Miracle-dz/UniFAR-FTUs huggingface dataset:
Fibroblast growth factor 23 signaling in hippocampal cells: impact on neuronal morphology and synaptic density

Endocrine fibroblast growth factor 23 (FGF23) is predominantly secreted by osteocytes and facilitates renal phosphate excretion. However, FGF23 is also present in cerebrospinal fluid. In chronic kidney disease, FGF23 serum levels are excessively elevated and associated with learning and memory deficits. Structural plasticity of the hippocampus such as formation of new synapses or an altered dendritic arborization comprises a cellular and morphological correlate of memory formation. Therefore, we hypothesize that FGF23 alters hippocampal neuron morphology and synapses. To address this, we prepared primary murine hippocampal cultures and incubated them with recombinant FGF23 alone or together with a soluble isoform of its co‐receptor α‐Klotho. Neuronal expression of a fluorescent reporter allowed for a detailed evaluation of the neuronal morphology by Sholl analysis. Additionally, we evaluated synaptic density, identified by stainings, for synaptic markers. We show an enhanced number of primary neurites combined with a reduced arborization, resulting in a less complex morphology of neurons treated with FGF23. Moreover, FGF23 enhances the synaptic density in a FGF‐receptor (FGF‐R) dependent manner. Finally, we addressed the corresponding signaling events downstream of FGF‐R employing a combination of western blots and quantitative immunofluorescence. Interestingly, FGF23 induces phospholipase Cγ activity in primary hippocampal neurons. Co‐application of soluble α‐Klotho leads to activation of the Akt‐pathway and modifies FGF23‐impact on neuronal morphology and synaptic density. Compared with other FGFs, this alternative signaling pattern is a possible reason for differential effects of FGF23 on hippocampal neurons and may thereby contribute to learning and memory deficits in chronic kidney disease patients.
Glasgow motor scale alone is equivalent to Glasgow Coma Scale at identifying children at risk for serious traumatic brain injury

BACKGROUND Glasgow Coma Scale (GCS) is a validated assessment of neurologic state. Assessment of the eye and verbal components is difficult to reliably obtain in children. We hypothesized that an abnormal Glasgow motor scale (GMS) score alone will reliably identify children with serious traumatic brain injury (TBI). METHODS We reviewed all children with a diagnosis of TBI from 2002 to 2011 at two urban Level I pediatric trauma centers. We used logistic regression to model GCS, GMS, Glasgow verbal scale (GVS), and Glasgow eye scale (GES) for seven outcomes: need for craniotomy, intracranial pressure monitoring, admission to the intensive care unit, hospital stay of 5 days or longer, discharge to rehabilitation, dependence on caretakers at follow-up, and survival to hospital discharge. We then used three measures of fit analysis to determine which scale offered the best fit for each of the outcomes. RESULTS A total of 2,341 patients (mean [SD] age, 6.9 [5.8] years; 64.7% male) with TBI and GCS data available were identified. The median GCS on presentation was 15 (interquartile range [IQR], 8–15); the median GMS on presentation was 6 (IQR, 4–6). The median GVS was 5 (IQR, 1–5), and the median GES was 4 (IQR, 2–4). GCS as a whole offered the best fit for the data in predicting need for intensive care unit admission, need for intracranial pressure monitoring, prolonged hospital length of stay, and discharge to rehabilitation but was equivalent to GMS in predicting need for craniotomy, survival to hospital discharge, or dependence on a caretaker at follow-up. Further analysis revealed that GMS was more predictive of these outcomes than GVS + GES, indicating that GMS provides the greatest contribution to the predictive ability of the GCS. CONCLUSION GMS score alone and GCS do not differ in identifying children with serious TBI. Eliminating the eye and verbal components of GCS does not adversely affect the accuracy of this tool to identify children at risk for serious TBI. LEVEL OF EVIDENCE Prognostic study, level III.
Altered mRNP granule dynamics in FTLD pathogenesis

In neurons, RNA‐binding proteins (RBPs) play a key role in post‐transcriptional gene regulation, for example alternative splicing, mRNA localization in neurites and local translation upon synaptic stimulation. There is increasing evidence that defective or mislocalized RBPs – and consequently altered mRNA processing – lead to neuronal dysfunction and cause neurodegeneration, including frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Cytosolic RBP aggregates containing TAR DNA‐binding protein of 43 kDa (TDP‐43) or fused in sarcoma (FUS) are a common hallmark of both disorders. There is mounting evidence that translationally silent mRNP granules, such as stress granules or transport granules, play an important role in the formation of these RBP aggregates. These granules are thought to be ‘catalytic convertors’ of RBP aggregation by providing a high local concentration of RBPs. As recently shown in vitro, RBPs that contain a so‐called low‐complexity domain start to ‘solidify’ and eventually aggregate at high protein concentrations. The same may happen in mRNP granules in vivo, leading to ‘solidified’ granules that lose their dynamic properties and ability to fulfill their physiological functions. This may result in a disturbed stress response, altered mRNA transport and local translation, and formation of pathological TDP‐43 or FUS aggregates, all of which may contribute to neuronal dysfunction and neurodegeneration. Here, we discuss the general functional properties of these mRNP granules, how their dynamics may be disrupted in frontotemporal lobar degeneration/amyotrophic lateral sclerosis, for example by loss or gain of function of TDP‐43 and FUS, and how this may contribute to the development of RBP aggregates and neurotoxicity.
Estradiol‐induced neurogenesis in the female accessory olfactory bulb is required for the learning of the male odor

Odors processed by the main and accessory olfactory bulbs (MOB, AOB) are important for sexual behavior. Interestingly, both structures continue to receive new neurons during adulthood. A role for olfactory neurogenesis in sexual behavior in female mice has recently been shown and gonadal hormones such as estradiol can modulate adult neurogenesis. Therefore, we wanted to determine the role of estradiol in learning the odors of sexual partners and in the adult neurogenesis of female aromatase knockout mice (ArKO), unable to produce estradiol. Female wild‐type (WT) and ArKO mice were exposed to male odors during 7 days, and olfactory preferences, cell proliferation, cell survival and functional involvement of newborn neurons were analyzed, using BrdU injections, in combination with a marker of cell activation (Zif268) and neuronal fate (doublecortin, NeuN). Behavioral tasks indicated that both WT and ArKO females were able to discriminate between the odors of two different males, but ArKO mice failed to learn the familiar male odor. Proliferation of newborn cells was reduced in ArKO mice only in the dentate gyrus of the hippocampus. Olfactory exposure decreased cell survival in the AOB in WT females, suggesting a role for estradiol in a structure involved in sexual behavior. Finally, newborn neurons do not seem to be functionally involved in the AOB of ArKO mice compared with WT, when females were exposed to the odor of a familiar male, suggesting that estradiol‐induced neurogenesis in the AOB is required for the learning of the male odor in female mice.
The anatomy of vocal divergence in North American Elk and European red deer

Loud and frequent vocalizations play an important role in courtship behavior in Cervus species. European red deer (Cervus elaphus) produce low‐pitched calls, whereas North American elk (Cervus canadensis) produce high‐pitched calls, which is remarkable for one of the biggest land mammals. Both species engage their vocal organs in elaborate maneuvers but the precise mechanism is unknown. Vocal organs were compared by macroscopic and microscopic dissection. The larynx is sexually dimorphic in red deer but not in elk. The laryngeal lumen is more constricted in elk, and narrows further during ontogeny. Several elements of the hyoid skeleton and two of four vocal tract segments are longer in red deer than in elk allowing greater vocal tract expansion and elongation. We conclude that elk submit the larynx and vocal tract to much higher tension than red deer, whereby, enormously stressed vocal folds of reduced effective length create a high resistance glottal source. The narrow, high impedance laryngeal vestibulum matches glottal and vocal tract impedance allowing maximum power transfer. In red deer longer and relaxed vocal folds create a less resistant glottal source and a wider vestibulum matches the low glottal impedance to the vocal tract, thereby also ensuring maximum power transfer. J. Morphol. , 2013. © 2012 Wiley Periodicals, Inc.
The testicular sperm ducts and genital kidney of male Ambystoma maculatum (Amphibia, Urodela, Ambystomatidae)

The ducts associated with sperm transport from the testicular lobules to the Wolffian ducts in Ambystoma maculatum were examined with transmission electron microscopy. Based on the ultrastructure and historical precedence, new terminology for this network of ducts is proposed that better represents primary hypotheses of homology. Furthermore, the terminology proposed better characterizes the distinct regions of the sperm transport ducts in salamanders based on anatomy and should, therefore, lead to more accurate comparisons in the future. While developing the above ontology, we also tested the hypothesis that nephrons from the genital kidney are modified from those of the pelvic kidney due to the fact that the former nephrons function in sperm transport. Our ultrastructural analysis of the genital kidney supports this hypothesis, as the basal plasma membrane of distinct functional regions of the nephron (proximal convoluted tubule, distal convoluted tubule, and collecting tubule) appear less folded (indicating decreased surface area and reduced reabsorption efficiency) and the proximal convoluted tubule possesses ciliated epithelial cells along its entire length. Furthermore, visible luminal filtrate is absent from the nephrons of the genital kidney throughout their entire length. Thus, it appears that the nephrons of the genital kidney have reduced reabsorptive capacity and ciliated cells of the proximal convoluted tubule may increase the movement of immature sperm through the sperm transport ducts or aid in the mixing of seminal fluids within the ducts. © J. Morphol. , 2013. © 2012 Wiley Periodicals, Inc.
Antiarrhythmic Effect of Cardiac Resynchronization Therapy with Triple-Site Biventricular Stimulation

The antiarrhythmic effect of triple-site biventricular stimulation (Tri-V) is poorly understood. This study aims to evaluate the effect of cardiac resynchronization therapy (CRT) on ventricular arrhythmia (VA) with Tri-V using a single right ven- tricular (RV) and double left ventricular (LV) lead. Methods and results Over a period of 3.5 years, 58 consecutive patients with New York Heart Association class II-IV heart failure, an LV ejection fraction of ≤0.35, and a QRS interval of ≥120 ms were enrolled. Acute haemodynamic responses to dual- site biventricular stimulation (Bi-V) and Tri-V were evaluated by assigning patients to a Bi-V or Tri-V group. Electrocar- diogram parameters (QT interval, JT interval, and transmural dispersion of repolarization (TDR)) were measured over time after CRT. Spontaneous VA detected by telemetry was reviewed and confirmed. During a mean follow-up of 481 days after implantation, VA occurred in 2 of 22 patients in the Tri-V group and 14 of 36 patients in Bi-V group. Triple-site biventricular stimulation was thus associated with a decreased VA risk (P ¼ 0.044). Multivariate Cox analysis showed that Tri-V pacing prevented arrhythmic events as compared with Bi-V pacing (hazard ratio, 0.13; 95% confidence interval, 0.029-0.610;P ¼ 0.009). Ventricular repolarization indices at 6 months were significantly shortened in Tri-V compared with Bi-V (QTc, 223.6 vs. 214.1%,P ¼ 0.008; JTc, 221.4 vs. 27.7%,P ¼ 0.005; TDRc, 239.9 vs. 217.0%,P , 0.001). Conclusion Compared with Bi-V, Tri-V reduced VA during long-term follow-up. Improvements in repolarization parameters may
Effect of albumin infusion on preventing the deterioration of renal function in patients with spontaneous bacterial peritonitis

OBJECTIVE: To determine whether plasma volume expansion with albumin could prevent impairment of renal function and reduce mortality in cirrhotic patients with either acute spontaneous bacterial peritonitis (SBP) or patients complicated with SBP. METHODS: A total of 112 patients was randomly allocated to two groups: 56 patients were allocated to be treated with ceftriaxone and 56 patients were allocated to treatment with ceftriaxone plus intra-venous albumin in 3 weeks. Serum creatinine and blood urea nitrogen levels were monitored. RESULTS: Of the 56 patients (group 2) treated with ceftriaxone and albumin, five patients had renal impairment. Of the 56 patients (group 1) treated with ceftriaxone alone, 19 had renal impairment. The incidence of renal impairment was significantly lower in patients treated with ceftriaxone and albumin (5/56; 10%) than in patients treated with ceftriaxone alone (19/56; 34%; P = 0.002). In addition, in-hospital mortality in group 2 was 10% (5/56), but was 33% (17/56) in group 1. Thus, in-hospital mortality was significantly reduced from 33% (17/56) in patients treated with ceftriaxone to 10% (5/56) in patients treated with ceftriaxone and albumin (P = 0.01). CONCLUSIONS: The addition of intravenous albumin to an antibiotic regimen reduces the incidence of renal impairment and mortality in cirrhotic patients with SBP.
Elevated intracellular Na+ concentrations in developing spinal neurons

Over 25 years ago it was first reported that intracellular chloride levels (Cl−in) were higher in developing neurons than in maturity. This finding has had significant implications for understanding the excitability of developing networks and recognizing the underlying causes of hyperexcitability associated with disease and neural injury. While there is some evidence that intracellular sodium levels (Na+in) change during the development of non‐neural cells, it has largely been assumed that Na+in is the same in developing and mature neurons. Here, using the sodium indicator SBFI, we test this idea and find that Na+in is significantly higher in embryonic spinal motoneurons and interneurons than in maturity. We find that Na+in reaches ~ 60 mM in mid‐embryonic development and is then reduced to ~ 30 mM in late embryonic development. By retrogradely labeling motoneurons with SBFI we can reliably follow Na+in levels in vitro for hours. Bursts of spiking activity, and blocking voltage‐gated sodium channels did not influence observed motoneuron sodium levels. On the other hand, Na+in was reduced by blocking the Na+‐K+‐2Cl− cotransporter NKCC1, and was highly sensitive to changes in external Na+ and a blocker of the Na+/K+ ATPase. Our findings suggest that the Na+ gradient is weaker in embryonic neuronal development and strengthens in maturity in a manner similar to that of Cl−.
Predictive modeling of respiratory tumor motion for real-time prediction of baseline shifts

Baseline shifts in respiratory patterns can result in significant spatiotemporal changes in patient anatomy (compared to that captured during simulation), in turn, causing geometric and dosimetric errors in the administration of thoracic and abdominal radiotherapy. We propose predictive modeling of the tumor motion trajectories for predicting a baseline shift ahead of its occurrence. The key idea is to use the features of the tumor motion trajectory over a 1 min window, and predict the occurrence of a baseline shift in the 5 s that immediately follow (lookahead window). In this study, we explored a preliminary trend-based analysis with multi-class annotations as well as a more focused binary classification analysis. In both analyses, a number of different inter-fraction and intra-fraction training strategies were studied, both offline as well as online, along with data sufficiency and skew compensation for class imbalances. The performance of different training strategies were compared across multiple machine learning classification algorithms, including nearest neighbor, Naïve Bayes, linear discriminant and ensemble Adaboost. The prediction performance is evaluated using metrics such as accuracy, precision, recall and the area under the curve (AUC) for repeater operating characteristics curve. The key results of the trend-based analysis indicate that (i) intra-fraction training strategies achieve highest prediction accuracies (90.5–91.4%); (ii) the predictive modeling yields lowest accuracies (50–60%) when the training data does not include any information from the test patient; (iii) the prediction latencies are as low as a few hundred milliseconds, and thus conducive for real-time prediction. The binary classification performance is promising, indicated by high AUCs (0.96–0.98). It also confirms the utility of prior data from previous patients, and also the necessity of training the classifier on some initial data from the new patient for reasonable prediction performance. The ability to predict a baseline shift with a sufficient look-ahead window will enable clinical systems or even human users to hold the treatment beam in such situations, thereby reducing the probability of serious geometric and dosimetric errors.
Injury in the aged: Geriatric trauma care at the crossroads

In the 2010 US Census, the number of persons age 65 years and older constituted 13% of the population and is projected to constitute 22% of the population by 2020.1 As the US population ages, there is an increasing volume of GTPs; injury is now the seventh leading cause of death for those age 65 years.2 Geriatric trauma is increasing both in absolute number and as a proportion of annual volume presenting to trauma centers. Based on the National Trauma Data Bank, the proportion of trauma patients aged 65 years or older in Level I and II trauma centers increased from 23% in 2003 to 30% in 2009. This is likely a significant underestimate because most GTPs are treated at lower-level or nontrauma centers.3,4 In Washington State, for example, the annual number of GTPs in the state registry has increased from 4,266 in 2000 to 11,226 in 2012, an increase from 30% to 42% of the total trauma population. Clearly, the management of injury in geriatric patients will continue to be a major challenge for trauma care providers. In his presidential address to the AAST entitled “For the care of the undeserved,” Dr. Robert Mackersie identified the growing population of elderly injured patients as medically underserved in terms of limited trauma center access, age-related treatment biases, and as a result, deprived of many of the recent advances in modern trauma care.5 To specifically address these inequalities, he convened an Ad Hoc Geriatric Committee and charged it, “To advise the AAST regarding the problems, issues, and needs of the geriatric patient. ” What follows is the work product of the Committee in responding to President Mackersie’s charge. The initial priority was to survey the membership of the AAST to better understand the current conditions under which hospitalized GTPs are receiving care. The second task of the Committee was to enumerate the major problems associated with the care of GTPs and to suggest potential solutions to the identified problems. While the Committee does not presume infallibility in its pronouncements, the material presented is intended to initiate discussion, stimulate research, and to ultimately result in evidence-based guidelines that will better serve this “underserved” segment of our population.
PKC epsilon‐dependent calcium oscillations associated with metabotropic glutamate receptor 5 prevent agonist‐mediated receptor desensitization in astrocytes

A critical role has been assigned to protein kinase C (PKC)ε in the control of intracellular calcium oscillations triggered upon activation of type 5 metabotropic glutamate receptor (mGluR5) in cultured astrocytes. Nevertheless, the physiological significance of this particular signalling profile in the response of astrocytes to glutamate remains largely unknown. Considering that kinases are frequently involved in the regulation of G protein‐coupled receptors, we have examined a putative link between the nature of the calcium signals and the response regulation upon repeated exposures of astrocytes to the agonist (S)‐3,5‐dihydroxyphenylglycine. We show that upon repeated mGluR5 activations, a robust desensitization was observed in astrocytes grown in culture conditions favouring the peak‐plateau‐type response. At variance, in cell cultures where calcium oscillations were predominating, the response was fully preserved even during repeated challenges with the agonist. Pharmacological inhibition of PKCε or genetic suppression of this isoform using shRNA was found to convert an oscillatory calcium profile to a sustained calcium mobilization and this latter profile was subject to desensitization upon repetitive mGluR5 activation. Our results suggest a yet undocumented scheme in which the activity of PKCε contributes to preserve the receptor sensitivity upon repeated or sustained activations.
Relationship among Stress, Depression, and Satisfaction to Clinical Practice among Nursing Students

Purpose: The purpose of this study was to investigate the relationship among stress, depression, and satisfaction to clinical practice in nursing students. Methods: Three hundred forty-five nursing college students were selected by convenient sampling and data were collected from October to November, 2011. Results: The nursing students experienced moderate stress level. The most severe stressors were adjustment to school and clinical practice. Also, they experienced more than moderate level of satisfaction on clinical practice. The most satisfiable factors were clinical practice circumstance and practice hours. The sophomore had more severe stress and depression and had lower clinical practice satisfaction than the junior. Satisfying with major in nursing as well as clinical practice had a significantly negative correlation with stress and depression. Conclusion: Based on this results, we need to develop programs for increasing satisfaction to clinical practice and major in nursing. The program will enhance adaptation ability to clinical practice.
An analysis of beam parameters on proton-acoustic waves through an analytic approach

It has been reported that acoustic waves are generated when a high-energy pulsed proton beam is deposited in a small volume within tissue. One possible application of proton-induced acoustics is to get real-time feedback for intra-treatment adjustments by monitoring such acoustic waves. A high spatial resolution in ultrasound imaging may reduce proton range uncertainty. Thus, it is crucial to understand the dependence of the acoustic waves on the proton beam characteristics. In this manuscript, firstly, an analytic solution for the proton-induced acoustic wave is presented to reveal the dependence of the signal on the beam parameters; then it is combined with an analytic approximation of the Bragg curve. The influence of the beam energy, pulse duration and beam diameter variation on the acoustic waveform are investigated. Further analysis is performed regarding the Fourier decomposition of the proton-acoustic signals. Our results show that the smaller spill time of the proton beam upsurges the amplitude of the acoustic wave for a constant number of protons, which is hence beneficial for dose monitoring. The increase in the energy of each individual proton in the beam leads to the spatial broadening of the Bragg curve, which also yields acoustic waves of greater amplitude. The pulse duration and the beam width of the proton beam do not affect the central frequency of the acoustic wave, but they change the amplitude of the spectral components.