Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of trimetazidine on 99Tcm-tetrofosmin uptake in patients with coronary artery disease

Myocardial uptake of 99Tcm-tetrofosmin in vivo is determined by a combination of flow and metabolic status of myocytes. The accumulation of tetrofosmin in the mitochondria is related to their ability to transduce metabolic energy into electronegative membrane potential. Trimetazidine (TMZ), an anti-ischaemic drug, appears to have a metabolic cytoprotective effect related to mitochondrial function, since it does not induce systemic or coronary haemodynamic changes. In this study, we evaluated the effects of TMZ on tetrofosmin uptake in hypoperfused myocardial regions in patients with coronary artery disease (CAD). Twenty-two patients, 14 with previous myocardial infarction (group A) and eight with a history of angina (group B), with angiographically documented CAD were studied. All patients underwent two tetrofosmin SPET studies at rest, before (baseline) and 1 week after TMZ administration (post-TMZ). On quantitative analysis, 131 segments showed less tetrofosmin uptake at baseline. In these segments, tetrofosmin uptake was 51±13% at baseline and 55±15% post-TMZ (P<0.001 vs control). In the 86 hypoperfused segments of group A, tetrofosmin uptake was 48±14% at baseline and 52±17% post-TMZ (P<0.001 vs control). In the 45 hypoperfused segments of group B, tetrofosmin uptake was 56±9% at baseline and 60±10% post-TMZ (P<0.001 vs control). In the remaining 309 segments, no significant difference in tetrofosmin uptake before and after TMZ was observed. In conclusion, our results suggest that TMZ administration may increase myocardial uptake of tetrofosmin in hypoperfused regions at rest in patients with CAD, based on its metabolic effect.
An underlying mechanism for the increased mutagenesis of lagging-strand genes in Bacillus subtilis

Significance Replication and transcription can occur concurrently and use the same DNA template. This can cause genomic instability such as common fragile site instability in eukaryotes, and accelerated evolution of lagging-strand genes in bacteria. Here, we report an underlying mechanism that increases mutation rates of lagging-strand genes in Bacillus subtilis. We find that this process is mediated through the transcription-dependent activity of the Y-family polymerase, PolY1, in transcription-coupled nucleotide excision repair. We find that PolY1, likely through this mechanism, reduces the potentially problematic impacts of specifically lagging-strand transcription on replisome progression and genomic instability. This work shows that gene orientation, together with transcription, can cause differential activities of repair mechanisms, specifically increasing mutagenesis in lagging-strand genes. We previously reported that lagging-strand genes accumulate mutations faster than those encoded on the leading strand in Bacillus subtilis. Although we proposed that orientation-specific encounters between replication and transcription underlie this phenomenon, the mechanism leading to the increased mutagenesis of lagging-strand genes remained unknown. Here, we report that the transcription-dependent and orientation-specific differences in mutation rates of genes require the B. subtilis Y-family polymerase, PolY1 (yqjH). We find that without PolY1, association of the replicative helicase, DnaC, and the recombination protein, RecA, with lagging-strand genes increases in a transcription-dependent manner. These data suggest that PolY1 promotes efficient replisome progression through lagging-strand genes, thereby reducing potentially detrimental breaks and single-stranded DNA at these loci. Y-family polymerases can alleviate potential obstacles to replisome progression by facilitating DNA lesion bypass, extension of D-loops, or excision repair. We find that the nucleotide excision repair (NER) proteins UvrA, UvrB, and UvrC, but not RecA, are required for transcription-dependent asymmetry in mutation rates of genes in the two orientations. Furthermore, we find that the transcription-coupling repair factor Mfd functions in the same pathway as PolY1 and is also required for increased mutagenesis of lagging-strand genes. Experimental and SNP analyses of B. subtilis genomes show mutational footprints consistent with these findings. We propose that the interplay between replication and transcription increases lesion susceptibility of, specifically, lagging-strand genes, activating an Mfd-dependent error-prone NER mechanism. We propose that this process, at least partially, underlies the accelerated evolution of lagging-strand genes.
Cardiac sympathetic denervation modulates the sympathoexcitatory response to acute myocardial ischemia.

OBJECTIVES This study was designed to elucidate the influence of cardiac sympathetic denervation on the sympathoexcitatory response to acute myocardial ischemia during balloon coronary occlusion (BCO) in humans. BACKGROUND Alterations of cardiac sympathetic nerve function could modulate sympathetic reflexes originating from the ischemic area. METHODS In 23 patients with angina pectoris, we quantified the baseline cardiac sympathetic denervation of the ischemia-related area by iodine-123 metaiodobenzylguanidine ((123)I-MIBG), and transient changes in sympathetic activity during BCO by wavelet analysis of RR interval variability. RESULTS Balloon coronary occlusion resulted in a transient augmentation of low-frequency (LF: 0.04 to 0.14 Hz) spectral components of RR interval variability in 4 of 12 patients with cardiac denervation and in 8 of 11 patients without denervation (p < 0.01 by the chi-square test). Consequently, the increase in LF components was significantly less during BCO in patients with cardiac denervation (34%) than in those without denervation (273%) (interaction: p < 0.05). In seven patients with severe ischemia provoked by a fall of > or = 10% in the left ventricular ejection fraction, LF components increased by 506% during BCO, regardless of the condition of cardiac denervation. In contrast, in patients with mild ischemia provoked by a fall of <10% in the ejection fraction, changes of LF components during BCO were significantly less in patients with denervation than in those without denervation (84 vs. 344%, p < 0.05). CONCLUSIONS These findings suggest that if the provoked ischemia is not severe, cardiac sympathetic denervation could prevent ischemia-induced sympathoexcitation.
Behavioral Tests After Intracerebral Hemorrhage in the Rat

Background and Purpose— In humans, intracerebral hemorrhage (ICH) causes marked perihematomal edema formation and neurological deficits. A rat ICH model, involving infusion of autologous blood into the caudate, has been used extensively to study mechanisms of edema formation, but an examination of behavioral outcome would improve its preclinical utility and provide a more rigorous assessment of the pathological cascade of events over time. The purpose of this study was to use a battery of sensorimotor function tests to examine the neurological effects of ICH in the rat and to examine which components of the hematoma are involved in generating those effects. Methods— The behavioral tests used were forelimb placing, preference for forelimb use for weight shifts during vertical exploration of a cylindrical enclosure, and a corner turn test. Rats were tested from day 1 to day 28 after injection of autologous whole blood; injection of blood plus hirudin (thrombin inhibitor), packed red blood cells, thrombin, or saline; or needle placement only. Results— The battery of tests indicated that there were marked neurological deficits by day 1 after ICH, with progressive recovery of function over 4 weeks. The forelimb placing score paralleled changes in edema. Injection of thrombin caused and injection of hirudin reduced the ICH-induced neurological deficits. Injection of packed red blood cells, which causes delayed edema formation, induced delayed neurological deficits Conclusions— These tests allow continuous monitoring of neurological deficits after rat ICH and assessment of therapeutic interventions. The time course of the neurological deficit closely matched the time course of cerebral edema for both ICH and injection of blood components. There was marked recovery of function after ICH, which may be amenable to therapeutic manipulation.
An isolated case of first metatarsal tuberculosis

An apparently healthy adolescent presented to us with multiple discharging sinuses from his right foot for the past 1 year. All serological parameters were within normal limits. X-ray picture revealed an expansile osteolytic lesion of first metatarsal. Tissue biopsy and PCR confirmed it be of tubercular etiology. The incidence of isolated occurrence of metatarsal tuberculosis is very rare and the diagnostic dilemma it brings about is briefly discussed in the following report.
Asymmetric Wnt Pathway Signaling Facilitates Stem Cell-Like Divisions via the Nonreceptor Tyrosine Kinase FRK-1 in Caenorhabditis elegans

Asymmetric cell division is critical during development, as it influences processes such as cell fate specification and cell migration. We have characterized FRK-1, a homolog of the mammalian Fer nonreceptor tyrosine kinase, and found it to be required for differentiation and maintenance of epithelial cell types, including the stem cell-like seam cells of the hypodermis. A genomic knockout of frk-1, allele ok760, results in severely uncoordinated larvae that arrest at the L1 stage and have an excess number of lateral hypodermal cells that appear to have lost asymmetry in the stem cell-like divisions of the seam cell lineage. frk-1(ok760) mutants show that there are excess lateral hypodermal cells that are abnormally shaped and smaller in size compared to wild type, a defect that could be rescued only in a manner dependent on the kinase activity of FRK-1. Additionally, we observed a significant change in the expression of heterochronic regulators in frk-1(ok760) mutants. However, frk-1(ok760) mutants do not express late, nonseam hypodermal GFP markers, suggesting the seam cells do not precociously differentiate as adult-hyp7 cells. Finally, our data also demonstrate a clear role for FRK-1 in seam cell proliferation, as eliminating FRK-1 during the L3–L4 transition results in supernumerary seam cell nuclei that are dependent on asymmetric Wnt signaling. Specifically, we observe aberrant POP-1 and WRM-1 localization that is dependent on the presence of FRK-1 and APR-1. Overall, our data suggest a requirement for FRK-1 in maintaining the identity and proliferation of seam cells primarily through an interaction with the asymmetric Wnt pathway.
Robust non-negative least squares using sparsity

Sparse, non-negative signals occur in many applications. To recover such signals, estimation posed as non-negative least squares problems have proven to be fruitful. Efficient algorithms with high accuracy have been proposed, but many of them assume either perfect knowledge of the dictionary generating the signal, or attempts to explain deviations from this dictionary by attributing them to components that for some reason is missing from the dictionary. In this work, we propose a robust non-negative least squares algorithm that allows the generating dictionary to differ from the assumed dictionary, introducing uncertainty in the setup. The proposed algorithm enables an improved modeling of the measurements, and may be efficiently implemented using a proposed ADMM implementation. Numerical examples illustrate the improved performance as compared to the standard non-negative LASSO estimator.
Cyclosporine withdrawal from a mycophenolate mofetil–containing immunosuppressive regimen in stable kidney transplant recipients: a randomized, controlled study1,2

Background. Long-term maintenance immunosuppression with cyclosporine (CsA) is associated with chronic transplant nephropathy and adverse effects on blood pressure and lipid profile. Several nonrandomized studies suggest that CsA might safely be withdrawn from immunosuppressive regimens containing mycophenolate mofetil (MMF; CellCept). Methods. A randomized, controlled study with 187 patients enrolled from 21 centers was conducted to compare CsA withdrawal with ongoing CsA therapy in stable renal transplant recipients receiving a triple-drug immunosuppressive regimen of MMF (2 g/day), CsA (Neoral), and corticosteroids. The primary endpoint was creatinine clearance at 6 months after complete withdrawal. Results. In the intent-to-treat population, CsA withdrawal was associated with lower total cholesterol and low-density lipoprotein cholesterol (−0.3 mmol/L, P =0.02; −0.4 mmol/L, P =0.015). There was a trend toward improved creatinine clearance (4.5 mL/min, P =0.16) and serum creatinine (−1 vs. +4 &mgr;mol/L, P =0.34). In the per-protocol population, which excluded patients with acute rejections, the improvements in creatinine clearance and serum creatinine were statistically significant (7.5 mL/min, P =0.02; −11 vs. +4 &mgr;mol/L, P =0.0003). Reversible acute rejections, the majority of which were mild, occurred in nine CsA withdrawal versus two CsA continuation patients (10.6% vs. 2.4% of each group, P =0.03), with no graft loss. Conclusion. Withdrawal of CsA from an MMF-containing triple-drug immunosuppressive regimen improves renal function and lipid profile at the cost of a modest increase in acute rejections, without graft loss.
Learning about responsibility: lessons from homework

Background. Responsibility, it has been argued, can be usefully studied if it is defined in terms of specific principles, such as self-regulation. This study investigated children's practices and ideas about self-regulation for one particular aspect of school work, namely, completing homework. Aims. The research questions were: what practices do children report in regard to homework, what understandings do children display about being responsible for homework, and do these understandings vary as a function of the grade level or gender of the child? Sample. The sample comprised 98 Australian children, 34 from grade 2 and 32 from each of grades 4 and 6. Method. Children were interviewed individually, asked about homework practices and given questions which explored ideas about self-regulation. The taped interviews were transcribed and the open-ended responses coded by two independent judges. Results. Results indicated few age differences in reported practices, but an age-related shift in ideas, from other-regulation (grade 2) to self-regulation (grade 6). Conclusions. It is argued that activity contexts such as homework play an important role in both the development of self-regulated practice and in the understanding of responsibility. A proviso was given that such findings may be limited to middle class groups where completion of homework may be a parental priority.
Targeting EZH2 for Cancer Therapy: Progress and Perspective

Enhancer of Zeste Homolog 2 (EZH2) is the core component of the polycomb repressive complex 2 (PRC2), possessing the enzymatic activity in generating di/tri-methylated lysine 27 in histone H3. EZH2 has important roles during early development, and its dysregulation is heavily linked to oncogenesis in various tissue types. Accumulating evidences suggest a remarkable therapeutic potential by targeting EZH2 in cancer cells. The first part reviews current strategies to target EZH2 in cancers, and evaluates the available compounds and agents used to disrupt EZH2 functions. Then we provide insight to the future direction of the research on targeting EZH2 in different cancer types. We comprehensively discuss the current understandings of the 1) structure and biological activity of EZH2, 2) its role during the assembling of PRC2 and recruitment of other protein components, 3) the molecular events directing EZH2 to target genomic regions, and 4) post-translational modification at EZH2 protein. The discussion provides the basis to inspire the development of novel strategies to abolish EZH2-related effects in cancer cells.
The Effect of Stimulus Size on Stereoscopic Fusion Limits and Response Criteria

The stereoscopic fusion limit denotes the largest binocular disparity for which a single fused image is perceived. Several criteria can be employed when judging whether or not a stereoscopic display is fused, and this may be a factor contributing to a discrepancy in the literature. Schor, Wood, and Ogawa (1984 Vision Research, 24, 661–665) reported that fusion limits did not change as a function of bar width, while Roumes, Plantier, Menu, and Thorpe (1997 Human Factors, 39, 359–373) reported higher fusion limits for larger stimuli than for smaller stimuli. Our investigation suggests that differing criteria between the studies could contribute to this discrepancy. In experiment 1 we measured horizontal and vertical disparity fusion limits for thin bars and for the edge of an extended surface, allowing observers to use the criterion of either diplopia or rivalry when evaluating fusion for all stimuli. Fusion limits were equal for thin bars and extended surfaces in both horizontal and vertical disparity conditions. We next measured fusion limits for a range of bar widths and instructed observers to indicate which criterion they employed on each trial. Fusion limits were constant across all stimulus widths. However, there was a sharp change in criterion from diplopia to rivalry when the angular extent of the bar width exceeded about twice the fusion limit, expressed in angular terms. We conclude that stereoscopic fusion limits do not depend on stimulus size in this context, but the criterion for fusion does. Therefore, the criterion for fusion should be clearly defined in any study measuring stereoscopic fusion limits.
Dietary Nucleic Acid and Intestinal Microbiota Synergistically Promote a Shift in the Th1/Th2 Balance toward Th1-Skewed Immunity

Background: Intestinal microbiota are known to play an important role in the establishment of oral tolerance, thereby protecting the organism from food allergies. Dietary intake of nucleic acid (NA) is also reported to have such an anti-allergic effect; however, one unsolved question is whether or not dietary NA would act through a process of toll-like receptor 9 signaling activated by DNA containing a CpG motif, a well-known sequence leading to immunostimulatory activity. In this study, we focused on the question of whether the addition of dietary NA lacking CpG motifs would allow continued modulation of the Th1/Th2 balance. Methods: Germ free (GF) and Bifidobacterium-infantis-monoassociated BALB/c mice were maintained on either an NA-free casein diet or on an NA-supplemented casein diet for 4 weeks. Thereafter, both the in vivo anti-casein antibody levels and in vitro splenocyte cytokine secretion pattern were evaluated. Results: Feeding with a casein diet elicited a substantial increase in the serum anti-casein-specific IgG1, IgG2a, and IgE levels of GF mice fed the NA free-diet. The in vitro cytokine production profile showed that enhanced IL-4 production in the GF mice fed the NA free-diet was markedly reduced by the supplementation with dietary NA in both the GF and B. -infantis-monoassociated mice. In addition, IFN-γ secretion increased in the B. -infantis-reconstituted mice fed the diet containing NA. Conclusions: These results suggest that dietary intake of NA devoid of CpG motifs may prevent the development of allergies via acceleration of Th1-dominant immunity.
CD44 immunoreactivity in the developing human kidney: a marker of renal progenitor stem cells?

Abstract CD44 is a transmembrane adhesion glycoprotein, functioning as a hyaluronan receptor and participating in the uptake and degradation of hyaluronan. Recently, CD44 has been proposed in the adult kidney as a marker of activated glomerular parietal epithelial cells, the putative niche stem cells that, in case of damage to podocytes, might migrate inside the glomerular tuft and undergo transition to podocytes. Here, immunoreactivity for CD44 was tested in 18 human fetuses and newborns with a gestational age ranging from 11 to 39 weeks. CD44 immunoreactivity was observed in all but one developing kidneys, being localized in several renal cell types including intraglomerular, capsular, cortical and medullary interstitial cells and nerve cells. In some cases, CD44 marked scattered cells in nephrogenic subcapsular zone. Our data indicate that CD44 is involved in human nephrogenesis, probably marking a subset of progenitor/stem cells involved in early phases of kidney development and, putatively, in podocyte and/or interstitial cell differentiation.
Changes in retinal and choroidal gene expression during development of refractive errors in chicks.

PURPOSE During growth, the retina analyzes the projected image to achieve a close match between eye length and focal length. Because the messengers released by retina and choroid are largely unknown, genes that are differently expressed in response to changes in the retinal image were identified. In addition, because glucagon may be important in the visual control of eye growth, the transcript levels of proglucagon were studied. METHODS Reverse transcription-polymerase chain reaction differential display was used to identify genes that were differentially expressed in chick eyes that were deprived of sharp vision or treated with positive or negative lenses. Differences were analyzed through sequencing and database searches and confirmed by Northern blot analyses. RESULTS Combining 40 and 33 arbitrary primers with 3 oligo-dT-primers, approximately 48% and 40% of the retinal and choroidal mRNAs were screened, respectively. Twelve differences were detected in retinal tissue and five in choroidal tissue after 6 to 24 hours of exposure to defocus. Only one of 10 sequenced products could be identified as cytochrome-c oxidase, subunit I. Northern blot analysis confirmed its twofold upregulation after positive lens wear and also changes in four other unknown genes. Finally, it was shown that retinal glucagon mRNA content increased after treatment with positive lenses. CONCLUSIONS Visual conditions that induce refractive errors produce changes in gene expression in retina and choroid within 1 day. In line with previous immunohistochemical data, it was found that the amount of glucagon mRNA was upregulated during wearing of positive lenses.
VISUALLY EVOKED POTENTIAL (VEP) ACUITY: TESTABILITY IN A CLINICAL PEDIATRIC POPULATION

The visually evoked potential (VEP) elicited by pattern response is used to assess the visual acuity of preverbal infants in research situations, but few reports indicate the percentage of patients successfully completing the tests (testability). Data are presented to illustrate the testability of acuity assessed by VEPs with clinical populations of preverbal and neurologically handicapped children. 166 referrals in a 9‐month period to an electrodiagnostic clinic indicated that 75% of the referrals less than 3 years old, and 87% of the neurologically handicapped referrals were testable. The testability of VEP acuity is as great or greater than other procedures for examining the visual functions of non‐verbal or unco‐operative patients.
Segmentation of telemetry frames during message packing in wireless sensor networks

A model for evaluating wireless communication channel capacity with the noiseless coding of messages in the case of repeated transfer of damaged information packets is proposed. The optimum values of the information packet characteristics are calculated according to various ratios of the signal energy parameters and interference in the channels. An algorithm of telemetry frame segmentation into subframes is presented. The number of elements in the subframes is maximal approximated to the number of information elements in packets of optimal length. Here the multiplicity condition of telemetry frame length is considered in relation to the number of subframe elements. It is very important in a case of cyclic interrogation for measuring sensors.