Miracle-dz/UniFAR-FTUs huggingface dataset:
Apatinib combined with S-1 as second-line therapy in advanced gastric cancer

Abstract Advanced gastric cancer (AGC) patients are not tolerant to the toxicities of traditional chemotherapy and its second-line therapeutic regimens are limited. The aim of the present study is to evaluate the efficacy and safety of apatinib combined with S-1 as the second-line therapy for AGC patients. Patients with AGC were enrolled in this study. Patients received oral apatinib (250 mg to 500 mg once daily) and S-1(40 mg/m2 twice daily) on days 1–14. Each cycle was 28 days and one course of treatment consisted of 2 cycles. Clinical efficacy and adverse events (AEs) were observed. Kaplan–Meier method was used for survival analysis. From November 2015 to December 2017, 58 AGC patients who failed first-line chemotherapy were enrolled and assessed retrospectively. According to the Response Evaluation Criteria in Solid Tumors (RECIST) standard, all patients were evaluable for response. None achieved CR, and 10 (17.2%) achieved PR (95% CI 7.2%–27.3%). SD was observed in 58.6% (34/58) of patients (95% CI 45.6%–71.7%) and NR in 24.1% (14/58) of patients (95% CI 12.8%–35.5%). The objective response rate (ORR) and the disease control rate (DCR) were 17.2% and 75.8% respectively. The median progression-free survival (PFS) and median overall survival (OS) were 143.1 days (95% CI 121.7–164.5) and 211.6 days (95% CI 162.9–219.7) respectively. The multivariate analysis showed that the ECOG PS was the independent factor of PFS and OS for AGC patients (PFS: HR = 3.565, 95% CI: 2.25–5.65, P < .001; OS: HR = 3.676, 95% CI: 2.29–5.89, P < .001). The main AEs were fatigue (72.4%), hypertension (46.6%), and leukopenia (48.3%). Apatinib combined with S-1 showed promising efficiency and was well tolerated as the second-line therapy for AGC patients. ECOG PS was the independent factor of PFS and OS for AGC patients. AEs were moderate and controllable, and leukopenia or hypertension was predictable factors for the PFS and OS of AGC patients.
Anticancer Activity of Combretum fragrans F. Hoffm on Glioblastoma and Prostate Cancer Cell Lines

Background: Cancer incidence has been growing in an alarming rate worldwide and new therapeutics are needed, particularly for intractable and chemoresistant cases. We evaluated the cytotoxic effects of Combretum fragrans F. Hoffm (Combretaceae) on glioblastoma (U87MG and C6) and prostate (PC-3) cancer cell lines. Methods: The cytotoxic effect of the methanolic extract of the stem bark of Combretum fragrans was assessed using XTT (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) test. Expressions of Akt and ERK1/2 were determined using Western blot technique, while Caspase-3/7 kits were used to evaluate caspase-3/7 activity. Results: C. fragrans extract inhibited the proliferation of U87 (IC50 = 20.13 µg/mL), C6 (IC50 = 12.17 µg/mL), and PC-3 (IC50 = 11.50 µg/mL) cells. Treatment with the extract resulted in lower levels (p < 0.001) of phospho-ERK1/2 and phospho-Akt in U87 cells, and instead, higher levels of phospho-ERK1/2 (p < 0.001) in C6 and PC-3 cells. An increase in caspase-3/7 activity was observed, mainly after 24 hours of treatment, indicating the activation of apoptotic processes. Conclusion: Altogether, these results suggest that C. fragrans have potent anticancer properties. This plant should be further investigated for developing new anticancer drugs.
Superoxide dismutase: an updated review on its health benefits and industrial applications

Abstract Many short-lived and highly reactive oxygen species, such as superoxide anion (O2 - ) and hydrogen peroxide (H2O2), are toxic or can create oxidative stress in cells, a response involved in the pathogenesis of numerous diseases depending on their concentration, location, and cellular conditions. Superoxide dismutase (SOD) activities as an endogenous and exogenous cell defense mechanism include the potential use in treating various diseases, improving the potential use in treating various diseases, and improving food-stuffs preparation dietary supplements human nutrition. Published work indicates that SOD regulates oxidative stress, lipid metabolism, inflammation, and oxidation in cells. It can prevent lipid peroxidation, the oxidation of low-density lipoprotein in macrophages, lipid droplets' formation, and the adhesion of inflammatory cells into endothelial monolayers. It also expresses antioxidant effects in numerous cancer-related processes. Additionally, different forms of SOD may also augment food processing and pharmaceutical applications, exhibit anticancer, antioxidant, and anti-inflammatory effects, and prevent arterial problems by protecting the proliferation of vascular smooth muscle cells. Many investigations in this review have reported the therapeutic ability and physiological importance of SOD. Because of their antioxidative effects, SODs are of great potential in the medicinal, cosmetic, food, farming and chemical industries. This review discusses the findings of human and animal studies that support the advantages of SOD enzyme regulations to reduce the formation of oxidative stress in various ways.
Grand scale genome manipulation via chromosome swapping in Escherichia coli programmed by three one megabase chromosomes

Abstract In bacterial synthetic biology, whole genome transplantation has been achieved only in mycoplasmas that contain a small genome and are competent for foreign genome uptake. In this study, we developed Escherichia coli strains programmed by three 1-megabase (Mb) chromosomes by splitting the 3-Mb chromosome of a genome-reduced strain. The first split-chromosome retains the original replication origin (oriC) and partitioning (par) system. The second one has an oriC and the par locus from the F plasmid, while the third one has the ori and par locus of the Vibrio tubiashii secondary chromosome. The tripartite-genome cells maintained the rod-shaped form and grew only twice as slowly as their parent, allowing their further genetic engineering. A proportion of these 1-Mb chromosomes were purified as covalently closed supercoiled molecules with a conventional alkaline lysis method and anion exchange columns. Furthermore, the second and third chromosomes could be individually electroporated into competent cells. In contrast, the first split-chromosome was not able to coexist with another chromosome carrying the same origin region. However, it was exchangeable via conjugation between tripartite-genome strains by using different selection markers. We believe that this E. coli-based technology has the potential to greatly accelerate synthetic biology and synthetic genomics.
Insights into pathological extracellular matrix by non-invasive nuclear imaging with fibronectin-binding peptide A5 and FGF-2

The extracellular matrix (ECM) is the master mediator of cellular and tissue function in the body. Dysregulations of the ECM are found in a wide number of diseases like malignant tumours and fibrotic diseases. In the tumour microenvironment, the ECM is highly remodelled promoting tumour invasion and drug resistance, while fibrosis is characterised by an over-deposition of ECM proteins like collagen and fibronectin with the consequent organ failure. Direct targeting of the ECM might open access to the development of new tracers for the targeted drug-delivery of cancer therapeutics and for the diagnosis of fibrosis at an early stage. In vivo non-invasive imaging techniques (in particular nuclear imaging) using specific ECM-targeting probes are useful tools for the quantitative characterisation of the ECM and for diagnostic technique in cancer and fibrosis. However, the development of diagnostic tools and of therapeutics encounters some challenges because of the multifunctionality and the complexity of the ECM. In the first part of the thesis, the fibronectin-binding peptide FnBPA5 was evaluated for the targeting of ECM glycoprotein fibronectin (Fn) in cancer and fibrosis. Fn is a preferred bacterial adhesion target due to its high abundance in wounds and bacteria like Staphylococcus aureus express Fn-binding proteins on their cell wall and use them to colonise and penetrate into the host tissue. In an initial proof-of-concept study, it was demonstrated that the S. aureus-derived peptide FnBPA5 might be suitable for the targeting of Fn in tumours for in vivo imaging. For the experiments, FnBPA5 was labelled with a fluorescence moiety (Alexa 488, Cy5) for fluorescence staining and radiolabelled with In for Single Photon Emission Computed tomography (SPECT), respectively. In vitro, FnBPA5Alexa 488 showed Kd values of 75 ± 8 and 28 ± 6 nM for the binding to soluble Fn and fibrillar Fn, respectively. Additionally, the Fn-specific binding of FnBPA5-Alexa 488 was demonstrated in fibroblast-derived matrix and it could be showed that the binding behaviour was not altered by the labelling with Indium. Biodistribution and SPECT analysis performed in a murine prostate carcinoma model revealed that In-FnBPA5 accumulated mainly in the tumour, the kidneys and the liver with a maximum uptake at 1 hour post injection (p.i.) (4.74 ± 0.77 %IA/g, 140.58 ± 18.10 %IA/g, 7.52 ± 1.50 %IA/g, respectively). The uptake was Fn-specific in all tissues examined except for the kidneys. Our pharmacokinetic
Potential effects of mesenchymal stem cell derived extracellular vesicles and exosomal miRNAs in neurological disorders

Mesenchymal stem cells are multipotent cells that possess anti-inflammatory, anti-apoptotic and immunomodulatory properties. The effects of existing drugs for neurodegenerative disorders such as Alzheimer’s disease are limited, thus mesenchymal stem cell therapy has been anticipated as a means of ameliorating neuronal dysfunction. Since mesenchymal stem cells are known to scarcely differentiate into neuronal cells in damaged brain after transplantation, paracrine factors secreted from mesenchymal stem cells have been suggested to exert therapeutic effects. Extracellular vesicles and exosomes are small vesicles released from mesenchymal stem cells that contain various molecules, including proteins, mRNAs and microRNAs. In recent years, administration of exosomes/extracellular vesicles in models of neurological disorders has been shown to improve neuronal dysfunctions, via exosomal transfer into damaged cells. In addition, various microRNAs derived from mesenchymal stem cells that regulate various genes and reduce neuropathological changes in various neurological disorders have been identified. This review summarizes the effects of exosomes/extracellular vesicles and exosomal microRNAs derived from mesenchymal stem cells on models of stroke, subarachnoid and intracerebral hemorrhage, traumatic brain injury, and cognitive impairments, including Alzheimer’s disease.
Differential development and electrophysiological activity in cultured cortical neurons from the mouse and cynomolgus monkey

In vitro cultures of primary cortical neurons are widely used to investigate neuronal function. However, it has yet to be fully investigated whether there are significant differences in development and function between cultured rodent and primate cortical neurons, and whether these differences influence the utilization of cultured cortical neurons to model pathological conditions. Using in vitro culture techniques combined with immunofluorescence and electrophysiological methods, our study found that the development and maturation of primary cerebral cortical neurons from cynomolgus monkeys were slower than those from mice. We used a microelectrode array technique to compare the electrophysiological differences in cortical neurons, and found that primary cortical neurons from the mouse brain began to show electrical activity earlier than those from the cynomolgus monkey. Although cultured monkey cortical neurons developed slowly in vitro, they exhibited typical pathological features-revealed by immunofluorescent staining-when infected with adeno-associated viral vectors expressing mutant huntingtin (HTT), the Huntington's disease protein. A quantitative analysis of the cultured monkey cortical neurons also confirmed that mutant HTT significantly reduced the length of neurites. Therefore, compared with the primary cortical neurons of mice, cultured monkey cortical neurons have longer developmental and survival times and greater sustained physiological activity, such as electrophysiological activity. Our findings also suggest that primary cynomolgus monkey neurons cultured in vitro can simulate a cell model of human neurodegenerative disease, and may be useful for investigating time-dependent neuronal death as well as treatment via neuronal regeneration. All mouse experiments and protocols were approved by the Animal Care and Use Committee of Jinan University of China (IACUC Approval No. 20200512-04) on May 12, 2020. All monkey experiments were approved by the IACUC protocol (IACUC Approval No. LDACU 20190820-01) on August 23, 2019 for animal management and use.
Caudate nucleus volume mediates the link between glutamatergic neurotransmission and problematic smartphone use in youth

Abstract Background and aims Problematic smartphone use (PSU) is growing rapidly among teens. It has similar presentations as other behavioral addictions in terms of excessive use, impulse control problems, and negative consequences. However, the underlying neurobiological mechanisms remain undiscovered. We hypothesized that structural changes in the striatum might serve as an important link between alteration in glutamate signaling and development of PSU. Methods Among 88 participants, twenty (F:M, 12:8; age 16.2 ± 1.1) reported high scores in the smartphone addiction proneness scale (SAPS) with a cut-off score of 42; the other 68 (F:M, 19:49; age 15.3 ± 1.7) comprised the control group. Sociodemographic data and depression, anxiety, and impulsivity traits were measured. Striatal volumes (caudate, putamen, and nucleus accumbens) were estimated from T1 imaging data. Serum glutamate levels were estimated from peripheral blood samples. Group comparisons of each data were performed after controlling for age and gender. Mediation analyses were conducted to test the indirect effects of glutamate level alteration on PSU through striatal volumetric alteration. Results The PSU group showed a decrease in both caudate volumes than the control group. Left caudate volume was positively correlated with serum glutamate level, and negatively with impulsivity traits and SAPS scores. The mediation model revealed a significant indirect effect of serum glutamate on SAS scores through the reduced left caudate volume. Discussion and conclusions This study suggests that altered glutamatergic neurotransmission may be associated with PSU among teens, possibly through reduced left caudate volume. Current findings might support neural mechanisms of smartphone addiction.
Dexmedetomidine protects SH‐SY5Y cells against MPP+‐induced declining of mitochondrial membrane potential and cell cycle deficits

Dexmedetomidine (Dex), an adrenergic α2 receptor agonist, is commonly used in deep‐brain stimulation surgery for Parkinson's disease (PD). However, there is evidence that the use of anaesthetics may accelerate the progression of neurodegenerative diseases. The effect of Dex on PD remains unclear. Here, we cultured the all‐trans‐retinoicacid (ATRA) differentiated SH‐SY5Y cells in vitro and then treated with MPP+ (1.5mM) with or without Dex (10nM) or Dex combined with Atipamezole (Ati,100nM, adrenergic α2 receptor inhibitor). The ratio of apoptotic cells, mitochondrial membrane potential (Δψm), reactive oxygen species (ROS), cell cycle and apoptotic markers (Cleaved caspase‐3, 9) were analysed by flow cytometry and immunofluorescence. We found that the levels of apoptotic ratio and cleaved caspase‐3, 9 increased, ROS accumulated, and mitochondrial membrane potential decreased after MPP+treatment, while these changes were partially reversed by Dex. Dex also prevented MPP+ induced cell arrest by increasing G1 phase cells, decreasing S phase cells, and decreasing the expression of cyclinD1 and Cdk4. Moreover the effects of Dex were partially reversed by Ati. These findings reveal that Dex attenuated MPP+‐induced apoptosis of SH‐SY5Y cells by preventing the loss of Δψm, reducing ROS, and regulating the cell cycle. Our findings indicated that Dex is more likely to be a potential drug for the treatment of PD.
Time-oriented attention improves accuracy in a paced finger tapping task

Finger tapping is a task widely used in a variety of experimental paradigms, in particular to understand sensorimotor synchronization and time processing in the range of hundreds of milliseconds (millisecond timing). Normally, subjects don’t receive any instruction about what to attend to and the results are seldom interpreted taking into account the possible effects of attention. In this work we show that attention can be oriented to the purely temporal aspects of a paced finger tapping task and that it affects performance. Specifically, time-oriented attention improves the accuracy in paced finger tapping and it also increases the resynchronization efficiency after a period perturbation. We use two markers of the attention level: auditory ERPs and subjective report of the mental workload. In addition, we propose a novel algorithm to separate the auditory, stimulus-related components from the somatosensory, response-related ones, which are naturally overlapped in the recorded EEG.
COVID-19 and prejudice against migrants: the mediating roles of need for cognitive closure and binding moral foundations. A comparative study

ABSTRACT What mitigates prejudice against migrants in situations of uncertainty? Addressing this question, we explored how individuals with greater COVID-19 concern perceive migrants as a greater threat and show prejudice against them, indirectly through the mechanism of need for cognitive closure and binding moral foundations. This study was conducted in two European countries: Malta and Italy. Six hundred and seventy-six individuals participated in this quantitative study (Malta: N = 204; Italy N = 472). Results from this study showed that the need for cognitive closure and binding moral foundations mediate the relationship between COVID-19 concern and prejudice against migrants in both countries. When testing the three binding moral foundations (loyalty, authority, and purity), the authority foundation seems to be the most consistent predictor. The implications of the findings contribute to theories about how situational uncertainty caused by COVID-19, together with the need for epistemic certainty and binding morality, contribute to increased prejudiced attitudes against migrants.
Impact of administration of nicorandil prior to percutaneous coronary intervention in treatment of acute myocardial infarction

Abstract Background: In order to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to assess the efficacy and safety of nicorandil prior to percutaneous coronary intervention in acute myocardial infarction (AMI) patients. Methods: This systematic review and meta-analysis will be performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently will search randomized controlled trials or observational studies about the treatment of nicorandil on AMI patients. Retrieved databases include Web of Science, ClinicalTrials.gov, Pubmed, Embase, and Cochrane Library. And retrieval time is limited from inception to June 2021. Key words are nicorandil, myocardial infarction, or similar expansion words without publication limitation. Biomechanical studies, in vitro studies, review articles, techniques, case reports, letters to the editor, and editorials are excluded. Results: The results of our review will be reported strictly following the PRISMA criteria and the review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. OSF registration number: 10.17605/OSF.IO/UEPKB.
Fabric defect detection based on golden image subtraction

To realise the universality and practicality of fabric defect detection in the textile industry, this paper proposes two approaches based on the Gabor filter and the golden image subtraction method. A method known as Gabor preprocessed golden image subtraction is first introduced, which filters a test fabric image by the real component of the Gabor filter with a 1 Hz centre frequency and a 90° angle. Golden image subtraction performs subtractions between the golden template and the filtered image to obtain a resultant image, and the segmentation threshold is determined by the direct threshold. The second method is Gabor preprocessed golden image subtraction based on a genetic algorithm, which can automatically select the parameter groups of the Gabor filter via the genetic algorithm. In addition, the paper also presents an extensive comparison between the proposed methods and wavelet preprocessed golden image subtraction. Meanwhile, the performances of the aforementioned three methods are tested in a real machine vision detection system to meet the actual demands of the textile industry. It can be concluded that Gabor preprocessed golden image subtraction provides the best detection results. The overall detection success rate is 95.62%, with 80 defect-free images and 80 defective images for fabric textures of common types.
Assessment of attention-deficit hyperactivity disorder in people with substance use disorder: Another case of what gets measured gets done

International guidelines recommend that attention-deficit hyperactivity disorder (ADHD) be identified and treated in all age groups, with increased focus on subpopulations with a high prevalence of ADHD. One such group is people who seek treatment for substance use disorder (SUD). ADHD doubles the risk of SUD and approximately one in four people with SUD have co-occurring ADHD. Although often complex and challenging, ADHD can be reliably diagnosed during active substance use and is often important for effective treatment of concurrent SUD (Van Emmerik-Van Oortmerssen et al., 2017). Despite this, ADHD is underdiagnosed among adults with SUD. ADHD often complicates the clinical profile and treatment of SUD. ADHD has been associated with increased complexity and chronicity of SUD and decreased SUD treatment efficacy and retention. Furthermore, ADHD among those with SUD can result in high rates of costly substance use–related acute care contacts, poor physical and mental health outcomes, increased contact with the criminal justice system, reduced quality of life, suicidal behaviour and premature mortality (Sciberras et al., in press). Without addressing the underlying impaired executive functioning and impulsivity – both central characteristics of ADHD – those with unidentified ADHD may engage in risk-taking behaviour increasing their risk of poor health and social outcomes, despite receiving treatment for SUD and other mental health disorders. Accordingly, a randomised controlled trial found that treating ADHD symptoms decreased substance use and criminal justice involvement (Konstenius et al., 2014).