Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct comparison of spectral-domain and swept-source OCT in the measurement of choroidal thickness in normal eyes

Objective To compare spectral-domain optic coherence tomography (SD-OCT) and swept-source OCT (SS-OCT) in the study of choroidal thickness (CT) in healthy eyes. Methods Prospective, cross-sectional, single-centre study. 82 healthy eyes of 46 patients were included. In a single session, Topcon 3D-2000 SD-OCT and 1050 nm SS-OCT prototype devices were used to perform OCT scans using a single line protocol. Two masked investigators independently, manually determined 13 CT measurements consisting of one subfoveal (SFCT), and six measurements on either side of the fovea (nasal and temporal) taken every 500 microns apart. The mean CT (MCT) was the mean average of these 13 measurements. Results SD-OCT was able to reproducibly measure the CT in 74.4% of eyes vs 100% with SS-OCT (p<0.05; Fisher's Exact test). In those eyes measured by both systems, mean SFCT was 279.4±96.9 μm (range, 84–506) with SD-OCT vs 285.7±88.9 μm (range 130–527) with SS-OCT (p=0.11; Student's t test paired data). Mean MCT was 243.8±78.8 μm (range 103.6–433.2) with SD-OCT vs 242.2±81.8 μm (range 97.6–459) with SS-OCT (p=0.64; Student's t test paired data). The difference in SFCT and MCT was not statistically significant between both devices. Intraclass correlation coefficient was higher than 0.9 interobserver and interdevice measurements. SFCT Bland–Altman plots showed 95% interobserver measurement agreement within ±34 for SD-OCT, ±22 for SS-OCT and ±60 μm intersystems. Conclusions SS-OCT permitted accurate identification of the choroido-scleral border in 100% of normal eyes, suggesting that SS-OCT was the superior modality for the measurement of CT.
The WWOX Gene Modulates High-Density Lipoprotein and Lipid Metabolism

Background—Low levels of high-density lipoprotein (HDL) cholesterol constitutes a major risk factor for atherosclerosis. Recent studies from our group reported a genetic association between the WW domain-containing oxidoreductase (WWOX) gene and HDL cholesterol levels. Here, through next-generation resequencing, in vivo functional studies and gene microarray analyses, we investigated the role of WWOX in HDL and lipid metabolism. Methods and Results—Using next-generation resequencing of the WWOX region, we first identified 8 variants significantly associated and perfectly segregating with the low-HDL trait in 2 multigenerational French Canadian dyslipidemic families. To understand in vivo functions of WWOX, we used liver-specific Wwoxhep−/− and total Wwox−/− mice models, where we found decreased ApoA-I and Abca1 levels in hepatic tissues. Analyses of lipoprotein profiles in Wwox−/−, but not Wwoxhep−/− littermates, also showed marked reductions in serum HDL cholesterol concentrations, concordant with the low-HDL findings observed in families. We next obtained evidence of a sex-specific effect in female Wwoxhep−/− mice, where microarray analyses revealed an increase in plasma triglycerides and altered lipid metabolic pathways. We further identified a significant reduction in ApoA-I and Lpl and an upregulation in Fas, Angptl4, and Lipg, suggesting that the effects of Wwox involve multiple pathways, including cholesterol homeostasis, ApoA-I/ABCA1 pathway, and fatty acid biosynthesis/triglyceride metabolism. Conclusions—Our data indicate that WWOX disruption alters HDL and lipoprotein metabolism through several mechanisms and may account for the low-HDL phenotype observed in families expressing the WWOX variants. These findings thus describe a novel gene involved in cellular lipid homeostasis, which effects may impact atherosclerotic disease development.
The buffer barrier hypothesis, [Ca2+]i homogeneity, and sarcoplasmic reticulum function in swine carotid artery

1 The goal of this study was to evaluate the buffer barrier hypothesis in an intact arterial smooth muscle. Specifically, we investigated the interrelationships between intracellular [Ca2+] ([Ca2+]i) homogeneity and sarcoplasmic reticulum function in swine carotid artery. 2 We measured focal changes in [Ca2+]i by exploiting the different characteristics of several [Ca2+]i indicators: (1) aequorin, which can detect focal increases in [Ca2+]i such as those that occur in the subplasmalemmal region ([Ca2+]pm); (2) fura‐2, which is primarily a measure of mean cytoplasmic [Ca2+] ([Ca2+]c); and (3) force, which reflects increases in [Ca2+] near the contractile apparatus. We then estimated the relative degree of [Ca2+]i homogeneity with the aequorin/fura‐2 ratio. Finally, we inhibited sarcoplasmic reticulum Ca2+ pumping with cyclopiazonic acid (CPA), an inhibitor of the sarco(endo)plasmic reticulum Ca2+‐ATPase (SERCA). 3 We found that, after Ca2+ depletion, the sarcoplasmic reticulum could be partially reloaded with Ca2+ by manipulations that increased the aequorin signal relatively more than the fura‐2 signal. Complete reloading required large increases in the fura‐2 signal. These data suggest that increases in [Ca2+]pm (as measured with aequorin) can partially reload the sarcoplasmic reticulum, but complete reloading required increases in [Ca2+]c (as measured with fura‐2). Reloading could be partially inhibited by 10 μM CPA, indicating that SERCA function was important for reloading. 4 In unstimulated arteries, 10 μM CPA increased the fura‐2 signal without altering the aequorin signal, thereby decreasing the aequorin/fura‐2 ratio. Removal of extracellular Ca2+ without CPA also reduced the aequorin/fura‐2 ratio. These data suggest that resting cells have a [Ca2+] gradient with [Ca2+]pm > [Ca2+]c; this gradient is maintained by SERCA function. 5 CPA slowed the decline in the fura‐2 signal observed when histamine stimulation was removed. This result is consistent with the concept of vectorial Ca2+ efflux in which Ca2+ pumping by SERCA reduces [Ca2+]c after stimulation. 6 Ca2+ depletion by prior treatment with 100 μM histamine and CPA transiently attenuated subsequent histamine‐induced aequorin and fura‐2 transients. The effect on contraction was smaller: a delay in contraction of approximately 10 s. These data suggest that histamine‐induced Ca2+ release has at least a small role in the initial phase of contraction; however, other contractile mechanisms appear to be able to compensate for loss of Ca2+ release with only modest changes in contraction kinetics. 7 These data suggest that there is a complex interrelationship between smooth muscle sarcoplasmic reticulum function and [Ca2+] in at least two cytoplasmic compartments. [Ca2+]pm and [Ca2+]c can differentially regulate sarcoplasmic reticulum Ca2+ filling; and sarcoplasmic reticulum function regulates [Ca2+]pm and [Ca2+]c.
Television viewing over the life course and the metabolic syndrome in mid-adulthood: a longitudinal population-based study

Background Accumulating evidence suggests that television (TV) viewing is associated with cardio-metabolic risk, but little is known about how this relationship unfolds over the life course. This study employs a life course epidemiological framework by examining the potential cumulative effect of frequent TV viewing during adolescence and young adulthood on the prevalence of metabolic syndrome in mid-adulthood; and whether TV viewing during adolescence constitutes a sensitive period for the development of the metabolic syndrome in mid-adulthood. Methods We used data from the Northern Swedish Cohort, a nationally representative cohort comprising 855 participants (80% of the baseline sample). Data were collected during 1981–2008 and analysed in 2013. Logistic regression was applied to examine the associations between TV viewing at ages 16, 21 and 30 years, and the metabolic syndrome at age 43 years. Results Cumulative frequent TV viewing was associated with subsequent prevalence of the metabolic syndrome after adjustment for potential confounders (p for trend=0.026). Watching ‘several shows a day’ compared with ‘one show/week’ or less at age 16 years was associated with the metabolic syndrome at age 43 years after adjustment for later exposure (TV viewing at ages 21 and 30 years) and potential confounders (OR 1.86, 95% CI 1.06 to 3.27). Conclusions The number of life periods of frequent TV viewing during adolescence and early adulthood influenced cardio-metabolic risk in mid-adulthood in a dose-dependent manner, corresponding to a cumulative risk life course model. Additionally, TV viewing in adolescence may constitute a sensitive period for the metabolic syndrome in mid-adulthood.
IRF‐4 expression in the human myeloid lineage: up‐regulation during dendritic cell differentiation and inhibition by 1α,25‐dihydroxyvitamin D3

Interferon (IFN) regulatory factor (IRF)‐4 is a lymphoid‐ and myeloid‐restricted transcription factor of the IRF family. We analyzed its expression during differentiation of human monocytes along the macrophage or the dendritic cell (DC) pathway and in blood myeloid and plasmacytoid DC (M‐DC and P‐DC, respectively) subsets. Monocyte differentiation into DC, driven by granulocyte macrophage‐colony stimulating factor (GM‐CSF)/interleukin‐4 or GM‐CSF/IFN‐β, resulted in a strong up‐regulation of IRF‐4 mRNA and protein, which was further increased by lipopolysaccharide. It is interesting that 1α,25‐dihydroxyvitamin D3 [1,25(OH)2D3], a potent inhibitor of DC differentiation, completely abolished IRF‐4 up‐regulation. IRF‐4 was also detected in blood P‐DC and M‐DC. However, up‐regulation upon in vitro culture and down‐regulation by 1,25(OH)2D3 was observed in M‐DC but not in P‐DC. These results point to IRF‐4 as a potential player in human myeloid DC differentiation and as a novel target for the immunomodulatory activity of 1,25(OH)2D3.
In vitro selection of DNA elements highly responsive to the human T-cell lymphotropic virus type I transcriptional activator, Tax

The human T-cell lymphotropic virus type I (HTLV-I) transactivator, Tax, the ubiquitous transcriptional factor cyclic AMP (cAMP) response element-binding protein (CREB protein), and the 21-bp repeats in the HTLV-I transcriptional enhancer form a ternary nucleoprotein complex (L. J. Zhao and C. Z. Giam, Proc. Natl. Acad. Sci. USA 89:7070-7074, 1992). Using an antibody directed against the COOH-terminal region of Tax along with purified Tax and CREB proteins, we selected DNA elements bound specifically by the Tax-CREB complex in vitro. Two distinct but related groups of sequences containing the cAMP response element (CRE) flanked by long runs of G and C residues in the 5' and 3' regions, respectively, were preferentially recognized by Tax-CREB. In contrast, CREB alone binds only to CRE motifs (GNTGACG[T/C]) without neighboring G- or C-rich sequences. The Tax-CREB-selected sequences bear a striking resemblance to the 5' or 3' two-thirds of the HTLV-I 21-bp repeats and are highly inducible by Tax. Gel electrophoretic mobility shift assays, DNA transfection, and DNase I footprinting analyses indicated that the G- and C-rich sequences flanking the CRE motif are crucial for Tax-CREB-DNA ternary complex assembly and Tax transactivation but are not in direct contact with the Tax-CREB complex. These data show that Tax recruits CREB to form a multiprotein complex that specifically recognizes the viral 21-bp repeats. The expanded DNA binding specificity of Tax-CREB and the obligatory role the ternary Tax-CREB-DNA complex plays in transactivation reveal a novel mechanism for regulating the transcriptional activity of leucine zipper proteins like CREB.
Stabilization of Dendritic mRNAs by Nitric Oxide Allows Localized, Activity‐dependent Enhancement of Hippocampal Protein Synthesis

A small number of mRNA species are not restricted to the neuronal cell body, but are also present in neuronal dendrites. The levels of two of these dendritic mRNAs, encoding the microtubule‐associated protein MAP2 and the a subunit of calcium/calmodulin‐dependent protein kinase II (CamKllα), are increased rapidly by high‐frequency synaptic activity or by release of nitric oxide. To test the hypothesis that post‐transcriptional mechanisms might contribute to this modulation, primary cultures of rat hippocampal neurons were exposed to s‐nitroso‐N‐acetyl penicillamine (SNAP, 200 μM) or vehicle, and mRNA stability was determined. The stability of both CamKllá mRNA and MAP2 mRNA was increased by SNAP treatment, whereas the stabilities of tubulin T26 mRNA and proenkephalin mRNA were unaffected. When the intensity of staining for MAP2 immunoreactivity and CamKllα immunoreactivity was monitored in cultured hippocampal neurons, nitric oxide‐releasing agents induced increases in staining intensity that were dependent on protein synthesis but not on mRNA synthesis. These results show that nitric oxide can selectively stabilize CamKllα mRNA and MAP2 mRNA, leading to increased synthesis of the corresponding proteins. This demonstrates a mechanism whereby the presence of a particular mRNA in the vicinity of a synapse permits the levels of the protein product to be regulated by synaptic activity in a manner that is both prolonged and also highly localized to the region of stimulation. Thus, the dependence of sustained synaptic plasticity on de novo protein synthesis need not entail a loss of anatomical specificity.
Beliefs about emotions mediate the relationship between emotional suppression and quality of life in irritable bowel syndrome

Abstract Background: Cross-sectional and experimental research has demonstrated an association between emotional suppression and IBS. However, the relationship is not well understood. Aim: To examine the relationships between emotional suppression, we compare the measures of beliefs about emotions and quality of life in irritable bowel syndrome (IBS) with healthy controls. Method: Online questionnaires measured beliefs about emotions, emotional suppression and IBS-related quality of life in participants with (n = 87) and without (n = 37) IBS. Mediation analyses and group comparisons were used to explore the role of emotional suppression and beliefs about emotions in this sample. Results: IBS participants held significantly more beliefs about the unacceptability of emotions compared to healthy controls despite no differences in emotional suppression. The relationship between beliefs about emotions and quality of life was not mediated by emotional suppression. However, the relationship between emotional suppression and quality of life was mediated by beliefs about emotions. Conclusion: The findings suggest a role of beliefs about emotions and emotional suppression in IBS, where emotional suppression may relate to changes in beliefs about emotions and consequently quality of life. This is discussed in relation to the cognitive-behavioural model of medically unexplained symptoms.
Predictive coding: a fresh view of inhibition in the retina

Interneurons exhibiting centre-surround antagonism within their receptive fields are commonly found in peripheral visual pathways. We propose that this organization enables the visual system to encode spatial detail in a manner that minimizes the deleterious effects of intrinsic noise, by exploiting the spatial correlation that exists within natural scenes. The antagonistic surround takes a weighted mean of the signals in neighbouring receptors to generate a statistical prediction of the signal at the centre. The predicted value is subtracted from the actual centre signal, thus minimizing the range of outputs transmitted by the centre. In this way the entire dynamic range of the interneuron can be devoted to encoding a small range of intensities, thus rendering fine detail detectable against intrinsic noise injected at later stages in processing. This predictive encoding scheme also reduces spatial redundancy, thereby enabling the array of interneurons to transmit a larger number of distinguishable images, taking into account the expected structure of the visual world. The profile of the required inhibitory field is derived from statistical estimation theory. This profile depends strongly upon the signal: noise ratio and weakly upon the extent of lateral spatial correlation. The receptive fields that are quantitatively predicted by the theory resemble those of X-type retinal ganglion cells and show that the inhibitory surround should become weaker and more diffuse at low intensities. The latter property is unequivocally demonstrated in the first-order interneurons of the fly’s compound eye. The theory is extended to the time domain to account for the phasic responses of fly interneurons. These comparisons suggest that, in the early stages of processing, the visual system is concerned primarily with coding the visual image to protect against subsequent intrinsic noise, rather than with reconstructing the scene or extracting specific features from it. The treatment emphasizes that a neuron’s dynamic range should be matched to both its receptive field and the statistical properties of the visual pattern expected within this field. Finally, the analysis is synthetic because it is an extension of the background suppression hypothesis (Barlow & Levick 1976), satisfies the redundancy reduction hypothesis (Barlow 1961 a, b) and is equivalent to deblurring under certain conditions (Ratliff 1965).
Estimation of ruminal bacteriophage numbers by pulsed-field gel electrophoresis and laser densitometry

To investigate phage activity in the rumen, a method for quantifying phage has been developed. By differential centrifugation and ultrafiltration, phage particles were separated and concentrated from ruminal fluid. Linear double-stranded DNA from this fraction containing predominantly tailed phage was isolated and separated by size, using pulsed-field gel electrophoresis (PFGE). Laser densitometry of gel photographs allowed the numbers of phages with DNA in each size region to be calculated and, therefore, the total numbers per milliliter of ruminal fluid to be estimated. Phage numbers were estimated to be between 3 x 10(9) and 1.6 x 10(10) particles ml of ruminal fluid-1. The phage population, as gauged by the appearance of DNA on PFGE gels, had two major components. A broad region of DNA between 30 and 200 kb was always present on PFGE gels. It appears this region comprises DNA from a great many different phages and would include most of the temperate phages. In addition, discrete DNA bands ranging in size from 10 to 850 kb were frequently observed. DNA from one such band, of 12 kb in size, was shown to consist primarily of a single DNA type, suggesting that it originated from a specific phage. It is postulated that the discrete bands are due to epidemics or blooms of phage activity from specific, probably lytic, phages. The method that has been developed will greatly enhance future investigations into the interactions between the ruminal phage population, the ruminal bacterial population, and animal nutrition and growth. (ABSTRACT TRUNCATED AT 250 WORDS)
The Effect of Cigarette Smoking and Smoking Cessation on Spinal Fusion

Study Design. The effect of cigarette smoking and smoking cessation on spinal fusion was studied in a retrospective review of 357 patients who had undergone instrumented spinal fusion. Objective To document the widely assumed but unreported benefit of cigarette smoking cessation on fusion rate and clinical outcome after spinal fusion surgery. Background Data. Cigarette smoking has been shown to inhibit lumbar spinal fusion and to adversely effect outcome in treatment of lumbar spinal disorders. Prior reports have compared smokers and nonsmokers, as opposed to comparing smokers and quitters. Methods. This study retrospectively identified 357 patients who underwent a posterior instrumented fusion at either L4–L5 or L4–S1 between 1992 and 1996. Analysis of the medical record and follow-up telephone surveys were conducted. Clinical outcome and fusion status was analyzed in relation to preoperative and postoperative smoking parameters. Results. In this study, the nonunion rate was 14.2% for nonsmokers and 26.5% for patients who continued to smoke after surgery (P < 0.05). Patients who quit smoking after surgery for longer than 6 months had a nonunion rate of 17.1%. The nonunion rate was not significantly affected by either the quantity that a patient smoked before surgery or the duration of preoperative smoking abatement. Return-to-work was achieved in 71% of nonsmokers, 53% of nonquitters, and 75% of patients who quit smoking for more than 6 months after surgery. Discussion. These results validate the hypothetical assumption that postoperative smoking cessation helps to reverse the impact of cigarette smoking on outcome after spinal fusion.
Synthetic receive aperture imaging with phase correction for motion and for tissue inhomogeneities. I. Basic principles

The use of a synthetic receive aperture (SRA) system to increase the resolution, of a phased-array imaging system severalfold, by utilizing the available number of parallel receiver channels to address a larger number of transducer elements through a multiplexer system, is considered. Recent studies indicate that transducers with a very large number of elements will improve the detectability of small or low contrast targets when adaptive focusing is used to compensate for the effects of acoustic velocity inhomogeneities in tissue. With the effectively increased transducer element count afforded by an SRA system, a 1-by-N phased array could be split into an M-by-N array in order to improve resolution in the elevation dimension. Simulation results illustrate the lateral resolution achievable with several types of imaging systems: SRA, synthetic focus, and conventional phased array. Simulated images demonstrate the improvement in contrast resolution achievable using SRA. Experimental results show the improvement in beam width achieved by an experimental SRA system. <<ETX>>
CD1d-Independent NKT Cells in β2-Microglobulin-Deficient Mice Have Hybrid Phenotype and Function of NK and T Cells 1

Unlike CD1d-restricted NK1.1+TCRαβ+ (NKT) cells, which have been extensively studied, little is known about CD1d-independent NKT cells. To characterize their functions, we analyzed NKT cells in β2-microglobulin (β2m)-deficient B6 mice. They are similar to NK cells and expressed NK cell receptors, including Ly49, CD94/NKG2, NKG2D, and 2B4. NKT cells were found in normal numbers in mice that are deficient in β2m, MHC class II, or both. They were also found in the male HY Ag-specific TCR-transgenic mice independent of positive or negative selection in the thymus. For functional analysis of CD1d-independent NKT cells, we developed a culture system in which CD1d-independent NKT cells, but not NK, T, or most CD1d-restricted NKT cells, grew in the presence of an intermediate dose of IL-2. IL-2-activated CD1d-indpendent NKT cells were similar to IL-2-activated NK cells and efficiently killed the TAP-mutant murine T lymphoma line RMA-S, but not the parental RMA cells. They also killed β2m-deficient Con A blasts, but not normal B6 Con A blasts, indicating that the cytotoxicity is inhibited by MHC class I on target cells. IL-2-activated NKT cells expressing transgenic TCR specific for the HY peptide presented by Db killed RMA-S, but not RMA, cells. They also killed RMA (H-2b) cells that were preincubated with the HY peptide. NKT cells from β2m-deficient mice, upon CD3 cross-linking, secreted IFN-γ and IL-2, but very little IL-4. Thus, CD1d-independent NKT cells are significantly different from CD1d-restricted NKT cells. They have hybrid phenotypes and functions of NK cells and T cells.