmental conditions, suggest that somatolactin and growth hormone play an important role in reproduction in teleost and can be responsible for the regulation of associated processes that indirectly affect reproductive status.
Comparison of short- and long-term dynamic group psychotherapy: randomised clinical trial
Authors: Lorentzen Steinar , Ruud Torleif , Fjeldstad Anette , H⊘glend Per 
Published: September 2013

BackgroundThere are no randomised clinical trials comparing the outcomes of short- with long-term psychodynamic group psychotherapy.AimsTo compare differences in outcome during and after short-and long-term group psychotherapy.MethodIn total, 167 out-patients with mood, anxiety and personality disorders were randomised to short- or long-term group therapy (20 or 80 weekly, 90 min sessions). Outcome measures were: symptoms (Symptom Checklist 90 – Revised), interpersonal problems (Inventory of Interpersonal Problems – Circumplex) and psychosocial functioning (Global Assessment of Functioning (GAF) split version: GAF-Symptom and GAF-Function). Change over the 3-year study period was assessed using linear mixed models. The study was registered in clinicalTrials.gov as NCT00521417.ResultsPatients in both groups made significant gains. A significantly larger symptomatic change over time was found for long-term compared with short-term therapy, but no significant differences were detected for the three remaining outcome variables. There was a higher number of premature terminations in the long-term (33.3%) compared with the short-term group (8.6%).ConclusionsShort- and long-term therapy seem equally effective for typical out-patients seeking group psychotherapy, except for symptomatic distress.
Twice-Daily Subcutaneous Injection of Kisspeptin-54 Does Not Abolish Menstrual Cyclicity in Healthy Female Volunteers
Authors: Jayasena C. N. , Comninos A. N. , Nijher G. M. K. , Abbara A. , De Silva A. , Veldhuis J. D. , Ratnasabapathy R. , Izzi-Engbeaya C. , Lim A. , Patel D. A. , Ghatei M. A. , Bloom S. R. , Dhillo W. S. 
Published: September 2013

Background:
Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously.

Aim:
Our aim was to determine the effects of follicular-phase kisspeptin-54 treatment on menstrual cyclicity in healthy women.

Methods:
We performed a prospective, single-blinded, 1-way crossover study. Healthy women received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline during menstrual days 7–14 (n = 5 per treatment arm). Serial assessments of basal reproductive hormones, ultrasound parameters, LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were performed.

Results:
Menstrual cyclicity persisted in all women after follicular-phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish acute stimulation of LH after injection of kisspeptin-54 or GnRH. In addition, kisspeptin-54 treatment was associated with a shorter mean length of the menstrual cycle (mean length of menstrual cycle was 28.6 ± 1.4 days with saline vs 26.8 ± 3.1 days with kisspeptin, P &lt; .01), earlier onset of highest recorded serum LH (mean menstrual day of highest LH was 15.2 ± 1.3 with saline vs 13.0 ± 1.9 with kisspeptin, P &lt; .05), and earlier onset of the luteal phase (mean menstrual day of progesterone increase was 18.0 ± 2.1 with saline vs 15.8 ± 0.9 with kisspeptin, P &lt; .05).

Conclusion:
Our data suggest that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women. Further work is needed to determine whether kisspeptin could be used to treat certain anovulatory disorders.
A strategy for the generation, characterization and distribution of animal models by The Michael J. Fox Foundation for Parkinson's Research
Authors: Baptista Marco A. S. , Dave Kuldip D. , Sheth Niketa P. , De Silva Shehan N. , Carlson Kirsten M. , Aziz Yasmin N. , Fiske Brian K. , Sherer Todd B. , Frasier Mark A. 
Published: September 2013

Summary
Progress in Parkinson's disease (PD) research and therapeutic development is hindered by many challenges, including a need for robust preclinical animal models. Limited availability of these tools is due to technical hurdles, patent issues, licensing restrictions and the high costs associated with generating and distributing these animal models. Furthermore, the lack of standardization of phenotypic characterization and use of varying methodologies has made it difficult to compare outcome measures across laboratories. In response, The Michael J. Fox Foundation for Parkinson’s Research (MJFF) is directly sponsoring the generation, characterization and distribution of preclinical rodent models, enabling increased access to these crucial tools in order to accelerate PD research. To date, MJFF has initiated and funded the generation of 30 different models, which include transgenic or knockout models of PD-relevant genes such as Park1 (also known as Park4 and SNCA), Park8 (LRRK2), Park7 (DJ-1), Park6 (PINK1), Park2 (Parkin), VPS35, EiF4G1 and GBA. The phenotypic characterization of these animals is performed in a uniform and streamlined manner at independent contract research organizations. Finally, MJFF created a central repository at The Jackson Laboratory (JAX) that houses both non-MJFF and MJFF-generated preclinical animal models. Funding from MJFF, which subsidizes the costs involved in transfer, rederivation and colony expansion, has directly resulted in over 2500 rodents being distributed to the PD community for research use.
Mass and volume growth of larval insect tracheal system within a single instar
Authors: Helm Bryan R. , Davidowitz Goggy 
Published: September 2013

SummaryOrganisms must accommodate oxygen delivery to developing tissues as body mass increases during growth. In insects, the growth of the respiratory system has been assumed to occur only when it molts, whereas body mass and volume increase during the larval stages between molts. This decouples whole body growth from the growth of the oxygen supply system. This assumption is derived from the observation that the insect respiratory system is an invagination of the exoskeleton, which must be shed during molts for continued growth to occur. Here, we provide evidence that this assumption is incorrect. We found that the respiratory system increases substantially in both mass and volume within the last larval instar of Manduca sexta larvae, and that the growth of the respiratory system changes with diet quality, potentially as a consequence of shifting metabolic demands.