Miracle-dz/UniFAR-FTUs huggingface dataset:
Measurement of Renal Depth in Dynamic Renal Scintigraphy Using Ultralow-Dose CT

Purpose Renal depths predicted using predefined formulas are commonly used for camera-based evaluation of renal function. We investigated the feasibility and utility of renal depth measurement using ultralow-dose CT images acquired in conjunction with dynamic renal scintigraphy. Methods Dynamic renal scintigraphy with 99mTc-MAG3 was performed in 117 patients (225 kidneys) using a SPECT/CT scanner, and ultralow-dose CT (estimated effective dose of 0.17 mSv) was performed during free breathing immediately before tracer injection. The clarity of the renal contour on the CT images was evaluated visually. The renal depths were measured by 2 methods and compared with depths predicted by 2 previously reported methods. The accuracy of camera-based clearance using predicted and measured depths was evaluated using a single-sample method as a standard. Results The clarity of the renal contour was poor in 18 of 225 kidneys, and 12 of 117 patients were considered ineligible for depth measurement. The measurement for eligible patients showed excellent intraobserver and interobserver repeatabilities. Although mean depths were similar among the 2 CT measurement methods and 2 prediction methods, absolute differences of more than 1 cm were observed in approximately 20% of kidneys between CT measurement and prediction. CT measurement of renal depth failed to improve the accuracy of camera-based clearance evaluation. Conclusion Ultralow-dose CT allowed measurement of renal depth in most patients. Substantial differences in renal depth between prediction and CT measurement indicated potential usefulness of CT measurement, although no actual improvement in the accuracy of clearance estimation was demonstrated in this study.
Inadequate Modulation of Excitability With Voluntary Dorsiflexion in Parkinson's Disease

Background: Freezing phenomenon at onset of movement causes gait disturbance in Parkinson's disease (PD), but the pathophysiology is unclear. We studied motor property at onset of dorsiflexion in PD. Methods: In 9 patients with PD and 8 normal subjects, motor evoked potential was recorded from the tibialis anterior muscle under 3 conditions: at rest, during tonic contraction, and at onset of contraction. Motor threshold, size of motor evoked potential and the relationship between the intensity of transcranial magnetic stimulation, and the size of motor evoked potentials (recruitment gain) were examined. Results: Motor threshold decreased with voluntary contraction in both PD and normal subjects, but the threshold at rest and during tonic contraction was lower in Parkinson's disease. The size of motor evoked potential with maximal stimulus intensity increased with voluntary contraction in both groups; this tendency was more pronounced in normal subjects. The recruitment gain during contraction was steeper than at rest in normal subjects. However, there was no such increase in PD. Conclusions: There was no increase in recruitment gain with voluntary contraction in PD, which was obvious in normal subjects, especially at onset of voluntary contraction. Modulation of motor excitability at onset of voluntary contraction was impaired in PD.
The effects of saliency on manual reach trajectories and reach target selection.

Reaching trajectories curve toward salient distractors, reflecting the competing activation of reach plans toward target and distractor stimuli. We investigated whether the relative saliency of target and distractor influenced the curvature of the movement and the selection of the final endpoint of the reach. Participants were asked to reach a bar tilted to the right in a context of gray vertical bars. A bar tilted to the left served as distractor. Relative stimulus saliency was varied via color: Either the distractor was red and the target was gray, or vice versa. Throughout, we observed that reach trajectories deviated toward the distractor. Surprisingly, relative saliency had no effect on the curvature of reach trajectories. Moreover, when we increased time pressure in separate experiments and analyzed the curvature as a function of reaction time, no influence of relative stimulus saliency was found, not even for the fastest reaction times. If anything, curvature decreased with strong time pressure. In contrast, reach target selection under strong time pressure was influenced by relative saliency: Reaches with short reaction times were likely to go to the red distractor. The time course of reach target selection was comparable to saccadic target selection. Implications for the neural basis of trajectory deviations and target selection in manual and eye movements are discussed. Meeting abstract presented at VSS 2015.
Mucolipin‐2 Localizes to the Arf6‐Associated Pathway and Regulates Recycling of GPI‐APs

In mammals, the mucolipin family includes three members mucolipin‐1, mucolipin‐2, and mucolipin‐3 (MCOLN1–3). While mutations in MCOLN1 and MCOLN3 have been associated with mucolipidosis type IV and the varitint‐waddlermouse phenotype, respectively, little is known about the function and cellular distribution of MCOLN2. Here we show that MCOLN2 traffics via the Arf6‐associated pathway and colocalizes with major histocompatibility protein class I (MHCI) and glycosylphosphatidylinositol‐anchored proteins (GPI‐APs), such as CD59 in both vesicles and long tubular structures. Expression of a constitutive active Arf6 mutant, or activation of endogenous Arf6 by transfection with EFA6 or treatment with aluminum fluoride, caused accumulation of MCOLN2 in enlarged vacuoles that also contain MHCI and CD59. In addition, overexpression of MCOLN2 promoted efficient activation of Arf6 in vivo,thus suggesting that MCOLN2 may have a role in the traffic of cargo through the Arf6‐associated pathway. In support of this we found that overexpression of a MCOLN2 inactive mutant decreases recycling of CD59 to the plasma membrane. Therefore, our results indicate that MCOLN2 localizes to the Arf6‐regulated pathway and regulates sorting of GPI‐APs.
Direct Evidence for the Formation of Precatenanes during DNA Replication*

Background: Changes in DNA topology during replication are still poorly understood. Results: Classical genetics and two-dimensional agarose gel electrophoresis showed that RIs tensioned in the absence of Topo IV. Conclusion: The results indicated that replication forks swivel in vivo leading to the formation of precatenanes as replication progresses. Significance: This conclusion ends a long lasting debate on the formation of precatenanes during replication. The dynamics of DNA topology during replication are still poorly understood. Bacterial plasmids are negatively supercoiled. This underwinding facilitates strand separation of the DNA duplex during replication. Leading the replisome, a DNA helicase separates the parental strands that are to be used as templates. This strand separation causes overwinding of the duplex ahead. If this overwinding persists, it would eventually impede fork progression. In bacteria, DNA gyrase and topoisomerase IV act ahead of the fork to keep DNA underwound. However, the processivity of the DNA helicase might overcome DNA gyrase and topoisomerase IV. It was proposed that the overwinding that builds up ahead of the fork could force it to swivel and diffuse this positive supercoiling behind the fork where topoisomerase IV would also act to maintain replicating the DNA underwound. Putative intertwining of sister duplexes in the replicated region are called precatenanes. Fork swiveling and the formation of precatenanes, however, are still questioned. Here, we used classical genetics and high resolution two-dimensional agarose gel electrophoresis to examine the torsional tension of replication intermediates of three bacterial plasmids with the fork stalled at different sites before termination. The results obtained indicated that precatenanes do form as replication progresses before termination.
Angiotensin II–Dependent Hypertension Requires Cyclooxygenase 1–Derived Prostaglandin E2 and EP1 Receptor Signaling in the Subfornical Organ of the Brain

Cyclooxygenase (COX)-derived prostanoids have long been implicated in blood pressure (BP) regulation. Recently prostaglandin E2 (PGE2) and its receptor EP1 (EP1R) have emerged as key players in angiotensin II (Ang II)–dependent hypertension (HTN) and related end-organ damage. However, the enzymatic source of PGE2, that is, COX-1 or COX-2, and its site(s) of action are not known. The subfornical organ (SFO) is a key forebrain region that mediates systemic Ang II–dependent HTN via reactive oxygen species (ROS). We tested the hypothesis that cross-talk between PGE2/EP1R and ROS signaling in the SFO is required for Ang II HTN. Radiotelemetric assessment of blood pressure revealed that HTN induced by infusion of systemic “slow-pressor” doses of Ang II was abolished in mice with null mutations in EP1R or COX-1 but not COX-2. Slow-pressor Ang II–evoked HTN and ROS formation in the SFO were prevented when the EP1R antagonist SC-51089 was infused directly into brains of wild-type mice, and Ang-II-induced ROS production was blunted in cells dissociated from SFO of EP1R−/− and COX-1−/− but not COX-2−/− mice. In addition, slow-pressor Ang II infusion caused a ≈3-fold increase in PGE2 levels in the SFO but not in other brain regions. Finally, genetic reconstitution of EP1R selectively in the SFO of EP1R-null mice was sufficient to rescue slow-pressor Ang II–elicited HTN and ROS formation in the SFO of this model. Thus, COX 1–derived PGE2 signaling through EP1R in the SFO is required for the ROS-mediated HTN induced by systemic infusion of Ang II and suggests that EP1R in the SFO may provide a novel target for antihypertensive therapy.
Resistant Starch Fraction Prepared from Kintoki Bean Affects Gene Expression of Genes Associated with Cholesterol Metabolism in Rats

Feeding rats beans with resistant starch reduces the serum cholesterol concentration; however, the mechanism is not fully understood. We examined the effects of resistant starch of kintoki (Phaseolus vulgaris, variety) bean on serum cholesterol and hepatic mRNAs in rats. Male F344/Du Crj rats were fed a cholesterol-free diet either with 5 g of cellulose powder (control)/100 g or 5 g of pancreatin-resistant fraction prepared from kintoki bean (kintoki)/100 g diet for 4 weeks. There were no differences in the body weight gain, food intake, liver weight, and mass of cecum contents between the groups. Serum total cholesterol, very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) + low density lipoprotein (LDL)-cholesterol, and high density lipoprotein (HDL)-cholesterol levels in the kintoki group were significantly (at least P < 0.05) lower than in the control group throughout the feeding period. There was no difference in the serum triglyceride concentration between two groups throughout the feeding period. Total hepatic cholesterol in the control group was significantly (P < 0.01) lower than in the kintoki groups. Fecal bile acid, cecal acetate, propionate and n-butyrate concentrations in the kintoki group all were significantly (P < 0.05) higher than in the control group. Likewise, hepatic cholesterol 7α-hydroxylase, LDL receptor, and SR-B1 mRNA levels in the kintoki group were significantly (P < 0.05) higher than in the control group. The results suggest that resistant starch of kintoki bean reduces serum cholesterol level by increasing hepatic LDL receptor, SR-B1, and cholesterol 7α-hydroxylase mRNAs.
Noninvasive Determination of Anaerobic Threshold by Monitoring the %SpO2 Changes and Respiratory Gas Exchange

Nikooie, R, Gharakhanlo, R, Rajabi, H, Bahraminegad, M, and Ghafari, A. Noninvasive determination of anaerobic threshold by monitoring the %Spo2 changes and respiratory gas exchange. J Strength Cond Res 23(7): 2107-2113, 2009-The purpose of this study was to determine the validity of noninvasive anaerobic threshold (AT) estimation using %SpO2 (arterial oxyhemoglobin saturation) changes and respiratory gas exchanges. Fifteen active, healthy males performed 2 graded exercise tests on a motor-driven treadmill in 2 separated sessions. Respiratory gas exchanges and heart rate (HR), lactate concentration, and %SpO2 were measured continuously throughout the test. Anaerobic threshold was determined based on blood lactate concentration (lactate-AT), %SpO2 changes (%SpO2-AT), respiratory exchange ratio (RER-AT), V-slope method (V-slope-AT), and ventilatory equivalent for O2 (EqO2-AT). Blood lactate measuring was considered as gold standard assessment of AT and was applied to confirm the validity of other noninvasive methods. The mean O2 corresponding to lactate-AT, %SpO2-AT, RER-AT, V-slope -AT, and EqO2-AT were 2176.6 ± 206.4, 1909.5 ± 221.4, 2141.2 ± 245.6, 1933.7 ± 216.4, and 1975 ± 232.4, respectively. Intraclass correlation coefficient (ICC) analysis indicates a significant correlation between 4 noninvasive methods and the criterion method. Blond-Altman plots showed the good agreement between O2 corresponding to AT in each method and lactate-AT (95% confidence interval (CI). Our results indicate that a noninvasive and easy procedure of monitoring the %SpO2 is a valid method for estimation of AT. Also, in the present study, the respiratory exchange ratio (RER) method seemed to be the best respiratory index for noninvasive estimation of anaerobic threshold, and the heart rate corresponding to AT predicted by this method can be used by coaches and athletes to define training zones.
Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction.

BACKGROUND As compared with thrombolytic therapy, primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction reduces the rates of death, reinfarction, and stroke, but recurrent ischemia, restenosis, and reocclusion of the infarct-related artery remain problematic. When used in combination with PTCA, coronary stenting and platelet glycoprotein IIb/IIIa inhibitors may further improve outcomes. METHODS Using a 2-by-2 factorial design, we randomly assigned 2082 patients with acute myocardial infarction to undergo PTCA alone (518 patients), PTCA plus abciximab therapy (528), stenting alone with the MultiLink stent (512), or stenting plus abciximab therapy (524). RESULTS Normal flow was restored in the target vessel in 94.5 to 96.9 percent of patients and did not vary according to the reperfusion strategy. At six months, the primary end point - a composite of death, reinfarction, disabling stroke, and ischemia-driven revascularization of the target vessel - had occurred in 20.0 percent of patients after PTCA, 16.5 percent after PTCA plus abciximab, 11.5 percent after stenting, and 10.2 percent after stenting plus abciximab (P<0.001). There were no significant differences among the groups in the rates of death, stroke, or reinfarction; the difference in the incidence of the primary end point was due entirely to differences in the rates of target-vessel revascularization (ranging from 15.7 percent after PTCA to 5.2 percent after stenting plus abciximab, P<0.001). The rate of angiographically established restenosis was 40.8 percent after PTCA and 22.2 percent after stenting (P<0.001), and the respective rates of reocclusion of the infarcted-related artery were 11.3 percent and 5.7 percent (P=0.01), both independent of abciximab use. CONCLUSIONS At experienced centers, stent implantation (with or without abciximab therapy) should be considered the routine reperfusion strategy.
ANALYZING COUNTS, DURATIONS, AND RECURRENCES IN CLINICAL TRIALS

In 1985 the (Byar and Blackard, Urology, Vol. X, 556–561, 1978) data set on bladder cancer became available to researchers. Since then, a number of studies have made use of it. However, none of these has fully utilized all of the data nor have they developed a methodology in which it is possible to estimate models of the number of recurrences and durations that are consistent with each other. The purpose of this research is to determine which, if any, of the two drugs used in the trial, pyridoxine and theotepa, were effective and, by example, illustrate procedures that could be useful in the analysis of other clinical trial data sets. First, the number of recurrences is modeled as a count using the Poisson and negative binomial distributions with covariates. Then Poisson models are tested on the durations. Finally, durations and tumor counts per recurrence are fitted to more general autoregressive Wiebull and negative binomial distributions, respectively. Poisson models for durations are rejected in favor of the more general autoregressive models. The data on durations and tumor counts are shown to be more reliable from an inference point of view than the data on the number of recurrences. The data on durations and tumor counts show quite conclusively that both drugs are effective in treating bladder cancer, a result that differs from what others have found.
A new function of the Fas‐FasL pathway in macrophage activation

Upon infection with the protozoan parasite Leishmania major, susceptible BALB/c mice develop unhealing lesions associated with the maturation of CD4+Th2 cells secreting IL‐4. In contrast, resistant C57BL/6 mice heal their lesions, because of expansion and secretion of IFN‐γ of CD4+ Th1 cells. The Fas‐FasL pathway, although not involved in Th cell differentiation, was reported to be necessary for complete resolution of lesions. We investigate here the role of IFN‐γ and IL‐4 on Fas‐FasL nonapoptotic signaling events leading to the modulation of macrophage activation. We show that addition of FasL and IFN‐γ to BMMø led to their increased activation, as reflected by enhanced secretion of TNF, IL‐6, NO, and the induction of their microbicidal activity, resulting in the killing of intracellular L. major. In contrast, the presence of IL‐4 decreased the synergy of IFN‐γ/FasL significantly on macrophage activation and the killing of intracellular L. major. These results show that FasL synergizes with IFN‐γ to activate macrophages and that the tight regulation by IFN‐γ and/or IL‐4 of the nonapoptotic signaling events triggered by the Fas‐FasL pathway affects significantly the activation of macrophages to a microbicidal state and may thus contribute to the pathogenesis of L. major infection.
Mesh Networking Backbone with Equalized Power Consumption Cells to Prolong the Lifetime ofLarge Sensor Networks

Energy efficiency is crucial for a sensor network. Although many schemes have been proposed to prolong the lifetime of sensor networks, most schemes do not take into account that the nodes near the data sink encounter higher data traffic and will run out of energy sooner disconnecting the data sink and the network. The uneven traffic becomes more serious when the size of the network increases. This paper proposes to combine cellular structures and mesh networks to form a backbone of a large sensor network. In this algorithm, the sensor network is partitioned into many equal cells. Each cell has a local controller with enough needed resources at the center to collect the data and to form the mesh networking backbone. The collected data is then forwarded to the data sink by the local controller for further analysis. Each cell is divided into the same number of circular layers. By equalizing the lifetime of each layer in one cell, all layers in that cell will run out of energy simultaneously and consequently so will the entire network. In addition, a scheme to direct the route requests towards the local controller in each cell is proposed to reduce the flooding in route discovery.
Biexponential transverse relaxation (T2) of the proton MRS creatine resonance in human brain

Differences in proton MRS T2 values for phosphocreatine (PCr) and creatine (Cr) methyl groups (3.0 ppm) were investigated in studies of phantoms and human brain. Results from phantom studies revealed that T2 of PCr in solution is significantly shorter than T2 of Cr. Curve‐fitting results indicated that the amplitude‐TE curves of the total Cr resonance at 3.0 ppm in human brain (N = 26) fit a biexponential decay model significantly better than a monoexponential decay model (P < 0.006), yielding mean T2 values of 117 ± 21 ms and 309 ± 21 ms. Using a localized, long‐TE (272 ms) point‐resolved spectroscopy (PRESS) proton MRS during 2 min of photic stimulation (PS), an increase of 12.1% ± 3.5% in the mean intensity of the total Cr resonance in primary visual cortex (VI) was observed at the end of stimulation (P < 0.021). This increase is consistent with the conversion of 26% of PCr in VI to Cr, which is concordant with 31P MRS findings reported by other investigators. These results suggest a significantly shorter T2 for PCr than for Cr in vivo. This difference possibly could be exploited to quantify regional activation in functional spectroscopy studies, and could also lead to inaccuracies in some circumstances when the Cr resonance is used as an internal standard for 1H MRS studies in vivo. Magn Reson Med 47:232–238, 2002. © 2002 Wiley‐Liss, Inc.
Ceftaroline Is Active against Heteroresistant Methicillin-Resistant Staphylococcus aureus Clinical Strains despite Associated Mutational Mechanisms and Intermediate Levels of Resistance

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is an important infectious human pathogen responsible for diseases ranging from skin and soft tissue infections to life-threatening endocarditis. β-Lactam resistance in MRSA involves acquisition of penicillin-binding protein 2a (PBP2a), a protein with low affinity for β-lactams that mediates cell wall assembly when the normal staphylococcal PBPs (PBP1 to -4) are blocked by these agents. Many MRSA strains display heterogeneous expression of resistance (HeR) against β-lactam antibiotics. The β-lactam-mediated homoresistant (HoR) phenotype is associated with both expression of the mecA gene and activation of the LexA-RecA-mediated SOS response, a regulatory network induced in response to DNA damage. Ceftaroline (CPT) is the only FDA-approved cephalosporin targeting PBP2a. We investigated the mechanistic basis of CPT activity against HeR-MRSA strains, including a set of strains displaying an intermediate level of resistance to CPT. Mechanistically, we found that 1 exposure of HeR-MRSA to subinhibitory concentrations of CPT selected for the HoR derivative activated the SOS response and increased mutagenesis. Importantly, CPT-selected HoR cells remained susceptible to CPT while still being resistant to most β-lactams, and 2-CPT activity in HeR-MRSA resided in an attenuated induction of mecA expression in comparison to other β-lactams. In addition, 3-CPT intermediate-resistant strains displayed a significant increase in CPT-induced mecA expression accompanied by mutations in PBP2, which together may interfere with the complete repression by CPT of both PBP2a and PBP2a-PBP2 interactions and thus be a determining factor in the low level of CPT resistance in the absence of mecA gene mutations. The present study provides mechanistic evidence that CPT represents an alternative therapeutic option for the treatment of heteroresistant MRSA strains.