Miracle-dz/UniFAR-FTUs huggingface dataset:
Metformin corrects RAGE overexpression caused signaling dysregulation and NF-κB targeted gene change

Background: Advanced glycation end products, known as AGEs, are substances that can be a factor in the development or worsening of many degenerative diseases, such as diabetes. The negative effect of AGEs has been noticed and studied on human keratinocytes but it is still poorly understood about the effect of diabetic drug on AGE caused skin damage despite the skin complications are critical problem of long course diabetes. Materials and methods: In order to study the effect of diabetic drug metformin on AGEs caused signaling dysregulation on human keratinocytes, we used lentiviral vector to overexpress the receptor for advanced glycation end products (RAGE) in immortalized human keratinocytes (HaCaT cells). Results: We showed that phosphorylation of p38, ERK1/2, JNK and Akt was dysregulated and all of them were corrected by metformin treatment. Moreover, the expressions of NFkBp65 and downstream factors ICAM1, TNF-α, Cox-2, IL-6, and IL-1β were also changed, in which the expression of those were rectified by metformin. Conclusions: This study is the first to show the therapeutic effects of diabetic drug metformin on AGEs caused signaling dysregulation on human keratinocytes.
Phase relations of Fe3C and Fe7C3 up to 185 GPa and 5200 K: Implication for the stability of iron carbide in the Earth's core

We have investigated phase relations and melting behavior of Fe3C and Fe7C3 using X‐ray diffraction in a laser‐heated diamond cell up to 185 GPa and 5200 K. Our results show that the starting Fe3C sample decomposes into a mixture of solid orthorhombic Fe7C3 and hcp‐Fe at above 145 GPa upon laser heating and then transforms into Fe‐C liquid and solid Fe7C3 at temperatures above 3400 K. Using the intensity of the diffuse scattering as a primary criteria for detecting melting, the experimentally derived liquidus for a bulk composition of Fe3C fitted with the Simon‐Glatzel equation is Tm(K) = 1800 × [1 + (Pm − 5.7)/15.10 ± 2.55]1/2.41 ± 0.17 at 24–185 GPa, which is ~500 K higher than the melting curve of iron reported by Anzellini et al. (2013) at Earth's core pressures. The higher melting point and relative stability of Fe7C3 in Fe‐rich Fe‐C system at Earth's core conditions indicate that Fe7C3 could solidify out of the early Earth's molten core to become a constituent of the innermost inner core.
Classic Vulvar Intraepithelial Neoplasia With Superimposed Lichen Simplex Chronicus: A Unique Variant Mimicking Differentiated Vulvar Intraepithelial Neoplasia

High-grade vulvar intraepithelial neoplasia, a precursor lesion to vulvar squamous cell carcinoma, is subdivided into 2 types, classic or usual vulvar intraepithelial neoplasia (CVIN) and differentiated vulvar intraepithelial neoplasia (DVIN). CVIN, which is a human papilloma virus (HPV)-dependent lesion, is typically distinguished from DVIN, a p53 mutation-dependent process, by its distinct histomorphologic and immunohistochemical characteristics. However, distinguishing between the 2 entities becomes challenging in cases of CVIN with superimposed inflammatory changes, especially lichen simplex chronicus (LSC). Twelve cases of DVIN, 9 cases of LSC, and 9 cases of CVIN with superimposed LSC were assessed for a number of morphologic features, including hyperkeratosis, hypergranulosis, acanthosis, hypercellularity, abnormal maturation (i.e. abnormal keratinization close to the base and/or dyskeratosis), hyperchromasia, and basal atypia. Immunohistochemistry for p53, p16, and MIB-1 was performed for all cases. When sufficient tissue was available, HPV genotyping was performed for cases of CVIN with superimposed LSC. DVIN uniformly demonstrated abnormal maturation, and atypia involving the basal cell layer; they were all p16 negative and demonstrated p53 positivity of moderate to strong intensity in a basal and parabasal distribution. CVIN with superimposed LSC frequently displayed hyperchromasia involving the basal 3 to 4 cell layers, basal to full-thickness atypia, and apoptosis. CVIN with superimposed LSC demonstrated intense p16 positivity extending from the basal cells to the mid-epithelium and a reduction or loss of staining in maturing keratinocytes. P53 staining revealed a unique pattern of parabasal and mid-epithelial weak to moderate staining with sparing of the basal layer. Cases of LSC demonstrated heterogenous p53 positivity and were negative for p16. MIB-1 staining showed a similar range of positivity for all diagnoses. HPV genotyping revealed HPV 16 in all 5 cases of CVIN with LSC that underwent testing. We conclude that, although CVIN with superimposed LSC can closely resemble DVIN, morphologic features such as nuclear hyperchromasia uniformly involving the basal 3 to 4 cell layers, apoptosis, and absent or less pronounced cytoplasmic maturation are more suggestive of CVIN with superimposed LSC. In cases where the morphology remains ambiguous, immunohistochemistry for both p16 and p53 can be helpful. In particular, p53 parabasal and mid-epithelial staining without involvement of the basal layer appears to be a characteristic finding in CVIN with superimposed LSC. MIB-1 staining is of little utility in distinguishing between these entities and should not be routinely performed.
Protective Effects of Selected Botanical Agents on Bone

Osteoporosis is a serious health problem affecting more than 200 million elderly people worldwide. The early symptoms of this disease are hardly detectable. It causes progressive bone loss, which ultimately renders the patients susceptible to fractures. Osteoporosis must be prevented because the associated fragility fractures result in high morbidity, mortality, and healthcare costs. Many plants used in herbal medicine contain bioactive compounds possessing skeletal protective effects. This paper explores the anti-osteoporotic properties of selected herbal plants, including their actions on osteoblasts (bone forming cells), osteoclasts (bone resorbing cells), and bone remodelling. Some of the herbal plant families included in this review are Berberidaceae, Fabaceae, Arecaceae, Labiatae, Simaroubaceaea, and Myrsinaceae. Their active constituents, mechanisms of action, and pharmaceutical applications were discussed. The literature shows that very few herbal plants have undergone human clinical trials to evaluate their pharmacological effects on bone to date. Therefore, more intensive research should be performed on these plants to validate their anti-osteoporotic properties so that they can complement the currently available conventional drugs in the battle against osteoporosis.
Alterations in the Three Components of Selfhood in Persons with Post-Traumatic Stress Disorder Symptoms: A Pilot qEEG Neuroimaging Study

Background and Objective: Understanding how trauma impacts the self-structure of individuals suffering from the Post-Traumatic Stress Disorder (PTSD) symptoms is a complex matter and despite several attempts to explain the relationship between trauma and the “Self”, this issue still lacks clarity. Therefore, adopting a new theoretical perspective may help understand PTSD deeper and to shed light on the underlying psychophysiological mechanisms. Methods: In this study, we employed the “three-dimensional construct model of the experiential selfhood” where three major components of selfhood (phenomenal first-person agency, embodiment, and reflection/narration) are related to three Operational Modules (OMs) of the self-referential brain network. These modules can be reliably estimated through operational synchrony analysis of the Electroencephalogram (EEG). Six individuals with PTSD symptoms and twenty-nine sex-, age- and demographic- (race, education, marital status) matched healthy controls underwent resting state EEG signal acquisition with the following estimation of the synchrony strength within every OM. Results: Our results indicate that subjects with PTSD symptoms had significantly stronger EEG operational synchrony within anterior and right posterior OMs as well as significantly weaker EEG operational synchrony within left posterior OM compared to healthy controls. Moreover, increased the functional integrity of the anterior OM was positively associated with hyperactivity symptoms, reduced synchrony of the left posterior OM was associated with greater avoidance, and increased right posterior OM integrity was positively correlated with intrusion and mood symptoms. Conclusion: The results are interpreted in light of the triad model of selfhood and its theoretical and clinical implications (including a new treatment approach) are discussed.
Automatic Annotation of Semantic Term Types in the Complete ACL Anthology Reference Corpus

In the present paper, we present an automated tagging approach aimed at enhancing a well-known resource, the ACL Anthology Reference Corpus, with semantic class labels for more than 20,000 technical terms that are relevant to the domain of computational linguistics. We use state-of-the-art classiﬁcation techniques to assign semantic class labels to technical terms extracted from several reference term lists. We also sketch a set of research questions and approaches directed towards the integrated analysis of scientiﬁc corpora. To this end, we query the data set resulting from our annotation effort on both the term and the semantic class level level.
Bone marrow IRF4 level in multiple myeloma: an indicator of peripheral blood Th17 and disease

Interferon regulator factor 4 (IRF4) is characterized to be a member of interferon regulatory family, which is predominantly expressed in bone marrow plasma cells of patients with multiple myeloma (MM). Recent studies indicated IRF4 is critical for T-help cells (Th17) differentiation and interleukin-17 (IL-17) secretion. Here, a total of 58 MM patients were enrolled in this study, the proportions of Th17 cells and T regulatory (Treg) cells in peripheral blood mononuclear cells (PBMCs) were determined by flow cytometric analysis. Immunohistochemistry was employed to detect the IRF4 expression in bone marrow. Herein, we observed a significant increase of IRF4 in bone marrow accompanied with a notable up-regulation of Th17 cells in PBMC within MM patients compared with healthy donors. Furthermore, the proportions of Th17 cells and serum IL-17 levels were higher in patients with stage III than stage I & II MM patients, and those parameters were positively correlated with the expression of IRF4 in these cases. These results for the first time indicate that a crosstalk between IRF4 and Th17 cells is associated with MM prognosis, and IRF4 may be served an important target for MM immunotherapy.
Three‐Dimensional Structure of the Nasal Passageway of a Hagfish and its Implications for Olfaction

From high‐resolution (65 μm) data acquired by magnetic resonance imaging, we have reconstructed the nasal passageway of a single adult hagfish specimen (probably Eptatretus stoutii). We have used this reconstruction to investigate how the anatomy and morphometry of the nasal passageway influence the olfactory ability of the hagfish. We found that the long, broad section of the passageway preceding the nasal chamber will delay the response to an odor by 1–2 s. Diffusion of odorant to the olfactory epithelium, on which the olfactory sensitivity of an animal depends, will be favored by the relatively large surface area of the olfactory epithelium (∼140 mm2) and a modest expansion in the nasal chamber. Oscillating flow (0.3–0.4 Hz) within the narrow (65–130 μm) sensory channels of the nasal chamber is laminar (Reynolds number ∼ 5) and quasi‐steady (Womersley number generally less than one). Distribution of flow over the olfactory epithelium may be aided by: (a) a narrowing before the nasal chamber; (b) partial blockage of the nasal passageway by a protrusion on the central olfactory lamella; and (c) the inward inclination of the olfactory lamellae. Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.
IDH‐mutated astrocytomas with 19q‐loss constitute a subgroup that confers better prognosis

IDH‐mutant gliomas are classified into astrocytic or oligodendroglial tumors by 1p/19q status in the WHO 2016 classification, with the latter presenting with characteristic morphology and better prognosis in general. However, the morphological and genetic features within each category are varied, and there might be distinguishable subtypes. We analyzed 170 WHO grade II‐IV gliomas resected in our institution. 1p/19q status was analyzed by microsatellite analysis, and genetic mutations were analyzed by next‐generation sequencing and Sanger sequencing. For validation, the Brain Lower Grade Glioma dataset of The Cancer Genome Atlas was analyzed. Of the 42 grade III IDH‐mutated gliomas, 12 were 1p‐intact/19q‐intact (anaplastic astrocytomas [AA]), 7 were 1p‐intact/19q‐loss (AA), and 23 showed 1p/19q‐codeletion (anaplastic oligodendrogliomas). Of the 88 IDH‐wild type glioblastomas (GBMs), 14 showed 1p‐intact/19q‐loss status. All of the seven 1p‐intact/19q‐loss AAs harbored TP53 mutation, but no TERT promotor mutation. All 19q‐loss AAs had regions presenting oligodendroglioma‐like morphology, and were associated with significantly longer overall survival compared to 19q‐intact AAs (P = .001). This tendency was observed in The Cancer Genome Atlas Lower Grade Glioma dataset. In contrast, there was no difference in overall survival between the 19q‐loss GBM and 19q‐intact GBM (P = .4). In a case of 19q‐loss AA, both oligodendroglial morphology and 19q‐loss disappeared after recurrence, possibly indicating correlation between 19q‐loss and oligodendroglial morphology. We showed that there was a subgroup, although small, of IDH‐mutated astrocytomas harboring 19q‐loss that present oligodendroglial morphology, and also were associated with significantly better prognosis compared to other 19q‐intact astrocytomas.
Satellite observations of long range transport of a large BrO plume in the Arctic

Abstract. Ozone Depletion Events (ODE) during polar springtime are a well known phenomenon in the Arctic and Antarctic boundary layer. They are caused by the catalytic destruction of ozone by halogens producing reactive halogen oxides like bromine monoxide (BrO). The key halogen bromine can be rapidly transferred into the gas phase in an autocatalytic process – the so called "Bromine Explosion". However, the exact mechanism, which leads to an initial bromine release as well as the influence of transport and chemical processes on BrO, is still not clearly understood. In this study, BrO measurements from the satellite instrument GOME-2 are used together with model calculations with the dispersion model FLEXPART to study an arctic BrO event in March 2007, which could be tracked over several days and a large area. Full BrO activation was observed within one day east of Siberia with subsequent transport to Hudson Bay. The event was linked to a cyclone with very high surface wind speeds, which could have been involved in the production and lifting of aerosols or blowing snow. Considering the short life time of BrO, transported aerosols or snow can also provide the surface for BrO recycling within the plume for several days. The evolution of the BrO plume could be reproduced by FLEXPART simulations of a passive tracer indicating that the activated air mass was transported all the way from Siberia to Hudson Bay. To localise the most probable transport height, model runs initialised in different heights have been performed showing similar transport patterns throughout the troposphere but best agreement with the measurements between the surface and 3 km. The influence of changes in tropopause height on measured BrO values has been considered, but cannot completely explain the observed high BrO values. Backward trajectories from the area of BrO initialisation show upward lifting from the surface up to 3 km and no indication for intrusion of stratospheric air. These observations are consistent with a scenario in which bromine in the air mass was activated on the surface within the cyclone, lifted upwards and transported over several thousand kilometres to Hudson Bay.
A Geometric Characterization of Observability in Inertial Parameter Identification

This paper presents an algorithm to geometrically characterize inertial parameter identifiability for an articulated robot. The geometric approach tests identifiability across the infinite space of configurations using only a finite set of conditions and without approximation. It can be applied to general open-chain kinematic trees ranging from industrial manipulators to legged robots, and it is the first solution for this broad set of systems that is provably correct. The high-level operation of the algorithm is based on a key observation: Undetectable changes in inertial parameters can be represented as sequences of inertial transfers across the joints. Drawing on the exponential parameterization of rigid-body kinematics, undetectable inertial transfers are analyzed in terms of observability from linear systems theory. This analysis can be applied recursively, and lends an overall complexity of $O(N)$ to characterize parameter identifiability for a system of $N$ bodies. Matlab source code for the new algorithm is provided.
How Top Management's Social Capital Fosters the Development of Specialized Marketing Capabilities: A Cross-Cultural Comparison

The main purpose of this research is to investigate the role of top management's social capital as a microlevel origin of four specialized marketing capabilities: pricing, product development, distribution, and marketing communication. The authors investigate the moderating effect of national culture on the link between social capital and marketing capability using survey data from 891 firms across four countries (China, Germany, Hong Kong, and the United States). The findings indicate that the elements of social capital—managerial tie utilization, trust, and solidarity—are strong drivers of the four marketing capabilities. Managerial tie utilization and solidarity tend to be more important when national culture's power distance is low, collectivism is high, and uncertainty avoidance is low, whereas the effect of trust is not subject to national cultural variations. From a managerial perspective, this research emphasizes the strong role and responsibility of top management team members, including marketing managers who are at this level, in building organization-level marketing capabilities.
UvA-DARE ( Digital Academic Repository ) Medication safety in pediatric care

Introduction Many hospitalized patients are affected by medication errors (MEs) that may cause discomfort, harm and even death. Especially, children are considered to be at high risk of experiencing harm due to MEs. More insight into the prevalence, type and severity of harm caused by MEs could help reduce the frequency of these harmful events. The primary objectives of our study were to establish the prevalence of different types of MEs and the severity of harm caused by MEs in hospitalized children from birth to 18 years of age. In addition, we investigated correlations between harmful MEs and characteristics of the patients, the medication and the medication process. Methods In this cross-sectional study, we identified MEs by reviewing clinical records, making direct observations, monitoring pharmacy logs and reviewing voluntary incident reports. Subsequently, the MEs were classified according to type of error, medication group and stage of the medication process. Pediatricians rated the severity of the observed harm. Results We collected data from 426 hospitalized children admitted during August to October 2011. A total of 322 MEs were identified, of which 39 caused patient harm. Harmful events were mainly due to wrong time (41%). Pediatricians rated the observed harm as minor in 77% of the incidents and significant in 23%. None of the harmful MEs resulted in permanent harm or was considered life threatening or fatal. Patients admitted for a surgical procedure were at higher risk for a harmful event compared to patients admitted for nonsurgical reasons (adjusted odds ratio 2.79, 95% CI 1.35-5.80). Nonopioid analgesics and anti-emetic drugs accounted for 67% of the harmful MEs. Harmful MEs occurred most frequently during medication prescription (28%) and administration (62%). Conclusion Surgical pediatric patients seem to be at high risk for harmful MEs. Although the harm was considered minor in most cases, it still caused discomfort for the patients, and the high prevalence is a source of concern. Interventions to prevent the MEs should focus on the prescription and administration of non-opioid analgesics and anti-emetic drugs.
ABSTRACT Setting the Minimum Wage

The process leading to the setting of the minimum wage so far has been fairly overlooked by economists. This paper suggests that this is a serious limitation as the setting regime contributes to explain cross-country variation in the fine-tuning of the minimum wage, hence in the way in which the trade-off between reducing poverty among working people and shutting down low productivity jobs is addressed. There are two common ways of setting national minimum wages: they are either government legislated or are the outcome of collective bargaining agreements, which are extended erga omnes to all workers. We develop a simple model relating the level of the minimum wage to the setting regime. Next, we exploit a new data set on minimum wages in 66 countries that had already or introduced a minimum wage in the period 1981-2005 to test the implications of the model. We find that a Government legislated minimum wage is lower than a wage floor set within collective agreements. This effect survives to several robustness checks and hints at a causal relation between the setting regime and the level of the minimum wage.
The public sector and convergence with spatial interdependence: empirical evidence from Spain

ABSTRACT We propose a framework to analyse convergence between regions, incorporating the public sector and technological knowledge spillovers in the context of a Neoclassical Growth Model. Second, we apply novel estimation methods pertaining to the spatial econometrics literature introducing a spatial Durbin panel data model based on instrumental variables and maximum-likelihood estimation. Our model makes it possible to analyse, in terms of convergence, the results obtained in Spanish regions with the policies implemented during the period 1980–2011. The results support the idea that education and fiscal policies have a positive effect on regional development and cohesion. Therefore, we can conclude that it is possible to obtain better results for regional convergence with higher rates of public investment in education and tax revenues. We also obtain interesting results that confirm the existence of spillover effects in economic growth and public policies, identifying their magnitude and significance.