Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of Somatosensory Function in Patients With Idiopathic Dry Eye Symptoms.

Importance Somatosensory dysfunction likely underlies dry eye (DE) symptoms in many individuals yet remains an understudied component of the disease. Its presence has important diagnostic and therapeutic implications. Objective To assess the integrity of nociceptive system processes in persons with DE and ocular pain using quantitative sensory testing (QST) techniques applied at a site remote from the eye. Design, Setting, and Participants A cross-sectional study conducted at Miami Veterans Affairs Hospital included 118 individuals with a wide variety of DE symptoms and signs. The study was conducted from October 31, 2013, to January 28, 2016. Interventions Individuals completed questionnaires regarding ocular symptoms (5-Item Dry Eye Questionnaire [DEQ5], Ocular Surface Disease Index [OSDI], and Neuropathic Pain Symptom Inventory modified for the eye [NPSI-E]), psychological status, and medication use and underwent an ocular surface examination. The QST metrics included measures of vibratory and thermal thresholds and cold and hot pain temporal summation (surrogate measures of central sensitization) on the forearm. Main Outcomes and Measures Correlations among DE and ocular pain symptom severity with QST metrics measured on the forearm. The OSDI score ranges from 0 to 100, with 100 indicating the most severe DE symptoms. The DEQ5 score ranges from 0 to 22, with the highest score indicating the most severe symptoms, and the NPSI-E score ranges from 0 to 100, with the highest score indicating the most severe symptoms. Psychological state was measured with the 9-item Patient Health Questionnaire, the PTSD Checklist-Military Version for PTSD, and the Symptom Checklist-90 for anxiety. Results Of the 118 patients who participated in the study, 105 (88.9%) were men (mean [SD] age, 60 [10] years), and a mean of 41% had PTSD, 10% depression, and 0.93% anxiety. Using stepwise linear regression analyses, significant associations were identified between overall DE symptom severity and posttraumatic stress disorder scores and tear breakup time (DEQ5 model: R = 0.54; OSDI model: R = 0.61, P < .001). All other variables (ie, demographics, comorbidities, medications, tear film factors, and QST metrics) dropped out of these models. When specifically considering neuropathic-like qualities of DE pain, however, anxiety and hot pain temporal summation at the forearm explained 17% of the variability in ocular burning (R = 0.41; P < .001), and PTSD score, tear breakup time, and hot pain temporal summation at the forearm explained 25% of the variability in sensitivity to wind (R = 0.50; P < .001) and 30% of the variability in total NPSI-E scores (R = 0.55; P < .001). Conclusions and Relevance Our findings demonstrate that neuropathic-like DE pain symptom severity correlates with quantitative measures of pain sensitivity at a site remote from the eye. This result provides additional evidence that DE symptoms are not only manifestations of a local disorder but also involve somatosensory dysfunction beyond the trigeminal system.
A comparison of spontaneously conceived twins and twins conceived by artificial reproductive technologies

Summary Evidence on pregnancy outcomes of twins conceived by artificial reproductive technology (ART) compared with those naturally conceived (NC) is conflicting. We retrospectively audited outcomes of ART and NC twin births at Royal Maternity Hospital, Belfast from 01.01. 2002–31.12. 2003. Of 202 twins, 53 (26%) were ART and 149 (74%) were NC. ART group had increased maternal age (p < 0.001), more primiparous mothers (p < 0.001), used more peri-conceptual folic acid (p = 0.01), booked earlier for antenatal care (p < 0.05), delivered by caesarean section (p = 0.035) more often at a later gestation (p = 0.048) with a higher birth weight (p < 0.05). The NC group had increased congenital anomalies (p = 0.005) and babies requiring neonatal intensive care (p = 0.003). Of confirmed cases, ART twins were all dichorionic compared with 81.7% of NC (p = 0.002). Most neonatal outcome differences disappeared when NC dichorionic twins were compared with ART twins. ART twins have fewer complications than NC twins. Chorionicity accounts for most of these differences.
A new order reduction approach based on elementary operation for Roesser state-space model

In this paper, a new order reduction approach will be proposed for Roesser state-space model of multidimensional (n-D) systems based on the elementary operation order reduction approach proposed by the co-authors very recently. It will be shown that the n-D order reduction problem can be formulated again into an elementary operation problem of an well-initialized n-D polynomial matrix but the standard objective matrix has a more general form than the existing one. As a consequence, the existing elementary operation order reduction approach can be viewed as a special case of the new proposed approach. Moreover, a basic order reduction procedure is presented and corresponding examples are given to illustrate the details as well as the effectiveness of the proposed approach.
Lipid Biology and Lymphatic Function: A Dynamic Interplay with Important Physiological and Pathological Consequences

Lymphatic vessels have been traditionally considered as passive transporters of lipids particularly from the intestine. However, it became apparent from emerging research that lymphatic vessel can play a more extensive role in lipid metabolism than previously realized. Moreover, recent evidence reveals that lipid deposition in the form of white adipose tissue or cholesterol as observed in obesity or hypercholesterolemia, respectively, may perturb lymphatic function. This Review summarizes the evidence supporting a bidirectional relationship between lymphatic function and the deposition of white adipose or cholesterol in peripheral tissue in the context of obesity and hypercholesterolemia. We also discuss potential mechanisms whereby excessive fat or cholesterol accumulation in tissue may account for lymphatic dysfunction. We particularly consider how phenotypic and functional changes in adipose tissue as well as in macrophages accompanying obesity and hypercholesterolemia may affect the lymphatic vasculature. In addition to their transport function, lymphatic vessels play essential roles in regulating inflammatory and adaptive immune responses. Therefore, we highlight how lymphatic dysfunction associated with hypercholesterolemia may influence immunity, inflammation and the significance to atherosclerosis. The emerging importance of the lymphatic system in lipid metabolism and immunity underscores the urgent need to find pharmacological or surgical interventions that can improve lymphatic function which are currently not available.
Bacterial Transcription as a Target for Antibacterial Drug Development

SUMMARY Transcription, the first step of gene expression, is carried out by the enzyme RNA polymerase (RNAP) and is regulated through interaction with a series of protein transcription factors. RNAP and its associated transcription factors are highly conserved across the bacterial domain and represent excellent targets for broad-spectrum antibacterial agent discovery. Despite the numerous antibiotics on the market, there are only two series currently approved that target transcription. The determination of the three-dimensional structures of RNAP and transcription complexes at high resolution over the last 15 years has led to renewed interest in targeting this essential process for antibiotic development by utilizing rational structure-based approaches. In this review, we describe the inhibition of the bacterial transcription process with respect to structural studies of RNAP, highlight recent progress toward the discovery of novel transcription inhibitors, and suggest additional potential antibacterial targets for rational drug design.
Inhibition of functional HER family members increases the sensitivity to docetaxel in human ovarian cancer cell lines

Human epidermal growth factor (HER) family-targeted therapy combined with standard cytotoxic agents might improve the treatment of ovarian cancer. Human ovarian cancer cell lines OVCAR-3, IGROV-1, and SKOV-3 with differential EGFR, HER2, and HER3 expression levels were used to study whether EGFR-directed (cetuximab) or HER2-directed (trastuzumab, pertuzumab) monoclonal antibodies inhibited cell growth and abrogated activated receptor signaling routes. Possible increase of antiproliferative effects and further activation of caspase-3 as a read-out for apoptosis were analyzed when monoclonal antibodies were combined with docetaxel. Cetuximab alone inhibited cell growth in OVCAR-3 and IGROV-1, which was more pronounced when combined with pertuzumab in OVCAR-3. SKOV-3 cell growth was not significantly affected by any of the antibodies. Cetuximab increased the 50% growth-inhibiting effects of docetaxel in OVCAR-3 and IGROV-1, but not in SKOV-3. Coaddition of pertuzumab to cetuximab plus docetaxel in OVCAR-3 and IGROV-1, and, to a lesser extent trastuzumab in OVCAR-3, inhibited cell growth even further. Caspase-3 activation by docetaxel was enhanced after addition of cetuximab in OVCAR-3 and after addition of cetuximab plus pertuzumab in IGROV-1 and SKOV-3. Functional EGFR-signaling, HER2-signaling, and HER3-signaling routes as shown from abrogation of EGF-stimulated and heregulin-stimulated phosphorylated ERK1/2 by cetuximab, trastuzumab, and pertuzumab, respectively, were shown in OVCAR-3 and IGROV-1, but hardly in SKOV-3. Pertuzumab was able to abrogate phosphorylated HER2 by EGF and heregulin, except in SKOV-3. In conclusion, a combination of docetaxel with inhibitors of HER family members, such as cetuximab plus pertuzumab, may be considered for a clinical trial in ovarian carcinomas with functional receptors.
Strain-Dependent Interactions between MK-801 and Cocaine on Retention of C57BL/6 and DBA/2 Mice Tested in a One-Trial Inhibitory Avoidance Task: Involvement of Dopaminergic Mechanisms

Two sets of experiments were carried out with C57BL/6 (C57) and DBA/2 (DBA) mice tested in a one-trial inhibitory avoidance task. In the first set C57 and DBA mice were injected posttraining with saline or with the D1 DA receptor antagonist SCH 23390 and then with saline, cocaine (5 mg/kg), MK-801 (0.1 mg/kg), or with a combination of these two drugs. Cocaine enhanced retention in the C57 strain and impaired it in the DBA strain, and MK-801 potentiated the effects of cocaine in both strains. Furthermore, pretreatment with SCH 23390 completely antagonized the potentiation of the effects of cocaine exerted by MK-801. In the second set of experiments mice belonging to these same two strains were injected posttraining with vehicle or with the D2 DA receptor antagonist (-)-sulpiride and then with saline, cocaine (5 mg/kg), MK-801 (0.1 mg/kg), or with a combination of these two drugs. Pretreatment with the D2 DA receptor antagonist completely antagonized in both strains the potentiation of the effect of cocaine exerted by MK-801. The results of the present research show that the noncompetitive NMDA receptor antagonist MK-801 enhances the effect of cocaine on retention performance in C57 and DBA mice and that dopaminergic mechanisms are involved in this potentiation.
Daily sitting time associated with the risk of metabolic syndrome in Korean adolescents

Abstract Background: This study aimed to investigate the relationship between daily sitting time and the risk of metabolic syndrome in Korean adolescents. Methods: Data from 486 adolescents aged 12–18 years were obtained from national surveys. Daily sitting time was measured using questionnaires and divided into three intervals: <8 h; 8–12 h; and ≥12 h. Results: The mean daily sitting time and prevalence of positive metabolic components were 620.9±9.9 min/day and 45.5±2.7%, respectively. In a multivariate logistic regression analysis, adolescents who sat longer were more likely to have metabolic components (p<0.05), independent of age, sex, area of residence, sleeping time and body mass index. Conclusions: Longer daily sitting time appears to be associated with an increased risk of metabolic syndrome in adolescents. These findings highlight the need to focus on reducing sitting time for all adolescents, not just for those at risk of obesity.
Synthesis and Biodistribution of a New 99mTc‐oxo Complex with Deoxyglucose Dithiocarbamate for Tumor Imaging

The deoxyglucose dithiocarbamate (DGDTC) was radiolabeled with 99mTc(V)‐glucoheptonate (GH), for the potential use as radiopharmaceuticals for tumor imaging. For labeling, 99mTcO‐DGDTC was prepared by ligand‐exchange reaction with 99mTc‐GH. The radiochemical purity of the 99mTcO‐DGDTC complex was over 90% by thin‐layer chromatography and high‐performance liquid chromatography, without any notable decomposition at room temperature over a period of 6 h. Its partition coefficient indicated that it was a hydrophilic complex. The ligand‐exchange reaction occured at neutral condition and under 100 °C for 15 min to achieve high radiochemical purity. In vitro cell studies showed there was an increase in the uptake of 99mTcO‐DGDTC as a function of incubation time and the cellular uptake of 99mTcO‐DGDTC was possibly mediated by way of a d‐glucose mechanism. The biodistribution of 99mTcO‐DGDTC in mice bearing S 180 tumor showed that the complex accumulated in the tumor with good uptake and excellent retention. As compared with other reported 99mTc radiolabeled glucose derivatives, 99mTcO‐DGDTC showed the highest tumor uptake and good tumor/muscle ratios. The tumor/muscle ratio of 99mTcO‐DGDTC uptake was higher than that of [18F] FDG uptake. Single photon emission computed tomography (SPECT) image studies showed there was a visible accumulation in tumor sites, suggesting 99mTcO‐DGDTC would be a promising candidate for tumor imaging.
Validity of the Three‐Column Theory of Thoracolumbar Fractures: A Biomechanic Investigation

Study Design This study validated the three-column theory of fractures by correlating the multidirectional instabilities and the vertabral injuries to each of the three columns, using a biomechanic trauma model. Objectives The objective was to validate the three-column theory as applied to the thoracolumbar fractures. Summary of Background Data The widely used three-column theory of fractures for classification and evaluation was based on retrospective analysis of radiographs. No biomechanic study, using realistic spinal fractures and multidirectional instability measurements, was available. Methods Using 16 fresh cadaveric thoracolumbar human spine specimens, two groups of burst fractures were produced by either simple axial compression or flexion-compression, using a high-speed trauma model. Multidirectional flexibility was measured before and after the trauma, thus quantifying the instability of the burst fracture. Computed tomography scans were taken after the fracture, and a newly developed injury scoring scheme quantified the injuries to the anterior, middle, and posterior columns. Statistical correlations were obtained between the flexibility parameters and injuries to each of the three columns. Results In the axial compression group, the middle column injury, compared with the other two columns, showed the highest correlations to eight of the nine flexibility parameters (average R2 = 0.77). In the flexion-compression group, again the middle column injury showed the highest correlations to eight of the nine flexibility parameters (average R2 = 0.85). Conclusions The results of this study supported the three-column theory of the thoracolumbar fractures and bolstered the concept of the middle column being the primary determinant of mechanical stability of this region of the spine.
Research on Reliability and Lifetime of Solid Insulation Structures in Pulsed Power Systems

Based on the Weibull statistical distribution and the thickness effect on dielectric breakdown strength EBD, a formula to evaluate the reliability of solid insulation structures (SISs) in pulsed power systems is derived. By calculating this formula, it is concluded that an increase of 1.4 times in the dielectric thickness d or a 3/4 decrease in the applied voltage U will increase the reliability of SISs by “9. ” Moreover, by introducing the variable of pulse number N into the Weibull statistical distribution, a formula to evaluate the lifetime of SISs is also derived. It is concluded that when the time shape parameter a is equal to 1, an SIS is in its normal lifetime stage, and the lifetime can be described by the Martin's formula; when a is not equal to 1, the Martin's formula should be revised. To verify the lifetime formula, experiments were designed and conducted. In the end, useful suggestions on design of SISs are summarized.
Transcriptome Expression Profiling in Response to Drought Stress in Paulownia australis

The response and adaptation to drought remains poorly understood for Paulownia australis. To investigate this issue, transcriptome profiling of four P. australis accessions (two diploid and the other two autotetraploid) under water stress condition were studied using Illumina Genome Analyzer IIx analysis. The current study aimed to identify genes of P. australis metabolism pathways that might be involved in this plant’s response to water deficit. Potted seedlings were subjected to well-watered conditions and drought stress, respectively. More than 290 million raw transcript reads were assembled into 111,660 unigenes, with a mean length of 1013 bp. Clusters of orthologous groups, gene ontology and the Kyoto Encyclopedia of Genes and Genomes annotations analyses were performed on the unigenes. Many differentially expressed genes and several metabolic pathways were identified. Quantitative real-time polymerase chain reaction was used to verify the expression patterns of 14 genes. Our study identified altered gene expression in P. australis induced by drought stress and provided a comprehensive map of drought-responsive genes and pathways in this species. To our knowledge, this is the first publicly available global transcriptome study of P. australis. This study provides a valuable genetic resource for this species.
Statistical analysis of soft breakdown in ultrathin gate oxides

It is found that the Weibull slope /spl beta/ of the time-to-soft breakdown (t/sub SBD/) distributions coincides with that of time-to-hard breakdown (t/sub BD/) distributions over the oxide thickness range 1.9-4.8 nm, and /spl beta/ linearly decreases with decrease of oxide thickness. Such decrease in /spl beta/ of both t/sub SBD/ and t/sub BD/ distributions is well correlated to measured Si-O-Si bond angle reduction induced by compressive stress in the SiO/sub 2/ network. These results suggest that soft breakdown (SBD) as well as hard breakdown (HBD) are triggered by a common physical mechanism such as defect generation from strained Si-O-Si bonds.
Anti-factor VIII antibodies

Summary The development of anti-factorVIII (FVIII) antibodies is currently one of the most serious complications in the treatment of haemophilia A patients. Numerous studies in literature report on their epitope specificity, their mechanism of FVIII inactivation, and their relationship with FVIII genetic alterations. During the last two years, however, a particular effort has been made to better understand their generation, with particular emphasis on the interplay of T cells and B cells specific for FVIII and the generation of anti-FVIII antibodies. Moreover, novel strategies to improve the management or treatment of patients with anti- FVIII antibodies have been recently proposed: the use of less immunogenic engineered recombinant FVIII molecules, neutralization of inhibitors by blocking their deleterious activity either by low molecular weight peptide decoys or by anti-idiotypic antibodies, and attempts to suppress the T-cell response involved in the antibody formation. All of these represent promising therapeutic approaches. This review attempts to sum up current knowledge of the nature and properties of anti-FVIII antibodies, their mechanism of action, their neutralization by anti-idiotypic antibodies, and the role of T cells in FVIII inhibitor formation. In the final part, some of the new strategies susceptible to improve the management or the eradication of anti-FVIII antibodies are presented.
Direct synthesis of anisotropic polymer nanoparticles.

No (self-)assembly required: Both spherical and anisotropic “dumbbell” polymer nanoparticles with targeted shapes in the <100-nm size range were prepared by direct synthesis not relying on self-assembly. Atom-transfer polymerization techniques at high concentrations produce both spherical and dumbbell-like nanoparticles directly from simple vinyl monomers on a multigram scale.
Clinical Value of Electrocardiographic Parameters in Genotyped Individuals with Familial Long QT Syndrome

MOENNIG, G. , et al.: Clinical Value of Electrocardiographic Parameters in Genotyped Individuals with Familial Long QT Syndrome. Rate corrected QT interval (QTc) and QT dispersion (QTd) have been suggested as markers of an increased propensity to arrhythmic events and efficacy of therapy in patients with long QT syndrome (LQTS). To evaluate whether QTc and QTd correlate to genetic status and clinical symptoms in LQTS patients and their relatives, ECGs of 116 genotyped individuals were analyzed. JTc and QTc were longest in symptomatic patients (n = 28). Both QTd and JTd were significantly higher in symptomatic patients than in asymptomatic (n = 29) or unaffected family members (n = 59). The product of QTd/JTd and QTc/JTc was significantly different among all three groups. Both dispersion and product put additional and independent power on identification of mutation carriers when adjusted for sex and age in a logistic regression analysis. Thus, symptomatic patients with LQTS show marked inhomogenity of repolarization in the surface ECG. QT dispersion and QT product might be helpful in finding LQTS mutation carriers and might serve as additional ECG tools to identify asymptomatic LQTS patients.
In vitro Model for Assessing Arrhythmogenic Properties of Drugs Based on High-resolution Impedance Measurements

Background/Aims: Cardiac dysfunction is one of the main cause of drug candidate failures in the preclinical and/or clinical studies and responsible for the retraction of large number of drugs from the market. The prediction of arrhythmic risk based on preclinical trials during drug development remains limited despite intensive and costly investigation. Moreover, methods for analyzing beating behavior of cardiomyocytes (CMs) in culture to diagnose arrhythmias are not well developed. Methods: In this study, we combined two emerging technologies, induced pluripotent stem (iPS) cell-derived CMs and impedance-based real-time (xCELLigence RTCA Cardio Instrument) monitoring of CM electrical activity, to assess the effect of drugs known affect cardiac activity such as isoproterenol, carbachol, terfenadine, sotalol and doxorubicin. Cells were exposed to a drug in a single dose or repeated dose scenarios and data were analyzed using RTCA Cardio software, Poincaré plot and detrended fluctuation analysis. Results: The results revealed significant changes in beating parameters of iPS-CMs induced by reference compounds. Heptanol, gap junction blocker, completely disrupted the synchronous beating pattern of iPS-CMs. Decrease of beating rate, amplitude and beat-to-beat signal variations of iPS-CMs monolayer observed in the presence of doxorubicin revealed severe abnormality detected by the system. Additionally, the irregular beating rhythms recorded in the presence of Terfenadine and Sotalol at high concentration, reflect abnormalities in cell contraction and/or relaxation which may lead to arrhythmia. Conclusions: All these results indicated that xCELLigence RTCA Cardio system combined with iPS cells, has the potential to be an attractive high-throughput tool for studying CMs during prolonged culture times and to screen potential drugs for cardiotoxic side effects.