We study the ground-state phases of a two-dimensional dipolar supersolid subjected to external periodic confinement by numerically solving the extended Gross--Pitaevskii equation. Focusing on a regime in which the unconfined system forms an intrinsic triangular droplet crystal, we consider triangular, honeycomb, and square optical lattices and classify them into isostructural and heterostructural settings relative to the spontaneous supersolid order. We map out the stationary states as functions of the lattice depth $V_0$ and the commensurability ratio between the intrinsic droplet spacing and the external lattice period. For triangular and honeycomb confinements, the competition between the soft self-organized supersolid lattice and the rigid external potential can generate long-wavelength moiré superstructures in the weak- to intermediate-lattice regime, together with a sequence of reconstructed states including ring-like clusters and stripe-segment configurations. By contrast, the square lattice introduces strong symmetry mismatch between the intrinsic $C_6$ order and the imposed $C_4$ geometry, leading to frustration-induced anisotropic states and symmetry-reduced cluster arrangements. Our results establish dipolar supersolids under periodic confinement as an unconventional route to exploring moiré physics, where moiré superstructures arise from the competition between a self-organized soft lattice and an externally imposed rigid one.
Yukino Shirakawa, Takafumi Nakano, Keisuke Sato
et al.
Abstract Background Atovaquone (Atov), a second-line drug, is used to treat patients with Pneumocystis pneumonia (PCP) who cannot tolerate sulfamethoxazole/trimethoprim (SMX/TMP). However, the efficacy and safety of Atov are based on clinical trials conducted in patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome, with limited data available on HIV-uninfected individuals with PCP (non-HIV PCP). In this study, we retrospectively evaluated the clinical outcomes of switching from SMX/TMP to Atov in patients with non-HIV PCP. Methods The study included patients with non-HIV PCP who were admitted to Fukuoka University Hospital between 2016 and 2023 and initially received SMX/TMP therapy. The primary endpoint was 30-day survival rate from the date of PCP diagnosis. Secondary endpoints included factors associated with mortality and the cumulative incidence of switching from SMX/TMP to Atov. Results Of the 56 patients receiving SMX/TMP therapy for PCP, 17 were switched to Atov due to SMX/TMP-related side effects. The Kaplan–Meier estimated 30-day survival was 76.9% in the “remained on” SMX/TMP group and 82.4% in the “switched to” Atov group (log-rank test, P = 0.58). Univariable logistic regression analysis of 30-day mortality showed that switching to Atov was not associated with higher mortality compared with continued SMX/TMP therapy (odds ratio 0.71, 95% confidence interval 0.17 to 3.05). The Kaplan–Meier estimated cumulative incidence of switching from SMX/TMP to Atov during the PCP treatment period was 33.8%. Conclusion Our data suggest that switching from SMX/TMP to Atov may not be associated with worse survival. Long-term administration of SMX/TMP is often challenging due to its side effects, and in this study, more than 30% of patients were unable to tolerate its therapeutic dose. Our findings support the role of Atov as a viable second-line treatment for PCP in immunocompromised patients, such as those with non-HIV PCP.
Therapeutics. Pharmacology, Pharmacy and materia medica
Aim. To determine the clinical and diagnostic features of the course of thoracic back pain syndrome, to investigate life quality data in patients with degenerative-dystrophic pathology of the thoracic spine (DDPS) depending on the indicators of vertebrodynamics in order to conduct differentiated kinesiotherapy technique.
Materials and methods. Rehabilitation measures were conducted for 124 patients with DDPS complicated by thoracalgia syndrome at the post-acute stage. All patients had a functional block of the 2nd degree in the thoracic spine. They were divided into two groups. The first group (n = 56) received basic rehabilitation, including drug therapy, massage, personalized therapeutic exercises, and physical therapy. The second group (n = 68) additionally underwent post-isometric and post-reciprocal muscle relaxation, mobilization techniques (K. Lewit, R. Maigne, V. Gubenko), and original kinesiotherapy methods tailored to vertebrodynamics indicators. The outpatient rehabilitation cycle lasted 14 days.
Results. Assessment of the effectiveness of patients treatment in the study groups before and after the rehabilitation measures according to the visual analogue scale for measuring pain intensity, the PainDETECT and LANSS scales for screening components of neuropathic pain in people with chronic pain, the Roland-Morris quality of life questionnaire and EQ-5D (EQ-5D-3L) indicate a statistically significant intergroup difference (p < 0.05) with higher quality of life and lower intensity of pain manifestations in patients of the 2nd group compared to patients of the 1st group. According to the results of the Spearman correlation analysis the progression of signs of mental disorders is directly proportionally associated with the intensity of manifestations of myofascial syndromes due to DDPS, as showed statistically significant relationships between the values of the results of the Spielberger anxiety and Montgomery–Asberg depression rating scales, on the one hand, and the integral indicator of the cumulative thoracic vertebral-mechanical index (Rs = +0.69 and +0.78 at p < 0.01 for all cases), confirming the important pathogenetic relationship between these pathological processes, which indicates the urgent need for rehabilitation measures according to generally accepted (A. Stoddard, K. Lewit) and optimized methods proposed by us to reduce anxiety-depressive disorders and normalize the mental state in general. According to the Pearson agreement criterion, patients with DDPS in the comparison group had significantly more frequently registered values of the five-component EuroQOL-5D system of more than 4 points (χ2 = 11.63; p < 0.01).
Conclusions. Against the background of the course treatment, more than 90 % of patients with clinical manifestations of DDPS at the thoracic level achieved reliable positive results (significant reduction in pain syndrome, increased range of motion in blocked vertebral-motor segments, improved quality of life indicators).
<b>Background</b>: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive disease that easily develops into cirrhosis and hepatocellular carcinoma, but its pathogenesis is not clear, and most therapeutic drugs have obvious limitations. However, Babao Dan (BBD) has a good therapeutic effect on liver disease, but its treatment mechanism is still to be studied. Therefore, we further investigated the mechanism of BBD in treating MASH. <b>Methods</b>: We predicted BBD-related targets through network pharmacology and further verified the binding ability of BBD-related targets through molecular docking. We also detected relevant indicators before and after model treatment, as well as metabolomics analysis and identification of the mechanism of action of BBD on MASH. <b>Results</b>: Through network pharmacology methods, 158 key cross targets and the top 10 core targets were identified, and it was determined that the PI3K-AKT signaling pathway plays an important regulatory role in the treatment of MASH with BBD. The molecular docking results indicate that the representative compounds quercetin and 17 Beta Estradiol have good binding activity with five core targets. Metabolomics has identified four metabolic biomarkers, such as Piceid, and it is determined that the key pathway for BBD treatment of MASH is the bile secretion pathway. <b>Conclusions</b>: BBD effectively treats MASH by modulating Piceid and other biomarkers, targeting ESR1 and other core proteins via quercetin and 17-beta-estradiol, and regulating the PI3K-AKT and bile secretion pathways to alleviate liver injury.
Marija Ćorović, Anja Petrov Ivanković, Ana Milivojević
et al.
<b>Background/Objectives</b>: Numerous intrinsic and extrinsic stressors can disrupt the balance of the skin microbiome, leading to the development of various skin diseases. It has been proven that coagulase-negative staphylococci (CoNS) are important commensals for maintaining skin microbiome homeostasis and fighting cutaneous pathogens such as <i>Staphylococcus aureus</i> (<i>S. aureus</i>). Here, we examined the influence of polyphenol-rich enzymatic blackcurrant extract (EBCE) on pathogenic coagulase-positive <i>S. aureus</i> strains and beneficial CoNS, like <i>Staphylococcus epidermidis</i> (<i>S. epidermidis</i>), to explore its potential for rebalancing the skin microbiota. <b>Methods</b>: The polyphenol profile of EBCE was determined by ultra-high-pressure liquid chromatography–tandem mass spectrometry. Microwell plate assays were employed to study the effect of EBCE on five <i>S. aureus</i> strains isolated from the skin of atopic dermatitis patients. An in vitro human <i>stratum corneum</i> model was used to test its effect on mixed bacterial cultures. <b>Results</b>: EBCE inhibited the growth of all tested <i>S. aureus</i> strains by 80–100% at the highest tested concentration after 7 h. No microbial growth was observed at the highest tested EBCE concentration using the <i>stratum corneum</i> model inoculated with one selected pathogen (<i>S. aureus</i> SA-DUS-017) and one commensal laboratory strain (<i>S. epidermidis</i> DSM 20044). The lowest tested concentration did not interfere with <i>S. aureus</i> growth but strongly stimulated the growth of <i>S. epidermidis</i> (~300-fold colony forming unit increase). In addition, low EBCE concentrations strongly stimulated CoNS growth in microbiome samples taken from the armpits of healthy volunteers that were spiked with <i>S. aureus</i> SA-DUS-017. <b>Conclusions</b>: These preclinical data support further testing of EBCE-enriched topical preparations as potential cutaneous prebiotics in human studies.
Pradnya S. Jadhav, Siddhi Hathiwala, MR Arjun
et al.
Background:
Tobacco use remains a significant public health concern in both rural and urban populations, contributing to a wide array of oral and systemic health complications. Dental professionals play a pivotal role in identifying and educating patients about the risks of tobacco use and facilitating cessation. However, awareness levels and accessibility to cessation support may vary between rural and urban populations. This study aims to assess and compare the awareness of tobacco cessation among dental patients in rural and urban settings.
Materials and Methods:
A cross-sectional, questionnaire-based survey was conducted over a period of three months across two dental clinics—one located in an urban setting and the other in a rural area. A total of 400 patients were recruited (200 urban, 200 rural). A structured and validated questionnaire assessed awareness regarding the health risks of tobacco, knowledge of cessation methods, and attitude towards quitting. Data were analyzed using SPSS software Version 26.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics and Chi-square tests were employed to determine significant differences between groups, with a significance level set at P < 0.05.
Results:
Out of the total 400 participants, 58% of urban patients demonstrated high awareness of tobacco-related health risks compared to 34% in the rural group. Knowledge of cessation aids like nicotine replacement therapy (NRT) and counseling was reported in 42% of urban respondents and only 18% of rural respondents. Willingness to quit tobacco use within the next six months was significantly higher among urban participants (64%) than rural participants (39%) (P = 0.002). The difference in awareness and readiness to quit between the two groups was statistically significant.
Conclusion:
The study reveals a considerable disparity in tobacco cessation awareness between urban and rural dental patients. Targeted educational and cessation interventions tailored to rural populations are essential to bridge this gap and promote healthier behaviors across all demographics.
: The new outlook on Chinese herbal medicine （ CHM ） safety ， proposed by Professor XIAO Xiaohe ， encompasses several key elements ： a framework of innovative cognitions ， two evaluation models ， the Three - factor Toxicity Theory ， four - quadrant risk decision - making ， and a five - level safety assessment evidence framework. This outlook provides significant guidance for ensuring the safe and rational use of CHM in line with contemporary needs ， safeguarding public medication safety ， and promoting the healthy development of traditional Chinese medicine （ TCM ） . Integrating the characteristics and requirements of clinical pharmacy practice in hospitals ， this article systematically explores the application of this outlook and derived insights into clinical safety and rational use of CHM medica⁃ tions. Specifically ， it conducts a evaluation on the disease - syndrome toxicology of Radix Aconiti Lateralis Preparata ， a commonly used toxic Chinese medicinal. Additionally ， the article proposes a series of recommendations for the safe and rational use of Radix et Rhizoma Asari ， a high - risk medicinal in CHM .
We previously synthesized the xanthine oxidoreductase (XOR) inhibitor WN1703. In addition to showing XOR inhibitory effects, WN1703 also showed anti-inflammatory effects in a rat hyperuricemia model. Here, we studied WN1703's anti-inflammatory effects on gout and explored the underlying mechanisms. Tohoku Hospital Pediatrics-1 (THP-1) cells were stimulated by lipopolysaccharide/interferon-γ/monosodium urate (MSU). The levels of inflammatory cytokines in the supernatant and protein expression in THP-1 cells were detected using enzyme-linked immunosorbent assay (ELISA) kits and western blotting, respectively, to verify the inhibitory effects of WN1703 and its mechanism. Potassium oxonate, hypoxanthine, and MSU were administered to establish a hyperuricemia rat model complicated by acute gouty arthritis. At 1–24 h after MSU injection, the degree of ankle swelling was recorded to compare the anti-inflammatory effects at each time point. The potential mechanism was further explored using immunohistochemistry and ELISA. WN1703 significantly downregulated expression of nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, toll-like receptor-4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), nuclear factor-kappa B (NF-κB), and relevant cytokine levels in THP-1 cells. Identical doses of WN1703 and febuxostat had comparable effects on these proteins and cytokines. In the gout rats, the same dose of WN1703 and febuxostat showed equivalent inhibitory effects on NLRP3, ASC, and NF-κB; however, WN1703 showed weaker impacts on alleviating ankle swelling than febuxostat showed. In conclusion, WN1703 showed significant anti-inflammatory effects in hyperuricemic rats with acute gout. Such effects were related to the inhibition of the NLRP3/ASC/Caspase-1 and TLR4/MyD88/NF-κB signaling pathways, thereby downregulating inflammation-related protein expression and decreasing inflammatory cytokine secretion.
Pharmacy and materia medica, Therapeutics. Pharmacology
Inarah Fajriaty, Siti Nani Nurbaeti, Hariyanto IH
et al.
Malnutrition is characterized by slow growth and excessive loss of body fat. The fats needed during the growth period of toddlers are essential fatty acids, which are important for the human body and cannot be made in the body but must come from food. specifically omega-3, which is beneficial for children's growth and brain intelligence. The plant that contains this content is the tengkawang fruit. The aim of this study was to examine the effect of tengkawang fruit on motor behavior and organ indices in malnourished male white rats (Rattus norvegicus L.) of the Wistar strain. Research methods include making low-protein animal feed, making test preparations, and grouping animals. Mice were divided into 5 groups, namely positive control, negative control, normal control, and two dose groups; then behavioral observations and organ index observations were observed. The organs observed were the spleen, heart, lungs, liver, and kidneys. The results of behavioral observations in the tengkawang fruit extract group showed that the platform observation increased again after being given the test preparation like the normal group, and the same as motor activity, there was an increase back to normal conditions, especially in the tengkawang fruit extract group at a dose of 100 mg/kgBB, where there was an increase exceeding the normal group by 40%. Observation of organ indices did not show a significant increase (p 0.05) in the lymph organs, heart, lungs, liver, and kidneys compared to the normal group. Giving tengkawang fruit extract at a dose of 100 mg/kgBB and a dose of 300 mg/kgBB can make the behavior and organ index of malnourished mice return to normal. However, it did not show a significant increase (p 0.05) between the two dose groups and the negative control group, so it is recommended that further research be carried out using an inert solvent with tengkawang tungul extract.
Pharmacy and materia medica, Therapeutics. Pharmacology
Yu Ando, Nora Jee-Young Park and, Gun Oh Chong
et al.
Screening is critical for prevention and early detection of cervical cancer but it is time-consuming and laborious. Supervised deep convolutional neural networks have been developed to automate pap smear screening and the results are promising. However, the interest in using only normal samples to train deep neural networks has increased owing to class imbalance problems and high-labeling costs that are both prevalent in healthcare. In this study, we introduce a method to learn explainable deep cervical cell representations for pap smear cytology images based on one class classification using variational autoencoders. Findings demonstrate that a score can be calculated for cell abnormality without training models with abnormal samples and localize abnormality to interpret our results with a novel metric based on absolute difference in cross entropy in agglomerative clustering. The best model that discriminates squamous cell carcinoma (SCC) from normals gives 0.908 +- 0.003 area under operating characteristic curve (AUC) and one that discriminates high-grade epithelial lesion (HSIL) 0.920 +- 0.002 AUC. Compared to other clustering methods, our method enhances the V-measure and yields higher homogeneity scores, which more effectively isolate different abnormality regions, aiding in the interpretation of our results. Evaluation using in-house and additional open dataset show that our model can discriminate abnormality without the need of additional training of deep models.
Origami structures have been widely explored in robotics due to their many potential advantages. Origami robots can be very compact, as well as cheap and efficient to produce. In particular, they can be constructed in a flat format using modern manufacturing techniques. Rotational motion is essential for robotics, and a variety of origami rotational joints have been proposed in the literature. However, few of these are even approximately flat-foldable. One potential enabler of flat origami rotational joints is the inclusion of lightweight pneumatic pouches which actuate the origami's folds; however, pouch actuators only enable a relatively small amount of rotational displacement. The previously proposed Four-Vertex Origami is a flat-foldable structure which provides an angular multiplier for a pouch actuator, but suffers from a degenerate state. This paper presents a novel rigid origami, the Self-Lock Origami, which eliminates this degeneracy by slightly relaxing the assumption of flat-foldability. This joint is analysed in terms of a trade-off between the angular multiplier and the mechanical advantage. Furthermore, the Self-Lock Origami is a modular joint which can be connected to similar or different joints to produce complex movements for various applications; three different manipulator designs are introduced as a proof of concept.
Remote sensing change detection between bi-temporal images receives growing concentration from researchers. However, comparing two bi-temporal images for detecting changes is challenging, as they demonstrate different appearances. In this paper, we propose a dual attentive generative adversarial network for achieving very high-resolution remote sensing image change detection tasks, which regards the detection model as a generator and attains the optimal weights of the detection model without increasing the parameters of the detection model through generative-adversarial strategy, boosting the spatial contiguity of predictions. Moreover, We design a multi-level feature extractor for effectively fusing multi-level features, which adopts the pre-trained model to extract multi-level features from bi-temporal images and introduces aggregate connections to fuse them. To strengthen the identification of multi-scale objects, we propose a multi-scale adaptive fusion module to adaptively fuse multi-scale features through various receptive fields and design a context refinement module to explore contextual dependencies. Moreover, the DAGAN framework utilizes the 4-layer convolution network as a discriminator to identify whether the synthetic image is fake or real. Extensive experiments represent that the DAGAN framework has better performance with 85.01% mean IoU and 91.48% mean F1 score than advanced methods on the LEVIR dataset.
The label-free model evaluation aims to predict the model performance on various test sets without relying on ground truths. The main challenge of this task is the absence of labels in the test data, unlike in classical supervised model evaluation. This paper presents our solutions for the 1st DataCV Challenge of the Visual Dataset Understanding workshop at CVPR 2023. Firstly, we propose a novel method called K-means Clustering Based Feature Consistency Alignment (KCFCA), which is tailored to handle the distribution shifts of various datasets. KCFCA utilizes the K-means algorithm to cluster labeled training sets and unlabeled test sets, and then aligns the cluster centers with feature consistency. Secondly, we develop a dynamic regression model to capture the relationship between the shifts in distribution and model accuracy. Thirdly, we design an algorithm to discover the outlier model factors, eliminate the outlier models, and combine the strengths of multiple autoeval models. On the DataCV Challenge leaderboard, our approach secured 2nd place with an RMSE of 6.8526. Our method significantly improved over the best baseline method by 36\% (6.8526 vs. 10.7378). Furthermore, our method achieves a relatively more robust and optimal single model performance on the validation dataset.
Jassica S. L. Leu, Jasy J. X. Teoh, Angel L. Q. Ling
et al.
Due to their distinctive structural features, lyotropic nonlamellar liquid crystalline nanoparticles (LCNPs), such as cubosomes and hexosomes, are considered effective drug delivery systems. Cubosomes have a lipid bilayer that makes a membrane lattice with two water channels that are intertwined. Hexosomes are inverse hexagonal phases made of an infinite number of hexagonal lattices that are tightly connected with water channels. These nanostructures are often stabilized by surfactants. The structure’s membrane has a much larger surface area than that of other lipid nanoparticles, which makes it possible to load therapeutic molecules. In addition, the composition of mesophases can be modified by pore diameters, thus influencing drug release. Much research has been conducted in recent years to improve their preparation and characterization, as well as to control drug release and improve the efficacy of loaded bioactive chemicals. This article reviews current advances in LCNP technology that permit their application, as well as design ideas for revolutionary biomedical applications. Furthermore, we have provided a summary of the application of LCNPs based on the administration routes, including the pharmacokinetic modulation property.
Khanh T. T. Nguyen, Daan Zillen, Franca F. M. van Heijningen
et al.
In a previous attempt to achieve ileo-colonic targeting of bovine intestinal alkaline phosphatase (BIAP), we applied a pH-dependent coating, the ColoPulse coating, directly on powder bed printed (PBP) tablets. However, the high surface roughness necessitated an additional sub-coating layer [Nguyen, K. T. T., <i>Pharmaceutics</i> 2022]. In this study, we aimed to find a production method for PBP tablets containing BIAP that allows the direct application of coating systems. Alterations of the printing parameters, binder content, and printing layer height, when combined, were demonstrated to create visually less rough PBP tablets. The addition of ethanol vapor treatment further improved the surface’s smoothness significantly. These changes enabled the direct application of the ColoPulse, or enteric coating, without a sub-coating. In vitro release testing showed the desired ileo-colonic release or upper-intestinal release for ColoPulse or enteric-coated tablets, respectively. Tablets containing BIAP, encapsulated within an inulin glass, maintained a high enzymatic activity (over 95%) even after 2 months of storage at 2–8 °C. Importantly, the coating process did not affect the activity of BIAP. In this study, we demonstrate, for the first time, the successful production of PBP tablets with surfaces that are directly coatable with the ColoPulse coating while preserving the stability of the encapsulated biopharmaceutical, BIAP.
Uptake drug transporters play a significant role in the pharmacokinetic of drugs within the brain, facilitating their entry into the central nervous system (CNS). Understanding brain drug disposition is always challenging, especially with respect to preclinical to clinical translation. These transporters are members of the solute carrier (SLC) superfamily, which includes organic anion transporter polypeptides (OATPs), organic anion transporters (OATs), organic cation transporters (OCTs), and amino acid transporters. In this systematic review, we provide an overview of the current knowledge of uptake drug transporters in the brain and their contribution to drug disposition. Here, we also assemble currently available proteomics-based expression levels of uptake transporters in the human brain and their application in translational drug development. Proteomics data suggest that in association with efflux transporters, uptake drug transporters present at the BBB play a significant role in brain drug disposition. It is noteworthy that a significant level of species differences in uptake drug transporters activity exists, and this may contribute toward a disconnect in inter-species scaling. Taken together, uptake drug transporters at the BBB could play a significant role in pharmacokinetics (PK) and pharmacodynamics (PD). Continuous research is crucial for advancing our understanding of active uptake across the BBB.