Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation of a screening tool for the rapid and reliable detection of CGG trinucleotide repeat expansions in FMR1.

AIMS Most individuals with intellectual disability and/or autism are tested for Fragile X syndrome at some point in their lifetime. Greater than 99% of individuals with Fragile X have an expanded CGG trinucleotide repeat motif in the promoter region of the FMR1 gene, and diagnostic testing involves determining the size of the CGG repeat as well as methylation status when an expansion is present. RESULTS Using a previously described triplet repeat-primed polymerase chain reaction, we have performed additional validation studies using two cohorts with previous diagnostic testing results available for comparison purposes. The first cohort (n=88) consisted of both males and females and had a high percentage of abnormal samples, while the second cohort (n=624) consisted of only females and was not enriched for expansion mutations. Data from each cohort were completely concordant with the results previously obtained during the course of diagnostic testing. CONCLUSIONS This study further demonstrates the utility of using laboratory-developed triplet repeat-primed FMR1 testing in a clinical setting.
Dehydroepiandrosterone inhibits B16 mouse melanoma cell growth by induction of differentiation.

BACKGROUND Low serum concentrations of dehydroepiandrosterone (DHEA) and its sulfate are associated with an increased incidence of various human malignancies. DHEA has chemopreventive and antiproliferative effects in experimental studies. Accordingly, the effects of DHEA on B16 mouse melanoma cells were studied. MATERIALS AND METHODS The effects of DHEA on cell number and melanin production of the melanoma cells were measured. Specific DHEA receptor was detected by a cytosol binding assay. Protein kinase C (PKC) activity of the melanoma cells was detected by phosphorylation of PKC specific substrate. RESULTS DHEA dose-dependently inhibited the growth of melanoma cells and enhanced melanin production, which indicated the induction of differentiation. There was a [3H]DHEA specific binding protein in the melanoma cell cytosol. Although DHEA did not promote the translocation of PKC from the cytosolic to the membrane fraction, the total PKC activity was upregulated by treatment with DHEA. CONCLUSIONS DHEA inhibited the growth of B16 mouse melanoma cells by the induction of differentiation, possibly related to PKC upregulation mediated by DHEA receptor.
A consideration of neuropsychologically normal schizophrenia

Abstract Neuropsychological deficits are considered by many to be core features of schizophrenia. However, about 20% of patients with schizophrenia appear to have normal neuropsychological function. This study investigates this subgroup by comparing a “neuropsychologically normal” schizophrenia group to a non-schizophrenic, non-brain damaged patient comparison (PC) sample, and to patients with definitive brain damage who performed normally on neuropsychological testing. All patients completed the Halstead-Reitan Neuropsychological Test Battery and were classified as neuropsychologically normal or impaired using the Average Impairment Rating (AIR). In a sample of 113 patients with schizophrenia, 19.5% were classified as neuropsychologically normal. The brain damaged neuropsychologically normal group (BD-NN) consisted of 14.3% of 124 subjects. These groups were compared with a patient non-schizophrenic, non-brain damaged group who were selected on the basis of having an Average Impairment Rating in the neuropsychologically normal range. The neuropsychologically normal schizophrenic group performed less well than the non-brain damaged, non-schizophrenic patient comparison group on a number of tests, indicating that patients in this group may not be completely neuropsychologically normal, and would be better characterized as “high-functioning” or near normal. The results are discussed in regard to possible neurobiological differences between neuropsychologically impaired and intact schizophrenic patients, and implications for course and outcome. (JINS, 2003, 9, 56–63.)
Matriptase-mediated cleavage of EpCAM destabilizes claudins and dysregulates intestinal epithelial homeostasis

Congenital tufting enteropathy (CTE) is a severe autosomal recessive human diarrheal disorder with characteristic intestinal epithelial dysplasia. CTE can be caused by mutations in genes encoding EpCAM, a putative adhesion molecule, and HAI-2, a cell surface protease inhibitor. A similar phenotype occurs in mice whose intestinal epithelial cells (IECs) fail to express the tight junction–associated protein claudin-7. EpCAM stabilizes claudin-7 in IECs, and HAI-2 regulates the cell surface serine protease matriptase, a known modifier of intestinal epithelial physiology. Therefore, we hypothesized that HAI-2, matriptase, EpCAM, and claudin-7 were functionally linked. Herein we have demonstrated that active matriptase cleaves EpCAM after Arg80 and that loss of HAI-2 in IECs led to unrestrained matriptase activity and efficient cleavage of EpCAM. Cleavage of EpCAM decreased its ability to associate with claudin-7 and targeted it for internalization and lysosomal degradation in conjunction with claudin-7. CTE-associated HAI-2 mutant proteins exhibited reduced ability to inhibit matriptase and also failed to efficiently stabilize claudin-7 in IECs. These results identify EpCAM as a substrate of matriptase and link HAI-2, matriptase, EpCAM, and claudin-7 in a functionally important pathway that causes disease when it is dysregulated.
Detecting Korean characters in natural scenes by alphabet detection and agglomerative character construction

This paper considers the Korean character detection problem. Unlike English where an alphabet constitutes a character, the Korean character is composed of more than two Korean alphabets, where they could be either connected or separated, relying on the Korean character font. Also, the Korean has two character structures which constitute a nested structure. These properties make the Korean character detection problem difficult. In this paper, we divide the Korean character detection problem into two subproblems, Korean alphabet detection and Korean character construction, and redefine the Korean character structures to efficiently detect Korean characters. Based on the new structures, we train four independent Korean alphabet detectors, and perform a sequential alphabet detection process with a specific detection order, to eliminate false alarms caused during detection procedure. Finally, the detected alphabets are grouped into the Korean characters by an agglomerative character construction algorithm. To evaluate our method, we carried out some experiments on a public dataset with several alternatives, and showed that our proposed Korean character detection method has outperformed other methods.
Sustained tetracycline‐regulated transgene expression in vivo in rat retinal ganglion cells using a single type 2 adeno‐associated viral vector

Viral vector delivery of neurotrophic‐expressing transgenes in the retina may retard or prevent the onset of blindness associated with photoreceptor degeneration. A key safety issue is to achieve regulated expression of these genes in the retina. The purpose of our study was to evaluate whether a single recombinant AAV‐2 (rAAV) encoding for a tetracycline (Tet)‐regulated destabilized reporter gene could provide quantitative profiles of gene regulation targeted to the rat neuroretina.
α-Synuclein in CSF of patients with severe traumatic brain injury

Objective: The study aims to examine α-synuclein in the CSF of patients with severe traumatic brain injury (TBI) and its relationship with clinical characteristics and long-term outcomes. Methods: This prospective case-control study enrolled patients with severe TBI (Glasgow Coma Score ≤8) who underwent ventriculostomy. CSF samples were taken from each TBI patient at admission and daily for up to 8 days after injury and successively assessed by ELISA. Control CSF was collected for analysis from subjects receiving lumbar puncture for other medical reasons. We used trajectory analysis to identify distinct temporal profiles of CSF α-synuclein that were compared with clinical outcomes. Results: CSF α-synuclein was elevated in TBI patients after injury as compared to controls (p = 0.0008). Overall, patients who died had higher concentrations (area under the curve) over 8 days of observation compared to those who survived at 6 months postinjury (p = 0.002). Two distinct temporal α-synuclein profiles were recognized over time. Subjects who died had consistently elevated α-synuclein levels compared to those who survived with α-synuclein levels near controls. High-risk trajectory was a strong and accurate predictor of death with 100% specificity and a very high sensitivity (83%). Conclusions: Taken together, these data support the hypothesis that in severe TBI patients, substantial increase of CSF α-synuclein may indicate widespread neurodegeneration and reflect secondary neuropathologic events occurring after injury. The determination of CSF α-synuclein may be a valuable prognostic marker, adding to the clinical assessment and creating opportunities for medical intervention.
A New Algorithm for Real-Time Optimal Dispatch of Active and Reactive Power Generation Retaining Nonlinearity

This paper presents a new method for optimal dispatch of real and reactive power generation which is based on cartesian coordinate formulation of economic dispatch problem and reclassification of state and control variables associated with generator buses. The voltage and power at these buses are classified as parametric and functional inequality constraints, and are handled by reduced gradient technique and penalty factor approach respectively. The advantage of this classification is the reduction in the size of the equality constraint model, leading to less storage requirement. The rectangular coordinate formulation results in an exact equality constraint model in which the coefficient matrix is real, sparse, diagonally dominant, smaller in size and need be computed and factorized once only in each gradient step. In addition, Lagragian multipliers are calculated using a new efficient procedure. A natural outcome of these features is the solution of the economic dispatch problem, faster than other methods available to date in the literature. Rapid and reliable convergence is an additional desirable characteristic of the method. Digital simulation results are presented on several IEEE test systems to illustrate the range of application of the method vis- à-vis the popular Dommel-Tinney (DT) procedure. It is found that the proposed method is more reliable, 3-4 times faster and requires 20-30 percent less storage compared to the DT algorithm, while being just as general.
NANODOSIMETRY: TOWARDS A NEW CONCEPT OF RADIATION QUALITY

The biological action of ionizing charged particles is initiated at the DNA level, and the effectiveness with which the initial physical effect changes into measurable biological damage is likely ruled by the stochastics of ionizations produced by the incident ions in subcellular nanometric volumes. Based on this hypothesis, experimental nanodosimetry aims at establishing a new concept of radiation quality that builds on measurable characteristics of the particle track structure at the nanometer scale. Three different nanodosimetric detection systems have been developed to date that allow measurements of the number of ionizations produced by the passage of a primary particle in a nanometer-size gas volume (in unit density scale). Within the Italian project MITRA (MIcrodosimetry and TRAck structure), funded by the Italian Istituto Nazionale di Fisica Nucleare (INFN) and the EMRP Joint Research Project 'BioQuaRT' (Biologically Weighted Quantities in Radiotherapy), experiments have been carried out, in which the frequency distribution of ionizations produced by proton and carbon ion beams of given energy was measured with the three nanodosimetric detectors. Descriptors of the track structure can be derived from these distributions. In particular, the first moment M1, representing the mean number of ionizations produced in the target volume, and the cumulative probability Fk of measuring a number ν ≥ k of ionizations. The correlation between measured nanodosimetric quantities and experimental radiobiological data available in the literature is here presented and discussed.
Observation, Reflection, and Reinforcement: Surgery Faculty Members' and Residents' Perceptions of How They Learned Professionalism

Purpose To explore perceptions of how professionalism is learned in the current academic environment. Professionalism is a core competency in surgery (as in all of medical practice), and its presence or absence affects all aspects of clinical education and practice, but the ways in which professional values and attitudes are best transmitted to developing generations of surgeons have not been well defined. Method The authors conducted 34 semistructured interviews of individual surgery residents and faculty members at two academic institutions from 2004 to 2006. Interviews consisted of open-ended questions on how the participants learned professionalism and what they perceived as challenges to learning professionalism. Two researchers analyzed the interview transcripts for emergent themes by using a grounded-theory approach. Results Faculty members' and residents' perceptions of how they learned professionalism reflected four major themes: (1) personal values and upbringing, including premedical education experiences, (2) learning by example from professional role models, (3) the structure of the surgery residency, and (4) formal instruction on professionalism. Of these, role modeling was the dominant theme: Participants identified observation, reflection, and reinforcement as playing key roles in their learning from role models and in distinguishing the sometimes blurred boundary between positive and negative role models. Conclusions The theoretical framework generated out of this study proposes a focus on specific activities to improve professional education, including an active approach to role modeling through the intentional and explicit demonstration of professional behavior during the course of everyday work; structured, reflective self-examination; and timely and meaningful evaluation and feedback for reinforcement.
Fecal calprotectin in healthy children

Abstract Calprotectin is a protein found in the cytosol of inflammatory cells and is a marker of the presence and the degree of inflammation in the bowel system. Calprotectin in feces has great diagnostic value in the matter of inflammatory bowel disease (IBD). In feces, the protein is stable up to seven days, and since the protein can easily be measured with an ELISA, the use of fecal calprotectin (FC) means no invasive measures. For adults and children over 4 years, a cut-off level of 50 mg/kg has been well established for diagnostic purposes. Because previous studies have proven that children under the age of four in general have higher FC values than older children and adults, there is a need for a cut-off level for this age group. In order to establish that, the normal values for FC in children from 0–4 years were investigated. Some 75 stool samples from healthy children were collected and the levels of FC were analyzed. The results were compared to 157 pediatric cases where FC analysis had been performed for diagnostic purposes. As a result, three cut-off levels were established based on the 97.5% percentiles of FC in different age groups: 538 mg/kg (1 < 6 months), 214 mg/kg (6 months < 3 years) and 75 mg/kg (3 < 4 years).
Community structure and distribution of functional microbial groups within two complex environments

In der vorliegenden Arbeit wurden funktionelle Gruppen von Mikroorganismen in zwei auserst unterschiedlichen Okosystemen, die beide eine komplexe mikrobielle Gemeinschaftsstruktur aufweisen, untersucht. Der erste Teil dieser Arbeit befasst sich mit der Populationsdynamik und Verbreitung von potentiell sulfatreduzierenden Mikroorganismen in terrestrischen Feuchtgebieten. Die dissimilatorische Sulfatreduktion, welche ausschlieslich von Mikroorganismen mit Hilfe der dissimilatorischen (Bi-)Sulfit-Reduktase (Dsr) durchgefuhrt wird, wurde bereits in fruheren Studien im Untersuchungsgebiet Schloppnerbrunnen nachgewiesen. Unter Verwendung verschiedener molekularbiologischer Techniken zur Analyse der 16S-rRNS- und dsrAB-Gensequenzen konnte in diesem hoch diversen und von Acidobacteria dominierten Moor eine zeitlich stabile, raumlich jedoch variable Zusammensetzung der potentiell sulfatreduzierenden Populationen gezeigt werden. Hierbei waren bisher nicht charakterisierte, tiefzweigende dsrAB-Sequenzen signifikant haufiger als bekannte dsrAB-Linien. Des Weiteren bestatigte die Analyse acht weiterer Feuchtgebiete das verbreitete Vorkommen dieser tiefzweigenden dsrAB-Linien in Mooren. Die Anwendung von DNS-Mikroarray basierten Methoden deckte auserdem signifikante und systematisch angeordnete Schwankungen der detektierten Signalstarken in diesen Nukleinsaure-basierten Hybridisierungs-Assays auf. Aufgrund dieser raumlichen Gradienten wurde hierbei die Anzahl an detektierten Zielmolekulen vom Rand zur Mitte des Arrays halbiert. Modellsimulationen wiesen auf Limitierungen im Massetransport der Zielmolekule als mogliche Ursache hin. Im zweiten Teil dieser Arbeit wurden die mikrobiellen Gemeinschaften in marinen Schwammen untersucht. Eine umfassende Analyse aller offentlich verfugbaren 16S-rRNS-Sequenzen aus Schwammen und weitere 184 Sequenzen von drei bisher nicht untersuchten Schwammen, bestatigte das Vorhandensein monophyletischer, Schwamm-spezifischer 16S-rRNS Gensequenz-Cluster, wobei etwa ein Drittel der analysierten Sequenzen zu diesen Clustern zugeordnet werden konnten. Daruber hinaus zeigten 16S-rRNS- und Ammonium Monooxygenase-Gen basierte Analysen die Anwesenheit von potentiell ammoniumoxidierenden Archaea (AOA) in einer Reihe von Schwammen aus dem westlichen Pazifik, der Karibik und des Mittelmeers auf. Das zusatzliche Vorhandensein dieser AOAs in den entsprechenden Schwamm-Larven, weist darauf hin, dass AOAs in Schwammen vertikal ubertragen werden.
Diagnostic performance of multidetector CT angiography for assessment of coronary artery disease: meta-analysis.

PURPOSE To review the literature on the diagnostic performance of multidetector computed tomographic (CT) angiography for assessment of symptomatic coronary artery disease, with conventional coronary angiography as the reference standard. MATERIALS AND METHODS A PubMed and manual search of the literature published between January 1998 and May 2006 on use of multidetector CT angiography compared with coronary angiography in patients with symptomatic coronary artery disease was performed. Summary estimates of diagnostic odds ratio, sensitivity, and specificity were calculated. Random-effects models were used to compare the diagnostic performance of four-, 16-, and 64-detector CT angiographic units, and the proportion of nonassessable coronary arterial segments was evaluated. RESULTS Fifty-four studies were included in the meta-analysis: 22 studies with four-detector CT angiography, 26 with 16-detector CT angiography, and six with 64-detector CT angiography. The pooled sensitivity and specificity for detecting a greater than 50% stenosis per segment were 0.93 (95% confidence interval [CI]: 0.88, 0.97) and 0.96 (95% CI: 0.96, 0.97) for 64-detector CT angiography, 0.83 (95% CI: 0.76, 0.90) and 0.96 (95% CI: 0.95, 0.97) for 16-detector CT angiography, and 0.84 (95% CI: 0.81, 0.88) and 0.93 (95% CI: 0.91, 0.95) for four-detector CT angiography, respectively. Results of regression analysis indicated that the diagnostic performance significantly improved with the newer generations of multidetector CT scanners (64- and 16-detector vs four-detector units), adjusted for exclusion of nonassessable segments, and contrast agent concentration used (P < .05). Simultaneously, the nonassessable proportion of segments significantly decreased with the newer generations of multidetector CT scanners, adjusted for heart rate, prevalence of significant disease, and mean age. CONCLUSION With the newer generations of multidetector CT scanners, the diagnostic performance for the assessment of coronary artery disease has significantly improved, and the proportion of nonassessable segments has decreased.
Expression of Respiratory Syncytial Virus-Induced Chemokine Gene Networks in Lower Airway Epithelial Cells Revealed by cDNA Microarrays

ABSTRACT The Paramyxovirus respiratory syncytial virus (RSV) is the primary etiologic agent of serious epidemic lower respiratory tract disease in infants, immunosuppressed patients, and the elderly. Lower tract infection with RSV is characterized by a pronounced peribronchial mononuclear infiltrate, with eosinophilic and basophilic degranulation. Because RSV replication is restricted to airway epithelial cells, where RSV replication induces potent expression of chemokines, the epithelium is postulated to be a primary initiator of pulmonary inflammation in RSV infection. The spectrum of RSV-induced chemokines expressed by alveolar epithelial cells has not been fully investigated. In this report, we profile the kinetics and patterns of chemokine expression in RSV-infected lower airway epithelial cells (A549 and SAE). In A549 cells, membrane-based cDNA macroarrays and high-density oligonucleotide probe-based microarrays identified inducible expression of CC (I-309, Exodus-1, TARC, RANTES, MCP-1, MDC, and MIP-1α and -1β), CXC (GRO-α, -β, and -γ, ENA-78, interleukin-8 [IL-8], and I-TAC), and CX3C (Fractalkine) chemokines. Chemokines not previously known to be expressed by RSV-infected cells were independently confirmed by multiprobe RNase protection assay, Northern blotting, and reverse transcription-PCR. High-density microarrays performed on SAE cells confirmed a similar pattern of RSV-inducible expression of CC chemokines (Exodus-1, RANTES, and MIP-1α and -1β), CXC chemokines (I-TAC, GRO-α, -β, and -γ, and IL-8), and Fractalkine. In contrast, TARC, MCP-1, and MDC were not induced, suggesting the existence of distinct genetic responses for different types of airway-derived epithelial cells. Hierarchical clustering by agglomerative nesting and principal-component analyses were performed on A549-expressed chemokines; these analyses indicated that RSV-inducible chemokines are ordered into three related expression groups. These data profile the temporal changes in expression by RSV-infected lower airway epithelial cells of chemokines, chemotactic proteins which may be responsible for the complex cellular infiltrate in virus-induced respiratory inflammation.