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Abstract Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR’s, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or 14 was found in PTPR-B1 tumors but not in PTPR-B2. Examination of clinical outcome showed that nearly half (14/30, 47%) of examined patients experienced tumor progression with significant difference among the subtypes (p value = 0.046). Our analysis extends the understanding of this uncommon but distinct neuroepithelial tumor by describing its molecular heterogeneity and clinical outcomes, including its tendency towards tumor recurrence.

IntroductionIdentification of key microbiome components has been suggested to help address the maintenance of oral and intestinal health in humans. The core microbiome is similar in all individuals, whereas the diverse microbiome varies across individuals, based on their unique lifestyles and phenotypic and genotypic determinants. In this study, we aimed to predict the metabolism of core microorganisms in the gut and oral environment based on enterotyping and orotyping.Materials and methodsGut and oral samples were collected from 83 Korean women aged 50 years or older. The extracted DNA was subjected to next-generation sequencing analysis of 16S rRNA hypervariable regions V3–V4.ResultsGut bacteria were clustered into three enterotypes, while oral bacteria were clustered into three orotypes. Sixty-three of the core microbiome between the gut and oral population were correlated, and different metabolic pathways were predicted for each type. Eubacterium_g11, Actinomyces, Atopobium, and Enterococcus were significantly positively correlated between the gut and oral abundance. The four bacteria were classified as type 3 in orotype and type 2 in enterotype.ConclusionOverall, the study suggested that collapsing the human body’s multidimensional microbiome into a few categories may help characterize the microbiomes better and address health issues more deeply.

Swabs are useful and common sampling tools in various research fields, such as medicine, ecology, biotechnology, forensic medicine, and pollutant monitoring systems. Collection reagents are one of the essential components in sampling. It is important to develop a sample collection kit and designate an appropriate storage temperature because samples need to be stored for a long time. The purpose of this study was to identify the effects of three collection reagents and three storage temperatures on the recovery of living bacteria without media. We selected Escherichia coli and Staphylococcus aureus as representative environmental bacteria. Distilled water (DW), phosphate buffered saline (PBS), and Tris-EDTA (TE) buffer were used as collection reagents and stored at 22°C, 4°C, and −70°C after sampling. The results of using each collection reagent and storage temperature on the bacteria were compared using relative light units (RLU) and the number of colony forming units (CFU). When using −70°C storage temperature and the TE buffer, the number of living bacteria and the RLU values remained constant. It is therefore recommended that the sample be stored at −70°C immediately after collection and a TE buffer solution be used as the collection reagent.

Neutrophils and other leukocytes invade the mouse uterus at term birth, which is normal for activating the uterus for labor. To better understand the regulation of this migration at term and interleukin (IL)-1β—induced preterm birth, we developed a mouse leukocyte migration assay (mLMA) and used it with rytvela, an IL-1 receptor allosteric antagonist. The mLMA uses term peripheral blood leukocytes that migrate in a Boyden chamber in response to a chemoattractant. We tested several mouse uterine tissues after homogenization and sedimentation of debris for chemoattractant activity. The most active chemoattractant homogenate came from the mouse lower uterus on gestational day (GD) 18.5. Using flow cytometry, we demonstrated that 99% of the cells that migrate are neutrophils. IL-1β administered on GD 16 stimulated neutrophil migration and invasion into the uterus and the fetal brain along with preterm birth on GD 17. Preterm birth and the increased leukocyte invasion of the maternal uterus and fetal brain were all blocked by the co-administration of rytvela. To test where the site of IL-1β action might be, we examined the potency of lower uterine chemoattractant and the activation of leukocytes following IL-1β +/- rytvela administration. IL-1β did not increase lower uterus homogenate chemoattractant activity, but it significantly (p < 0.05) increased leukocyte activation as defined by cytokine and chemokine expression. Rytvela blocked this activation of leukocytes by IL-1β. We conclude that IL-1β stimulates preterm birth in mice by increasing leukocyte activation leading to increased uterine and fetal brain leukocyte invasion.

This study investigates the significance of sexuality education for individuals with disabilities in Taiwan. It highlights the importance of understanding sexuality as a fundamental aspect of identity, encompassing intimate relationships and connection to others. Since the implementation of the Gender Equity Education Act in 2004, Taiwan has made efforts to include comprehensive sexuality education in the school curriculum and integrate disabled students into mainstream education. However, disabled individuals still face barriers due to ableism and heteronormativity, which impede their access to sexual and reproductive health services, including sexuality education. To address this issue, we conducted a qualitative investigation using narrative and policy data, drawing on Scott's phenomenology of nothingness and crip theory to explore the intersection of sexualities and disabilities in educational contexts. Our findings reveal that individuals with disabilities in Taiwan often rely on pornography and other erotic materials as informal sources of sex education. Hand Angels, a volunteer-based group established in 2013, has been actively promoting sexual rights within disability rights organisations, advocating for a comprehensive, sex-positive, pleasure-focused, and rights-based approach to sexuality education. However, there are still gaps in knowledge production and policy implementation, which systematically deny people with disabilities their right to sexual agency.

Purpose: The purpose of this study was to develop the augmented reality (AR) educational program combined with the instructional guidance for supportive learning, which enhanced the thinking process cooperative discussion and problem-solving skills in chemistry subject. Design/methodology/approach: The method used the quasi-experimental research design. Of the 45 students who attended this experiment, only 25 with low achievement qualified in operating the AR learning system of saponification and transesterification environment (ARLS-STE) system. Findings: These results confirmed that the AR educational program could have increased substantial benefits in improvements of students' knowledge and the ability of the thinking process for the participants with the lowest score. In semi-structured interviews, most of participants enjoyed manipulating the ARLS-STE system, which was realistic, motived and interesting for learning science subjects. Originality/value: The low-achieving students have often been known with a low learning capability, and they lack in developing constructional knowledge, despite being keen for learning. Regarding educational concerns for this population, providing orientated learning and supportive materials could increase their learning effects. Virtual worlds are an efficient learning tool in educational setting. The AR can offer visual concepts and physical interaction for students with low achievement in learning. Thus, this study investigates the acceptability of an educational program designed in the ARLS-STE, which involves the learning effects of academic knowledge and the capability of thinking process for students with low achievement. The ARLS-STE system was developed for this proposal, based upon the marker-based AR technologies combined with hands-on manipulation.

Steel slag is a secondary product from steelmaking process through alkaline oxygen furnace or electric arc furnace (EAF). The disposal of steel slag has become a thorny environmental protection issue, and it is mainly used as unbound aggregates, e.g., as a secondary component of asphalt concrete used for road paving. In this study, the characteristics of compacted porous steel slag disc (SSD) and its application in phosphorous (P)-rich water filtration are discussed. The SSD with an optimal porosity of 10 wt% and annealing temperature of 900 °C, denoted as SSD-P (10, 900) meets a compressive strength required by ASTM C159-06, which has the capability of much higher than 90% P removal (with the effluent standard < 4 mg P/L) within 3 h, even after eight filtration times. No harmful substances from SSD have been detected in the filtered water, which complies with the effluent standard ISO 14001. The reaction mechanism for P-rich water filtration is mediated by water, followed by two reaction steps—CaO in SSD hydrolyzed from the matrix of SSD to Ca2+ and reacting with PO43−. However, the microenvironment of water is influenced by the pH value of the P-rich water at different filtration times and the kind of P-rich water with different free positive ion that interferes the reactions of the release of Ca2+. This study demonstrates the application of circular economy in reducing steel slag deposits, filtering P-rich water, and collecting Ca3(PO4)2 precipitate into fertilizers.

Cisplatin is an effective chemotherapy drug that induces peripheral neuropathy in cancer patients. In rodent dorsal root ganglion neurons, cisplatin binds nuclear and mitochondrial DNA (mtDNA) inducing DNA damage and apoptosis. Platinum-mtDNA adducts inhibit mtDNA replication and transcription leading to mitochondrial degradation. Cisplatin also induces climbing deficiencies associated with neuronal apoptosis in adult Drosophila melanogaster. Here we used Drosophila larvae that express green fluorescent protein in the mitochondria of motor neurons to observe the effects of cisplatin on mitochondrial dynamics and function. Larvae treated with 10 μg/ml cisplatin had normal survival with deficiencies in righting and heat sensing behavior. Behavior was abrogated by, the pan caspase inhibitor, p35. However, active caspase 3 was not detected by immunostaining. There was a 27% decrease in mitochondrial membrane potential and a 42% increase in reactive oxygen species (ROS) in mitochondria along the axon. Examination of mitochondrial axonal trafficking showed no changes in velocity, flux or mitochondrial length. However, cisplatin treatment resulted in a greater number of stationary organelles caused by extended pausing during axonal motility. These results demonstrate that cisplatin induces behavior deficiencies in Drosophila larvae, decreased mitochondrial activity, increased ROS production and mitochondrial pausing without killing the larvae. Thus, we identified particular aspects of mitochondrial dynamics and function that are affected in cisplatin-induced peripheral neuropathy and may represent key therapeutic targets.

Following injury, the mammalian spinal cord forms a glial scar and fails to regenerate. In contrast, vertebrate fish spinal cord tissue regenerates significantly to restore function. Cord transection in zebrafish (Danio rerio) initially causes paralysis and neural cell death. Subsequently, ependymal glia proliferate, bipolar glia extend across the lesion, and new neurons are born; axons from spared and nascent neurons extend along trans-lesional glial bridges to restore functional connectivity. Here we report that glucocorticoids, used in the clinical management of spinal cord injury, directly inhibit neural repair by targeting ependymal glia independently of hematogenous cells and microglia. After transecting injury, the glucocorticoid receptor in ependymal glia is regulated differentially in zebrafish (becoming inactive) vs. the rat (becoming active). Glucocorticoid blockade of neural regeneration via a direct effect on ependymal glia has important therapeutic implications for the putative benefit of corticosteroids in early management of spinal cord injury.

Strontium oxide (SrO) is an effective catalyst for transesterification. SrO powder that is firmly deposited onto a light titanium plate (TiO2_P), denoted as SrO/TiO2_P, can be reinforced by forming strontium titanate (SrTiO3) at the interface. Exposed SrO agglomerates can promote subsequent continuous transesterification process. In this work, conversion efficiency and production of biodiesel from olive oil on SrO/TiO2_P is investigated. The as-designed SrO/TiO2_P was followed by dip-coating and heat treatment. The physical properties of SrO/TiO2_P were verified through ASTM D3359; the chemical structures before and after transesterification, were respectively identified by X-ray photoelectron spectroscopy and Raman spectroscopy. A focused microwave heating system was utilized for transesterification. In the optimized sample SrO/TiO2_P (x) (x = 0.5 M), SrO firmly bonds with TiO2_P and forms the SrTiO3 structure. With the support of TiO2_P, the tested oil with SrO agglomerates subsequently reacts with SrO under microwave heating. The biodiesel conversion rate reaches 87.7% after a reaction time of 4 min, while the biodiesel product has an average of 39.37 MJ/kg of combustion heat and less than 1 vol% of water content. The as-designed SrO/TiO2_P (0.5) thus has great potential for biodiesel production and is promising with high stability in particular for a continuous fluid flow system.

Ependymomas are primary CNS tumors representing 3%-6% of all CNS tumors, and 34.5% of ependymomasoccur in the spine. Spinal ependymomas occur most frequently in the cervical spine. Rarely, tumor-associatedsyringomyelia and hematomyelia may complicate cervical spinal ependymomas. Here, the authors present a case ofa 37 year-old gentleman with cervical intramedullary WHO Grade II ependymoma with hematomyelia extendingcephalad to the brainstem. The authors also detail their operative procedure using the OmniGuide CO2 laser andreview current literature on the management of cervical intramedullary ependymoma with tumor-associatedsyringomyelia and/or hematomyelia.

Abstract Background The purpose of this study is to analyze changes in mandibular width and frontal view ramus inclination using cone beam CT in patients with skeletal class III malocclusion who underwent BSSRO, with the removal of bone interference between segments. Methods For all 20 subjects, cone-beam CT imaging was performed prior to surgery (T1), immediately post-surgery (T2), and 6 months after surgery (T3). Reorientation was performed using R2GATE software (MegaGen, Seoul, Korea). The gonion and antegonial notch were used as reference points in the sagittal view, and the most lateral point of the condyle head was used as the reference point in the frontal view. All measurements were recorded in the frontal view. Results Inter-gonial width decreased by 2.64 mm at T3-T2 (P

Abstract CD73 is a cell-surface ectoenzyme that hydrolyzes the conversion of extracellular adenosine monophosphate to adenosine, which in turn can promote resistance to immune checkpoint blockade therapy. Immune response may therefore be improved by targeting tumor CD73, and this possibility underlines the need to non-invasively assess tumor CD73 level. In this study, we developed a cysteine site-specific 89Zr-labeled anti-CD73 (89Zr-CD73) IgG immuno-PET technique that can image tumor CD73 expression in living bodies. Anti-CD73 IgG was reduced with tris(2-carboxyethyl)phosphine, underwent sulfohydryl moiety–specific conjugation with deferoxamine–maleimide, and was radiolabeled with 89Zr. CT26 mouse colon cancer cells, CT26/CD73 cells engineered to constitutively overexpress CD73, and 4T1.2 mouse breast cancer cells underwent cell binding assays and western blotting. Balb/c nude mice bearing tumors underwent 89Zr-CD73 IgG PET imaging and biodistribution studies. 89Zr-CD73 IgG showed 20-fold higher binding to overexpressing CT26/CD73 cells compared to low-expressing CT26 cells, and moderate expressing 4T1.2 cells showed uptake that was 38.9 ± 1.51% of CT26/CD73 cells. Uptake was dramatically suppressed by excess unlabeled antibody. CD73 content proportionately increased in CT26 and CT26/CD73 cell mixtures was associated with linear increases in 89Zr-CD73 IgG uptake. 89Zr-CD73 IgG PET/CT displayed clear accumulation in CT26/CD73 tumors with greater uptake compared to CT26 tumors (3.13 ± 1.70%ID/g vs. 1.27 ± 0.31%ID/g at 8 days; P = 0.04). Specificity was further supported by low CT26/CD73 tumor-to-blood ratio of 89Zr-isotype-IgG compared to 89Zr-CD73 IgG (0.48 ± 0.08 vs. 2.68 ± 0.52 at 4 days and 0.53 ± 0.07 vs. 4.81 ± 1.02 at 8 days; both P

In repairing or replacing damaged bones, a dual concentric porous titanium scaffold (P-Tix-y) has emerged as a promising bio-mimic design. Herein, various P-Tix-y were made and sintered with relatively dense (x = 10, 20, or 30% porosity) and loose (y = 45, 55, or 65 porosity) structures. Firstly, NaCl was used as the pore-forming additive and followed by a hydrothermal removal method. The compressive strength of the as-formed P-Tix_y and surface morphology, nanomechanical property, and cells’ affinity on the cross-sectioned surface of P-Tix_y (CP-Tix_y) were then characterized. The results demonstrate that the compressive strength of P-Ti10_45, P-Ti20_45, or P-Ti20_55 exhibits a relatively mild decline (e.g., in the range of 181 and 97 MPa, higher than the required value of 70 MPa) and suitable porosities for the intended structure. Nano-hardness on the solid surface of CP-Tix_y shows roughly consistent with that of CP-Ti (i.e., ~8.78 GPa), thus, the porous structure of CP-Tix_y remains mostly unaffected by the addition of NaCl and subsequent sintering process. Most of the surfaces of CP-Tix_y exhibit high fibroblast (L929) cell affinity with low cell mortality. Notably, in the hFOB 1.19 cell adhesion and proliferation test, CP-Ti20_55 and CP-Ti20_65 reveal high cell viability, most probably relating with the assembly of dual porosities with interconnected pores. Overall, the sample P-Ti20_55 provides a relatively load-bearable design with high cell affinity and is thus promising as a three-dimensional bio-scaffold.

Health risks posed by the exposure to trace amounts of pesticide residue in agricultural products have gained a lot of concerns, due to their neurotoxic nature. The applications of surface-enhanced Raman Scattering (SERS) as a detection technique have consistently shown its potential as a rapid and sensitive means with minimal sample preparation. In this study, gold nanoparticles (Au NPs) in elliptical shapes were collected into a layer of ordered zirconia concave pores. The porous zirconia layer (pZrO2) was then deposited with Au NPs, denoted as Au NPs (x)/pZrO2, where x indicates the deposition thickness of Au NPs in nm. In the concave structure of pZrO2, Au-ZrO2 and Au-Au interactions provide a synergistic and physical mechanism of SERS, which is anticipated to collect and amplify SERS signals and thereafter improve the enhancement factor (EF) of Au NPs/pZrO2. By taking Rhodamine 6G (R6G) as the test molecule, EF of Au NPs/pZrO2 might reach to 7.0 × 107. Au NPs (3.0)/pZrO2 was then optimized and competent to detect pesticides, e.g., phosmet and carbaryl at very low concentrations, corresponding to the maximum residue limits of each, i.e., 0.3 ppm and 0.2 ppm, respectively. Au NPs (3.0)/pZrO2 also showed the effectiveness of distinguishing between phosmet and carbaryl under mixed conditions. Due to the strong affinities of the phosphoric groups and sulfur in phosmet to the Au NPs (3.0)/pZrO2, the substrate exhibited selective detection to this particular pesticide. In this study, Au NPs (3.0)/pZrO2 has thus demonstrated trace detection of residual pesticides, due to the substrate design that intended to provide collective amplification of SERS.

Strontium oxide (SrO) deposited onto a porous titanium (Ti)-based scaffold (P-Ti) is a promising and novel approach for high-throughput transesterification. Notably, a highly porous and calcinated scaffold provides a load-bearable support for a continuous process, while the calcinated SrO catalyst, as it is well distributed inside the porous matrix, can extend its surface contact area with the reactant. In this work, the formation of transesterification reaction with the conversion and production of olive oil to biodiesel inside the porous matrix is particularly examined. The as-designed SrO-coated porous titanium (Ti)-based scaffold with 55% porosity was prepared via a hydrothermal procedure, followed by a dip coating method. Mechanical tests of samples were conducted by a nanoindentator, whereas the physical and chemical structures were identified by IR and Raman Spectroscopies. The results implied that SrO catalysts can be firmly deposited onto a load-bearable, highly porous matrix and play an effective role for the transesterification reaction with the oil mass. It is promising to be employed as a load-bearable support for a continuous transesterification process, such as a process for batch or continuous biodiesel production, under an efficient heating source by a focused microwave system.

BackgroundDexmedetomidine is an α2-adrenoreceptor agonist with sedative, analgesic and anxiolytic effects, and it has more selective α2-adrenergic effect than clonidine. We evaluate the effect of preansethetic dexmedetomidine 1 µg/kg single infusion on sedation, hemodynamics, anesthetic consumption, and recovery profiles during anesthesia.MethodsForty-two female patients with American Society of Anesthesiologists physical status I or II undergoing gynecologic surgery with anticipated operation time of 2 h, were randomly assigned to receive dexmedetomidine 1 µg/kg (Dex group) or saline (control group) iv over 10 min before anesthetic induction. After tracheal intubation with propofol 2 mg/kg, cisatracurium 0.15 mg/kg iv, anesthesia was maintained with sevoflurane, O2 50%, N2O 50% around a BIS value of 40.ResultsAfter study drug infusion, BIS of Dex group was lower than that of control group (93.9 ± 3.1 vs 51.5 ± 5.2, P < 0.05). Mean arterial pressure (MAP) and heart rate (HR) after intubation were increased in control group, but did not change in Dex group. During maintenance, there was no difference in MAP between groups, but HR of Dex group was lower compared to that of control group. End-tidal concentration (2.0 ± 0.5 vol% vs 1.4 ± 0.3 vol%, P < 0.05) and total cumulative consumption of sevoflurane (34.6 ± 3.8 ml vs 26.5 ± 5.3 ml, P < 0.05) were lower in Dex group than in control group. Recovery profiles, modified Aldrete score, postoperative nausea vomiting, and visual analogue pain score were not significantly different between groups.ConclusionsPreanesthetic dexmetomidine 1 µg/kg single infusion is a simple, easy, and economic general anesthetic adjuvant that maintains stable hemodynamics and decrease anesthetic consumption without the change of recovery profiles.

BackgroundWe designed this double-blind, placebo-controlled study to compare the efficacy of remifentanil in reducing the pain of both propofol and rocuronium injection during rapid-sequence induction.MethodsNinety-five patients, scheduled for elective surgery under general anesthesia, were divided into 3 groups: saline (Group S, n = 31), remifentanil 1 µg/kg (Group R, n = 32), and lidocaine 1.5 mg/kg (Group L, n = 32) were administered after tourniquet application. The occlusion was released after 1 min and 5 ml of 1% propofol was injected over 10 s. Pain on propofol injection was evaluated by a 10-point verbal numeric rating scale (VNRS). The rest of the induction dose of propofol and 1 mg/kg of rocuronium, were injected. Pain on rocuronium injection was evaluated by a four-point score (FPS).ResultsThe VNRS of propofol injection was as follows: R (0.78) = L (1.34) < S (4.26). The incidence of withdrawal response due to rocuronium was as follows: R (6.3%) < L (53.1%) < S (83.9%). The FPS of rocuronium injection was as follows: R (0.81) < L (1.78) < S (2.93).ConclusionsPretreatment with a bolus of remifentanil was effective in simultaneously reducing injection pain of propofol and rocuronium. In addition, remifentanil pretreatment was more effective in suppression of withdrawal response by rocuronium than lidocaine.

IntroductionThe degree of perceived smoking stigma can differ, based on various factors such as gender; this may influence the effect of smoking cessation interventions, including denormalization. This study investigates the gender differences in smoking stigma recognized by Korean smokers and explores the effect of these differences on the success of smoking cessation messages that aim to initiate an identity crisis among smokers. It aims to contribute to effective smoking cessation intervention strategies for female smokers.MethodsThe smoker-gender Implicit Association Test (IAT) was used to measure gender-based smoking stigma; the test comprised photos of people smoking, with positive and negative descriptors. Participants were 120 smokers aged 19–35 years (60 males and 60 females). Participants’ cognitive attitudes toward smoking and cessation intentions were assessed at baseline. To investigate the effect of social stigmatization on smokers, participants were asked to watch anti-smoking campaigns that stigmatized either smoking behavior or smokers’ self-identity. Cognitive attitudes and cessations intention were used to show differences in gender and message conditions.ResultsThe IAT D-score showed that female smokers perceived other female smokers significantly more negatively than they did male smokers, suggesting a higher level of smoking stigma. Female smokers in the socially stigmatizing condition reduced their negativity toward smoking less than those who were not stigmatized. Moreover, cessation intentions did not improve when female smokers received identity-threatening messages, indicating that female smokers tended to resist stigmatizing messages.DiscussionsThese findings provide empirical evidence that the gender of Korean smokers is significantly related to differences in smoking stigma. The negative perception and resistance responses of female smokers shown in this study are consistent with the findings of previous studies on the stigma of substance use disorders and addiction. High smoking stigma can also be a risk factor in anti-smoking interventions, including health communication; therefore, these findings should be interpreted with caution.

Herein, we reported the dual functions of molybdenum disulfide/sulfur-doped graphitic carbon nitride (MoS2/SGCN) composite as a sensing material for electrochemical detection of 4-NP and a catalyst for 4-NP degradation. The MoS2 nanosheet, sulfur-doped graphitic carbon nitride (SGCN) and MoS2/SGCN were characterized using field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) spectroscopy and X-ray photoelectron spectroscopy (XPS). Electrochemical characterization of these materials with electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) in 1 mM K4[Fe(CN)6]3-/4- show that the composite has the lowest charge transfer resistance and the best electrocatalytic activity. The limit of detection (LOD) and the linear range of 4-nitrophenol at MoS2/SGCN modified glassy carbon electrode (MoS2/SGCN/GCE) were computed as 12.8 nM and 0.1 – 2.6 μM, respectively. Also, the percentage recoveries of 4-NP in spiked tap water samples ranged from 97.8 – 99.1 %. The electroanalysis of 4-NP in the presence of notable interferons shows that the proposed electrochemical sensor features outstanding selectivity toward 4-NP. Additionally, the results of the catalytic degradation of 4-NP at MoS2/SGCN show that the nanocatalyst catalyzed the transformation of 4-NP to 4-aminophenol (4-AP) with a first-order rate constant (k) estimated to be 4.2 ×10−2 s−1. The results of this study confirm that the MoS2/SGCN nanocatalyst is a useful implement for electroanalytical monitoring and catalytic degradation of the hazardous 4-NP in water samples.

BackgroundThe aim of this study was to elucidate individual difference factors that modulate the attentional processing of game stimuli to explain the heterogeneity of extant findings. The current study examined whether individual differences in components of attentional control (AC-shifting and AC-focusing) moderated the link between internet gaming addiction symptom and attentional engagement to and disengagement biases from game-relevant cues.MethodsA total of 75 male undergraduate students who have played League of Legend (LOL) for more than 2 years completed well-established self-report questionnaires of internet gaming disorder symptoms and attentional control. The attentional bias toward game stimuli was measured for attentional engagement and disengagement using the attentional response to the distal vs. proximal emotional information (ARDPEI) task.ResultsThe results revealed that attentional control was a significant moderator of the relationship between internet game addiction symptoms and attentional disengagement bias. Further analyses revealed a positive relationship between internet game addiction symptoms and attentional disengagement bias only among those with low levels of AC-shifting ability. Contrary to our expectations, AC-shifting also moderated the relationship between internet gaming disorder and attentional engagement bias. The positive relationship between internet game addiction symptoms and attentional engagement bias only appeared among those with low levels of AC-shifting ability. Individual differences in AC-focusing did not moderate the relationship between internet gaming disorder and any attentional bias.ConclusionThis study confirmed that the greater the symptoms of game addiction, the stronger the attentional bias, especially in individuals with low AC-shifting ability. Therefore, it is necessary to examine sub-factors of AC in understanding the nature of attentional bias mechanisms in the development of internet game addiction and consider it as a psychological intervention to improve attentional bias.

BackgroundDigital serious games (SGs) have rapidly become a promising strategy for entertainment-based health education; however, developing SGs for children with chronic diseases remains a challenge. ObjectiveIn this study, we attempted to provide an updated scope of understanding of the development and evaluation of SG educational tools and develop a framework for SG education development to promote self-management activities and behavior change in children with chronic diseases. MethodsThis study consists of a knowledge base and an analytical base. This study followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. To build the knowledge base, 5 stages of research were developed, including refining the review question (stage 1), searching for studies (stage 2), selecting relevant studies (stage 3), charting the information (stage 4), and collating the results (stage 5). Eligible studies that developed SG prototypes and evaluated SG education for children with chronic diseases were searched for in PubMed, Embase, Google Scholar, and peer-reviewed journals. In the analytical base, the context-mechanism-output approach and game taxonomy were used to analyze relevant behavioral theories and essential game elements. Game taxonomy included social features, presentation, narrative and identity, rewards and punishment, and manipulation and control. A total of 2 researchers selected the domains for the included behavioral theories and game elements. The intended SG framework was finalized by assembling SG fragments. Those SG fragments were appropriately reintegrated to visualize a new SG framework. ResultsThis scoping review summarized data from 16 randomized controlled trials that evaluated SG education for children with chronic diseases and 14 studies on SG frameworks. It showed that self-determination theory was the most commonly used behavioral theory (9/30, 30%). Game elements included feedback, visual and audio designs, characters, narratives, rewards, challenges, competitions, goals, levels, rules, and tasks. In total, 3 phases of a digital SG framework are proposed in this review: requirements (phase 1), design and development (phase 2), and evaluation (phase 3). A total of 6 steps are described: exploring SG requirements (step 1), identifying target users (step 2), designing an SG prototype (step 3), building the SG prototype (step 4), evaluating the SG prototype (step 5), and marketing and monitoring the use of the SG prototype (step 6). Safety recommendations to use digital SG-based education for children in the post–COVID-19 era were also made. ConclusionsThis review summarizes the fundamental behavioral theories and game elements of the available literature to establish a new theory-driven step-by-step framework. It can support game designers, clinicians, and educators in designing, developing, and evaluating digital, SG-based educational tools to increase self-management activities and promote behavior change in children with chronic diseases.

ObjectivesOvarian carcinosarcoma (OCS) is a rare and lethal type of ovarian cancer. Despite its incredibly poor prognosis, it has received little research attention. In this study, we aim to evaluate the molecular features of OCS and elucidate their clinical significance.Study methodsWe examined 30 OCS by immunohistochemistry (IHC) and targeted panel sequencing collected from a single institution (2003–2013) as the initial molecularly characterized cohort (Cohort A). From November 2016 to April 2023, we collected an additional 67 OCS cases from three institutions across British Columbia and Alberta as the contemporary cohort (Cohort B) for clinical correlation. The Kaplan–Meier method was used to estimate overall and progression-free survival, and differences in survival rates were compared using the log-rank test. All tests were two-sided. A p-value of less than 0.05 was considered statistically significant.ResultsThe majority of OCS (82%) in the initial Cohort A were p53-mutated, and the carcinomatous component displayed the histological and molecular features of a high-grade tubo-ovarian serous carcinoma (HGSC-like). In a minority of OCS, the epithelial components were characteristics of endometrioid or clear cell carcinomas, and IHC staining was wild type for p53. In the contemporary Cohort B, we observed the same histological findings related to the p53 IHC staining pattern. The median overall survival of the p53-mutated HGSC-like OCS (47 patients) was significantly higher (43.5 months) compared with that of the p53 wild-type OCS (10 patients, 8.8 months; P < 0.01). Pathogenic BRCA1/2 germline/somatic mutations were observed in 7 patients (17.5%) of HGSC-like OCS, and all these patients were alive at 3 years from diagnosis compared to a 51% 3-year survival among the patients with BRCA1/2 wild-type HGSC-like OCS (33 patients) (p = 0.022). Majority of patients (6/7) with BRCA1/2-mutated OCS received poly (ADP-ribose) polymerase inhibitor as maintenance therapy in this cohort.ConclusionsMost OCSs have a morphologic and molecular profile resembling HGSC; however, some OCSs display a molecular profile that suggests origin through non-serous oncogenic pathways. This molecular distinction has both prognostic and treatment (predictive) implications. These findings underscore the importance of routine p53 IHC testing on all OCS and BRCA1/2 testing on p53-mutated OCS.

Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.

Background Immunotherapy can be associated with prolonged disease control even after cessation of treatment without the need for further cancer-directed therapy. Treatment-related adverse events (TRAEs) can also persist after discontinuation of therapy. Treatment-free survival (TFS) with and without toxicity as a component of a partitioned survival model can characterize patient survival time, which is not captured by standard outcome measures.Methods Data from 1096 patients with advanced renal cell carcinoma treated with first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the CheckMate 214 trial were analyzed. TFS was defined as the area between two Kaplan-Meier curves for time from randomization to protocol therapy discontinuation and time from randomization to subsequent systemic therapy initiation or death, estimated as the difference in 60-month restricted mean times with confidence intervals (CIs) obtained using bootstrap sampling. Time on protocol therapy and TFS were further characterized as time with and without grade 2+ and 3+TRAEs. Survival functions were estimated in subgroups including International Metastatic Renal Cell Carcinoma Database Consortium risk groups using the Kaplan-Meier method.Results At 5 years from randomization, 48% of patients treated with NIVO+IPI and 37% of patients treated with SUN were alive. In the intent-to-treat population, 18% of the NIVO+IPI-treated and 5% of SUN-treated patients are surviving treatment-free. For favorable-risk patients, the 60-month mean TFS was 14.4 months for NIVO+IPI versus 5.5 months for SUN (difference 8.9 months (95% CI 4.9 to 12.8)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 5.0 and 2.1 months, respectively, and with grade 3+TRAEs was 1.2 and 0.3 months, respectively. For intermediate/poor-risk patients, the 60-month mean TFS was 10.1 months for NIVO+IPI versus 4.1 months for SUN (difference 6.1 months (95% CI 4.2 to 7.9)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 4.0 versus 2.0 months, respectively, and 0.6 versus 0.3 months with grade 3+TRAEs.Conclusions Although overall survival was similar, favorable-risk patients treated with NIVO+IPI spent more time surviving treatment-free with and without toxicity versus SUN after 60 months of follow-up. Intermediate/poor-risk patients treated with NIVO+IPI had longer survival and longer TFS without toxicity versus SUN.Trial registration number NCT02231749.

Trace detection of common pesticide residue is necessary to assure safety of fruit and vegetables, given that the potential health risk to consumers is attributed to the contamination of the sources. A simple, rapid and effective means of finding the residue is however required for household purposes. In recent years, the technique in association with surface-enhanced Raman scattering (SERS) has been well developed in particular for trace detection of target molecules. Herein, gold nanoparticles (Au NPs) were integrated with sol-gel spin-coated Zirconia nanofibers (ZrO2 NFs) as a chemically stable substrate and used for SERS application. The morphologies of Au NPs/ZrO2 NFs were adjusted by the precursor concentrations (_X, X = 0.05–0.5 M) and the effect of SERS on Au NPs/ZrO2 NFs_X was evaluated by different Raman laser wavelengths using rhodamine 6G as the probe molecule at low concentrations. The target pesticides, phosmet (P1), carbaryl (C1), permethrin (P2) and cypermethrin (C2) were thereafter tested and analyzed. Au NPs/ZrO2 NFs_0.3 exhibited an enhancement factor of 2.1 × 107, which could detect P1, C1, P2 and C2 at the concentrations down to 10−8, 10−7, 10−7 and 10−6 M, respectively. High selectivity to the organophosphates was also found. As the pesticides were dip-coated on an apple and then measured on the diluted juice containing sliced apple peels, the characteristic peaks of each pesticide could be clearly identified. It is thus promising to use NPs/ZrO2 NFs_0.3 as a novel SERS-active substrate for trace detection of pesticide residue upon, for example, fruits or vegetables.

In the last decade, there's been a rising emphasis on eco-friendly solvents in industry and academia due to environmental concerns. Vegetable oils are now recognized as a practical, non-toxic option for extracting phytochemicals from herbs. This study presents a novel, green, and user-friendly method for extracting phenolic content from Crocus sativus L. waste using ultrasound. It replaces conventional organic solvents with sustainable sunflower oil, making the process eco-friendly and cost-effective. The effects of temperature (18–52 °C), ultrasonic time (5–55 min), and solid-solvent ratio (5–31 g/100 mL) were assessed by applying response surface methodology (RSM) and Central composite design. The combined impact of solid-solvent ratio, temperature, and ultrasonic time led to heightened phenolic content and antioxidant activity in the enriched oil. However, when these variables were at their maximum levels, there was a decline in these attributes. The specific conditions found to be ideal were a solid-to-liquid ratio of 26 g/100 mL, a temperature of 45 °C, and a duration of 45 min. The optimum extraction condition yielded the expected highest phenolic content (317.15 mg/ Kg), and antioxidant activity (89.34%). The enriched oil with flower saffron enabled the utilization of renewable natural ingredients, ensuring the production of a healthy extract or product. Also, enriched oils find diverse applications in areas such as food, aquaculture, and cosmetics.

Porous titanium (P_Ti) is considered as an effective material for bone scaffold to achieve a stiffness reduction. Herein, biomimetic (bio-)scaffolds were made of sintered P_Ti, which used NaCl as the space holder and had it removed via the hydrothermal method. X-ray diffraction results showed that the subsequent sintering temperature of 1000 °C was the optimized temperature for preparing P_Ti. The compressive strength of P_Ti was measured using a compression test, which revealed an excellent load-bearing ability of above 70 MPa for that with an addition of 50 wt % NaCl (P_Ti_50). The nano-hardness of P_Ti, tested upon their solid surface, was presumably consistent with the density of pores vis-à-vis the addition of NaCl. Overall, a load-bearable P_Ti with a highly porous structure (e.g., P_Ti_50 with a porosity of 43.91% and a pore size around 340 μm) and considerable compressive strength could be obtained through the current process. Cell proliferation (MTS) and lactate dehydrogenase (LDH) assays showed that all P_Ti samples exhibited high cell affinity and low cell mortality, indicating good biocompatibility. Among them, P_Ti_50 showed relatively good in-cell morphology and viability, and is thus promising as a load-bearable bio-scaffold.

Lily Koo Lin1, Han Lee2, Eli Chang11Department of Oculoplastics, Doheny Eye Institute, Los Angeles, CA, USA; 2Department of Dermatology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USABackground: Pigmented basal cell carcinoma (PBCC) of the eyelid has not been well cited in the literature, and is often overlooked in the differential diagnosis of pigmented eyelid lesions. We aim to describe PBCC of the eyelid in Hispanic patients.Methods: Retrospective review of patients with eyelid skin cancer who presented to the Department of Dermatology at the Keck School of Medicine of the University of Southern California and the Doheny Eye Institute from January 2002 to November 2005.Results: Sixty-nine of the 79 patients with eyelid skin cancer had basal cell carcinoma. Eight of these patients were Hispanic. Four of the eight Hispanic patients had PBCC.Conclusions: Although eyelid PBCC is regarded as a rare condition, it may occur more commonly in the Hispanic population and should be remembered in the differential diagnosis of pigmented eyelid lesions.Keywords: pigmented basal cell carcinoma, eyelid, skin cancer, lesions

Zebrafish (Danio rerio) is a widely used model organism in genetics and developmental biology research. Genetic screens have proven useful for studying embryonic development of the nervous system in vivo, but in vitro studies utilizing zebrafish have been limited. Here, we introduce a robust zebrafish primary neuron culture system for functional nerve growth and guidance assays. Distinct classes of central nervous system neurons from the spinal cord, hindbrain, forebrain, and retina from wild type zebrafish, and fluorescent motor neurons from transgenic reporter zebrafish lines, were dissociated and plated onto various biological and synthetic substrates to optimize conditions for axon outgrowth. Time-lapse microscopy revealed dynamically moving growth cones at the tips of extending axons. The mean rate of axon extension in vitro was 21.4±1.2 µm hr(-1) s.e.m. for spinal cord neurons, which corresponds to the typical ∼0.5 mm day(-1) growth rate of nerves in vivo. Fluorescence labeling and confocal microscopy demonstrated that bundled microtubules project along axons to the growth cone central domain, with filamentous actin enriched in the growth cone peripheral domain. Importantly, the growth cone surface membrane expresses receptors for chemotropic factors, as detected by immunofluorescence microscopy. Live-cell functional assays of axon extension and directional guidance demonstrated mammalian brain-derived neurotrophic factor (BDNF)-dependent stimulation of outgrowth and growth cone chemoattraction, whereas mammalian myelin-associated glycoprotein inhibited outgrowth. High-resolution live-cell Ca(2+)-imaging revealed local elevation of cytoplasmic Ca(2+) concentration in the growth cone induced by BDNF application. Moreover, BDNF-induced axon outgrowth, but not basal outgrowth, was blocked by treatments to suppress cytoplasmic Ca(2+) signals. Thus, this primary neuron culture model system may be useful for studies of neuronal development, chemotropic axon guidance, and mechanisms underlying inhibition of neural regeneration in vitro, and complement observations made in vivo.

Filaggrin (FLG) is an essential structural protein expressed in differentiated keratinocytes. Insufficient FLG expression contributes to the pathogenesis of chronic inflammatory skin diseases. Saikosaponin A (SSA), a bioactive oleanane-type triterpenoid, exerts anti-inflammatory activity. However, the effects of topically applied SSA on FLG expression in inflamed skin remain unclear. This study aimed to evaluate the biological activity of SSA in restoring reduced FLG expression. The effect of SSA on FLG expression in HaCaT cells was assessed through various biological methods, including reverse transcription PCR, quantitative real-time PCR, immunoblotting, and immunofluorescence staining. TNFα and IFNγ decreased FLG mRNA, cytoplasmic FLG protein levels, and FLG gene promoter–reporter activity compared to the control groups. However, the presence of SSA restored these effects. A series of FLG promoter–reporter constructs were generated to investigate the underlying mechanism of the effect of SSA on FLG expression. Mutation of the AP1-binding site (mtAP1) in the −343/+25 FLG promoter–reporter abrogated the decrease in reporter activities caused by TNFα + IFNγ, suggesting the importance of the AP1-binding site in reducing FLG expression. The SSA treatment restored FLG expression by inhibiting the expression and nuclear localization of FRA1 and c-Jun, components of AP1, triggered by TNFα + IFNγ stimulation. The ERK1/2 mitogen-activated protein kinase signaling pathway upregulates FRA1 and c-Jun expression, thereby reducing FLG levels. The SSA treatment inhibited ERK1/2 activation caused by TNFα + IFNγ stimulation and reduced the levels of FRA1 and c-Jun proteins in the nucleus, leading to a decrease in the binding of FRA1, c-Jun, p-STAT1, and HDAC1 to the AP1-binding site in the FLG promoter. The effect of SSA was evaluated in an animal study using a BALB/c mouse model, which induces human atopic-dermatitis-like skin lesions via the topical application of dinitrochlorobenzene. Topically applied SSA significantly reduced skin thickening, immune cell infiltration, and the expression of FRA1, c-Jun, and p-ERK1/2 compared to the vehicle-treated group. These results suggest that SSA can effectively recover impaired FLG levels in inflamed skin by preventing the formation of the repressor complex consisting of FRA1, c-Jun, HDAC1, and STAT1.

We investigated whether radiomics of computed tomography (CT) image data enables the differentiation of bone metastases not visible on CT from unaffected bone, using pathologically confirmed bone metastasis as the reference standard, in patients with gastric cancer. In this retrospective study, 96 patients (mean age, 58.4 ± 13.3 years; range, 28–85 years) with pathologically confirmed bone metastasis in iliac bones were included. The dataset was categorized into three feature sets: (1) mean and standard deviation values of attenuation in the region of interest (ROI), (2) radiomic features extracted from the same ROI, and (3) combined features of (1) and (2). Five machine learning models were developed and evaluated using these feature sets, and their predictive performance was assessed. The predictive performance of the best-performing model in the test set (based on the area under the curve [AUC] value) was validated in the external validation group. A Random Forest classifier applied to the combined radiomics and attenuation dataset achieved the highest performance in predicting bone marrow metastasis in patients with gastric cancer (AUC, 0.96), outperforming models using only radiomics or attenuation datasets. Even in the pathology-positive CT-negative group, the model demonstrated the best performance (AUC, 0.93). The model’s performance was validated both internally and with an external validation cohort, consistently demonstrating excellent predictive accuracy. Radiomic features derived from CT images can serve as effective imaging biomarkers for predicting bone marrow metastasis in patients with gastric cancer. These findings indicate promising potential for their clinical utility in diagnosing and predicting bone marrow metastasis through routine evaluation of abdominopelvic CT images during follow-up.