Miracle-dz/UniFAR-FTUs huggingface dataset:
CDKN2A-Inactivated Pancreatic Ductal Adenocarcinoma Exhibits Therapeutic Sensitivity to Paclitaxel: A Bioinformatics Study

The mutation of cyclin dependent kinase inhibitor 2A (CDKN2A) is frequently found in pancreatic ductal adenocarcinoma (PDAC). However, its prognostic and therapeutic roles in PDAC have not been extensively investigated yet. In this study, we mined and integrated the cancer genomics and chemogenomics data to investigate the roles of CDKN2A genetic alterations in PDAC patients’ prognosis and treatment. We found that functional CDKN2A inactivation caused by mutations and deep deletions predicted poor prognosis in PDAC patients. CDKN2A inactivation was associated with the upregulation of genes related to estrogen response, which can be overcome by CDKN2A restoration. Chemosensitivity profiling of PDAC cell lines and patient-derived organoids found that CDKN2A inactivation was associated with the increased sensitivity to paclitaxel and SN-38 (the active metabolite of irinotecan). However, only paclitaxel can mimic the effect of CDKN2A restoration, and its drug sensitivity was correlated with genes related to estrogen response. Therefore, our study suggested that CDKN2A-inactivated PDAC patients could benefit from the precision treatment with paclitaxel, whose albumin-stabilized nanoparticle formulation (nab-paclitaxel) has been approved for treating PDAC.
The Antimicrobial Peptide Temporin G: Anti-Biofilm, Anti-Persister Activities, and Potentiator Effect of Tobramycin Efficacy Against Staphylococcus aureus

Bacterial biofilms are a serious threat for human health, and the Gram-positive bacterium Staphylococcus aureus is one of the microorganisms that can easily switch from a planktonic to a sessile lifestyle, providing protection from a large variety of adverse environmental conditions. Dormant non-dividing cells with low metabolic activity, named persisters, are tolerant to antibiotic treatment and are the principal cause of recalcitrant and resistant infections, including skin infections. Antimicrobial peptides (AMPs) hold promise as new anti-infective agents to treat such infections. Here for the first time, we investigated the activity of the frog-skin AMP temporin G (TG) against preformed S. aureus biofilm including persisters, as well as its efficacy in combination with tobramycin, in inhibiting S. aureus growth. TG was found to provoke ~50 to 100% reduction of biofilm viability in the concentration range from 12.5 to 100 µM vs ATCC and clinical isolates and to be active against persister cells (about 70–80% killing at 50–100 µM). Notably, sub-inhibitory concentrations of TG in combination with tobramycin were able to significantly reduce S. aureus growth, potentiating the antibiotic power. No critical cytotoxicity was detected when TG was tested in vitro up to 100 µM against human keratinocytes, confirming its safety profile for the development of a new potential anti-infective drug, especially for treatment of bacterial skin infections.
Role of Nutraceuticals in COVID-19 Mediated Liver Dysfunction

COVID-19 is known as one of the deadliest pandemics of the century. The rapid spread of this deadly virus at incredible speed has stunned the planet and poses a challenge to global scientific and medical communities. Patients with COVID-19 are at an increased risk of co-morbidities associated with liver dysfunction and injury. Moreover, hepatotoxicity induced by antiviral therapy is gaining importance and is an area of great concern. Currently, alternatives therapies are being sought to mitigate hepatic damage, and there has been growing interest in the research on bioactive phytochemical agents (nutraceuticals) due to their versatility in health benefits reported in various epidemiological studies. Therefore, this review provides information and summarizes the juncture of antiviral, immunomodulatory, and hepatoprotective nutraceuticals that can be useful during the management of COVID-19.
The Relationship Between Children’s Exposure to Intimate Partner Violence and an Emotional–Behavioral Disability: A Scoping Review

Children’s exposure to intimate partner violence (IPV) is an adverse childhood experience that often results in academic, behavior, and mental health difficulties. This study reviewed the empirical studies examining the relationship between children’s exposure to IPV and an emotional–behavioral disability (EBD). Studies were included in the review if they examined the relationship between exposure to IPV and EBD among children under 18. This research identified three empirical studies that analyzed the relationship between exposure to IPV and EBD. The review demonstrated that few studies had been conducted that explored the relationship between children’s exposure to IPV and EBD and that most of the extant studies are dated. Findings from this review showed that children exposed to IPV were more likely to have EBD compared to other disabilities such as a learning disability, hearing disability, speech and language disability, and an intellectual disability. Higher frequency of violence exposure was associated with EBD. Practice implications include assessing children’s functioning at school and discussing with families or caregivers the option of requesting an evaluation for EBD for children with severe emotional or behavioral difficulties. Special education evaluators assessing children for EBD should consider screening for children’s exposure to IPV and providing resources for IPV. Future research should conceptualize the full range of IPV experiences and collect exposure data from children directly using a validated measure.
Fabrication of Cu/Co bilayer gate electrodes using selective chemical vapor deposition and soft lithographic patterning

A templated Cu/Co bilayer gate electrode was fabricated using the combined method of consecutive and selective chemical vapor deposition (CVD), and octadecyltrichlorosilane (OTS) microcontact printing techniques. Soft lithographically patterned self-assembled monolayers (SAMs) can direct the growth of Co occurring at the low temperatures 50–90 °C and serve as a template for the consecutive and selective growth of Cu, thereby forming stable and high quality Cu/Co bilayer gate electrodes on a glass substrate. This simple process provides fewer process steps and higher performance than other conventional processes, and can be applied to the fabrication of large area and high resolution thin film transistor liquid crystal displays.
Unilateral and Bilateral Strength Asymmetry among Young Elite Athletes of Various Sports

Background and objective: Type of physical activity may influence morphological and muscular asymmetries in the young population. However, less is known about the size of this effect when comparing various sports. The aim of this study was to identify the degree of bilateral asymmetry (BA) and the level of unilateral ratio (UR) between isokinetic strength of knee extensors (KE) and flexors (KF) among athletes of three different types of predominant locomotion in various sports (symmetric, asymmetric and hybrid). Material and methods: The analyzed group consisted of young elite athletes (n = 50). The maximum peak muscle torque of the KE and KF in both the dominant (DL) and non-dominant (NL) lower limb during concentric muscle contraction at an angular velocity of 60°·s−1 was measured with an isokinetic dynamometer. Results: Data analysis showed a significant effect of the main factor (the type of sport) on the level of monitored variables (p = 0.004). The type of sport revealed a significant difference in the bilateral ratio (p = 0.01). The group of symmetric and hybrid sports achieved lower values (p = 0.01) of BA in their lower limb muscles than those who played asymmetric sports. The hybrid sports group achieved higher UR values (p = 0.01) in both lower limbs. Conclusions: The results indicate that sports with predominantly symmetrical, asymmetrical, and hybrid types of locomotion affected the size of the BA, as well as the UR between KE and KF in both legs in young athletes. We recommend paying attention to regular KE and KF strength diagnostics in young athletes and optimizing individual compensatory exercises if a higher ratio of strength asymmetry is discovered.
Prevalence and risk factor assessment of digital eye strain among children using online e-learning during the COVID-19 pandemic: Digital eye strain among kids (DESK study-1).

Purpose The aim of this study was to determine prevalence, symptoms frequency and associated risk factors of digital eye strain (DES) among children attending online classes during COVID-19 pandemic. Methods The online electronic survey form was prepared on the Google app. Children/parents were asked to indicate the total duration of digital device use before and during COVID era. The symptoms of DES, its severity and frequency were recorded & measured with the Computer Vision Syndrome Questionnaire. Results Two hundred and sixty one parents responded to the questionnaire, of these 217 were complete. Mean age of children was 13 ± 2.45 years. Mean duration of digital device used during COVID era was 3.9 ± 1.9 h which is more than pre COVID era (1.9 ± 1.1 h, P = <0.0001). 36.9% (n = 80) were using digital devices >5 h in COVID era as compared to 1.8% (n = 4) before COVID era. The most common digital device used were smartphones (n = 134, 61.7%). One hundred and eight children (49.8%) were attending online classes for >2 h per day. Prevalence of DES in our cohort is 50.23% (109/217). Of these 26.3% were mild, 12.9% moderate and 11.1% of severe grade. Most common symptoms were itching and headache (n = 117, 53.9%). Multivariate analysis revealed age >14 years (P = 0.04), male gender (P = 0.0004), smartphone use (P = 0.003), use of device >5 h (P = 0.0007) and mobile games >1 h/day (P = 0.0001) as independent risk factors for DES in children. Conclusion There is an increased prevalence of DES among children in COVID era. Parents should be considerate about duration, type and distance of digital device use to avoid DES symptoms in children.
Facilitating Clinical Trials Participation of Low Socioeconomic Status Patients

a College of Medicine, University of Illinois, Chicago, IL, USA; b Department of Dermatology, Henry Ford Health System, Detroit, MI, USA; c Division of Dermatology, Department of Medicine, University of California, Los Angeles, CA, USA; d Division of Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR, USA Received: May 29, 2020 Accepted: September 18, 2020 Published online: December 15, 2020
Temporal Changes in In Vivo Glutamate Signal during Demyelination and Remyelination in the Corpus Callosum: A Glutamate-Weighted Chemical Exchange Saturation Transfer Imaging Study

Background: Glutamate-weighted chemical exchange saturation transfer (GluCEST) is a useful imaging tool that can be used to detect changes in glutamate levels in vivo and could also be helpful in the diagnosis of brain myelin changes. We investigated glutamate level changes in the cerebral white matter of a rat model of cuprizone-administered demyelination and remyelination using GluCEST. Method: We used a 7 T pre-clinical magnetic resonance imaging (MRI) system. The rats were divided into the normal control (CTRL), cuprizone-administered demyelination (CPZDM), and remyelination (CPZRM) groups. GluCEST data were analyzed using the conventional magnetization transfer ratio asymmetry in the corpus callosum. Immunohistochemistry and transmission electron microscopy analyses were also performed to investigate the myelinated axon changes in each group. Results: The quantified GluCEST signals differed significantly between the CPZDM and CTRL groups (−7.25 ± 1.42% vs. −2.84 ± 1.30%; p = 0.001). The increased GluCEST signals in the CPZDM group decreased after remyelination (−6.52 ± 1.95% in CPZRM) to levels that did not differ significantly from those in the CTRL group (p = 0.734). Conclusion: The apparent temporal signal changes in GluCEST imaging during demyelination and remyelination demonstrated the potential usefulness of GluCEST imaging as a tool to monitor the myelination process.
Motion-form interaction: Motion and form aftereffects induced by distorted static natural scenes

Spatially varying distortions (SVDs) are common artifacts of spectacles like progressive additional lenses (PALs). To habituate to distortions of PALs, the visual system has to adapt to distortion-induced image alterations, termed skew adaptation. But how this visual adjustment is achieved is largely unknown. This study examines the properties of visual adaptation to distortions of PALs in natural scenes. The visual adaptation in response to altered form and motion features of the natural stimuli were probed in two different psychophysical experiments. Observers were exposed to distortions in natural images, and form and motion aftereffects were tested subsequently in a constant stimuli procedure where subjects were asked to judge the skew, or the motion direction of an according test stimulus. Exposure to skewed natural stimuli induced a shift in perceived undistorted form as well as motion direction, when viewing distorted dynamic natural scenes, and also after exposure to static distorted natural images. Therefore, skew adaptation occurred in form and motion for dynamic visual scenes as well as static images. Thus, specifically in the condition of static skewed images and the test feature of motion direction, cortical interactions between motion-form processing presumably contributed to the adaptation process. In a nutshell, interfeature cortical interactions constituted the adaptation process to distortion of PALs. Thus, comprehensive investigation of adaptation to distortions of PALs would benefit from taking into account content richness of the stimuli to be used, like natural images.
Accelerated Spatial Fibrin Growth and Impaired Contraction of Blood Clots in Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease associated with thrombotic complications. To elucidate pathogenic mechanisms, hemostatic disorders in RA were correlated with other laboratory and clinical manifestations. Hemostasis was assessed using relatively new complementary tests, the spatial growth of a plasma clot (Thrombodynamics assay), and contraction of whole blood clots. Platelet functionality was assessed with flow cytometry that quantified the expression of P-selectin and the fibrinogen-binding capacity of platelets before and after activation with a thrombin receptor-activating peptide. Parameters of fibrin clot growth and the kinetics of contraction of blood clots were significantly altered in patients with RA compared to the control group. In Thrombodynamics measurements, an increase in the clot growth rate, size, and optical density of plasma clots altogether indicated chronic hypercoagulability. The rate and extent of blood clot contraction in patients with RA was significantly reduced and associated with platelet dysfunction revealed by an impaired response to activation. Changes in the parameters of clot growth and contraction correlated with the laboratory signs of systemic inflammation, including hyperfibrinogenemia. These results confirm the pathogenic role of hemostatic disorders in RA and support the validity of fibrin clot growth and the blood clot contraction assay as indicators of a (pro)thrombotic state.
Computed tomography angiography-derived extracellular volume fraction predicts early recovery of left ventricular systolic function after transcatheter aortic valve replacement.

AIMS Recovery of left ventricular ejection fraction (LVEF) after aortic valve replacement has prognostic importance in patients with aortic stenosis (AS). The mechanism by which myocardial fibrosis impacts LVEF recovery in AS is not well characterized. We sought to evaluate the predictive value of extracellular volume fraction (ECV) quantified by cardiac CT angiography (CTA) for LVEF recovery in patients with AS after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS In 109 pre-TAVR patients with LVEF <50% at baseline echocardiography, CTA-derived ECV was calculated as the ratio of change in CT attenuation of the myocardium and the left ventricular (LV) blood pool before and after contrast administration. Early LVEF recovery was defined as an absolute increase of ≥10% in LVEF measured by post-TAVR follow-up echocardiography within 6 months of the procedure. Early LVEF recovery was observed in 39 (36%) patients. The absolute increase in LVEF was 17.6 ± 8.8% in the LVEF recovery group and 0.9 ± 5.9% in the no LVEF recovery group (P < 0.001). ECV was significantly lower in patients with LVEF recovery compared with those without LVEF recovery (29.4 ± 6.1% vs. 33.2 ± 7.7%, respectively, P = 0.009). In multivariable analysis, mean pressure gradient across the aortic valve [odds ratio (OR): 1.07, 95% confidence interval (CI): 1.03-1.11, P: 0.001], LV end-diastolic volume (OR: 0.99, 95% CI: 0.98-0.99, P: 0.035), and ECV (OR: 0.92, 95% CI: 0.86-0.99, P: 0.018) were independent predictors of early LVEF recovery. CONCLUSION Increased myocardial ECV on CTA is associated with impaired LVEF recovery post-TAVR in severe AS patients with impaired LV systolic function.
A Preliminary Study on the Differentiation of Linseed and Poppy Oil Using Principal Component Analysis Methods Applied to Fiber Optics Reflectance Spectroscopy and Diffuse Reflectance Imaging Spectroscopy

This paper presents results from the examination of a set of experimental samples using fibre optic reflectance spectroscopy (FORS) and diffuse reflectance imaging spectroscopy in the short-wave infrared (SWIR) range, combined with statistical analysis of the data for the discrimination and mapping of poppy and linseed oil. The aim was to evaluate the efficacy of this non-invasive approach for the study of paint samples with a view to the application of the method for characterisation of the two drying oils in painted art. The approach allowed discrimination between the two drying oils based on FORS spectra and the hyperspectral cube, indicating the influence of the spectral region around 1700 nm on the statistical discrimination based on the anti-symmetric and symmetric first overtone stretching of methylenic CH2 groups. This method is being studied as a potential non-invasive method of organic analysis of oil types that have formerly been studied using gas chromatography-mass spectrometry (GC-MS), which requires micro-samples.
Hydrogen sulfide restores sevoflurane postconditioning mediated cardioprotection in diabetic rats: Role of SIRT1/Nrf2 signaling‐modulated mitochondrial dysfunction and oxidative stress

Diabetic hearts are vulnerable to myocardial ischemia/reperfusion injury (IRI), but are insensitive to sevoflurane postconditioning (SPC), activating peroxiredoxins that confer cardioprotection. Previous studies have demonstrated that hydrogen sulfide (H2S) can suppress oxidative stress of diabetic rats through increasing the expression of silent information regulator factor 2‐related enzyme 1 (SIRT1), but whether cardioprotection by SPC can be restored afterward remains unclear. Diabetic rat was subjected to IRI (30 min of ischemia followed by 120 min reperfusion). Postconditioning treatment with sevoflurane was administered for 15 min upon the onset of reperfusion. The diabetic rats were treated with GYY4137 (H2S donor) 5 days before the experiment. Myocardial infarct size, mitochondrial structure and function, ATP content, activities of complex I‐IV, marker of oxidative stress, SIRT1, nuclear factor E2‐related factor 2 (Nrf2), heme oxygenase‐1 (HO‐1), and NADPH Oxidase‐2 (Nox‐2) protein expression were detected after reperfusion, and cardiac function was evaluated by echocardiography at 24 h after reperfusion. After H2S activated SIRT1 in the impaired myocardium of diabetic rats, SPC significantly upregulated the expression of Nrf2 and its downstream mediator HO‐1, thus reduced the expression of Nox‐2. In addition, H2S remarkably increased cytoplasmic and nuclear SIRT1 which was further enhanced by SPC. Furthermore, H2S combined with SPC reduced the production of reactive oxygen species, increased the content of ATP, and maintained mitochondrial enzyme activity. Finally, myocardial infarct size and myocardium damage were decreased, and cardiac function was improved. Taken together, our study proved that H2S could restore SPC‐induced cardioprotection in diabetic rats by enhancing and promoting SIRT1/Nrf2 signaling pathway mediated mitochondrial dysfunction and oxidative stress.
Adaptive post-transcriptional reprogramming of metabolism limits response to targeted therapy in BRAFV600 melanoma

Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by a residual disease that results in relapse. This residual disease is characterized by drug-induced adaptation, that in melanoma includes altered metabolism. Here, we examined how targeted therapy reprograms metabolism in BRAF-mutant melanoma cells using a genome-wide RNAi screen and global gene expression profiling. This systematic approach revealed post-transcriptional regulation of metabolism following BRAF inhibition, involving selective mRNA transport and translation. As proof of concept we demonstrate the RNA binding kinase UHMK1 interacts with mRNAs that encode metabolic proteins and selectively controls their transport and translation during adaptation to BRAF targeted therapy. Inactivation of UHMK1 improves metabolic response to BRAF targeted therapy and delays resistance to BRAF and MEK combination therapy in vivo. Our data support a model wherein post-transcriptional gene expression pathways regulate metabolic adaptation underpinning targeted therapy response and suggest inactivation of these pathways may delay disease relapse.
Intraspecific variation alters ecosystem and next-generation performance as much as temperature

Phenotypic or genotypic variation within species affects ecological processes, from populations to ecosystems. However, whether the ecological imprint of intraspecific variation is substantial compared to key environmental drivers, and persistent enough to carry over to next generations is still questioned. Here, we experimentally showed that intraspecific variation manipulated in a freshwater fish (the European minnow, Phoxinus phoxinus) led to ecological and transgenerational carry-over effects that were as strong as those of varying temperature by 2°C. Specifically, variation in fish body mass, growth rate and activity altered the size and abundance of prey, which ultimately affected traits and survival of the next fish generation. Temperature variation modulated other ecosystem functions (e.g. litter decomposition) that were also associated to transgenerational carry-over effects. Our results demonstrate that shifting genotypes or phenotypes in wild populations can have substantial and persistent consequences on ecosystems with a similar intensity than climatic variation.