Miracle-dz/UniFAR-FTUs huggingface dataset:
Examination of Lower Level Motion Mechanisms That Provide Information to Object Tracking: An Examination Using Dichoptic Stimulation

In this study, we examined the operation of first- and second-order motion mechanisms with respect to object tracking using dichoptic presentation. A bistable apparent motion stimulus composed of four rectangles arranged in square- and diamond-shapes in every other frame was presented binocularly, monocularly, or dichoptically using a stereoscope. Since past motion studies showed that the first-order motion mechanism cannot function under dichoptic stimulation, we evaluated the upper temporal frequency limits of object tracking with dichoptic presentation and compared these results with those obtained with ordinary binocular or monocular (nondichoptic) presentation. We found that the temporal limits were 4 -5 Hz, regardless of the viewing conditions. These limits are similar to those for within-attribute (first- and second-order) object tracking (4 -5 Hz) obtained in our previous study. Thus, this putative mechanism may be responsible for object tracking, based only on second-order components, even in the case of first-order stimuli.
Induction of G0/G1 phase arrest and apoptosis by CRISPR/Cas9-mediated knockout of CDK2 in A375 melanocytes

Cutaneous melanoma is one of the most common malignant skin tumors, with a continuously increasing incidence. Cyclin-dependent kinase (CDK) 2 is a key regulator of G1-S transition and modulation of G2 progression; however, its role in cancer is a matter of debate. In the present study, a lentivirus expressing single-guide RNA (sgRNA) was constructed to knock out CDK2 using CRISP/Cas9 technology, in order to confirm the role of CDK2 in A375 human melanoma cells. The results demonstrated that CDK2 knockout induced G0/G1 phase arrest and early apoptosis by downregulating the expression of CDK4 and cyclin A2, and by upregulating the expression of cyclin D1. These results suggest that therapeutic strategies designed to target CDK2 using CRISP/Cas9 may improve the treatment outcome of cutaneous melanoma.
Inhibition of the Nrf2-TrxR Axis Sensitizes the Drug-Resistant Chronic Myelogenous Leukemia Cell Line K562/G01 to Imatinib Treatments

Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen species (ROS) production, and apoptosis induction in imatinib-resistant CML K562/G01 cells and explored their potential mechanisms. Stable K562/G01 cells with knockdown of Nrf2 were established by infection of siRNA-expressing lentivirus. The mRNA and protein expression levels of Nrf2 and TrxR were determined by real-time quantitative polymerase chain reaction and western blot, respectively. ROS generation and apoptosis were assayed by flow cytometry, while drug sensitivity was measured by the Cell Counting Kit-8 assay. Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells at both mRNA and protein levels. Expression levels of Nrf2 and TrxR were positively correlated in K562/G01 cells. Knockdown of Nrf2 in K562/G01 cells enhanced the intracellular ROS level, suppressed cell proliferation, and increased apoptosis in response to imatinib treatments. Nrf2 expression contributes to the imatinib resistance of K562/G01 cells and is positively correlated with TrxR expression. Targeted inhibition of the Nrf2-TrxR axis represents a potential therapeutic approach for imatinib-resistant CML.
A noninvasive, machine learning–based method for monitoring anthocyanin accumulation in plants using digital color imaging

Premise When plants are exposed to stress conditions, irreversible damage can occur, negatively impacting yields. It is therefore important to detect stress symptoms in plants, such as the accumulation of anthocyanin, as early as possible. Methods and Results Twenty‐two regression models in five color spaces were trained to develop a prediction model for plant anthocyanin levels from digital color imaging data. Of these, a quantile random forest regression model trained with standard red, green, blue (sRGB) color space data most accurately predicted the actual anthocyanin levels. This model was then used to noninvasively monitor the spatial and temporal accumulation of anthocyanin in Arabidopsis thaliana leaves. Conclusions The digital imaging–based nature of this protocol makes it a low‐cost and noninvasive method for the detection of plant stress. Applying a similar protocol to more economically viable crops could lead to the development of large‐scale, cost‐effective systems for monitoring plant health.
Evaluation of Final-Year Turkish Dental Students' Knowledge, Attitude, and Self-Perceived Competency towards Preventive Dentistry

Background Dental education plays an important role in providing students with the opportunity to develop their evidence-based knowledge and clinical skills regarding patient-specific preventive care and caries management strategies. The aims of this study were to examine the knowledge, attitude, and self-perceived competency towards preventive dentistry among final-year dental students and to investigate their preventive practice for high-caries-risk children. Methods. Data were collected from a convenience sample of 126 dental students using a questionnaire. The IBM SPSS Statistics version 21 was used for data analysis. Results A total of 126 students completed the questionnaire, and 63% of the respondents were female. Significant gender differences were found in the total Professional Preventive Knowledge Scale (PPKS) (p=0.016) and its subscales of the noncariogenic nutrition (p=0.015), dental hygiene/clinical examination (p < 0.001), caries-preventive practice (p=0.02), and the Hiroshima University-Dental Behavioral Inventory (HU-DBI) (p=0.028). Significant differences were observed in the total PPKS (p=0.003) and its subscales of the noncariogenic nutrition (p=0.043) and caries risk management (p=0.006) in terms of self-perceived need to receive education and training. Caries-preventive practice was correlated with the self-perceived competency (r = 0.279; p=0.002), the attitudes (r = 0.394; p < 0.001), the total PPKS (r = 0.457; p < 0.001) and its all subscales of dental hygiene and clinical examination (r = 0.425; p < 0.001), noncariogenic nutrition (r = 0.410; p < 0.001), and caries risk management (r = 0.184; p=0.039). The self-perceived competency was positively correlated with the total PPKS (r = 0.192; p=0.031) and its subscale of noncariogenic nutrition (r = 0.259; p=0.003). Greater self-perceived competence, more positive attitudes, and good knowledge regarding preventive dentistry were found to be important predictors of the caries-preventive practice of dental students, explaining 31% of the variance (adjusted R2 = 0.312, p < 0.001). Conclusion 40% of dental students reported educational and training needs regarding the diagnosis, caries-preventive agents, and risk-based treatment plan. These results should be taken into account by the stakeholders in developing the national core curriculum for undergraduate Turkish dental education.
Emerging antimicrobial resistance and newer tools to address the resistance

Antimicrobial resistance (AMR) is globally a serious threat in public health causing unfavorable effects which could be clinical (death or treatment failure) or economic (care cost and stay period). [1] The current data on antibiotic resistance are signaling to a difficult situation as this could land any country into drastic health as well as economic crisis. There is a global increase of 65% in antibiotic consumption in the year 2015 as compared to 2000. [2] It is estimated that by 2050, there would be a decrease in gross domestic product rate by 23.5% as a consequence of AMR. [1]
Definitive therapy of colonic angioectasia by submucosal coagulation

Abstract Background and study aims Colonic angioectasia are the most common vascular lesions in the gastrointestinal tract and are among the most common causes for chronic or recurrent lower gastrointestinal bleeding. Endoscopic treatment involves a variety of techniques, all of which focus on destruction of the mucosal abnormality. However, recurrent bleeding after endoscopic treatment is common, with more than one treatment frequently necessary. We report a technique for definitive treatment of colonic angioectasia by targeting the feeding submucosal vessel. Patients and methods Analogous to endoscopic mucosal resection, a submucosal injection is made beneath the target lesion which is then removed by electrocautery snare resection of the mucosal lesion. The exposed feeding vessel is then destroyed by application of coagulation current. The resection defect is closed by clips. Results Six patients with a total of 14 colonic angioectasia were treated over the study period. All lesions were destroyed without adverse events. Conclusion Elevation, hot snare resection and coagulation (ESC) of the visible vessel for treating colonic angioectasia appears safe and effective. Larger prospective comparative studies are required to assess its specific role.
A 3D-printed microfluidic-enabled hollow microneedle architecture for transdermal drug delivery

Embedding microfluidic architectures with microneedles enables fluid management capabilities that present new degrees of freedom for transdermal drug delivery. To this end, fabrication schemes that can simultaneously create and integrate complex millimeter/centimeter-long microfluidic structures and micrometer-scale microneedle features are necessary. Accordingly, three-dimensional (3D) printing techniques are suitable candidates because they allow the rapid realization of customizable yet intricate microfluidic and microneedle features. However, previously reported 3D-printing approaches utilized costly instrumentation that lacked the desired versatility to print both features in a single step and the throughput to render components within distinct length-scales. Here, for the first time in literature, we devise a fabrication scheme to create hollow microneedles interfaced with microfluidic structures in a single step. Our method utilizes stereolithography 3D-printing and pushes its boundaries (achieving print resolutions below the full width half maximum laser spot size resolution) to create complex architectures with lower cost and higher print speed and throughput than previously reported methods. To demonstrate a potential application, a microfluidic-enabled microneedle architecture was printed to render hydrodynamic mixing and transdermal drug delivery within a single device. The presented architectures can be adopted in future biomedical devices to facilitate new modes of operations for transdermal drug delivery applications such as combinational therapy for preclinical testing of biologic treatments.
Retinal correlates of neurological disorders

Considering the retina as an extension of the brain provides a platform from which to study diseases of the nervous system. Taking advantage of the clear optical media of the eye and ever-increasing resolution of modern imaging techniques, retinal morphology can now be visualized at a cellular level in vivo. This has provided a multitude of possible biomarkers and investigative surrogates that may be used to identify, monitor and study diseases until now limited to the brain. In many neurodegenerative conditions, early diagnosis is often very challenging due to the lack of tests with high sensitivity and specificity, but, once made, opens the door to patients accessing the correct treatment that can potentially improve functional outcomes. Using retinal biomarkers in vivo as an additional diagnostic tool may help overcome the need for invasive tests and histological specimens, and offers the opportunity to longitudinally monitor individuals over time. This review aims to summarise retinal biomarkers associated with a range of neurological conditions including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and prion diseases from a clinical perspective. By comparing their similarities and differences according to primary pathological processes, we hope to show how retinal correlates can aid clinical decisions, and accelerate the study of this rapidly developing area of research.
MoRBP9 Encoding a Ran-Binding Protein Microtubule-Organizing Center Is Required for Asexual Reproduction and Infection in the Rice Blast Pathogen Magnaporthe oryzae

Like many fungal pathogens, the conidium and appressorium play key roles during polycyclic dissemination and infection of Magnaporthe oryzae. Ran-binding protein microtubule-organizing center (RanBPM) is a highly conserved nucleocytoplasmic protein. In animalia, RanBPM has been implicated in apoptosis, cell morphology, and transcription. However, the functional roles of RanBPM, encoded by MGG_00753 (named MoRBP9) in M. oryzae, have not been elucidated. Here, the deletion mutant ΔMorbp9 for MoRBP9 was generated via homologous recombination to investigate the functions of this gene. The ΔMorbp9 exhibited normal conidial germination and vegetative growth but dramatically reduced conidiation compared with the wild type, suggesting that MoRBP9 is involved in conidial production. ΔMorbp9 conidia failed to produce appressoria on hydrophobic surfaces, whereas ΔMorbp9 still developed aberrantly shaped appressorium-like structures at hyphal tips on the same surface, suggesting that MoRBP9 is involved in the morphology of appressorium-like structures from hyphal tips and is critical for development of appressorium from germ tubes. Taken together, our results indicated that MoRBP9 played a pleiotropic role in polycyclic dissemination and infection-related morphogenesis of M. oryzae.
miR-195-Sirt3 Axis Regulates Angiotensin II-Induced Hippocampal Apoptosis and Learning Impairment in Mice

Objective Apoptosis plays an essential role in cell development and aging, which is associated with a series of diseases, such as neurodegeneration. MircoRNAs exert important roles in the regulation of gene expression. As a stress-responsive deacetylase in mitochondria, sirtuin-3 (sirt3) is a key regulator for mitochondrial function and apoptosis. Also, miR-195 has been demonstrated to be involved in cell cycle and apoptosis. Therefore, this study aimed to investigate the effects of miR-195-sirt3 axis on angiotensin II (ANG II)-induced hippocampal apoptosis and behavioral influence. Materials and methods ANG II infusion was used to establish the hypertensive model in HT22 cells and 129S6/SvEvTac mice, respectively. TUNEL assay was used to evaluate the apoptosis level. Mitochondrial membrane potential (MMP) was measured to evaluate the mitochondrial property. Immunohistochemistry, RT-PCR, Western blotting, and luciferase reporter assay were conducted to determine the underlying molecular mechanism. Results The results revealed that ANG II treatment promoted apoptosis in the hippocampal cells and tissues, along with increased sirt3 and decreased miR-195 expression. Silencing sirt3 by genetic engineering or siRNA reversed ANG II-induced hippocampal apoptosis. Sirt3 was identified as a direct target gene of miR-195. Forced expression of miR-195 could play counteractive roles in hippocampal apoptosis induced by ANG II. Furthermore, the behavioral assay demonstrated that ANG II-induced hippocampal apoptosis impaired the performance in the spatial navigation task, but not in the spatial memory task. Conclusion The results suggested that miR-195-sirt3 axis plays an important role in the ANG II-induced hippocampal apoptosis via altering mitochondria-apoptosis proteins and mitochondria permeability and that hippocampal apoptosis is associated with impaired learning capability in hypertensive mice. This study provides insights into the molecular architecture of apoptosis-related neurodegenerative diseases.
Biomechanical and Morphologic Effects of Collagen Cross-Linking in Human Tarsus

Purpose To investigate the feasibility of increasing the stiffness of human tarsal tissue following treatment with riboflavin and ultraviolet A (UVA) to induce cross-linking of collagen fibers. Methods In this case control study, 18 right and left upper eyelids were excised en bloc from 18 fresh-frozen cadavers. One side served as the control while the samples from the opposite side were cross-linked. Four 2 × 6-mm vertical strips of central tarsus were cut from the superior to inferior border of each tarsal plate. Sample tissue was irradiated with UVA at 6 mW/cm2 for 18 minutes. A microtensile load cell and an optical coherence tomography scanner allowed calculation of stiffness (Young's modulus). Six cross-linked samples and corresponding controls were stained with hematoxylin and eosin (H&E) and Masson trichrome stains. Four controls and four cross-linked samples were also reviewed with a transmission electron microscope. Results Mean Young's modulus in the linear region for controls was 28 ± 9 MPa and was much higher at 138 ± 8 MPa for cross-linked samples (P < 0.001), yielding a 493% mean stiffness increase. Staining with H&E and Masson did not reveal any histologic changes. Transmission electron microscopy showed a decrease in average diameter of 50 randomly selected collagen fibers from 47.2 ± 1.9 nm prior to cross-linking to 34.2 ± 1.1 nm post cross-linking (P < 0.001). Qualitatively, the collagen fibers appeared more closely packed following cross-linking. Conclusions The findings of this study suggest that collagen cross-linking is a viable and effective modality for increasing the stiffness of human tarsal plates. Translational Relevance This work provides proof that collagen cross-linking produces stiffening of the human tarsal plate and may be used in disorders that cause eyelid laxity.
Enhancement of Quercetin-Induced Apoptosis by Cotreatment with Autophagy Inhibitor Is Associated with Augmentation of BAK-Dependent Mitochondrial Pathway in Jurkat T Cells

A flavonoid antioxidant quercetin promotes dose-dependent activation of the ATM-CHK-p53 pathway, downregulation of antiapoptotic survivin, and upregulation of proapoptotic NOXA in human T cell acute lymphoblastic leukemia Jurkat clones (J/Neo and J/BCL-XL). However, the downregulation of antiapoptotic BAG3 and MCL-1 occurred in J/Neo cells but not in J/BCL-XL cells overexpressing BCL-XL. Additionally, several BCL-XL-sensitive intrinsic mitochondrial apoptotic events including apoptotic sub-G1 cell accumulation, TUNEL-positive DNA fragmentation, BAK activation, mitochondrial membrane potential (Δψm) loss, caspase-9/caspase-8/caspase-3 activation, and PARP cleavage were induced only in J/Neo cells. Both cytosolic and mitochondrial ROS levels were elevated in quercetin-treated J/Neo cells; however, the ROS elevations were almost completely abrogated in J/BCL-XL cells, suggesting the ROS elevations were downstream of BCL-XL-sensitive mitochondrial damage and dysfunction. Wild-type A3, FADD-deficient I2.1, and caspase-8-deficient I9.2 Jurkat clones exhibited similar susceptibilities to the cytotoxicity of quercetin, excluding an involvement of extrinsic pathway in triggering the apoptosis. The autophagic events such as attenuation of AKT-mTOR pathway, formation of acridine orange-stainable acidic vesicular organelles, conversion of microtubule-associated protein 1 light chain 3-I (LC3-I) to LC3-II, and downregulation of p62/SQSTM1 level were detected in quercetin-treated J/Neo and J/BCL-XL cells, regardless of BCL-XL overexpression. Cotreatment with the autophagy inhibitor (3-methyladenine, LY294002, or chloroquine) resulted in a significant enhancement of quercetin-induced BAK activation and subsequently the mitochondrial damage-mediated apoptosis pathway by augmenting the downregulation of BAG3 and MCL-1 levels in J/Neo cells. These results demonstrated that quercetin induces intrinsic apoptosis and cytoprotective autophagy, and autophagy inhibition can potentiate BAK-dependent apoptotic activity of quercetin in Jurkat T cells.
An Evaluation Of Single And Dual Long-Acting Bronchodilator Therapy As Effective Interventions In Maintenance Therapy-Naïve Patients With COPD

Background Ideally, treatment recommendations for maintenance therapy-naïve patients with COPD should be based on studies conducted specifically in this population. We have reviewed evidence from previous studies of pharmacological treatments in maintenance therapy-naïve patients with COPD and performed a new post-hoc analysis of dual bronchodilator treatment in this population, aiming to assess the effectiveness of these interventions. Materials and methods A literature review identified clinical trials that included analyses of patients with COPD who were maintenance therapy-naïve with long-acting β2-agonists (LABA) or long-acting muscarinic antagonists (LAMA). Additionally, a post-hoc subgroup analysis was conducted for maintenance therapy-naïve patients with COPD in two large phase III, randomized, double-blind, 24-week trials investigating the efficacy of aclidinium bromide/formoterol fumarate (AB/FF) fixed-dose combination versus monotherapy or placebo (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]). Results Treatment-naïve patients with COPD often represent a population of patients at the earliest stage at which most patients seek treatment. Of nine relevant studies identified, all reported positive findings for efficacy of LABA, LAMA, or LABA/LAMA treatment in maintenance therapy-naïve populations. Improvements were observed in lung function, symptoms, and health status versus monotherapy or placebo. Post-hoc analysis of ACLIFORM and AUGMENT demonstrated that AB/FF was effective in improving lung function in patients who had received no prior maintenance therapy. AB/FF showed improvements in 1 hr post-dose FEV1, trough FEV1, and patient-reported outcomes versus placebo and monotherapies. Combined with reviews of previous studies in maintenance therapy-naïve patients, these findings suggest that earlier intervention with a dual bronchodilator maintenance therapy, such as AB/FF, may provide significantly greater benefits than LAMA or LABA mono-bronchodilator therapy as a first maintenance treatment for COPD. Conclusion These data show that therapeutic intervention is effective in treatment-naïve patients. Intervention with dual bronchodilator therapy as a first maintenance treatment for COPD may provide greater benefits than LAMA or LABA monotherapy.