Miracle-dz/UniFAR-FTUs huggingface dataset:
DGGE‐based whole‐gene mutation scanning of the dystrophin gene in Duchenne and Becker muscular dystrophy patients

Duchenne and Becker muscular dystrophy (DMD and BMD) are caused by mutations in the dystrophin gene. Large rearrangements in the gene are found in about two‐thirds of DMD patients, with ∼60% carrying deletions and 5–10% carrying duplications. Most of the remaining 30–35% of patients are expected to have small nucleotide substitutions, insertions, or deletions. To detect these subtle changes within the coding and splice site determining sequences of the dystrophin gene, we established a semiautomated denaturing gradient gel electrophoresis (DGGE) mutation scanning system. The DGGE scan covers the dystrophin gene with 95 amplicons, PCRed either individually or in a multiplex setup. PCR and pooling were performed semiautomatically, using a pipetting robot and 384‐well plates, enabling concurrent amplification of DNA of four patients in one run. Amplification of individual fragments was performed using one PCR program. The products were pooled just before gel loading; DGGE requires only a single gel condition. Validation was performed using DNA samples harboring 39 known DMD variants, all of which could be readily detected. DGGE mutation scanning was applied to analyze 135 DMD/BMD patients and potential DMD carriers without large deletions or duplications. In DNA from 25 out of 44 DMD patients (57%) and from 5 out of 39 BMD patients (13%), we identified clear pathogenic changes. All mutations were different, with the exception of one DMD mutation, which occurred twice. In DNA from 10 out of 44 potential DMD carriers, including four obligate carriers, we detected causative changes, including one pathogenic change in every obligate carrier. In addition to these pathogenic changes, we detected 15 unique unclassified variants, i.e., changes for which a pathogenic nature is uncertain. Hum Mutat 23:57–66, 2004. © 2003 Wiley‐Liss, Inc.
Heparan sulfate proteoglycans initiate dengue virus infection of hepatocytes

Dengue viruses (DEN) cause a broad spectrum of clinical manifestations including potentially life‐threatening conditions such as hemorrhagic shock syndrome and less frequently acute hepatitis with liver failure and encephalopathy. In addition, dengue viruses provide a potential model to understand the initiation of hepatocyte infection by the structurally closely related hepatitis C virus (HCV), because this virus at present cannot be grown in cell culture. Although the initial steps of viral infection are a critical determinant of tissue tropism and therefore pathogenesis, little is known about the molecular basis of binding and endocytic trafficking of DEN or of any other flavivirus. Our studies revealed that binding of radiolabeled DEN to the human hepatoma cell line HuH‐7 was strictly pH dependent and substantially inhibitable by the glycosaminoglycan heparin. Ligand‐blot analysis, performed as a viral overlay assay, showed two heparan sulfate (HS) containing cell‐surface binding proteins resolving at 33 and 37 kd. Based on the sensitivity of unprotected virus and the viral binding site on the cell surface to trypsin, viral internalization was quantified as an increase in trypsin protected virus over time. Virus trafficking to the site of degradation was inhibited by pH dissociation of the clathrin coat and dependent on IP3‐mediated homotypic endosomal fusion. These findings confirm the hypothesis that binding and internalization of DEN by hepatocytes are mediated primarily by HS containing proteoglycans and suggest that flaviviruses traffic the major clathrin‐dependent endocytic pathway during infection.
Prognostic value of tumour regression grading and depth of neoplastic infiltration within the perirectal fat after combined neoadjuvant chemo-radiotherapy and surgery for rectal cancer

Objective: To evaluate histological variables correlated with pathological response to chemo-radiotherapy protocols for rectal cancer and with local recurrence and survival. Methods: From 1994 to 2003, 58 patients with rectal cancer were enrolled in a non-randomised study based on standardised treatment with radiotherapy, 5-fluorouracil, and surgical resection, followed by histological examination, including tumour regression grading and depth of neoplastic infiltration within the perirectal fat. All patients were followed up. Mean (SD) length of follow up was 55.3 (28.1) months, range 5 to 108. Results: No case was found with no regression (grade 0). Tumour regression was defined as grade 1 in 24.5% of cases, grade 2 in 58.5%, grade 3 in 7.5%, and grade 4 (complete regression) in 9.5%. Neoplastic infiltration of >4 mm within the perirectal fat was found in 25.6% of cases in grade 1, 55.8% in grade, 2.7% in grade 3, and 11.6% in grade 4. In 80% cases of pT4 depth of neoplastic infiltration within the perirectal fat was >4 mm (100% were pN+), and the same spread was also found in 53.4% of pT2 and 86.2% of pT3. Pathological response was associated with regression grade (p = 0.006) and depth of neoplastic infiltration within the perirectal fat (p = 0.04). Tumour regression grading was an independent variable for pT (p = 0.0002), pN status (p = 0.00004), pathological staging (p = 0.000001), and local recurrence (p = 0.003). Conclusions: Involvement of the lateral resection margins correlates with a poor prognosis and indicates the likelihood of local recurrence of rectal cancer. Tumour regression grading and the depth of neoplastic infiltration within the perirectal fat are important prognostic factors that need to be evaluated routinely.
Metabolic parameters and perinatal outcomes of gestational diabetes mellitus in women with polycystic ovary syndrome

Abstract Aims: To investigate metabolic characteristics and perinatal outcomes of gestational diabetes mellitus (GDM) in women with polycystic ovary syndrome (PCOS). Methods: We evaluated 34 GDM in women with PCOS and 70 GDM in women without PCOS in this prospective study. All GDM women were treated with medical nutrition therapy (MNT). Pre-pregnancy clinical data, fasting glucose, fasting insulin (FINS), blood lipid, homeostasis model assessment index of insulin resistance (HOMA-IR) and perinatal outcomes were investigated. Results: GDM in women with PCOS had higher pre-pregnancy body mass index (BMI), higher incidence of overweight than in the non-PCOS group (each P<0.001). Incidence of history of infertility was also significantly higher in the PCOS group than in the non-PCOS group (20.6% vs. 2.9%, P<0.01). A higher incidence of early pregnancy loss (EPL) was found in the PCOS group than in the non-PCOS group (20.6% vs. 7.1%, P<0.05). Significantly higher in vitro fertilization and embryo transfer (IVF-ET) rate and insulin administration was also observed in the PCOS group than in the controls. No significant difference was found in the prevalence of preeclampsia, premature delivery, macrosomia, fetal death and neonatal congenital anomaly between GDM in women with and without PCOS (all P<0.05). Conclusions: Compared with the controls, no significant increase in the incidence of adverse perinatal outcomes was detected in GDM in women with PCOS by appropriate management.
A Unified Analysis of Stochastic Optimization Methods Using Jump System Theory and Quadratic Constraints

We develop a simple routine unifying the analysis of several important recently-developed stochastic optimization methods including SAGA, Finito, and stochastic dual coordinate ascent (SDCA). First, we show an intrinsic connection between stochastic optimization methods and dynamic jump systems, and propose a general jump system model for stochastic optimization methods. Our proposed model recovers SAGA, SDCA, Finito, and SAG as special cases. Then we combine jump system theory with several simple quadratic inequalities to derive sufficient conditions for convergence rate certifications of the proposed jump system model under various assumptions (with or without individual convexity, etc). The derived conditions are linear matrix inequalities (LMIs) whose sizes roughly scale with the size of the training set. We make use of the symmetry in the stochastic optimization methods and reduce these LMIs to some equivalent small LMIs whose sizes are at most 3 by 3. We solve these small LMIs to provide analytical proofs of new convergence rates for SAGA, Finito and SDCA (with or without individual convexity). We also explain why our proposed LMI fails in analyzing SAG. We reveal a key difference between SAG and other methods, and briefly discuss how to extend our LMI analysis for SAG. An advantage of our approach is that the proposed analysis can be automated for a large class of stochastic methods under various assumptions (with or without individual convexity, etc).
Development of a Set of Indicators to Evaluate Injury Control Research Centers

Background: Few methods have been defined for evaluating the individual and collective impacts of academic research centers. In this project, with input from injury center directors, we systematically defined indicators to assess the progress and contributions of individual Injury Control Research Centers (ICRCs) and, ultimately, to monitor progress of the overall injury center program. Method: We used several methods of deriving a list of recommended priority and supplemental indicators. This included published literature review, telephone interviews with selected federal agency staff, an e-mail survey of injury center directors, an e-mail survey of staff at the Centers for Disease Control and Prevention, a two-stage Delphi process (e-mailed), and an in-person focus group with injury center directors. We derived the final indicators from an analysis of ratings of potential indicators by center directors and CDC staff. We also examined qualitative responses to open-ended items that address conceptual and implementation issues. Results: All currently funded ICRCs participated in at least one part of the process, resulting in a list of 27 primary indicators (some with subcomponents), 31 supplemental indicators, and multiple suggestions for using the indicators. Conclusion: Our results support an approach that combines standardized definitions and quantifiable indicators with qualitative reporting, which allows consideration of center distinctions and priorities. The center directors urged caution in using the indicators, given funding constraints and recognition of unique institutional environments. While focused on injury research centers, we suggest these indicators also may be useful to academic research centers of other types.
Far-Infrared Census of Starburst-Seyfert Connection

Far-infrared flux densities are newly extracted from the IRAS database for the Revised Shapley-Ames and CfA complete samples of Seyfert galaxies. These data are used to classify the Seyfert galaxies into those where the far-infrared continuum emission is dominated by the active galactic nucleus (AGN), circumnuclear starburst, or host galaxy. While AGN-dominant objects consist of comparable numbers of Seyfert 1 and 2 galaxies, starburst- and host-dominant objects consist preferentially of Seyfert 2 galaxies. Thus, in addition to the dusty torus, the circumnuclear starburst region and host galaxy are important in hiding the broad-line region. Morphologically, starburst-dominant Seyfert galaxies are of later types and more strongly interacting than AGN-dominant Seyfert galaxies. In a later type galaxy, the AGN central engine has a lower Eddington luminosity, and the gaseous content is higher. The gas is efficiently supplied to the starburst via a galaxy-galaxy interaction. Morphologies of host-dominant Seyfert galaxies are of various types. Since starbursts in Seyfert galaxies are older than those in classical starburst galaxies, we propose an evolution from starburst to starburst-dominant Seyfert to host-dominant Seyfert for a late-type galaxy. An evolution from AGN-dominant Seyfert to host-dominant Seyfert is proposed for an early-type galaxy. These sequences have durations of a few times 108 yr and occur repeatedly within a galaxy during its evolution from a late type to an early type.
Proteomic profiling of cerebrospinal fluid identifies prostaglandin D2 synthase as a putative biomarker for pediatric medulloblastoma: A pediatric brain tumor consortium study

The aims of this study were to demonstrate the feasibility of centrally collecting and processing high‐quality cerebrospinal fluid (CSF) samples for proteomic studies within a multi‐center consortium and to identify putative biomarkers for medulloblastoma in CSF. We used 2‐DE to investigate the CSF proteome from 33 children with medulloblastoma and compared it against the CSF proteome from 25 age‐matched controls. Protein spots were subsequently identified by a combination of in‐gel tryptic digestion and MALDI‐TOF TOF MS analysis. On average, 160 protein spots were detected by 2‐DE and 76 protein spots corresponding to 25 unique proteins were identified using MALDI‐TOF. Levels of prostaglandin D2 synthase (PGD2S) were found to be six‐fold decreased in the tumor samples versus control samples (p<0.00001). These data were further validated using ELISA. Close examination of PGD2S spots revealed the presence of complex sialylated carbohydrates at residues Asn78 and Asn87. Total PGD2S levels are reduced six‐fold in the CSF of children with medulloblastoma most likely representing a host response to the presence of the tumor. In addition, our results demonstrate the feasibility of performing proteomic studies on CSF samples collected from patients at multiple institutions within the consortium setting.
Assessing the value of laser in situ keratomileusis by patient-reported outcomes using quality of life assessment.

PURPOSE To assess the value of laser in situ keratomileusis (LASIK) by patient-reported outcomes using quality of life assessment. METHOD This study included 288 consecutive patients treated by LASIK between July and December 2001 at two eye clinics. A Myopia-specific Quality of Life Questionnaire was developed in this study. The baseline quality of life corresponding to the situation where refractive error was corrected by glasses or contact lenses before LASIK treatment was evaluated by self-administered questionnaire. The evaluation was repeated at 4 days, and 1, 3, and 6 months after LASIK treatment. All question items were rated on a scale ranging from 1 (maximal dysfunction) to 5 (minimal dysfunction). RESULTS Factor analysis identified 34 questions in 4 subscales-visual function, visual symptoms, social role function, and psychological well-being. The Myopia-specific Quality of Life Questionnaire subscales proved to be internally consistent (Cronbach alpha = 0.70-0.95). Criterion validity was assessed by evaluating Spearman correlation between the overall or domain-specific quality of life and traditional measures of patient status. Overall Myopia-specific Quality of Life Questionnaire score changed from 3.21 preoperatively to 3.76, 4.00, 4.07, and 4.11 at 4 days, and 1, 3, and 6 months after surgery, respectively. Social role function showed the biggest improvement (score change: 1.51, P < .05), followed by psychological well-being (0.90, P < .05), visual function (0.72, P < .05), and visual symptoms (0.49, P < .05). Regression analysis results showed that the degree of uncorrected visual acuity, discomfort associated with myopia preoperatively, and location of eye center were significant factors affecting the magnitude of changes in quality of life after LASIK. CONCLUSIONS This study confirms that the value of LASIK went beyond the clinical achievement of refractive correction and extended to the improvement of quality of life.
Cost-effectiveness analysis of the direct and indirect impact of intranasal live attenuated influenza vaccination strategies in children: alternative country profiles

Background Influenza poses a significant burden on healthcare systems and society, with under-recognition in the paediatric population. Existing vaccination policies (largely) target the elderly and other risk groups where complications may arise. Objective The goal of this study was to evaluate the cost-effectiveness of annual paediatric vaccination (in 2–17-year-olds) with live attenuated influenza vaccination (LAIV), as well as the protective effect on the wider population in England and Wales (base). The study aimed to demonstrate broad applications of the model in countries where epidemiological and transmission data is limited and that have sophisticated vaccination policies (Brazil, Spain, and Taiwan). Methods The direct and indirect impact of LAIV in the paediatric cohort was simulated using an age-stratified dynamic transmission model over a 5-year time horizon of daily cycles and applying discounting of 3.5% in the base case. Pre-existing immunity structure was based on a 1-year model run. Sensitivity analyses were conducted. Results In the base case for England and Wales, the annual paediatric strategy with LAIV was associated with improvements in influenza-related events and quality-adjusted life years (QALYs) lost, yielding an incremental cost per QALY of £6,208. The model was robust to change in the key input parameters. The probabilistic analysis demonstrated LAIV to be cost effective in more than 99% of iterations, assuming a willingness-to-pay threshold of £30,000. Incremental costs per QALY for Brazil were £2,817, and for the cases of Spain and Taiwan the proposed strategy was dominant over the current practice. Conclusion In addition to existing policies, annual paediatric vaccination using LAIV provides a cost-effective strategy that offers direct and indirect protection in the wider community. Paediatric vaccination strategies using LAIV demonstrated clinical and economic benefits over alternative (current vaccination) strategies in England and Wales as well as Brazil, Spain, and Taiwan.
Renal effects of rapamycin in the spontaneously hypertensive rat

The effects of rapamycin (RAPA), administered at therapeutic doses, were investigated in the spontaneously hypertensive rat (SHR). Additionally, the reversibility of RAPA's renal effects was investigated at a supratherapeutic dose. At doses that were active in preventing heart and kidney allograft rejection in the rat (0.01–0.08 mg/kg i.v.), RAPA had no effect on kidney function or rat body weight gain. At higher doses (0.8 mg/kg), RAPA produced significant changes in kidney function parameters and caused a loss in body weight. Histopathologic changes, including necrotizing vasculopathy and tubular atrophy, were noted at therapeutic doses. The effects of RAPA on kidney function were completely reversible after a 2-week washout period, though the histopathologic changes were still evident. These studies demonstrate that RAPA does not impair kidney function at therapeutic doses when administered for 2 weeks but does appear to accelerate the naturally occurring renal lesions of the SHR.
MIMO-OFDM Channel Tracking Using a Dynamic ANN Topology

All the available algorithms for blind estimation namely constant modulus algorithm (CMA), Decision-Directed Algorithm (DDA/DFE) suffer from the problem of convergence to local minima. Also, if the channel drifts considerably, any DDA looses track of the channel. So, their usage is limited in varying channel conditions. The primary limitation in such cases is the requirement of certain overhead bits in the transmit framework which leads to wasteful use of the bandwidth. Also such arrangements fail to use channel state information (CSI) which is an important aid in improving the quality of reception. In this work, the main objective is to reduce the overhead imposed by the pilot symbols, which in effect reduces the system throughput. Also we formulate an arrangement based on certain dynamic Artificial Neural Network (ANN) topologies which not only contributes towards the lowering of the overhead but also facilitates the use of the CSI. A 2×2 Multiple Input Multiple Output (MIMO) system is simulated and the performance variation with different channel estimation schemes are evaluated. A new semi blind approach based on dynamic ANN is proposed for channel tracking in varying channel conditions and the performance is compared with perfectly known CSI and least square (LS) based estimation. Keywords—MIMO, Artificial Neural Network (ANN), CMA, LS, CSI.
An Educational Video to Increase Clinical Trials Enrollment among Lung Cancer Patients

Introduction: Only 3 to 5% of new adult cancer patients participate in clinical trials nationwide. The lack of knowledge and awareness about clinical trials is a significant barrier to clinical trials participation. A randomized trial was conducted to test the effect of an educational video on positively changing patients’ knowledge and attitudes regarding clinical trials and thereby increasing enrollment rates. Methods: Lung cancer patients were randomized to viewing either an 18-minute video about clinical trials before first clinic appointment or to standard care. Participants completed a baseline and 2-week postintervention survey to assess their knowledge and attitudes toward trials participation. Fisher’s exact test tests, t tests, and regression were used to compare patient characteristics and outcomes between arms. Results: Of 145 subjects randomized, 126 (63/arm) satisfied all inclusion criteria and were included in the analysis. A linear regression showed that the video intervention was significantly associated with patients’ self-assessed likelihood to enroll score measured at 2-week follow-up (p = 0.019). Although statistically insignificant, enrollment rates were found to be higher in the intervention arm for therapeutic trials alone (17.5% versus 11.1%) and for therapeutic and nontherapeutic trials combined (25.4% versus 15.9%). Conclusions: The brief educational video seems to be effective in positively changing lung cancer patients’ attitudes about participation in clinical trials. Higher enrollment rates were also observed in the intervention group but the differences did not reach statistical significance. These findings suggest a potential impact of the educational video on clinical trial enrollment; however, larger studies are needed to confirm these findings.
An SSB encoded by and operating on linear killer plasmids from Kluyveromyces lactis

The Kluyveromyces lactis linear plasmids k1 and k2 belong to the family of protein‐primed linear DNA genomes, which includes adenoviruses. Here we identify the 18 kDa gene product of k2ORF5 as a novel putative single‐stranded DNA binding protein, SSB. As judged from Western analysis using an epitope‐tagged fusion protein and ssDNA–agarose affinity chromatography, the Orf5 protein preferentially binds to ssDNA in vitro. Consistently, electrophoretic mobility shift assays demonstrate that ssDNA plasmid probes from k1 and k2 are retarded by this Orf5‐associated SSB activity. ORF5 gene shuffle‐mediated mutagenesis in vivo results in k1/k2 plasmid instability, pointing towards a role for the Orf5 protein in plasmid replication. Consistently, the Orf5 protein protects ssDNA from exonuclease digestion and stimulates Klenow enzyme. Our findings suggest a functional role for the Orf5 protein as a putative SSB probably required during k1/k2 plasmid DNA synthesis. Copyright © 2001 John Wiley & Sons, Ltd.
Variation in the human Achilles tendon moment arm during walking

Abstract The Achilles tendon (AT) moment arm is an important determinant of ankle moment and power generation during locomotion. Load and depth-dependent variations in the AT moment arm are generally not considered, but may be relevant given the complex triceps surae architecture. We coupled motion analysis and ultrasound imaging to characterize AT moment arms during walking in 10 subjects. Muscle loading during push-off amplified the AT moment arm by 10% relative to heel strike. AT moment arms also varied by 14% over the tendon thickness. In walking, AT moment arms are not strictly dependent on kinematics, but exhibit important load and spatial dependencies.