Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of PI3K and R‐ras signaling promotes the extension of sensory axons on inhibitory chondroitin sulfate proteoglycans

Chondroitin sulfate proteoglycans (CSPGs) are extracellular inhibitors of axon extension and plasticity, and cause growth cones to exhibit dystrophic behaviors. Phosphoinositide 3‐kinase (PI3K) is a lipid kinase activated by axon growth promoting signals. In this study, we used embryonic chicken dorsal root ganglion neurons to determine if CSPGs impair signaling through PI3K. We report that CSPGs inhibit PI3K signaling in axons and growth cones, as evidenced by decreased levels of phosphorylated downstream kinases (Akt and S6). Direct activation of PI3K signaling, using a cell permeable phosphopeptide (PI3Kpep), countered the effects of CSPGs on growth cones and axon extension. Both overnight and acute treatment with PI3Kpep promoted axon extension on CSPG‐coated substrates. The R‐Ras GTPase is an upstream positive regulator of PI3K signaling. Expression of constitutively active R‐Ras promoted axon extension and growth cone elaboration on CSPGs and permissive substrata. In contrast, an N‐terminus‐deleted constitutively active R‐Ras, deficient in PI3K activation, promoted axon extension but not growth cone elaboration on CSPGs and permissive substrata. These data indicate that activation of R‐Ras‐PI3K signaling may be a viable approach for manipulating axon extension on CSPGs. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 918–933, 2014
Efficient Intracytoplasmic Labeling of Human Umbilical Cord Blood Mesenchymal Stromal Cells with Ferumoxides

Mesenchymal stromal cells (MSCs) are multipotent cells found in several adult tissues; they have the capacity to differentiate into mesodermal, ectodermal, and endodermal tissues in vitro. There have been several reports that MSCs have therapeutic effects in a variety of diseases. Therefore, using a cell labeling technique, monitoring their temporal and spatial migration in vivo, would be useful in the clinical setting. Magnetic resonance imaging (MRI)—tracking of superparamagnetic iron oxide (SPIO)-labeled cells—is a noninvasive technique for determining the location and migration of transplanted cells. In the present study, we evaluated the influence and toxicity of SPIO (ferumoxides) labeling on multiple differentiated MSCs. To evaluate the influence and toxicity of ferumoxides labeling on differentiation of MSCs, a variety of concentrations of ferumoxides were used for labeling MSCs. We found that the cytoplasm of adherent cells was effectively labeled at low concentrations of ferumoxides. Compared with unlabeled controls, the ferumoxides-labeled MSCs exhibited a similar proliferation rate and apoptotic progression. The labeled MSCs differentiated into osteoblasts and adipocytes in an identical fashion as the unlabeled cells. However, chondrogenesis and neurogenesis were inhibited at high concentrations of ferumoxides. Our results suggest the effective concentration for ferumoxides use in tracking MSCs.
Personal Narratives of Illness in Schizophrenia: Associations with Neurocognition and Symptoms

Abstract Controversy exists regarding whether unawareness/denial of illness in schizophrenia results from neurocognitive deficits or a rejection of stigmatized social roles. One possibility is that some elements of a narrative of mental illness are primarily a matter of personal/social construction while others may be uniquely curtailed by neurocognitive deficits. Accordingly, we gathered narratives of illness among 52 persons with schizophrenia spectrum disorders using a semi-structured interview. Ratings of the plausibility, adequacy of detail, and temporal conceptual organization of each narrative were correlated with assessments of neurocognition, symptoms, and traditional insight measures. Degree of plausibility was significantly related to performance on the Wisconsin Card Sorting Test (WCST), a measure of executive function and levels of Positive symptoms on the Positive and Negative Syndrome Scale (PANSS). When entered into a regression to predict plausibility, positive symptoms and WCST performance made unique contributions (R2 = .51, p < .0001). Higher levels of Positive symptoms were associated with poorer temporal conceptual organization within narratives. Adequacy of detail within narratives of illness was related to traditional insight measures but not neurocognition or symptoms.
Missing links of Molar Incisor Hypomineralization: A review

Dental enamel is an unusual tissue in that once formed it is not remodeled, unlike other hard tissues such as bone. Because of its non remodeling nature, alterations of enamel during its formation are permanently recorded on the tooth surface. As enamel formation can be affected by many factors, the changes induced in the enamel formation, can provide clues as to the timing and nature of these events. Enamel defects may thus be studied as a marker of many adverse biological events occurring during the time of its development. One such developmental defect of the enamel occurring due to changes in the environmental factors causing permanent damage of the enamel is Molar Incisor Hypomineralization (MIH). It describes the clinical picture of hypomineralization of systemic origin affecting one or more first permanent molars that are associated frequently with affected incisors. The treatment comprises of complex care including management of behavior and anxiety of the young child along with aiming to provide a durable restoration under pain free conditions. This paper aims at describing the various etiological factors of this condition and to identify the individuals at potential risk to develop MIH thereby attempting to prevent damage caused due to this condition.
Hemodynamics and wall mechanics after stent placement in swine iliac arteries: comparative results from six stent designs.

PURPOSE To compare the hemodynamics and wall mechanics of swine iliac arteries after placement of six types of stent. MATERIALS AND METHODS Stents were placed in the iliac artery of 18 pigs (three pigs each underwent placement with one of six types of stent); 16 untreated pigs served as control animals. Iliac arterial hemodynamics and wall mechanics were measured 4 days after placement. RESULTS Four stents (Palmaz-Schatz, Cordis, Warren, NJ; and Strecker, Cragg, and Symphony, Boston Scientific/Vascular, Natick, Mass) caused decreased pulsatile flow rate in the treated and contralateral iliac arteries; one (Memotherm; Bard, Covington, Ga) caused increased flow pulsatility; and one (Wallstent; Schneider, Plymouth, Minn) had no effect. No compliance mismatching was noted for the Cragg, Symphony, and Memotherm stents, whereas a decrease in compliance was noted for the Palmaz-Schatz, Strecker, and Wallstent designs. The Palmaz-Schatz and Strecker stents caused increased arterial wall rigidity, the Symphony and Wallstent designs had no effect, and the Memotherm and Cragg stents caused decreased wall rigidity. Stents made of stiff metal yielded different early results than did stents made of the less rigid nitinol. CONCLUSION Soon after implantation, the six stent designs elicited varying changes in blood flow, arterial compliance, and arterial wall mechanics. Contralateral arterial flow also was affected.
The Impact of Achievement Goals on Cardiorespiratory Fitness: Does Self-Efficacy Make a Difference?

Purpose: The relationships among students' self-efficacy, 2 × 2 achievement goals (mastery-approach [MAp], mastery-avoidance [MAv], performance-approach [PAp], and performance-avoidance goals), and achievement performance remain largely unanswered. We tested a model of the mediating role of self-efficacy on the relationship between 2 × 2 achievement goals and cardiorespiratory fitness. Method: A sample of 276 middle school students (115 boys and 161 girls; 91 sixth graders, 87 seventh graders, and 98 eighth graders), aged 12 to 15 years (M age = 13.34, SD = 0.96), responded to the Achievement Goals Questionnaire (Conroy, Elliot, & Hofer, 2003) and Self-Efficacy Questionnaire (Gao, Newton, & Carson, 2008) referenced to the fitness test. Their cardiorespiratory fitness was assessed via the Progressive Aerobic Cardiorespiratory Endurance Run (PACER) 3 days later. Results: Structural equation modeling demonstrated an acceptable model fit to the data, χ 2 (2, N = 105) = 1.66. Self-efficacy had a statistically significant direct effect on the PACER after controlling for the effects of the achievement goals (γ self-efficacy-PACER = .21). MAv and PAp also had direct effects on PACER performance (γ MAv-PACER = − .24, and γ PAp-PACER = .24, respectively). MAp failed to exert direct effect on the PACER. However, the indirect effect of MAp on the PACER via self-efficacy was small although it was statistically significant. Additionally, the indirect effects of MAv and PAp on PACER through self-efficacy were not significant. Conclusions: Students' self-efficacy fully mediated the effect of MAp on fitness performance, as well as partially mediated the effects of MAv and PAp on cardiorespiratory fitness performance. Study implications are provided for educators and practitioners.
Community Water Governance on Mount Kenya: An Assessment Based on Ostrom’s Design Principles of Natural Resource Management

Kenyan river basin governance underwent a pioneering reform in the Water Act of 2002, which established new community water-management institutions. This article focuses on community water projects in the Likii Water Resource Users Association in the Upper Ewaso Ng’iro River basin on Mount Kenya, and the extent to which their features are consistent with Ostrom’s design principles of natural resource management. Although the projects have developed solid institutional structures, pressures such as hydroclimatic change, population growth, and water inequality challenge their ability to manage their water resources. Institutional homogeneity across the different water projects and congruence with the design principles is not necessarily a positive factor. Strong differences in household water flows within and among the projects point to the disconnection between apparently successful institutions and their objectives, such as fair and equitable water allocation.
The spectrum of ZEB2 mutations causing the Mowat–Wilson syndrome in Japanese populations

Mowat–Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by moderate or severe intellectual disability, a characteristic facial appearance, microcephaly, epilepsy, agenesis or hypoplasia of the corpus callosum, congenital heart defects, Hirschsprung disease, and urogenital/renal anomalies. It is caused by de novo heterozygous loss of function mutations including nonsense mutations, frameshift mutations, and deletions in ZEB2 at 2q22. ZEB2 encodes the zinc finger E‐box binding homeobox 2 protein consisting of 1,214 amino acids. Herein, we report 13 nonsense and 27 frameshift mutations from 40 newly identified MWS patients in Japan. Although the clinical findings of all the Japanese MWS patients with nonsense and frameshift mutations were quite similar to the previous review reports of MWS caused by nonsense mutations, frameshift mutations and deletions of ZEB2, the frequencies of microcephaly, Hirschsprung disease, and urogenital/renal anomalies were small. Patients harbored mutations spanning the region between the amino acids 55 and 1,204 in wild‐type ZEB2. There was no obvious genotype–phenotype correlation among the patients. A transfection study demonstrated that the cellular level of the longest form of the mutant ZEB2 protein harboring the p.D1204Rfs*29 mutation was remarkably low. The results showed that the 3′‐end frameshift mutation of ZEB2 causes MWS due to ZEB2 instability. © 2014 Wiley Periodicals, Inc.
SoK: Consensus in the Age of Blockchains

The core technical component of blockchains is consensus: how to reach agreement among a distributed network of nodes. A plethora of blockchain consensus protocols have been proposed---ranging from new designs, to novel modifications and extensions of consensus protocols from the classical distributed systems literature. The inherent complexity of consensus protocols and their rapid and dramatic evolution makes it hard to contextualize the design landscape. We address this challenge by conducting a systematization of knowledge of blockchain consensus protocols. After first discussing key themes in classical consensus protocols, we describe: (i) protocols based on proof-of-work; (ii) proof-of-X protocols that replace proof-of-work with more energy-efficient alternatives; and (iii) hybrid protocols that are compositions or variations of classical consensus protocols. This survey is guided by a systematization framework we develop, to highlight the various building blocks of blockchain consensus design, along with a discussion on their security and performance properties. We identify research gaps and insights for the community to consider in future research endeavours.
Cirrhosis in hepatitis C virus-infected patients can be excluded using an index of standard biochemical serum markers

Objective Assessment of liver histology is pivotal in prognostication and decision-making regarding therapeutic intervention in patients with chronic hepatitis C virus (HCV). Being an invasive procedure, the liver biopsy is associated with complications, and a non-invasive alternative would be preferable. Material and methods Sera samples from 179 patients with chronic HCV infection collected at the time of liver biopsy were analyzed using routinely available biochemical markers of liver disease, and liver histology was evaluated using the Ishak protocol. The relationship between the serum biochemical markers and cirrhosis (Ishak stage ≥ 5) as well as bridging fibrosis (Ishak stage ≥ 3) was examined. Results Conclusions A strong association was found in the multivariate logistic regression analysis between fibrosis stage and aspartate aminotransferase (AST), platelet count and prothrombin-INR (international normalized ratio). An index (the Göteborg University Cirrhosis Index (GUCI)) was calculated using these variables: normalized AST×prothrombin-INR×100/platelet count (×109/l). Using a cut-off value of 1.0, the sensitivity was 80% and the specificity 78% for diagnosis of cirrhosis, and the negative predictive values (NPV) and positive predictive values (PPV) were 97% and 31%, respectively. The GUCI score proved slightly superior for sensitivity, specificity, NPV, PPV, and the area under the receiver operating characteristic (ROC) curve for prediction of cirrhosis and bridging fibrosis compared with the AST to platelet ratio index (APRI), which has been reported as a predictor of significant fibrosis and cirrhosis. An index using routinely available biochemical markers can with a high degree of accuracy discriminate patients with from those without hepatitis C-related cirrhosis.
Effects of the combined use of glutamine and growth hormone in the intestinal adaptation after massive resection of the small bowel in rats.

PURPOSE The aim of this study was to investigate the effects of the combined use of glutamine (GL) and growth hormone (GH) in the intestine of rats submitted to 80% small bowel resection. METHODS [24] Twenty four Wistar rats were randomized to receive either a standard rat chow--control group (CG, n = 12) or the same diet added to 4% glutamine--GL-GH group (n = 12) after 80% enterectomy. The latter group received subcutaneously 0.6 UI/day of GH. Groups of six rats in each group were killed on the 5th and 14th days. The following variables were studied: body weight, mucosal weight, histomorphometry and DNA content in the resected specimen and in the adapted intestines after necropsy. RESULTS All animals lost weight stabilizing after the 5th PO day in both groups. There was not any statistical difference in the mucosal weight associated to groups and dates. However, ileal mucosal weight decreased from basal to final results when compared to jejunal mucosa (p = 0.02). The DNA content increased from the initial to the final results (p < 0.001) in both groups, though, this increase was greater in GL-GH animals (CG = 0.53 [95% CI, 0.44-0.62] g/cm(-1) vs. GL-GH = 0.85 [95%CI, 0.76-0.94] g/cm(-1); p < 0.01), especially at the 14th day. Ileal DNA content was significantly greater than jejunal (p = 0.01). There was a significant increase in the intestinal wall width and crypt depth in the control group (p < 0.01). CONCLUSION Gut adaptation after massive resection is improved with the combined use of glutamine and GH.
Paving the way for new agents; is standard chemotherapy part of the treatment paradigm for chronic lymphocytic leukemia in the future?

ABSTRACT Introduction: First and second generation tyrosine kinase inhibitors, represent a new, fully biologic and targeted approach to chronic lymphocytic leukemia and allowed to obtain high responses and acceptable tolerability even in elderly and high risk patients. On the other hand, prolonged experience with these agents has raised some questions on unexpected toxicities, response quality, treatment duration and onset of resistances. Areas covered: This review analyzes the main published studies with the aim to discuss whether, in future, new agents could become a part of standard treatments or even replace the chemo-immunotherapy in chronic lymphocytic leukemia. Expert commentary: Despite different trials has been already published and many are still ongoing, follow up times are, at present, too short. A chemo-free approach surely represents a desirable goal for chronic lymphocytic leukemia, nevertheless longer observation is warranted to better define the correct use of targeted therapies.
Esophagogastric anastomosis performed with a stapler: the occurrence of leakage and stricture.

The circular stapler has lowered the leakage rate of an esophageal anastomosis to a level hitherto achieved by only a few surgeons performing hand anastomosis on selected patients with carcinoma of the esophagus. However, the esophageal anastomosis performed with a stapler is also associated with a high stricture rate. Our prospective study was conducted to determine the leakage rate and the incidence of stricture after esophagogastric anastomosis was performed with a stapler, the relationship of stricture to the size of the stapler, and the risk of stricture in relation to time. In a group of 174 patients with carcinoma of the thoracic esophagus, resection was performed, and a one-stage esophagogastric anastomosis was constructed. There were 33 hand anastomoses, 64 anastomoses with an EEA stapler (U.S. Surgical Corp., Norwalk, Conn.), and 77 anastomoses with an ILS stapler (Ethicon Ltd., Edinburgh, U.K.). The anastomotic leakage rate was 3.4% (6/174); 3% with the hand technique and 3.5% with the stapler technique (4.7% for the EEA and 2.6% for the ILS). After leakages and hospital deaths were excluded, 133 discharged patients were evaluated for the occurrence of anastomotic strictures. Only those who complained of dysphagia were investigated. The incidence of stricture for hand anastomosis was 8.7%-EEA 20% and ILS 10%; the overall incidence of anastomoses with a stapler was 14.5%. The true incidence would probably be higher if all patients were assessed by endoscopic or radiologic examination after operation. All three sizes of EEA staplers had a high incidence of stricture. For the ILS stapler the 25 mm size had the highest stricture rate (28.6%) of all groups, but for the 29 and 33 mm sizes, the incidences were 5.3% and 0%, respectively. Actuarial analysis showed an increasing risk of stricture with a reduction in the size of stapler used and was 32.5% and 35%, respectively, for the ILS 25 mm and EEA 25 mm staplers at 131/2 months. The risk of stricture occurrence was highest in the first 4 months. Treatment by bougienage was satisfactory. In conclusion, esophagogastric anastomosis performed with a stapler is a very safe procedure with respect to leakage but is associated with a high risk of stricture, except when the largest ILS staplers are used. However, dilatation readily overcomes the stricture occurrence and adequately compensates for the reduced leakage rate and its attendant serious consequences.
Spatial and temporal expression of RP58, a novel zinc finger transcriptional repressor, in mouse brain

RP58, a novel zinc finger protein containing a POZ domain, is a sequence‐specific transcriptional repressor. To understand the role of this protein, we examined RP58 gene expression in the developing mouse brain by quantitative polymerase chain reaction (PCR) and in situ hybridization. RP58 mRNA expression was detected at embryonic day (E) 10 in the neuroepithelium, and subsequently in the ventricular zones of the cerebral cortex in the E12 embryo. Strong expression was observed in the preplate in the cerebral cortex from this stage onward. High levels of expression continued to be detected in the cortical plate and subventricular zone of the neocortex, hippocampus, and parts of the amygdala, but not in the thalamus or striatum. These results suggest that RP58 plays a crucial role in neuronal proliferation, migration, and differentiation in the developing cerebral cortex. RP58 is also expressed in the adult mouse neocortex, hippocampus, parts of the amygdala, and granule cells in the cerebellum. Double in situ hybridization using GAD67 or VGLUT1 probes revealed that RP58 is expressed in glutamatergic excitatory neurons. J. Comp. Neurol. 502:1098–1108, 2007. © 2007 Wiley‐Liss, Inc.
Morphological differences of intraneuronal ubiquitin‐positive inclusions in the dentate gyrus and parahippocampal gyrus of motor neuron disease with dementia

Semiquantitative morphological analysis of cerebral intraneuronal ubiquitin‐positive tau‐negative inclusions, a pathologic marker for motor neuron disease with dementia (MND‐D), was performed in the dentate gyrus and parahippocampal gyrus of 20 clinicopathologically confirmed patients with MND‐D. The forms of the inclusions were tentatively classified into three types: (i) C‐type, consisting of relatively large and intensely stained crescent or circular structures; (ii) L‐type, showing fine linear structures around the nuclei; and (iii) G‐type, showing faintly stained granular structures. The frequencies of the C‐type, L‐type and G‐type was 0.5–9.3%, 0.2–6.5% and 0–6.6% of dentate granule cells, respectively. In contrast to the dentate gyrus, almost all inclusions showed either the C‐type or L‐type form in the parahippocampal gyrus. A positive correlation was noted only between incidences of C‐type inclusion of the dentate gyrus and that of the parahippocampal gyrus (r = 0.69, P < 0.05). The morphological differences of the inclusions probably reflect different stages of their formation.
Management innovation enters the game: Re-considering the link between technological innovation and financial performance

The aim of this study is to investigate the innovation–performance relationship at the organizational level by empirically examining the role of management innovation in the link between technological innovation and financial performance. We adopt a view that is less present in the innovation literature and examine how technological innovations spur the need for new managerial solutions, which in turn result in improved firm performance. We apply a research methodology of testing our model via structural equation modeling on data gathered from 604 firms in three countries: Slovenia, Spain, and South Korea. The findings indicate that management innovation is the mechanism that enables firms to fully benefit from their technological discoveries in order to result in superior financial performance. The conclusions of the paper are related to shifting the view that presumes the crucial and almost exclusive importance of technological innovation for enhancing firm performance.