Miracle-dz/UniFAR-FTUs huggingface dataset:
Poly-l-aspartic Acid Enhances and Prolongs Gentamicin-mediated Suppression of the CFTR-G542X Mutation in a Cystic Fibrosis Mouse Model*

Aminoglycosides such as gentamicin have the ability to suppress translation termination at premature stop mutations, leading to a partial restoration of protein expression and function. This observation led to studies showing that this approach may provide a viable treatment for patients with genetic diseases such as cystic fibrosis that are caused by premature stop mutations. Although aminoglycoside treatment is sometimes associated with harmful side effects, several studies have shown that the co-administration of polyanions such as poly-l-aspartic acid (PAA) can both reduce toxicity and increase the intracellular aminoglycoside concentration. In the current study we examined how the co-administration of gentamicin with PAA influenced the readthrough of premature stop codons in cultured cells and a cystic fibrosis mouse model. Using a dual luciferase readthrough reporter system in cultured cells, we found that the co-administration of gentamicin with PAA increased readthrough 20–40% relative to cells treated with the same concentration of gentamicin alone. Using a Cftr-/- hCFTR-G542X mouse model, we found that PAA also increased the in vivo nonsense suppression induced by gentamicin. Following the withdrawal of gentamicin, PAA significantly prolonged the time interval during which readthrough could be detected, as shown by short circuit current measurements and immunofluorescence. Because the use of gentamicin to suppress disease-causing nonsense mutations will require their long term administration, the ability of PAA to reduce toxicity and increase both the level and duration of readthrough has important implications for this promising therapeutic approach.
MRI evaluation of inflammatory activity in Crohn's disease.

OBJECTIVE We wanted to assess the capability of MRI to quantitatively evaluate the therapeutic response to Crohn's disease (CD) relapse. SUBJECTS AND METHODS Twenty patients with histologically proven CD were prospectively evaluated with MRI and ileocolonoscopy over a 2-year period. The MRI protocol included axial and coronal T2-weighted and contrast-enhanced T1-weighted sequences. MRI examinations were performed twice, once during an acute relapse of CD and the other at clinical remission. The terminal ileum and colon were divided into six segments/patient, and the endoscopy and histology findings were considered the standard of reference. These were compared on a segmental basis with the quantitative MRI findings regarding wall thickness and contrast enhancement. The results obtained in active and remission CD phases were likewise compared with the findings in 10 control subjects who underwent complete ileocolonoscopy for other reasons and had no pathological findings on ileocolonoscopy. RESULTS Fifty three of 120 (44.2%) bowel segments showed pathologic changes on endoscopy and histology consistent with CD in active phase. On changing from the active disease phase to clinical remission, a significant decrease was observed in the wall thickness and contrast enhancement of the affected bowel wall. In the active phase of CD, the pathologic bowel segments presented with significantly greater contrast enhancement and wall thickness values compared with the healthy segments of CD and controls. On converting clinically into remission, contrast enhancement tended to normalize, whereas bowel wall thickness remained increased compared with the controls. CONCLUSION MRI is able to detect pathologic bowel segments in CD, as it allows the measurement of significant variations in wall thickness and contrast enhancement on changing from the active phase of the disease to remission.
Accuracy of Pancreatic Neuroendocrine Tumour Grading by Endoscopic Ultrasound-Guided Fine Needle Aspiration: Analysis of a Large Cohort and Perspectives for Improvement

Introduction: Since the WHO Classification of Tumours of the Digestive System has been published in 2010, resected pancreatic neuroendocrine tumours (pNETs) are graded as grade 1 (G1), grade 2 (G2) or grade 3 (G3) using the Ki67 labelling index (Ki67-LI). Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is often used for diagnosis, but few studies have assessed its value for grading. Aims: The aims of this study were to compare the Ki67-LI obtained by cytological grading (cG) with that obtained by histological grading (hG) and to assess (1) the influence of tumour size and the number of counted cells on FNA grading as well as (2) the overall survival (OS) and progression-free survival based on cG. Materials and Methods: EUS-FNA was performed for 102 pNETs (57 resected). cG (200 cells counted) was done on all FNAs. For 29 FNAs, >2,000 cells were counted (14 resected). A comparison was made between hG and cG for the 57 resected patients. Patients were followed up until June 2016. Results: cG was consistent with hG in 39 of 57 patients with a concordance rate of 72% using a Ki67-LI cut-off of 5% for G1/G2. For Ki67-LI absolute values, the correlation was r = 0.443 and increased to r = 0.824 (p < 0.001) when only FNAs with >2,000 cells were counted. Twenty-one of 22 pNETs <2 cm had the same grading on cG and hG, whereas grading was discordant for 15 of 16 pNETs >2 cm. Thirty-eight patients died after 70.5 months of follow-up. OS for the whole cohort was 235 months and differed between cG1 (235 months), cG2 (36.3 months) and cG3 (10.9 months). Conclusion: cG of pNETs is more accurate when tumours measure <2 cm and more cells are counted on FNA. Discrepancies are seen between G2 tumours which are often considered G1 on FNA due to tumour heterogeneity. EUS-FNA is valuable to distinguish between patients with good (cG1) and poor (cG3) prognosis.
Decompression and Coflex Interlaminar Stabilization Compared With Decompression and Instrumented Spinal Fusion for Spinal Stenosis and Low-Grade Degenerative Spondylolisthesis: Two-Year Results From the Prospective, Randomized, Multicenter, Food and Drug Administration Investigational Device Exempti

Study Design. Prospective, randomized, multicenter, Food and Drug Administration Investigational Device Exemption trial. Objective. To evaluate the safety and efficacy of Coflex interlaminar stabilization compared with posterior spinal fusion in the treatment of 1- and 2-level spinal stenosis and degenerative spondylolisthesis. Summary of Background Data. Long-term untoward sequelae of lumbar fusion for stenosis and degenerative spondylolisthesis have led to the search for motion-preserving, less-invasive alternatives. Methods. Three hundred twenty-two patients (215 Coflex and 107 fusions) from 21 sites in the United States were enrolled between 2006 and 2010. Subjects were randomized to receive laminectomy and Coflex interlaminar stabilization or laminectomy and posterolateral spinal fusion with spinal instrumentation in a 2:1 ratio. Overall device success required a 15-point reduction in Oswestry Disability Index, no reoperations, no major device-related complications, and no postoperative epidural injections. Results. Patient follow-up at minimum 2 years was 95.3% and 97.2% in the Coflex and fusion control groups, respectively. Patients taking Coflex experienced significantly shorter operative times (P < 0.0001), blood loss (P < 0.0001), and length of stay (P < 0.0001). There was a trend toward greater improvement in mean Oswestry Disability Index scores in the Coflex cohort (P = 0.075). Both groups demonstrated significant improvement from baseline in all visual analogue scale back and leg parameters. Patients taking Coflex experienced greater improvement in Short-Form 12 physical health outcomes (P = 0.050) and equivalent mental health outcomes. Coflex subjects experienced significant improvement in all Zurich Claudication Questionnaire outcomes measures compared with fusion (symptom severity [P = 0.023]; physical function [P = 0.008]; satisfaction [P = 0.006]). Based on the Food and Drug Administration composite for overall success, 66.2% of Coflex and 57.7% of fusions succeeded (P = 0.999), thus demonstrating noninferiority. The overall adverse event rate was similar between the groups, but Coflex had a higher reoperation rate (10.7% vs. 7.5%, P = 0.426). At 2 years, fusions exhibited increased angulation (P = 0.002) and a trend toward increased translation (P = 0.083) at the superior adjacent level, whereas Coflex maintained normal operative and adjacent level motion. Conclusion. Coflex interlaminar stabilization is a safe and efficacious alternative, with certain advantages compared with lumbar spinal fusion in the treatment of spinal stenosis and low-grade spondylolisthesis. Level of Evidence: 1
Bridging the Semantic Gap for Satellite Image Annotation and Automatic Mapping Applications

This paper brings a solution for bridging the gap between the results of state-of-the-art automatic classification algorithms and high semantic human-defined manually created terminology of cartographic data. Using a recent pure-spectral rule-based fully automatic classifier to define the basic 'vocabulary', we provide a hybrid method to automatically understand and describe semantic rules that link existent mapping data according to different specifications with the end-results of unsupervised computer information mining methods. Following an agreement between the learning model and the cartographic scale implied, we exploit Latent Dirichlet Allocation model (LDA) to map heterogeneous pixels with similar intermediate-level semantic meaning into land cover classes of various mapping products. By discovering the set of rules that explain semantic classes in existent vector systems, we introduce the prototype of an interactive learning loop that uses the concept of direct semantics applied on satellite imagery. We solve a big problem in generating cartographic information layers from a fully automatic classification map and demonstrate it for the typical case of Landsat images.
An Image Quality Assessment Index Based on Visual Saliency and Gradient Amplitude for Telemedicine Application

This paper proposes an image quality assessment method based on visual saliency and gradient amplitude. Multi-scale decomposition is used, then with the analysis of the image's phase spectrum in frequency domain, the visual saliency map can be obtained. Meanwhile, the gradient amplitude map is obtained through analyzing the image's contrast feature. The weighted products of the visual saliency map and the gradient amplitude map of all scales are synthesized to get the objective quality evaluation value. Many experiments are made on three image quality assessment (IQA) databases which are available to the public, including TID2008, IVC and A57. The experimental results demonstrate that the method proposed in this paper can obtain greater consistency with human subjective evaluation than that of other related image quality assessment indexes.
Complex families, the social determinants of health and psychosocial interventions: Deconstruction of a day in the life of hospital social workers

ABSTRACT The roles of hospital social workers are delineated in the literature; however, their daily interventions have only been described anecdotally. This study analyzes the daily work of social workers in a pediatric hospital through a survey completed which examined factors related to interventions utilized and time spent per case over a 1-day period. Length and types of interventions were associated with the social determinants of health, time since diagnosis, biopsychosocial issues, and perception of complexity. The study offers a snapshot of the personalized expertise, provided by social workers that addresses complex contextual and biopsychosocial concerns of patient and families
Exponential Growth Model: From Horizontal to Linear Asymptote

We present a smooth function that can be used as regression curve for modeling growth phenomena requiring an increasing curvilinear concave asymptote. This model is obtained as the product of a concave asymptotic curve and the exponential model. In addition to its increasing character with a curvilinear asymptote, including horizontal or linear increasing asymptote, the resulting model provides curves with a single inflection point. Numerical examples are presented.
Using information theory to measure call site information of system call in anomaly detection

It is an important and effective approach for the detection of network attacks by means of monitoring and analyzing the running behavior of the program. Traditionally, a program can be characterized by system call issued by it. The call site information of system call, however, is often ignored by many system-call-based detection models. This paper evaluates the influence of the specific information on program behavior by means of information-theoretic measure. Experimental results show that the information could lower conditional entropy as well as relative conditional entropy, which contribute to more precise model and more effective detection for intrusions.
COMFIRMATION AS A KEY FOR PATIENT SAFETY : A NETWORK ANALYSIS OF INCIDENT REPORTS

According to the results of the statistical analysis on incident reports released by the Japanese Ministry of Health, Labour and Welfare, drug-related medical accidents account for more than half of all medical accidents. With respect to the causes of medical accidents, those caused by human carelessness, such as “incorrect drugs” or “incorrect drug dosages,” account for more than 40% of all medical accidents. Therefore, establishing a method to prevent the occurrence of accidents due to human carelessness is a highly contributing factor in achieving safe, worry-free medical care. Accordingly, the purpose of this research is to construct a knowledge base that is useful for examining accident prevention measures by specifying a drug group closely related to the accident as well as the causes of the accident through the structuring of bibliographical information. Natural language processing and network analysis are used as research methods. The network analysis method facilitates analysis on various relationships that are not only direct relationships but also indirect relationships, which are at least two steps away from the former. The incident reports in Japan are used as the subjects of this research. First, the frequently appearing characteristic words were extracted according to the three categories of the accident’s background, details, and solutions described in the report, and then networks using these extracted words were created. Next, using the pharmaceutical dictionary and our own rules for dissolving the “discrepancy in descriptions,” drug information was extracted from the accident report, and a drug network was created. From the above analyses it has become clear that inadequate information on drug labels, physician’s instructions, and patient misunderstanding are the more important factors in medical accidents. Moreover, drugs and the combinations of drugs that frequently cause accidents have been revealed. The POAS (Point of Act System) is known as a cutting-edge medical information system that prevents confirmation errors made by humans. Finally, using the above results, the degree of effectiveness of POAS in the prevention of drug-related accidents was calculated. Of all the drugs that were returned through POAS, the ones that had actually caused medical accidents accounted for 31.6%. In addition, with regard to the ten most frequently returned drugs through POAS, the Pearson’s Correlation between the number of drugs returned and the number of accident cases was high at 0.508, thus confirming the effectiveness of POAS implementation. From this point forward, in order to achieve an even more effective analysis, the following factors are important in incident reports: (i) unification of descriptions pertaining to drug(s) and prevention of discrepancy in descriptions; and (ii) encouraging more descriptions pertaining to the confirmation details.
Ephraim McDowell and the first successful elective laparotomy.

I occasionally carry out the interesting exercise of asking a group of my medical students if they can guess the date of the first successful elective laparotomy, the name of the surgeon who performed the procedure and where it took place. After a long and profound silence, someone might suggest ‘around 1870 or 1880’, guess at some well-known name, such as Joseph Lister (who, in fact, never performed a laparotomy), and opine that the venue must have been one of the great British teaching hospitals or a famous continental clinic. None of these could be further from the truth – the place was Danville, Kentucky, the surgeon Ephraim McDowell and the date 1809 – just 200 years ago.
A MS data search method for improved 15N‐labeled protein identification

Quantitative proteomics using stable isotope labeling strategies combined with MS is an important tool for biomarker discovery. Methods involving stable isotope metabolic labeling result in optimal quantitative accuracy, since they allow the immediate combination of two or more samples. Unfortunately, stable isotope incorporation rates in metabolic labeling experiments using mammalian organisms usually do not reach 100%. As a consequence, protein identifications in 15N database searches have poor success rates. We report on a strategy that significantly improves the number of 15N‐labeled protein identifications and results in a more comprehensive and accurate relative peptide quantification workflow.
Expression of an inwardly rectifying K 1 channel, Kir4.1, in satellite cells of rat cochlear ganglia

Expression of an inwardly rectifying K 1 channel, Kir4.1, in satellite cells of rat cochlear ganglia. Am. J. Physiol. 277 ( Cell Physiol. 46): C638–C644, 1999. —Satellite cells are glial cells wrapped around somata of sensory and autonomic ganglion neurons. Neither their functional roles nor electrical properties have been fully clariﬁed so far. Using immunohistochemistry, we found that inwardly rectifying K 1 channel subunit Kir4.1 (also called Kir1.2 or K AB -2) was expressed promi- nently in the satellite cells of cochlear ganglia. The Kir4.1 immunoreactivity was localized speciﬁcally at the myelin sheaths of satellite cells wrapping the somata of the ganglion neurons. Developmental expression of Kir4.1 in satellite cells paralleled development of the action potential in the auditory nerve. These results suggest that this channel in satellite cells may be responsible for the regulation of K 1 extruded from the ganglion neurons during excitation.
Effects of grain size and frequency on eddy current loss in Si-Fe sheets

The effect of frequency on eddy current loss was studied for nonoriented Si-Fe sheets of different grain sizes. In high-frequency regions, the eddy current loss accounts for a larger proportion of the core loss than in low-frequency regions; hence, the smaller the grain size, the smaller becomes the core loss. The eddy current loss is strongly influenced by the skin effect, especially in a weak magnetic field. This skin effect can be estimated using the Bozorth formula. >
The Valuation of Option Subject to Default Risk

There is no sufficient margin settlement mechanism for unlisted options, thus the credit risk of the option writer must be considered when investors evaluate the price of unlisted options. This paper intends to extend option pricing model and derive a path-dependent valuation model for option subject to counterparty default risk. Numerical examples show that our model can effectively identify the impacts of counterparty credit risk on vulnerable option value. The most important result of sensitivity analysis is that the effect of the correlation between counterparty’s asset value and underlying stock price on vulnerable option value is obscured. Keyword: option, option pricing, credit risk, default risk, path-dependent
Evolutionary Adaptation to Freeze‐Thaw‐Growth Cycles in Escherichia coli

Fifteen populations of Escherichia coli were propagated for 150 freeze‐thaw‐growth (FTG) cycles in order to study the phenotypic and genetic changes that evolve under these stressful conditions. Here we present the phenotypic differences between the evolved lines and their progenitors as measured by competition experiments and growth curves. Three FTG lines evolved from an ancestral strain that was previously used to start a long‐term evolution experiment, while the other 12 FTG lines are derived from clones that had previously evolved for 20,000 generations at constant 37°C. Competition experiments indicate that the former FTG group improved their mean fitness under the FTG regime by about 90% relative to their progenitor, while the latter FTG group gained on average about 60% relative to their own progenitors. These increases in fitness result from both improved survival during freezing and thawing and more rapid recovery to initiate exponential growth after thawing. This shorter lag phase is specific to recovery after freezing and thawing. Future work will seek to identify the mutations responsible for evolutionary adaptation to the FTG environment and use them to explore the physiological mechanisms that allow increased survival and more rapid recovery.
Characterization of polymorphic microsatellite loci in the marine isopod Sphaeroma terebrans (Crustacea, Isopoda)

Nine polymorphic microsatellites were characterized in the marine isopod Sphaeroma terebrans (Isopoda, Sphaeromatidae) for phylogeographic and parentage analyses. The number of alleles ranged from 3 to 10. Observed heterozygosity ranged from 0.428 to 0.950, while expected heterozygosity ranged from 0.532 to 0.889. Heterozygote deficiency was detected for one locus, possibly the result of null alleles.
Iron enzyme ribulose-5-phosphate 3-epimerase in Escherichia coli is rapidly damaged by hydrogen peroxide but can be protected by manganese

H2O2 is commonly generated in biological habitats by environmental chemistry and by cellular immune responses. H2O2 penetrates cells, disrupts metabolism, and blocks growth; it therefore is of interest to identify the major cellular molecules that H2O2 damages and the strategies by which cells protect themselves from it. We used a strain of Escherichia coli that lacks catalases and peroxidases to impose protracted low-grade H2O2 stress. Physiological analysis indicated that the pentose–phosphate pathway, in particular, was poisoned by submicromolar intracellular H2O2. Assays determined that ribulose-5-phosphate 3-epimerase (Rpe) was specifically inactivated. In vitro studies demonstrated that Rpe employs a ferrous iron atom as a solvent-exposed cofactor and that H2O2 rapidly oxidizes this metal in a Fenton reaction. The oxidized iron is released immediately, causing a loss of activity. Most Rpe proteins could be reactivated by remetallation; however, a small fraction of proteins were irreversibly damaged by each oxidation cycle, and so repeated cycles of oxidation and remetallation progressively led to permanent inactivation of the entire Rpe pool. Manganese import and iron sequestration are key elements of the H2O2 stress response, and we found that manganese can activate Rpe in vitro in place of iron, converting the enzyme to a form that is unaffected by H2O2. Indeed, the provision of manganese to H2O2–stressed cells protected Rpe and enabled the pentose–phosphate pathway to retain function. These data indicate that mononuclear iron enzymes can be primary targets of H2O2 stress and that cells adapt by shifting from iron- to manganese-centered metabolism.