Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment of Cardiovascular Dysfunction With PDE5-Inhibitors – Temperature Dependent Effects on Transport and Metabolism of cAMP and cGMP

Introduction Cardiovascular dysfunction is a potentially lethal complication of hypothermia. Due to a knowledge gap, pharmacological interventions are not recommended at core temperatures below 30°C. Yet, further cooling is induced in surgical procedures and survival of accidental hypothermia is reported after rewarming from below 15°C, advocating a need for evidence-based treatment guidelines. In vivo studies have proposed vasodilation and afterload reduction through arteriole smooth muscle cGMP-elevation as a favorable strategy to prevent cardiovascular dysfunction in hypothermia. Further development of treatment guidelines demand information about temperature-dependent changes in pharmacological effects of clinically relevant vasodilators. Materials and Methods Human phosphodiesterase-enzymes and inverted erythrocytes were utilized to evaluate how vasodilators sildenafil and vardenafil affected cellular efflux and enzymatic breakdown of cAMP and cGMP, at 37°C, 34°C, 32°C, 28°C, 24°C, and 20°C. The ability of both drugs to reach their cytosolic site of action was assessed at the same temperatures. IC50- and Ki-values were calculated from dose–response curves at all temperatures, to evaluate temperature-dependent effects of both drugs. Results Both drugs were able to reach the intracellular space at all hypothermic temperatures, with no reduction compared to normothermia. Sildenafil IC50 and Ki-values increased during hypothermia for enzymatic breakdown of both cAMP (IC50: 122 ± 18.9 μM at 37°C vs. 269 ± 14.7 μM at 20°C, p < 0.05) and cGMP (IC50: 0.009 ± 0.000 μM at 37°C vs. 0.024 ± 0.004 μM at 32°C, p < 0.05), while no significant changes were detected for vardenafil. Neither of the drugs showed significant hypothermia-induced changes in IC50 and Ki–values for inhibition of cellular cAMP and cGMP efflux. Conclusion Sildenafil and particularly vardenafil were ableto inhibit elimination of cGMP down to 20°C. As the cellular effects of these drugs can cause afterload reduction, they show potential in treating cardiovascular dysfunction during hypothermia. As in normothermia, both drugs showed higher selectivity for inhibition of cGMP-elimination than cAMP-elimination at low core temperatures, indicating that risk for cardiotoxic side effects is not increased by hypothermia.
Response of Leaf Traits of Eastern Qinghai-Tibetan Broad-Leaved Woody Plants to Climatic Factors

Plant ecologists have long been interested in quantifying how leaf traits vary with climate factors, but there is a paucity of knowledge on these relationships given a large number of the relevant leaf traits and climate factors to be considered. We examined the responses of 11 leaf traits (including leaf morphology, stomatal structure and chemical properties) to eight common climate factors for 340 eastern Qinghai-Tibetan woody species. We showed temperature as the strongest predictor of leaf size and shape, stomatal size and form, and leaf nitrogen and phosphorus concentrations, implying the important role of local heat quantity in determining the variation in the cell- or organ-level leaf morphology and leaf biochemical properties. The effects of moisture-related climate factors (including precipitation and humidity) on leaf growth were mainly through variability in leaf traits (e.g., specific leaf area and stomatal density) related to plant water-use physiological processes. In contrast, sunshine hours affected mainly cell- and organ-level leaf size and shape, with plants developing small/narrow leaves and stomata to decrease leaf damage and water loss under prolonged solar radiation. Moreover, two sets of significant leaf trait-climate relationships, i.e., the leaf/stomata size traits co-varying with temperature, and the water use-related leaf traits co-varying with precipitation, were obtained when analyzing multi-trait relationships, suggesting these traits as good indicators of climate gradients. Our findings contributed evidence to enhance understanding of the regional patterns in leaf trait variation and its environmental determinants.
The Effects of Gender, Functional Condition, and ADL on Pressure Pain Threshold in Stroke Patients

Background Somatosensory impairments and pain are common symptoms following stroke. However, the condition of perception and pain threshold for pressure stimuli and the factors that can influence this in individuals with stroke are still unclear. This study aimed to investigate the gender differences in pressure pain threshold (PPT) and positive somatosensory signs for pressure stimuli, and explore the effects of joint pain, motor function, and activities of daily living (ADL) on pain threshold in post-stroke patients. Design A cross-sectional study. Methods A total of 60 participants with stroke were recruited, and their pain condition, motor functions, and ADL were evaluated by the Fugl-Meyer assessment of joint pain scale, motor function scale, and Barthel index, respectively. PPTs in eight tested points at the affected and unaffected sides were assessed. Results Significant differences in PPTs were found between male and female patients in all measured muscles (p < 0.05). Positive somatosensory signs for pressure stimuli, including hypoalgesia and hyperalgesia, were frequently found at the affected side, particularly in the extremity muscles, but such signs were not significantly influenced by gender (p > 0.05). More equal PPTs between both sides and relatively lower PPTs at the affected side in the trunk and medial gastrocnemius muscles (p < 0.05) were observed in patients with less pain, better motor functions, and ADL. Conclusion Gender differences widely exist in post-stroke survivors either at the affected or unaffected side, which are multifactorial. Sensory loss and central and/or peripheral sensitization, such as hypoalgesia and hyperalgesia for pressure stimuli, caused by a brain lesion are common signs in male and female stroke patients. Moreover, patients who are in a better condition show a more symmetrical pain sensitivity between both sides in the trunk and in female lower extremities, indicating the bidirectional improvement of somatosensory abnormalities caused by a possible neural plasticity.
Numerical Study of Divergence Cleaning and Coronal Heating/Acceleration Methods in the 3D COIN-TVD MHD Model

In the solar coronal numerical simulation, the coronal heating/acceleration and the magnetic divergence cleaning techniques are very important. The coronal–interplanetary total variation diminishing (COIN-TVD) magnetohydrodynamic (MHD) model is developed in recent years that can effectively realize the coronal–interplanetary three-dimensional (3D) solar wind simulation. In this study, we focus on the 3D coronal solar wind simulation by using the COIN-TVD MHD model. In order to simulate the heating and acceleration of solar wind in the coronal region, the volume heating term in the model is improved efficiently. Then, the influence of the different methods to reduce the ∇ ⋅ B constraint error on the coronal solar wind structure is discussed. Here, we choose Carrington Rotation (CR) 2199 as a study case and try to make a comparison of the simulation results among the different magnetic divergence cleaning methods, including the diffusive method, the Powell method, and the composite diffusive/Powell method, by using the 3D COIN-TVD MHD model. Our simulation results show that with the different magnetic divergence cleaning methods, the ∇ ⋅ B error can be reduced in different levels during the solar wind simulation. Among the three divergence cleaning methods we used, the composite diffusive/Powell method can maintain the divergence cleaning constraint better to a certain extent, and the relative magnetic field divergence error can be controlled in the order of 10−9. Although these numerical simulations are performed for the background solar corona, these methods are also suitable for the simulation of CME initiation and propagation.
Astrocytic IP3Rs: Beyond IP3R2

Astrocytes are sensitive to ongoing neuronal/network activities and, accordingly, regulate neuronal functions (synaptic transmission, synaptic plasticity, behavior, etc.) by the context-dependent release of several gliotransmitters (e.g., glutamate, glycine, D-serine, ATP). To sense diverse input, astrocytes express a plethora of G-protein coupled receptors, which couple, via Gi/o and Gq, to the intracellular Ca2+ release channel IP3-receptor (IP3R). Indeed, manipulating astrocytic IP3R-Ca2+ signaling is highly consequential at the network and behavioral level: Depleting IP3R subtype 2 (IP3R2) results in reduced GPCR-Ca2+ signaling and impaired synaptic plasticity; enhancing IP3R-Ca2+ signaling affects cognitive functions such as learning and memory, sleep, and mood. However, as a result of discrepancies in the literature, the role of GPCR-IP3R-Ca2+ signaling, especially under physiological conditions, remains inconclusive. One primary reason for this could be that IP3R2 has been used to represent all astrocytic IP3Rs, including IP3R1 and IP3R3. Indeed, IP3R1 and IP3R3 are unique Ca2+ channels in their own right; they have unique biophysical properties, often display distinct distribution, and are differentially regulated. As a result, they mediate different physiological roles to IP3R2. Thus, these additional channels promise to enrich the diversity of spatiotemporal Ca2+ dynamics and provide unique opportunities for integrating neuronal input and modulating astrocyte–neuron communication. The current review weighs evidence supporting the existence of multiple astrocytic-IP3R isoforms, summarizes distinct sub-type specific properties that shape spatiotemporal Ca2+ dynamics. We also discuss existing experimental tools and future refinements to better recapitulate the endogenous activities of each IP3R isoform.
The Role of Host Cell DNA Methylation in the Immune Response to Bacterial Infection

Host cells undergo complex transcriptional reprogramming upon infection. Epigenetic changes play a key role in the immune response to bacteria, among which DNA modifications that include methylation have received much attention in recent years. The extent of DNA methylation is well known to regulate gene expression. Whilst historically DNA methylation was considered to be a stable epigenetic modification, accumulating evidence indicates that DNA methylation patterns can be altered rapidly upon exposure of cells to changing environments and pathogens. Furthermore, the action of proteins regulating DNA methylation, particularly DNA methyltransferases and ten-eleven translocation methylcytosine dioxygenases, may be modulated, at least in part, by bacteria. This review discusses the principles of DNA methylation, and recent insights about the regulation of host DNA methylation during bacterial infection.
Associations of Autism Traits With Obsessive Compulsive Symptoms and Well-Being in Patients With Obsessive Compulsive Disorder: A Cross-Sectional Study

The aim of this study is to examine the association of autism traits with long-term obsessive compulsive disorder (OCD) symptoms and well-being levels in patient with OCD. Participants comprised 18 outpatients from a tertiary hospital and 100 adults who were registered in a large Japanese internet marketing research company and met OCD criteria by the Mini-International Neuropsychiatric Interview and were between the ages of 20 and 65 years. Clinical characteristics, autism trait assessed using the Autism Spectrum Quotient (AQ), OCD symptoms assessed using Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and well-being assessed using the Flourishing Scale were assessed. Multiple regression analyses showed that a greater total score of AQ, a greater subscale score “imagination” was associated with a greater score of Y-BOCS. Greater total score of AQ, a greater subscale score “social skill,” and “imagination” were associated with lower well-being score. Autism traits, especially lack of imagination, were associated with more severe OCD symptoms. Further, autism traits, especially social skill problems and lack of imagination, were associated with lower levels of well-being. Assessment of autism traits before treatment and a strategy designed for OCD patients with autism traits may be warranted.
Possible Environmental Influence on Eyewall Expansion During the Rapid Intensification of Hurricane Helene (2006)

Tropical cyclone (TC) rapid intensification (RI) is usually accompanied by a rapid eyewall contraction, followed by a slow contraction, and then a nearly steady eyewall. However, this study shows that Hurricane Helene (2006) exhibited an eyewall expansion during its 30-h rapid intensification period. The possible environmental influence on the eyewall expansion during the RI of Helene is examined. It is found that the synoptic-scale circulations led to additional low-level inflows and upper-level outflows that may play an important role in the eyewall expansion during the RI of Helene. Examination of the divergence of the absolute angular momentum flux (AAMF) associated with the environmental circulation suggests that the synoptic-scale atmospheric circulation played an important role in the eyewall expansion during the RI of Helene. In the lower and middle troposphere, the synoptic-scale cross-equatorial flow, which was enhanced by the Helene-induced wave train, led to the horizontal convergence of absolute angular momentum flux, while the TC-trough interaction and the related outflow in the upper troposphere resulted in the divergence of AAMF. The environment-induced low-level convergence and upper-level divergence of AAMF were superimposed on the secondary circulation of Helene and may be important to the eyewall expansion during the RI by accelerating the tangential wind outside of the eyewall. This study suggests that RI can occur with an eyewall expansion.
Long-Term Surgical Outcomes of Liver Resection for Hepatocellular Carcinoma in Patients With HBV and HCV Co-Infection: A Multicenter Observational Study

Background Hepatocellular carcinoma (HCC) is one of the most serious consequences of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study sought to investigate long-term outcomes after liver resection for HCC among patients with HBV/HCV co-infection (HBV/HCV-HCC) compared with patients with HBV infection (HBV-HCC). Methods Patients who underwent curative-intent liver resection for HCC were identified from a multicenter Chinese database. Using propensity score matching (PSM), patients with HBV/HCV-HCC were matched one-to-one to patients with HBV-HCC. Overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups before and after PSM. Results Among 2,467 patients identified, 93 (3.8%) and 2,374 (96.2%) patients had HBV/HCV-HCC and HBV-HCC, respectively. Compared with patients with HBV-HCC, patients with HBV/HCV-HCC were older, have poorer liver-related characteristics but better tumor-related characteristics. PSM created 88 pairs of patients with comparable liver- and tumor-related characteristics (all P > 0.2). In the PSM cohort, the 3- and 5-year RFS rates in patients with HBV/HCV-HCC were 48.3% and 38.9%, which were significantly poorer than patients with HBV-HCC (61.8% and 49.2%, P = 0.037). Meanwhile, the 3- and 5-year OS rates in patients with HBV/HCV-HCC were also poorer than patients with HBV-HCC (65.4% and 51.1% vs. 73.7% and 63.0%), with a difference close to be significant between them (P = 0.081). Conclusion Comparing to patients with HBV-HCC, liver resection resulted in relatively poorer long-term surgical outcomes in patients with HBV/HCV-HCC.
A Complete Two-Dimensional Avalanche Photodiode Based on MoTe2−WS2−MoTe2 Heterojunctions With Ultralow Dark Current

Two-dimensional (2D)-material-based photodetectors have recently received great attention due to their potentials in developing ultrathin and highly compact devices. Avalanche photodiodes (APDs) are widely used in a variety of fields such as optical communications and bioimaging due to their fast responses and high sensitivities. However, conventional APDs based on bulk materials are limited by their relatively high dark current. One solution to tackle this issue is by employing nanomaterials and nanostructures as the active layers for APDs. In this study, we proposed and fabricated an atomically-thick APD based on heterojunctions formed by 2D transition metal dichalcogenides (TMDs). A typical device structure was formed by stacking a semiconducting monolayer WS2 onto two metallic few-layer MoTe2 flakes. Due to the Schottky barrier formed between the TMD layers and their atomic thicknesses, the dark current of the APD is greatly reduced down to 93 pA. In addition, the APD can operate through a broad spectral range from visible to near-infrared region, with a responsivity of 6.02 A/W, an external quantum eﬃciency of 1,406%, and an avalanche gain of 587. We believe that the 2D APD demonstrated here provides a feasible approach for developing all-2D optoelectronic devices with simultaneous high-sensitivity and low noise.
MitoTracker Deep Red (MTDR) Is a Metabolic Inhibitor for Targeting Mitochondria and Eradicating Cancer Stem Cells (CSCs), With Anti-Tumor and Anti-Metastatic Activity In Vivo

MitoTracker Deep Red (MTDR) is a relatively non-toxic, carbocyanine-based, far-red, fluorescent probe that is routinely used to chemically mark and visualize mitochondria in living cells. Previously, we used MTDR at low nano-molar concentrations to stain and metabolically fractionate breast cancer cells into Mito-high and Mito-low cell sub-populations, by flow-cytometry. Functionally, the Mito-high cell population was specifically enriched in cancer stem cell (CSC) activity, i) showing increased levels of ESA cell surface expression and ALDH activity, ii) elevated 3D anchorage-independent growth, iii) larger overall cell size (>12-μm) and iv) Paclitaxel-resistance. The Mito-high cell population also showed enhanced tumor-initiating activity, in an in vivo preclinical animal model. Here, we explored the hypothesis that higher nano-molar concentrations of MTDR could also be used to therapeutically target and eradicate CSCs. For this purpose, we employed an ER(+) cell line (MCF7) and two triple negative cell lines (MDA-MB-231 and MDA-MB-468), as model systems. Remarkably, MTDR inhibited 3D mammosphere formation in MCF7 and MDA-MB-468 cells, with an IC-50 between 50 to 100 nM; similar results were obtained in MDA-MB-231 cells. In addition, we now show that MTDR exhibited near complete inhibition of mitochondrial oxygen consumption rates (OCR) and ATP production, in all three breast cancer cell lines tested, at a level of 500 nM. However, basal glycolytic rates in MCF7 and MDA-MB-468 cells remained unaffected at levels of MTDR of up to 1 μM. We conclude that MTDR can be used to specifically target and eradicate CSCs, by selectively interfering with mitochondrial metabolism, by employing nano-molar concentrations of this chemical entity. In further support of this notion, MTDR significantly inhibited tumor growth and prevented metastasis in vivo, in a xenograft model employing MDA-MB-231 cells, with little or no toxicity observed. In contrast, Abemaciclib, an FDA-approved CDK4/6 inhibitor, failed to inhibit metastasis. Therefore, in the future, MTDR could be modified and optimized via medicinal chemistry, to further increase its potency and efficacy, for its ultimate clinical use in the metabolic targeting of CSCs for their eradication.
Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy

Hypoxia is an important characteristic of most solid malignancies, and is closely related to tumor prognosis and therapeutic resistance. Hypoxia is one of the most important factors associated with resistance to conventional radiotherapy and chemotherapy. Therapies targeting tumor hypoxia have attracted considerable attention. Hypoxia-activated prodrugs (HAPs) are bioreductive drugs that are selectively activated under hypoxic conditions and that can accurately target the hypoxic regions of solid tumors. Both single-agent and combined use with other drugs have shown promising antitumor effects. In this review, we discuss the mechanism of action and the current preclinical and clinical progress of several of the most widely used HAPs, summarize their existing problems and shortcomings, and discuss future research prospects.
Evaluation of difference limen for frequency, intensity and duration in individuals with visual impairment

Abstract Introduction Individuals with visual impairment are known to have better auditory abilities than individuals with normal vision. There is a literature shortage that has attempted to assess differential sensitivity for frequency, intensity, and duration in individuals with visual impairment. Objective Thus, the study attempted to determine differences in difference limen for frequency, intensity, and duration between individuals with visual impairment and individuals with normal vision. Methods 30 individuals with normal vision and 30 individuals with visual impairment (15 males and 15 females in each) participated in the study, and their DLI, DLF, DLT were assessed using the mlp toolbox. Results The study results showed that the differential sensitivity was superior for individuals with visual impairment compared to sighted people. Conclusions The results agree with previous studies, suggesting a superior auditory performance in individuals with visual impairment. Further studies on a larger group of population are essential for better generalisation of the results.
Analysis of spatiotemporal patterns of plastics in the Baltic Sea

Marine plastic pollution has become an increasing area of concern in recent years. In spite of this, there are still gaps in our knowledge about the distribution and transport of plastics in the sea. In this thesis project, our aim is to analyze the spatiotemporal patterns of plastics via a summary of data from the literature and a simulation of plastic transport. We will restrict our attention to the Baltic Sea for the literature review, and to the Gullmar Fjord in Sweden for the simulation, in order to limit the scope of the project. The main finding from the literature is that microplastic particles tend to be more abundant in shallow waters, followed by near the ocean floor, with few particles in intermediate layers. The main finding from the simulation case study is that wind transport tends to be the most important factor in plastic transport when wind is present, and that otherwise tidal effects play a large role.
A Study on the Importance of OCB Skills at Academic Institutions

Organizational citizenship behaviour can in simple words be defined as the over and above behaviour exhibited by the employees for their organization without being formally rewarded for the same. By far the concept of OCB has been gaining a lot of acknowledgement and importance by every organization. After a lot of research and studies it has been discovered that OCB is very much responsible for various positives like job contentment resulting in better organization performance and output. The present study is a detailed research for the importance of OCB skills for the academic profession and academic institutions in short. Even the teaching community at what level of education it may be need to feel contented about their job in order to deliver their best outcome to the students. Hence the need and importance of OCB skills have been highlighted even at the academic institutions and among teaching fraternity like the other firms and their employees. This became even more popular when you know that the outcome of academic institutions is far more important resources for the nation. Collecting all the issues mentioned above the current study makes an endeavour to put up the association between OCB skills and the academic institutions by bringing up the relevant literature and a detailed analysis proving the same through their findings. Finally ending up with the possible suggestions to help ensure that OCB skills are practised at the academic institutions at pace ensuring the desired results as expected.