bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of cathepsins S and D signals a distinctive biochemical trait in CD34+ hematopoietic stem cells of relapsing–remitting multiple sclerosis patients
Authors: Martino Sabata , Montesano Simona , di Girolamo Ilaria , Tiribuzi Roberto , Di Gregorio Maria , Orlacchio Antonio , Datti Alessandro , Calabresi Paolo , Sarchielli Paola , Orlacchio Aldo 
Published: February 2013

Background: The elucidation of mechanistic aspects of relapsing–remitting multiple sclerosis (RRMS) pathogenesis may offer valuable insights into diagnostic decisions and medical treatment. Results: Two lysosomal proteases, cathepsins S and D (CatS and CatD), display an exclusive pattern of expression in CD34+ hematopoietic stem cells (HSCs) from peripheral blood of acute MS (A-MS) patients ( n = 20). While both enzymes normally exist as precursor forms in the HSCs of healthy individuals ( n = 30), the same cells from A-MS patients consistently exhibit mature enzymes. Further, mature cathepsins are expressed at lower rates in stable MS subjects (S-MS, n = 15) and revert to precursor proteins after interferon-β1a treatment ( n = 5). Mature CatD and CatS were induced in HSCs of healthy donors that were either co-cultured with PBMCs of A-MS patients or exposed to their plasma, suggesting a functional involvement of soluble agents. Following HSC exposure to several cytokines known to be implicated in MS, and based on relative cytokine levels displayed in A-MS, S-MS and control individuals, we identified IL-16 as a specific cell signaling factor associated with cathepsin processing. Conclusions: These data point to an evident correlation between CatS and CatD expression and MS clinical stage, and define a biochemical trait in HSCs with functional, medical, and diagnostic relevance.
Assessment of Interventricular Septal Motion Using Colour Tissue Doppler Imaging in Adult Patients with Atrial Septal Defect
Authors: Kardesoglu E , Cebeci BS , Celik T , Cingozbay BY , Dincturk M , Demiralp E 
Published: February 2013

We aimed to characterize changes in interventricular septum (IVS) motion and any relationship between them and the pulmonary-to-systemic flow ratio (Qp/Qs) in adult patients with atrial septal defect (ASD). Patients and controls were studied using colour tissue Doppler imaging (TDI). The septum length (SL) and distance from the colour change point (CCP) on the IVS to the aortic valve (the CCP distance) were measured on parasternal long axis views. Values normalized for body surface area, and the CCP distance to SL ratio, were calculated. Q p/ Q s values were correlated with CCP distance, normalized CCP distance and CCP distance: SL ratio. Statistically significant differences in CCP distance, normalized CCP distance and CCP distance: SL ratio were found between the two groups. In the ASD group, there was no correlation between Q p/ Q s and the echocardiographic measurements. The point between the motions in two different directions from the IVS shifted toward the apex in ASD patients compared with controls, and may be a mechanism involved in paradoxical septal motion.
Treatment of extra-articular and simple articular distal radial fractures with intramedullary nail versus volar locking plate
Authors: Safi A. , Hart R. , Těknědžjan B. , Kozák T. 
Published: February 2013

The purpose of this prospective, randomized and blinded study was to compare the clinical outcomes of distal radial fractures treated with either an intramedullary nail or a volar locking plate. Sixty two patients were enrolled in the study and randomized to treatment with a MICRONAILTM (Group 1, 31 patients) or an adaptive plate (Group 2, 31 patients). Fracture types included were unstable extra-articular metaphyseal distal radial fractures and simple or multifragmentary sagittal articular distal radial fractures (AO classification types A2, A3, B1.1 and B1.2). All patients were evaluated at 6 weeks, 3 months and 12 months after surgery. Outcome measures included standard radiographic parameters, active wrist range of motion, the disabilities of the arm, shoulder and hand (DASH) and Mayo wrist scores. We concluded that treatment of this subset of distal radius fractures with minimally invasive intramedullary nailing gives better clinical outcomes at 6 weeks after surgery than treatment with a volar locking plate. By 3 and 12 months following surgery, there are no significant differences in outcome between the two treatment methods. Disadvantages of the MICRONAIL™ fixation system include risk of injury to the superficial branch of the radial nerve and a narrower spectrum of indications than volar locking plates.
Comparison of body-array MRI and Partin tables for predicting extracapsular prostate cancer
Authors: Armitage James N , Igali Laszlo , Ball Richard Y , Mills Robert D , Kumar Vivekanandan 
Published: February 2013

Objective: The objective of this article is to evaluate the performance of magnetic resonance imaging (MRI) and Partin tables at predicting extracapsular disease (ECD) in men with prostate cancer. Patients and methods: We identified all patients who had a radical prostatectomy at our institution in 2008. MRI and Partin predictions of ECD were compared with the histopathological stage. Oncological outcome at one year was assessed by biochemical recurrence (BCR) (prostate-specific antigen (PSA) ≥ 0.4 ng/dl followed by another rise). Results: Staging and follow-up data were available for 69 of the 80 patients (86%) who had had radical prostatectomy. Thirty-five of 69 patients had a body-array MRI scan. MRI predicted ECD (≥ rT3) with a sensitivity of 41% and specificity of 69%. Partin tables (> 50% risk ECD) had a sensitivity of 81% and specificity of 54%. Of the 35 patients who had an MRI scan, 22 (63%) had ECD and nine (26%) had BCR. Of the 34 men who were not staged with an MRI, only 10 (29%) had ECD and four (12%) had BCR. Conclusion: MRI performed no better than Partin tables at predicting ECD. Furthermore, patients who did not have an MRI, because of favourable prognostic clinical variables, had a low risk of ECD and BCR. We question the role of body-array MRI for staging prostate cancer and recognise an urgent need for prospective evaluation of multiparametric MRI.
Biomechanical Evaluation of Mini-Fragment Hardware for Supination External Rotation Fractures of the Distal Fibula
Authors: Bariteau Jason T. , Blankenhorn Brad D. , Lareau Craig R. , Paller David J. , DiGiovanni Christopher W. 
Published: February 2013

Background. Supination external rotation distal fibula fractures are common, requiring fixation when associated with talar displacement. Subcutaneous distal fibula hardware may become painful, necessitating operative removal. We hypothesize that mini-fragment and small-fragment constructs will demonstrate similar biomechanical stability. Methods. A biomechanical comparison was performed in synthetic osteoporotic sawbones. The first arm compared two 2.4-mm lag screws with one 3.5-mm lag screw for fixation of a simulated supination external rotation distal fibula fracture. The second arm compared a 2.4-mm plate-screw construct with a 3.5-mm lag screw and one-third tubular neutralization plate. During torsional testing, torque and displacement were recorded, and stiffness and peak torque were determined. Results. Differences in mean stiffness and mean load at failure were not statistically significant with lag screw–only fixation. The 3.5-mm plate-screw construct outperformed the 2.4-mm plate-screw construct, but neither mean stiffness nor mean load at failure were statistically significantly different. Dynamic testing also demonstrated similar results. Conclusion. Our data suggest that isolated 2.4-mm screws function similarly to one 3.5-mm screw. Although the 3.5-mm plate-screw construct was stiffer, mean load at failure was equivalent for the 2 constructs. These data provide biomechanical evidence to support further investigation in the use of mini-fragment hardware for distal fibula fracture fixation. Levels of Evidence: Therapeutic, Level V
Demographics, treatment patterns, safety, and real-world effectiveness in patients aged 70 years and over with chronic lymphocytic leukemia receiving bendamustine with or without rituximab: a retrospective study
Authors: Kolibaba Kathryn S. , Sterchele James A. , Joshi Avani D. , Forsyth Michael , Alwon Erin , Beygi Hooman , Kennealey Gerard T. 
Published: February 2013

Objectives: Bendamustine is a unique cytotoxic agent active against various human malignancies, including chronic lymphocytic leukemia (CLL). In vitro studies suggest that cytotoxic activity of bendamustine on CLL-derived cells is synergized by rituximab. A retrospective chart review was conducted to characterize treatment-naïve outpatients and those with relapsed disease aged 70 years and over with CLL receiving bendamustine (with or without rituximab) and to evaluate real-world patterns of care, safety, and effectiveness. Methods: Using McKesson Specialty Care/US Oncology Network iKnowMed databases, 91 outpatients with at least two recorded visits and at least two cycles of bendamustine monotherapy or bendamustine–rituximab combination therapy were identified and included. Mean age at diagnosis and start of first therapy was 70.3 and 77.4 years respectively, and 63.7% of patients were men. Results: Observed overall response rate was 56.3% in pooled treatment-naïve patients [ n = 9; complete response (CR) 18.8%; partial response (PR) 37.5%; nodular partial response (nPR) 0%] and 58.7% in pooled patients with relapsed disease ( n = 44; CR 13.3%; PR 44.0%; nPR 1.3%). Median time to progressive disease has not been reached for the 16 treatment-naïve patients (median follow up 15.1 months), and was 18.4 months for those with relapsed disease ( n = 73). No unexpected toxicities were observed. Overall rate of blood/bone marrow toxicities (all grades) was 40.7%; grade 3/4 rates were 18.8% in treatment-naïve patients and 25.3% in those with relapsed disease. Most frequent nonhematologic adverse events were fatigue and rash. Conclusion: In this retrospective chart review of 91 outpatients with CLL aged 70 years and over, bendamustine (with or without rituximab) was an effective therapeutic option with manageable toxicity.
Non-AIDS–Defining Cancers in New Orleans
Authors: Ruiz Marco , Johnson Daniel , Reske Tom , Cefalu Charles , Estrada John 
Published: February 2013

Background: Non-AIDS–defining cancers in HIV-infected patients in the highly active antiretroviral therapy era have increased. To our knowledge a comprehensive review of non-AIDS–related malignancies in New Orleans has not yet been conducted. Methods: Databases from main institutions in New Orleans were queried retrospectively for the years 2001 to 2011. The International Classification of Diseases, Ninth Revision codes were used to search for HIV infection and cancer comorbidity. Results: A total of 16 patients were diagnosed with lung cancer (mean age 50 years) with 81% of the patients presenting with advanced stages. In all, 20 (mean age 47 years) were diagnosed with anal cancer, and 35% presented in late stages. In all, 14 patients (mean age 42 years) were diagnosed with Hodgkin Lymphoma, and 64% were diagnosed at late stage. A total of 5 women (mean age 44 years) were diagnosed with breast cancer with 40% of them presenting at late stage. Conclusion: Malignancies were diagnosed at late stages in the majority of the cases, presented with worse outcomes, and had higher recurrence rates. The role of HIV and other viruses (Epstein Barr virus, human papillomavirus) and the potential mechanisms or pathways of oncogene activation also need to be clarified.
Migraine predicts physical and pain symptoms among psychiatric outpatients
Authors: Hung Ching-I , Liu Chia-Yih , Wang Shuu-Jiun 
Published: February 2013

Abstract

Background
No study has been performed to compare the impacts of migraine and major depressive episode (MDE) on depression, anxiety and somatic symptoms, and health-related quality of life (HRQoL) among psychiatric outpatients. The aim of this study was to investigate the above issue.

Methods
This study enrolled consecutive psychiatric outpatients with mood and/or anxiety disorders who undertook a first visit to a medical center. Migraine was diagnosed according to the International Classification of Headache Disorders, 2nd edition. Three psychometric scales and the Short-Form 36 were administered. General linear models were used to estimate the difference in scores contributed by either migraine or MDE. Multiple linear regressions were employed to compare the variance of these scores explained by migraine or MDE.

Results
Among 214 enrolled participants, 35.0% had migraine. Bipolar II disorder patients (70.0%) had the highest percentage of migraine, followed by major depressive disorder (49.1%) and only anxiety disorder (24.5%). Patients with migraine had worse depression, anxiety, and somatic symptoms and lower SF-36 scores than those without. The estimated differences in the scores of physical functioning, bodily pain, and somatic symptoms contributed by migraine were not lower than those contributed by MDE. The regression model demonstrated the variance explained by migraine was significantly greater than that explained by MDE in physical and pain symptoms.

Conclusions
Migraine was common and the impact of migraine on physical and pain symptoms was greater than MDE among psychiatric outpatients. Integration of treatment strategies for migraine into psychiatric treatment plans should be considered.
HLA class II SNP interactions and the association with type 1 diabetes mellitus in Bengali speaking patients of Eastern India
Authors: Raha Oindrila , Sarkar Biswanath , Lakkakula Bhaskar VKS , Pasumarthy Veerraju , Godi Sudhakar , Chowdhury Subhankar , Raychaudhuri Pradip , Vadlamudi Raghavendra Rao 
Published: February 2013

Abstract

Background
Several studies have demonstrated a fundamental role for the HLA in the susceptibility of, or protection to, type 1 diabetes mellitus (T1DM). However, this has not been adequately studied in Asian Indian populations. To assess the frequency of HLA class II (DPA1, DPB1, DQA1, DQB1 and DRB1) associated to susceptibility or protection toT1DM in a Bengali population of India with diabetes.

Results
Single nucleotide polymorphism study. The HLA genotyping was performed by a polymerase chain reaction followed by their HLA-DP, DQ, and DRB1 genotypes and haplotypes by sequencing method. The results are studied by Plink software. The χ
2 tests were used for the inferential statistics. To our knowledge, this study is the first of a kind which has attempted to check the HLA association with T1DM by SNPs analysis. The study recruited 151 patients with T1DM and same number of ethno-linguistic, sex matched non-diabetic controls. The present study found a significant SNP rs7990 of HLA-DQA1 (p = 0.009) negative correlation, again indicating that risk from HLA is considerably more with T1DM.

Conclusions
This study demonstrates that the HLA class-II alleles play a major role in genetic basis of T1DM.
Identification of germ cell-specific genes in mammalian meiotic prophase
Authors: Li Yunfei , Ray Debjit , Ye Ping 
Published: February 2013

Abstract

Background
Mammalian germ cells undergo meiosis to produce sperm or eggs, haploid cells that are primed to meet and propagate life. Meiosis is initiated by retinoic acid and meiotic prophase is the first and most complex stage of meiosis when homologous chromosomes pair to exchange genetic information. Errors in meiosis can lead to infertility and birth defects. However, despite the importance of this process, germ cell-specific gene expression patterns during meiosis remain undefined due to difficulty in obtaining pure germ cell samples, especially in females, where prophase occurs in the embryonic ovary. Indeed, mixed signals from both germ cells and somatic cells complicate gonadal transcriptome studies.

Results
We developed a machine-learning method for identifying germ cell-specific patterns of gene expression in microarray data from mammalian gonads, specifically during meiotic initiation and prophase. At 10% recall, the method detected spermatocyte genes and oocyte genes with 90% and 94% precision, respectively. Our method outperformed gonadal expression levels and gonadal expression correlations in predicting germ cell-specific expression. Top-predicted spermatocyte and oocyte genes were both preferentially localized to the X chromosome and significantly enriched for essential genes. Also identified were transcription factors and microRNAs that might regulate germ cell-specific expression. Finally, we experimentally validated Rps6ka3, a top-predicted X-linked spermatocyte gene. Protein localization studies in the mouse testis revealed germ cell-specific expression of RPS6KA3, mainly detected in the cytoplasm of spermatogonia and prophase spermatocytes.

Conclusions
We have demonstrated that, through the use of machine-learning methods, it is possible to detect germ cell-specific expression from gonadal microarray data. Results from this study improve our understanding of the transition from germ cells to meiocytes in the mammalian gonad. Further, this approach is applicable to other tissues for which isolating cell populations remains difficult.
Impact of care management processes and integration of care on blood pressure control in diabetes
Authors: Wong Ken , Boulanger Luke , Smalarz Amy , Wu Ning , Fraser Kimberly , Wogen Jenifer 
Published: February 2013

Abstract

Background
Fragmentation within health care systems may negatively impact the quality of chronic disease patient care. We sought to evaluate the relationship between care management processes (CMP), integration of services, and blood pressure (BP) control among diabetic patients.

Methods
Retrospective chart reviews were performed for a random sample of adult diabetic hypertensive patients (n = 2,162) from 28 physician organizations in the United States (US). A modified version of the Physician Practice Connection Readiness Survey (PPC-RS) was completed by the chief medical officer at each site. The PPC-RS measured health system organization, delivery system redesign, decision support, clinical information systems, and self-management support, and an integration scale measured structure, functions, and financial risk. Correlations between PPC and integration scores and BP outcomes were assessed using Spearman correlation coefficients.

Results
Approximately 39.9% of diabetic patients had controlled BP. Mean total PPC score across sites was 55, with highest mean scores for health system organization (81), followed by design support (60), clinical information systems (57), self-management support (39), and delivery system redesign (39). Mean integration score was 46 (SD 27, range 4–93), and means of subscores were 64 for structure, 33 for financial risk, and 42 for function. Clinical information systems subscore was correlated with uncontrolled BP (r = −0.38, p < 0.05), while association with total PPC score was strong but not significant at p < 0.05 (r = −0.32). Total integration score and the structure subscore were significantly correlated with BP control (r = 0.38, p < 0.05, and r = 0.49, p < 0.01).

Conclusions
This study suggests that CMP and service integration may be associated with better outcomes in diabetes, though results were mixed and limited by a small number of participating sites. Primary care implementation of integrated electronic medical records may have a beneficial effect on patient outcomes for diabetes and other chronic diseases.
Attenuated antigen-specific T cell responses in cirrhosis are accompanied by elevated serum interleukin-10 levels and down-regulation of HLA-DR on monocytes
Authors: Peter Jack , Frey Oliver , Stallmach Andreas , Bruns Tony 
Published: February 2013

AbstractBackgroundAdvanced liver disease predisposes to bacterial translocation and endotoxaemia which can contribute to elevated circulating levels of IL-10 and down-regulation of MHC class II on antigen-presenting cells. We sought to evaluate antigen-specific T-cell responses toward common viral antigens in order to investigate defects in cellular immunity in cirrhosis.MethodsPeripheral blood was obtained from 22 cirrhotic patients with systemic inflammation, 13 cirrhotic patients without systemic inflammation and 14 healthy controls. C-reactive protein was used as an indicator for systemic inflammation using a cut-off of 10 mg/l. Intracellular Th1 cytokines were quantified after T cell-stimulation with the viral peptides EBNA1 and BZLF1 or the bacterial superantigen SEB by flow cytometry. Serum levels of lipopolysaccharide-binding protein (LBP) and IL-10 were quantified by ELISA.ResultsCompared to healthy controls, patients with cirrhosis had higher circulating levels of LBP and IL-10, an expansion of peripheral blood CD14+monocytes with low HLA-DR expression and an increased fraction of CD25-positive CD4+and CD8+T cells. These findings were most pronounced in cirrhotic patients with systemic inflammation but fell short of reaching statistical significance when comparing against cirrhotic patients without systemic inflammation. In the former group TNF-α production in CD4+and CD8+T cells was reduced after stimulation with SEB, whereas there was no significant difference between the total cohort of cirrhotic patients and controls. After stimulation with the overlapping peptide pools for viral antigens EBNA1 and BZLF1, the number of responding T cells and the amount of TNF-α or IFN-γ production did not differ between the three pre-defined groups. However, cirrhotic patients with null-responses to EBV peptides had significantly higher serum IL-10 levels than responders to EBV peptides. Furthermore, TNF-α production in responding T cells was attenuated in patients with a high frequency of CD14+HLA-DR-monocytes.ConclusionOur data suggest that bacterial translocation, endotoxaemia, inflammation and T cell activation in cirrhosis are accompanied by an increase in circulating anti-inflammatory cytokines, reduced monocytic MHC class II expression and attenuated cytokine production in T cells. These changes are likely to contribute to altered adaptive immune responses during infection or after vaccination.
Promoter hypomethylation, especially around the E26 transformation-specific motif, and increased expression of poly (ADP-ribose) polymerase 1 in BRCA-mutated serous ovarian cancer
Authors: Bi Fang-Fang , Li Da , Yang Qing 
Published: February 2013

Abstract

Background
Poly (ADP-ribose) polymerase 1 (PARP1) overexpression plays a critical role in ovarian cancer progression and the clinical development of PARP1 inhibitors to treat BRCA-mutated ovarian cancer has advanced rapidly. However, the mechanism regulating PARP1 expression remains unknown. Alterations in gene expression mediated by promoter methylation are being increasingly recognized and have frequently been reported in ovarian cancer. We therefore investigated the methylation status of the PARP1 promoter region and its correlation with PARP1 expression in BRCA-mutated ovarian cancer.

Methods
DNA from BRCA-mutated serous ovarian cancer samples and adjacent normal ovarian tissues were analyzed by bisulfite sequence using primers focusing on the CpG island in the promoter region of PARP1. Expression levels of PARP1 were assessed by immunohistochemistry and real-time PCR.

Results
Serous ovarian cancer tissues displayed decreased DNA methylation in the promoter region of PARP1 compared to normal tissue, and methylation intensity correlated inversely with PARP1 mRNA levels. More importantly, E26 transformation-specific (ETS) defined CpG sites were significantly less methylated in ovarian cancer samples.

Conclusions
These results indicate that hypomethylation of the promoter region, especially around the ETS motif might play a role in the upregulation of PARP1 expression in the progression of ovarian cancer.