Miracle-dz/UniFAR-FTUs huggingface dataset:
Flecainide Paradoxically Activates Cardiac Ryanodine Receptor Channels under Low Activity Conditions: A Potential Pro-Arrhythmic Action

Cardiac ryanodine receptor (RyR2) mutations are implicated in the potentially fatal catecholaminergic polymorphic ventricular tachycardia (CPVT) and in atrial fibrillation. CPVT has been successfully treated with flecainide monotherapy, with occasional notable exceptions. Reported actions of flecainide on cardiac sodium currents from mice carrying the pro-arrhythmic homozygotic RyR2-P2328S mutation prompted our explorations of the effects of flecainide on their RyR2 channels. Lipid bilayer electrophysiology techniques demonstrated a novel, paradoxical increase in RyR2 activity. Preceding flecainide exposure, channels were mildly activated by 1 mM luminal Ca2+ and 1 µM cytoplasmic Ca2+, with open probabilities (Po) of 0.03 ± 0.01 (wild type, WT) or 0.096 ± 0.024 (P2328S). Open probability (Po) increased within 0.5 to 3 min of exposure to 0.5 to 5.0 µM cytoplasmic flecainide, then declined with higher concentrations of flecainide. There were no such increases in a subset of high Po channels with Po ≥ 0.08, although Po then declined with ≥5 µM (WT) or ≥50 µM flecainide (P2328S). On average, channels with Po < 0.08 were significantly activated by 0.5 to 10 µM of flecainide (WT) or 0.5 to 50 µM of flecainide (P2328S). These results suggest that flecainide can bind to separate activation and inhibition sites on RyR2, with activation dominating in lower activity channels and inhibition dominating in more active channels.
Towards an Islanding Detection Method Using a Digital Twin Concept

In this paper, the development of a mathematical model for islanding detection method based on the concept of a digital twin is presented. The model estimates the grid impedance seen by a distributed energy resource. The proposed algorithm has characteristics of passive and active islanding detection methods. Using a discrete state-space representation of a dq0 axis power system as equality constraints, a digital twin is optimized to match the power system of interest. The concept is to use the estimated grid impedance as the parameter to identify the difference between normal operation and islanding scenarios. Selecting arbitrary initial values, the digital twin approximates the response of the actual system and therefore a value for the system impedance. Results indicate that the proposed method has the potential to estimate the grid impedance at the point of common coupling.
USP19 and RPL23 as Candidate Prognostic Markers for Advanced-Stage High-Grade Serous Ovarian Carcinoma

Simple Summary Although ovarian cancer is one of the leading causes of deaths among female patients with cancer, some patients live longer than others. In order to predict the outcome of patients with ovarian cancer, we investigated the expression levels of all human genes in 51 patients with ovarian cancer and constructed a prediction model based on artificial intelligence. The model identified two genes—USP19 and RPL23—as the most important genes for this prediction. Cancer recurrence occurred more frequently in the patients with lower USP19 mRNA levels and those with higher RPL23 mRNA levels. The same pattern was observed in 208 independent patients with ovarian cancer listed in The Cancer Genome Atlas. Therefore, we suggest USP19 and RPL23 as candidate biomarkers for predicting the survival of patients with ovarian cancer. Abstract Ovarian cancer is one of the leading causes of deaths among patients with gynecological malignancies worldwide. In order to identify prognostic markers for ovarian cancer, we performed RNA-sequencing and analyzed the transcriptome data from 51 patients who received conventional therapies for high-grade serous ovarian carcinoma (HGSC). Patients with early-stage (I or II) HGSC exhibited higher immune gene expression than patients with advanced stage (III or IV) HGSC. In order to predict the prognosis of patients with HGSC, we created machine learning-based models and identified USP19 and RPL23 as candidate prognostic markers. Specifically, patients with lower USP19 mRNA levels and those with higher RPL23 mRNA levels had worse prognoses. This model was then used to analyze the data of patients with HGSC hosted on The Cancer Genome Atlas; this analysis validated the prognostic abilities of these two genes with respect to patient survival. Taken together, the transcriptome profiles of USP19 and RPL23 determined using a machine-learning model could serve as prognostic markers for patients with HGSC receiving conventional therapy.
An Overview on Thermosensitive Oral Gel Based on Poloxamer 407

In this review, we describe the application of thermosensitive hydrogels composed of poloxamer in medicine, especially for oral cavities. Thermosensitive hydrogels remain fluid at room temperature; at body temperature, they become more viscous gels. In this manner, the gelling system can remain localized for considerable durations and control and prolong drug release. The chemical structure of the poloxamer triblock copolymer leads to an amphiphilic aqueous solution and an active surface. Moreover, the poloxamer can gel by forming micelles in an aqueous solution, depending on its critical micelle concentration and critical micelle temperature. Owing to its controlled-release effect, a thermosensitive gel based on poloxamer 407 (P407) is used to deliver drugs with different characteristics. As demonstrated in studies on poloxamer formulations, an increase in gelling viscosity decreases the drug release rate and gel dissolution time to the extent that it prolongs the drug’s duration of action in disease treatment. This property is used for drug delivery and different therapeutic applications. Its unique route of administration, for many oral diseases, is advantageous over traditional routes of administration, such as direct application and systemic treatment. In conclusion, thermosensitive gels based on poloxamers are suitable and have great potential for oral disease treatment.
Influences of Kinesio Taping with Therapeutic Exercise in Patients with Low Back Pain

The aim of this study was to evaluate the effect of core stability exercise combined with Kinesio taping on pain, endurance, and balance in patients with lower back pain (LBP). 46 patients with LBP were recruited and randomly allocated into the core stability exercise with taping (CSET) group and the core stability exercise (CSE) group. All participants performed core stability exercises for 40 min/day, 5 times/week for 8 weeks, and additional Kinesio taping was applied to the lower backs in the CSET group. The primary outcome measure was the pain intensity using the visual analog scale, and secondary outcome measures were trunk endurance and balance using the Biering-Sorensen test and force plate, respectively. After the intervention, the CSET group showed significant improvements in pain and postural balance compared to the CSE group (p < 0.05). However, there was no significant difference in trunk endurance between two groups (p > 0.05). This study found that core stability exercise was effective in reducing pain and enhancing balance in patients with LBP, and demonstrated that the application of additional Kinesio taping further increased these effects. Therefore, we recommend that core exercise combined with Kinesio taping may be used to improve the pain and postural balance of patients with LBP in clinics.
The Impact of Suture Button Removal in Syndesmosis Fixation

The suture button (SB) device was introduced to negate the need for routine hardware removal in the treatment of syndesmosis injuries. However, a considerable SB removal rate has been reported, and the impact of removal is unknown. This study aimed to evaluate the radiographic and clinical outcomes after removal of SB for syndesmosis fixation. A total of 36 patients who underwent removal surgery after syndesmosis fixation using SB were identified. The mean postoperative time to removal was 12.2 months. On a plain radiograph, tibiofibular clear space (TFCS) was measured and compared at three follow-up time points. In patients with computed tomography (CT) imaging (n = 18), the anterior-to-posterior (A/P) ratio was measured to evaluate changes in quality of reduction. Additionally, clinical outcomes were assessed. There were no significant differences in TFCS between the three follow-up periods. None of the patients exhibited recurrent diastasis after SB removal. Although CT analysis demonstrated malreduction in six patients (33.3%), five of six patients had a subsequent spontaneous reduction of the syndesmosis. Clinically, all patients described the resolution of symptoms related to painful hardware at the final follow-up. Our results demonstrate that SB removal at one year following syndesmosis fixation leads to improved clinical symptoms without negatively impacting the quality of syndesmosis reduction.
Clinical Relevance of the Sympathetic–Vascular Interactions in Health and Disease

The sympathetic nervous system is known to play a pivotal role in the short- and long-term regulation of different cardiovascular functions. In recent decades, increasing evidence has demonstrated that sympathetic neural influences are involved not only in the vasomotor modulation of small resistance arteries but also in the control of large arteries. Sympathetic activity and vascular function, which are key factors in the pathophysiology and prognosis of cardiovascular disease, are linked by a close relationship. Evidence from experimental studies indicates that the sympathetic nervous system is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, namely nitric oxide, reactive oxygen species and endothelin. Additionally, there is evidence of a reciprocal influence between endothelial function and sympathetic mechanisms. This paper will provide an overview of the relationships between endothelial function and the sympathetic nervous system characterizing physiological states. It will also briefly mention the alterations described in cardiovascular disease, with particular emphasis on essential hypertension and congestive heart failure, i.e., the two pathological states in which endothelial dysfunction and neuroadrenergic activation appear to be relevant factors for determining cardiovascular prognosis.
Low Psychological Resilience in Older Individuals: An Association with Increased Inflammation, Oxidative Stress and the Presence of Chronic Medical Conditions

The term resilience, which has been present in science for almost half a century, stands for the capacity of some system needed to overcome an amount of disturbance from the environment in order to avoid a change to another stable state. In medicine, the concept of resilience means the ability to deal with daily stress and disturbance to our homeostasis with the intention of protecting it from disturbance. With aging, the organism becomes more sensitive to environmental impacts and more susceptible to changes. Mental disturbances and a decline in psychological resilience in older people are potentiated with many social and environmental factors along with a subjective perception of decreasing health. Distinct from findings in younger age groups, mental and physical medical conditions in older people are closely associated with each other, sharing common mechanisms and potentiating each other’s development. Increased inflammation and oxidative stress have been recognized as the main driving mechanisms in the development of aging diseases. This paper aims to reveal, through a translational approach, physiological and molecular mechanisms of emotional distress and low psychological resilience in older individuals as driving mechanisms for the accelerated development of chronic aging diseases, and to systematize the available information sources on strategies for mitigation of low resilience in order to prevent chronic diseases.
High Hydrostatic Pressure Induced Changes in the Physicochemical and Functional Properties of Milk and Dairy Products: A Review

High-pressure processing (HPP) is a nonthermal technology used for food preservation capable of generating pasteurized milk products. There is much information regarding the inactivation of microorganisms in milk by HPP, and it has been suggested that 600 MPa for 5 min is adequate to reduce the number of log cycles by 5–7, resulting in safe products comparable to traditionally pasteurized ones. However, there are many implications regarding physicochemical and functional properties. This review explores the potential of HPP to preserve milk, focusing on the changes in milk components such as lipids, casein, whey proteins, and minerals, and the impact on their functional and physicochemical properties, including pH, color, turbidity, emulsion stability, rheological behavior, and sensory properties. Additionally, the effects of these changes on the elaboration of dairy products such as cheese, cream, and buttermilk are explored.
Multi-Walled Carbon Nanotube-Assisted Encapsulation Approach for Stable Perovskite Solar Cells

Perovskite solar cells (PSCs) are regarded as the next-generation thin-film energy harvester, owing to their high performance. However, there is a lack of studies on their encapsulation technology, which is critical for resolving their shortcomings, such as their degradation by oxygen and moisture. It is determined that the moisture intrusion and the heat trapped within the encapsulating cover glass of PSCs influenced the operating stability of the devices. Therefore, we improved the moisture and oxygen barrier ability and heat releasing capability in the passivation of PSCs by adding multi-walled carbon nanotubes to the epoxy resin used for encapsulation. The 0.5 wt% of carbon nanotube-added resin-based encapsulated PSCs exhibited a more stable operation with a ca. 30% efficiency decrease compared to the ca. 63% decrease in the reference devices over one week under continuous operation. Specifically, the short-circuit current density and the fill factor, which are affected by moisture and oxygen-driven degradation, as well as the open-circuit voltage, which is affected by thermal damage, were higher for the multi-walled carbon nanotube-added encapsulated devices than the control devices, after the stability test.
Characterization and Prediction of the Clinical Outcome of Intense Pulsed Light-Based Treatment in Dry Eye Associated to Meibomian Gland Dysfunction

This non-comparative prospective case series was conducted to characterize the clinical impact of intense pulsed light (IPL)-based treatment in dry eyes associated to Meibomian gland dysfunction (MGD), defining the predicting factors for a successful outcome with this therapy in a large case series. A total of 390 eyes (195 patients, range: 23–93 years) received four sessions of Optima IPL system (Lumenis, Yokneam, Israel). Significant changes were observed in tear film osmolarity in both eyes (p < 0.001) and in meibum quality (p < 0.001), with more eyes showing clear or yellow secretions after therapy. Mean change in the ocular surface disease index (OSDI) was −8.61, ranging from −27.00 to 11.00. This change was significantly correlated with the baseline value of OSDI (r = −0.489, p < 0.001). The change in osmolarity correlated significantly with the baseline osmolarity in both eyes (right r = −0.636, left r = −0.620, p < 0.001). A linear predicting model of the change in OSDI with therapy was obtained: change OSDI = 10.99 − 0.35 × OSDI − 1.03 × NIBUTRE-LE (mean non-invasive break up time of right and left eye) − 2.03 × Meibum quality grade (p = 0.001; R2: 0.325). In conclusion, the improvement in symptomatology achieved with an IPL-based therapy can be predicted at baseline using a linear model considering the level of MGD and the magnitude of OSDI and NIBUT (non-invasive break-up time).
SoK: Quantifying Cyber Risk

This paper introduces a causal model inspired by structural equation modeling that explains cyber risk outcomes in terms of latent factors measured using reflexive indicators. First, we use the model to classify empirical cyber harm studies. We discover cyber harms are not exceptional in terms of typical or extreme losses. The increasing frequency of data breaches is contested and stock market reactions to cyber incidents are becoming less damaging over time. Focusing on harms alone breeds fatalism; the causal model is most useful in evaluating the effectiveness of security interventions. We show how simple statistical relationships lead to spurious results in which more security spending or applying updates are associated with greater rates of compromise. When accounting for threat and exposure, indicators of security are shown to be important factors in explaining the variance in rates of compromise, especially when the studies use multiple indicators of the security level.
Current Treatment Strategies for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia

Simple Summary Interstitial pneumonia is a poor prognostic comorbidity in patients with non-small-cell lung cancer. No matter how effective the treatment for lung cancer is, once an acute exacerbation of pre-existing interstitial pneumonia occurs, it will be fatal to the patient at a high rate. Therefore, it is important to choose a therapy that is unlikely to induce acute exacerbation of interstitial pneumonia. In this review article, we summarize the current evidence on pharmacotherapy, surgery and perioperative treatment, and radiation therapy for non-small-cell lung cancer with comorbid interstitial pneumonia, and discuss future perspectives. Abstract Of patients with advanced non-small-cell lung cancer (NSCLC), 5–10% have interstitial pneumonia (IP) at the time of diagnosis. To avoid fatal acute exacerbations of pre-existing IP, appropriate patient selection and low-risk treatment choices are warranted. Risk factors for acute exacerbation of pre-existing IP with cytotoxic drugs include honeycomb lungs on computed tomography (CT) and low forced vital capacity, but risk factors with immune checkpoint inhibitors (ICIs) have not been fully investigated. For advanced or recurrent NSCLC with comorbid IP, carboplatin plus nanoparticle albumin-bound paclitaxel is the standard of care for first-line treatment, but second-line or later treatment has not been established. ICI holds great promise for long-term survival, but many challenges remain, including safety and appropriate patient selection. Since the indications for pharmacotherapy and radiotherapy for NSCLC with comorbid IP are quite limited, surgical resection should be considered as much as possible for patients with operable stages. A scoring system has been reported to predict the risk of postoperative acute exacerbation of pre-existing IP, but perioperative treatment has not been established. In the future, it is necessary to accumulate more cases and conduct further research, not only in Japan but also worldwide.
The Influence of Short Coir, Glass and Carbon Fibers on the Properties of Composites with Geopolymer Matrix

The aim of the article is to analyze the influence of short coir, glass and carbon fiber admixture on the mechanical properties of fly ash-based geopolymer, such as: flexural and compressive strength. Glass fiber and carbon fibers have been chosen due to their high mechanical properties. Natural fibers have been chosen because of their mechanical properties as well as for the sake of comparison between their properties and the properties of the artificial ones. Fourth series of fly ash-based geopolymers for each fiber was cast: 1, 2, and 5% by weight of fly ash and one control series without any fibers. Each series of samples were tested on flexural and compressive strength after 7, 14, and 28 days. Additionally, microstructural analysis was carried out after 28 days. The results have shown an increase in compressive strength for composites with fibers—an improvement in properties between 25.0% and 56.5% depending on the type and amount of fiber added. For bending strength, a clear increase in the strength value is visible for composites with 1 and 2% carbon fibers (62.4% and 115.6%). A slight increase in flexural strength also occurred for 1% addition of glass fiber (4.5%) and 2% addition of coconut fibers (5.4%). For the 2% addition of glass fibers, the flexural strength value did not change compared to the value obtained for the matrix material. For the remaining fiber additions, i.e., 5% glass fiber as well as 1 and 5% coconut fibers, the flexural strength values deteriorated. The results of the research are discussed in a comparative context and the properties of the obtained composites are juxtaposed with the properties of the standard materials used in the construction industry.
Molecular Regulatory Networks for Improving Nitrogen Use Efficiency in Rice

Nitrogen is an important factor limiting the growth and yield of rice. However, the excessive application of nitrogen will lead to water eutrophication and economic costs. To create rice varieties with high nitrogen use efficiency (NUE) has always been an arduous task in rice breeding. The processes for improving NUE include nitrogen uptake, nitrogen transport from root to shoot, nitrogen assimilation, and nitrogen redistribution, with each step being indispensable to the improvement of NUE. Here, we summarize the effects of absorption, transport, and metabolism of nitrate, ammonium, and amino acids on NUE, as well as the role of hormones in improving rice NUE. Our discussion provide insight for further research in the future.
The Role of Taurine in Mitochondria Health: More Than Just an Antioxidant

Taurine is a naturally occurring sulfur-containing amino acid that is found abundantly in excitatory tissues, such as the heart, brain, retina and skeletal muscles. Taurine was first isolated in the 1800s, but not much was known about this molecule until the 1990s. In 1985, taurine was first approved as the treatment among heart failure patients in Japan. Accumulating studies have shown that taurine supplementation also protects against pathologies associated with mitochondrial defects, such as aging, mitochondrial diseases, metabolic syndrome, cancer, cardiovascular diseases and neurological disorders. In this review, we will provide a general overview on the mitochondria biology and the consequence of mitochondrial defects in pathologies. Then, we will discuss the antioxidant action of taurine, particularly in relation to the maintenance of mitochondria function. We will also describe several reported studies on the current use of taurine supplementation in several mitochondria-associated pathologies in humans.