bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll-Like Receptor 4-Linked Janus Kinase 2 Signaling Contributes to Internalization of Brucella abortus by Macrophages
Authors: Lee Jin Ju , Kim Dong Hyeok , Kim Dae Geun , Lee Hu Jang , Min Wongi , Rhee Man Hee , Cho Jae Youl , Watarai Masahisa , Kim Suk 
Published: April 2013

ABSTRACTBrucella abortusis an intracellular pathogen that uses a crafty strategy to invade and proliferate within host cells, but the distinct signaling pathways associated with phagocytic mechanisms ofB. abortusremain unclear. The present study was performed to test the hypothesis that Toll-like receptor 4 (TLR4)-linked signaling interacting with Janus kinase 2 (JAK2) plays an essential role inB. abortusphagocytosis by macrophages. The effects of TLR4-JAK2 signaling onB. abortusphagocytosis in murine macrophage RAW 264.7 cells were observed through an infection assay and confocal microscopy. We determined that the uptake ofB. abortuswas negatively affected by the dysfunction of TLR4 and JAK2. F-actin polymerization detected by flow cytometry and F-actin assay was amplified forB. abortusentry, whereas that event was attenuated by the disruption of TLR4 and JAK2. Importantly, JAK2 phosphorylation and actin skeleton reorganization were suppressed immediately afterB. abortusinfection in bone marrow-derived macrophages (BMDMs) from TLR4−/−mice, showing the cooperation of JAK2 with TLR4. Furthermore, small GTPase Cdc42 participated in the intermediate pathway of TLR4-JAK2 signaling onB. abortusphagocytosis. Consequently, TLR4-associated JAK2 activation in the early cellular signaling events plays a pivotal role inB. abortus-induced phagocytic processes in macrophages, implying the pathogenic significance of JAK2-mediated entry. Here, we elucidate that this specific phagocytic mechanism ofB. abortusmight provide achievable strategies for inhibitingB. abortusinvasion.
Physical Activity, Tumor PTGS2 Expression, and Survival in Patients with Colorectal Cancer
Authors: Yamauchi Mai , Lochhead Paul , Imamura Yu , Kuchiba Aya , Liao Xiaoyun , Qian Zhi Rong , Nishihara Reiko , Morikawa Teppei , Shima Kaori , Wu Kana , Giovannucci Edward , Meyerhardt Jeffrey A. , Fuchs Charles S. , Chan Andrew T. , Ogino Shuji 
Published: April 2013

AbstractBackground: Higher levels of physical activity are associated with lower colorectal carcinoma incidence and mortality, perhaps through influencing energy balance, cellular prosta7 systemic inflammation. Although evidence suggests interactive effects of energetics, sedentary lifestyle, and tumor CTNNB1 (β-catenin) or CDKN1B (p27) status on colon cancer prognosis, interactive effects of physical activity and tumor PTGS2 (the official symbol for COX-2) status on clinical outcome remain unknown.Methods: Using molecular pathological epidemiology database of 605 stage I–III colon and rectal cancers in two prospective cohort studies (the Nurse's Health Study and the Health Professionals Follow-up Study), we examined patient survival according to postdiagnosis physical activity and tumor PTGS2 status (with 382 PTGS2-positive and 223 PTGS2-negative tumors by immunohistochemistry). Cox proportional hazards models were used to calculate colorectal cancer-specific mortality HR, adjusting for clinical and other tumor variables including microsatellite instability status.Results: Among PTGS2-positive cases, compared with the least active first quartile, the multivariate HRs (95% confidence interval) were 0.30 (0.14–0.62) for the second, 0.38 (0.20–0.71) for the third, and 0.18 (0.08–0.41) for the fourth quartile of physical activity level (Ptrend = 0.0002). In contrast, among PTGS2-negative cases, physical activity level was not significantly associated with survival (Ptrend = 0.84; Pinteraction = 0.024, between physical activity and tumor PTGS2 status).Conclusions: Postdiagnosis physical activity is associated with better survival among patients with PTGS2-positive tumors but not among patients with PTGS2-negative tumors.Impact: Immunohistochemical PTGS2 expression in colorectal carcinoma may serve as a predictive biomarker in pathology practice, which may predict stronger benefit from exercise. Cancer Epidemiol Biomarkers Prev; 22(6); 1142–52. ©2013 AACR.
Myeloid-Derived Suppressor Cells Attenuate TH1 Development through IL-6 Production to Promote Tumor Progression
Authors: Tsukamoto Hirotake , Nishikata Ryutaro , Senju Satoru , Nishimura Yasuharu 
Published: April 2013

Abstract
Collaborative action between tumor cells and host-derived suppressor cells leads to peripheral tolerance of T cells to tumor antigens. Here, we showed that in tumor-bearing mice, generation of tumor antigen-specific effector T-helper cells (TH1) was significantly attenuated, and impaired TH1 differentiation was restored by the temporal blockade of interleukin (IL)-6 activity at the T-cell priming phase. Furthermore, we found that Gr-1+ myeloid-derived suppressor cells (MDSC) served as a source of IL-6 in tumor-bearing mice. Adoptive transfer of effector CD4+ T cells revealed that MDSC-sensitized effector CD4+ T cells were less potent in mounting antitumor immune responses, although effector T cells generated together with Gr-1+ cells from tumor-free mice eradicated established tumors. CD8+ T cells, IFN-γ, and MHC-class II expression in host mice were indispensable for the antitumor activity initiated by effector CD4+ T cells. Despite comparable suppressive activity of IL-6+/+ and IL-6−/− MDSC on primary T-cell activation, transfer of IL-6+/+ MDSC, but not IL-6−/− MDSC, dampened the efficient induction of effector TH1 cells and counteracted CD4+ T cell–mediated antitumor immunity including cognate help for CD8+ T cells in vivo. These findings suggest that, apart from the inhibitory effects on primary T-cell activation, MDSC promote tumor progression by attenuating functional differentiation of tumor-specific CD4+ T cells into effector TH1 cells through IL-6 production to promote tumor progression. This novel mode of MDSC-induced tolerance of effector CD4+ T cells should be considered as the basis for the rational design of effective T cell–mediated antitumor therapies. Cancer Immunol Res; 1(1); 64–76. ©2013 AACR.
Do hyperechoic thyroid nodules on B-ultrasound represent calcification?
Authors: Wu Gang , Zhou Zhongwen , Li Tianyi , Cai Duan , Wang Yi 
Published: April 2013

Objective To explore the correlation between hyperechoic thyroid nodules observed on B-ultrasound and histological calcification seen in paraffin-wax sections. Methods Records of patients who underwent surgical removal of thyroid nodules diagnosed on preoperative B-ultrasound were analysed retrospectively. Calcification present on B-ultrasound was compared with calcification seen in postoperative pathology specimens. Results Of the 1 655 patients included in the study, 518 had malignant and 1 137 had benign thyroid nodules. Calcification on B-ultrasound was seen in 366 patients with malignant, and 414 with benign nodules. Calcification was confirmed on histology in 209 and 127 of these patients, respectively, giving a sensitivity and specificity for B-ultrasound in diagnosing calcification (compared with histology) of 95.87% and 47.67%, respectively, in thyroid cancer and 90.71%, and 71.21% respectively in benign thyroid nodules. Microcalcification was seen in 483 patients on B-ultrasound and in 186 on histology, of whom 294 (60.87%) and 152 (81.72%), respectively, had thyroid cancer. Conclusions B-ultrasound is a useful and accurate test for detecting calcification in thyroid nodules, with a high sensitivity. There is a close association between calcification (especially microcalcification) and thyroid cancer on both B-ultrasound and pathological examination.
Hypothalamic dopaminergic stimulation in cluster headache
Authors: Lepper Anne , Frese Achim , Summ Oliver , Nofer Jerzy-Roch , Evers Stefan 
Published: April 2013

Background Cluster headache is associated with structural abnormalities of the hypothalamus. We were interested in the association of cluster headache with endocrinological functional abnormalities. Therefore, we applied the apomorphine challenge test, which is a specific test of hypothalamic dopaminergic activation. Methods We enrolled 13 patients with cluster headache outside the bout and without medication. They were stimulated with 0.005 mg/kg of body weight subcutaneous apomorphine hydrochloride. After 45 and 60 minutes, growth hormone (GH), prolactin and cortisol were measured. The test was also applied to 14 sex- and age-matched healthy control subjects. Results There were significantly higher GH levels in healthy subjects as compared to cluster headache patients 45 minutes after injection (10.8 ± 10.8 versus 4.4 ± 7.4 ng/ml; p = 0.038). Only in cluster headache, the GH level after 60 minutes was not significantly different from the baseline. The levels of prolactin and cortisol did not show any significant differences between cluster headache patients and in healthy subjects. Discussion Our data suggest that cluster headache is associated with an impaired dopaminergic stimulation. This finding supports the body of evidence that cluster headache is associated with a functional abnormality of the hypothalamus and that this association is a primary (i.e. idiopathic) and not a secondary phenomenon during the bout.
After an inpatient suicide: the aim and outcome of review mechanisms
Authors: Vine Ruth , Mulder Claudia 
Published: April 2013

Objective: To describe the intent and process of reviews undertaken following the death by suicide of an inpatient and suggest possible improvements. Method: The current processes of review undertaken in Victoria following the death by suicide of an inpatient were considered in the context of a review of unnatural, unexpected or violent inpatient deaths undertaken by the Chief Psychiatrist of Victoria in late 2011. Results: Review processes seeking to elucidate a cause or to find errors in the system that may have contributed to an incident are not always suitable nor sufficient in cases of inpatient suicide, where the patient’s actions (as opposed to the actions or inactions of clinicians) led to patient death; therefore, the cause of death is not independent of the patient’s condition and the treatment provided. Conclusion: While Root Cause Analysis remains a useful methodology, review of inpatient suicides should go beyond examination of systems issues only, and include consideration of the care and treatment provided: whether it met accepted clinical standards and was delivered by staff with adequate skills to consider the inherent risks of mental illness. Review of aggregate data has a useful role in identifying significant common features associated with inpatient deaths.
Genome-wide transcriptional responses of two metal-tolerant symbiotic Mesorhizobium isolates to Zinc and Cadmium exposure
Authors: Maynaud Géraldine , Brunel Brigitte , Mornico Damien , Durot Maxime , Severac Dany , Dubois Emeric , Navarro Elisabeth , Cleyet-Marel Jean-Claude , Le Quéré Antoine 
Published: April 2013

AbstractBackgroundMesorhizobium metalliduransSTM 2683TandMesorhizobiumsp. strain STM 4661 were isolated from nodules of the metallicolous legumeAnthyllis vulnerariafrom distant mining spoils. They tolerate unusually high Zinc and Cadmium concentrations as compared to other mesorhizobia. This work aims to study the gene expression profiles associated with Zinc or Cadmium exposure and to identify genes involved in metal tolerance in these two metallicolousMesorhizobiumstrains of interest for mine phytostabilization purposes.ResultsThe draft genomes of the twoMezorhizobiumstrains were sequenced and used to map RNAseq data obtained after Zinc or Cadmium stresses. Comparative genomics and transcriptomics allowed the rapid discovery of metal-specific or/and strain-specific genes. Respectively 1.05% (72/6,844) and 0.97% (68/6,994) predicted Coding DNA Sequences (CDS) for STM 2683 and STM 4661 were significantly differentially expressed upon metal exposure. Among these, a significant number of CDS involved in transport (13/72 and 13/68 for STM 2683 and STM 4661, respectively) and sequestration (15/72 and 16/68 for STM 2683 and STM 4661, respectively) were identified. Thirteen CDS presented homologs in both strains and were differentially regulated by Zinc and/or Cadmium. For instance, several PIB-type ATPases and genes likely to participate in metal sequestration were identified. Among the conserved CDS that showed differential regulation in the two isolates, we also foundznuABC homologs encoding for a high affinity ABC-type Zinc import system probably involved in Zinc homeostasis. Additionally, global analyses suggested that both metals also repressed significantly the translational machinery.ConclusionsThe comparative RNAseq-based approach revealed a relatively low number of genes significantly regulated in the twoMesorhizobiumstrains. Very few of them were involved in the non-specific metal response, indicating that the approach was well suited for identifying genes that specifically respond to Zinc and Cadmium. Among significantly up-regulated genes, several encode metal efflux and sequestration systems which can be considered as the most widely represented mechanisms of rhizobial metal tolerance. Downstream functional studies will increase successful phytostabilization strategies by selecting appropriate metallicolous rhizobial partners.
Lipoprotein subclass profiles in young adults born preterm at very low birth weight
Authors: Hovi Petteri , Kajantie Eero , Soininen Pasi , Kangas Antti J , Järvenpää Anna-Liisa , Andersson Sture , Eriksson Johan G , Ala-Korpela Mika , Wehkalampi Karoliina 
Published: April 2013

Abstract

Background
Adults born preterm at very low birth weight (VLBW ≤ 1500g) have increased risk factors for cardiovascular diseases including high blood pressure and impaired glucose regulation. Non-optimal lipoprotein profile is generally also likely to affect the increased cardiovascular risk, but lipoprotein subclass level data on adults born at VLBW are sparse.

Subjects and methods
We studied 162 subjects born at VLBW and 169 term-born controls, aged 19 to 27 years. Total lipid, triglyceride and cholesterol concentrations of 14 lipoprotein subclasses were determined by proton nuclear magnetic resonance spectroscopy in the fasting state and in 2-hour serum samples from an oral glucose tolerance test.

Findings
In comparison to controls, VLBW subjects had significantly higher fasting concentration of triglycerides in chylomicrons and largest very-low-density lipoprotein particles [XXL-VLDL-TG, difference 0.026 (95% CI: 0.004 to 0.049), P = 0.024], and of triglycerides in small high-density lipoprotein particles [S-HDL-TG, 0.026 (95% CI: 0.002 to 0.051), P = 0.037]. The seemingly important role of triglycerides was further supported by principal component analysis in which the first component was characterized by multiple lipoprotein triglyceride measures.

Conclusions
Young adults born at VLBW and their peers born at term had triglyceride-related differences in both VLDL and HDL subclasses. These differences suggest that the increased risk factors for cardiovascular diseases among the VLBW individuals in adulthood may partly relate to impaired triglyceride metabolism.
HCV Envelope protein 2 sequence comparison of Pakistani isolate and In-silico prediction of conserved epitopes for vaccine development
Authors: Idrees Sobia , Ashfaq Usman A , Khaliq Saba 
Published: April 2013

Abstract

Background
HCV is causing hundreds of cases yearly in Pakistan and has become a threat for Pakistani population. HCV E2 protein is a transmembrane protein involved in viral attachment and thus can serve as an important target for vaccine development but because of its variability, vaccine development against it has become a challenge. Therefore, this study was designed to isolate the HCV E2 gene from Pakistani HCV infected patients of 3a genotype, to perform In-silico analysis of HCV E2 isolated in Pakistan and to analyze HCV E2 protein sequence in comparison with other E2 proteins belonging to 3a and 1a genotypes to find potential conserved B-cells and T-cell epitopes that can be important in designing novel inhibitory compounds and peptide vaccine against genotype 3a and 1a.

Patients and methods
Patients were selected on the basis of elevated serum ALT and AST levels at least for six months, histological examination, and detection of serum HCV RNA anti-HCV antibodies (3rd generation ELISA). RNA isolation, cDNA synthesis, amplification, cloning and sequencing was performed from 4 patient’s serum samples in order to get the HCV E2 sequence. HCV E2 protein of Pakistani origin was analyzed using various bioinformatics tools including sequence and structure tools.

Results
HCV E1 protein modeling was performed with I-TASSER online server and quality of the model was assessed with ramchandran plot and Z-score. A total of 3 B-cell and 3 T-cell epitopes were found to be highly conserved among HCV 3a and 1a genotype.

Conclusion
The present study revealed potential conserved B-cell and T-cell epitopes of the HCV E2 protein along with 3D protein modeling. These conserved B-cell and T-cell epitopes can be helpful in developing effective vaccines against HCV and thus limiting threats of HCV infection in Pakistan.
Bone morphogenetic proteins and the polycystic ovary syndrome
Authors: van Houten E Leonie AF , Laven Joop SE , Louwers Yvonne V , McLuskey Anke , Themmen Axel PN , Visser Jenny A 
Published: April 2013

Abstract

Background
Polycystic Ovary Syndrome (PCOS) is defined by two out of the following three criteria being met: oligo- or anovulation, hyperandrogenism, and polycystic ovaries. Affected women are often obese and insulin resistant. Although the etiology is still unknown, members of the Transforming Growth Factor β (TGFβ) family, including Bone Morphogenetic Proteins (BMPs) and anti-Müllerian hormone (AMH), have been implicated to play a role. In this pilot study we aimed to measure serum BMP levels in PCOS patients.

Methods
Twenty patients, fulfilling the definition of PCOS according to the Rotterdam Criteria, were randomly selected. Serum BMP2, -4, -6 and −7 levels were measured using commercially available BMP2, BMP4, BMP6 and BMP7 immunoassays.

Results
Serum BMP2, serum BMP4 and serum BMP6 levels were undetectable. Three patients had detectable serum BMP7 levels, albeit at the lower limit of the standard curve.

Conclusions
BMP levels were undetectable in almost all patients. This suggests that with the current sensitivity of the BMP assays, measurement of serum BMP levels is not suitable as a diagnostic tool for PCOS.
Homologous recombination into the eosinophil peroxidase locus generates a strain of mice expressing Cre recombinase exclusively in eosinophils
Authors: Doyle Alfred D , Jacobsen Elizabeth A , Ochkur Sergei I , Willetts Lian , Shim Kelly , Neely Joseph , Kloeber Jake , LeSuer Will E , Pero Ralph S , Lacy Paige , Moqbel Redwan , Lee Nancy A , Lee James J 
Published: April 2013

ABSTRACT
Eosinophils are generally linked to innate host defense against helminths, as well as the pathologies associated with allergic diseases, such as asthma. Nonetheless, the activities of eosinophils remain poorly understood, which in turn, has prevented detailed definitions of their role(s) in health and disease. Homologous recombination in embryonic stem cells was used to insert a mammalianized Cre recombinase in the ORF encoding Epx. This knock-in strategy overcame previous inefficiencies associated with eosinophil-specific transgenic approaches and led to the development of a knock-in strain of mice (eoCRE), capable of mediating recombination of “floxed” reporter cassettes in &gt;95% of peripheral blood eosinophils. We also showed that this Cre expression was limited exclusively to eosinophil-lineage committed cells with no evidence of Cre-mediated toxicity. The efficiency and specificity of Cre expression in eoCRE mice were demonstrated further in a cross with a knock-in mouse containing a “(flox-stop-flox)” DTA cassette at the ROSA26 locus, generating yet another novel, eosinophil-less strain of mice. The development of eoCRE mice represents a milestone in studies of eosinophil biology, permitting eosinophil-specific gene targeting and overexpression in the mouse as part of next-generation studies attempting to define eosinophil effector functions.
Isolated latissimus dorsi transfer to restore shoulder external rotation in adults with brachial plexus injury
Authors: Ghosh S. , Singh V. K. , Jeyaseelan L. , Sinisi M. , Fox M. 
Published: April 2013

In adults with brachial plexus injuries, lack of active external rotation at the shoulder is one of the most common residual deficits, significantly compromising upper limb function. There is a paucity of evidence to address this complex issue. We present our experience of isolated latissimus dorsi (LD) muscle transfer to achieve active external rotation. This is a retrospective review of 24 adult post-traumatic plexopathy patients who underwent isolated latissimus dorsi muscle transfer to restore external rotation of the shoulder between 1997 and 2010. All patients were male with a mean age of 34 years (21 to 57). All the patients underwent isolated LD muscle transfer using a standard technique to correct external rotational deficit. Outcome was assessed for improvement in active external rotation, arc of movement, muscle strength and return to work. The mean improvement in active external rotation from neutral was 24° (10° to 50°). The mean increase in arc of rotation was 52° (38° to 55°). Mean power of the external rotators was 3.5 Medical Research Council (MRC) grades (2 to 5). A total of 21 patients (88%) were back in work by the time of last follow up. Of these, 13 had returned to their pre-injury occupation. Isolated latissimus dorsi muscle transfer provides a simple and reliable method of restoring useful active external rotation in adults with brachial plexus injuries with internal rotational deformity. Cite this article: Bone Joint J 2013;95-B:660–3.
Survival rates and causes of revision in cemented primary total knee replacement
Authors: Gøthesen Ø. , Espehaug B. , Havelin L. , Petursson G. , Lygre S. , Ellison P. , Hallan G. , Furnes O. 
Published: April 2013

We evaluated the rates of survival and cause of revision of seven different brands of cemented primary total knee replacement (TKR) in the Norwegian Arthroplasty Register during the years 1994 to 2009. Revision for any cause, including resurfacing of the patella, was the primary endpoint. Specific causes of revision were secondary outcomes. Three posterior cruciate-retaining (PCR) fixed modular-bearing TKRs, two fixed non-modular bearing PCR TKRs and two mobile-bearing posterior cruciate-sacrificing TKRs were investigated in a total of 17 782 primary TKRs. The median follow-up for the implants ranged from 1.8 to 6.9 years. Kaplan-Meier 10-year survival ranged from 89.5% to 95.3%. Cox’s relative risk (RR) was calculated relative to the fixed modular-bearing Profix knee (the most frequently used TKR in Norway), and ranged from 1.1 to 2.6. The risk of revision for aseptic tibial loosening was higher in the mobile-bearing LCS Classic (RR 6.8 (95% confidence interval (CI) 3.8 to 12.1)), the LCS Complete (RR 7.7 (95% CI 4.1 to 14.4)), the fixed modular-bearing Duracon (RR 4.5 (95% CI 1.8 to 11.1)) and the fixed non-modular bearing AGC Universal TKR (RR 2.5 (95% CI 1.3 to 5.1)), compared with the Profix. These implants (except AGC Universal) also had an increased risk of revision for femoral loosening (RR 2.3 (95% CI 1.1 to 4.8), RR 3.7 (95% CI 1.6 to 8.9), and RR 3.4 (95% CI 1.1 to 11.0), respectively). These results suggest that aseptic loosening is related to design in TKR. Cite this article: Bone Joint J 2013;95-B:636–42.