Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term, targeted genetic modification of the aqueous humor outflow tract coupled with noninvasive imaging of gene expression in vivo.

PURPOSE To address a problem impeding research into glaucoma-associated genetic mutations and glaucoma gene therapy and achieve permanent, targeted transgene expression in the trabecular meshwork (TM). Lentiviral vectors are known to transduce human donor eye TM ex vivo, but efficacy in vivo has not been shown. More generally in the field of gene therapy, the authors hypothesized that distinctive properties of the intraocular aqueous circulation could facilitate solving problems of accessibility, targeting, and scale that have hindered realization of gene therapy in other settings. METHODS A domestic cat model was developed in which long-term in vivo studies were performed. After dose-response studies in primary human TM cells, 19 cats received anterior chamber (AC) injections of stepped doses (10(6)-10(8) transduction units) of lentiviral vectors encoding different marker transgenes (beta-galactosidase, Aequorea victoria green fluorescent protein [GFP], or Renilla reniformis GFP). Animals were monitored serially for transgene expression and IOP. RESULTS High-grade, stable transgene expression in the TM was achieved and monitored noninvasively over time in living animals. Extensive expression resulted after a single transcorneal injection, persisted for at least 10 months (time of death in the present studies), and was targeted to the TM. The initial IOP did not differ significantly from the IOP at the end of the study (P = 0.4). Aequorea GFP was superior to Renilla GFP. Vectors were effective enough to cause GFP-specific overexpression cytotoxicity at the highest dose, which was solved by dose reduction. CONCLUSIONS High-grade transgene expression in this large-animal model persisted stably for at least 10 months after a single transcorneal lentiviral vector injection, was highly targeted, and could be monitored serially and noninvasively in living animals. These studies provide a basis for developing realistic disease models and administering glaucoma gene therapy.
A pilot study to evaluate aflatoxin exposure in a rural Ugandan population

The fungal metabolite aflatoxin is a common contaminant of foodstuffs, especially when stored in damp conditions. In humans, high levels can result in acute hepatic necrosis and death, while chronic exposure is carcinogenic. We conducted a pilot study nested within an existing population cohort (the General Population Cohort), to assess exposure to aflatoxin, among people living in rural south‐western Uganda.
Performance Under Acute Stress: A Qualitative Study of Soldiers' Experiences of Hand-to-Hand Combat

The chief aim of this study was to obtain in-depth descriptions of soldiers’ first-person experiences of hand-to-hand combat during wartime operations using a stress and coping framework (Lazarus & Folkman, 1984). The results of phenomenological interviews revealed 4 major themes which, based on several participants’ own words, were labeled “immediate threat,” “flip the switch,” “fast,” and “adrenaline. ” It was concluded that the hand-to-hand combat experiences of these soldiers (a) imposed stressors from a variety of sources, (b) required coping responses comprising a swift and accurate interpretation of environmental conditions and rapid deployment of problemfocused strategies, and (c) evoked a constellation of powerful physiological and psychological reactions. Implications of this study for military personnel include the importance of “expecting the unexpected” in seemingly routine yet potentially hazardous combat operations, an emphasis on developing highly automated, problem-focused coping strategies and physical fighting skills, and the need for training in variable and unpredictable environments that demand rapid skill adaptations to context specific stressors.
Effects of dietary cholesterol on bile acid synthesis in liver and hepatomas.

Summary The effects of cholesterol feeding on bile acid production in vitro in liver were contrasted with those in a strain of Morris hepatoma active in sterol synthesis. The principal conclusions are as follows: Bile acid production de novo from acetate in liver is suppressible by dietary cholesterol in a fashion exactly comparable with, and related to, the cholesterol negative feedback phenomenon. In liver, a dual, reciprocating precursor supply is available for bile acid formation. Dietary cholesterol, when present, functions in the presence of blockaded sterol synthesis, as the sole precursor of bile acid. In the presence of a high-cholesterol diet, liver has the ability to convert mevalonate and stored dietary cholesterol simultaneously to bile acid. Bile acid synthesis by a malignant tumor is described in this report. The tumor (Morris hepatoma 3924A) is active in bile acid production from both acetate and mevalonate, but these syntheses are totally unaffected by dietary cholesterol. Moreover, dietary cholesterol cannot itself be utilized by the tumor for bile acid synthesis.
A Study of English Listening Strategies Applied by Technological University Students

Listening ability is one of the important skills in foreign language learning. Among four language skills, researches show that listening skill is employed most frequently. Therefore, strategies for listening and the ability to use them effectively are particularly significant in language learning. This study intended to investigate the listening strategies employed by university students in Taiwan. There were 239 technological university students attended this study. The questionnaire consists of 30 questions including the metacognitive strategies, cognitive strategies, social and affective strategies. The findings indicated that most students were still unable to apply the strategies properly in EFL listening and needed guidance from instructors. The results of this study provide references for both educators and learners to evaluate their teaching and learning listening experiences in the classroom as well as the application in daily communication.
From Mechanosensitivity to Inflammatory Responses: New Players in the Pathology of Glaucoma

Abstract Purpose of the study: Many blinding diseases of the inner retina are associated with degeneration and loss of retinal ganglion cells (RGCs). Recent evidence implicates several new signaling mechanisms as causal agents associated with RGC injury and remodeling of the optic nerve head. Ion channels such as Transient receptor potential vanilloid isoform 4 (TRPV4), pannexin-1 (Panx1) and P2X7 receptor are localized to RGCs and act as potential sensors and effectors of mechanical strain, ischemia and inflammatory responses. Under normal conditions, TRPV4 may function as an osmosensor and a polymodal molecular integrator of diverse mechanical and chemical stimuli, whereas P2X7R and Panx1 respond to stretch- and/or swelling-induced adenosine triphosphate release from neurons and glia. Ca2+ influx, induced by stimulation of mechanosensitive ion channels in glaucoma, is proposed to influence dendritic and axonal remodeling that may lead to RGC death while (at least initially) sparing other classes of retinal neuron. The secondary phase of the retinal glaucoma response is associated with microglial activation and an inflammatory response involving Toll-like receptors (TLRs), cluster of differentiation 3 (CD3) immune recognition molecules associated with the T-cell antigen receptor, complement molecules and cell type-specific release of neuroactive cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). The retinal response to mechanical stress thus involves a diversity of signaling pathways that sense and transduce mechanical strain and orchestrate both protective and destructive secondary responses. Conclusions: Mechanistic understanding of the interaction between pressure-dependent and independent pathways is only beginning to emerge. This review focuses on the molecular basis of mechanical strain transduction as a primary mechanism that can damage RGCs. The damage occurs through Ca2+-dependent cellular remodeling and is associated with parallel activation of secondary ischemic and inflammatory signaling pathways. Molecules that mediate these mechanosensory and immune responses represent plausible targets for protecting ganglion cells in glaucoma, optic neuritis and retinal ischemia.
The challenges for scientific publishing, 60 years on

The most obvious difference in science publishing between ‘then’ and ‘now’ is the dramatic change in the communication of data and in their interpretation. The democratization of science via the Internet has brought not only benefits but also challenges to publishing including fraudulent behavior and plagiarism, data and statistics reporting standards, authorship confirmation and other issues which affect authors, readers, and publishers in different ways. The wide accessibility of data on a global scale permits acquisition and meta‐analysis to mine for novel synergies, and has created a highly commercialized environment. As we illustrate here, identifying unacceptable practices leads to changes in the standards for data reporting.
St. Jude Medical Trifecta™ aortic valve perioperative performance in 200 patients.

OBJECTIVES The St. Jude Medical Trifecta aortic bioprosthesis (St. Jude Medical, Inc., St. Paul, MN, USA) is a new stented pericardial tissue heart valve. The aim of the study was to evaluate the clinical and haemodynamic performance of the Trifecta bioprosthesis in the early postoperative period. METHODS From July 2010 to September 2012, a total of 200 consecutive patients underwent aortic valve replacement with the Trifecta valve in our institution. All intraoperative and postoperative data were prospectively collected. Mean EuroSCORE II was 3.98%. Echocardiography was performed at discharge in all patients. RESULTS The mean age was 71.2 ± 7.7 (range 39-89 years). Extubation in the operating theatre was successfully performed in 96% of patients. Mean hospital stay was 8.5 days. The prosthesis sizes were 19 mm (n = 33), 21 mm (n = 81), 23 mm (n = 59), 25 mm (n = 23) and 27 mm (n = 4). Mean systolic pressure gradients ranged from 9.4 mmHg (size 19 valve) to 4.8 mmHg (size 27 valve). Mean effective orifice area (EOA) ranged from 1.61 cm(2) (size 19 valve) to 2.5 cm(2) (size 27 valve). Severe mismatch (<0.65 cm(2)/m(2)) did not occur in any patient. Of note, 99.5% of patients had mild or no aortic insufficiency at discharge. The early (30-day) mortality was 2.5% (n = 5). CONCLUSIONS The Trifecta valve offers good clinical results and excellent haemodynamic performance. Special care must be taken to avoid oversizing, which can lead to difficulty in implantation and can produce gradient increases due to an excess of prosthetic leaflet tissue.
PrivBayes: private data release via bayesian networks

Privacy-preserving data publishing is an important problem that has been the focus of extensive study. The state-of-the-art goal for this problem is differential privacy, which offers a strong degree of privacy protection without making restrictive assumptions about the adversary. Existing techniques using differential privacy, however, cannot effectively handle the publication of high-dimensional data. In particular, when the input dataset contains a large number of attributes, existing methods require injecting a prohibitive amount of noise compared to the signal in the data, which renders the published data next to useless. To address the deficiency of the existing methods, this paper presents PrivBayes, a differentially private method for releasing high-dimensional data. Given a dataset D, PrivBayes first constructs a Bayesian network N, which (i) provides a succinct model of the correlations among the attributes in D and (ii) allows us to approximate the distribution of data in D using a set P of low-dimensional marginals of D. After that, PrivBayes injects noise into each marginal in P to ensure differential privacy, and then uses the noisy marginals and the Bayesian network to construct an approximation of the data distribution in D. Finally, PrivBayes samples tuples from the approximate distribution to construct a synthetic dataset, and then releases the synthetic data. Intuitively, PrivBayes circumvents the curse of dimensionality, as it injects noise into the low-dimensional marginals in P instead of the high-dimensional dataset D. Private construction of Bayesian networks turns out to be significantly challenging, and we introduce a novel approach that uses a surrogate function for mutual information to build the model more accurately. We experimentally evaluate PrivBayes on real data, and demonstrate that it significantly outperforms existing solutions in terms of accuracy.
Hispanic Minority College Students at Selective Colleges

Hispanic college enrollment in 2011 surpassed all other minority groups. However, Hispanic graduation rates continue to lag. This study examines background, academic integration, social integration, perception of prejudice and discrimination factors, and social capital factors, and how these affect Hispanic undergraduate 6-year completion rates at selective colleges. The results demonstrate that social capital during the high school senior year and attending a private or liberal arts college positively affect Hispanic students’ graduation rates.
Association of Serum Asymmetric Dimethylarginine With Muscle Strength and Gait Speed: A Cross‐Sectional Study of the HEIJO‐KYO Cohort

Muscle strength and gait speed are related with functional limitations and disabilities and also predict cardiovascular and all‐cause mortality. Nitric oxide (NO) plays an important role in regulating physiological process in skeletal muscles; however, the association between serum asymmetric dimethylarginine (ADMA) level, an endogenous competitive inhibitor of NO synthesis, and physical performance has not yet been studied. We investigated the associations of serum ADMA level with muscle strength and usual gait speed in a cross‐sectional study of 550 elderly individuals (mean age, 71.2 ± 6.6 years). Mean ADMA level was 0.45 ± 0.06 µmol/L; mean grip and quadriceps strengths were 27.7 ± 8.4 kg and 165.1 ± 81.6 Nm, respectively; and mean gait speed was 1.37 ± 0.30 m/s. In multivariate linear regression analysis adjusted for potential confounding factors (age, gender, body weight, smoking and drinking status, household income, hypertension, diabetes, renal function, and physical activity), higher serum ADMA level was significantly associated with lower grip and quadriceps strengths and slower gait speed (grip strength: β, –1.257; 95% confidence interval [CI], –1.990 to –0.525; p = 0.001; quadriceps strength: β, –11.730; 95% CI, –20.924 to –2.536; p = 0.012; gait speed: β, –0.065; 95% CI, –0.108 to –0.022; p = 0.003). Our findings indicate the significant association between serum ADMA level and physical performance among elderly individuals, which was independent of the important potential confounders. © 2015 American Society for Bone and Mineral Research.
Functional Analysis of the Group 4 Late Embryogenesis Abundant Proteins Reveals Their Relevance in the Adaptive Response during Water Deficit in Arabidopsis1[C][W][OA]

Late-Embryogenesis Abundant (LEA) proteins accumulate to high levels during the last stages of seed development, when desiccation tolerance is acquired, and in vegetative and reproductive tissues under water deficit, leading to the hypothesis that these proteins play a role in the adaptation of plants to this stress condition. In this work, we obtained the accumulation patterns of the Arabidopsis (Arabidopsis thaliana) group 4 LEA proteins during different developmental stages and plant organs in response to water deficit. We demonstrate that overexpression of a representative member of this group of proteins confers tolerance to severe drought in Arabidopsis plants. Moreover, we show that deficiency of LEA proteins in this group leads to susceptible phenotypes upon water limitation, during germination, or in mature plants after recovery from severe dehydration. Upon recovery from this stress condition, mutant plants showed a reduced number of floral and axillary buds when compared with wild-type plants. The lack of these proteins also correlates with a reduced seed production under optimal irrigation, supporting a role in fruit and/or seed development. A bioinformatic analysis of group 4 LEA proteins from many plant genera showed that there are two subgroups, originated through ancient gene duplication and a subsequent functional specialization. This study represents, to our knowledge, the first genetic evidence showing that one of the LEA protein groups is directly involved in the adaptive response of higher plants to water deficit, and it provides data indicating that the function of these proteins is not redundant to that of the other LEA proteins.
Surgical Approaches in Nonlesional Neocortical Epilepsy

There is inherent difficulty in identifying the epileptogenic zone in nonlesional neocortical epilepsy, which leads to the incomplete resection. However, with careful interpretation of other studies including functional neuroimaging and the presence of concordant results, surgical treatment can benefit selected patients with nonlesional neocortical epilepsy. Two recent large studies including ours demonstrated that seizure free outcomes were 47 and 55% for nonlesional TLE, and 41 and 43% for nonlesional extratemporal lobe epilepsy patients. Concordance with two or more presurgical evaluations among interictal EEG, ictal EEG, FDG-PET, and ictal SPECT was significantly related to a seizure-free outcome. However, we should be cautious to the possibility of false localization of ictal EEG or functional neuroimaging in nonlesional neocortical epilepsy. Careful placement of intracranial electrodes on the presumed epileptogenic zone and the adjacent areas should be needed for these patients. The repositioning of intracranial electrodes after the failure in identifying ictal onset zone at the initial intracranial study might identify a new ictal onset zone. Consideration of one-week interval repositioning of intracranial electrodes could be helpful in selected patients. Intracranial EEG is one of the most important procedures in planning surgery and achieving a good surgical outcome in resective epilepsy surgery. Slow propagation and focal or regional ictal onset rather than widespread onset were associated with a seizure-free outcome. Complete resection including the area with initial three second ictal rhythm and interictal abnormalities predicts a good surgical outcome.
Correlation between Microdilution, E-test, and Disk Diffusion Methods for Antifungal Susceptibility Testing of Posaconazole against Candida spp

ABSTRACT Agar-based antifungal susceptibility testing is an attractive alternative to the microdilution method. We examined the correlation between the microdilution, E-test, and disk diffusion methods for posaconazole against Candida spp. A total of 270 bloodstream isolates of Candida spp. with a broad range of posaconazole MICs were tested using the CLSI M27-A2 method for microdilution, as well as the M-44A method and E-test methods for agar-based testing on Mueller-Hinton agar supplemented with 2% glucose and 0.5 μg of methylene blue. MICs and inhibitory zone diameters at the prominent growth reduction endpoint were recorded at 24 and 48 h. The Candida isolates included Candida albicans (n = 124), C. parapsilosis (n = 44), C. tropicalis (n = 41), C. glabrata (n = 36), C. krusei (n = 20), C. lusitaniae (n = 3), and C. dubliniensis (n = 2). The overall concordance (i.e., the percentage of isolates within two dilutions) between the E-test and microdilution was 64.8% at 24 h and 82.6% at 48 h. When we considered an arbitrary breakpoint of ≤1 μg/ml, the agreement between the E-test and microdilution methods was 87.8% at 24 h and 93.0% at 48 h. The correlation of MICs with disk diffusion zone diameters was better for the E-test than the microdilution method. Zone correlation for diameters produced by the disks of two manufacturers was high, with a Pearson test value of 0.941 at 24 h. The E-test and microdilution MICs show good concordance and interpretative agreement. The disk diffusion zone diameters are highly reproducible and correlate well with both the E-test and the microdilution method, making agar-based methods a viable alternative to microdilution for posaconazole susceptibility testing.
The association between physical self-discrepancies and women's physical activity: the mediating role of motivation.

The objectives of this study were to test the associations between physical self-discrepancies (actual:ideal and actual:ought) and physical activity behavior, and to examine whether motivational regulations mediate these associations using self-discrepancy (Higgins, 1987) and organismic integration (Deci & Ryan, 1985) theories as guiding frameworks. Young women (N = 205; M(age) = 18.87 years, SD = 1.83) completed self-report questionnaires. Main analyses involved path analysis using a polynomial regression approach, estimation of direct and indirect effects, and evaluation of response surface values. Agreement between actual and ideal (or ought) physical self-perceptions was related to physical activity both directly and indirectly as mediated by the motivational regulations (R(2) = . 24-. 30). Specifically, when actual and ideal self-perceptions scores were similar, physical activity levels increased as actual and ideal scores increased. Furthermore, physical activity levels were lower when the discrepancy was such that ideal or ought self were higher than actual self. These findings provide support for integrating self-discrepancy and organismic integration theories to advance research in this area.
The sibutramine metabolite M2 improves muscle glucose uptake and reduces hepatic glucose output: preliminary data

The satiety agent sibutramine acts in part through a primary amine metabolite, M2. To investigate whether M2 could affect glycaemia independently of satiety and weight loss, groups of normal mice received a single dose of M2 (1 or 10 mg/kg) and food was withheld. Compared with controls (who received vehicle only), M2 (10 mg/kg) decreased basal plasma glucose concentrations, with a maximal decrease of about 25% at 4-8 hours (p<0.05). Soleus muscles were isolated from the mice at intervals: insulin-mediated glucose uptake by the muscles from controls progressively decreased over 24 hours whereas uptake was maintained by muscles from M2-treat-ed mice. Hepatic gluconeogenesis was reduced about 40% by liver snips isolated from M2-treated mice after 24 hours (p<0.05). These preliminary results suggest that the M2 metabolite of sibutramine can reduce glycaemia, maintain insulin-mediated muscle glucose uptake and reduce hepatic gluconeogenesis independently of satiety and weight loss.