Miracle-dz/UniFAR-FTUs huggingface dataset:
Long Non-Coding RNA TRPM2-AS Promotes Cell Migration and Invasion by Serving as a ceRNA of miR-138 and Inducing SOX4-Mediated EMT in Laryngeal Squamous Cell Carcinoma

Background Laryngeal squamous cell carcinoma (LSCC) is a common type of malignant tumors of larynx, and in this study, we aimed to evaluate the functional role of long non-coding RNA TRPM2-AS in LSCC. Methods The expression levels of TRPM2-AS in LSCC tissues and cell lines were detected by RT-qPCR analysis. In vitro functional assays, including MTT assay and transwell assay, were performed to explore the biological effects of TRPM2-AS on LSCC cells. The expression levels of EMT-relevant proteins were detected by Western blot analysis. The interaction between TRPM2-AS and miR-138 in LSCC, predicted by bioinformatic method, was verified by dual-luciferase reporter assay. Results We observed that TRPM2-AS was highly expressed in human LSCC tissues and cell lines. LSCC patients with advanced clinical stage exhibited higher intratumoral TRPM2-AS expression. The results of functional assays demonstrated that TRPM2-AS knockdown remarkably inhibited the proliferation, migration and invasion of LSCC cells, whereas TRPM2-AS overexpression showed opposite effects. In mechanism, we further observed that TRPM2-AS directly bound to miR-138 and served as competing endogenous RNA (ceRNA), thereby increasing SOX4 expression and promoting EMT in LSCC. The oncogenic effects of TRPM2-AS in LSCC cells were partly diminished by miR-138 restoration. Conclusion In short, our findings provided first evidence that TRPM2-AS is highly expressed and exerts its oncogenic role in LSCC partly by miR-138/SOX4 axis.
Diversity of benthic marine mollusks of the Strait of Magellan, Chile (Polyplacophora, Gastropoda, Bivalvia): a historical review of natural history

Abstract An increase in richness of benthic marine mollusks towards high latitudes has been described on the Pacific coast of Chile in recent decades. This considerable increase in diversity occurs specifically at the beginning of the Magellanic Biogeographic Province. Within this province lies the Strait of Magellan, considered the most important channel because it connects the South Pacific and Atlantic Oceans. These characteristics make it an interesting area for marine research; thus, the Strait of Magellan has historically been the area with the greatest research effort within the province. However, despite efforts there is no comprehensive and updated list of the diversity of mollusks within the Strait of Magellan up to now. This study consisted of a complete bibliographic review of all available literature that included samples of mollusks in the Strait of Magellan. More than 300 articles were reviewed, covering 200 years of scientific knowledge. There were 2579 records belonging to 412 taxa, of which 347 are valid species. Of the total valid species, 44 (~13%) are considered of doubtful presence in the Strait. This work increases the known richness of mollusks of the Strait of Magellan by 228%; it is also the first report that integrates all available diversity studies of the three most speciose classes of benthic mollusks (Gastropoda, Bivalvia and Polyplacophora) from the Strait of Magellan.
Acupuncture Modulates Disrupted Whole-Brain Network after Ischemic Stroke: Evidence Based on Graph Theory Analysis

Background Stroke can lead to disruption of the whole-brain network in patients. Acupuncture can modulate the functional network on a large-scale level in healthy individuals. However, whether and how acupuncture can make a potential impact on the disrupted whole-brain network after ischemic stroke remains elusive. Methods 26 stroke patients with a right hemispheric subcortical infarct were recruited. We gathered the functional magnetic resonance imaging (fMRI) from patients with stroke and healthy controls in the resting state and after acupuncture intervention, to investigate the instant alterations of the large-scale functional networks. The graph theory analysis was applied using the GRETNA and SPM12 software to construct the whole-brain network and yield the small-world parameters and network efficiency. Results Compared with the healthy subjects, the stroke patients had a decreased normalized small-worldness (σ), global efficiency (Eg), and the mean local efficiency (Eloc) of the whole-brain network in the resting state. There was a correlation between the duration after stroke onset and Eloc. Acupuncture improved the patients' clustering coefficient (Cp) and Eloc but did not make a significant impact on the σ and Eg. The postacupuncture variables of the whole-brain network had no association with the time of onset. Conclusion The poststroke whole-brain network tended to a random network with reduced network efficiency. Acupuncture was able to modulate the disrupted patterns of the whole-brain network following the subcortical ischemic stroke. Our findings shed light on the potential mechanisms of the functional reorganization on poststroke brain networks involving acupuncture intervention from a large-scale perspective.
Simultaneous Determination of Five Components of Chaihu-Shugan-San in Beagle Plasma by HPLC-MS/MS and Its Application to a Pharmacokinetic Study after a Single Dose of Chaihu-Shugan-San

Chaihu-shugan-san (CHSGS) has been widely used in China to treat depression and gastrointestinal diseases for thousands of years, but little is known about its pharmacokinetic properties. The purpose of our study is to develop a reliable and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to detect five components in beagle plasma and study their pharmacokinetic after oral administration of CHSGS in beagles. An Agilent C18 column (2.1 × 150 mm, 3.5 μm) was used to separate the analytes, and the column temperature was maintained at 40°C. A gradient elution procedure was used with solvent A (acetonitrile) and solvent B (0.1% formic acid, aqueous) as mobile phases. The elution procedure was 60% B—10% B (0–3 min) and 10% B—60% B (3.1–4 min). The flow rate was 0.3 mL/min, and the total measurement time was 4 min. Within the determined range, the standard calibration curves of the five analytes had a satisfactory linear relationship (r2 ≥ 0.9923). The recovery rate (n = 6) of the five analytes was between 85.42% and 90.85%, and the matrix effects (n = 6) were between 94.52% and 103.91%. These results show that the validated method could be successfully applied to study the pharmacokinetic in beagles after a single dose of CHSGS.
Tropomyosin autoantibodies associated with checkpoint inhibitor myositis

ABSTRACT This brief report details the measurement and identification of IgA antibodies to tropomyosin in a case of presumed ocular myositis with paraspinal myositis in a patient with metastatic uveal melanoma treated with checkpoint inhibitors. High-throughput functional protein microarray analysis and pathway analysis was conducted to identify IgG and IgA antibodies of interest. Antibody levels were compared to generic antibody screening results and levels of the antibodies in a cohort of melanoma patients without myositis (n = 100) at baseline prior to undergoing immunotherapy. The finding of specific muscle antibodies in this clinical case indicates the pathogenic potential of anti-tropomyosin IgA in the development of checkpoint inhibitor associated myositis and requires further investigation.
Investigating self-recognition in bonobos: mirror exposure reduces looking time to self but not unfamiliar conspecifics

The question of whether animals have some sort of self-awareness is a topic of continued debate. A necessary precondition for self-awareness is the ability to visually discriminate the self from others, which has traditionally been investigated through mirror self-recognition experiments. Although great apes generally pass such experiments, interpretations of results have remained controversial. The aim of this study was to investigate how bonobos (Pan paniscus) respond to different types of images of themselves and others, both before and after prolonged mirror exposure. We first presented presumably mirror-naive subjects with representations of themselves in three different ways (mirror image, contingent and non-contingent video footage) as well as representations of others (video footage of known and unknown conspecifics). We found that subjects paid significantly less attention to contingent images of themselves (mirror image, video footage) than to non-contingent images of themselves and unfamiliar individuals, suggesting they perceived the non-contingent self-images as novel. We then provided subjects with three months of access to a large mirror centrally positioned in the enclosure. Following this manipulation, subjects showed significantly reduced interest in the non-contingent self-images, while interest in unknown individuals remained unchanged, suggesting that the mirror experience has led to a fuller understanding of their own self. We discuss implications of this preliminary investigation for the on-going debate on self-awareness in animals.
Simultaneous production of alpha and beta amylase enzymes using separate gene bearing recombinant vectors in the same Escherichia coli cells

The present study describes the simultaneous expression of thermostable industrial alpha (α) and beta (β) amylase enzymes that have been used widely in starch industry. Genomic DNA of Bacillus stearothermophilus DSM 22 strain for α amylase and, Thermoanaerobacterium (Clostridium) thermosulfurogenes DSM 2229 strain for β amylase were used as gene sources. Both genes were ligated into pETDuet-1 expression vector separately and resulting recombinant vectors were transformed into Escherichia coli BL21 competent cells by electroporation. The cells were first transformed by pETDuet-1/ αAmy recombinant plasmid, then the competent cells carrying this plasmid were prepared for the transformation of pETDuet-1/ βAmy plasmid. Enzymatic activities of bacterial colonies were detected on LB agar staining with iodide. Both enzymes were more produced by IPTG induction in BL21 cells and were purified using Ni-NTA agarose column. SDS-PAGE and western blot analyses showed that the molecular weight of purified α and β amylase to be approximately 60 kDa and 55kDa, respectively. The concentration of the purified α and β amylase were calculated as 4.59 μg/mL and 3.17 μg/mL with IPTG as an inducer in LB medium. The present study proposes a novel and efficient method for the production of thermostable α and β amylases at the same E coli cells containing separate engineered plasmid vectors.
The NKL-code for innate lymphoid cells reveals deregulated expression of NKL homeobox genes HHEX and HLX in anaplastic large cell lymphoma (ALCL)

NKL homeobox genes encode developmental transcription factors and display an NKL-code according to their physiological expression pattern in hematopoiesis. Here, we analyzed public transcriptome data from primary innate lymphoid cells (ILCs) for NKL homeobox gene activities and found that ILC3 expressed exclusively HHEX while in ILC1 and ILC2 these genes were silenced. Deregulation of the NKL-code promotes hematopoietic malignancies, including anaplastic large cell lymphoma (ALCL) which reportedly may derive from ILC3. Accordingly, we analyzed NKL homeobox gene activities in ALCL cell lines and investigated their role in this malignancy. Transcriptome analyses demonstrated low expression levels of HHEX but powerfully activated HLX. Forced expression of HHEX in ALCL cell lines induced genes involved in apoptosis and ILC3 differentiation, indicating tumor suppressor activity. ALCL associated NPM1-ALK and JAK-STAT3-signalling drove enhanced expression of HLX while discounting HHEX. Genomic profiling revealed copy number gains at the loci of HLX and STAT3 in addition to genes encoding both STAT3 regulators (AURKA, BCL3, JAK3, KPNB1, NAMPT, NFAT5, PIM3, ROCK1, SIX1, TPX2, WWOX) and targets (BATF3, IRF4, miR135b, miR21, RORC). Transcriptome data of ALCL cell lines showed absence of STAT3 mutations while MGA was mutated and downregulated, encoding a novel potential STAT3 repressor. Furthermore, enhanced IL17F-signalling activated HLX while TGFbeta-signalling inhibited HHEX expression. Taken together, our data extend the scope of the NKL-code for ILCs and spotlight aberrant expression of NKL homeobox gene HLX in ALCL. HLX represents a direct target of ALCL hallmark factor STAT3 and deregulates cell survival and differentiation in this malignancy.
Serum Creatinine Electrochemical Biosensor on Printed Electrodes Using Monoenzymatic Pathway to 1-Methylhydantoin Detection

The rising prevalence of Chronic Kidney Disease (CKD) has necessitated efforts towards the development of cost-effective and accurate biosensors for serum creatinine, which is a potent biomarker reflecting kidney function. This work presents a novel and cost-effective technique to estimate serum creatinine without any sample preprocessing. The technique involves the conversion of creatinine by a monoenzymatic pathway to 1-methylhydantoin. The concentration of 1-methylhydantoin is then quantified by utilizing its innate ability to form a complex with transition metals such as cobalt. The complex formation has been validated using optical spectroscopy and the transmittance at 290 nm wavelength is used to identify the optimum concentration of cobalt chloride in sensing chemistry. This chemical assay is shown to be robust against interference from serum albumin, the abundant plasma protein that can potentially influence the sensor response. The electrochemical biosensor developed using screen-printed electrodes thus provides highly selective creatinine estimation over the range of 0.2–4 mg/dL in a sample volume of 300 μL with no preprocessing and hence can be easily translated into a viable point-of-care (POC) device.
Cognitive Effects of Anticholinergic Load in Women with Overactive Bladder

Abstract Overactive bladder syndrome (OAB) is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of urinary tract infection or other obvious pathology. The mainstay of treatment of OAB is anticholinergic/antimuscarinic medication. These drugs block muscarinic receptors throughout the body, not only the bladder, including in the brain, which may lead to cognitive side effects. Anticholinergic load or burden is the cumulative effect of taking drugs that are capable of producing anticholinergic adverse effects. The elderly are more susceptible to these effects, especially as there is increased permeability of the blood brain barrier. The anticholinergic drugs for OAB are able to enter the central nervous system and lead to central side effects. There is increasing evidence that a high anticholinergic load is linked to the development of cognitive impairment and even dementia. Some studies have found an increased risk of mortality. In view of this, care is needed when treating OAB in the elderly. Trospium chloride is a quaternary amine anticholinergic, which has a molecular structure, which theoretically means it is less likely to cross the blood brain barrier and exert central side effects. Alternatively, mirabegron can be used, which is a beta-3 adrenoceptor agonist, which does not add to the anticholinergic load or exert central nervous system side effects. Conservative therapy can be used as an alternative to pharmacological treatment in the form of behavioral modification, fluid management and bladder retraining. Neuromodulation or the use of botox can also be alternatives, but success may be less in the older adult and will require increased hospital attendances.
Bioprinting in space and International Journal of Bioprinting stays ahead of the game

Now, bioprinting in space is no longer a dream but a reality! Early December 2018, a magnetic three-dimensional (3D) bioprinter was successfully sent to International Space Station by Russian spacecraft Soyuz MS-11. Since then, various tissue/organ printing experiments have been conducted, and the results are expected to be released in February 2019. The scientific question whether living tissues printed under zero gravity maturates faster than that printed on earth will soon be answered. These extraordinary experiments conducted in space could shed light on new strategies of quality tissue construction while achieving rapid tissue maturation. The other exciting news is the continued development of International Journal of Bioprinting (IJB). The table below shows the achievement of IJB in 2018. According to Clarivate Analytics, IJB is on track to be evaluated for inclusion into SCI around October 2019. When accepted, IJB will receive official impact factor in June 2020. • Special issue: Bioprinting in the USA (Guest Editor: Ming Leu). • Special issue: Bioprinting and biofabrication for tissue engineering in Asia (Guest Editor: Jerry Fuh). • Special issue: Bioprinting in Germany (Guest Editor: Boris N. Chichkov). • Special issue: Bioprinting in Europe (except Germany) (Guest Editors: Shoufeng Yang and Jing Yang). Being one of the leading journals in bioprinting, the January 2019 issue of IJB is proud to present a total of 12 original research articles and reviews. Four of them report on a new and emerging bioprinting process, namely the electrohydrodynamic printing technology. Kolan et al. printed 3D biomimetic structures using a polymer/ bioactive glass composite[1], while Sun et al. developed a microscopic image identification technique to monitor the printing process[2]. Gao and Zhou reviewed the mechanisms of electrohydrodynamic printing[3] as well its state-of-theart designs and applications[4]. Cheptsov et al. reviewed new microorganism isolation techniques with emphasis on laser printing[5]. Khan et al. presented the optimization outcome of printing novel ultrashort peptide bioinks[6]. Moreover, Liu et al. reported a hybrid fabrication approach of printing polymer/hydrogel scaffolds but with in-process plasma treatment[7]. Similarly, Moldovan et al. reviewed the potential of hybrid biofabrication of 3D tissue analogs in future[8]. Both works suggest that hybrid bioprinting could be a new direction in research. In addition, Yang et al. reviewed additive manufacturing of bone scaffolds[9], and Mir et al. offered a perspective on how to overcome the obstacles and challenges in tissue engineering through bioprinting[10]. Finally, Rodriguez-Salvador and her colleagues, report two bibliometric studies on recent trends in bioprinting, one in the dentistry applications[11] and the other in the optical tissue phantoms[12].
Complete and long-lasting clinical responses in immune checkpoint inhibitor-resistant, metastasized melanoma treated with adoptive T cell transfer combined with DC vaccination

ABSTRACT Development of T cell-directed immune checkpoint inhibitors (ICI) has revolutionized metastatic melanoma (MM) therapy, but <50% of treated patients experience durable responses. This phase I trial (NCT01946373) investigates the safety/feasibility of tumor-infiltrating lymphocyte (TIL) adoptive cell therapy (ACT) combined with dendritic cell (DC) vaccination in MM patients progressing on ICI. An initial cohort (5 patients) received TIL therapy alone to evaluate safety and allow for optimization of TIL expansion protocols. A second cohort (first-in-man, 5 patients) received TIL combined with autologous tumor lysate-loaded DC vaccination. All patients received cyclophosphamide/fludarabine preconditioning prior to, and intravenous (i.v.) IL-2 after, TIL transfer. The DC vaccine was given as five intradermal injections after TIL and IL-2 administration. [18F]-FDG PET/CT radiology was performed to evaluate clinical response, according to RECIST 1.1 (on the CT part). Immunological monitoring was performed by flow cytometry and T-cell receptor (TCR) sequencing. In the safety/optimization cohort, all patients had a mixed response or stable disease, but none durable. In the combination cohort, two patients experienced complete responses (CR) that are still ongoing (>36 and >18 months, respectively). In addition, two patients had partial responses (PR), one still ongoing (>42 months) with only a small bone-lesion remaining, and one of short duration (<4 months). One patient died early during treatment and did not receive DC. Long-lasting persistency of the injected TILs was demonstrated in blood. In summary, we report clinical responses by TIL therapy combined with DC vaccination in 4 out of 4 treated MM patients who previously failed ICI.
Impact of pseudoprogression and treatment beyond progression on outcome in patients with non-small cell lung cancer treated with immune checkpoint inhibitors

ABSTRACT Background Immune checkpoint inhibitors (ICI) have become an important treatment option for non-small cell lung cancer (NSCLC). We aimed to evaluate the clinical impact of pseudoprogression (PsP) and treatment beyond RECIST1.1-defined progressive disease (TBP) on outcome in NSCLC patients treated with ICI. Methods NSCLC patients treated with ICI between Mar 2016 and July 2018 were recruited in a consecutive manner. Response was assessed every 8–12 weeks using RECIST1.1 and iRECIST. Based on iRECIST, PsP was defined as progressive disease (PD) on RECIST1.1 subsequently reset to non-PD categories. Using log-rank test, progression-free survival (PFS) was compared between patients with and without PsP, and overall survival (OS) was compared between patients treated with and without TBP. The impact of TBP on OS was evaluated through multivariate Cox proportional hazard models. Results Of the 189 patients, seven (3.7%) experienced PsP which mostly occurred approximately 3 months after baseline. The median PFS was significantly longer in patients with PsP (not reached) than those without PsP (3.8 months, P = .02). Among patients who demonstrated PD according to RECIST1.1, median OS was significantly longer in patients with TBP (17.2 months) than those without TBP (7.4 months, P < .001). On multivariate analysis adjusting other covariates, TBP (HR, 0.4; 95% CI, 0.2–0.7) remained as a significant protective factor for mortality. Conclusion PsP occurred in 3.7% of NSCLC patients under ICI treatment. Based on iRECIST scheme, PsP and TBP may be associated with survival benefit.
Transformation of Strawberry Using Agrobacterium tumefaciens

わが国のイチゴの主要3品種である‘女峰’,‘とよのか’および‘宝交早生’に Agrobacterium tumefaciens を用いてNPT II遺伝子およびGUS遺伝子を導入した. その結果, 形質転換カルスおよび不定芽の作出においては,‘女峰’が最も効率がよく,‘とよのか’と‘宝交早生’についても低率ながら形質転換不定芽を得た. ‘とよのか’の葉柄からの形質転換カルスの作出において, アセトシリンゴンを含むA. tumefaciens 懸濁液に浸漬した後, カルス形成培地で6日間共存培養すると形質転換率が向上した. 形質転換個体のGUS活性をX-Glucにより酵素組織化学的に検出したところ, GUSの発現量は, 葉では中肋部, 葉柄では維管束部, 根では生長点部で非常に高かった.