Miracle-dz/UniFAR-FTUs huggingface dataset:
Cutting Edge: Nanogel-Based Delivery of an Inhibitor of CaMK4 to CD4+ T Cells Suppresses Experimental Autoimmune Encephalomyelitis and Lupus-like Disease in Mice

Treatment of autoimmune diseases is still largely based on the use of systemically acting immunosuppressive drugs, which invariably cause severe side effects. Calcium/calmodulin-dependent protein kinase IV is involved in the suppression of IL-2 and the production of IL-17. Its pharmacologic or genetic inhibition limits autoimmune disease in mice. In this study, we demonstrate that KN93, a small-molecule inhibitor of calcium/calmodulin-dependent protein kinase IV, targeted to CD4+ T cells via a nanolipogel delivery system, markedly reduced experimental autoimmune encephalomyelitis and was 10-fold more potent than the free systemically delivered drug in the lupus mouse models. The targeted delivery of KN93 did not deplete T cells but effectively blocked Th17 cell differentiation and expansion as measured in the spinal cords and kidneys of mice developing experimental autoimmune encephalomyelitis or lupus, respectively. These results highlight the promise of cell-targeted inhibition of molecules involved in the pathogenesis of autoimmunity as a means of advancing the treatment of autoimmune diseases.
Methyl 2-Cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate Is a Peroxisome Proliferator-Activated Receptor-γ Agonist That Induces Receptor-Independent Apoptosis in LNCaP Prostate Cancer Cells

Methyl 2-cyano-3,11-dioxo-18β-olean-1,12-diene-30-oate (β-CDODA-Me) is a synthetic analog of the naturally occurring triterpenoid glycyrrhetinic acid, which contains a 2-cyano substituent in the A-ring. β-CDODA-Me was a potent inhibitor of LNCaP prostate cancer cell growth (IC50 ∼1 μM) and activated peroxisome proliferator-activated receptor γ (PPARγ), whereas analogs without the cyano group were weakly cytotoxic and did not activate PPARγ. β-CDODA-Me induced p21 and p27, down-regulated cyclin D1 protein expression, and induced two other proapoptotic proteins, namely nonsteroidal anti-inflammatory drug-activated gene-1 and activating transcription factor-3. However, induction of these responses by β-CDODA-Me was PPARγ-independent and due to activation of phosphatidylinositol-3-kinase, mitogen-activated protein kinase, and jun N-terminal kinase pathways by this compound. In contrast, β-CDODA-Me also decreased androgen receptor (AR) and prostate-specific antigen (PSA) mRNA and protein levels through kinase-independent pathways. β-CDODA-Me repressed AR mRNA transcription, whereas decreased PSA mRNA levels were dependent on protein synthesis and were reversed by cycloheximide. Thus, potent inhibition of LNCaP cell survival by β-CDODA-Me is due to PPARγ-independent activation of multiple pathways that selectively activate growth-inhibitory and proapoptotic responses.
Experimental Pain Sensitivity in Women With Temporomandibular Disorders and Pain-free Controls: The Relationship to Orofacial Muscular Contraction and Cardiovascular Responses

ObjectiveChronic pain may result both from a generalized hypersensitivity to acute pain, suggestive of central sensitization processes, and dysfunction of the endogenous pain regulatory system. One purpose of this study was to compare experimental pain sensitivity at several anatomic sites in temporomandibular disorder (TMD) patients and pain-free controls during baseline and after standardized mechanical load of the orofacial region. A second purpose was to compare the pain-modulating effects of cardiovascular responses in TMD patients and pain-free controls. MethodsExperimental pain was induced by electrocutaneous stimulation of the dorsal left hand and pressure algometry at the right masseter muscle and the sternum. The pain sensitivity of the orofacial region was manipulated by isometric contraction of the masseter muscles. Elevations of mean arterial pressure and heart rate were induced by a simulated job interview. ResultsAt baseline, the TMD patients exhibited a significantly higher electrocutaneous pain threshold. Relative to the healthy controls, the TMD patients reported increased electrocutaneous and pressure pain sensitivity after isometric contraction of the orofacial region. In addition, there were correlations between mean arterial pressure and pain sensitivity in the TMD group only. DiscussionSignificant increases in generalized pain sensitivity occurred in the TMD group, but not in the control group, after isometric contraction of the orofacial muscles, suggestive of a central sensitization process in TMD. Moreover, only in the TMD group there were significant associations between cardiovascular responsesand pain sensitivity, challenging previous assumptions of this relationship occurring mainly in pain-free individuals.
Prefabricated Free Fibula Flap for Reconstruction of a Maxillary Defect: A Case Report

The present article describes a case of prosthetic rehabilitation with the new technique of prefabricated osteo-cutaneous free fibula flap for reconstructing a maxillary defect which had resulted from ameloblastoma. The fibula and a cuff of 6-8 mm were prepared with its pedicle intact. The bone flap was left in place with its pedicle intact for 2 to 3 months; the skin graft and the flap were free of inflammation. The fibula flap was then transferred to the maxilla. Implant placement was performed 4 to 6 months after transfer of the flap to the oral cavity. Three titanium implants, with a width of 4 mm and a length of 13 mm, were placed using a conventional two-stage protocol. A cement-retained 5-unit metal-ceramic fixed partial denture was fabricated.
Maternal Feeding Practices and Beliefs and Their Relationships to Overweight in Early Childhood

To better explore possible factors that may lead to childhood obesity, we developed and analyzed two new instruments that assess maternal feeding practices and beliefs. The Infant Feeding Questionnaire (IFQ) assesses feeding during the entire first year of life and was administered to 453 mothers of children 11 to 23 months old. The Preschooler Feeding Questionnaire (PFQ) assesses feeding of young children between the ages of 2 to 5 years and was administered to 634 mothers of children this age. Each questionnaire was factor analyzed and mean factor scores were calculated and linked with the children's measured and mothers' self-reported weight and height. Mean factor scores from the IFQ and PFQ were compared between mothers who were obese (body mass index ≥30 kg/m2) and those who were nonobese, between those who did and those who did not have an overweight child (weight-for-height ≥90th percentile), and between those who had a low income (≤185% of the poverty level) and those who had a high income. To control for confounding variables and to detect interaction among variables, hierarchical linear regression was used. Results from this study did not suggest that there is a particular "feeding style" that is associated with overweight in young children; however, there were differences found in feeding behaviors between high and low income mothers.
Acupuncture for Depression: A Critique of the Evidence Base

Aim: The aim of this review is to examine the evidence for acupuncture's effectiveness as a depression intervention. Unlike other reviews, which consider methodological concerns relevant to all experimental evaluations, this review focuses on the scope of studies, and uses a PICO (patients, intervention, comparison, and outcome) structure to determine what can potentially be learned from primary studies that have already been screened for methodological quality by reviewers. Discussion: The review identified a number of study limitations. (i) Patients: majority of trial reports have not described a rationale for the selection of patients or inclusion/exclusion criteria. Prognostic indicators were not reported and there were also concerns about the generalizability of study populations. (ii) Intervention: most trials investigate poorly rationalized standardized acupuncture protocols thus quality of care may be an issue and generalizability to routine clinical practice is a main concern. In trials using other methods generalizability is also poor. (iii) Comparisons: concerns were raised about using therapeutically inappropriate acupuncture. (iv) Outcomes: short‐term focus and the narrow range of outcomes explored. According to more recent systematic review evidence it is probable the shortcomings identified in the PICO review have not been addressed by subsequent research. The concept of model validity, proposed by other researchers, is discussed, and suggestions put forward about complex intervention evaluation methods, which may be better suited to evaluating acupuncture care. Conclusion: Uncertainty remains about the value of acupuncture care, as it is routinely practiced in the West, and this uncertainty has not been resolved by trials to date. Existing evaluations may however be useful for guiding decisions about the value of specific techniques for patients with depression.
Assessing the Skill of Precipitation and Temperature Seasonal Forecasts in Spain: Windows of Opportunity Related to ENSO Events

The skill of state-of-the-art operational seasonal forecast models in extratropical latitudes is assessed using a multimodel ensemble from the Development of a European Multimodel Ensemble System for Seasonalto-Interannual Prediction (DEMETER) project. In particular, probabilistic forecasts of surface precipitation and maximum temperature in Spain are analyzed using a high-resolution observation gridded dataset (Spain02). To this aim, a simple statistical test based on the observed and predicted tercile anomalies is used. First, the whole period 1960–2000 is considered and it is shown that the only significant skill is found for dry events in autumn. Then, the influence of ENSO events as a potential source of conditional predictability is
Controlling pore assembly of staphylococcal γ‐haemolysin by low temperature and by disulphide bond formation in double‐cysteine LukF mutants

Staphylococcal LukF and Hlg2 are water‐soluble monomers of γ‐haemolysin that assemble into oligomeric pores on the erythrocyte membranes. Here, we have created double‐cysteine LukF mutants, in which single disulphide bonds connect either the prestem domain and the cap domain (V12C‐T136C, Cap–Stem), or two β‐strands within the prestem domain (T117C‐T136C, Stem–Stem) to control pore assembly of γ‐haemolysin at intermediate stages. The disulphide‐trapped mutants were inactive in erythrocyte lysis, but gained full haemolytic activity if the disulphide bonds were reduced. The disulphide bonds blocked neither the membrane binding ability nor the intermediate prepore oligomerization, but efficiently inhibited the transition from prepores to pores. The prepores of Cap–Stem were dissociated into monomers in 1% SDS. In contrast, the prepores of Stem–Stem were stable in SDS and had ring‐shaped structures similar to those of wild‐type LukF, as observed by transmission electron microscopy. The transition of both mutants from prepores to pores could even be achieved by reducing disulphide bonds at low temperature (2°C), whereas prepore oligomerization was effectively inhibited by low temperature. Finally, real‐time transition of Stem–Stem from prepores to pores on ghost cells, visualized using a Ca2+‐sensitive fluorescent indicator (Rhod2), was shown by the sequential appearance of fluorescence spots, indicating pore‐opening events. Taken together, these data indicate that the prepores are legitimate intermediates during γ‐haemolysin pore assembly, and that conformational changes around residues 117 and 136 of the prestem domain are essential for pore formation, but not for membrane binding or prepore oligomerization. We propose a mechanism for γ‐haemolysin pore assembly based on the demonstrated intermediates.
Ultrasound versus MRI: is there a difference in measurements of the fetal lateral ventricles?

Abstract Objective: To evaluate whether fetal brain lateral ventricle measurements differ between ultrasound (US) and MRI. Methods: We evaluated 115 fetuses with US and MRI performed within 24 h of each other. Ventricular measurements were performed in the axial plane at the level of the atria for both modalities and the right and left ventricles were evaluated separately. We compared mean measurements; mean differences, association with gestational age (GA), association with the presence of a brain anomaly, and agreement between MRI and US. Results: The LV and RV were measured in 65 and 64 cases, respectively. LV and RV size estimates were significantly greater when measured by MRI compared with US (p < 0.001). Therefore, LV and RV were 0.87 mm and 0.89 mm larger in MRI versus US, respectively. Neither GA at measurement or presence/absence of a brain anomaly was significantly associated with differences in measurements. When comparing the agreement between the US and MRI measurements for ventriculomegaly; the kappa level of agreement for the LV and RV was 0.74 for each. Conclusion: MRI measurements of ventricles are significantly larger than the measurements by US by ∼1 mm. There is a good level of agreement when categorizing by normal, mild and severe ventriculomegaly.
Molecular detection of Mycoplasma conjunctivae in English sheep affected by infectious keratoconjunctivitis

INFECTIOUS keratoconjunctivitis (IKc) is a localised inflammatory condition of the conjunctiva and cornea in small domestic and wild ruminants. In the early stages, the disease may present as a unilateral or bilateral conjunctivitis with hyperaemia of the vessels, but untreated cases may progress to mucopurulent keratitis and corneal ulceration resulting in opaque or perforated corneas and transient blindness. Bacterial causes of the disease include Chlamydia, Rickettsia and Mycoplasma species (Egwu 1991). Mycoplasma conjunctivae is the major single cause of IKC in domestic and wild sheep and goats and has been reproduced experimentally (Jones and others 1976, ter Laak and others 1988, Giacometti and others 1998), but Mycoplasma arginini and Acholeplasma oculi have also been isolated from sheep with ocular infections (Leach 1970, Arbuckle and Bonson 1980). Pink-eye, the common name for IKC, was suspected in a flock of sheep on a farm in Gloucestershire, England, after the farmer noted that some animals were disoriented and suffering unilateral and transient blindness; some had conjunctivitis or corneal oedema, neither of which responded to topical or intramuscular tetracycline treatment. IKC was diagnosed but the nature of the ocular lesions was reminiscent of those seen in sheep infected with Mycoplasma agalactiae and some members of the Mycoplasma mycoides cluster which are exotic to the UK. This prompted farm visits for further studies to determine the exact cause and eliminate the possibility of exotic causative agents. In the first visit, 20 sheep were examined and in the second visit, three months later, 19 sheep, 11 of which were repeat examinations from the first visit, were sampled from this farm. Conjunctival swabs were taken from sheep for bacteriological and molecular investigations in the laboratory. At penside, individual swabs were inoculated into 3 ml aliquots of Eaton's broth with antibiotics (Nicholas and Baker 1998) and enriched pleuropneumonia-like organism broth (Giacometti and others 1998), and streaked onto Eaton's agar plates. 1 ml of sample was removed from each Eaton's broth sample and used for molecular studies. The inoculated broths and agar plates were incubated at 37°C and 5 per cent carbon dioxide and monitored daily for signs of mycoplasmal growth as described previously (Nicholas and Baker 1998). Mycoplasmas grew only on Eaton's agar plates and Eaton's broths and were identified by their biochemical characteristics and by the growth inhibition and epifluorescence tests as M conjunctivae using specific antisera (Bradbury 1998, Poveda and Nicholas 1998). M agalactiae was not isolated and M conjunctivae was present in four of 39 samples. Sediments collected by centrifugation of 1 ml of sample in Eaton's broth were resuspended in 200 i1l TNE ( 0-01M TrisHCI, pH 8-0, 0-O0M NaCl, 0-01M EDTA) buffer and DNA was
Big Data in Fashion Industry: Color Cycle Mining from Runway Data

Color is a powerful selling tool, especially in the fashion and textile industry, in which products aim to inspire consumers visually. Color Cycle Analysis studies the recurring cycle of trends. Traditional fashion color cycle analysis and prediction is performed by observing and extrapolating from trends apparent on fashion runways. With the emergence of big data, there is a potential to apply data analytics method in fashion industry. We propose and develop a data-driven methodology to analyze color trends by mining online textual data of global fashion runways collected from the Style.com website. By capturing three important elements in color hue, saturation and brightness, we are able effectively extract their presence and variations in textual data. We illustrate the reoccurrence of seven Color Cycle phases: High Chroma, Multicolored, Subdued, Earth Tones, Achromatic, and Purple Phase from runway review data.
Convergent and Alternative Designs in the Digital Adhesive Pads of Scincid Lizards

Prasinohaema virens, an arboreal scincid lizard, differs from its closest relatives in that it exhibits subdigital adhesive setae resembling those of anoles in shape and those of geckos in some aspects of size. The other scincid species in this genus as well as those in a presumed ancestral genus exhibit pad scales with surface folds and ruffles but no setae; at least one of these species uses an adhesive grip similar to that of anoles and geckos. Thus, there appear to be two strikingly different epidermal specializations for adhesive grip within this small radiation.
Electrocardiogram (ECG) Signal Processing

Signal processing of electrocardiographic signals has a long and rich history and has greatly helped to enhance the diagnostic capability, especially when signals are recorded in noisy environments. This article gives an introductory presentation of the basic set of algorithms used for conditioning the ECG with respect to different types of noise and artifacts, detecting heartbeats, extracting basic ECG measurements, and performing data compression. Signal processing in clinical applications is exemplified by the high-resolution ECG and T wave alternans.
The relation between an adverse psychological and social environment in childhood and the development of adult obesity: a systematic literature review

The prevalence of obesity is on a global‐wide increase, but still the aetiology of adult obesity is poorly understood. It has been shown that overweight children suffer from adverse psychological events, but less is known about the potential effects of adverse psychological factors among normal weight children for later development of obesity. The purpose of this study was to systematically review current literature on associations between psychological factors in childhood and development of obesity in adulthood. A systematic search was conducted in three electronic databases MEDLINE (silverplatter 1977–2008), PsycINFO (1972–2008) and PsycINFO Weekly (week 1 January 2007–week 3 July 2008) to identify studies of interest. Six prospective and two retrospective studies were identified. Psychosocial factors related to adult obesity were lack of childhood care, abuse and childhood anxiety disorders. In addition, depression in adolescence tended to be related to adult obesity but among young girls only. Learning difficulties and scholastic proficiencies below average were also risk factors. The current literature suggests that specific psychosocial factors in childhood may act as determinants for developing obesity in adulthood.
Oxidative Damage of Cardiomyocytes Is Limited by Extracellular Regulated Kinases 1/2-mediated Induction of Cyclooxygenase-2*

Oxidative stress causes cardiac damage following ischemia/reperfusion and in response to anthracyclines. Extracellular signal-regulated kinases (ERK) 1/2 are activated by oxidative stress in cardiac myocytes and protect cardiac myocytes from apoptosis. Prostaglandins (PG) also protect cells from injury in a number of tissues, including the cardiomyocyte. Cyclooxygenase (COX) the rate-limiting enzyme in PG biosynthesis has two isoforms, the constitutive COX-1 and an inducible COX-2. Here, we examined the effects of two oxidative stresses, hydrogen peroxide (H2O2) and the anthracycline doxorubicin on the activity of ERK1/2 and the expression of COX isoforms and PG formation in neonatal rat primary cardiomyocytes. These cells expressed COX-1 at rest and both COX isoforms on treatment with phorbol 12-myristate 13-acetate. Exposure to 50 μmH2O2 for 10 min or doxorubicin at 10 and 100 μg/ml caused expression of COX-2 that was prevented by free radical scavengers. COX-2 induction was associated with activation of ERK1/2 and the specific ERK-inhibitor PD098059 abolished COX-2 expression. Treatment of cells with decoy oligonucleotides corresponding to COX-2 promoter elements implicated the AP-1 and NF-κB-2 but not the NF-κB-1 in the transcription of COX-2. Induction of COX-2 mRNA and protein was accompanied by increased prostacyclin formation, which was abolished by the selective COX-2 inhibitor, NS-398, and PD098059. H2O2 and doxorubicin enhanced the release of lactate dehydrogenase and free radical scavengers prevented this. NS-398 enhanced the release of lactate dehydrogenase in response to H2O2 and doxorubicin, whereas the injury was prevented by iloprost, a stable prostacyclin analogue. In cardiomyocytes cell injury by H2O2 and doxorubicin is limited by an increase in prostacyclin formation that reflects induction of COX-2 mediated by ERK1/2 activation.
Models of individual trajectories in computer-assisted instruction for deaf students.

In this report we present a new approach to evaluation of curriculum. Many of us who have been engaged in curriculum reform efforts have been dissatisfied with the wait-and-see approach required when classical evaluation of a new curriculum is used. We have in mind evaluation by comparing pretests and posttests, with an analysis of posttest grade-placement distributions as a function of pretest distribution and exposure in some form to the new curriculum. In line with approaches used in other parts of science, it is natural to ask if a more predictive-control approach could be used and made an integral part of the curriculum to ensure greater benefits, especially for the disadvantaged or handicapped student. The approach discussed in this report is aimed precisely at this question. The strategy is to develop a theory of prediction for individual student progress This research was funded by Office of Education Grant No. OEG-0-70-4797(607), OE Project No. 142280.
Information-seeking behavior of medical residents in clinical practice in Bahia, Brazil.

To explore the information needs and behavior of housestaff at this institution, the researchers surveyed a group of residents from October 2004 through December 2004. The team hypothesized that (a) consultation of scientific information constituted a crucial element of patient care; (b) residents were familiar with available information resources; and (c) they were able to handle these resources efficiently. This survey also aimed to identify the role of health sciences libraries and resources available in Brazil in meeting physicians’ information needs for clinical practice.