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Abstract Fragile X syndrome (FXS) is the leading cause of inherited autism and intellectual disabilities. Aberrant protein synthesis due to the loss of fragile X messenger ribonucleoprotein (FMRP) is the major defect in FXS, leading to a plethora of cellular and behavioral abnormalities. However, no treatments are available to date. In this study, we found that activation of metabotropic glutamate receptor 7 (mGluR7) using a positive allosteric modulator named AMN082 represses protein synthesis through ERK1/2 and eIF4E signaling in an FMRP-independent manner. We further demonstrated that treatment of AMN082 leads to a reduction in neuronal excitability, which in turn ameliorates audiogenic seizure susceptibility in Fmr1 KO mice, the FXS mouse model. When evaluating the animals’ behavior, we showed that treatment of AMN082 reduces repetitive behavior and improves learning and memory in Fmr1 KO mice. This study uncovers novel functions of mGluR7 and AMN082 and suggests the activation of mGluR7 as a potential therapeutic approach for treating FXS.

Abstract This study explores how social media constructs sexual deviance and violence against women. Based on vigorous debates on Facebook about the cheating of case two Hong Kong celebrities, we analyzed how cheating and promiscuity are constructed as sexual deviance on social media in Hong Kong through a politics of claims-making. Research has demonstrated how promiscuity and cheating are facilitated through the Internet. It has yet to show how social media sustains compulsory monogamy and constructs promiscuity and cheating as deviance to induce violence against women. Our study contributes to understanding how CM is sustained and how it constructs sexual deviance in scoial media. We discovered that discussing taboo sexual practices through Facebook involves mainly punitive informal social control and only strengthens the stigmatization of them, regulating gender and sexual morality, sustaining compulsory monogamy, and oppressing women and practitioners of marginalized sexual behaviors. We call for updated measures on social media outlets like Facebook to regulate cyber violence and encourage civilized discussions on taboo sexual topics.

Abstract Aging results from the accumulation of molecular damage that impairs normal biochemical processes. We previously reported that age‐linked damage to amino acid sequence NGR (Asn‐Gly‐Arg) results in “gain‐of‐function” conformational switching to isoDGR (isoAsp‐Gly‐Arg). This integrin‐binding motif activates leukocytes and promotes chronic inflammation, which are characteristic features of age‐linked cardiovascular disorders. We now report that anti‐isoDGR immunotherapy mitigates lifespan reduction of Pcmt1−/− mouse. We observed extensive accumulation of isoDGR and inflammatory cytokine expression in multiple tissues from Pcmt1−/− and naturally aged WT animals, which could also be induced via injection of isoDGR‐modified plasma proteins or synthetic peptides into young WT animals. However, weekly injection of anti‐isoDGR mAb (1 mg/kg) was sufficient to significantly reduce isoDGR‐protein levels in body tissues, decreased pro‐inflammatory cytokine concentrations in blood plasma, improved cognition/coordination metrics, and extended the average lifespan of Pcmt1−/− mice. Mechanistically, isoDGR‐mAb mediated immune clearance of damaged isoDGR‐proteins via antibody‐dependent cellular phagocytosis (ADCP). These results indicate that immunotherapy targeting age‐linked protein damage may represent an effective intervention strategy in a range of human degenerative disorders.

Accurate sex estimation is crucial for comprehensive analysis of the biological profiles of unidentified human skeletal remains. However, there is a notable lack of research specifically addressing the morphometrics of the hard palate. Therefore, this study aimed to derive discriminant equations using the hard palate and assess their applicability for sexing partial skeletal remains in a contemporary Korean population. Statistical analyses were performed for 24 measurements derived from three-dimensional models of the hard palate, generated using computed tomography scans of 301 individuals (156 males, 145 females). Descriptive statistics revealed significant sexual dimorphism in the mean comparison of hard palate sizes between Korean males and females, with males exhibiting larger palates across all measurements (p < 0.05). Discriminant function score equations were generated to aid in sex determination. Univariate analysis yielded an accuracy range of 57.8–75.1%, whereas the stepwise method achieved an accuracy of 80.7% with five selected variables: IF-PNS, GFL-GFR, IF-GFR, Pr-EcL, and Pr-EnR. The results of this metric analysis demonstrate the usefulness of the hard palate for sex estimation in the contemporary Korean population. These findings have potential implications for forensic investigations, archeological studies, and population-specific anatomical research. [ABSTRACT FROM AUTHOR]

Purpose: To report the efficiency of OT utilisation and perioperative outcomes with a dedicated spine team approach in AIS patients who underwent posterior spinal fusion (PSF) surgeries in a consecutive case operation list. Methods: Three AIS patients operated in a day (8:00 AM–8:00 PM) by a dedicated spine team were recruited between 2021 and 2022. The dedicated team comprised of three senior spine consultants who operated using a dual attending surgeon strategy, an anaesthetic consultant, dedicated surgical scrub nurses, anaesthesiology nurses, radiographers, and neuromonitoring technicians. Patients were categorised according to the sequence of operation list of the day (Case 1, Case 2, and Case 3). OT efficiency was represented by OT time in five stages (preoperative time, operative time, postoperative time, total OT time, and turnover time). OT time and perioperative outcomes were compared. Results: 102 cases were analysed. On average, Case 1 began at 8:38 AM whereas Case 3 ended by 5:54 PM. OT efficiency was consistent throughout the day of operation with comparable OT time in all five stages between groups (p > 0.05). The mean turnover time was 15.1 ± 13.5 min and the mean operative time was 123.0 ± 28.1 min. Intraoperative arterial blood gas (ABG) parameters were maintained in an optimal range. The complication rate was 2.0% (N = 2/102). Conclusion: Consistent OT efficiency was demonstrated with a dedicated spine team approach. Despite performing three AIS cases in a consecutive case operation list, patients' safety was not compromised as perioperative outcomes between groups were comparable. [ABSTRACT FROM AUTHOR]

Hate crimes and racist incidents are occurring with alarming and increasing frequency on college and university campuses. As colleges work to reduce racist incidents on campus, there is still a need to prepare students to respond to racism when it occurs. When students are prepared to respond to racist incidents, they tend to have better mental health. We draw on prior literature to examine whether learning about critical race theory (CRT) and receiving CRT-informed mentoring—as embedded in an undergraduate research experience program—related to four-year college students' self-assessed ability to respond to racism. Specifically, we propose and test a conceptual model to examine the benefits of participating in an undergraduate research experience program that required students to learn about CRT and receiving CRT-informed mentorship. Consistent with prior literature on undergraduate research experience programs, we found that the intervention positively related to students' sense of self-efficacy and science identity, but it did not have an independent, direct relationship with self-assessed ability to respond to racism. However, the intervention indirectly supports students' preparedness to respond to racism through its positive relationship with self-efficacy. As state legislatures around the country work to ban CRT, this paper offers empirical evidence that embedding CRT in university programs can support student development in multiple related ways. [ABSTRACT FROM AUTHOR]

Purpose: Ductal carcinoma in situ (DCIS) of the breast is one of the most common pre-invasive cancers diagnosed in women. Quality of life (QoL) is extremely important to assess in studies including these patients due to the favorable prognosis of the disease. The primary objective of this systematic review was to compile a comprehensive list of QoL issues, all existing QoL assessment tools, and patient-reported outcome measures used to assess DCIS. Methods: A search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases from inception to August 2023, using keywords such as “ductal carcinoma in-situ”, “quality of life”, and “patient-reported outcomes.” QoL issues and QoL tools in primary research studies were extracted. Results: A total of 67 articles identified issues pertaining to patients with DCIS spanning physical, functional, and psychosocial QoL domains. Physical and functional issues observed in patients included pain, fatigue, and impaired sexual functioning. Psychosocial issues such as anxiety, depression, and confusion about one’s disease were also common. QoL tools included those that assessed general QoL, breast cancer-specific tools, and issue-specific questionnaires. Conclusion: The current instruments available to assess QoL in patients with DCIS do not comprehensively capture the issues that are pertinent to patients. Thus, the modification of existing tools or the creation of a DCIS-specific QoL tool is recommended to ensure that future research will be sensitive towards challenges faced by patients with DCIS. [ABSTRACT FROM AUTHOR]

The Suwolbong tuff ring is a basaltic monogenetic volcano in the Quaternary intraplate volcanic field of Jeju Island, Korea. The tuff ring was formerly interpreted to have had a congested magma plumbing system consisting of multiply-sourced dike complexes, based on stepped and mixed chemical trends of alkaline to sub-alkaline glassy pyroclasts. Microscopic observations, petrological analysis, and componentry analysis of the glassy pyroclasts reveal, however, that some of the glassy pyroclasts in the tuff ring are accidental and inappropriate for interpreting magmatic processes. Juvenile particles are vesicular, alkaline in composition, mainly contain olivine, clinopyroxene, and plagioclase phenocrysts, and comprise about 35 vol% of the deposits. In contrast, accidental particles are non-vesicular, alkaline to subalkaline in composition, less abundant (avg. 8 vol%), and show alteration rims. The accidental particles are interpreted to have been derived from the volcaniclastic layers deposited before the eruption of the Suwolbong tuff ring. When removing the effects of the accidental particles and considering only the geochemical characteristics of the newly defined juvenile particles, the Suwolbong tuff ring is interpreted to have had a rather simple, not necessarily congested, plumbing system fed by independently ascending multiple magma batches. This study shows that the interpretation of the properties of the source magma and the magma plumbing system in monogenetic volcanoes must be performed after clearly distinguishing between juvenile and accidental particles based on rigorous microscopic analysis of pyroclastic materials. [ABSTRACT FROM AUTHOR]

Purpose: Dopamine transporter imaging is crucial for assessing presynaptic dopaminergic neurons in Parkinson's disease (PD) and related parkinsonian disorders. While 18F-FP-CIT PET offers advantages in spatial resolution and sensitivity over 123I-β-CIT or 123I-FP-CIT SPECT imaging, accurate quantification remains essential. This study presents a novel automatic quantification method for 18F-FP-CIT PET images, utilizing an artificial intelligence (AI)-based robust PET spatial normalization (SN) technology that eliminates the need for anatomical images. Methods: The proposed SN engine consists of convolutional neural networks, trained using 213 paired datasets of 18F-FP-CIT PET and 3D structural MRI. Remarkably, only PET images are required as input during inference. A cyclic training strategy enables backward deformation from template to individual space. An additional 89 paired 18F-FP-CIT PET and 3D MRI datasets were used to evaluate the accuracy of striatal activity quantification. MRI-based PET quantification using FIRST software was also conducted for comparison. The proposed method was also validated using 135 external datasets. Results: The proposed AI-based method successfully generated spatially normalized 18F-FP-CIT PET images, obviating the need for CT or MRI. The striatal PET activity determined by proposed PET-only method and MRI-based PET quantification using FIRST algorithm were highly correlated, with R2 and slope ranging 0.96–0.99 and 0.98–1.02 in both internal and external datasets. Conclusion: Our AI-based SN method enables accurate automatic quantification of striatal activity in 18F-FP-CIT brain PET images without MRI support. This approach holds promise for evaluating presynaptic dopaminergic function in PD and related parkinsonian disorders. [ABSTRACT FROM AUTHOR]

Purpose: Infectious spondylitis is caused by hematogenous seeding or adjacent soft tissue infection. No study has provided evidence that incubating biopsy specimens in blood culture bottles could enhance detection rates, nor has any study compared this method with conventional culture techniques. We aimed to assess the diagnostic yield of open microsurgical biopsies for infectious spondylitis and the efficacy of various culture media in the presence and absence of pre-biopsy antibiotic therapy. Methods: This retrospective study, which was conducted at a university-affiliated teaching hospital in Korea, enrolled 165 adult patients with suspected infectious spondylitis between February 2014 and September 2020. The diagnostic yield of open biopsy was compared among three culture media, namely, blood culture bottles, swab culture using transport media, and tissue culture using plain tubes, while considering preoperative antibiotic exposure. Results: Causative bacteria were identified in 84.2% of all cases. Blood culture bottles had the highest positivity rate (83.5%), followed by swab cultures (64.4%) and tissue cultures (44.9%). The differences in positivity rates were significant (P < 0.001). Preoperative antibiotic therapy reduced detection rates across all media, particularly in tissue cultures. Conclusions: We established the high diagnostic yield of open microsurgical biopsy using blood culture bottles, suggesting that pre-biopsy antibiotic therapy significantly affects bacterial detection, thereby underscoring the importance of culture medium selection in the diagnosis of infectious spondylitis. [ABSTRACT FROM AUTHOR]

This study explores the development of biofoundries, emphasizing the integration of synthetic biology with artificial intelligence (AI) and robotics. It outlines critical challenges such as the necessity for interdisciplinary collaboration and the development of hardware, software, and AI specific to biofoundry operations. To address these challenges, we recommend strategies like rapid prototyping, soft integration, and the strategic implementation of AI. We underscore the vital role of synthetic biology researchers in advancing biofoundry capabilities and advocate for collaborative, multidisciplinary efforts to optimize the development and functionality of biofoundries. [ABSTRACT FROM AUTHOR]

The use of auxiliary information concept (AIC) and variable sampling interval (VSI) feature in control charts is shown to enhance the sensitivity of the charts in out-of-control detection. In this paper, the VSI hybrid exponentially weighted moving average (HEWMA) chart based on auxiliary information (denoted as the VSI AIC-HEWMA) for the process mean is proposed, where two levels of sampling interval are considered, with test statistic that considers both information from the study and auxiliary characteristics. Monte-Carlo simulation is used to compute the average time to signal (ATS), standard deviation of the time to signal (SDTS) and expected ATS (EATS) of the chart. The VSI AIC-HEWMA chart is then compared with the auxiliary information based variable sampling interval exponentially weighted moving average (VSI AIC-EWMA) and AIC-HEWMA charts. Results show that the VSI AIC-HEWMA chart is more sensitive than the competing charts for all sizes of shift in out-of-control detection, by having the smallest out-of-control ATS and EATS values. [ABSTRACT FROM AUTHOR]

Purpose: Radiation dermatitis (RD) is a painful side effect of radiation therapy (RT). The objective of this analysis was to investigate the validity and reliability of the Skin Symptom Assessment (SSA) questionnaire in evaluating the severity of patient- and clinician-reported outcomes for RD in breast cancer patients by comparing it to a validated assessment tool, the Radiation-Induced Skin Reaction Assessment Scale (RISRAS) questionnaire. Methods: This study compared patient and clinician-reported outcomes for RD from previous clinical trials conducted in a Canadian cancer centre. The analysis included 376 and 38 patients in the two trials using Mepitel Film (doi.org/10.1200) and StrataXRT (clinicaltrials.gov identifier: NCT05594498), respectively. Patients in both studies completed the SSA and RISRAS questionnaires at baseline, 2-weeks post-RT, and 3 months after completion of RT. Clinician SSA and RISRAS assessments were collected at baseline and 2-weeks post-RT. These time points were analyzed longitudinally to investigate the SSA’s validity in RD symptom assessment. Results: The majority of patient-reported items on the SSA and RISRAS assessments demonstrated positive significant associations between symptoms of itchiness, between pain/soreness and pain/discomfort, and between blistering or erythema with burning sensation items. All items in the clinician-reported SSA and clinician component of RISRAS showed positive statistical significance between items measuring erythema, pigmentation or edema with dry desquamation, and blistering/peeling with moist desquamation. Conclusions: The SSA has been validated for assessing patient- and clinician-reported symptoms of RD accurately as outcomes correlate well with the previously validated RISRAS assessment. [ABSTRACT FROM AUTHOR]

Background: Barrier films or dressings were reported to be effective in preventing radiation dermatitis (RD) in breast cancer patients, but their comparative efficacy is unknown. Methods: A systematic literature search was performed on Embase, MEDLINE and Cochrane CENTRAL Registry of Clinical Trials from inception to October 20, 2023. Randomised controlled trials (RCTs) comparing barrier films or dressings to the standard of care (SOC) or other interventions were included. We estimated summary odds ratios and mean differences using network meta-analysis with random effects. This study was registered with PROSPERO (ID: CRD42023475021). Results: Fourteen RCTs met inclusion criteria. Six interventions were analysed: 3M™ Moisturizing Double Barrier Cream (MDBC), 3M™ No Sting Barrier Film (BF), Hydrofilm® (HF), Mepitel® Film (MF), Silver Leaf Nylon Dressing and StrataXRT®. HF, MF and StrataXRT® reduced the incidence of moist desquamation compared to SOC (HF: OR = 0.08; p = 0.02; MF: OR = 0.31 p < 0.01; StrataXRT®: OR = 0.22, p = 0.04). The ranking of agents from most to least effective in preventing moist desquamation according to P-scores was HF (92.5%), MF (78.5%), StrataXRT® (70.1%), BF (46.4%), Silver Leaf Nylon Dressing (24.9%), MDBC (22.9%) and SOC (14.7%). Only four RCTs on HF and MF included patient-reported outcome (PRO) assessments that allowed pooling for analysis. HF and MF were more effective in reducing pain, itchiness and burning sensation compared to SOC (p < 0.01 for all symptoms). Conclusion: HF and MF were effective in preventing RD in breast cancer. Future RCTs should compare these interventions to effective cream preparations, such as topical corticosteroids. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells play a crucial role in immunotherapy for cancer due to their natural ability to target and destroy cancer cells. However, current methods to visualize NK cells' activity against tumors in live organisms are limited. We introduce an imaging method that non-invasively tracks NK cell activation by cancer cells through the STAT1 protein. To achieve this, we modified NK cells to include a specific genetic sequence that binds to STAT1 when activated. These engineered NK cells (GAS-NK) demonstrate their functionality through various biological tests and analysis. Observations of changes in cancer environments and patient-derived cancer organoid models further confirm the effectiveness of this approach. Our method provides a way to monitor NK cell activity, which could improve the prediction and effectiveness of NK cell-based cancer therapies, contributing to advances in cancer treatment. Imaging technique reveals STAT1-mediated activation of engineered NK cells, offering a novel method to monitor antitumor activity and enhance the effectiveness of NK cell-based cancer therapies. [ABSTRACT FROM AUTHOR]

Concrete pouring in winter is critical to both concrete manufacturers and end users owing to the possibility of concrete damage due to cold weather. In this context, various methods have been used to prevent frost damage to concrete in winter, including adjusting the concrete mix using a chemical admixture and heat-curing with tents. Of these methods, the insulated-gang-form approach does not require concrete-mix adjustment via a chemical-admixture addition. Furthermore, its positive effect on the initial quality of concrete during concrete construction in winter has previously been confirmed. In this study, the power consumption of the conventional gang form was compared with that of the insulated gang form to evaluate the efficiency of the two protection methods. A thermal vision camera was used to examine the surface heat loss of the gang forms after concrete pouring. The insulated gang form significantly outperformed the conventional one through its significantly reduced power consumption and reduced surface heat loss. These findings can contribute to the standardization of insulated gang form application to concrete protection in cold-weather conditions. [ABSTRACT FROM AUTHOR]

This article discusses a study that explores the potential of combining a CDK7 inhibitor with FLT3 inhibitors for the treatment of FLT3-ITD-mutated acute myeloid leukemia (AML). The researchers found that this combination treatment demonstrated synergistic inhibition of cell proliferation in AML cell lines and induced apoptotic cell death in AML cells. The study suggests that targeting both CDK7 and FLT3 could be a promising therapeutic strategy for patients with FLT3-ITD-mutated AML. The study was supported by grants and the authors have no competing interests. [Extracted from the article]

Metabolic dysfunction–associated fatty liver disease (MAFLD) is a common liver disease associated with obesity and is caused by the accumulation of ectopic fat without alcohol consumption. Coxsackievirus and adenovirus receptor (CAR) are vital for cardiac myocyte-intercalated discs and endothelial cell-to-cell tight junctions. CAR has also been reported to be associated with obesity and high blood pressure. However, its function in the liver is still not well understood. The liver of obese mice exhibit elevated CAR mRNA and protein levels. Furthermore, in the liver of patients with non-alcoholic steatohepatitis, CAR is reduced in hepatocyte cell–cell junctions compared to normal levels. We generated liver-specific CAR knockout (KO) mice to investigate the role of CAR in the liver. Body and liver weights were not different between wild-type (WT) and KO mice fed a paired or high-fat diet (HFD). However, HFD induced significant liver damage and lipid accumulation in CAR KO mice compared with WT mice. Additionally, inflammatory cytokines transcription, hepatic permeability, and macrophage recruitment considerably increased in CAR KO mice. We identified a new interaction partner of CAR using a protein pull-down assay and mass spectrometry. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) demonstrated a complex relationship with CAR, and hepatic CAR expression tightly regulated its level. Moreover, Apolipoprotein B (ApoB) and Low-density lipoprotein receptor (LDLR) levels correlated with APOBEC3C expression in the liver of CAR KO mice, suggesting that CAR may regulate lipid accumulation by controlling APOBEC3C activity. In this study, we showed that hepatic CAR deficiency increased cell-to-cell permeability. In addition, CAR deletion significantly increased hepatic lipid accumulation by inducing ApoB and LDLR expression. Although the underlying mechanism is unclear, CARs may be a target for the development of novel therapies for MAFLD. [ABSTRACT FROM AUTHOR]

Despite recent advancements, artificial muscles have not yet been able to strike the right balance between exceptional mechanical properties and dexterous actuation abilities that are found in biological systems. Here, we present an artificial magnetic muscle that exhibits multiple remarkable mechanical properties and demonstrates comprehensive actuating performance, surpassing those of biological muscles. This artificial muscle utilizes a composite configuration, integrating a phase-change polymer and ferromagnetic particles, enabling active control over mechanical properties and complex actuating motions through remote laser heating and magnetic field manipulation. Consequently, the magnetic composite muscle can dynamically adjust its stiffness as needed, achieving a switching ratio exceeding 2.7 × 10³. This remarkable adaptability facilitates substantial load-bearing capacity, with specific load capacities of up to 1000 and 3690 for tensile and compressive stresses, respectively. Moreover, it demonstrates reversible extension, contraction, bending, and twisting, with stretchability exceeding 800%. We leverage these distinctive attributes to showcase the versatility of this composite muscle as a soft continuum robotic manipulator. It adeptly executes various programmable responses and performs complex tasks while minimizing mechanical vibrations. Furthermore, we demonstrate that this composite muscle excels across multiple mechanical and actuation aspects compared to existing actuators. Artificial muscles often struggle to match the performance of biological systems. Here, the authors report an artificial magnetic muscle that shows remarkable mechanical and actuating capabilities, comparable to natural muscles. [ABSTRACT FROM AUTHOR]

Introduction: Entrustable professional activities (EPAs) are one way to assess competencies, and are designed to bridge the gap between theoretical competencies and real world clinical practice. Aims: This was a systematic review which aims to answer the question: "Which EPAs related to Emergency Medicine are described for medical schools?". Methods: We included original qualitative, interventional and observational studies (cross-sectional, case-control, and cohort studies) that described EPAs relevant to Emergency Medicine for Medical School. The search strategy was created using a combination of keywords and standardized index terms related to EPAs and Emergency Medicine. Results: The search strategy identified 991 citations. After screening the titles and abstracts, we identified 85 potentially relevant studies. After the full-text review, a total of 11 reports met the criteria for inclusion. Conclusion: Recognizing a patient requiring urgent or emergent care and initiating evaluation and management is the most common EPA related to Emergency Medicine described at Medical Schools. Use of EPAs is associated with increased student satisfaction and improved competences. However, there is a lack of undergraduate EM specific EPAs being systematically developed and published, and this should be an area to be explored in future studies. [ABSTRACT FROM AUTHOR]

Objectives: The COVID-19 pandemic has brought substantial mental health challenges as well as significant changes in the delivery of clinical care and interventions, such as switching from traditional face-to-face to online mode. This study aimed to compare the effectiveness and the course experience of a video-conferencing mindfulness-based intervention (MBI) with that delivered face-to-face. Method: Schoolteachers (N = 170) were randomly assigned to face-to-face group (n = 94) and video-conferencing group (n = 76) for an 8-week MBI. The schoolteachers' well-being, including psychological distress, insomnia, perceived stress, mindfulness, positive and negative affect, and life satisfaction, was measured before and after the MBI. Attendance, treatment fidelity, home practice compliance, and program acceptability were collected after the MBI. Qualitative feedback from the two groups was also collected to explore the differences in participants' subjective experiences. Results: Both face-to-face and video-conferencing formats of MBI resulted in better general mental health, more positive affect, and higher life satisfaction, as well as significantly lower levels of insomnia, stress, and negative affect. Observed improvement was comparable between face-to-face and video-conferencing MBI. The two groups also showed comparable adherence, intervention fidelity, and program acceptability. Qualitative results showed that while video-conferencing MBI might be weaker in group process, it provided better accessibility for participants. Conclusions: This study supported the effectiveness and feasibility of video-conferencing MBIs, which are highly accessible for teachers in need of mental health support. Further research exploring enhancements to the group process in video-conferencing MBIs may further improve the effectiveness of online programs. Preregistration: This study is not pre-registered. [ABSTRACT FROM AUTHOR]

Long waiting time in outpatient departments is a crucial factor in patient dissatisfaction. We aim to analytically interpret the waiting times predicted by machine learning models and provide patients with an explanation of the expected waiting time. Here, underestimating waiting times can cause patient dissatisfaction, so preventing this in predictive models is necessary. To address this issue, we propose a framework considering dissatisfaction for estimating the waiting time in an outpatient department. In our framework, we leverage asymmetric loss functions to ensure robustness against underestimation. We also propose a dissatisfaction-aware asymmetric error score (DAES) to determine an appropriate model by considering the trade-off between underestimation and accuracy. Finally, Shapley additive explanation (SHAP) is applied to interpret the relationship trained by the model, enabling decision makers to use this information for improving outpatient service operations. We apply our framework in the endocrinology metabolism department and neurosurgery department in one of the largest hospitals in South Korea. The use of asymmetric functions prevents underestimation in the model, and with the proposed DAES, we can strike a balance in selecting the best model. By using SHAP, we can analytically interpret the waiting time in outpatient service (e.g., the length of the queue affects the waiting time the most) and provide explanations about the expected waiting time to patients. The proposed framework aids in improving operations, considering practical application in hospitals for real-time patient notification and minimizing patient dissatisfaction. Given the significance of managing hospital operations from the perspective of patients, this work is expected to contribute to operations improvement in health service practices. [ABSTRACT FROM AUTHOR]

Graphene, a promising carbon nanomaterial, has garnered significant attention owing to its chemical stability, exceptional mechanical properties, and remarkable electrical conductivity and is being used in various electrical engineering applications ranging from solar cells to touch screens. The inherent mechanical strength and electric charge capacity of graphene enable efficient designs of diaphragms used in electrostatic loudspeakers, specifically within the high-frequency domain. This study incorporated single-layer and multi-layer graphene sheets, synthesized via chemical vapor deposition, as electrically charged diaphragms in electrostatic loudspeakers paired with an indium tin oxide film electrode to produce Coulomb force. Subsequently, the sound pressure levels of these distinct graphene- based electrostatic loudspeakers were determined through frequency response measurements. Based on our findings, we propose an optimal graphene film configuration for future electrostatic loudspeaker applications. [ABSTRACT FROM AUTHOR]

Purpose: We examined the association between progesterone (P4), estradiol (E2), and human chorionic gonadotropin (hCG) levels in early pregnancy and the development of hypertensive diseases of pregnancy among women undergoing assisted reproduction. Methods: Retrospective study including patients who underwent frozen embryo transfer (FET), ovarian stimulation (OS), or unassisted conception (UC) and had a live singleton birth. The primary outcome was the development of hypertensive diseases of pregnancy (gestational hypertension, preeclampsia, HELLP, or eclampsia). Secondary outcomes were the development of fetal intrauterine growth restriction (IUGR), gestational diabetes mellitus, birth weight, and pre-term birth. Hormone levels and the development of the outcomes were correlated. Results: A total of 681 patients were included; 189 had FET, 193 had OS, and 299 had UC. Patients undergoing FET or OS were not more likely to develop hypertensive diseases of pregnancy compared with UC patients. While median levels of E2 and P4 were significantly different between P-FET and NC-FET patients (E2: 252 vs 317 pg/mL, P4: 64 vs 29 ng/mL, respectively; both p < 0.01), rates of hypertensive diseases of pregnancy did not significantly differ between those two groups. In the multivariate analyses, P4, E2, and hCG were not associated with the development of hypertensive diseases of pregnancy, but progesterone levels were significantly higher among those with IUGR. This remained consistent when the analysis was limited to FET patients. Conclusion: P4, E2, and hCG levels did not correlate with the development of hypertensive diseases of pregnancy but elevated progesterone levels did correlate with the development of IUGR. [ABSTRACT FROM AUTHOR]

Purpose: To determine the bioavailability, safety, and tolerability of a single dose of oral docetaxel plus encequidar (oDox + E) and compare its pharmacokinetic exposure with current standard of care IV docetaxel. Introduction: Docetaxel is a taxane widely used as an anti-neoplastic agent. Due to low oral bioavailability secondary to gut P-glycoprotein (P-gp) efflux, its current use is limited to intravenous administration. Oral docetaxel may provide a less resource intensive, more convenient, and tolerable alternative. Encequidar is a first in class, minimally absorbed, oral gut-specific P-gp inhibitor. We tested whether oDox + E can achieve comparable pharmacokinetic exposure to IV docetaxel. Methods: A multicentre, phase I open-label, pharmacokinetic trial was undertaken to determine the bioavailability, safety, and tolerability of a single dose of oDox + E (at 75 mg/m2 + 15 mg, 150 mg/m2 + 15 mg, and 300 mg/m2 + 15 mg) in metastatic prostate cancer (mPC) patients compared to standard of care IV docetaxel as prescribed by their oncologists. The 15 mg of Encequidar at each dose level was given one hour prior to oral docetaxel. Results: 11 patients were enrolled; 9 patients completed the study. Oral docetaxel exposure increased with dose, achieving the highest at 300 mg/m2 oDox + E (with AUC0 − infinity of 1343.3 ± 443.0 ng.h/mL compared to the IV docetaxel AUC0 − infinity of 2000 ± 325 ng.h/mL) and became non-linear at 300 mg/m2. The mean absolute bioavailability of oDox + E across all 3 dose levels was 16.14% (range: 8.19-25.09%). No patient deaths, dose limiting toxicity, treatment-related serious adverse event or grade 4 toxicity were observed. Maximal tolerated dose was not reached. Conclusion: oDox + E has a safe and tolerable adverse event profile in patients with metastatic prostate cancer. The increase in oral bioavailability of oDox + E suggests a multi-dose oDox + E regimen could theoretically achieve exposures comparable with standard of care IV docetaxel. Further development to examine the optimal multiple dose regimen of oDox + E is warranted. Trial registration number: U1111-1173-5473. [ABSTRACT FROM AUTHOR]

Background: Alloplastic chin augmentation is the most common esthetic surgical treatment to reshape the chin. However, factory-made chin implants are typically standardized rather than custom-made and have potential to cause complications. Although the fabrication of custom-made implants by using computer-assisted planning and 3D-printing technology has become widespread, the process has several disadvantages, including long preoperative prosthesis preparation times, high costs, and unsuitability for patients with asymmetric chins or those who undergo combined mandibuloplasty before implant placement. The present study developed an innovative chin augmentation technique involving stacked expanded polytetrafluoroethylene (e-PTFE) sheets that is suitable for most patients and has minimal side effects. Materials and Methods: A retrospective review of a single surgeon's experience was performed over a 2 year period for patients who underwent a procedure involving piled-up e-PTFE sheets for alloplastic chin augmentation. This study analyzed the outcomes, complications (temporary nerve numbness, wound infection, hematoma formation, and implant displacement), and patient satisfaction during follow-up. Results: Between January 2018 and December 2020, 38 patients underwent the procedure involving piled-up e-PTFE sheets for alloplastic chin augmentation. Six patients (15.8%) experienced nerve-related temporary numbness, and one (2.6%) experienced wound infection. None had developed major complications such as implant displacement or wound infection at follow-up. Moreover, the patients demonstrated a high level of satisfaction with the surgical results. Conclusion: Piled-up e-PTFE sheets can be used to produce custom-fit porous polyethylene chin implants that result in minimal complications and a very high satisfaction rate. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Security of modern classical data encryption often relies on computationally hard problems, which can be trivialized with the advent of quantum computers. A potential remedy for this is quantum communication which takes advantage of the laws of quantum physics to provide secure exchange of information. Here, quantum key distribution (QKD) represents a powerful tool, allowing for unconditionally secure quantum communication between remote parties. At the same time, microwave quantum communication is set to play an important role in future quantum networks because of its natural frequency compatibility with superconducting quantum processors and modern near-distance communication standards. To this end, we present an experimental realization of a continuous-variable QKD protocol based on propagating displaced squeezed microwave states. We use superconducting parametric devices for generation and single-shot quadrature detection of these states. We demonstrate unconditional security in our experimental microwave QKD setting. The security performance is shown to be improved by adding finite trusted noise on the preparation side. Our results indicate feasibility of secure microwave quantum communication with the currently available technology in both open-air (up to ~ 80 m) and cryogenic (over 1000 m) conditions. Microwave-based quantum key distribution would allow a secure exchange of information in superconducting local area networks and, potentially beyond, in open-air conditions. Here, the authors provide a proof-of-principle implementation within a cryogenic environment, based on propagating displaced squeezed microwave states. [ABSTRACT FROM AUTHOR]

To investigate long-term outcomes and develop a risk model for pathological multi–station N2 (pN2b) in patients who underwent upfront surgery for clinical single–station N2 (cN2a) non–small cell lung cancer (NSCLC). From 2006 to 2018, 547 patients who had upfront surgery for suspected cN2a NSCLC underwent analysis. A risk model for predicting pN2b metastasis was developed using preoperative clinical variables via multivariable logistic analysis. Among 547 clinical cN2a NSCLC patients, 118 (21.6%), 58 (10.6%), and 371 (67.8%) had pN0, pN1, and pN2. Among 371 pN2 NSCLC patients, 77 (20.8%), 165 (44.5%), and 129 (34.7%) had pN2a1, pN2a2, and pN2b. The 5-year overall survival rates for pN2a1 and pN2a2 were significantly higher than for pN2b (p = 0.041). Histologic type (p < 0.001), age ≤ 50 years (p < 0.001), preoperatively confirmed N2 metastasis (p < 0.001), and clinical stage IIIB (vs. IIIA) (p = 0.003) were independent risk factors for pN2b metastasis. The risk scoring system based on this model demonstrated good discriminant ability for pN2b disease (area under receiver operating characteristic: 0.779). In cN2a NSCLC patients, those with multiple N2 metastases indicate worse prognosis than those with a single N2 metastasis. Our risk scoring system effectively predicts pN2b in these patients. [ABSTRACT FROM AUTHOR]

The reliability of terminal–substrate bonding in power modules for electric vehicles (EVs) was investigated by evaluating the effects of bonding method and substrate surface finish on the microstructural and mechanical properties of the joint. Ceramic substrates with bare Cu, electroless Ag, or electroless Ni-immersion Au surface finishes were bonded to Cu terminals by reflow soldering or ultrasonic welding. The interfacial intermetallic compound layers of the reflow-soldered joints exhibited varying compositions and morphologies according to the substrate surface finish, leading to differences in the shear strengths of the terminal joints. In contrast, the ultrasonic-welded joints did not exhibit any significant differences in morphology according to surface finish. Therefore, an electron backscatter diffraction analysis was conducted to observe the ultrasonic-welded joints in more detail. The results indicated that ultrasonic welding caused dynamic recrystallization (DRX) at the interface between the Cu terminal and ceramic substrate, resulting in grain refinement, and that the bare Cu substrate exhibited greater DRX than the other substrates. Consequently, both the bonding method and substrate surface finish were determined to significantly affect the mechanical properties of the power module terminal bond. This study is expected to contribute valuable insights to inform the improvement of terminal bonding for power modules, especially in EV applications. [ABSTRACT FROM AUTHOR]

Background: The International Federation for Emergency Medicine (IFEM) published its model curriculum for medical student education in emergency medicine in 2009. Because of the evolving principles of emergency medicine and medical education, driven by societal, professional, and educational developments, there was a need for an update on IFEM recommendations. The main objective of the update process was creating Intended Learning Outcomes (ILOs) and providing tier-based recommendations. Method: A consensus methodology combining nominal group and modified Delphi methods was used. The nominal group had 15 members representing eight countries in six regions. The process began with a review of the 2009 curriculum by IFEM Core Curriculum and Education Committee (CCEC) members, followed by a three-phase update process involving survey creation [The final survey document included 55 items in 4 sections, namely, participant & context information (16 items), intended learning outcomes (6 items), principles unique to emergency medicine (20 items), and content unique to emergency medicine (13 items)], participant selection from IFEM member countries and survey implementation, and data analysis to create the recommendations. Results: Out of 112 invitees (CCEC members and IFEM member country nominees), 57 (50.9%) participants from 27 countries participated. Eighteen (31.6%) participants were from LMICs, while 39 (68.4%) were from HICs. Forty-four (77.2%) participants have been involved with medical students' emergency medicine training for more than five years in their careers, and 56 (98.2%) have been involved with medical students' training in the last five years. Thirty-five (61.4%) participants have completed a form of training in medical education. The exercise resulted in the formulation of tiered ILO recommendations. Tier 1 ILOs are recommended for all medical schools, Tier 2 ILOs are recommended for medical schools based on perceived local healthcare system needs and/or adequate resources, and Tier 3 ILOs should be considered for medical schools based on perceived local healthcare system needs and/or adequate resources. Conclusion: The updated IFEM ILO recommendations are designed to be applicable across diverse educational and healthcare settings. These recommendations aim to provide a clear framework for medical schools to prepare graduates with essential emergency care capabilities immediately after completing medical school. The successful distribution and implementation of these recommendations hinge on support from faculty and administrators, ensuring that future healthcare professionals are well-prepared for emergency medical care. [ABSTRACT FROM AUTHOR]

Phlomoides umbrosa Turczaninow (PU), a traditional Korean medicinal herb, exhibits osteogenic and anti-inflammatory effects. This research explored the effect of PU extracts on hyperimmune responses within the respiratory tract using lipopolysaccharide-stimulated RAW 264.7 cells and an ovalbumin-induced hyper-responsiveness model. The inflammatory cytokines, protein expression linked to airway inflammation, antioxidant enzyme activity, histopathological observation, and expectorant activity were measured. The results revealed that PU treatment led to a concentration-dependent reduction in Th2 cytokines and the expression of nuclear factor (NF)-κB, phosphatase-tensin homolog, mitogen-activated protein kinase (MAPK), and inducible nitric oxide synthase (iNOS). Simultaneously, antioxidant enzyme activity increased. Furthermore, PU exhibited substantial enhancements in lung tissue condition and expectorant activity relative to the allergic rhinitis-induced group. These findings indicate the potential of PU to mitigate airway inflammation and excessive mucus production by suppressing NF-κB, MAPK, and iNOS pathways. Consequently, PU emerges as a promising anti-inflammatory agent for respiratory tract applications. [ABSTRACT FROM AUTHOR]

Neuroinflammation and endothelial cell apoptosis are prominent features of blood–brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular β-amyloid (Aβ) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting β-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aβ-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/β-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients. [ABSTRACT FROM AUTHOR]

This research presents the development of a gold-nickel (Au-Ni) nanoparticle alloy sensor for accurately quantifying L-carnitine in sports nutritional products. Addressing the limitations of traditional methods like HPLC and mass spectrometry, this sensor integrates the high conductivity of gold with the electrocatalytic activity of nickel, offering a more efficient alternative. The study focused on synthesizing Au-Ni nanoparticle films, optimizing enzyme sensor configuration, and evaluating performance metrics in real sample analysis. The sensor, utilizing carnitine acetyltransferase, displayed a significant sensitivity enhancement with a detection limit of 50 nM, and a broad dynamic range from 1 to 400 µM. In practical applications, the sensor showed a remarkable stability, retaining 90% of its initial response after extensive use, and achieved high accuracy in sample analysis with recovery rates between 97.3% and 103.5%. These findings demonstrate the sensor's potential for improving quality control in the sports nutrition industry, offering a rapid, cost-effective, and highly sensitive tool for L-carnitine measurement. [ABSTRACT FROM AUTHOR]

The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Here, we develop a mouse model (Streptozotocin with high-fat diet, STZ + HFD) that gradually develops fatty liver, metabolic dysfunction-associated steatohepatitis (MASH), hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. The hepatic transcriptomic features of STZ + HFD mice closely reflect those of patients with obesity accompanying type 2 diabetes mellitus, MASH, and MASLD-related HCC. Dietary changes and tirzepatide administration alleviate MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ + HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients is successfully established. Metabolic dysfunction-associated steatotic liver disease (MASLD) characterizes a spectrum of liver disorders initiated by hepatic lipid accumulation associated with metabolic syndrome. Here, the authors generate a mouse model that recapitulates the main histopathologic, transcriptomics, and metabolic alterations observed in MASLD patients. [ABSTRACT FROM AUTHOR]

Self-healing approaches are increasingly being explored in various fields as a potential method to recover damaged material properties. By self-recovering without external intervention, self-healing techniques emerge as a potential solution to arrest or prevent the development of large strains problems in soils (e.g., landslides) and other ground effects that influence the serviceability of structures (e.g., differential settlement). In this study, a microcapsule-based self-healing sand was developed, and its performance during mixing and compaction, shearing, and recovery of shear strength was demonstrated. The cargo used for sand improvement, a hardening oil, tung oil, was encapsulated in calcium alginate capsules by the ionic gelation method. The surface properties, internal structure, thermal stability and molecular structure of the capsules were evaluated by advanced material characterization techniques. The survivability of capsules during mixing and compaction was assessed by measuring the content of tung oil released into the sand, while their influence on sand shear strength and its recovery was assessed with shear box tests. The results showed that the capsules could rupture due to movement of the sand particles, releasing the tung oil cargo, leading to its hardening and minimizing its strain-softening response and enhancing up to 76% of the sand shear strength (at a normal stress of 10 kPa and capsules content of 4%). This study demonstrates the potential of a capsules-based self-healing system to provide 'smart' autonomous soil strength recovery and thus with potential to actively control the large strain behavior of soils. [ABSTRACT FROM AUTHOR]

Purpose of Review: Cardiac Allograft vasculopathy (CAV) is a major barrier to improving outcomes after heart transplantation. Coronary angiography has very low sensitivity to detect early CAV and intravascular ultrasound (IVUS) only improves it to some extent. In this article, we detail the current evidence surrounding use of Optical Coherence tomography (OCT) in patients with CAV. Recent Findings: OCT has the ability to recognize CAV at earlier stages with intimal thickness < 150 μm, can characterize CAV in almost pathologic / microscopic detail – plaque characteristics are better visualized and novel early features such as layered fibrotic plaques and microchannels have been identified. Progression of CAV can be monitored also, with promise shown in automated serial measurements also. Summary: OCT has significantly advanced our understanding of the pathophysiology—as well as permits precise monitoring and surveillance of the disease. Potential treatment options could also be evaluated using OCT. [ABSTRACT FROM AUTHOR]

Background: Left atrial thrombus (LAT) formation is associated with thromboembolic events. Objective: To investigate the incidence and associated factors of LAT in patients with atrial fibrillation (AF) who had been receiving anticoagulation therapy for more than 4 weeks, and to develop a prediction model using clinical and echocardiographic features. Methods: Medical records of 1,122 patients with AF (mean age, 59.4 ± 11.0 years, 58.3% male) who were on anticoagulation more than 4 weeks and underwent transesophageal echocardiography (TEE) were evaluated. The main outcome was the presence of LAT on TEE. Results: Warfarin and non-vitamin K oral anticoagulants were used in 74.4% and 25.6% of the patients at the time of examination, respectively. LAT was present in 60 patients (5.3%). Presence of LAT on TEE was associated with age ≥ 75 years (odds ratio [OR] 2.13 [95% confidence interval, 0.94–4.58]), persistent/permanent AF (OR 2.61 [1.42–4.93]), CHA2DS2-VASc score ≥ 3 points (OR 1.91 [1.05–3.48]), left ventricular ejection fraction < 40% (OR 2.35 [1.07–4.81]), and severe left atrial enlargement (OR 3.52 [1.89–6.79]). The presence of moderate-to-severe mitral regurgitation was associated with a lower risk of LAT (OR 0.13 [0.04–0.34]). A scoring system composed of the aforementioned predictors showed excellent discrimination performance (area under the curve 0.791 [95% CI, 0.727–0.854]). Conclusions: LAT was present in a considerable number of patients who were already receiving anticoagulation therapy. A prediction model that combines clinical and echocardiographic predictors could be useful in distinguishing patients who require imaging evaluations before left atrial intervention. Incidnece and predictors of LAT in patients with AF under anticoagulation therapy. AF, atrial fibrillation; CVS, CHA2DS2-VASc score; LA, left atrium; LAA, left atrial appendage; LAE, left atrial enlargement; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; OAC, oral anticoagulant; PeAF, persistent atrial fibrillation; TEE, transesophageal echocardiography [ABSTRACT FROM AUTHOR]

Adenosine receptor (AR) suppresses inflammation and fibrosis by activating cyclic adenosine monophosphate (cAMP) signaling. We investigated whether altered AR expression contributes to the development of fibrotic diseases and whether A2AAR and A2BAR upregulation inhibits fibrotic responses. Primary human lung fibroblasts (HLFs) from normal (NHLFs) or patients with idiopathic pulmonary fibrosis (DHLF) were used for in vitro testing. Murine models of fibrotic liver or pulmonary disease were developed by injecting thioacetamide intraperitoneally, by feeding a high-fat diet, or by intratracheal instillation of bleomycin. Modafinil, which activates cAMP signaling via A2AAR and A2BAR, was administered orally. The protein amounts of A2AAR, A2BAR, and exchange protein directly activated by cAMP (Epac) were reduced, while collagen and α-smooth muscle actin (α-SMA) were elevated in DHLFs compared to NHLFs. In liver or lung tissue from murine models of fibrotic diseases, A2AAR and A2BAR were downregulated, but A1AR and A3AR were not. Epac amounts decreased, and amounts of collagen, α-SMA, KCa2.3, and KCa3.1 increased compared to the control. Modafinil restored the amounts of A2AAR, A2BAR, and Epac, and reduced collagen, α-SMA, KCa2.3, and KCa3.1 in murine models of fibrotic diseases. Transforming growth factor-β reduced the amounts of A2AAR, A2BAR, and Epac, and elevated collagen, α-SMA, KCa2.3, and KCa3.1 in NHLFs; however, these alterations were inhibited by modafinil. Our investigation revealed that A2AAR and A2BAR downregulation induced liver and lung fibrotic diseases while upregulation attenuated fibrotic responses, suggesting that A2AAR and A2BAR-upregulating agents, such as modafinil, may serve as novel therapies for fibrotic diseases. [ABSTRACT FROM AUTHOR]

The development of optimized dosing regimens plays a crucial role in oncology drug development. This study focused on the population pharmacokinetic modelling and simulation of docetaxel, comparing the pharmacokinetic exposure of oral docetaxel plus encequidar (oDox + E) with the standard of care intravenous (IV) docetaxel regimen. The aim was to evaluate the feasibility of oDox + E as a potential alternative to IV docetaxel. The article demonstrates an approach which aligns with the FDA's Project Optimus which aims to improve oncology drug development through model informed drug development (MIDD). The key question answered by this study was whether a feasible regimen of oDox + E existed. The purpose of this question was to provide an early GO / NO-GO decision point to guide drug development and improve development efficiency. Methods: A stepwise approach was employed to develop a population pharmacokinetic model for total and unbound docetaxel plasma concentrations after IV docetaxel and oDox + E administration. Simulations were performed from the final model to assess the probability of target attainment (PTA) for different oDox + E dose regimens (including multiple dose regimens) in relation to IV docetaxel using AUC over effective concentration (AUCOEC) metric across a range of effective concentrations (EC). A Go / No-Go framework was defined—the first part of the framework assessed whether a feasible oDox + E regimen existed (i.e., a PTA ≥ 80%), and the second part defined the conditions to proceed with a Go decision. Results: The overall population pharmacokinetic model consisted of a 3-compartment model with linear elimination, constant bioavailability, constant binding mechanics, and a combined error model. Simulations revealed that single dose oDox + E regimens did not achieve a PTA greater than 80%. However, two- and three-dose regimens at 600 mg achieved PTAs exceeding 80% for certain EC levels. Conclusion: The study demonstrates the benefits of MIDD using oDox + E as a motivating example. A population pharmacokinetic model was developed for the total and unbound concentration in plasma of docetaxel after administration of IV docetaxel and oDox + E. The model was used to simulate oDox + E dose regimens which were compared to the current standard of care IV docetaxel regimen. A GO / NO-GO framework was applied to determine whether oDox + E should progress to the next phase of drug development and whether any conditions should apply. A two or three-dose regimen of oDox + E at 600 mg was able to achieve non-inferior pharmacokinetic exposure to current standard of care IV docetaxel in simulations. A Conditional GO decision was made based on this result and further quantification of the "effective concentration" would improve the ability to optimise the dose regimen. [ABSTRACT FROM AUTHOR]

Purpose: To detect otherwise undiagnosed asymptomatic sexually transmitted infection (STI), and for estimating prevalence among men who have sex with men (MSM). Methods: In this community-based study in Hong Kong, adult MSM were recruited. After completion of an online survey, free multi-anatomic sites self-sampling kits (urine specimens, pharyngeal and rectal swabs) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) tests were delivered to requesting participants. Factors associated with STI positivity were analyzed in logistic regression. Results: From September 2021 to October 2022, 712 MSM were recruited, with 86% aged 18–39, and 16% reported history of chemsex engagement. A majority (81%) had previously undergone HIV testing, 68% had ever tested for STI, and 35% previously diagnosed with STI. Totally 428 (60%) had requested self-sampling kits, and 276 (39%) returned collected samples. Among participants who returned the samples, about half had never been tested in the past and had no history of STI. Overall 21% tested positive for CT and/or NG (CT/NG)—CT positive 16% and NG positive 7%. By anatomic site, 16% of rectal swabs, 7% of pharyngeal swabs, but just 3% of urine specimens were CT/NG positive. The prevalence of CT/NG was not significantly different by history of STI diagnosis and testing. Conclusion: Self-sampled STI testing is a potentially useful means for enhancing uptake of screening in MSM in the community, which could uncover otherwise undiagnosed asymptomatic infections. Internet-based self-sampling for STI testing could complement the current clinic-based STI testing for supporting epidemiologic evaluation of STI control in the community. [ABSTRACT FROM AUTHOR]

This study aimed to establish sex- and age-specific reference values for motor performance (MP) in Hong Kong preschoolers aged 3–5 years old and examine the relationship between MP and BMI status. A cross-sectional study was conducted among 5579 preschoolers in Hong Kong. Three MP tests were administered, and height and weight information were collected. GAMLSS was used to compute the normative values of the motor tests. Boys outperformed girls in activities requiring muscle strength and power, while girls outperformed boys in activities requiring balance and coordination. The MP scores increased with age for both overarm beanbag throw and standing long jump for both sexes, while the one-leg balance scores showed larger differences between P50 and P95 in older preschoolers. Children with excessive weight performed worse in standing long jump and one-leg balance compared to their healthy weight peers. This study provides valuable information on the MP of preschoolers in Hong Kong, including sex- and age-specific reference values and the association between BMI status and MP scores. These findings can serve as a reference for future studies and clinical practice and highlight the importance of promoting motor skill development in preschoolers, particularly those who are overweight or obese. [ABSTRACT FROM AUTHOR]

Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have improved patient survival in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (mBC) in clinical trials and real-world studies. However, investigations of survival gains in broader HR+/HER2− mBC populations using epidemiological approaches are limited. Methods: This retrospective study used SEER registry data to assess breast cancer-specific survival (BCSS) in patients diagnosed with HR+/HER2− de novo mBC from 2010 to 2019. Kaplan–Meier and Cox proportional hazards models were used to compare BCSS in patients diagnosed before (2010‒2013 with follow-up to 2014) and after (2015‒2018 with follow-up to 2019) the 2015 guideline recommendations for CDK4/6i use. A comparison was made to patients with HR+/HER2-positive (HER2+) de novo mBC, for which no major guideline changes occurred during 2015–2018. Results: Data from 11,467 women with HR+/HER2− mBC and 3260 women with HR+/HER2+ mBC were included. After baseline characteristic adjustment, patients with HR+/HER2− mBC diagnosed post-2015 (n = 6163), had an approximately 10% reduction in risk of BC-specific death compared with patients diagnosed pre-2015 (n = 5304; HR = 0.895, p < 0.0001). Conversely, no significant change was observed in HR+/HER2+ BCSS post-2015 (n = 1798) versus pre-2015 (n = 1462). Similar results were found in patients aged ≥ 65 years. Conclusion: Using one of the largest US population-based longitudinal cancer databases, significant improvements in BCSS were noted in patients with HR+/HER2− mBC post-2015 versus pre-2015, potentially due to the introduction of CDK4/6i post-2015. No significant improvement in BCSS was observed in patients with HR+/HER2+ mBC post-2015 versus pre-2015, likely due to the availability of HER2-directed therapies in both time periods. [ABSTRACT FROM AUTHOR]

Background: Vitamin D is critical to bone health by regulating intestinal absorption of calcium, whereas proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, are known to increase bone resorption. We hypothesized that vitamin D and these cytokines at the time of breast cancer diagnosis were predictive for fragility fractures in women receiving aromatase inhibitors (AIs). Methods: In a prospective cohort of 1,709 breast cancer patients treated with AIs, we measured the levels of 25-hydroxyvitamin D (25OHD), IL-1β, IL-6, IL-12, and TNF-α from baseline blood samples. The associations of these biomarkers were analyzed with bone turnover markers (BALP and TRACP), bone regulatory markers (OPG and RANKL), bone mineral density (BMD) close to cancer diagnosis, and risk of fragility fractures during a median of 7.5 years of follow up. Results: Compared to patients with vitamin D deficiency, patients with sufficient levels had higher bone turnover, lower BMD, and higher fracture risk; the latter became non-significant after controlling for covariates including BMD and no longer existed when patients taking vitamin D supplement or bisphosphonates or with history of fracture or osteoporosis were excluded. There was a non-significant trend of higher levels of IL-1β and TNF-α associated with higher risk of fracture (highest vs. lowest tertile, IL-1β: adjusted HR=1.37, 95% CI=0.94-1.99; TNF-α: adjusted HR=1.38, 95% CI=0.96-1.98). Conclusions: Our results do not support proinflammatory cytokines or vitamin D levels as predictors for risk of fragility fractures in women receiving AIs for breast cancer. [ABSTRACT FROM AUTHOR]

Pressure ulcer (PU) is the representative skin injury and is a major limiting factor in the long-term use of the wearable robots. For the sake of the health of the wearable robot user and to improve the usability of the wearable robot, we developed a pressure ulcer breakout time estimation model (PUBTEM). The model estimates the possible breakout time of PU at the skin beneath the cuff of the wearable robot, hence, it can be used as a guide for the design, control, and operational strategy of wearable robot. To develop the model, PU breakout mechanisms were analyzed extensively in the biomechanical perspective. From the analysis, skin pressure, skin shear stress and compressive stress in muscle tissue were identified as major factors causing PU and their relationships with time were collected. However, the skin shear stress and compressive stress are either difficult or impossible to measure in the environment where the wearable robot is used. Hence, we converted those two factors into the pressure—a easily measureable quantity—by applying the FEM analysis of the human musculoskeletal model and the relationship with friction coefficient. Through this conversion process, the relationship of all three factors with PU breakout time could be modeled with respect to a single variable, the skin pressure. Finally, the most conservative relationship that has fastest PU occurrence time was established as the PUBTEM. The model was validated with the human subject experiments approved by the IRB. [ABSTRACT FROM AUTHOR]

Background: The upper mediastinum is the most common metastatic site of esophageal squamous cell carcinoma (ESCC), and complete dissection of this region is important for oncologic reasons. This study aimed to compare the oncologic outcomes and completeness of upper mediastinal dissection for ESCC patients undergoing the Ivor-Lewis (IL) or McKeown (MK) operations. Methods: Between 2013 and 2018, 680 patients (IL, 433; MK, 247) underwent upfront esophagectomy with two-field lymph node (LN) dissection for mid-to-lower ESCCs. Propensity score-matching (1:1 ratio) was performed to minimize the effects of confounding factors. Results: The mean age was 64.5 ± 8.8 years, and 635 (93.4%) of the patients were male. The median follow-up period was 71.66 months (interquartile range [IQR], 59.60–91.04 months). The IL group had a higher mean age, lower body mass index, higher proportion of advanced T and N, and higher adjuvant therapy rates, but these differences were well-balanced after propensity score-matching. The mean number of dissected LNs at the mediastinum and at the right recurrent laryngeal nerve (RLN) were similar between the two groups after matching, whereas the IL group exhibited a slightly greater number of dissected LNs at the left RLN. Among the matched patients, the IL and MK groups exhibited similar 5-year overall survival (OS: 75.1% vs 78.0%; p = 0.368). The multivariate model showed no differences in OS, disease-free survival, or recurrence-free survival for locoregional, upper mediastinum, or neck between the two groups. Conclusions: This study suggests that both the IL and MK operations are oncologically feasible for patients with mid-to-lower ESCC. [ABSTRACT FROM AUTHOR]