Miracle-dz/UniFAR-FTUs huggingface dataset:
Polar Infection of Echovirus-30 Causes Differential Barrier Affection and Gene Regulation at the Blood–Cerebrospinal Fluid Barrier

Echovirus-30 (E-30) is responsible for the extensive global outbreaks of meningitis in children. To gain access to the central nervous system, E-30 first has to cross the epithelial blood–cerebrospinal fluid barrier. Several meningitis causing bacteria preferentially infect human choroid plexus papilloma (HIBCPP) cells in a polar fashion from the basolateral cell side. Here, we investigated the polar infection of HIBCPP cells with E-30. Both apical and basolateral infections caused a significant decrease in the transepithelial electrical resistance of HIBCPP cells. However, to reach the same impact on the barrier properties, the multiplicity of infection of the apical side had to be higher than that of the basolateral infection. Furthermore, the number of infected cells at respective time-points after basolateral infection was significantly higher compared to apical infection. Cytotoxic effects of E-30 on HIBCPP cells during basolateral infection were observed following prolonged infection and appeared more drastically compared to the apical infection. Gene expression profiles determined by massive analysis of cDNA ends revealed distinct regulation of specific genes depending on the side of HIBCPP cells’ infection. Altogether, our data highlights the polar effects of E-30 infection in a human in vitro model of the blood–cerebrospinal fluid barrier leading to central nervous system inflammation.
STAT3, the Challenge for Chemotherapeutic and Radiotherapeutic Efficacy

Simple Summary STAT3, an oncogene, contributes to insensitivity of chemotherapy and radiotherapy in tumor, reduces the clinical efficacy. Meanwhile, STAT3β, a STAT3 splicing isoform, is related to the inhibition of tumor growth and chemosensitivity. STAT3 may become a potential target to overcome the chemo(radio)resistance, which benefit for developing novel drugs targeting STAT3 or alternative splicing regulators. Abstract Chemoradiotherapy is one of the most effective and extensively used strategies for cancer treatment. Signal transducer and activator of transcription 3 (STAT3) regulates vital biological processes, such as cell proliferation and cell growth. It is constitutively activated in various cancers and limits the application of chemoradiotherapy. Accumulating evidence suggests that STAT3 regulates resistance to chemotherapy and radiotherapy and thereby impairs therapeutic efficacy by mediating its feedback loop and several target genes. The alternative splicing product STAT3β is often identified as a dominant-negative regulator, but it enhances sensitivity to chemotherapy and offers a new and challenging approach to reverse therapeutic resistance. We focus here on exploring the role of STAT3 in resistance to receptor tyrosine kinase (RTK) inhibitors and radiotherapy, outlining the potential of targeting STAT3 to overcome chemo(radio)resistance for improving clinical outcomes, and evaluating the importance of STAT3β as a potential therapeutic approach to overcomes chemo(radio)resistance. In this review, we discuss some new insights into the effect of STAT3 and its subtype STAT3β on chemoradiotherapy sensitivity, and we explore how these insights influence clinical treatment and drug development for cancer.
Changing Emotions About Fukushima Related to the Fukushima Nuclear Power Station Accident—How Rumors Determined People’s Attitudes: Social Media Sentiment Analysis

Background Public interest in radiation rose after the Tokyo Electric Power Company (TEPCO) Fukushima Daiichi Nuclear Power Station accident was caused by an earthquake off the Pacific coast of Tohoku on March 11, 2011. Various reports on the accident and radiation were spread by the mass media, and people displayed their emotional reactions, which were thought to be related to information about the Fukushima accident, on Twitter, Facebook, and other social networking sites. Fears about radiation were spread as well, leading to harmful rumors about Fukushima and the refusal to test children for radiation. It is believed that identifying the process by which people emotionally responded to this information, and hence became gripped by an increased aversion to Fukushima, might be useful in risk communication when similar disasters and accidents occur in the future. There are few studies surveying how people feel about radiation in Fukushima and other regions in an unbiased form. Objective The purpose of this study is to identify how the feelings of local residents toward radiation changed according to Twitter. Methods We used approximately 19 million tweets in Japanese containing the words “radiation” (放射線), “radioactivity” (放射能), and “radioactive substances” (放射性物質) that were posted to Twitter over a 1-year period following the Fukushima nuclear accident. We used regional identifiers contained in tweets (ie, nouns, proper nouns, place names, postal codes, and telephone numbers) to categorize them according to their prefecture, and then analyzed the feelings toward those prefectures from the semantic orientation of the words contained in individual tweets (ie, positive impressions or negative impressions). Results Tweets about radiation increased soon after the earthquake and then decreased, and feelings about radiation trended positively. We determined that, on average, tweets associating Fukushima Prefecture with radiation show more positive feelings than those about other prefectures, but have trended negatively over time. We also found that as other tweets have trended positively, only bots and retweets about Fukushima Prefecture have trended negatively. Conclusions The number of tweets about radiation has decreased overall, and feelings about radiation have trended positively. However, the fact that tweets about Fukushima Prefecture trended negatively, despite decreasing in percentage, suggests that negative feelings toward Fukushima Prefecture have become more extreme. We found that while the bots and retweets that were not about Fukushima Prefecture gradually trended toward positive feelings, the bots and retweets about Fukushima Prefecture trended toward negative feelings.
Fabrication techniques for the preparation of orally administered insulin nanoparticles

Abstract The development of orally administered protein drugs is challenging due to their intrinsic unfavourable features, including large molecular size and poor chemical stability, both of which limit gastrointestinal (GI) absorption efficiency. Nanoparticles can overcome the GI barriers effectively and improve the oral bioavailability of proteins in the GI tract. They possess large surface area to volume ratio, and can facilitate the GI absorption of nanoparticles via the paracellular and transcellular routes. Nanoparticles can be prepared by various fabrication techniques that can encapsulate the fragile therapeutic proteins via hydrophobic bonding and electrostatic interaction. A desirable technique should involve minimal harsh conditions and encapsulate therapeutic proteins with preserved functionalities. The current review examines the characteristics of each preparation technique, and illustrates the examples of insulin-loaded nanoparticles that have been developed in each fabrication method. The following techniques, which include nanoprecipitation, hydrophobic conjugation, flash nanocomplexation, double emulsion, ionotropic gelation, and layer-by-layer adsorption, have been used to formulate ligand-modified nanoparticles for targeted delivery of insulin. Other techniques, including reduction, complex coacervation (polyelectrolyte complexation), hydrophobic ion pairing and emulsion solvent diffusion method, and sol-gel technology, were also discussed in the latter part of the review due to their extensive use in fabrication of insulin nanoparticles. This review also discusses the strategies that have been utilised during the formulation process to improve the stability and bioactivity of therapeutic proteins.
Room-temperature performance of 3 mm-thick cadmium-zinc-telluride pixel detectors with sub-millimetre pixelization.

Cadmium-zinc-telluride (CZT) pixel detectors represent a consolidated choice for the development of room-temperature spectroscopic X-ray imagers, finding important applications in medical imaging, often as detection modules of a variety of new SPECT and CT systems. Detectors with 3-5 mm thicknesses are able to efficiently detect X-rays up to 140 keV giving reasonable room-temperature energy resolution. In this work, the room-temperature performance of 3 mm-thick CZT pixel detectors, recently developed at IMEM/CNR of Parma (Italy), is presented. Sub-millimetre detector arrays with pixel pitch less than 500 µm were fabricated. The detectors are characterized by good room-temperature performance even at high bias voltage operation (6000 V cm-1), with energy resolutions (FWHM) of 3% (1.8 keV) and 1.6% (2 keV) at 59.5 keV and 122.1 keV, respectively. Charge-sharing investigations were performed with both uncollimated and collimated synchrotron X-ray beams with particular attention to recovering the charge losses at the inter-pixel gap region. High rate measurements demonstrated the absence of high-flux radiation-induced polarization phenomena up to 25 × 106 photons mm-2 s-1.
Au Nanoparticles-Doped Polymer All-Optical Switches Based on Photothermal Effects

This article demonstrated the Au nanoparticles-doped polymer all-optical switches based on photothermal effects. The Au nanoparticles have a strong photothermal effect, which would generate the inhomogeneous thermal field distributions in the waveguide under the laser irradiation. Meanwhile, the polymer materials have the characteristics of good compatibility with photothermal materials, low cost, high thermo-optical coefficient and flexibility. Therefore, the Au nanoparticles-doped polymer material can be applied in optically controlled optical switches with low power consumption, small device dimension and high integration. Moreover, the end-pumping method has a higher optical excitation efficiency, which can further reduce the power consumption of the device. Two kinds of all-optical switching devices have been designed including a base mode switch and a first-order mode switch. For the base mode switch, the power consumption and the rise/fall time were 2.05 mW and 17.3/106.9 μs, respectively at the wavelength of 650 nm. For the first-order mode switch, the power consumption and the rise/fall time were 0.5 mW and 10.2/74.9 μs, respectively at the wavelength of 532 nm. This all-optical switching device has the potential applications in all-optical networks, flexibility device and wearable technology fields.
Kinetic study and optimization of recombinant human tumor necrosis factor-alpha (rhTNF-α) production in Escherichia coli

Abstract Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that plays a major role in immune regulation, homeostatic function, and cellular organization. The present study was undertaken to overproduce recombinant human TNF-α (rhTNF-α) in Escherichia coli (E.coli) in high cell density culture. The use of a codon-optimized gene and strong promoter-based (T7) expression system, choice of Terrific Broth (TB) as medium, and subsequent optimization of culture conditions in shake flasks resulted in production of 0.95 g/L insoluble rhTNF-α comprising upto 50% of total cellular protein (TCP) The protein yield further increased upto 1.26 g/L in 1 L TB medium batch culture in bioreactor with the controlled temperature, pH, and dissolved oxygen. In a series of chemostats operated at dilution rates of 0.2 h−1, 0.3 h−1, 0.4 h−1 and 0.5 h−1 the specific growth rate (μ) positively correlated with specific yield (Yp / x ) and a maximum yield of 164 mg/g DCW was obtained at μ = 0.4 h−1 within 4 h post-induction. A fed-batch cultivation in TB with an exponential feeding profile (μ = ∼0.4 h−1) of concentrated feed resulted in an accumulation of 5.5 g/L of rhTNF-α within 14 h of cultivation which accounted for ∼29% of TCP.
Human Endogenous Retrovirus Expression Is Associated with Head and Neck Cancer and Differential Survival

Human endogenous retroviruses (HERVs) have been implicated in a variety of human diseases including cancers. However, technical challenges in analyzing HERV sequence data have limited locus-specific characterization of HERV expression. Here, we use the software Telescope (developed to identify expressed transposable elements from metatranscriptomic data) on 43 paired tumor and adjacent normal tissue samples from The Cancer Genome Atlas Program to produce the first locus-specific retrotranscriptome of head and neck cancer. Telescope identified over 3000 expressed HERVs in tumor and adjacent normal tissue, and 1078 HERVs were differentially expressed between the two tissue types. The majority of differentially expressed HERVs were expressed at a higher level in tumor tissue. Differentially expressed HERVs were enriched in members of the HERVH family. Hierarchical clustering based on HERV expression in tumor-adjacent normal tissue resulted in two distinct clusters with significantly different survival probability. Together, these results highlight the importance of future work on the role of HERVs across a range of cancers.
Gabapentin in pregnancy and the risk of adverse neonatal and maternal outcomes: A population-based cohort study nested in the US Medicaid Analytic eXtract dataset

Background Despite the widespread use, only sparse information is available on the safety of gabapentin during pregnancy. We sought to evaluate the association between gabapentin exposure during pregnancy and risk of adverse neonatal and maternal outcomes. Methods and findings Using the United States Medicaid Analytic eXtract (MAX) dataset, we conducted a population-based study of 1,753,865 Medicaid-eligible pregnancies between January 2000 and December 2013. We examined the risk of major congenital malformations and cardiac defects associated with gabapentin exposure during the first trimester (T1), and the risk of preeclampsia (PE), preterm birth (PTB), small for gestational age (SGA), and neonatal intensive care unit admission (NICUa) associated with gabapentin exposure early, late, or both early and late in pregnancy. Gabapentin-unexposed pregnancies served as the reference. We estimated relative risks (RRs) and 95% confidence intervals (CIs) using fine stratification on the propensity score (PS) to control for over 70 confounders (e.g., maternal age, race/ethnicity, indications for gabapentin, other pain conditions, hypertension, diabetes, use of opioids, and specific morphine equivalents). We identified 4,642 pregnancies exposed in T1 (mean age = 28 years; 69% white), 3,745 exposed in early pregnancy only (28 years; 67% white), 556 exposed in late pregnancy only (27 years; 60% white), and 1,275 exposed in both early and late pregnancy (29 years; 75% white). The reference group consisted of 1,744,447 unexposed pregnancies (24 years; 40% white). The adjusted RR for major malformations was 1.07 (95% CI 0.94–1.21, p = 0.33) and for cardiac defects 1.12 (0.89–1.40, p = 0.35). Requiring ≥2 gabapentin dispensings moved the RR to 1.40 (1.03–1.90, p = 0.03) for cardiac defects. There was a higher risk of preterm birth among women exposed to gabapentin either late (RR, 1.28 [1.08–1.52], p < 0.01) or both early and late in pregnancy (RR, 1.22 [1.09–1.36], p < 0.001), SGA among women exposed to gabapentin early (1.17 [1.02–1.33], p = 0.02), late (1.39 [1.01–1.91], p = 0.05), or both early and late in pregnancy (RR, 1.32 [1.08–1.60], p < 0.01), and NICU admission among women exposed to gabapentin both early and late in pregnancy (RR, 1.35 [1.20–1.52], p < 0.001). There was no higher risk of preeclampsia among women exposed to gabapentin after adjustment. Study limitations include the potential for residual confounding and exposure misclassification. Conclusions In this large population-based study, we did not find evidence for an association between gabapentin exposure during early pregnancy and major malformations overall, although there was some evidence of a higher risk of cardiac malformations. Maternal use of gabapentin, particularly late in pregnancy, was associated with a higher risk of PTB, SGA, and NICUa.
Fibroblast growth factor homologous factors tune arrhythmogenic late NaV1.5 current in calmodulin binding–deficient channels

The Ca2+-binding protein calmodulin has emerged as a pivotal player in tuning Na+ channel function, although its impact in vivo remains to be resolved. Here, we identify the role of calmodulin and the NaV1.5 interactome in regulating late Na+ current in cardiomyocytes. We created transgenic mice with cardiac-specific expression of human NaV1.5 channels with alanine substitutions for the IQ motif (IQ/AA). The mutations rendered the channels incapable of binding calmodulin to the C-terminus. The IQ/AA transgenic mice exhibited normal ventricular repolarization without arrhythmias and an absence of increased late Na+ current. In comparison, transgenic mice expressing a lidocaine-resistant (F1759A) human NaV1.5 demonstrated increased late Na+ current and prolonged repolarization in cardiomyocytes, with spontaneous arrhythmias. To determine regulatory factors that prevent late Na+ current for the IQ/AA mutant channel, we considered fibroblast growth factor homologous factors (FHFs), which are within the NaV1.5 proteomic subdomain shown by proximity labeling in transgenic mice expressing NaV1.5 conjugated to ascorbate peroxidase. We found that FGF13 diminished late current of the IQ/AA but not F1759A mutant cardiomyocytes, suggesting that endogenous FHFs may serve to prevent late Na+ current in mouse cardiomyocytes. Leveraging endogenous mechanisms may furnish an alternative avenue for developing novel pharmacology that selectively blunts late Na+ current.
Bonding Analysis of Compounds with Unusual Coordination of Carbon: Proposed Symmetric Systems with Six-Coordinate Carbon

The possibility of carbon tetravalence in geometries other than tetrahedral and of carbon hypervalence has been taken seriously since the 1970s. Computational modeling and subsequent experimental validation have established the existence of molecules with carbon atoms with planar tetravalence and as many as six objects in carbon’s coordination sphere. In this work, we develop insight into the nature of bonding to carbon in these unusual environs as provided by Bader’s Atoms in Molecules (AIM) analysis of the electron density, along with the electron localization function (ELF) and the non-covalent index (NCI). We review several well-established systems (spiropentadiene dication, hexamethyl benzene dication, dimethanospiro[2.2]octaplane dication, and 1,8-dimethoxy-9-dimethoxyanthracene cation) and propose new D2d–symmetric variants of a hexacoordinated species.
Neutralization of Lipocalin-2 Diminishes Stroke-Reperfusion Injury

Oxidative stress is a key contributor to the pathogenesis of stroke-reperfusion injury. Neuroinflammatory peptides released after ischemic stroke mediate reperfusion injury. Previous studies, including ours, have shown that lipocalin-2 (LCN2) is secreted in response to cerebral ischemia to promote reperfusion injury. Genetic deletion of LCN2 significantly reduces brain injury after stroke, suggesting that LCN2 is a mediator of reperfusion injury and a potential therapeutic target. Immunotherapy has the potential to harness neuroinflammatory responses and provides neuroprotection against stroke. Here we report that LCN2 was induced on the inner surface of cerebral endothelial cells, neutrophils, and astrocytes that gatekeep the blood–brain barrier (BBB) after stroke. LCN2 monoclonal antibody (mAb) specifically targeted LCN2 in vitro and in vivo, attenuating the induction of LCN2 and pro-inflammatory mediators (iNOS, IL-6, CCL2, and CCL9) after stroke. Administration of LCN2 mAb at 4 h after stroke significantly reduced neurological deficits, cerebral infarction, edema, BBB leakage, and infiltration of neutrophils. The binding epitope of LCN2 mAb was mapped to the β3 and β4 strands, which are responsible for maintaining the integrity of LCN2 cup-shaped structure. These data indicate that LCN2 can be pharmacologically targeted using a specific mAb to reduce reperfusion injury after stroke.
“Sometimes You Get Married on Facebook”: The Use of Social Media Among Nonmetropolitan Sexual and Gender Minority Youth

ABSTRACT Sexual and gender minority (SGM) youth experience risks due to their stigmatized SGM identities; however, supportive resources and people can mitigate these risks. In nonmetropolitan areas, SGM-affirming support may not be readily available. The internet and social media may be a way for SGM youth to access support and resources pertaining to their SGM identities, yet little research has been conducted in this area. This qualitative, exploratory study utilized in-depth interviews (N = 34) with nonmetropolitan SGM youth in one Midwestern state to better understand how they utilized the internet and social media related to their SGM identities. Grounded theory analysis revealed three categories of social media and internet usage among participants. Participants utilized the internet to establish a sense of community (access others, form relationships), express themselves (come out, vent), and access resources and information. These findings suggest important implications for practice and research.
Blind First-Order Perspective Distortion Correction Using Parallel Convolutional Neural Networks

In this work, we present a network architecture with parallel convolutional neural networks (CNN) for removing perspective distortion in images. While other works generate corrected images through the use of generative adversarial networks or encoder-decoder networks, we propose a method wherein three CNNs are trained in parallel, to predict a certain element pair in the 3×3 transformation matrix, M^. The corrected image is produced by transforming the distorted input image using M^−1. The networks are trained from our generated distorted image dataset using KITTI images. Experimental results show promise in this approach, as our method is capable of correcting perspective distortions on images and outperforms other state-of-the-art methods. Our method also recovers the intended scale and proportion of the image, which is not observed in other works.