Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Evaluation of a PCR and Mass Spectroscopy- based (PCR-MS) Method for Quantitative, Type-specific Detection of Human Papillomavirus

Knowledge of the central role of high-risk human papillomavirus (HPV) in cervical carcinogenesis, coupled with an emerging need to monitor the efficacy of newly introduced HPV vaccines, warrant development and evaluation of type-specific, quantitative HPV detection methods. In the present study, a prototype PCR and mass spectroscopy (PCR-MS)-based method to detect and quantitate 13 high-risk HPV types is compared to the Hybrid Capture 2 High Risk HPV DNA test (HC2; Digene Corp., Gaithersburg, MD) in 199 cervical scraping samples and to DNA sequencing in 77 cervical tumor samples. High-risk HPV types were detected in 76/77 (98.7%) cervical tumor samples by PCR-MS. Degenerate and type-specific sequencing confirmed the types detected by PCR-MS. In 199 cervical scraping samples, all 13 HPV types were detected by PCR-MS. Eighteen (14.5%) of 124 cervical scraping samples that were positive for high-risk HPV by HC2 were negative by PCR-MS. In all these cases, degenerate DNA sequencing failed to detect any of the 13 high-risk HPV types. Nearly half (46.7%) of the 75 cervical scraping samples © 2009 Elsevier B.V. All rights reserved. *Corresponding author: Mack T. Ruffin, IV, MD, MPH, Department of Family Medicine, University of Michigan Medical School, 1018 Fuller St., Ann Arbor, MI 48104-1213, Tel: 1 734 998 7120 x 310, Fax: 1 734 998 7335, mruffin@umich.edu. 1Deceased Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript J Virol Methods. Author manuscript; available in PMC 2010 December 21. Published in final edited form as: J Virol Methods. 2009 September ; 160(1-2): 78–84. doi:10.1016/j.jviromet. 2009.04. 024. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript that were negative for high-risk HPV by the HC2 assay were positive by PCR-MS. Type-specific sequencing in a subset of these samples confirmed the HPV type detected by PCR-MS. Quantitative PCR-MS results demonstrated that 11/75 (14.7%) samples contained as much HPV copies/cell as HC2-positive samples. These findings suggest that this prototype PCR-MS assay performs at least as well as HC2 for HPV detection, while offering the additional, unique advantages of type-specific identification and quantitation. Further validation work is underway to define clinically meaningful HPV detection thresholds and to evaluate the potential clinical application of future generations of the PCR-MS assay.
17 β -Estradiol Reverses Shear Stress-Mediated LDL Modifications

Within arterial bifurcations or branching points, oscillatory shear stress (OSS) induces oxidative stress mainly via the NADPH oxidase system. It is unknown whether 17 β -estradiol (E 2 ) can regulate OSS-mediated low density lipoprotein (LDL) modifications. Bovine aortic endothelial cells (BAECs) were pre-treated with E 2 at 5 nmol/L, followed by exposure to OSS (0 ± 3.0 dynes/ cm 2 sec and 60 cycles/min) in a flow system. E 2 decreased OSS-mediated NADPH oxidase mRNA expression, and E 2 -mediated ·NO production was mitigated by the ·NO synthase inhibitor L-NAME. The rates of O 2−· production in response to OSS increased steadily as determined by superoxide dismutase-inhibited ferricytochrome c reduction; however, pre-treatment with E 2 decreased OSS-mediated O 2−· production (n=4, P<0.05). In the presence of native LDL (50 μ g/ mL), E 2 also significantly reversed OSS-mediated LDL oxidation as determined by high performance liquid chromatography. In the presence of O 2−· donor, xanthine oxidase (XO), E 2 further reversed XO-induced LDL lipid peroxidation (n=3, P<0.001). Mass spectra were acquired in the m/z 400–1800 range, revealing XO-mediated LDL protein nitration involving tyrosine 2535 in the α -2 domains, whereas pre-treatment with E 2 reversed this observation, consistent with the changes in nitrotyrosine intensities by the dot blots. E 2 plays an indirect antioxidative role. In addition to up-regulation of eNOS and down-regulation of Nox4 expression, E 2 influences LDL modifications via lipid peroxidation and protein nitration.
The Prevalence and Role of Low Lying Peroneus Brevis Muscle Belly in Patients with Peroneal Tendon Pathologies: A Potential Source for Tendon Subluxation

A low lying peroneus brevis muscle belly is a rare anomaly. There are few published studies that support presence of this anomaly as an etiology for peroneal tendon tear. However, the association between a low lying peroneus muscle belly (LLMB) and tendon subluxation is not well explored. In this retrospective study, the magnetic resonance imaging (MRI) and intraoperative findings of 50 consecutive patients undergoing a primary peroneal tendon surgery, in a five year period, were assessed. The sensitivity and specificity of MRI, in comparison to intraoperative findings for identifying peroneal tendon disease was investigated. Presence of associated peroneal tendon pathologies in patients with and without LLMB was compared. Sensitivity of MRI was high in identifying peroneal tenosynovitis (81.58%) and tear (85.71%). Although the sensitivity of MRI for detecting a LLMB (3.23%) and tendon subluxation (10.00%) was low, MRI had high specificity at 94.74% and 100%, respectively. Intraoperatively, LLMB was seen in 62.00% of patients with chronic lateral ankle pain and was associated with 64.52% cases of tenosynovitis, 29.03% cases of tendon subluxation, and 80.65% cases of peroneus brevis tendon tear. While presence of a LLMB did not show any statistically significant association with peroneus brevis tendon subluxation, among the 10 patients with intraoperatively observed tendon subluxation, 9 had a concomitant LLMB. More studies with a larger patient population are needed to better study the role of a low lying muscle belly as a mass occupying lesion resulting in peroneal tendon subluxation. Intraoperatively observed peroneal tendon pathologies associated with a peroneus brevis low lying muscle belly (LLMB) are compared to those with normal muscle length. The most common pathology seen was presence of peroneus brevis tendon tear in both groups. Peroneus brevis tendon subluxation was present in 10 total patients in our study, 9 of which had concomitant low lying muscle belly.
Polarized secretion of .3-amyloid precursor protein and amyloid (8-peptide in MDCK cells

The j-amyloid precursor protein (PAPP) is a widely expressed integral membrane protein that is proteolytically processed to yield several secreted derivatives, Includig soluble APP (APP5), the 4-kDa amyloid P-peptide (AP), and a related 3-kDa peptide (p3). To understand PiAPP tafcng and processing, we analyzed the sorting of IJAPP in Madin-Darby canine kidney (MDCK) cells, an epithelial cell known to possess physiologically distinct apical and basolateral plasma membranes. Processing of IJAPP resulted in highly polarized secretion of APP5. More than 90% of APP5 was detected in the basolateral compartment, and less than 10% was found in the apical compartment. This was associated with a preferential lcalization of (JAPP on the bamlateral cell surface. Activation of protein kinase C, which is known to enhance the secretion of APP5, did not change the polarity of APPs release but signifi-cantiy increased the amount secreted. Al and p3 peptides were also secreted predominantly basolaterally. In addition, MDCK cells secreted a truncated form of A bnning at Arg-S. These data show that the proteolytic processing products of IJAPP undergo polarized secretion. Moreover, the results suggest that the amyloidogenic AP peptide is generated following the polarized sorting of PAPP. The polarized basolateral secretion of AIJ in these epithellal cells provides a potential m a particu-larly interesting model system for studying polarized trafficking, it is initially made as a transmembrane which is into a variety of secreted proteolytic products. Moreover, the analysis of vectorial transport of PAPP in MDCK cells may also help to identify the cellular locus of AP generation.
Phase 2 study of guadecitabine (SGI-110), a novel hypomethylating agent, in treatment-naïve patients with acute myeloid leukaemia who are not candidates for intensive chemotherapy

Background— Hypomethylating agents azacitidine and decitabine have shown efficacy in myelodysplastic syndromes and acute myeloid leukaemia (AML), but responses are limited and of short duration, possibly due to short half-lives and suboptimal bone marrow exposure. Guadecitabine (SGI-110), a dinucleotide of decitabine and deoxyguanosine, is resistant to degradation by cytidine deaminase thus achieving longer half-life and exposure of its active metabolite, decitabine. We aimed to assess the safety and clinical activity of subcutaneously given this open-label, study, objective to evaluate and compare the activity and safety of two doses and schedules of guadecitabine, with a primary endpoint of composite complete response complete CR with incomplete platelet and with incomplete neutrophil regardless platelets Response was evaluated in all as long guadecitabine Secondary endpoints included safety, pharmacodynamics. We present the final trial analyses, although at time of database lock, 15 patients still being monitored for including six continuing treatment. This study registered ClinicalTrials.gov,
THEORY OF LIGHT DIFFRACTION BY SINGLE SKELETAL MUSCLE FIBERS

A theoretical discussion is presented describing the diffraction of laser light by a single fiber of striated muscle. The complete three-dimensional geometry of the fiber has been taken into consideration. The basic repeated unit is taken as the sarcomere of a single myofibril, including its cylindrical geometry. The single fiber is considered as the sum of myofibrils up to the fiber dimensions. When proper phasing is taken into account, three cases of interest are analyzed. (a) When the adjacent myofibrils are totally aligned with respect to their index of refraction regions (e.g., A and I bands), then the diffraction pattern reflects that of a larger striated cylinder with the dimensions of the fiber. (b) When a particular skew plane develops for the myofibril elements, additional Bragg reflection occurs at certain specific sarcomere lengths, and intensity asymmetry amongst the diffracted orders occurs. (c) When the myofibril phasing changes in a random fashion, while all sarcomeres remain at the same length, then intensity decrease is directly related to the phase deviation from a reference phase point. This condition may well describe a fiber undergoing active isometric contraction.
Characterization of RNA-Pt Adducts Formed from Cisplatin Treatment of Saccharomyces cerevisiae

The numerous regulatory roles of cellular RNAs suggest novel potential drug targets, but establishing intracellular drug-RNA interactions is challenging. Cisplatin ( cis -diamminedichloridoplatinum(II)) is a leading anticancer drug that forms exchange-inert complexes with nucleic acids, allowing its distribution on cellular RNAs to be followed ex vivo . Although Pt adduct formation on DNA is well-known, a complete characterization of cellular RNA-Pt adducts has not been performed. In this study, the action of cisplatin on S. cerevisiae in minimal media was established with growth curves, clonogenic assays, and tests for apoptotic markers. Despite high toxicity, cisplatin-induced apoptosis in S. cerevisiae was not observed under these conditions. In-cell Pt concentrations and Pt accumulation on poly(A)-mRNA, rRNA, total RNA, and DNA quantified via ICP-MS indicate ~4–20 fold more Pt accumulation in total cellular RNA than in DNA. Interestingly, similar Pt accumulation is observed on rRNA and total RNA, corresponding to one Pt per (14,600 ± 1,500) and (5760 ± 580) nucleotides on total RNA following 100 and 200 µM cisplatin treatments, respectively. Specific Pt adducts mapped by primer extension analysis of a solvent-accessible 18S rRNA helix occur at terminal and internal loop regions and appear as soon as 1 hr post-treatment. Pt per nucleotide accumulation on poly(A)-mRNA is 4–6-fold lower than on rRNA, but could have consequences for low copy-number or highly regulated transcripts. Taken together, these data demonstrate significant accumulation of Pt adducts on cellular RNA species following in cellulo cisplatin treatment. These and other small molecule-RNA interactions could disrupt processes regulated by RNA.
TSH Increases Iodine Uptake by Thyroid Cancer Cells During BRAF Silencing

, Abstract BACKGROUND— The BRAF V600E mutation is present in 62% of radioactive iodine resistant (RAIR) thyroid tumors and is associated with down-regulation of the sodium-iodide-symporter (NIS) and TSH-receptor (TSHr). We sought to evaluate the combined effect of BRAF inhibition and TSH supplementation on 131 I uptake of BRAF V600E -mutant human thyroid cancer cells. MATERIALS AND METHODS— WRO cells (a BRAF V600E -mutant follicular-derived papillary thyroid carcinoma cell line) were transfected with siRNA targeting BRAF for 72 hours in a physiologic TSH environment. NIS and TSHr expression were then evaluated at three levels: gene expression, protein levels, and 131 I uptake. These three main outcomes were then reassessed in TSH-depleted media and media supplemented with supratherapeutic concentrations of TSH. RESULTS— NIS gene expression increased 5.5-fold 36 hours after transfection (p=0.01) and TSHr expression increased 2.8-fold at 24 hours (p=0.02). NIS and TSHr protein levels were similarly increased 48 and 24 hours post-transfection, respectively. Seventy two hours after BRAF inhibition, 131 I uptake showed was unchanged in TSH-depleted media, increased by 7.5-fold (p<0.01) in physiologic TSH media, and increased by 9.1-fold (p<0.01) in supratherapeutic TSH media. CONCLUSIONS— The combined strategy of BRAF inhibition and TSH supplementation results in greater 131 I uptake than when either technique is utilized alone. This represents a simple and feasible approach that may improve outcomes in patients with RAIR thyroid carcinomas for which current treatment algorithms are ineffective.
Optimal Power Flow Controller for Grid-Connected Microgrids using Grasshopper Optimization Algorithm

Despite the vast benefits of integrating renewable energy sources (RES) with the utility grid, they pose stability and power quality problems when interconnected with the existing power system. This is due to the production of high voltages and current overshoots/undershoots during their injection or disconnection into/from the power system. In addition, the high harmonic distortion in the output voltage and current waveforms may also be observed due to the excessive inverter switching frequencies used for controlling distributed generator’s (DG) power output. Hence, the development of a robust and intelligent controller for the grid-connected microgrid (MG) is the need of the hour. As such, this paper aims to develop a robust and intelligent optimal power flow controller using a grasshopper optimization algorithm (GOA) to optimize the dynamic response and power quality of the grid-connected MG while sharing the desired amount of power with the grid. To validate the effectiveness of proposed GOA-based controller, its performance in achieving the desired power sharing ratio with optimal dynamic response and power quality is compared with that of its precedent particle swarm optimization (PSO)-based controller under MG injection and abrupt load change conditions. The proposed controller provides tremendous system’s dynamic response with minimum current harmonic distortion even at higher DG penetration levels.
A Cost-Effectiveness Analysis of Low-Risk Deliveries: A Comparison of Midwives, Family Physicians and Obstetricians Analyse coût-efficacité des accouchements à faible risque : comparaison entre sages-femmes, médecins de famille et obstétriciens

Objective : To investigate the cost-effectiveness of in-hospital obstetrical care by obstetricians (OBs), family physicians (FPs) and midwives (MWs) for delivery of low-risk obstetrical patients. Methods : Cost-effectiveness analysis from the Ministry of Health perspective using a retrospective cohort study. The time horizon was from hospital admission of a low-risk pregnant patient to the discharge of the mother and infant. Costing data included human resource, intervention and hospital case-mix costs. Interventions measured were induction or augmentation of labour with oxytocin, epidural use, forceps or vacuum delivery and caesarean section. The outcome measured was avoidance of transfer to a neonatal intensive care unit (NICU). Model results were tested using various types of sensitivity analyses. Findings : The mean maternal age by provider groups was 29.7 for OBs, 29.8 for FPs and 31.2 for MWs – a statistically higher mean for the MW group. The MW deliveries had lower costs and better outcomes than FPs and OBs. FPs also dominated OB.s The differences in cost per delivery were small, but slightly lower in MW ($5,102) and FP ($5,116) than in OB ($5,188). Avoidance of transfer to an NICU was highest for MW at 94.0% (95% CI: 91.0–97.0), compared with 90.2% for FP (95% CI: 88.2–92.2) and 89.6% for OB (95% CI: 88.6–90.6). The cost-effectiveness of the MW group is diminished by increases in compensation, and the cost-effectiveness of the FP group is sensitive to changes in intervention rates and costs. Conclusions : The MW strategy was the most cost-effective in this hospital setting. Given data limitations to further examine patient characteristics between groups, the overall conservative findings of this study support investments and better integration for MWs in the current system.
Comparison between different fiber coatings and adhesives on steel surfaces for distributed optical strain measurements based on Rayleigh backscattering

Abstract. Optical fiber measurement systems have recently gained popularity following a multitude of intensive investigations. A new technique has been developed for these measurement systems that uses Rayleigh backscatter to determine the distributed strain measurement over the total length of a fiber. These measurement systems have great potential in civil engineering and structural health monitoring. This paper addresses some preliminary comparisons between three different fiber coatings and six different adhesives on steel structures. The results are based on a bending test with specimens made of precision flat steel; optical fiber strain measurements were compared with photogrammetric strain measurements. Analysis of the test data showed a strong correlation between the optical measurement system's results and the theoretical results up to the yielding point of the steel. Furthermore, the results indicate that fibers with the Ormocer® and polyimide coatings have almost the same strain values as the reference measurement method. The main results of this investigation are a guideline describing how to attach optical fibers to steel surfaces for distributed fiber optical strain measurements and recommendations for coatings to obtain realistic strain values. Additionally, the advantages of distributed strain measurements were revealed, which illustrates the potential of Rayleigh backscattering applications.
Long-Term Quality of Life After Swallowing and Salivary sparing Chemo-IMRT in survivors of HPV-related Oropharyngeal Cancer

Purpose/Objectives— IMRT has improved the toxicity profile of chemo-radiotherapy for head and neck cancer. Long-term patient-reported outcomes beyond two years, however, remain scarcely reported. Amidst concerns of delayed-onset dysphagia and other toxicities, we evaluated long-term health-related quality-of-life (HRQOL) in two prospective studies of chemo-IMRT for oropharyngeal cancer (OPC). Methods and Materials— 69 of 93 patients with stage III/IV OPC treated on prospective studies of swallowing and salivary organ-sparing chemo-IMRT were eligible for long-term HRQOL assessment. Three validated patient-reported instruments, the Head and Neck QOL [HNQOL], University of Washington [UW]QOL, and Xerostomia Questionnaire [XQ]), previously administered from baseline through two-years in the parent studies, were re-© administered at long-term follow-up along with the Short-Form 36. Long-term changes in HRQOL from pre-treatment and two-years were evaluated. Results— 40 patients (58%) with a median follow-up of 6.5 years participated, 39 of whom (97.5%) had confirmed HPV+ OPC. Long-term, no clinically significant worsening was detected in mean HRQOL scores compared with two-years, with stable or improved HRQOL from pre-treatment in nearly all domains. “Moderate” or greater severity problems were uncommon, reported by 5% of patients for eating, 5% for swallowing, and 2.5% and 5% by HNQOL and UWQOL summary scores, respectively. Freedom-from-PEG-tube dependence and stricture dilation beyond 2 years was 97.5% and 95%, respectively. 11% and 14% of patients reported “moderate” or “severe” long-term worsening in HNQOL Pain and Overall Bother domains, respectively, which were associated with mean dose to the cervical esophagus, larynx, and pharyngeal constrictors. Conclusions— At more than 6-year median follow-up, OPC patients treated with swallowing and salivary organ-sparing chemo-IMRT reported stable or improved HRQOL in nearly all domains compared to both pre-treatment and two-year follow-up. New late toxicity after two years was uncommon. Further emphasis on sparing the swallowing organs may yield additional HRQOL gains for long-term OPC survivors. In this longitudinal study of patients with locally advanced HPV-associated oropharyngeal cancer treated on two prospective studies of swallowing and salivary organ-sparing chemo-IMRT, health-related (HR)QOL at a median of 6.5 years follow-up remained stable or improved in nearly all HRQOL domains compared to pre-treatment and 2-year post-treatment assessments. A minority of patients (10–14%) reported long-term worsening in pain and overall bother, which were associated with mean dose to the cervical esophagus, larynx, and pharyngeal constrictors.
Residential Power Forecasting Using Load Identification and Graph Spectral Clustering

Forecasting energy or power usage is an important part of providing a stable supply of power to all customers on a power grid. We present a novel method that aims to forecast the power consumption of a single house, or a set of houses, based on non-intrusive load monitoring (NILM) and graph spectral clustering. In the proposed method, the aggregate power signal is decomposed into individual appliance signals and each appliance’s power is forecasted separately. Then the total power forecast is formed by aggregating forecasted power levels of individual appliances. We use four publicly available datasets (reference energy disaggregation dataset, rainforest automation energy, almanac of minutely power dataset version 2, tracebase) to test our forecasting method and report its accuracy. The results show that our method is more accurate compared to popular existing approaches, such as autoregressive integrated moving average, similar profile load forecast, artificial neural network, and recent NILM-based forecasting.