Miracle-dz/UniFAR-FTUs huggingface dataset:
Altering endoplasmic reticulum stress in a model of blast-induced traumatic brain injury controls cellular fate and ameliorates neuropsychiatric symptoms

Neuronal injury following blast-induced traumatic brain injury (bTBI) increases the risk for neuropsychiatric disorders, yet the pathophysiology remains poorly understood. Blood-brain-barrier (BBB) disruption, endoplasmic reticulum (ER) stress, and apoptosis have all been implicated in bTBI. Microvessel compromise is a primary effect of bTBI and is postulated to cause subcellular secondary effects such as ER stress. What remains unclear is how these secondary effects progress to personality disorders in humans exposed to head trauma. To investigate this we exposed male rats to a clinically relevant bTBI model we have recently developed. The study examined initial BBB disruption using Evan’s blue (EB), ER stress mechanisms, apoptosis and impulsive-like behavior measured with elevated plus maze (EPM). Large BBB openings were observed immediately following bTBI, and persisted for at least 6 h. Data showed increased mRNA abundance of stress response genes at 3 h, with subsequent increases in the ER stress markers C/EBP homologous protein (CHOP) and growth arrest and DNA damage-inducible protein 34 (GADD34) at 24 h. Caspase-12 and Caspase-3 were both cleaved at 24 h following bTBI. The ER stress inhibitor, salubrinal (SAL), was administered (1 mg/kg i.p.) to investigate its effects on neuronal injury and impulsive-like behavior associated with bTBI. SAL reduced CHOP protein expression, and diminished Caspase-3 cleavage, suggesting apoptosis attenuation. Interestingly, SAL also ameliorated impulsive-like behavior indicative of head trauma. These results suggest SAL plays a role in apoptosis regulation and the pathology of chronic disease. These observations provide evidence that bTBI involves ER stress and that the unfolded protein response (UPR) is a promising molecular target for the attenuation of neuronal injury.
Approximating the set of local minima in partial RNA folding landscapes

MOTIVATION We study a stochastic method for approximating the set of local minima in partial RNA folding landscapes associated with a bounded-distance neighbourhood of folding conformations. The conformations are limited to RNA secondary structures without pseudoknots. The method aims at exploring partial energy landscapes pL induced by folding simulations and their underlying neighbourhood relations. It combines an approximation of the number of local optima devised by Garnier and Kallel (2002) with a run-time estimation for identifying sets of local optima established by Reeves and Eremeev (2004). RESULTS The method is tested on nine sequences of length between 50 nt and 400 nt, which allows us to compare the results with data generated by RNAsubopt and subsequent barrier tree calculations. On the nine sequences, the method captures on average 92% of local minima with settings designed for a target of 95%. The run-time of the heuristic can be estimated by O(n(2)Dνlnν), where n is the sequence length, ν is the number of local minima in the partial landscape pL under consideration and D is the maximum number of steepest descent steps in attraction basins associated with pL.
An Effective System for Optical Microscopy Cell Image Segmentation, Tracking and Cell Phase Identification

The lacking of automatic screen systems that can deal with large volume of time-lapse optical microscopy imaging is a bottleneck of modern bio-imaging research. In this paper, we propose an effective automated analytic system that can be used to acquire, track and analyze cell-cycle behaviors of a large population of cells. We use traditional watershed algorithm for cell nuclei segmentation and then a novel hybrid merging method is proposed for fragments merging. After a distance and size based tracking procedure, the performance of fragments merging is improved again by the sequence context information. At last, the cell nuclei can be classified into different phases accurately in a continuous hidden Markov model (HMM). Experimental results show the proposed system is very effective for cell sequence segmentation, tracking and cell phase identification.
Hypoxia Induces Near-Native Mechanical Properties in Engineered Heart Valve Tissue

Background— Previous attempts in heart valve tissue engineering (TE) failed to produce autologous valve replacements with native-like mechanical behavior to allow for systemic pressure applications. Because hypoxia and insulin are known to promote protein synthesis by adaptive cellular responses, a physiologically relevant oxygen tension and insulin supplements were applied to the growing heart valve tissues to enhance their mechanical properties. Methods and Results— Scaffolds of rapid-degrading polyglycolic acid meshes coated with poly-4-hydroxybutyrate were seeded with human saphenous vein myofibroblasts. The tissue-engineered constructs were cultured under normal oxygen tension (normoxia) or hypoxia (7% O2) and incubated with or without insulin. Glycosaminoglycan production in the constructs approached that of native values under the influence of hypoxia and under the influence of insulin. Both insulin and hypoxia were associated with enhanced matrix production and improved mechanical properties; however, a synergistic effect was not observed. Although the amount of collagen and cross-links in the engineered tissues was still lower than that in native adult human aortic valves, constructs cultured under hypoxic conditions reached native human aortic valve levels of tissue strength and stiffness after 4 weeks of culturing. Conclusions— These results indicate that oxygen tension may be a key parameter for the achievement of sufficient tissue quality and mechanical integrity in tissue-engineered heart valves. Engineered tissues of such strength, based on rapid-degrading polymers, have not been achieved to date. These findings bring the potential use of tissue-engineered heart valves for systemic applications a step closer and represent an important improvement in heart valve tissue engineering.
Image Watermarking Scheme Based on Scale-Invariant Feature Transform

In this paper, a robust watermarking scheme is proposed that uses the scale-invariant feature transform (SIFT) algorithm in the discrete wavelet transform (DWT) domain. First, the SIFT feature areas are extracted from the original image. Then, one level DWT is applied on the selected SIFT feature areas. The watermark is embedded by modifying the fractional portion of the horizontal or vertical, high-frequency DWT coefficients. In the watermark extracting phase, the embedded watermark can be directly extracted from the watermarked image without requiring the original cover image. The experimental results showed that the proposed scheme obtains the robustness to both signal processing and geometric attacks. Also, the proposed scheme is superior to some previous schemes in terms of watermark robustness and the visual quality of the watermarked image.
Transcriptome Analysis of Gene Expression Provides New Insights into the Effect of Mild Therapeutic Hypothermia on Primary Human Cortical Astrocytes Cultured under Hypoxia

Hypothermia is increasingly used as a therapeutic measure to treat brain injury. However, the cellular mechanisms underpinning its actions are complex and are not yet fully elucidated. Astrocytes are the most abundant cell type in the brain and are likely to play a critical role. In this study, transcriptional changes and the protein expression profile of human primary cortical astrocytes cultured under hypoxic conditions for 6 h were investigated. Cells were treated either with or without a mild hypothermic intervention 2 h post-insult to mimic the treatment of patients following traumatic brain injury (TBI) and/or stroke. Using human gene expression microarrays, 411 differentially expressed genes were identified following hypothermic treatment of astrocytes following a 2 h hypoxic insult. KEGG pathway analysis indicated that these genes were mainly enriched in the Wnt and p53 signaling pathways, which were inhibited following hypothermic intervention. The expression levels of 168 genes involved in Wnt signaling were validated by quantitative real-time-PCR (qPCR). Among these genes, 10 were up-regulated and 32 were down-regulated with the remainder unchanged. Two of the differentially expressed genes (DEGs), p38 and JNK, were selected for validation at the protein level using cell based ELISA. Hypothermic intervention significantly down-regulated total protein levels for the gene products of p38 and JNK. Moreover, hypothermia significantly up-regulated the phosphorylated (activated) forms of JNK protein, while downregulating phosphorylation of p38 protein. Within the p53 signaling pathway, 35 human apoptosis-related proteins closely associated with Wnt signaling were investigated using a Proteome Profiling Array. Hypothermic intervention significantly down-regulated 18 proteins, while upregulating one protein, survivin. Hypothermia is a complex intervention; this study provides the first detailed longitudinal investigation at the transcript and protein expression levels of the molecular effects of therapeutic hypothermic intervention on hypoxic human primary cortical astrocytes. The identified genes and proteins are targets for detailed functional studies, which may help to develop new treatments for brain injury based on an in-depth mechanistic understanding of the astrocytic response to hypoxia and/or hypothermia.
Cerebral hemodynamic effects of phenylephrine and L-arginine after cortical impact injury.

OBJECTIVE To determine the effects of a pressor agent (phenylephrine and L-arginine) on the abnormal cerebral hemodynamics and on neurologic outcome after a severe cortical impact injury in rats. DESIGN Prospective, randomized study. SETTING University laboratory. SUBJECTS Male Long-Evans rats, weighing 300 to 400 g, fasted overnight. INTERVENTIONS The animals were anesthetized with isoflurane, and a severe cortical impact injury (velocity, 5 m/sec; deformation, 3 mm) was produced in the right parietal cortex. Five minutes after impact injury, one of the following three treatments were infused: 1 mL saline intravenously for 10 mins, 300 mg/kg L-arginine in 1 mL saline intravenously for 10 mins, or 0.3 microg/kg/min phenylephrine intravenously for 3 hrs. Mean arterial pressure, intracranial pressure (ICP), cerebral perfusion pressure (CPP), and laser Doppler flow (LDF) at the impact site and in the contralateral parietal cortex were monitored for 3 hrs after the impact injury. Histologic examination of the brain was performed at 2 wks after injury in a separate group of L-arginine- and saline-treated animals. MEASUREMENTS AND MAIN RESULTS The immediate response to the impact injury was an increase in ICP, and a decrease in mean arterial pressure, CPP, and LDF. In the saline-treated animals, LDF decreased to <25% of the baseline values at the impact site and stayed at that level for the entire 3-hr monitoring period. On the contralateral side, LDF decreased initially and recovered gradually to approximately 50% of the preimpact baseline value. Infusion of both phenylephrine and L-arginine increased LDF back to near-baseline levels. However, phenylephrine increased ICP significantly, whereas ICP with L-arginine did not change. L-arginine treatment reduced the contusion volume from a median value of 5.28 mm3 to 0.63 mm3. CONCLUSIONS Phenylephrine increased cerebral blood flow (CBF) by increasing CPP. L-arginine, however, increased CBF without changing CPP. The improvement in CBF was accompanied by a decrease in neurologic injury. Although the pressor agents are used currently to increase CBF after traumatic brain injury, other strategies may also increase CBF without the potential adverse effects of induced hypertension.
Assessment of hemispheric dominance for receptive language in pediatric patients under sedation using magnetoencephalography

Non-invasive assessment of hemispheric dominance for receptive language using magnetoencephalography (MEG) is now a well-established procedure used across several epilepsy centers in the context of pre-surgical evaluation of children and adults while awake, alert and attentive. However, the utility of MEG for the same purpose, in cases of sedated patients, is contested. Establishment of the efficiency of MEG is especially important in the case of children who, for a number of reasons, must be assessed under sedation. Here we explored the efficacy of MEG language mapping under sedation through retrospective review of 95 consecutive pediatric patients, who underwent our receptive language test as part of routine clinical evaluation. Localization of receptive language cortex and subsequent determination of laterality was successfully completed in 78% (n = 36) and 55% (n = 27) of non-sedated and sedated patients, respectively. Moreover, the proportion of patients deemed left hemisphere dominant for receptive language did not differ between non-sedated and sedated patients, exceeding 90% in both groups. Considering the challenges associated with assessing brain function in pediatric patients, the success of passive MEG in the context of the cases reviewed in this study support the utility of this method in pre-surgical receptive language mapping.
Serotonin receptors modulate rod signals: A neuropharmacological comparison of light- and dark-adapted retinas

Previous physiological studies have shown that serotonin (5-HT) reciprocally modulates ON and OFF channels in the mammalian retina. This study was undertaken to determine if the serotoninergic system is exclusively associated with the rod pathway. We tested drugs specific to 5-HT3 receptor, a serotonin-gated ion channel, in both dark- and light-adapted retina. Consistent with previous studies, we demonstrated that 5-HT3 receptors modulate the light-evoked responses of ganglion cells in the dark-adapted state. Moreover, we have extended these prior studies and shown that activation of the 5-HT3 receptor is capable of completely blocking the light-evoked response of OFF-center cells whereas inactivation of the 5-HT3 receptor is capable of completely blocking the light-evoked responses of ON-center cells. In contrast, in light-adapted retinae, serotonin agents failed to have any effect on retinal processing. These data suggest that the serotoninergic system in retina is (1) specifically associated with rod-related pathways; and (2) exerts a powerful modulatory force over information transfer in the retina. Together these observations suggests that serotonin plays an important physiological role in modulating retinal processing.
Synthesis of a spatially band-limited plane wave in the time-domain using wave field synthesis

Wave Field Synthesis (WFS) is a spatial sound reproduction technique aiming at a physically accurate reconstruction of a desired sound field within an extended listening area. It was shown in a recent study that the accuracy of the synthesized sound field can be improved in a local area by applying a spatial band-limitation to the driving function. However, the computational complexity of the frequency-domain driving function is demanding because of the involved Bessel functions. In this paper, a time-domain WFS driving function is introduced for the synthesis of a spatially band-limited plane wave. The driving function is obtained based on a time-domain representation of the sound field which is given as a superposition of plane waves with time-varying direction and amplitude. The performance of the proposed approach is evaluated by numerical simulations. Practical issues regarding the discretization of the analytic driving function and dynamic range control are discussed.
Electrohysterographic detection of uterine contractions in term pregnancy

Uterine-contraction detection is a fundamental component of pregnancy monitoring. Electrohysterography (EHG) provides a non-invasive and accurate alternative to intrauterine pressure (IUP) measurements, and several techniques provide an estimated IUP (eIUP) based on the EHG alone. Commonly, EHG contraction detection is based on amplitude thresholding of the eIUP. We aim at improving the reliability of contraction detection, such that automatic contraction detection can be realized. An algorithm for template-matching of the eIUP signal is proposed. This method is based on Bayesian evidence using a Gaussian likelihood function to classify uterine activity. Gaussian templates are matched to the input signal, with weights obtained empirically from manually-annotated contraction events in a training data-set. The results show an improvement in contraction detection accuracy compared to threshold-based methods. The template-matching method is adaptable to relevant features in the input training data, and is thus less sensitive to differences in eIUP derivation or measurement variability. The method allows for improved automatic uterine contraction detection in labor EHG data, while being extensible to e.g. preterm contraction detection.
Case-mix and variation in specialist referrals in general practice.

BACKGROUND The potential of a comprehensive measure of patient morbidity to explain variation in referrals to secondary care has not previously been examined in the UK. AIM To examine the relative role of age, sex and morbidity as defined by the Johns Hopkins ACG Case-Mix System in explaining variations in specialist referrals in general practice. DESIGN OF STUDY Retrospective study of a cohort of patients followed for 1 year. SETTING Two hundred and two general practices, with a total list size of 1,161,892, contributing data to the General Practice Research Database. METHOD Each patient was assigned an ACG and morbidity group, based on their diagnoses, age and sex. The variability in referrals explained by these factors was examined using multilevel logistic regression models by splitting it into variation between practices and variation between patients within practices. RESULTS The annual median (range) percentage of patients referred was 14.8% (range = 2.4-24.4%). The percentage of patients referred increased with age and morbidity. Morbidity explained 30.4% of the total variation in referrals (composed of variability between and within practices). Age and sex only explained 5.3% of the total variation. The variation attributable to practices was approximately 5%, thus most of the variation occurred within practices. Morbidity was also identified as a better predictor of referral compared to age and sex. CONCLUSIONS Morbidity explains almost six times more of the variation in general practice referrals than age and sex, although about two-thirds of the variation remains unexplained. Most of the unexplained variation is due to differences within rather than between practices. The amount of variability in referrals between practices may be less than implied by previous studies based on aggregate information. The implications are that any investigation of specialist referrals from general practice should be interpreted cautiously, even after adjustment for age, sex and morbidity.
Dexmedetomidine Overdose in the Perioperative Setting

OBJECTIVE To report 3 cases of accidental dexmedetomidine overdose in the perioperative setting and review the pathophysiology of α2-agonist overdose. CASE SUMMARIES Three patients accidentally received overdoses of dexmedetomidine, one intraoperatively (192 μg over 20 min) and 2 postoperatively (4 and 2 rather than 0.4 and 0.2 μg/kg/h; 0.5 μg/kg/min rather than 0.5 μg/kg/h). Hemodynamic parameters remained stable for all 3 patients. The most notable sign was oversedation diagnosed either clinically or using a bispectral index monitor; Naranjo criteria suggest possible or probable association of the reactions with dexmedetomidine. In all 3 cases, oversedation resolved within one hour of drug discontinuation. There were no other sequelae, and the remainder of each patient's hospital course was unremarkable. DISCUSSION As of this writing, dexmedetomidine dosing in excess of the label recommendation has been reported, but accidental dexmedetomidine overdose in clinical practice has not been described. Excessive levels of sedation were the only significant finding in all 3 patients. Dexmedetomidine's short redistribution half-life of 6 minutes should lead to rapid resolution of oversedation induced by overdoses if the overall duration of infusion is short (≤8 h). While the patients reported here were hemodynamically stable, dexmedetomidine may engender significant hemodynamic changes either because of sympatholysis at normal doses or vasoconstriction at higher than recommended doses. The absence of a significant hypertensive response to high dexmedetomidine concentrations suggests that dexmedetomidine-induced hypertension may be multifactorial, not simply related to plasma drug concentrations. CONCLUSIONS Practitioners presented with dexmedetomidine overdose should be prepared to manage oversedation. While hemodynamic alterations may be seen with dexmedetomidine use, hypertension from high dexmedetomidine plasma concentrations is not a consistent response. Practitioners using dexmedetomidine should carefully note that dosing for this agent is described by the manufacturer in μg/kg/h, not μg/kg/min.
Bending the power law : A CMPL theory of strategy shifts and the automatization of cognitive skills

The shift with practice from use of generic, multistep problem-solving strategies to fast and relatively effortless memory-based strategies, was explored in 2 experiments using pseudoarithmetic tasks. A complete transition to the memory strategy occurred by about the 60th exposure to each problem. The power law of practice did not hold in the overall data for either the mean or the standard deviation of response latency, but it did hold within each strategy (algorithm or retrieval). Learning was highly specific to the practiced problems. These results constitute the 1st clear demonstration of a skill for which the power law does not apply overall. The results do not support the instance theory of automatization (G. D. Logan, 1988) but are consistent with an alternative component 12ower laws (CMPL) theory that assumes that because of intrinsic attentional limitations, only 1 strategy can be executed at a time.
Efficacy of zinc sulphate on in-hospital outcome of community-acquired pneumonia in people aged 50 years and over.

SETTING Some studies have reported a beneficial effect of zinc sulphate in children with community-acquired pneumonia (CAP). OBJECTIVE To evaluate the effect of adjuvant zinc therapy in adult hospitalised CAP patients aged ⩾50 years on standard antibiotic treatment. METHODS In a randomised double-blind placebo-controlled clinical trial, 91 hospitalised patients diagnosed with CAP using standard clinical and radiological criteria were randomised to receive 220 mg (110 mg twice daily) zinc sulphate for 4 days or placebo, in addition to antibiotics. The primary endpoint was length of hospital stay, and secondary endpoints were time to normalisation of oxygen saturation, respiratory rate and temperature. Disease severity was scored using CURB-65 (mental Confusion, Urea >20 mg/dl, Respiratory rate ⩾30/min, low Blood pressure and age ⩾65 years) RESULTS The results did not show significant differences in length of hospital stay, time to normalisation of respiratory rate and oxygen saturation between patients in the zinc sulphate and placebo groups (P = 0.18, 0.65 and 0.26, respectively). CONCLUSION A short course of zinc supplementation does not improve outcome in hospitalised patients aged ⩾50 years with CAP. In this setting, it should not be recommended as routine adjunctive treatment.