Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and feasibility of the NanoKnife system for irreversible electroporation ablative treatment of canine spontaneous intracranial gliomas.

OBJECT Irreversible electroporation (IRE) is a novel nonthermal ablation technique that has been used for the treatment of solid cancers. However, it has not been evaluated for use in brain tumors. Here, the authors report on the safety and feasibility of using the NanoKnife IRE system for the treatment of spontaneous intracranial gliomas in dogs. METHODS Client-owned dogs with a telencephalic glioma shown on MRI were eligible. Dog-specific treatment plans were generated by using MRI-based tissue segmentation, volumetric meshing, and finite element modeling. After biopsy confirmation of glioma, IRE treatment was delivered stereotactically with the NanoKnife system using pulse parameters and electrode configurations derived from therapeutic plans. The primary end point was an evaluation of safety over the 14 days immediately after treatment. Follow-up was continued for 12 months or until death with serial physical, neurological, laboratory, and MRI examinations. RESULTS Seven dogs with glioma were treated. The mean age of the dogs was 9.3 ± 1.6 years, and the mean pretreatment tumor volume was 1.9 ± 1.4 cm(3). The median preoperative Karnofsky Performance Scale score was 70 (range 30-75). Severe posttreatment toxicity was observed in 2 of the 7 dogs; one developed fatal (Grade 5) aspiration pneumonia, and the other developed treatment-associated cerebral edema, which resulted in transient neurological deterioration. Results of posttreatment diagnostic imaging, tumor biopsies, and neurological examinations indicated that tumor ablation was achieved without significant direct neurotoxicity in 6 of the 7 dogs. The median 14-day post-IRE Karnofsky Performance Scale score of the 6 dogs that survived to discharge was 80 (range 60-90), and this score was improved over the pretreatment value in every case. Objective tumor responses were seen in 4 (80%) of 5 dogs with quantifiable target lesions. The median survival was 119 days (range 1 to > 940 days). CONCLUSION With the incorporation of additional therapeutic planning procedures, the NanoKnife system is a novel technology capable of controlled IRE ablation of telencephalic gliomas.
Motivating factors influencing choice of major in undergraduates in communication sciences and disorders

The purposes of this study were to determine: (1) whether background factors influence the choice of Communication Sciences and Disorders (CSD) as an academic major; (2) what motivates students to major in CSD; (3) the relationship between motivation to pursue CSD as a major and the attractiveness of the major; and (4) whether motivation influences the perceived value of a career in CSD. A survey of 143 undergraduates was created and administered to assess motivational factors that influence the choice of major. The participants had diverse ethnic/racial and cultural backgrounds and were enrolled in CSD courses in the Liberal Arts College of St John's University, a US American Institution in Queens, New York. Preliminary analyses indicated that ethnic/racial background and family income had no statistically significant relationship to motivations, attractiveness of CSD as a major, or career value of CSD as a major. Students scored highest on Intrinsic motivation factor (e.g., enjoy interacting with people) and the lowest on Science motivation (e.g., interested in science). Student confidence (e.g., in reaching career goals) was an important predictor in the perception of the career value of a CSD. Results of this study provide further insight into curriculum development and recruiting strategies.
Development and validation of simple isocratic high performance liquid chromatography-ultraviolet (HPLC- UV) method for determination of safflower yellow in Carthamus tinctorius (L.)-loaded nanostructured lipid carriers (NLC)

Carthamus tinctorius L. (safflower) is the traditional plant that is widely used in many regions around the Asia, including Thailand. With many reported biological activities, our group decided to formulate the cosmeceutical containing the florets extract of the plant. For enhancing the bioavailability of absorption of substances from its florets, the special carrier; nanostructured lipid carriers or nanostructured lipid carriers (NLC) was used. The simple isocratic high performance liquid chromatography-ultraviolet (HPLC-UV) method for determination of safflower yellow, which is the main constituent in the florets, was developed and validated to determine the potency of the formulated products. Cold methanol precipitation technique was used to extract unentrapped safflower from the wax matrix of NLC. For HPLC analysis, 60% methanol was used as a mobile phase with 1 ml/min flow rate, detected by UV detector at 401 nm. Accuracy and precision of the developed method was determined over the concentration range of 5 to 100 ppm. Specificity of the method was confirmed by high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC/ESI-MS). Linear range of the analysis was found in the concentration ranged of 5 to 100 ppm safflower yellow. Lower limit of detection and quantitation were 1.4 and 4.1 ppm, respectively. The developed method will be useful in the pharmaceutical and cosmeceutical industry applications concerning NLC containing safflower extract.
Systematic Screen Identifies miRNAs That Target RAD51 and RAD51D to Enhance Chemosensitivity

Homologous recombination mediates error-free repair of DNA double-strand breaks (DSB). RAD51 is an essential protein for catalyzing homologous recombination and its recruitment to DSBs is mediated by many factors including RAD51, its paralogs, and breast/ovarian cancer susceptibility gene products BRCA1/2. Deregulation of these factors leads to impaired DNA repair, genomic instability, and cellular sensitivity to chemotherapeutics such as cisplatin and PARP inhibitors. microRNAs (miRNA) are short, noncoding RNAs that posttranscriptionally regulate gene expression; however, the contribution of miRNAs in the regulation of homologous recombination is not well understood. To address this, a library of human miRNA mimics was systematically screened to pinpoint several miRNAs that significantly reduce RAD51 foci formation in response to ionizing radiation in human osteosarcoma cells. Subsequent study focused on two of the strongest candidates, miR-103 and miR-107, as they are frequently deregulated in cancer. Consistent with the inhibition of RAD51 foci formation, miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA-damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107–mediated chemosensitization. Furthermore, endogenous regulation of RAD51D by miR-103/107 was observed in several tumor subtypes. Taken together, these data show that miR-103 and miR-107 overexpression promotes genomic instability and may be used therapeutically to chemosensitize tumors. Implications: These findings demonstrate a role for miR-103 and -107 in regulating DNA damage repair, thereby identifying new players in the progression of cancer and response to chemotherapy. Mol Cancer Res; 11(12); 1564–73. ©2013 AACR.
Association of Baseline Knee Bone Size, Cartilage Volume, and Body Mass Index with Knee Cartilage Loss Over Time: A Longitudinal Study in Younger or Middle-aged Adults

Objective. To determine the association of knee bone size, cartilage volume, and body mass index (BMI) at baseline with knee cartilage loss over 2 years in younger or middle-aged adults. Methods. A total of 324 subjects (mean age 45 yrs, range 26–61) were measured at baseline and about 2 years later. Knee cartilage volume and bone size were determined using T1-weighted fat-saturated magnetic resonance imaging. Results. In multivariable analysis, baseline knee bone size was negatively associated with annual change in knee cartilage volume at medial and lateral tibial sites (ß = −0.62% to −0.47%/cm2, all p < 0.001). The associations disappeared at medial tibial site after adjustment for baseline cartilage volume and became of borderline statistical significance at lateral tibial site after adjustment for both baseline cartilage volume and osteophytes (ß = −0.29, p = 0.059). Baseline knee cartilage volume was consistently and negatively associated with annual change in knee cartilage volume at all 3 medial tibial, lateral tibial, and patellar sites (ß = −4.41% to −1.37%/ml, all p < 0.001). Baseline BMI was negatively associated with an annual change in knee cartilage volume, but only in subjects within the upper tertile of baseline cartilage volume, even after adjusting for cartilage defects (ß = −0.16% to −0.34%/kg/m2, all p < 0.05). Conclusion. Our study suggests that both higher baseline tibial bone area and knee cartilage volume (most likely due to cartilage swelling) are associated with greater knee cartilage loss over 2 years. A higher BMI was associated with greater knee cartilage loss only in subjects with higher baseline cartilage volume.
Z. Avram and E. Krishnan

Rheumatologists care for patients with gouty arthritis, a condition caused by chronic and uncontrolled hyperuricaemia. Hyperuricaemia, gout and renal dysfunction are often bedfellows, raising the possibility of the former causing the latter. We sought the answer to the question ‘Among patients with normal measures of glomerular filtration, does hyperuricaemia predict future renal disease’? We identified prospective cohort studies evaluating the relationship between serum uric acid and chronic kidney function from the past 20 yrs, through MEDLINE, Cochrane Library and EMBASE searches and bibliography cross-referencing. Nine cohort studies that met the selection criteria were found. Because of the extreme heterogeneity, a statistical meta-analysis was not performed. Most (eight out of nine) studies found an independent risk factor for deterioration of kidney function. Nearly all published prospective studies support the role of hyperuricaemia as an independent risk factor for renal dysfunction. In the absence of large randomized controlled trials of uric acid reduction, it remains uncertain if this relation is causal or merely an epiphenomenon. Regardless, our review suggests that hyperuricaemia is a useful, inexpensively measured, widely available and useful early marker for chronic kidney disease.
Recent advances in obstructive sleep apnea pathophysiology and treatment

Obstructive sleep apnea (OSA) is a sleep disorder characterized by recurring collapse of the pharyngeal airway leading to restricted airflow. OSA is becoming increasingly common with at least moderate disease now evident in 17% of middle aged men and 9% of women. The list of recognized adverse health consequences associated with OSA is growing and includes daytime symptoms of sleepiness, impaired cognition and risk of motor vehicle accidents as well as associations with hypertension, cardiovascular morbidity, malignancy and all-cause mortality. In this context adequate treatment of OSA is imperative; however, there are well-recognized pitfalls in the uptake and usage of the standard treatment modality, Continuous Positive Airway Pressure (CPAP). A broad range of pathophysiological mechanisms are now recognized beyond an anatomically smaller pharyngeal airway and impaired compensatory pharyngeal muscle responsiveness. Perturbations in ventilatory control stability, low arousal threshold, sleep-related decrease in lung volume and fluid redistribution as well as upper airway surface tension have all been shown to variously contribute to sleep-disordered breathing. Many new therapies are emerging from these advances in understanding of the mechanisms of OSA. Although many may not be universally effective, the promise of phenotyping patients according to their individual pathophysiology in order to target one or more therapies may prove highly effective and allow the treatment of OSA towards a personalized medicine approach.
A Review of Virtual Week for Prospective Memory Assessment: Clinical Implications

Abstract It is now recognised that prospective memory (PM) failures are commonly observed in clinical groups, and have important implications for functional independence. However, well-validated measures of PM have traditionally been lacking, making this construct difficult to assess in clinical practice. Rendell and Craik's (2000) Virtual Week measure was developed as an indicator of PM, and has been shown to have good psychometric properties and be sensitive to the effects of normal and abnormal adult ageing, as well as various forms of pathology. In this article, an overview of Virtual Week's characteristics is presented, and the literature relating to use of this measure in various populations reviewed. The potential implications of the development of a new computerised version of Virtual Week for clinical practice are discussed.
Children's Urinary Environmental Carbon Load. A Novel Marker Reflecting Residential Ambient Air Pollution Exposure?

Rationale: Ambient air pollution, including black carbon, entails a serious public health risk because of its carcinogenic potential and as climate pollutant. To date, an internal exposure marker for black carbon particles that have cleared from the systemic circulation into the urine does not exist. Objectives: To develop and validate a novel method to measure black carbon particles in a label‐free way in urine. Methods: We detected urinary carbon load in 289 children (aged 9‐12 yr) using white‐light generation under femtosecond pulsed laser illumination. Children's residential black carbon concentrations were estimated based on a high‐resolution spatial temporal interpolation method. Measurements and Main Results: We were able to detect urinary black carbon in all children, with an overall average (SD) of 98.2 × 105 (29.8 × 105) particles/ml. The urinary black carbon load was positively associated with medium‐term to chronic (1 mo or more) residential black carbon exposure: +5.33 × 105 particles/ml higher carbon load (95% confidence interval, 1.56 × 105 to 9.10 × 105 particles/ml) for an interquartile range increment in annual residential black carbon exposure. Consistently, children who lived closer to a major road (≤160 m) had higher urinary black carbon load (6.93 × 105 particles/ml; 95% confidence interval, 0.77 × 105 to 13.1 × 105). Conclusions: Urinary black carbon mirrors the accumulation of medium‐term to chronic exposure to combustion‐related air pollution. This specific biomarker reflects internal systemic black carbon particles cleared from the circulation into the urine, allowing investigators to unravel the complexity of particulate‐related health effects.
Visualization of Haplotype Sharing Patterns in Pedigree Samples

Objectives: A particular approach to the visualization of descent of founder DNA copies in a pedigree has been suggested, which helps to understand haplotype sharing patterns among subjects of interest. However, the approach does not provide the information in an ideal format to show haplotype sharing patterns. Therefore, we aimed to find an efficient way to visualize such sharing patterns and to demonstrate that our tool provides useful information for finding an informative subset of subjects for a sequence study. Methods: The visualization package, SharedHap, computes and visualizes a novel metric, the SharedHap proportion, which quantifies haplotype sharing among a set of subjects of interest. We applied SharedHap to simulated and real pedigree datasets to illustrate the approach. Results: SharedHap successfully represents haplotype sharing patterns that contribute to linkage signals in both simulated and real datasets. Using the visualizations we were also able to find ideal sets of subjects for sequencing studies. Conclusions: Our novel metric that can be computed using the SharedHap package provides useful information about haplotype sharing patterns among subjects of interest. The visualization of the SharedHap proportion provides useful information in pedigree studies, allowing for a better selection of candidate subjects for use in further sequencing studies.
Atherosclerotic Plaque Destabilization: Mechanisms, Models, and Therapeutic Strategies

Understanding the pathophysiology of atherogenesis and the progression of atherosclerosis have been major goals of cardiovascular research during the previous decades. However, the complex molecular and cellular mechanisms underlying plaque destabilization remain largely obscure. Here, we review how lesional cells undergo cell death and how failed clearance exacerbates necrotic core formation. Advanced atherosclerotic lesions are further weakened by the pronounced local activity of matrix-degrading proteases as well as immature neovessels sprouting into the lesion. To stimulate translation of the current knowledge of molecular mechanisms of plaque destabilization into clinical studies, we further summarize available animal models of plaque destabilization. Based on the molecular mechanisms leading to plaque instability, we outline the current status of clinical and preclinical trials to induce plaque stability with a focus on induction of dead cell clearance, inhibition of protease activity, and dampening of inflammatory cell recruitment.
Comparison of detergent-based cleaning, disinfectant-based cleaning, and detergent-based cleaning after enhanced domestic staff training within a source isolation facility

Source isolation facilities should be adequately cleaned to minimise the risk of cross-infection via the environment and fomites. The aim of this study was to compare the effectiveness of cleaning with detergent, cleaning with detergent followed by sodium hypochlorite and cleaning with detergent after enhanced training for domestic staff within isolation facilities in a district general hospital in southern England. Frequent `hand touch' sites in two isolation rooms were sampled, using contact plates. A total of 567 plates were collected. Bacterial total viable counts (TVCs) and environmental meticillin-resistant Staphylococcus aureus (MRSA) were used as surrogate markers to compare the efficacy of the cleaning methods. The results indicate that cleaning with water and detergent followed by sodium hypochlorite achieved significantly lower TVCs for most sampling sites, but only significantly lower environmental MRSA detections from a minority of sample sites. No one method of cleaning consistently eliminated MRSA from the environment. These results provide some preliminary evidence for the use of detergent and hypochlorite cleaning within source isolation facilities.
Local and nonlocal Fraunhofer-like pattern from an edge-stepped topological surface Josephson current distribution.

We report a surface-dominant Josephson effect in superconductor-topological insulator-superconductor (S-TI-S) devices, where a Bi1.5Sb0. 5Te1.7Se1. 3 (BSTS) crystal flake was adopted as an intervening TI between Al superconducting electrodes. We observed a Fraunhofer-type critical current modulation in a perpendicular magnetic field in an Al-TI-Al junction for both local and nonlocal current biasing. Fraunhofer-type modulation of the differential resistance was also observed in a neighboring Au-TI-Au normal junction when it was nonlocally biased by the Al-TI-Al junction. In all cases, the Fraunhofer-like signal was highly robust to the magnetic field up to the critical field of the Al electrodes, corresponding to the edge-stepped nonuniform supercurrent density arising from the top and rough side surfaces of the BSTS flake, which strongly suggests that the Josephson coupling in a TI is established through the surface conducting channels that are topologically protected.
P-0157BIOMARKERS SCREENING BETWEEN PREOPERATIVE AND POSTOPERATIVE PATIENTS IN PANCREATIC CANCER

Objective: To investigate discriminating protein patterns and potential biomarkers in serum samples between pre/postoperative pancreatic cancer patients and healthy controls. Methods: 23 serum samples from PC patients (12 preoperative and 11 postoperative) and 76 from healthy controls were analyzed using matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) technique combined with magnetic beads-based weak cation-exchange chromatography (MB-WCX). ClinProTools software selected several markers that made a distinction between pancreatic cancer patients and healthy controls. Results: 49 m/z distinctive peaks were found among the three groups, of which 33 significant peaks with a P < 0.001 were detected. Two proteins could distinguish the preoperative pancreatic cancer patients from the healthy controls. About 15 proteins may be potential biomarkers in assessment of pancreatic cancer resection. Conclusion: MB-MALDI-TOF-MS method could generate serum peptidome profiles of pancreatic cancer and provide a new approach to identify potential biomarkers for diagnosis and prognosis of this malignancy.
Extraspinal course of the fifth lumbar spinal nerve: An update of its topographical relationships

The fifth lumbar spinal nerve traverses a highly mobile transitional junction of the vertebral column. Evidence suggests that it is often implicated in the etiology of low‐back pain, notably in entrapment syndromes. There appears to be a high incidence of unsuccessful attempts at surgical decompression in cases of suspected entrapment of the nerve, suggesting that perhaps the anatomical information on the topography of the nerve is incomplete. The present study examined the course and relations of the fifth lumbar spinal nerve by gross dissection of human cadaveric material. The results showed that the nerve and its subdivisions follow a complex, tortuous course as they cross the lumbosacral junction. The trunk and ventral and dorsal rami are all related to strong ligaments that are thought to be protective. The nearness of these nerves to ligaments in such an area of high mobility, however, predisposes them to impingement or entrapment in the event of joint or ligamentous pathology. It is suggested therefore that investigations of spondylogenic low‐back pain should include a detailed evaluation of the status of all parts of the fifth lumbar spinal nerve as they traverse their individual osteoligamentous compartments.
Successful ceftolozane/tazobactam treatment of chronic pulmonary infection with pan‐resistant Pseudomonas aeruginosa

Introduction: The treatment of chronic Pseudomonas aeruginosa infections is challenging, with resistance and antibiogram diversity accumulating during successive therapies. Some isolates are resistant to all licensed agents, creating treatment problems and an urgent need for new therapies. Among antibiotics in advanced development, ceftolozane/tazobactam has potent in vitro antipseudomonal activity, with low MICs even for strains with AmpC β‐lactamase‐, impermeability‐ and efflux‐mediated resistance to other β‐lactams. Case presentation: A bronchiectasis exacerbation in a 59‐year‐old man involved pan‐resistant P. aeruginosa. Meropenem/colistin therapy failed. Named‐patient ceftolozane/tazobactam 2+1 g every 8 h for 14 days restored baseline respiratory and inflammatory marker status, and the patient was discharged; the ceftolozane/tazobactam MIC was 8 µg ml−1, with most growth inhibited at 2 µg ml−1. Conclusion: A positive outcome in this difficult infection due to an otherwise pan‐resistant P. aeruginosa is notable, especially as the patient had failed prior therapy with other agents. We urge formal evaluation of ceftolozane/tazobactam in chronic pseudomonal lung infections.