Miracle-dz/UniFAR-FTUs huggingface dataset:
BMP Signaling in the Development and Regeneration of Cranium Bones and Maintenance of Calvarial Stem Cells

The bone morphogenetic protein (BMP) signaling pathway is highly conserved across many species, and its importance for the patterning of the skeletal system has been demonstrated. A disrupted BMP signaling pathway results in severe skeletal defects. Murine calvaria has been identified to have dual-tissue lineages, namely, the cranial neural-crest cells and the paraxial mesoderm. Modulations of the BMP signaling pathway have been demonstrated to be significant in determining calvarial osteogenic potentials and ossification in vitro and in vivo. More importantly, the BMP signaling pathway plays a role in the maintenance of the homeostasis of the calvarial stem cells, indicating a potential clinic significance in calvarial bone and in expediting regeneration. Following the inherent evidence of BMP signaling in craniofacial biology, we summarize recent discoveries relating to BMP signaling in the development of calvarial structures, functions of the suture stem cells and their niche and regeneration. This review will not only provide a better understanding of BMP signaling in cranial biology, but also exhibit the molecular targets of BMP signaling that possess clinical potential for tissue regeneration.
Allergic Reactions and Immunity in Response to Tick Salivary Biogenic Substances and Red Meat Consumption in the Zebrafish Model

Ticks are arthropod ectoparasite vectors of pathogens and the cause of allergic reactions affecting human health worldwide. In humans, tick bites can induce high levels of immunoglobulin E antibodies against the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) present in glycoproteins and glycolipids from tick saliva that mediate anaphylactic reactions known as the alpha-Gal syndrome (AGS) or red meat allergy. In this study, a new animal model was developed using zebrafish for the study of allergic reactions and the immune mechanisms in response to tick salivary biogenic substances and red meat consumption. The results showed allergic hemorrhagic anaphylactic-type reactions and abnormal behavior patterns likely in response to tick salivary toxic and anticoagulant biogenic compounds different from α-Gal. However, the results showed that only zebrafish previously exposed to tick saliva developed allergic reactions to red meat consumption with rapid desensitization and tolerance. These allergic reactions were associated with tissue-specific Toll-like receptor-mediated responses in types 1 and 2 T helper cells (TH1 and TH2) with a possible role for basophils in response to tick saliva. These results support previously proposed immune mechanisms triggering the AGS and provided evidence for new mechanisms also potentially involved in the AGS. These results support the use of the zebrafish animal model for the study of the AGS and other tick-borne allergies.
A New Multivariable Grey Convolution Model Based on Simpson's Rule and Its Applications

Accurate estimations can provide a solid basis for decision-making and policy-making that have experienced some kind of complication and uncertainty. Accordingly, a multivariable grey convolution model (GMC (1, n )) having correct solutions is put forward to deal with such complicated and uncertain issues, instead of the incorrect multivariable grey model (GM (1, n )). However, the conventional approach to computing background values of the GMC (1, n ) model is inaccurate, and this model’s forecasting accuracy cannot be expected. Thereby, the drawback analysis of the GMC (1, n ) model is conducted with mathematical reasoning, which can explain why this model is inaccurate in some applications. In order to eliminate the drawbacks, a new optimized GMC (1, n ), shorted for OGMC (1, n ), is proposed, whose background values are calculated based on Simpson’ rule that is able to efficiently approximate the integration of a function. Furthermore, its extended version that uses the Gaussian rule to discretize the convolution integral, abbreviated as OGMC G (1, n ), is proposed to further enhance the model’s forecasting ability. In general, these two optimized models have such advantages as simplified structure, consistent forecasting performance, and satisfactory efficiency. Three empirical studies are carried out for verifying the above advantages of the optimized model, compared with the conventional GMC (1, n ), GMC G (1, n ), GM (1, n ), and DGM (1, n ) models. Results show that the new background values can effectively be calculated based on Simpson’s rule, and the optimized models significantly outperform other competing models in most cases.
T Telomere-Subtelomere-Telomerase System

For aging, defined as age-related decreasing fitness (or increasing mortality), there are two opposite explanations. They are mutually incompatible, radically different and with so many diverse assumptions and implications that may deserve the definition of distinct “paradigms” (Libertini 2015a) in the meaning proposed by Kuhn (1962). The first paradigm, defined as the “nonadaptive or non-programmed aging paradigm,” justifies aging as the cumulative effect of many degenerative factors that natural selection cannot sufficiently oppose (mutation accumulation, antagonistic pleiotropy, disposable soma, and damage accumulation hypotheses [Libertini 2015a, b]). The second paradigm, defined as the “adaptive or programmed aging paradigm,” explains aging as a physiological phenomenon evolutionarily favoured in terms of supra-individual natural selection (Libertini 2015a). For this paradigm, aging is a form of phenoptosis (Skulachev 1997; Libertini 2012), i.e., “programmed death of an organism” (Skulachev 1999, p. 1418), which is a very common type of phenomena in the biological world, well known as physiological events favored and modeled by natural selection (Finch 1990). An important and opposite implication of the two paradigms is that: (1) according to the nonadaptive aging paradigm, senescence cannot be caused by specific genetically determined and regulated mechanisms, and (2) on the contrary, according to the adaptive aging paradigm, such mechanisms must exist, and indeed their existence is indispensable in order to consider this paradigm valid (Libertini 2015a). Although the nonadaptive aging paradigm still represents the group of theories presented as the
Study of Oxidant (MDA) and Antioxidants (SOD & Vitamin E) in Hypertensive Patients and Normotensive Individuals

This study was undertaken to evaluate the serum lev els of Oxidant (MDA) & antioxidant (SOD & Vitamin E) and compare oxidative stress (MDA) level among normotensive and hypertensive subjects. Oxidative stress has been re lationship with mechanisms of EH (essential hypertension). A total number of 70 subjects were taken including both sex (Men and Women) between the ages of 35-70 years taken in this study. Exclus ion criteria were chronic diseases, alcohol consume r, obesity, smoking/tobacco con- sumer and current use of any medication. Antioxidant enzymes activity and lipid peroxidation (malondia ldehyde) were determined in serum. In 70 subjects out of 35 were found as an co ntrols normotensive individuals and the cases 35 hy pertensive patients. Serum MDA levels were highly significantly elevated in hypertensive patients in compared to normotensive individuals (4.39±0.98 µmol/l vs 1.51±0.70µmol/l and p < 0.0001). SOD acts as an ant ioxidant was highly significantly decrease in hyper tensive patients in compared to normotensive individuals (0.44±0.06U/mg protein/min vs 0.96±0.04 U/mg protein/min and p <0.0001). Vitamin E, which acts as a biomarker of hypertensive was significantly higher decrease in hypertensive in compared to normotensive individuals (0.69±0.08 vs 1.06±0.25 and p < 0.001). These findings demonst rate the strong association of SOD and Vitamin E le vel decrease in hypertensive patients and by MDA level increase in hypertensive patients. Oxidative stress in hypertensive patients increasing over time may play a role in the improvement of atherosclerosis and card iovascular disease, should be considered in further research.
Contracts Adjustment under Bilateral Information Updating in a Supply Chain

This paper investigates contracts adjustment between one manufacturer and one retailer under bilateral information updating. The manufacturer incurs uncertain production cost and the retailer faces uncertain demand, but they can acquire independent signals to update production cost and demand, respectively. They commit an initial agreement on an initial wholesale price, minimum order quantity, and information sharing as well as the transfer payment and decisions adjustment when information is updated. We find that due to the joint impact of production cost variation and market variation, the manufacturer may not decrease (increase) her wholesale price when the updated production cost is lower (higher) than expected. The retailer places an additional order even if the wholesale price rises when the market outlook is good, but places an order with the minimum order quantity even if the wholesale price falls when the market outlook is bad. Secondly, for a certain level of information accuracy of the production cost and market demand, the retailer is always better off with information updating, but the manufacturer may be worse off with information updating when facing a bad market outlook. Thirdly, when information accuracy of the production cost and market demand varies, the manufacturer only benefits from a high accuracy of production cost. Profits of the retailer and the supply chain are increasing (decreasing) with accuracy of production cost if the updated production cost is larger (smaller) than expected.
Short‐text feature expansion and classification based on nonnegative matrix factorization

In this paper, a non‐negative matrix factorization feature expansion (NMFFE) approach was proposed to overcome the feature‐sparsity issue when expanding features of short‐text. First, we took the internal relationships of short texts and words into account when segmenting words from texts and constructing their relationship matrix. Second, we utilized the Dual regularization non‐negative matrix tri‐factorization (DNMTF) algorithm to obtain the words clustering indicator matrix, which was used to get the feature space by dimensionality reduction methods. Thirdly, words with close relationship were selected out from the feature space and added into the short‐text to solve the sparsity issue. The experimental results showed that the accuracy of short text classification of our NMFFE algorithm increased 25.77%, 10.89%, and 1.79% on three data sets: Web snippets, Twitter sports, and AGnews, respectively compared with the Word2Vec algorithm and Char‐CNN algorithm. It indicated that the NMFFE algorithm was better than the BOW algorithm and the Char‐CNN algorithm in terms of classification accuracy and algorithm robustness.
City rebranding through co-creation with the residents - the case of Amsterdam

Purpose: There has been a lot of research about city rebranding, however in the realm of tourists and businesses as stakeholders. The aim of this study is to investigate the involvement of residents in the city brand as part of rebranding. This is an explicit and explorative research in how residents co-create their city during Amsterdam’s rebranding. Materials and Methods: Data for this research were collected through two different methods. The primary research method was netnography so as to investigate the involvement as well as the attitudes and beliefs of the residents for the city rebranding efforts of the city’s brand managers through the gathering and analysis of the different efforts found online. Moreover, two interviews were conducted with city brand managers and the sample was selected from the organization “Amsterdam Marketing”. The purpose was to gain a deeper understanding on their incentives when they attempt to encompass the residents within city’s rebranding. Conclusions: It was concluded that residents are mostly willing to co-create with city brand managers and other parties when they are unhappy with the activities that try to shape the city brand. Hence, they attempt to express their negativity and dissatisfaction about their city. In order for them to participate more in the several activities, it is recommended that residents become more aware and active about what the city offers to them. The residents’ place satisfaction model is found to connect with branding, hence the model was adapted to the found relations among the managers, the residents and other parties. This new model includes the concepts of co-creation and place brand satisfaction. (Less)
An Extended EDAS Method for Multicriteria Decision-Making Based on Multivalued Neutrosophic Sets

Neutrosophic set (NS) is a generalization of intuitionistic fuzzy set (IFS). It depicts not only the incomplete information but also the indeterminate information and inconsistent information which exist commonly in belief systems. In this paper, the evaluation based on distance from average solution (EDAS) method is extended to handle multicriteria decision-making problems with multivalued neutrosophic numbers (MVNNs). The average solution under all the criteria is calculated by the proposed convex weighted average operator of MVNNs. Then, the positive distance and the negative distance from each solution to the average solution are calculated, and the comprehensive evaluations of alternatives are obtained by integrating two kinds of distance values to get the ranking result. Finally, the rationality and efficiency of the proposed method are shown by the parameter analysis and comparisons with some existing methods.
Inference of nonlinear receptive field subunits with spike-triggered clustering

Responses of sensory neurons are often modeled using a weighted combination of rectified linear subunits. Since these subunits often cannot be measured directly, a flexible method is needed to infer their properties from the responses of downstream neurons. We present a method for maximum likelihood estimation of subunits by soft-clustering spike-triggered stimuli, and demonstrate its effectiveness in visual neurons. For parasol retinal ganglion cells in macaque retina, estimated subunits partitioned the receptive field into compact regions, likely representing aggregated bipolar cell inputs. Joint clustering revealed shared subunits between neighboring cells, producing a parsimonious population model. Closed-loop validation, using stimuli lying in the null space of the linear receptive field, revealed stronger nonlinearities in OFF cells than ON cells. Responses to natural images, jittered to emulate fixational eye movements, were accurately predicted by the subunit model. Finally, the generality of the approach was demonstrated in macaque V1 neurons.
Cardiovascular Regulation by the Neuronal BBSome

Supplemental Digital Content is available in the text. The BBSome, a complex of 8 BBS (Bardet-Biedl syndrome) proteins known for its role in the control of cilia function and other cellular processes, has been implicated in blood pressure control, but the underlying mechanisms are not fully understood. Here, we show that neuronal BBSome plays an important role in blood pressure regulation. Targeted inactivation of the BBSome in the nervous system through Bbs1 gene deletion causes sympathetically mediated increase in blood pressure in mice. This phenotype is reproduced by selective ablation of the Bbs1 gene from the LRb (leptin receptor)-expressing neurons. Strikingly, the well-known role of the BBSome in the regulation of cilia formation and function is unlikely to account for the prohypertensive effect of BBSome inactivation as disruption of the IFT (intraflagellar transport) machinery required for ciliogenesis by deleting the Ift88 gene in LRb neurons had no effect on arterial pressure and sympathetic nerve activity. Furthermore, we found that Bbs1 gene deletion from AgRP (agouti-related protein) neurons or POMC (proopiomelanocortin) neurons increased renal and splanchnic sympathetic nerve activity without altering blood pressure. This lack of blood pressure increase despite the sympathetic overdrive may be explained by vascular adrenergic desensitization as indicated by the reduced vascular contractile response evoked by phenylephrine and the decreased expression of adrenergic receptors. Our results identify the neuronal BBSome as a new player in hemodynamic, sympathetic, and vascular regulation, in a manner independent of cilia.
Nutritional status among women with preeclampsia and healthy pregnant women

Aim: Pregnancy-onset hypertension and proteinuria is defined as preeclampsia (PE). PE affects 2% to 8% of all pregnancies and causes both maternal and perinatal morbidity and mortality. The aim of the present study was to compare the nutritional status of women with PE with healthy pregnant. Methods: This research was carried out at local women health care, education and research hospital in Ankara, Turkey. Thirty pregnant women who were being followed up with the diagnosis of preeclampsia and 30 healthy pregnant women as a control group involved in the study. All participants were given an introduction to the research and a questionnaire regarding their nutritional status and habits. Anthropometric measurements and blood samples were taken. Results: Weight gain during pregnancy, gestational age and fetal birth weight were found to be significantly lower in preeclamptic pregnant women than healthy pregnant women (p<0.001). On the other hand, pre-pregnancy BMI was significantly higher in the preeclamptic group (p<0.001). Women with PE had higher blood pressure, fasting blood glucose concentration, serum total cholesterol, triglyceride and homocystein levels compared to healthy pregnant women (p<0.05). Average daily energy, carbohydrates, fiber, vitamin B6 intakes were significantly different between preeclamptic and healthy pregnant women (p<0.05). There were no statistically significant differences among the groups of the micronutrients except for vitamin B6. Conclusion: Further research that examines the effects of nutritional habits and nutritional supplementation on development of preeclampsia is needed in order to prevent hypertensive disorders in pregnancy.
Treatment patterns and medical cost of systemic lupus erythematosus patients in Japan: a retrospective claims database study

Abstract Aim: To describe the characteristics and medication treatment patterns, healthcare resource utilization (HRU), and associated costs in Japanese patients with systemic lupus erythematosus (SLE). Methods: Claims data from the Japan Medical Data Center (JMDC) database were used to identify patients with SLE-related claims from 2010 to 2017. Algorithms were developed to retrospectively categorize patients by disease severity, treatment experience, and SLE-related manifestations such as lupus nephritis and central nervous system lupus. Descriptive and multivariate analyses were used to describe treatment pattern and estimate HRU and associated costs for the SLE cohort overall and by disease severity and complications. Results: Among 4,733 eligible patients, 2,072 (43.8%) were treatment naïve, 2,214 (46.8%) were previously treated for SLE, and 447 (9.4%) did not receive any treatment. Mean (SD) age of the total SLE cohort was 45.2 (13.1) years and mean (SD) follow-up duration was 1,137.3 (758.0) d. Based on disease severity, 1,383 (29.2%) patients had mild, 2,619 (55.3%) patients had moderate, and 731 (15.4%) patients had severe SLE. Patients on glucocorticoids (both oral and parenteral) received add-on medications the most (35.5%, p < .001). Mean annual cost per SLE patient in the post-index period, inclusive of hospitalizations, outpatient visits, and pharmacy was ¥436,836; ¥1,010,772; and ¥2,136,780 for patients with mild, moderate, and severe SLE, respectively. Limitations: The database only captured information on patients up to 75 years of age. Due to the nature of the database, biases regarding conditions that attribute to the spectrum of SLE severity, flare incidences, or individual physical status cannot be ruled out. Conclusions: This study describes the treatment patterns and economic burden experienced by Japanese patients with SLE. The results highlight an unmet need to derive better treatment strategies for patients with SLE to effectively address the disease burden in Japan.
The macrolide drug erythromycin does not protect the hERG channel from inhibition by thioridazine and terfenadine

The macrolide antibiotic erythromycin has been associated with QT interval prolongation and inhibition of the hERG‐encoded channels responsible for the rapid delayed rectifier K+ current I(Kr). It has been suggested that low concentrations of erythromycin may have a protective effect against hERG block and associated drug‐induced arrhythmia by reducing the affinity of the pore‐binding site for high potency hERG inhibitors. This study aimed to explore further the notion of a potentially protective effect of erythromycin. Whole‐cell patch‐clamp experiments were performed in which hERG‐expressing mammalian (Human Embryonic Kidney; HEK) cells were preincubated with low to moderate concentrations of erythromycin (3 or 30 µM) prior to whole‐cell patch clamp recordings of hERG current (IhERG) at 37°C. In contrast to a previous report, exposure to low concentrations of erythromycin did not reduce pharmacological sensitivity of hERG to the antipsychotic thioridazine and antihistamine terfenadine. The IC50 value for IhERG tail inhibition by terfenadine was decreased by ~32‐fold in the presence of 3 µM erythromycin (p < .05 vs. no preincubation). Sensitivity to thioridazine remained unchanged (p > .05 vs. no preincubation). The effects of low concentrations of erythromycin were investigated for a series of pore blocking drugs, and the results obtained were consistent with additive and/or synergistic effects. Experiments with the externally acting blocker BeKm‐1 on WT hERG and a pore mutant (F656V) were used to explore the location of the binding site for erythromycin. Our data are inconsistent with the use of erythromycin for the management of drug‐induced QT prolongation.
Positive Hepatitis B Core Antibody Is Associated With Cirrhosis and Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.

OBJECTIVES Previous exposure to hepatitis B virus (HBV) may increase the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. We aim to study the impact of previous HBV infection on the severity and outcomes of patients with nonalcoholic fatty liver disease (NAFLD). METHODS This was a multicenter study of 489 patients with biopsy-proven NAFLD and 69 patients with NAFLD-related or cryptogenic HCC. Antihepatitis B core antibody (anti-HBc) was used to detect the previous HBV infection. RESULTS In the biopsy cohort, positive anti-HBc was associated with lower steatosis grade but higher fibrosis stage. 18.8% and 7.5% of patients with positive and negative anti-HBc had cirrhosis, respectively (P < 0.001). The association between anti-HBc and cirrhosis remained significant after adjusting for age and metabolic factors (adjusted odds ratio 2.232; 95% confidence interval, 1.202-4.147). At a mean follow-up of 6.2 years, patients with positive anti-HBc had a higher incidence of HCC or cirrhotic complications (6.5% vs 2.2%; P = 0.039). Among patients with NAFLD-related or cryptogenic HCC, 73.9% had positive anti-HBc. None of the patients had positive serum HBV DNA. By contrast, antihepatitis B surface antibody did not correlate with histological severity. DISCUSSION Positive anti-HBc is associated with cirrhosis and possibly HCC and cirrhotic complications in patients with NAFLD. Because a significant proportion of NAFLD-related HCC may develop in noncirrhotic patients, future studies should define the role of anti-HBc in selecting noncirrhotic patients with NAFLD for HCC surveillance.