Miracle-dz/UniFAR-FTUs huggingface dataset:
High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring

Sevoflurane is the most commonly used volatile anesthetic during pregnancy. The viability of neural stem cells directly affects the development of the brain. However, it is unknown whether the use of sevoflurane during the second trimester affects the survival of fetal neural stem cells. Therefore, in this study, we investigated whether exposure to sevoflurane in mid-gestation induces apoptosis of neural stem cells and behavioral abnormalities. On gestational day 14, pregnant rats were anesthetized with 2% or 3.5% sevoflurane for 2 hours. The offspring were weaned at 28 days and subjected to the Morris water maze test. The brains were harvested to examine neural stem cell apoptosis by immunofluorescence and to measure Nestin and SOX-2 levels by western blot assay at 6, 24 and 48 hours after anesthesia as well as on postnatal day (P) 0, 14 and 28. Vascular endothelial growth factor (VEGF) and phosphoinositide 3-kinase (PI3K)/AKT pathway protein levels in fetal brain at 6 hours after anesthesia were assessed by western blot assay. Exposure to high-concentration (3.5%) sevoflurane during mid-gestation increased escape latency and path length to the platform, and it reduced the average duration spent in the target quadrant and platform crossing times. At 6, 24 and 48 hours after anesthesia and at P0, P14 and P28, the percentage of Nestin/terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells was increased, but Nestin and SOX-2 protein levels were decreased in the hippocampus of the offspring. At 6 hours after anesthesia, VEGF, PI3K and phospho-AKT (p-AKT) levels were decreased in the fetal brain. These changes were not observed in animals given low-concentration (2%) sevoflurane exposure. Together, our findings indicate that exposure to a high concentration of sevoflurane (3.5%) in mid-gestation decreases VEGF, PI3K and p-AKT protein levels and induces neural stem cell apoptosis, thereby causing learning and memory dysfunction in the offspring.
M-Calpain Activation Facilitates Seizure Induced KCC2 Down Regulation

Potassium chloride co-transporter 2 (KCC2), a major chloride transporter that maintains GABAA receptor inhibition in mature mammalian neurons, is down-regulated in the hippocampus during epileptogenesis. Impaired KCC2 function accelerates or facilitates seizure onset. Calpain, with two main subtypes of m- and μ-calpain, is a Ca2+-dependent cysteine protease that mediates the nonlysosomal degradation of KCC2. Although recent studies have demonstrated that calpain inhibitors exert antiepileptic and neuroprotective effects in animal models of acute and chronic epilepsy, whether calpain activation affects seizure induction through KCC2 degradation remains unknown. Our results showed that: (1) Blockade of calpain by non-selective calpain inhibitor MDL-28170 prevented convulsant stimulation induced KCC2 downregulation, and reduced the incidence and the severity of pentylenetetrazole (PTZ) induced seizures. (2) m-calpain, but not μ-calpain, inhibitor mimicked MDL-28170 effect on preventing KCC2 downregulation. (3) Phosphorylation of m-calpain has been significantly enhanced during seizure onset, which was partly mediated by the calcium independent MAPK/ERK signaling pathway activation. (4) MAPK/ERK signaling blockade also had similar effect as total calpain blockade on both KCC2 downregulation and animal seizure induction. The results indicate that upregulated m-calpain activation by MAPK/ERK during convulsant stimulation down regulates both cytoplasm- and membrane KCC2, and in turn facilitates seizure induction. This finding may provide a foundation for the development of highly effective antiepileptic drugs targeting of m-calpain.
Quantification of the Underlying Mechanisms and Relationships Among Cancer, Metastasis, and Differentiation and Development

Recurrence and metastasis have been regarded as two of the greatest obstacles to cancer therapy. Cancer stem cells (CSCs) contribute to cancer development, with the distinctive features of recurrence and resistance to popular treatments such as drugs and chemotherapy. In addition, recent discoveries suggest that the epithelial mesenchymal transition (EMT) is an essential process in normal embryogenesis and tissue repair, as well as being a required step in cancer metastasis. Although there are many indications of the connections between metastasis and stem cells, these have often been studied separately or at most bi-laterally, not in an integrated way. In this study, we aimed to explore the global mechanisms and interrelationships among cancer, development, and metastasis, which are currently poorly understood. First, we constructed a core gene regulatory network containing specific genes and microRNAs of CSCs, EMT, and cancer. We uncovered seven distinct states emerging from the underlying landscape, denoted normal, premalignant, cancer, stem cell, CSC, lesion, and hyperplasia. Given the biological definition of each state, we also discuss the metastasis ability of each state. We show how and which types of cells can be transformed to a cancer state, and the connections among cancer, CSCs, and EMT. The barrier height and flux of the kinetic paths are explored to quantify how and which cells switch stochastically between the states. Our landscape model provides a quantitative approach to reveal the global mechanisms of cancer, development, and metastasis.
Empathy score among medical students in Mashhad, Iran: study of the Jefferson Scale of Physician Empathy

Background Empathy is one of the essential components of physician-patient relationship that has a significant effect on treatment outcomes. Objective The aim of this study was to assess the empathy score among medical students in Mashhad, Iran. Methods In this cross-sectional study in 2015, 624 medical students at Mashhad University of Medical Science (Iran) completed the Jefferson Scale of Physician Empathy (JSPE). Data were analyzed by SPSS ver. 16, using independent-samples t-test, Chi-square, MANOVA, Spearman correlation, and Confirmatory factor analysis. Results Of the 38.4% males and 65% females who participated in this study, the mean score of JSPE in the sample was 103.67 (±15.34) which was higher in women than in men. Also, the mean scores for each of the three factors of the scale were calculated. The total empathy score, compassionate care, and taking perspectives among different age groups were significant (p=0.000). Furthermore, students having high interest in their field were more empathic (p=0.008). Empathy of interns in relation to three areas of basic sciences (the first year, the second year and the first half of the third year), physiopathology (the second half of the third year, and the fourth year), and clinical trainings (the fifth year, and the first half of the sixth year), experienced significant reduction (p≤0.001). Conclusions This study showed that empathy was higher in women in their first medical year and who were of younger age. The overall rate of empathy in the basic sciences period was more than that in the clinical period. Therefore, the initial exposure to clinical education, especially patient education and empathy, has a very prominent effect on the ability of medical students.
Lexicosyntactic Inference in Neural Models

We investigate neural models’ ability to capture lexicosyntactic inferences: inferences triggered by the interaction of lexical and syntactic information. We take the task of event factuality prediction as a case study and build a factuality judgment dataset for all English clause-embedding verbs in various syntactic contexts. We use this dataset, which we make publicly available, to probe the behavior of current state-of-the-art neural systems, showing that these systems make certain systematic errors that are clearly visible through the lens of factuality prediction.
Changing the Game: A Micro Moving Target IPv6 Defense for the Internet of Things

This letter explores the uses of a micro moving target IPv6 defense (<inline-formula> <tex-math notation="LaTeX">$\mu $ </tex-math></inline-formula>MT6D). In this initial experiment we assess the power consumption overhead and detail the overall security benefits gained from use of this technique. Moving target defenses were seen as game changers in the security field and now we must change the game once more and look toward their application for IoT devices. With a need to provide privacy and a defense against targeted attacks on resource constrained devices that are a part of vital communication and control systems, <inline-formula> <tex-math notation="LaTeX">$\mu $ </tex-math></inline-formula>MT6D is a viable solution that we continue to develop and assess for future use.
Deciphering the Roles of PPARγ in Adipocytes via Dynamic Change of Transcription Complex

Peroxisome proliferator-activated receptor γ (PPARγ), a ligand-dependent transcription factor highly expressed in adipocytes, is a master regulator of adipogenesis and lipid storage, a central player in thermogenesis and an active modulator of lipid metabolism and insulin sensitivity. As a nuclear receptor governing numerous target genes, its specific signaling transduction relies on elegant transcriptional and post-translational regulations. Notably, in response to different metabolic stimuli, PPARγ recruits various cofactors and forms distinct transcriptional complexes that change dynamically in components and epigenetic modification to ensure specific signal transduction. Clinically, PPARγ activation via its full agonists, thiazolidinediones, has been shown to improve insulin sensitivity and induce browning of white fat, while undesirably induce weight gain, visceral obesity and other adverse effects. Thus, deciphering the combinatorial interactions between PPARγ and its transcriptional partners and their preferential regulatory network in the processes of development, function and senescence of adipocytes would provide us the molecular basis for developing novel partial agonists that promote benefits of PPARγ signaling without detrimental side effects. In this review, we discuss the dynamic components and precise regulatory mechanisms of the PPARγ-cofactors complexes in adipocytes, as well as perspectives in treating metabolic diseases via specific PPARγ signaling.
Away From Prying Eyes: Analyzing Usage and Understanding of Private Browsing

Previous research has suggested that people use the private browsing mode of their web browsers to conduct privacysensitive activities online, but have misconceptions about how it works and are likely to overestimate the protections it provides. To better understand how private browsing is used and whether users are at risk, we analyzed browsing data collected from over 450 participants of the Security Behavior Observatory (SBO), a panel of users consenting to researchers observing their daily computing behavior “in the wild” through software monitoring. We explored discrepancies between observed and self-reported private behaviors through a follow-up survey, distributed to both Mechanical Turk and SBO participants. The survey also allowed us to investigate why private browsing is used for certain activities. Our findings reveal that people use private browsing for practical and security reasons, beyond the expected privacy reasons. Additionally, the primary use cases for private browsing were consistent across the reported and empirical data, though there were discrepancies in how frequently private browsing is used for online activities. We conclude that private browsing does mitigate our participants’ concerns about their browsing activities being revealed to other users of their computer, but participants overestimate the protection from online tracking and targeted advertising.
Distinct Co-Modulation Rules of Synapses and Voltage-Gated Currents Coordinate Interactions of Multiple Neuromodulators

Multiple neuromodulators act in concert to shape the properties of neural circuits. Different neuromodulators usually activate distinct receptors but can have overlapping targets. Therefore, circuit output depends on neuromodulator interactions at shared targets, a poorly understood process. We explored quantitative rules of co-modulation of two principal targets of neuromodulation: synapses and voltage-gated ionic currents. In the stomatogastric ganglion of the male crab Cancer borealis, the neuropeptides proctolin (Proc) and the crustacean cardioactive peptide (CCAP) modulate synapses of the pyloric circuit and activate a voltage-gated current (IMI) in multiple neurons. We examined the validity of a simple dose-dependent quantitative rule, that co-modulation by Proc and CCAP is predicted by the linear sum of the individual effects of each modulator up to saturation. We found that this rule is valid for co-modulation of synapses, but not for the activation of IMI, in which co-modulation was sublinear. The predictions for the co-modulation of IMI activation were greatly improved if we assumed that the intracellular pathways activated by two peptide receptors inhibit one another. These findings suggest that the pathways activated by two neuromodulators could have distinct interactions, leading to distinct co-modulation rules for different targets even in the same neuron. Given the evolutionary conservation of neuromodulator receptors and signaling pathways, such distinct rules for co-modulation of different targets are likely to be common across neuronal circuits. SIGNIFICANCE STATEMENT We examine the quantitative rules of co-modulation at multiple shared targets, the first such characterization to our knowledge. Our results show that dose-dependent co-modulation of distinct targets in the same cells by the same two neuromodulators follows different rules: co-modulation of synaptic currents is linearly additive up to saturation, whereas co-modulation of the voltage-gated ionic current targeted in a single neuron is nonlinear, a mechanism that is likely generalizable. Given that all neural systems are multiply modulated and neuromodulators often act on shared targets, these findings and the methodology could guide studies to examine dynamic actions of neuromodulators at the biophysical and systems level in sensory and motor functions, sleep/wake regulation, and cognition.
Reed–Solomon Codes Over Small Fields With Constrained Generator Matrices

We give constructions of some special cases of <inline-formula> <tex-math notation="LaTeX">$[n,k]$ </tex-math></inline-formula> Reed–Solomon codes over finite fields of size at least <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$n+1$ </tex-math></inline-formula> whose generator matrices have constrained support. Furthermore, we consider a generalization of the GM-MDS conjecture proposed by Lovett in 2018. We show that Lovett’s conjecture is false in general and we specify when the conjecture is true.
EGFL7 promotes hepatocellular carcinoma cell proliferation and inhibits cell apoptosis through increasing CKS2 expression by activating Wnt/β‐catenin signaling

Epidermal growth factor‐like domain multiple 7 (EGFL7) is an important sport stimulating factor and motility related factors significantly enhanced the tumor cell metastasis and overexpressed in many cancers, including hepatocellular carcinoma (HCC), associated with tumorigenesis. However, the molecular mechanism by which EGFL7 regulates HCC cell proliferation and apoptosis and the correlation between EGFL7 and cyclin‐dependent kinases regulatory subunit 2 (CKS2), which is essential for biological function, have not fully explained. In this study, EGFL7 and CKS2 expression in patients with HCC was measured by real‐time polymerase chain reaction and immunohistochemistry. After HCC cells respectively transfected with pLKO.1‐EGFL7‐shRNA, pLVX‐Puro‐EGFL7 recombined vector or CKS2 small interfering RNA, cell counting kit‐8 and flow cytometry was performed to examine the cell proliferation and apoptosis, respectively, and the expression of β‐catenin, CKS2, CDK2, and cleaved caspase‐3 was measured by Western blot analysis. We found that EGFL7 and CKS2 were overexpressed in HCC tissues and a positive correlation was found between them. EGFL7 knockdown markedly inhibited proliferation and promoted apoptosis of HCC cells, along with decreased expression of CKS2 and CDK2, but increased cleaved caspase‐3 expression, while EGFL7 overexpression showed an opposite effect. EGFL7 silencing in nude mice also showed decreased tumor growth and altered protein expression similar to its effect in HCC cells in vitro. Importantly, CKS2 silencing significantly inhibited EGFL7‐induced HCC cell proliferation and protein expression, and Wnt/β‐catenin signaling pathway inhibitor IWR‐1‐endo significantly inhibited CKS2 expression in HCC cells. Taken together, EGFL7 promotes HCC cell proliferation and inhibits cell apoptosis through increasing CKS2 expression by activating Wnt/β‐catenin signaling.
Molecular characterization of lung adenocarcinoma: A potential four–long noncoding RNA prognostic signature

Lung adenocarcinoma (LUAD), mainly originated in lung glandular cells, is the most frequent pathological type of lung cancer and the 5‐year survival rate of LUAD patients is still very low. Therefore, we aim to identify a long noncoding RNA (lncRNA)–related signature as the sensitive and novel prognostic biomarkers.
Polyphenols from brown alga, Padina boergesenii (Allendar & Kraft) decelerates renal cancer growth involving cell cycle arrest and induction of apoptosis in renal carcinoma cells

In our previous work, we assessed the ameliorative effect of crude extract from Padina boergesenii. In this report, we have extended these study by fractionating the methanol extract with methanol:ethylacetate (1:3,v/v) (MME‐F) and assessed the cytotoxic effect of MME‐F fraction in human renal carcinoma cell lines (A498 and ACHN). The fraction had time‐and dose‐dependent inhibition of cancer cell proliferation, migration with deceleration of cancer growth at EC50—22.73 μg in A498 and 26.43 μg in ACHN cells. Cells treated at EC50 value 25 μg displayed twofold greater ability to induce early and late stage of apoptosis. The cells treated with polyphenolic fraction (MME‐F) induced cell cycle arrest at G2/M phase. HPLC/DAD chromatographic procedures quantified polyphenols from active fraction (MME‐F). These data revealed the functional activity of polyphenols from brown alga, P. boergesenii as a potent inhibitor of cancer proliferation with induction of apoptosis, it suggest their applicability in preventing cancer metastasis.
Bragg-Grating-Based Photonic Strain and Temperature Sensor Foils Realized Using Imprinting and Operating at Very Near Infrared Wavelengths

Thin and flexible sensor foils are very suitable for unobtrusive integration with mechanical structures and allow monitoring for example strain and temperature while minimally interfering with the operation of those structures. Electrical strain gages have long been used for this purpose, but optical strain sensors based on Bragg gratings are gaining importance because of their improved accuracy, insusceptibility to electromagnetic interference, and multiplexing capability, thereby drastically reducing the amount of interconnection cables required. This paper reports on thin polymer sensor foils that can be used as photonic strain gage or temperature sensors, using several Bragg grating sensors multiplexed in a single polymer waveguide. Compared to commercially available optical fibers with Bragg grating sensors, our planar approach allows fabricating multiple, closely spaced sensors in well-defined directions in the same plane realizing photonic strain gage rosettes. While most of the reported Bragg grating sensors operate around a wavelength of 1550 nm, the sensors in the current paper operate around a wavelength of 850 nm, where the material losses are the lowest. This was accomplished by imprinting gratings with pitches 280 nm, 285 nm, and 290 nm at the core-cladding interface of an imprinted single mode waveguide with cross-sectional dimensions 3 × 3 µm2. We show that it is possible to realize high-quality imprinted single mode waveguides, with gratings, having only a very thin residual layer which is important to limit bend losses or cross-talk with neighboring waveguides. The strain and temperature sensitivity of the Bragg grating sensors was found to be 0.85 pm/µε and −150 pm/°C, respectively. These values correspond well with those of previously reported sensors based on the same materials but operating around 1550 nm, taking into account that sensitivity scales with the wavelength.
Transcriptome mining of non‐BRCA1/A2 and BRCA1/A2 familial breast cancer

About 10% of all breast cancer cases are the familial type. Mutations in two highly penetrance breast cancer susceptibility genes, BRCA1 and BRCA2, can only explain 20% to 25% of genetic susceptibility to breast cancer, and most familial breast cancer cases have intact BRCA1 and BRCA2 genes that refer to non‐BRCA1/A2 or BRCAX familial breast cancer. Despite extensive studies, more than 50% of genetic susceptibility to breast cancer remained to be disclosed. Finding the differences between these two types of breast cancer (non‐BRCA1/A2 and BRCA1/A2) at genomic, transcriptomic, and proteomic levels can help us to elucidate fundamental molecular processes and develope more promising therapeutic targets. Here, we used expression data of 391 patients with familial breast cancer including 195 non‐BRCA1/A2 and 196 BRCA1 and/or BRCA2 cases from four independent studies by means of meta‐analysis to find differences in gene expression signature between these two types of familial breast cancer. As well as, we applied comprehensive network analysis to find crucial protein complexes and regulators for each condition. Our results revealed significant overexpression of cell cycle processes in BRCA1/A2 patients and significant overexpression of estrogen axis in non‐BRCA1/A2 patients. Moreover, we found FOXM1 as the central regulator of cell cycle processes and GATA3, FOXA1, and ESR1 as the main regulators of estrogen axis.
Interlimb Generalization of Learned Bayesian Visuomotor Prior Occurs in Extrinsic Coordinates

Visual Abstract Recent work suggests that the brain represents probability distributions and performs Bayesian integration during sensorimotor learning. However, our understanding of the neural representation of this learning remains limited. To begin to address this, we performed two experiments. In the first experiment, we replicated the key behavioral findings of Körding and Wolpert (2004), demonstrating that humans can perform in a Bayes-optimal manner by combining information about their own sensory uncertainty and a statistical distribution of lateral shifts encountered in a visuomotor adaptation task. In the second experiment, we extended these findings by testing whether visuomotor learning occurring during the same task generalizes from one limb to the other, and relatedly, whether this learning is represented in an extrinsic or intrinsic reference frame. We found that the learned mean of the distribution of visuomotor shifts generalizes to the opposite limb only when the perturbation is congruent in extrinsic coordinates, indicating that the underlying representation of learning acquired during training is available to the untrained limb and is coded in an extrinsic reference frame.
The impact of user experience levels on web credibility judgments

Users judge the credibility of websites while browsing for information. The criteria that influence how they judge the credibility depend on many factors. In this study we found that computer expertise had a strong impact on what criteria users used in their credibility judgments. Participants evaluated websites they found while searching and described their credibility evaluation process. The criteria identified from their evaluations differed between novice and intermediate/expert users.