Miracle-dz/UniFAR-FTUs huggingface dataset:
Electroacupuncture improves learning and memory functions in a rat cerebral ischemia/reperfusion injury model through PI3K/Akt signaling pathway activation

Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia, but the underlying mechanism has not yet been fully elucidated. Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment, and the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway plays an important role in autophagy regulation. To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models, we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method. Starting at 2 hours after modeling, electroacupuncture was delivered at the Shenting (GV24) and Baihui (GV20) acupoints, with a dilatational wave (1–20 Hz frequency, 2 mA intensity, 6 V peak voltage), for 30 minutes/day over 8 consecutive days. Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury, increased the mRNA expression levels of the PI3K/Akt signaling pathway-related factors Beclin-1, mammalian target of rapamycin (mTOR), and PI3K, increased the protein expression levels of phosphorylated Akt, Beclin-1, PI3K, and mTOR in the ischemic cerebral cortex, and simultaneously reduced p53 mRNA and protein expression levels. In the Morris water maze test, the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. In the spatial probe test, the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. Electroacupuncture stimulation applied to the Shenting (GV24) and Baihui (GV20) acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, China (approval No. 8150150901) on March 10, 2016.
‘Leads’ that lead: A patient with tachypnoea, tachycardia, hypotension and an uncommon ECG finding

This case is being reported to draw the attention of non-cardiac practicing physicians including pulmonologists, intensivists, and, as a matter of fact all primary care and emergency clinicians, towards a relatively uncommon ECG finding that could be the potential lead in suspecting the diagnosis of a commonly encountered, often fatal medical condition. Together with a high clinical index of suspicion, this alone could guide the decision-making process for further work-up and specific therapy.
Junctional kyphosis and junctional failure after multi-segmental posterior cervicothoracic fusion – A retrospective analysis of 64 patients

Introduction: Junctional kyphosis (JK) and junctional failure (JF) are known complications after thoracolumbar spinal deformity surgery. This study aims to define the incidence and possible risk factors for JK/JF following multi-segmental cervicothoracic fusion. Methods: This is a retrospective analysis of 64 consecutive patients undergoing cervicothoracic fusion surgery, including at least five segments. Clinical and radiographic outcome measures were analyzed. A univariate analysis was performed to determine the effect of the level of upper instrumented vertebra (UIV) and lower instrumented vertebra (LIV), fusion status, C2 sagittal vertical axis (SVA), C2–C7 lordotic angle and T1 slope angle on the occurrence of JK/JF. Results: A total of 46 patients were followed up for a median of 1.1 years (range 0.3–4) with a median age of 65.5 years (range 42.2–84.5). Indication for surgery was spinal stenosis in 87%, trauma in 7%, and tumor in 6% of cases. The median number of levels fused was 7; the most frequent UIV was C2, and the most frequent LIV was T2. Solid fusion was achieved in 78% at the last follow-up. Postoperatively, the median C2 SVA was 32 mm (range − 7–75), median T1 slope angle was 33° (range 2°–57°), C2–C7 sagittal cobb angle was 4° (−29°–12°). JK developed in 4% of cases, no case of JF was observed. No statistically significant impact of bone density, level of UIV, level of LIV or postoperative sagittal parameters on the occurrence of JK/JF was observed, even though fusion status and pathologic T1 slope angle showed a trend toward significance. Conclusion: In this cohort of patients with mildly pathologic sagittal balance, JK was a rare event after multi-segmental fusion, observed in only 4% of cases. Neither level of UIV nor LIV had an influence on its occurrence; however, nonunion and pathologic sagittal alignment showed a nonsignificant trend.
Investigating Algorithmic Stock Market Trading using Ensemble Machine Learning Methods

Recent advances in the machine learning field have given rise to efficient ensemble methods that accurately forecast time-series. In this paper, we use the Quantopian algorithmic stock market trading simulator to assess ensemble methods performance in daily prediction and trading. The ensemble methods used are Extremely Randomized Trees, Random Forest, and Gradient Boosting. All methods are trained using multiple technical indicators and automatic stock selection is used. Simulation results show significant returns relative to the benchmark and large values of alpha are produced from all methods. These results strengthen the role of ensemble method based machine learning in automated stock market trading.
Serotypes and Vaccine Coverage of Streptococcus Pneumoniae Colonization in the Nasopharynx of Thai Children in Congested Areas in Chiang Mai

Streptococcus pneumoniae causes around 10% of all deaths in children younger than five years of age. This study aimed to examine the serogroups/serotypes of S. pneumoniae colonization and vaccine serotype coverage of this organism among Thai children. Nasopharyngeal swabs of children less than or equal to 15 years of age were obtained in congested areas in Chiang Mai from 1 February 2013 to 1 August 2013. The serotyping of S. pneumoniae isolates was performed using the ImmuLex™ kit and the vaccine serotype coverage for this organism was evaluated. A total of 292 children were enrolled. One hundred and thirty children (44.5%) had nasopharyngeal colonization with Streptococcus pneumoniae. Eighty-seven (66.9%) isolates were from children younger than five years of age, seventeen (13.1%) were from children aged 6–10 years, and twenty-six (20%) were from children aged 11–15 years. The five most common serogroups/serotypes isolated were 6 (6A, 6B, 6C) (46.1%), 23 (23F, 23A, 23B) (14.6%), 19 (19F, 19A, 19B, 19C) (8.5%), 15 (15F, 15A, 15B, 15C) (6.9%), and 14 (6.1%). Vaccine serotype coverages in pneumococcal conjugate vaccines (PCV):PCV7, PCV10, and PCV13 were 79.1%, 83.6%, and 85.9%, respectively. There were significant increases in coverage between PCV7 and PCV10 (from 79.1% to 83.6%, p < 0.001), PCV7 and PCV13 (from 79.1% to 85.9%, p < 0.001), and PCV10 and PCV13 (from 83.6% to 85.9%, p < 0.001). The majority of pneumococcal serogroup/serotype colonization in the nasopharynx of Thai children in the studied areas was included in the current licensed pneumococcal conjugated vaccines (PCVs). PCV vaccination should be considered for high-risk children to reduce the incidence of invasive pneumococcal disease among Thai children.
Exploiting GRK2 Inhibition as a Therapeutic Option in Experimental Cancer Treatment: Role of p53-Induced Mitochondrial Apoptosis

Simple Summary The involvement of GRK2 in cancer growth and an inverse correlation with p53 levels were suggested in breast cancer. Furthermore, increased GRK2 expression and activity were detected in thyroid cancer, but its effects and mechanisms of action were not investigated yet. This study aimed to explore the role of GRK2 in thyroid cancer both in vitro and in vivo and its crosstalk with p53. We demonstrated that thyroid cancer cells bearing a mutant form of p53 but not p53 null cells rely on GRK2 as a mechanism of proliferation by regulating p53 levels. Indeed, GRK2 indirectly induces p53 degradation through means of its catalytic activity. The pharmacological inhibition of the kinase effectively inhibits cancer growth by inducing p53-dependent mitochondrial pathways of apoptosis. Our results demonstrate a p53-dependent effect of GRK2 in cancer and suggest kinase inhibition as a potential therapeutic strategy for thyroid cancer. Abstract The involvement of GRK2 in cancer cell proliferation and its counter-regulation of p53 have been suggested in breast cancer even if the underlying mechanism has not yet been elucidated. Furthermore, the possibility to pharmacologically inhibit GRK2 to delay cancer cell proliferation has never been explored. We investigated this possibility by setting up a study that combined in vitro and in vivo models to underpin the crosstalk between GRK2 and p53. To reach this aim, we took advantage of the different expression of p53 in cell lines of thyroid cancer (BHT 101 expressing p53 and FRO cells, which are p53-null) in which we overexpressed or silenced GRK2. The pharmacological inhibition of GRK2 was achieved using the specific inhibitor KRX-C7. The in vivo study was performed in Balb/c nude mice, where we treated BHT-101 or FRO-derived tumors with KRX-C7. In our in vitro model, FRO cells were unaffected by GRK2 expression levels, whereas BHT-101 cells were sensitive, thus suggesting a role for p53. The regulation of p53 by GRK2 is due to phosphorylative events in Thr-55, which induce the degradation of p53. In BHT-101 cells, the pharmacologic inhibition of GRK2 by KRX-C7 increased p53 levels and activated apoptosis through the mitochondrial release of cytochrome c. These KRX-C7-mediated events were also confirmed in cancer allograft models in nude mice. In conclusion, our data showed that GRK2 counter-regulates p53 expression in cancer cells through a kinase-dependent activity. Our results further corroborate the anti-proliferative role of GRK2 inhibitors in p53-sensitive tumors and propose GRK2 as a therapeutic target in selected cancers.
Violent behavior by involuntarily committed female offenders with mental disorders: A population‐based case series

The goal of the current study was to investigate the socio‐demographic, psychiatric, and criminological characteristics of female violent offenders with mental disorders involuntarily committed to a forensic psychiatric hospital. The present study was a population‐based retrospective case series including all female offenders with mental disorders found not guilty by reason of insanity by the criminal courts in the state of Rio de Janeiro, Brazil, and involuntarily committed to a forensic psychiatric facility (n = 27). Patients were assessed with Structured Clinical Interview for DSM‐IV Axis I Disorders and the Positive and Negative Syndrome Scale. We found that most offenders were Afro‐Brazilian, uneducated unmarried women. Schizophrenia with active psychotic symptoms was the most common clinical condition. Relatives were the frequent victims of aggressive behavior. Most patients had already been diagnosed with a mental disorder and placed under psychiatric treatment, but poor adherence and treatment dropout were common. Violent behavior in psychiatrically ill female patients is associated with a specific socio‐demographic and clinical profile and is thus potentially amenable to prevention particularly if the mental health and social services are to provide the much‐needed support for economically, socially, and psychologically vulnerable women.
The DDX23 Negatively Regulates Translation and Replication of Foot-and-Mouth Disease Virus and Is Degraded by 3C Proteinase

DEAD-box helicase 23 (DDX23) is a host nuclear helicase, which is a part of the spliceosomal complex and involved in pre-mRNA splicing. To investigate whether DDX23, an internal ribosomal entry sites transacting factor (ITAF) affects foot-and-mouth disease virus (FMDV) replication and translation through internal ribosome entry site (IRES)-dependent manner. For this, we utilized a pull-down assay, Western blotting, quantitative real-time PCR, confocal microscopy, overexpression and small interfering RNA knockdown, as well as the median tissue culture infective dose. Our findings showed that FMDV infection inhibited DDX23 expression and the overexpression of DDX23 reduced viral replication, however, CRISPR Cas9 knockout/small interfering RNA knockdown increased FMDV replication. FMDV IRES domain III and IV interacted with DDX23, whereas DDX23 interacted with FMDV 3C proteinase and significantly degraded. The enzymatic activity of FMDV 3C proteinase degraded DDX23, whereas FMDV degraded DDX23 via the lysosomal pathway. Additionally, IRES-driven translation was suppressed in DDX23-overexpressing cells, and was enhanced in DDX23 knocked down. Collectively, our results demonstrated that DDX23 negatively affects FMDV IRES-dependent translation, which could be a useful target for the design of antiviral drugs.
Sensitivity Analysis of Single-Drive, 3-axis MEMS Gyroscope Using COMSOL Multiphysics

In this paper, a COMSOL Multiphysics-based methodology is presented for evaluation of the microelectromechanical systems (MEMS) gyroscope. The established finite element analysis (FEA) model was successfully validated through a comparison with analytical and Matlab/Simulink analysis results. A simplified single-drive, 3-axis MEMS gyroscope was analyzed using a mode split approach, having a drive resonant frequency of 24,918 Hz, with the x-sense, y-sense, and z-sense being 25,625, 25,886, and 25,806 Hz, respectively. Drive-mode analysis was carried out and a maximum drive-displacement of 4.0 μm was computed for a 0.378 μN harmonic drive force. Mechanical sensitivity was computed at 2000 degrees per second (dps) input angular rate while the scale factor for roll, pitch, and yaw was computed to be 0.014, 0.011, and 0.013 nm/dps, respectively.
Behaviour of Human Oral Epithelial Cells Grown on Invisalign® SmartTrack® Material

Invisalign aligners have been widely used to correct malocclusions, but their effect on oral cells is poorly known. Previous research evaluated the impact of aligners’ eluates on various cells, but the cell behavior in direct contact with aligners is not yet studied. In the present study, we seeded oral epithelial cells (cell line Ca9-22) directly on Invisalign SmartTrack material. This material is composed of polyurethane and co-polyester and exhibit better mechanical characteristics compared to the predecessor. Cell morphology and behavior were investigated by scanning electron microscopy and an optical cell moves analyzer. The effect of aligners on cell proliferation/viability was assessed by cell-counting kit (CCK)-8 and 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay and live/dead staining. The expression of inflammatory markers and proteins involved in epithelial barrier function was measured by qPCR. Cells formed cluster-like structures on aligners. The proliferation/viability of cells growing on aligners was significantly lower (p < 0.05) compared to those growing on tissue culture plastic (TCP). Live/dead staining revealed a rare occurrence of dead cells on aligners. The gene expression level of all inflammatory markers in cells grown on aligners’ surfaces was significantly increased (p < 0.05) compared to cells grown on TCP after two days. Gene expression levels of the proteins involved in barrier function significantly increased (p < 0.05) on aligners’ surfaces after two and seven days of culture. Aligners’ material exhibits no cytotoxic effect on oral epithelial cells, but alters their behavior and the expression of proteins involved in the inflammatory response, and barrier function. The clinical relevance of these effects has still to be established.
Inhibition of HDAC Enzymes Contributes to Differential Expression of Pro-Inflammatory Proteins in the TLR-4 Signaling Cascade

Class I and II histone deacetylases (HDAC) are considered important regulators of immunity and inflammation. Modulation of HDAC expression and activity is associated with altered inflammatory responses but reports are controversial and the specific impact of single HDACs is not clear. We examined class I and II HDACs in TLR-4 signaling pathways in murine macrophages with a focus on IκB kinase epsilon (IKKε) which has not been investigated in this context before. Therefore, we applied the pan-HDAC inhibitors (HDACi) trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) as well as HDAC-specific siRNA. Administration of HDACi reduced HDAC activity and decreased expression of IKKε although its acetylation was increased. Other pro-inflammatory genes (IL-1β, iNOS, TNFα) also decreased while COX-2 expression increased. HDAC 2, 3 and 4, respectively, might be involved in IKKε and iNOS downregulation with potential participation of NF-κB transcription factor inhibition. Suppression of HDAC 1–3, activation of NF-κB and RNA stabilization mechanisms might contribute to increased COX-2 expression. In conclusion, our results indicate that TSA and SAHA exert a number of histone- and HDAC-independent functions. Furthermore, the data show that different HDAC enzymes fulfill different functions in macrophages and might lead to both pro- and anti-inflammatory effects which have to be considered in therapeutic approaches.
Acrylate dimerisation under ionic liquid-supercritical carbon dioxide conditions

Ionic liquid 1-n-butyl-3-methylimidazolium tetrafluoroborate and supercritical CO2 have been used for the biphasic palladium-catalysed dimerisation of methyl acrylate. Substrate and product distribution between the two phases and extraction capability of scCO2 are evaluated. The effect of the biphasic medium on the catalyst performance is also addressed. The selectivity for the tail-to-tail dimers is >98%, as high as under monophasic conditions. The same trend stands for turnover number and frequency although there is a lower substrate to palladium ratio in the IL phase. The CO2-rich phase acts as a substrate and product reservoir, a suitable case for studying the reaction under continuous feed and extraction regime.
Patient-provided e-support in reduced intensity obesity treatment: The INSPIRE randomized controlled trial.

OBJECTIVE There are two types of patient supporters, peers (two individuals initiating health behavior change who support one another) and mentors (a previously successful patient who supports incoming patients). Social comparison theory suggests that peers and mentors may elicit social comparison processes (patients may compare their progress to that of their peer/mentor), and these social comparisons could impact treatment outcomes. This randomized controlled trial is the first to examine the differential impact of peers and mentors on obesity treatment outcomes and social comparison processes when added to reduced intensity treatment. METHOD Participants (N = 278) were randomly assigned to reduced intensity behavioral weight loss treatment alone (rBWL), rBWL plus peer e-support (rBWL + Peer), or rBWL plus mentor e-support (rBWL + Mentor). rBWL involved periodic group sessions that decreased over time; when group sessions decreased, intensity of peer/mentor e-support increased. Weight and social comparison processes were assessed throughout the 12-month intervention. RESULTS There was a significant treatment effect; when group sessions became less frequent and peer/mentor e-support became more frequent, rBWL + Peer had significantly greater weight loss than rBWL alone, and rBWL + Mentor was not significantly different from the other two. Social comparison processes differed by treatment arm; rBWL + Peer participants tended to report more lateral social comparisons ("my weight loss progress is 'similar' to my peer's"), whereas rBWL + Mentor participants reported more upward comparisons ("my weight loss progress is 'worse than' my mentor's"). Upward comparisons were associated with poorer weight loss outcomes. CONCLUSIONS Peer e-support may be an effective, low-cost, sustainable method for improving longer-term weight loss outcomes in reduced intensity obesity treatment. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Effective RNA Knockdown Using CRISPR-Cas13a and Molecular Targeting of the EML4-ALK Transcript in H3122 Lung Cancer Cells

RNAi technology has significant potential as a future therapeutic and could theoretically be used to knock down disease-specific RNAs. However, due to frequent off-target effects, low efficiency, and limited accessibility of nuclear transcripts, the clinical application of the technology remains challenging. In this study, we first assessed the stability of Cas13a mRNA and guide RNA. Next, we titrated Cas13a and guide RNA vectors to achieve effective knockdown of firefly luciferase (FLuc) RNA, used as a target transcript. The interference specificity of Cas13a on guide RNA design was next explored. Subsequently, we targeted the EML4-ALK v1 transcript in H3122 lung cancer cells. As determined by FLuc assay, Cas13a exhibited activity only toward the orientation of the crRNA–guide RNA complex residing at the 5′ of the crRNA. The activity of Cas13a was maximal for guide RNAs 24–30 bp in length, with relatively low mismatch tolerance. After knockdown of the EML4-ALK transcript, cell viability was decreased up to 50%. Cas13a could effectively knock down FLuc luminescence (70–76%), mCherry fluorescence (72%), and EML4-ALK at the protein (>80%) and transcript levels (26%). Thus, Cas13a has strong potential for use in RNA regulation and therapeutics, and could contribute to the development of personalized medicine.
Application of the RBBP9 Serine Hydrolase Inhibitor, ML114, Decouples Human Pluripotent Stem Cell Proliferation and Differentiation

Retinoblastoma binding protein 9 (RBBP9) is required for maintaining the expression of both pluripotency and cell cycle genes in human pluripotent stem cells (hPSCs). An siRNA-based study from our group showed it does so by influencing cell cycle progression through the RB/E2F pathway. In non-pluripotent cells, RBBP9 is also known to have serine hydrolase (SH) activity, acting on currently undefined target proteins. The role of RBBP9 SH activity in hPSCs, and during normal development, is currently unknown. To begin assessing whether RBBP9 SH activity might contribute to hPSC maintenance, hPSCs were treated with ML114—a selective chemical inhibitor of RBBP9 SH activity. Stem cells treated with ML114 showed significantly reduced population growth rate, colony size and progression through the cell cycle, with no observable change in cell morphology or decrease in pluripotency antigen expression—suggesting no initiation of hPSC differentiation. Consistent with this, hPSCs treated with ML114 retained the capacity for tri-lineage differentiation, as seen through teratoma formation. Subsequent microarray and Western blot analyses of ML114-treated hPSCs suggest the nuclear transcription factor Y subunit A (NFYA) may be a candidate effector of RBBP9 SH activity in hPSCs. These data support a role for RBBP9 in regulating hPSC proliferation independent of differentiation, whereby inhibition of RBBP9 SH activity de-couples decreased hPSC proliferation from initiation of differentiation.