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Background: We aimed to elucidate the quantitative relationship between the neuromuscular blockade depth and intraoperative motor-evoked potential amplitudes. Methods: This prospective, single-arm, open-label, observational study was conducted at a single university hospital in Seoul, Korea, and included 100 adult patients aged ≥19 years undergoing brain tumor removal surgery under general anesthesia. We measured the neuromuscular blockade degree and motor-evoked potential amplitude in the deltoid, abductor pollicis brevis, tibialis anterior, and abductor hallucis muscles until dural opening. Results: The pharmacokinetic-pharmacodynamic model revealed the exposure-response relationship between the rocuronium effect-site concentration and motor-evoked potential amplitudes. The mean motor-evoked potential amplitudes decreased proportionally with increasing neuromuscular blockade depth. As the mean amplitude increased, the coefficient of variation decreased bi-exponentially. The critical ratio of the first evoked response to the train-of-four stimulation (T1)/control response (Tc) thresholds beyond which the coefficient of variation exhibited minimal change were found to be 0.63, 0.65, 0.68, and 0.63 for the deltoid, abductor pollicis brevis, tibialis anterior, and abductor hallucis muscles, respectively. Conclusions: Our results reveal that the motor-evoked potential amplitude exhibits deterioration proportional to the degree of neuromuscular blockade. In light of the observed bi-exponential decline of the coefficient of variation with the motor-evoked potential amplitude, we recommend maintaining a T1/Tc ratio higher than 0.6 for partial neuromuscular blockade. [ABSTRACT FROM AUTHOR]

This 4‐year prospective study investigated the dynamic relationship between stress, self‐compassion, and resilience among university students, a population with increasing rates of mental health challenges. Drawing on stress theories, the research explored whether the combination of stress and self‐compassion strengthens resilience over time. A sample of 1137 university students (47.6% White, 38% female) completed measures of stress, resilience, and self‐compassion annually during the Spring semester across their four undergraduate years. A random intercept cross‐lagged panel model with latent interactions was used to test the hypothesized causal relationships. Contrary to the common belief that stress is debilitating, the results revealed a positive association between an increase in stress and a subsequent increase in self‐compassion. Moreover, when stress levels increased alongside self‐compassion, students demonstrated higher resilience. Notably, an increase in either stress or self‐compassion alone did not enhance resilience. These findings highlight the synergetic effect between self‐compassion and stress in enhancing resilience; under the right conditions, stress can lead to positive outcomes and increased capacity for coping with future stressors. [ABSTRACT FROM AUTHOR]

The increasing utilization of artificial intelligence algorithms in drug development has proven to be highly efficient and effective. One area where deep learning-based approaches have made significant contributions is in drug repositioning, enabling the identification of new therapeutic applications for existing drugs. In the present study, a trained deep-learning model was employed to screen a library of FDA-approved drugs to discover novel inhibitors targeting JAK2. To accomplish this, reference datasets containing active and decoy compounds specific to JAK2 were obtained from the DUD-E database. RDKit, a cheminformatic toolkit, was utilized to extract molecular features from the compounds. The DeepChem framework's GraphConvMol, based on graph convolutional network models, was applied to build a predictive model using the DUD-E datasets. Subsequently, the trained deep-learning model was used to predict the JAK2 inhibitory potential of FDA-approved drugs. Based on these predictions, ribociclib, topiroxostat, amodiaquine, and gefitinib were identified as potential JAK2 inhibitors. Notably, several known JAK2 inhibitors demonstrated high potential according to the prediction results, validating the reliability of our prediction model. To further validate these findings and confirm their JAK2 inhibitory activity, molecular docking experiments were conducted using tofacitinib—an FDA-approved drug for JAK2 inhibition. Experimental validation successfully confirmed our computational analysis results by demonstrating that these novel drugs exhibited comparable inhibitory activity against JAK2 compared to tofacitinib. In conclusion, our study highlights how deep learning models can significantly enhance virtual screening efforts in drug discovery by efficiently identifying potential candidates for specific targets such as JAK2. These newly discovered drugs hold promises as novel JAK2 inhibitors deserving further exploration and investigation. [ABSTRACT FROM AUTHOR]

Piezoelectric biomaterials can generate piezoelectrical charges in response to mechanical activation. These generated charges can directly stimulate bone regeneration by triggering signaling pathway that is important for regulating osteogenesis of cells seeded on the materials. On the other hand, mechanical forces applied to the biomaterials play an important role in bone regeneration through the process called mechanotransduction. While mechanical force and electrical charges are both important contributing factors to bone tissue regeneration, they operate through different underlying mechanisms. The utilizations of piezoelectric biomaterials have been explored to serve as self-charged scaffolds which can promote stem cell differentiation and the formation of functional bone tissues. However, it is still not clear how mechanical activation and electrical charge act together on such a scaffold and which factors play more important role in the piezoelectric stimulation to induce osteogenesis. In our study, we found Poly(l-lactic acid) (PLLA)-based piezoelectric scaffolds with higher piezoelectric charges had a more pronounced osteoinductive effect than those with lower charges. This provided a new mechanistic insight that the observed osteoinductive effect of the piezoelectric PLLA scaffolds is likely due to the piezoelectric stimulation they provide, rather than mechanical stimulation alone. Our findings provide a crucial guide for the optimization of piezoelectric material design and usage. [ABSTRACT FROM AUTHOR]

Proving the "expectation-threshold" conjecture of Kahn and Kalai [Combin. Probab. Comput. 16 (2007), pp. 495–502], we show that for any increasing property \mathcal {F} on a finite set X, \[ p_c(\mathcal {F})=O(q(\mathcal {F})\log \ell (\mathcal {F})), \] where p_c(\mathcal {F}) and q(\mathcal {F}) are the threshold and "expectation threshold" of \mathcal {F}, and \ell (\mathcal {F}) is the maximum of 2 and the maximum size of a minimal member of \mathcal {F}. [ABSTRACT FROM AUTHOR]

This article discusses the efficacy of a novel Noninvasive Monopolar Radiofrequency (NMRF) device, XERF, in skin tightening. The study focuses on the effects of delivering thermal energy to the dermis and beyond, particularly collagen remodeling. The authors conducted an investigation using a porcine model and found that the dual-frequency setting of 6.78+2 MHz induced immediate alterations in collagen bundle configurations and thickening of both the superficial and deep fascial layers. These findings suggest that the 6.78+2 MHz NMRF device has the potential to improve skin texture and elasticity and address profound skin concerns. Further research is needed to explore the long-term clinical outcomes and applications of this technology. [Extracted from the article]

Background Aims Methods Results Conclusion Noninvasive monopolar radiofrequency (NMRF) is widely used for dermal and subdermal volumetric heating, yet detailed research on its effects on dermal temperature is scarce.This study evaluates the impact of NMRF on dermal temperature and its potential for dermal remodeling using a porcine model.Noninvasive monopolar radiofrequency was applied to porcine skin with temperature monitoring via optic fiber technology and forward‐looking infrared thermal imaging. Safety was evaluated using nitro blue tetrazolium chloride assessments, and effectiveness was determined through histological examinations before and after treatment.Noninvasive monopolar radiofrequency treatment in a porcine model achieved effective dermal remodeling with no thermal damage, recording peak temperatures of 50°C, 60°C, and 70°C. Histological analysis showed increased collagen density, indicating successful tissue remodeling.Noninvasive monopolar radiofrequency is effective in delivering controlled dermal heating and enhancing collagen synthesis, promoting safe and efficient skin tightening and dermal remodeling in a porcine model. It presents a viable option for skin rejuvenation therapies. [ABSTRACT FROM AUTHOR]

This study explores the innovative use of machine learning (ML) to identify novel tryptase inhibitors from a library of FDA-approved drugs, with subsequent confirmation via molecular docking and experimental validation. Tryptase, a significant mediator in inflammatory and allergic responses, presents a therapeutic target for various inflammatory diseases. However, the development of effective tryptase inhibitors has been challenging due to the enzyme's complex activation and regulation mechanisms. Utilizing a machine learning model, we screened an extensive FDA-approved drug library to identify potential tryptase inhibitors. The predicted compounds were then subjected to molecular docking to assess their binding affinity and conformation within the tryptase active site. Experimental validation was performed using RBL-2H3 cells, a rat basophilic leukemia cell line, where the efficacy of these compounds was evaluated based on their ability to inhibit tryptase activity and suppress β-hexosaminidase activity and histamine release. Our results demonstrated that several FDA-approved drugs, including landiolol, laninamivir, and cidofovir, significantly inhibited tryptase activity. Their efficacy was comparable to that of the FDA-approved mast cell stabilizer nedocromil and the investigational agent APC-366. These findings not only underscore the potential of ML in accelerating drug repurposing but also highlight the feasibility of this approach in identifying effective tryptase inhibitors. This research contributes to the field of drug discovery, offering a novel pathway to expedite the development of therapeutics for tryptase-related pathologies., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Chromatin regulators alter the physical properties of chromatin to make it more or less permissive to transcription by modulating another protein's access to a specific DNA sequence through changes in nucleosome occupancy or histone modifications at a particular locus. Mammalian SWI/SNF complexes are a group of ATPase-dependent chromatin remodelers. In mouse embryonic stem cells, there are three primary forms of mSWI/SNF: canonical BAF (cBAF), polybromo-associated BAF (pBAF), and GLTSCR-associated BAF (gBAF). Nkx2-9 is bivalent, meaning nucleosomes at the locus have active and repressive modifications. In this study, we used unique BAF subunits to recruit each of the three complexes to Nkx2-9 using dCas9-mediated inducible recruitment (FIRE-Cas9). We show that recruitment of cBAF complexes leads to a significant loss of the polycomb repressive-2 H3K27me3 histone mark and polycomb repressive-1 and repressive-2 complex proteins, whereas gBAF and pBAF do not. Moreover, nucleosome occupancy alone cannot explain the loss of these marks. Our results demonstrate that cBAF has a unique role in the direct opposition of polycomb-associated histone modifications that gBAF and pBAF do not share., (© 2024 Bergwell et al.)

Although there is consensus among dentists that visual aids not only improve vision but also help improve posture, evidence is scarce. This study aimed to evaluate the effect of visual aids (loupe and microscope) on the muscle workload of dentists during crown preparation on dentiform first molars in each quadrant of a phantom head, considering dentists' muscles, patients' tooth positions and surfaces. Six right-handed dentists from a single tertiary hospital participated. Surface electromyography device recorded the muscle workload of the bilateral upper trapezius, sternocleidomastoid, cervical erector spinae, and anterior deltoid during crown preparation. The results showed significantly lower workload in all examined muscles when using a microscope compared to the naked eye (p < 0.05), whereas the loupe showed reduced workload in some specific muscles. The muscle with the highest workload for all visual aids was the cervical erector spinae, followed by the upper trapezius. When analyzed by tooth surface, while the loupe did not significantly reduce overall workload compared to the naked eye for each surface, the microscope significantly reduced workload for most surfaces (p < 0.05). Therefore, during crown preparation, the workload of the studied muscles can successfully be reduced with the use of a loupe or microscope., (© 2024. The Author(s).)

Introduction: Nurses, who care for patients with various traumas, may also experience post-traumatic stress disorder due to indirect or direct exposure to traumatic situations. This study examined the effectiveness of an Internet-based trauma recovery intervention for Korean nurses., Methods: This randomized controlled trial was conducted with 112 nurses aged 23-40 years who were randomly assigned to the intervention ( n = 56) or control group ( n = 56) from May 7 to December 20, 2020. Nurses in the intervention group attended eight sessions, and the same intervention was administered to the control group. Repeated measures were collected at pre-test, post-test 1 (immediately after the intervention), and post-test 2 (4 weeks after the intervention). A total of 102 nurses (intervention group: n = 49; control group: n = 53) were completed because 10 nurses dropped out before the first session. Data were analyzed using the χ 2 test, Fisher's exact test, t -test, Mann-Whitney U test, and repeated measures ANOVA (intention-to-treat and per protocol)., Results: There were significant changes in functional health, resilience, post-traumatic stress, depressive symptoms, state anxiety, and trait anxiety over time and in the group-by-time interactions (intention-to-treat and per protocol). There was a significant difference in social support in the group-by-time interactions, but there were no significant changes between the two groups or over time (intention-to-treat and per protocol)., Conclusion: The Internet-based trauma recovery nursing intervention is effective in clinical and community settings for nurses who cannot participate in fixed-schedule programs due to shift work. This study's findings are relevant for implementing Internet-based trauma recovery programs for nurses and the general population, including survivors and relatives of patients who suffered from COVID-19. This program will also be very useful for people in other high-stress situations. Nurse leaders should consider different populations and situations when offering effective coping strategies suitable for changing environments., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Rationale: Visceral artery aneurysm is a rare and potentially fatal vascular condition that typically affects the superior mesenteric or inferior mesenteric arteries, the splenic, hepatic, and celiac arteries, as well as their branches. Visceral artery aneurysms can usually be treated using endovascular intervention, open surgery, or percutaneous thrombin injection., Patient Concerns: A 9-year-old girl was admitted to our trauma center with abdominal and bilateral leg pain after a car accident involving a head-on collision., Diagnosis: Abdominal computed tomography (CT) showed bowel herniation through a muscle defect in the left lateral abdominal wall. There was a small amount of fluid around the liver and spleen, mild thickening of the small bowel wall, and infiltration in the small bowel mesentery, indicating the possibility of small bowel injury., Interventions: Emergent exploratory laparotomy was performed. After resection of the ischemic parts of the terminal ileum and sigmoid colon, intestinal continuity was reestablished. Primary repair was performed on a traumatic left lateral abdominal wall hernia. She recovered well postoperatively without any complications. A follow-up abdominal CT scan after 2 months showed a pseudoaneurysm of the ileal branch of the superior mesenteric artery. Despite the absence of any gastrointestinal symptoms, the pseudoaneurysm was treated by endovascular intervention using numerous coils because of the significant risk of delayed rupture or massive bleeding., Outcomes: Follow-up abdominal CT scan after 6 months showed complete occlusion and resorption of the pseudoaneurysm., Lessons: Although it is technically challenging, endovascular coil embolization may be a feasible technique in children with traumatic visceral artery pseudoaneurysms without complications., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The global shortage of human blood for medical use has prompted the development of alternative blood sources. Nonhuman primates (NHPs) are commonly used owing to their physiological similarities to humans. The objective of the current study was to establish a controlled-blood-loss model in NHPs to explore their clinical and biological responses., Methods: Blood was sequentially withdrawn from 10 cynomolgus monkeys (10, 14, 18, 22, and 25% of the total blood volume); their vital signs were monitored, and blood parameters were serially analyzed. Humoral mediators in the blood were measured using flow cytometry and enzyme-linked immunosorbent assays., Results: In NHPs subjects to 25% blood loss and presenting with related clinical symptoms, the systolic blood pressure ratio on day 0 after bleeding was significantly lower than that of the animals from the other groups (median: 0.65 vs. 0.88, P = 0.0444). Red blood cell counts from day 0-14 and hematocrit levels from day 0-7 were markedly decreased relative to the baseline ( P < 0.01). These parameters showed a direct correlation with the extent of blood loss. The levels of creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase exhibited increases in response to blood loss and had a stronger correlation with the hemoglobin ratio than the volume of blood loss. The levels of C3a and C4a, as well as interleukin (IL)-1α and IL-15, displayed a strong correlation, with no apparent association with blood loss., Conclusion: The findings of the present study showed that only NHPs with 25% blood loss exhibited clinical decompensation and significant systolic blood pressure reduction without fatalities, suggesting that this level of blood loss is suitable for evaluating blood transfusion efficacy or other treatments in NHP models. In addition, the ratio of hemoglobin may serve as a more dependable marker for predicting clinical status than the actual volume of blood loss. Thus, our study could serve as a basis for future xenotransfusion research and to predict biological responses to massive blood loss in humans where controlled experiments cannot be ethically performed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Roh, Park, Lee, Hwang, Kim, Park and Kang.)

Background: Plasmodium vivax (P. vivax) is one of the highly prevalent human malaria parasites. Due to the presence of extravascular reservoirs, P. vivax is extremely challenging to manage and eradicate. Traditionally, flavonoids have been widely used to combat various diseases. Recently, biflavonoids were discovered to be effective against Plasmodium falciparum ., Methods: In this study, in silico approaches were utilized to inhibit Duffy binding protein (DBP), responsible for Plasmodium invasion into red blood cells (RBC). The interaction of flavonoid molecules with the Duffy antigen receptor for chemokines (DARC) binding site of DBP was investigated using a molecular docking approach. Furthermore, molecular dynamic simulation studies were carried out to study the stability of top-docked complexes., Results: The results showed the effectiveness of flavonoids, such as daidzein, genistein, kaempferol, and quercetin, in the DBP binding site. These flavonoids were found to bind in the active region of DBP. Furthermore, the stability of these four ligands was maintained throughout the 50 ns simulation, maintaining stable hydrogen bond formation with the active site residues of DBP., Conclusion: The present study suggests that flavonoids might be good candidates and novel agents against DBP-mediated RBC invasion of P. vivax and can be further analyzed in in vitro studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)