Miracle-dz/UniFAR-FTUs huggingface dataset:
Manganese-enhanced MRI studies of alterations of intraretinal ion demand in models of ocular injury.

PURPOSE To provide proof-of-concept that the extent of intraretinal manganese uptake after systemic MnCl(2) injection, detected with manganese-enhanced MRI (MEMRI), assesses alterations in intraretinal ion demand in models of ocular insult. METHODS In Sprague-Dawley rats, retinal ion demand and thickness were measured from MEMRI data collected before, 4 hours after, or 1, 3, and 7 days after intraperitoneal injection of MnCl(2). Choroidal contribution or blood-retinal barrier permeability surface area product (BRB PS') was determined using MRI after Gd-DTPA injection. Ocular injury was evaluated 24 hours after intravitreal injection of phosphate-buffered saline (PBS, vehicle) or PBS + ouabain, or after intraperitoneal injection of sodium iodate. Manganese retinal toxicity was assessed by comparing full-field, white-flash electroretinographic (ERG) data obtained before and after systemic MnCl(2) administration. Rat choroidal thickness was measured from cross-sections prepared from paraformaldehyde-perfused adult rats. RESULTS Comparing pre- and post-Gd-DTPA images demonstrated minimal choroidal contribution to intraretinal analysis. Intraretinal signal intensity returned to baseline by 7 days after MnCl(2) injection. After ouabain injection, receptor and postreceptor uptake of manganese were subnormal (P < 0.05). After sodium iodate exposure, intraretinal manganese uptake was supernormal (P < 0.05) and did not increase with increasing BRB PS'. ERG data did not show any effect of MnCl(2) on photoreceptor a-wave and postreceptor b-wave relative to baseline at either observation time. CONCLUSIONS MEMRI measurements of uptake of systemically administered and nontoxic doses of manganese appear to be a powerful approach for measuring alteration in intraretinal ion demand in models of ocular injury.
Childhood Maltreatment, Shame-Proneness and Self-Criticism in Social Anxiety Disorder: A Sequential Mediational Model.

UNLABELLED Previous research has shown a robust link between emotional abuse and neglect with social anxiety symptoms. However, the mechanisms through which these links operate are less clear. We hypothesized a model in which early experiences of abuse and neglect create aversive shame states, internalized into a stable shame-based cognitive-affective schema. Self-criticism is conceptualized as a safety strategy designed to conceal flaws and prevent further experiences of shame. However, self-criticism maintains negative self-perceptions and insecurity in social situations. To provide preliminary, cross-sectional support for this model, a nonclinical community sample of 219 adults from Israel (110 females, mean age = 38.7) completed measures of childhood trauma, shame-proneness, self-criticism and social anxiety symptoms. A sequential mediational model showed that emotional abuse, but not emotional neglect, predicted shame-proneness, which in turn predicted self-criticism, which in turn predicted social anxiety symptoms. These results provide initial evidence supporting the role of shame and self-criticism in the development and maintenance of social anxiety disorder. The clinical implications of these findings are discussed. KEY PRACTITIONER MESSAGE Previous research has shown that histories of emotional abuse and emotional neglect predict social anxiety symptoms, but the mechanisms that underlie these associations are not clear. Using psycho-evolutionary and emotion-focused perspectives, the findings of the current study suggest that shame and self-criticism play an important role in social anxiety and may mediate the link between emotional abuse and symptoms. These findings also suggest that therapeutic interventions specifically targeting shame and self-criticism should be incorporated into treatments for social anxiety, especially with socially anxious patients with abuse histories.
Long-term functional results and isokinetic strength evaluation after arthroscopic tenotomy of the long head of biceps tendon

Introduction: The objective of this study is to evaluate the biomechanical function of the upper arm after arthroscopic long head of biceps (LHB) tenotomy at long-term follow-up. Materials and Methods: Twenty-five male subjects ranging from 30 to 63 years old were evaluated at a mean follow-up of 7.0 years after tenotomy. Bilateral isokinetic testing was performed to obtain peak torque values, as well as total work done throughout the full range of elbow flexion and supination. Results: Magnetic resonance imaging scans revealed nine unrecognized LHB ruptures in the contralateral arm, leaving 16 subjects to complete the testing protocol. The mean quickDASH score was 8.1 (standard error [SE] 2.5). The mean oxford elbow score was 97.9 (SE 1.6). The tenotomy arm recorded a decrease in peak flexion torque of 7.0% (confidence interval [CI] 1.2-12.8), and a decrease in the peak supination torque of 9.1% (CI 1.8-16.4) relative to the contralateral arm. The total work carried out through the full range of joint motion was reduced in elbow flexion by 5.1% (CI −1.3-11.4) and in forearm supination by 5.7% (CI-2.4-13.9). Discussion: Maximum strength in elbow flexion and forearm supination is significantly reduced compared with the contralateral arm. However, this impairment is partially compensated for by relatively greater strength sustained through the latter stages of joint motion. This results in comparable total work measurements between the tenotomised and contralateral side, potentially accounting for ongoing high levels of patient satisfaction and clinical function in the long term after LHB tenotomy. Level of Evidence IV: Case series without comparison group.
Hearing in Time: Evoked Potential Studies of Temporal Processing

This article reviews the temporal aspects of human hearing as measured using the auditory evoked potentials. Interaural timing cues are essential to the detection and localization of sound sources. The temporal envelope of a sound—how it changes in amplitude over time—is crucially important for speech perception. Time is taken to integrate, identify, and dissolve auditory streams. These temporal aspects of human hearing can be examined using the auditory evoked potentials, which measure the millisecond-by-millisecond activity of populations of neurons as they form an auditory percept. Important measurements are the time taken to localize sounds on the basis of their interaural time differences as measured by the cortical N1 wave, the contribution of the vocal cord frequency and phonemic frequency to the perception of speech sounds as indicated by the envelope-following responses, the temporal integration of sound as assessed using the steady state responses, and the duration of auditory memory as shown in the refractory periods of the slow auditory evoked potentials. Disorders of temporal processing are a characteristic feature of auditory neuropathy, a significant component of the hearing problems that occur in the elderly, and a possible etiological factor in developmental dyslexia and central auditory processing disorders. Auditory evoked potentials may help in the diagnosis and monitoring of these disorders.
From convolutional to recurrent: Case study in Nasopharyngeal Carcinoma segmentation

Convolutional Neural Network (CNN) is the prevalent framework of image classification, and is also widely used in other image applications including semantic segmentation. Advantages of CNN include hierarchical extraction of patterns, effective training and a small number of parameters. Do they make CNN the ideal candidate for all image processing tasks? In a patch-based semantic image segmentation experiment of Nasopharyngeal Carcinoma (NPC), three different network structures are tested on the same input — CNN, Recurrent Neural Network (RNN) and a mixed model. Results show that RNN achieves comparable accuracy to CNN, and replacing fully- connected layers with RNN further improves performance. A 2D Graph Cut algorithm follows each network to post-process heat maps for a global optimal solution. Within the limited scope of a patch, CNN, RNN and RNN-injected CNN return similar performance metrics, but it becomes a more complex issue to design an appropriate network structure for the complete image, which may be much larger or even in higher dimension. Fully Convolutional Networks (FCNs) have also been proposed for semantic image segmentation, in which the full image goes through consecutive convolutional units for coarse-grained features, then the smaller feature maps must be up-sampled to match the original size. A multidimensional recurrent network at the pixel level or on top of CNN-processed patches will be explored next, aiming at a larger receptive field and higher training efficiency.
Proteomic analysis of spinal protein expression in rats exposed to repeated intrathecal morphine injection

Repeated administration of morphine for treating severe chronic pain may lead to neuroadaptive changes in the spinal cord that are thought to underlie molecular mechanisms of the development of morphine tolerance and physical dependence. Here, we employed a 2‐D gel‐based proteomic technique to detect the global changes of the spinal cord protein expression in rats that had developed morphine tolerance. Morphine tolerance at the spinal cord level was induced by repeated intrathecal injections of morphine (20 μg/10 μL) twice daily for 5 days and evaluated by measurements of paw withdrawal latencies and maximal possible analgesic effect at day 5. After behavioral tests, the lumbar enlargement segments of spinal cord were harvested and proteins resolved by 2‐DE. We found that eight proteins were significantly up‐regulated or down‐regulated in spinal cord after morphine tolerance development, including proteins involved in targeting and trafficking of the glutamate receptors and opioid receptors, proteins involved in oxidative stress, and cytoskeletal proteins, some of which were confirmed by Western blot analysis. Morphine‐induced expressional changes of these proteins in the spinal cord might be involved in the central mechanisms that underlie the development of morphine tolerance. It is very likely that these identified proteins may serve as potential molecular targets for prevention of the development of morphine tolerance and physical dependence.
Dopamine receptor blockade in the rat medial prefrontal cortex reduces spontaneous and amphetamine-induced activity and does not affect prepulse inhibition

The functions and interactions of cortical and subcortical dopamine systems are of interest because alterations in these systems have been implicated in neuropsychiatric diseases, such as schizophrenia. It has been proposed that prefrontal dopamine transmission may oppose dopamine transmission in subcortical sites, such as the nucleus accumbens. Accordingly, reduced prefrontal dopamine transmission would be expected to enhance or induce behavioral effects that have been associated with stimulation of accumbal dopamine receptors. In rats, spontaneous and amphetamine-induced activity is supported by dopamine receptor stimulation in the nucleus accumbens, while prepulse inhibition (PPI) of the acoustic startle response, which is used to measure sensorimotor gating and is disrupted in schizophrenia, is reduced by increased accumbal dopamine receptor stimulation. In the present experiments, we found that bilateral infusion of the dopamine D1/D2 receptor antagonist cis-flupenthixol dihydrochloride into the medial prefrontal cortex of Wistar rats (25 μg each side) reduced spontaneous activity and completely blocked induction of hyperactivity by systemic administration of D-amphetamine sulfate (1 mg/kg), while not affecting PPI. These findings do not support an antagonism between prefrontal and accumbal dopamine in the control of behavior. Rather, our data demonstrate that prefrontal dopamine transmission may modulate some behavioral processes in a similar way to accumbal dopamine.
Efficient pattern-matching with don't cares

We present a randomized algorithm for the <i>string matching with don't cares</i> problem. Based on the simple fingerprint method of Karp and Rabin for ordinary string matching [4], our algorithm runs in time <i>O</i>(<i>n</i> log <i>m</i>) for a text of length <i>n</i> and a pattern of length <i>m</i> and is simpler and slightly faster than the previous algorithms [3, 5, 1].
Characterization of a transcriptionally active Tc1-like transposon in the microsporidian Nosema bombycis

The Tc1 transposable element has been found in a wide variety of organisms including vertebrates, insects and fungi but has not been previously reported in Microsporidia. In this study we characterize an intact DNA transposon (NbTc1) from the microsporidian Nosema bombycis. This transposable element encodes a 337 amino acid transposase sequence, which contains the D,D34E functional motif required for transposition. A Southern blot of N. bombycis DNA separated by pulsedesis shows that copies of the NbTc1 transposon are present on 10 of the 14 chromosomes of N. bombycis. Amino acid sequence variation among copies of the NbTc1 is low, suggesting a conserved function for this transposon within N. bombycis. Phylogenetic analysis indicates that NbTc1 is a new member of the Tc1 family lineage, quite distinct from all previously described Tc1 elements, including those from fungi, indicating that NbTc1 forms a unique clade of the Tc1 superfamily. However, the Tc1 transposon is too divergent to resolve the major phylogenetic relationships among these superfamilies. Reverse transcriptase PCR and Solexa sequencing suggest that NbTc1 possesses transcriptional activity. Considering the interest in Microsporidia as biological control agents, the NbTc1 transposon may be a useful vector for the efficient transfection of these important parasites into host species.
Expression of Efflux Pump Gene pmrA in Fluoroquinolone-Resistant and -Susceptible Clinical Isolates of Streptococcus pneumoniae

ABSTRACT Thirty-four ciprofloxacin-resistant (MIC ≥ 2 μg/ml) and 12 ciprofloxacin-susceptible clinical isolates of Streptococcus pneumoniae were divided into four groups based upon susceptibility to norfloxacin and the effect of reserpine (20 μg/ml). The quinolone-resistance-determining regions of parC, parE, gyrA, and gyrB of all ciprofloxacin-resistant clinical isolates were sequenced, and the activities of eight other fluoroquinolones, acriflavine, ethidium bromide, chloramphenicol, and tetracycline in the presence and absence of reserpine were determined. Despite a marked effect of reserpine upon the activity of norfloxacin, there were only a few isolates for which the activity of another fluoroquinolone was enhanced by reserpine. For most isolates the MICs of acriflavine and ethidium bromide were lowered in the presence of reserpine despite the lack of effect of this efflux pump inhibitor on fluoroquinolone activity. The strains that were most resistant to the fluoroquinolones were predominantly those with mutations in three genes. Expression of the gene encoding the efflux pump PmrA was examined by Northern blotting (quantified by quantitative competitive reverse transcriptase PCR) and compared with that of S. pneumoniae R6 and R6N. Within each group there were isolates that had high-, medium-, and low-level expression of this gene; however, increased expression was not exclusively associated with those isolates with a phenotype suggestive of an efflux mutant. These data suggest that there is another reserpine-sensitive efflux pump in S. pneumoniae that extrudes ethidium bromide and acriflavine but not fluoroquinolones.
Minimally Important Differences in Patient or Proxy-Reported Outcome Studies Relevant to Children: A Systematic Review

Through a rigorous systematic review, this study provides a compendium of MIDs to better interpret the magnitude of treatment effects for PROs relevant to children. CONTEXT: No study has characterized and appraised all anchor-based minimally important differences (MIDs) associated with patient-reported outcome (PRO) instruments in pediatric studies. OBJECTIVE: To complete a comprehensive systematic survey and appraisal of published anchor-based MIDs associated with PRO instruments used in children. DATA SOURCES: Medline, Embase, and PsycINFO (1989 to February 11, 2015). STUDY SELECTION: Studies reporting empirical ascertainment of anchor-based MIDs among PROs used in pediatric care. DATA EXTRACTION: All pertinent data items related to the characteristics of PRO instruments, anchors, and MIDs. RESULTS: Of 4179 unique citations, 30 studies (including 32 cohorts) proved eligible and reported on 28 unique PROs (8 generic, 13 disease-specific, 5 symptoms-specific, 2 function-specific), with 9 (32%) classified as patient-reported, 11 (39%) proxy-reported, and 8 (29%) both patient- and proxy-reported. Of the 30 studies, we rated 14 (44%) as providing highly credible estimates of the MID. Most cohorts (n = 20, 62%) recorded patients’ direct response to the target PRO and the use of an independent standard of comparison (n = 25, 78%). Most, however, failed to effectively report measurement properties of the anchor (n = 24, 75%). LIMITATIONS: We have not yet addressed the measurement properties of instrument to measure credibility; our search was restricted to 3 electronic sources, and we used a single data abstractor. CONCLUSIONS: Our study found 28 PROs that have been developed for children, with fewer than half providing credible estimates. Clinicians, clinical trialists, systematic reviewers, and guideline developers seeking to effectively summarize and interpret results of studies addressing PROs in child health are likely to find our comprehensive compendium of MIDs of use, both in providing best estimates of MIDs and identifying credible estimates.
Exploring polyethylenimine‐mediated DNA transfection and the proton sponge hypothesis

The relatively high transfection efficiency of polyethylenimine (PEI) vectors has been hypothesized to be due to their ability to avoid trafficking to degradative lysosomes. According to the proton sponge hypothesis, the buffering capacity of PEI leads to osmotic swelling and rupture of endosomes, resulting in the release of the vector into the cytoplasm.
Psychological and neuroendocrine measures related to functional immune changes in anticipation of HIV‐1 serostatus notification.

&NA; Our previous work indicated that gay males ultimately found to be seronegative showed impaired lymphocyte proliferative responses to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) upon entering a study in which they would be notified of their human immunodeficiency virus‐Type 1 (HIV‐1) antibody status. To examine the degree to which alterations in various neuroendocrine and psychological markers might be related to this phenomenon we measured plasma cortisol, beta‐endorphin, denial coping strategies, intrusive thoughts related to AIDS risk, and several affective distress markers in 46 HIV‐1 seronegative subjects at each of the timepoints previously studied. Results indicated that cortisol levels were elevated at study entry and decreased across the subsequent five‐week period—mirroring the changes in mitogen responsivity across these timepoints. Analyses of individual differences showed that higher baseline cortisol and lower denial coping scores predicted lower PHA values at baseline. Persisting intrusive thoughts about risk of HIV‐1 infectivity (after seronegativity notification) were consistently associated with higher plasma cortisol levels. Finally, beta‐endorphin levels did not change significantly across the 10‐week observation period, were not associated with psychological variables, and were inconsistently associated with immune functioning.
Incidence of multiple sclerosis in Iceland, 2002–2007: a population-based study

Background: We conducted a study to determine the incidence of multiple sclerosis (MS) among the whole Icelandic population during a 6-year period (2002–2007). Methods: We included all Icelandic residents diagnosed with MS during the study period. Cases were identified from records of the only neurology department in Iceland, plus the records of all practicing neurologists and all radiology departments. All patients had experienced at least two confirmed MS relapses (i.e. clinically definite MS) or had primary progressive MS as defined by the Poser criteria. Results:We identified 136 individuals who met the inclusion criteria, including 102 (75%) women. The mean age at diagnosis was 36.3 years (women 35.7 years, men 38.3 years). Average annual incidence was 7.6 per 100,000 population. All but one patient (99%) had an MRI study done at diagnosis and 61% of these (83/135) fulfilled the Barkhof criteria for diagnosis of MS; one had a normal MRI. A visual evoked potential test was done in 68% (93/136) at the time of diagnosis and 44% (41/93) were abnormal. Spinal fluid was obtained from 78% (106/136), and 75% (80/106) had oligoclonal bands. Conclusion:A total population study is the most reliable method of determining the spectrum of clinical symptoms and the results of investigations in MS patients at diagnosis.
Smart charging of electric vehicles for low voltage grids optimization

In this paper, an innovative methodology to monitor and optimize the behavior of low voltage electric distribution systems through optimized electric vehicles charging operations is presented. This work is aimed at promoting short-term improvements, showing that charging times of electric vehicles, that in many cases represent one of the major obstacles to the full spreading of electric mobility, can be well managed without drastic interventions on distribution networks. The proposed approach is based on the formulation of a Three-Phase Optimal Power Flow (TOPF) problem.
Phenotypic divergence despite high levels of gene flow in Galápagos lava lizards (Microlophus albemarlensis)

The extent of evolutionary divergence of phenotypes between habitats is predominantly the result of the balance of differential natural selection and gene flow. Lava lizards (Microlophus albemarlensis) on the small island of Plaza Sur in the Galápagos archipelago inhabit contrasting habitats: dense vegetation on the western end of the island thins rapidly in a transitional area, before becoming absent on the eastern half. Associated with these habitats are phenotypic differences in traits linked to predator avoidance (increased wariness, sprint speed, and endurance in lizards from the sparsely vegetated habitat). This population provides an opportunity to test the hypothesis that reduced gene flow is necessary for phenotypic differentiation. There was no evidence of any differences among habitats in allele frequencies at six out of seven microsatellite loci examined, nor was there any indication of congruence between patterns of genetic variability and the change in vegetation regime. We infer that gene flow between the habitats on Plaza Sur must be sufficiently high to overcome genetic drift within habitats but that it does not preclude phenotypic differentiation.