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The present research utilizes an inverse 3D CFD technique, coupled with the least squares approach and laboratory temperature readings, to predict the suitable turbulence flow model and unknown heat transfer rates within a cubic hot box. This enclosure features four cylindrical horizontal tubes arranged in a diamond configuration, functioning as heaters to generate heat within the space. Furthermore, the heat dissipation from each tube, flow field and temperature contours are also established. The energy equation for tubes and the governing equations for air are solved by coupling. The present estimates are obtained assuming a constant heat transfer rate. The range of the Rayleigh number is from 60,294 to 76,824. Testing various turbulence models revealed that the zero-equation turbulence model reduces the root mean square discrepancy between the simulated thermal behavior and laboratory outcomes compared to other methodologies. To verify the chosen flow model's accuracy, the Nusselt numbers and flow field distributions aress compared with existing correlations and interferometer photographs. The maximum errors between the estimates of heat loss and heat transfer rate and the corresponding values from previous studies are 44 and 28% for St = 0.036, 34 and 3% for St = 0.045, and 37 and 18% for St = 0.054. To assess the impact of tube surface and spacing on the flow field model, calculation results are compared with those from four square-arranged tubes, revealing a lack of existing studies on this specific investigation. [ABSTRACT FROM AUTHOR]

Background: The effects of physical activity on the development of different types of cancers have not been comprehensively studied. This nationwide, population-based cohort study investigated the effects of leisure-time physical activity (LTPA) on the development of different types of cancer in Taiwanese adults. A total of 67,890 adult participants (≥ 18 y old) from five rounds (2001, 2005, 2009, 2013, and 2017) of the Taiwan National Health Interview Survey were included. LTPA was measured as the metabolic equivalent of task (MET) expenditure per week and was classified as inactive (< 1 MET-h), low (1-7.49 MET-h), or high (≥ 7.5 MET-h). The LTPA and other covariates were collected through in-person interviews at baseline. New-onset cancer was ascertained from histopathological reports. The Fine-Gray sub-distribution method, with death as a competing risk, was used to determine the impact of LTPA on incident cancer risk. Results: During the 844,337 person-years of follow-up, 4,435 individuals developed cancer. Compared to inactive adults, individuals engaging in high levels of LTPA (≥ 7.5 MET-h/week) were significantly associated with a reduced risk of developing cancer (adjusted hazard ratio [aHR] = 0.93; 95% confidence interval [CI] = 0.87–0.99). However, those with low levels of LTPA (1-7.49 MET-h/week) did not exhibit a significant association with a reduced risk of developing cancer (aHR = 1.00; 95% CI = 0.92–1.10). When considering specific types of cancers, participants with high levels of LTPA (≥ 7.5 MET-h/week) had a significantly lower risk of developing bladder cancer (aHR = 0.68; 95% CI = 0.47–0.99), cervical cancer (aHR = 0.48; 95% CI = 0.24–0.95), and thyroid cancer (aHR = 0.64; 95% CI = 0.44–0.93). Conclusions: Our findings suggest that high LTPA (≥ 7.5 MET-h/week) is significantly associated with a low risk of incident bladder, cervical, and thyroid cancers. Key points: This prospective cohort study with a mean follow-up of 12.4 years found that high leisure-time physical activity (≥ 7.5 MET-h/week) was significantly associated with a lower risk of incident cancer, including bladder, cervical, and thyroid cancer. Healthcare professionals should encourage inactive adults to perform leisure-time physical activities to reduce cancer risk. [ABSTRACT FROM AUTHOR]

cFLIP, a master anti-apoptotic regulator, targets the FADD-induced DED complexes of procaspase-8 in death receptor and ripoptosome signaling pathways. Several tumor cells maintain relatively high levels of cFLIP in achieving their immortality. However, understanding the three-dimensional regulatory mechanism initiated or mediated by elevated levels of cFLIP has been limited by the absence of the atomic coordinates for cFLIP-induced DED complexes. Here we report the crystal plus cryo-EM structures to uncover an unconventional mechanism where cFLIP and procaspase-8 autonomously form a binary tandem DED complex, independent of FADD. This complex gains the ability to recruit FADD, thereby allosterically modulating cFLIP assembly and partially activating caspase-8 for RIPK1 cleavage. Our structure-guided mutagenesis experiments provide critical insights into these regulatory mechanisms, elucidating the resistance to apoptosis and necroptosis in achieving immortality. Finally, this research offers a unified model for the intricate bidirectional hierarchy-based processes using multiprotein helical assembly to govern cell fate decisions. FADD binds Casp-8 and then cFLIP to form the FADD-Casp8-cFLIP complex. The authors found that the DED complex could assemble in reverse order, where cFLIP oligomerizes to bind Casp-8. The resultant complex could bind FADD, generating the cFLIP-Casp-8-FADD complex by a different mechanism. [ABSTRACT FROM AUTHOR]

Recently, the correspondence between the air track scenario and quantum database search algorithm was revealed. The conservation laws of linear momentum and nonlinear kinetic energy in the former case, which involve sequential elastic collisions, have their analogs in the latter case. Obviously, probability normalization combined with the Born rule serves as an analog for kinetic energy conservation. Here we explore the linear conservation laws in a generic quantum database search. Regarding the non-uniform distribution of the marked state, the uneven state is initially prepared. In this way, the Grover diffusion operator results in a linear but nonphysical conservation law. On the other hand, in the CTC-assisted database search with the vast reduction of query complexity, the nonlinear instead of linear conservation laws are found. Finally, we conjecture that there are no conservation laws in the generalized Grover’s algorithm including the imaginary number i. [ABSTRACT FROM AUTHOR]

Objective: As the global use of extracorporeal membrane oxygenation (ECMO) treatment increases, survival rates have not correspondingly improved, emphasizing the need for refined patient selection to optimize resource allocation. Currently, prognostic markers at the molecular level are limited. Methods: Thirty-four cardiogenic shock (CS) patients were prospectively enrolled, and peripheral blood mononuclear cells (PBMCs) were collected at the initiation of ECMO (t0), two-hour post-installation (t2), and upon removal of ECMO (tr). The PBMCs were analyzed by comprehensive epigenomic assays. Using the Wilcoxon signed-rank test and least absolute shrinkage and selection operator (LASSO) regression, 485,577 DNA methylation features were analyzed and selected from the t0 and tr datasets. A random forest classifier was developed using the t0 dataset and evaluated on the t2 dataset. Two models based on DNA methylation features were constructed and assessed using receiver operating characteristic (ROC) curves and Kaplan–Meier survival analyses. Results: The ten-feature and four-feature models for predicting in-hospital mortality attained area under the curve (AUC) values of 0.78 and 0.72, respectively, with LASSO alpha values of 0.2 and 0.25. In contrast, clinical evaluation systems, including ICU scoring systems and the survival after venoarterial ECMO (SAVE) score, did not achieve statistical significance. Moreover, our models showed significant associations with in-hospital survival (p < 0.05, log-rank test). Conclusions: This study identifies DNA methylation features in PBMCs as potent prognostic markers for ECMO-treated CS patients. Demonstrating significant predictive accuracy for in-hospital mortality, these markers offer a substantial advancement in patient stratification and might improve treatment outcomes. [ABSTRACT FROM AUTHOR]

The climate characteristics of remote rainfall events in Taiwan from September to February over 41 years (1980–2020) are studied. These events are induced by the interaction between the northeasterly flow and the typhoon's outer circulation. Our findings reveal that rainfall in northeastern Taiwan becomes more prominent when tropical cyclones move to the remote rainfall‐prone area, located in the north Philippine area to the northern South China Sea, and when the background northeasterly wind speed exceeds 7 m s−1. Under these criteria, the confluence of the typhoon's outer circulation and the northeasterly flow creates a convergence area that enhances rainfall in northeastern Taiwan, increasing the occurrence of moderate to extreme rainfall (ER) events. This leads to an average enhancement in rainfall amount of 80–220 mm per day. Additionally, when typhoons are in the remote rainfall‐prone area, there is a greater than 20% chance for events with maximum rainfall over 200 mm day−1 to occur, particularly in the region of 20°–22°N, 116°−124°E, and north to Luzon Island. In this area, the occurrence rate can exceed more than a 45% chance. The highest risk of ER events occurs between 20°–22°N and 118°−120°E, with a probability of over 90%. Notably, the convergence area for the Taiwan cases does not necessarily coincide with the baroclinic forcing as that associated with remote rainfall events observed in Japan, Korea, and North America. Plain Language Summary: We studied a particular pattern of rainfall in Taiwan that occurs between September and February over a 41‐year period (1980–2020). Our research found that when tropical cyclones (TCs) are far from Taiwan and there is a strong northeasterly wind, it causes more rainfall in northeastern Taiwan. This can lead to moderate to extreme rainfall, with an increase in rainfall of 80–220 mm per day. When tropical storms are in a specific area north of Luzon Island, there is a higher chance of heavy rain, with some places receiving more than 200 mm per day. The highest probability of extreme rain events occurs when TCs are in a specific area between 20°–22°N and 118°−120°E, where the chance of extreme rain in Taiwan is over 90%. It happens because the TC circulation meets with the northeasterly flow and creates a convergence area. It's important to note that the way remote rainfall events happen in Taiwan may not be the same as in Japan, Korea, and North America. Key Points: Northeastern Taiwan experiences heavy rainfall as tropical cyclone (TC) move toward North South China Sea while northeasterly flow >7 m/sTyphoons' outer flow and the northeasterly convergence enhanced remote rainfall events to 80–220 mm/dayAbove 45% of events with max daily rainfall over 200 mm occur when TCs are in the 20°–22°N, 116°–124°E area and north to Luzon Island [ABSTRACT FROM AUTHOR]

A lightweight, high‐definition vector map (HDVM) enables fully autonomous vehicles. However, the generation of HDVM remains a challenging problem, especially in complex urban scenarios. Moreover, numerous factors in the urban environment can degrade the accuracy of HDVM, necessitating a reliable error quantification. To address these challenges, this paper presents an open‐source and generic HDVM generation pipeline that integrates the global navigation satellite system (GNSS), inertial navigation system (INS), light detection and ranging (LiDAR), and camera. The pipeline begins by extracting semantic information from raw images using the Swin Transformer. The absolute 3D information of semantic objects is then retrieved using depth from the 3D LiDAR, and pose estimation from GNSS/INS integrated navigation system. Vector information (VI), such as lane lines, is extracted from the semantic information to construct the HDVM. To assess the potential error of the HDVM, this paper systematically quantifies the impacts of two key error sources, segmentation and LiDAR‐camera extrinsic parameter error. An error propagation scheme is first formed to illustrate how these errors fundamentally influence the accuracy of the HDVM. The effectiveness of the proposed pipeline is demonstrated through our codeavailable at https://github.com/ebhrz/HDMap. The performance is verified using typical datasets, including indoor garages and complex urban scenarios. [ABSTRACT FROM AUTHOR]

Data on primary care antibiotic prescription practices for children in Singapore, which are essential for health care policy, are lacking. We aimed to address this gap and to benchmark prescription practices against international standards. A retrospective cohort database study on antibiotic prescriptions for children (aged < 18 years) who visited six public primary care clinics in Singapore between 2018 and 2021 was conducted. Data were categorised according to the World Health Organization's Access, Watch, Reserve (WHO AWaRe) classification. Quality indicators from the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) and the National Institute for Health and Care Excellence (NICE) guidelines were used as a measure of appropriateness of antibiotic prescribing at the individual and overall patient level. In 831,669 polyclinic visits by children between 2018 and 2021, there was a significant reduction in mean antibiotics prescribed per month during pandemic years (2020–2021) compared to pre-pandemic (2018–2019) (MD 458.3, 95% CI 365.9–550.7). Most prescriptions (95.8%) for acute conditions fell within the WHO AWaRe "Access" group. Antibiotic prescription significantly exceeded (55.2%) the relevant quality indicator for otitis media (0–20%). The proportion of children receiving appropriate antibiotics for acute respiratory infections (n = 4506, 51.3%) and otitis media (n = 174, 49.4%) was low compared to the quality indicator (80–100%). There is a need to develop local evidence-based primary care antibiotic guidelines, as well as to support the development of stewardship programmes. [ABSTRACT FROM AUTHOR]

In cystic lung diseases such as lymphangioleiomyomatosis (LAM), a CT-based cyst score that measures the percentage of the lung volume occupied by cysts is a common index of the cyst burden in the lungs. Although the current semi-automatic measurement of the cyst score is well established, it is susceptible to human operator variabilities. We recently developed a fully automatic method incorporating adaptive features in place of manual adjustments. In this clinical study, the automatic method is validated against the standard method in several aspects. These include the agreement between the cyst scores of the two methods, the agreement of each method with independent tests of pulmonary function, and the temporal consistency of the measurements in the consecutive visits of the same patients. We found that the automatic method agreed with the standard method as well as the agreement between two trained operators running the same standard method; both methods obtained the same level of correlation with laboratory pulmonary function tests; the automated method had better temporal consistency than the standard method (p < 0.0001). The study indicates that the automatic method could replace the standard method and provide better consistency in assessing the extent of cystic changes in the lungs of patients. [ABSTRACT FROM AUTHOR]

Risk stratification based on prediction models has become increasingly important in preventing and managing chronic diseases. However, due to cost- and time-limitations, not every population can have resources for collecting enough detailed individual-level information on a large number of people to develop risk prediction models. A more practical approach is to use prediction models developed from existing studies and calibrate them with relevant summary-level information of the target population. Many existing studies were conducted under the population-based case–control design. Gail et al. (J Natl Cancer Inst 81:1879–1886, 1989) proposed to combine the odds ratio estimates obtained from case–control data and the disease incidence rates from the target population to obtain the baseline hazard function, and thereby the pure risk for developing diseases. However, the approach requires the risk factor distribution of cases from the case–control studies be same as the target population, which, if violated, may yield biased risk estimation. In this article, we propose two novel weighted estimating equation approaches to calibrate the baseline risk by leveraging the summary information of (some) risk factors in addition to disease-free probabilities from the targeted population. We establish the consistency and asymptotic normality of the proposed estimators. Extensive simulation studies and an application to colorectal cancer studies demonstrate the proposed estimators perform well for bias reduction in finite samples. [ABSTRACT FROM AUTHOR]

Multipath is recognized as one of the major error sources for GNSS urban navigation. This study proposes a random forest (RF)-based multipath parameter estimator that uses random forest regression for parameter estimation, thereby mitigating multipath effect by removing the estimated reflected signal components. The proposed estimator is evaluated and compared with the multipath estimation delay-lock loop (MEDLL) for one-multipath and three-multipath cases, respectively. Simulation results demonstrate that the RF-based estimator is less affected by the front-end bandwidth of received signals, compared with MEDLL. The proposed RF-based estimator shows better performance than MEDLL for signals with front-end bandwidths of lower than 6 MHz. In 20 sets of tests on signals with a front-end bandwidth of 10 MHz in the three-multipath case, the RF-based estimator obtains smaller standard deviations than MEDLL. In experiments using real data with a front-end bandwidth of 2 MHz, the RF-based estimator reduces the 2D and 3D positioning errors by 8.5% and 8.7% over 180 epochs, respectively, against the conventional delayed-locked loop (DLL). [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is commonly associated with distressing psychological symptoms. Pathologic changes associated with AUD have been described in both the gut microbiome and brain, but the mechanisms underlying gut‐brain signaling in individuals with AUD are unknown. This study examined associations among the gut microbiome, brain morphometry, and clinical symptoms in treatment‐seeking individuals with AUD. Methods: We performed a secondary analysis of data collected during inpatient treatment for AUD in subjects who provided gut microbiome samples and had structural brain magnetic resonance imaging (MRI; n = 16). Shotgun metagenomics sequencing was performed, and the morphometry of brain regions of interest was calculated. Clinical symptom severity was quantified using validated instruments. Gut‐brain modules (GBMs) used to infer neuroactive signaling potential from the gut microbiome were generated in addition to microbiome features (e.g., alpha diversity and bacterial taxa abundance). Bivariate correlations were performed between MRI and clinical features, microbiome and clinical features, and MRI and microbiome features. Results: Amygdala volume was significantly associated with alpha diversity and the abundance of several bacteria including taxa classified to Blautia,Ruminococcus, Bacteroides, and Phocaeicola. There were moderate associations between amygdala volume and GBMs, including butyrate synthesis I, glutamate synthesis I, and GABA synthesis I & II, but these relationships were not significant after false discovery rate (FDR) correction. Other bacterial taxa with shared associations to MRI features and clinical symptoms included Escherichia coli and Prevotella copri. Conclusions: We identified gut microbiome features associated with MRI morphometry and AUD‐associated symptom severity. Given the small sample size and bivariate associations performed, these results require confirmation in larger samples and controls to provide meaningful clinical inferences. Nevertheless, these results will inform targeted future research on the role of the gut microbiome in gut‐brain communication and how signaling may be altered in patients with AUD. [ABSTRACT FROM AUTHOR]

In this study, the inverse 3D computational fluid dynamics method combined with the least squares method and excessive experimental temperature measurements is employed for the prediction of the unknown heat transfer rate and free convection heat transfer features and select an approximate flow model for the plate-finned tube heat exchanger. The results indicate that the heat transfer coefficient h ¯ f2 on the second fin estimated by the ZEM is closer to the existing inverse result than other flow models. In addition, its root-mean-square error is also small enough in all used flow models. The obtained values of h ¯ f2 and RMSE agree with those obtained from the isothermal assumption. Thus, this inverse technique has good accuracy and reliability. This inverse technique also needs less experimental temperature data than the isothermal assumption. The temperature and heat dissipation for each pipe and fin can also be estimated. The influence of the flow model and the vertical distance between two vertical pipes on the obtained estimates is also investigated. The mean dissipative heat transfer rates of per pipe for the vertical distances between centers of two pipes (Stv) of 0.054 m, 0.045 m, and 0.036 m are 10.72 W, 12.12 W, and 10.28 W, respectively. The heat losses in this study for Stv = 0.054 m, 0.045 m, and 0.036 m are 2.7%, 3.0%, and 4.5%, respectively. [ABSTRACT FROM AUTHOR]

During orthodontic treatments, orthodontists want to simultaneously measure different kinds of intraoral pressure of a patient to determine a suitable orthodontic treatment plan for the patient. To achieve this, an intraoral pressure sensors-array with a specific arrangement in the oral cavity is needed. Hence, in this paper, we design a smart magnetic thin-sheet structure based wireless sensors-array arrangement for intraoral-pressure sensing for orthodontics to determine the above suitable treatment plan. In general, the sensors-array consists of multiple sensing modules. Each module consists of two parts: the first part is a transmitting/receiving electromagnet which is connected to a reference electromagnet in a balanced inductance bridge configuration while the second part is a smart magnetic thin-sheet structure based high-permeable sensing diaphragm. A voltage input is applied to the reference electromagnet and transmitting/receiving electromagnet, while the voltage output is measured from the transmitting/receiving electromagnet, respectively (the transmitting/receiving electromagnet can transmit the magnetic flux as well as receive or sense the change of magnetic flux). When the sensing diaphragm (which is placed in proximity to the transmitting/receiving electromagnet) undergoes a displacement, the gap between the sensing diaphragm and transmitting/receiving electromagnet changes. This subsequently changes surrounding magnetic flux, and consequently results in a change in magnetic reluctance between the sensing diaphragm and transmitting/receiving electromagnet. Thus, the voltage output of the transmitting/receiving electromagnet is changed accordingly. Based on this operation principle, furthermore, we use multiple transmitting/receiving electromagnets to form a compact (specifically arranged) sensors-array. The results show that specifically arranged sensors-array can provide measurement results in multiple points in the oral cavity to the orthodontists, as a simplified decision-making reference for the orthodontists to determine the clinical treatment plan for patients. [ABSTRACT FROM AUTHOR]

Molecular photoswitches are widely used in material sciences, physics, chemistry, and biology. As needs grow more complex, materials have to react more than one‐dimensionally. The use of multiple photoswitches at once opens manifold opportunities for further improved and more complicated systems. However, this requires independent addressability, i.e., orthogonality, and reversible processes. Herein, the first study on ultrafast excited state dynamics of two orthogonal photoswitches, a push‐pull azobenzene and a donor‐acceptor Stenhouse adduct is reported. In order to gain detailed insight in their interactions and mutual influences on their photoswitching behavior, they are addressed individually and simultaneously via transient absorption spectroscopy supported by quantum chemical calculations. They show reversible photoswitchability and in addition, can be used in 4D printing to provide easy access to a plethora of functional devices. Furthermore, environmental influences on the excited state dynamics are examined using different solvents and thin films. Both compounds photoisomerize independently when addressed individually or simultaneously and only little impacts on the excited state dynamics are found. Especially the vibrational relaxation is affected by different surroundings changing the energy dissipation while hardly affecting the electronic states involved. The orthogonal and simultaneous addressability is thereby crucial for their usage in 4D printed microactuators. [ABSTRACT FROM AUTHOR]

In response to the growing demand for high-resolution rainfall data to support disaster prevention in Taiwan, this study presents an innovative approach for downscaling precipitation data. We employed a hierarchical architecture of Multi-Scale Residual Networks (MSRN) to downscale rainfall from a coarse 0.25-degree resolution to a fine 0.0125-degree resolution, representing a substantial challenge due to a resolution increase of over 20 times. Our results demonstrate that the hierarchical MSRN outperforms both the one-step MSRN and linear interpolation methods when reconstructing high-resolution daily rainfall. It surpasses the linear interpolation method by 15.1 and 9.1% in terms of mean absolute error and root mean square error, respectively. Furthermore, the hierarchical MSRN excels in accurately reproducing high-resolution rainfall for various rainfall thresholds, displaying minimal biases. The threat score (TS) highlights the hierarchical MSRN's capability to replicate extreme rainfall events, achieving TS scores exceeding 0.54 and 0.46 at rainfall thresholds of 350 and 500 mm per day, outperforming alternative methods. This method is also applied to an operational global model, the ECMWF's daily rainfall forecasts over Taiwan. The evaluation results indicate that our approach is effective at improving rainfall forecasts for thresholds greater than 100 mm per day, with more significant improvement for the 1- to 3-day lead forecast. This approach also offers a realistic visual representation of fine-grained rainfall distribution, showing promise for making significant contributions to disaster preparedness and weather forecasting in Taiwan. [ABSTRACT FROM AUTHOR]

In this presentation, we explored the molecular mechanisms of N. nucifera leaf water extracts (NLWEs) and polyphenol extract (NLPE) on scopolamine‐induced cell apoptosis and cognition defects. The administration of NLWE and NLPE did not alter the body weight and serum biomarker rs and significantly ameliorated scopolamine‐induced cognition impairment according to Y‐maze test analysis. In mice, treatment with scopolamine disrupted normal histoarchitecture in the hippocampus, whereas the administration of NLWE and NLPE reversed the phenomenon. Western blot analysis revealed that scopolamine mitigated the expression of doublecortin (DCX), nestin, and NeuN, and cotreatment with NLWE or NLPE significantly recovered the expression of these proteins. NLWE and NLPE upregulated DCX and NeuN expression in the hippocampus region, as evidenced by immunohistochemical staining analysis of scopolamine‐treated mice. NLWE and NLPE obviously elevated brain‐derived neurotrophic factor (BDNF) and enhanced its downstream proteins activity. NLWE and NLPE attenuated scopolamine‐induced apoptosis by reducing Bax and increased Bcl‐2 expression. In addition, scopolamine also triggered apoptosis in human neuroblastoma SH‐SY5Y cells whereas co‐treatment with NLWE or quercetin‐3‐glucuronide (Q3G) reversed the phenomenon. NLWE or Q3G enhanced Bcl‐2 and reduced Bax expression in the presence of scopolamine in SH‐SY5Y cells. NLWE or Q3G recovered the inhibitory effects of scopolamine on neurogenesis and BDNF signals in SH‐SY5Y cells. Overall, our results revealed that N. nucifera leaf extracts and Q3G promoted adult hippocampus neurogenesis and prevented apoptosis to mitigate scopolamine‐induced cognition dysfunction through the regulation of BDNF signaling pathway. [ABSTRACT FROM AUTHOR]

Missing data in covariates can result in biased estimates and loss of power to detect associations. We consider Cox regression in which some covariates are subject to missing. The inverse probability weighted approach is often applied to regression analysis with missing covariates. Inverse probability weighted estimators typically are less efficient than likelihood‐based estimators, but in general are more robust against model misspecification. In this article, we propose a robust best linear weighted estimator for Cox regression with missing covariates. Our proposed estimator is the projection of the simple inverse probability weighted estimator onto the orthogonal complement of the score space based on a working regression model of the observed data. The efficiency gain is from the use of the association between the survival outcome variable and the available covariates, which is the working regression model. The asymptotic distribution is derived, and the finite sample performance of the proposed estimator is examined via extensive simulation studies. The methods are applied to a colorectal cancer study to assess the association of the microsatellite instability status with colorectal cancer‐specific mortality. [ABSTRACT FROM AUTHOR]

Multipath (MP) reception has been among the main issues for accurate and reliable positioning in urban environments. It has been shown to introduce positioning errors of up to tens of meters for conventional two-step (2SP) receivers. The direct position estimation (DPE) has been introduced as a more robust positioning algorithm compared to the conventional two-step (2SP) receivers in terms of MP mitigation. However, its high computational load prevents DPE from real-time positioning for commercial receivers. Thus, we present a novel grid-based maximum likelihood estimation (MLE) algorithm based on DPE by making use of pseudorange measurements to obtain the correlogram on a predefined searching space. Unlike DPE, which performs correlations at the intermediate frequency (IF) level, correlations are done by directly comparing the code phase of each candidate position, velocity, and timing with the incoming pseudorange. This way, the proposed method retains MP mitigation properties from DPE through the use of MLE from DPE and allows for a significantly reduced computational load compared to DPE. The proposed method was tested with both open-sourced datasets collected in urban environments as well as IF simulation data, and its performance is evaluated against a 2SP receiver. Results show that the proposed method manages to acquire the MP mitigation capability of DPE and outperforms 2SP by up to around 23% in the tested urban datasets and 91% in the simulation data, at a much-reduced computational time. The resilience of our proposed method against MP and NLOS could even potentially offer applications in geodetic networks, where robust estimators are traditionally employed to counteract outliers. [ABSTRACT FROM AUTHOR]

Background and Aims: The impact of antibody responses following direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV)-infected recipients before and after liver transplantation (LT) is still undetermined. Methods: In this observational cohort study, we aimed to explore the association between changes in anti-HCV antibody titers following pre-LT DAA therapy and allograft injury, including biliary complications (BCs) and acute cellular rejection (ACR). Results: A total of 153 cases were enrolled from January 2015 to February 2021. Serum anti-HCV antibody titers were assessed before and after (day 30) LT. Among all recipients, 31/153 (20.3%) had pre-LT DAA therapy (the DAA group) and 122/153 (79.7%) did not undergo pre-LT DAA therapy (the DAA-naïve group). A higher incidence of post-LT BCs was observed in the DAA group (p = 0.028). Compared with the DAA-naïve group, the DAA group had a significantly higher mean level of anti-HCV titer upregulation (p = 0.0024); furthermore, among the recipients with BCs (n = 28) and ACR (n = 41), those in the DAA group exhibited significantly higher mean levels of anti-HCV antibody titer upregulation (p < 0.005). Conclusions: In conclusion, we speculate that the upregulation of anti-HCV antibody titers, which might have been induced via the restoration of HCV-specific immune responses through pre-LT DAA therapy, was associated with post-LT allograft injury. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis (TB) remains endemic in Singapore. Singapore's clinical practice guidelines for the management of tuberculosis were first published in 2016. Since then, there have been major new advances in the clinical management of TB, ranging from diagnostics to new drugs and treatment regimens. The National TB Programme convened a multidisciplinary panel to update guidelines for the clinical management of drug-susceptible TB infection and disease in Singapore, contextualising current evidence for local practice. Method: Following the ADAPTE framework, the panel systematically reviewed, scored and synthesised English-language national and international TB clinical guidelines published from 2016, adapting recommendations for a prioritised list of clinical decisions. For questions related to more recent advances, an additional primary literature review was conducted via a targeted search approach. A 2-round modified Delphi process was implemented to achieve consensus for each recommendation, with a final round of edits after consultation with external stakeholders. Results: Recommendations for 25 clinical questions spanning screening, diagnosis, selection of drug regimen, monitoring and follow-up of TB infection and disease were formulated. The availability of results from recent clinical trials led to the inclusion of shorter treatment regimens for TB infection and disease, as well as consensus positions on the role of newer technologies, such as computer-aided detectionartificial intelligence products for radiological screening of TB disease, next-generation sequencing for drugsusceptibility testing, and video observation of treatment. Conclusion: The panel updated recommendations on the management of drug-susceptible TB infection and disease in Singapore. [ABSTRACT FROM AUTHOR]

Purpose: This study explores the creation of online brand relationships from the personal, social and brand perspectives of social media and its influence on the community citizenship behavior to establish an integrative model. With social identity theory (SIT) and the theory of socially shared cognition (TSSC) as the theoretical basis for model integration, this study identifies the key factors that maintain the relationship between online community members and brands and prompt brand members to establish a close emotional connection with the brand and generate community citizenship behavior for the brand. Design/methodology/approach: This study examines community members who own products from luxury fashion brands (e.g. Louis Vuitton, Chanel and Hermès) and have followed the official Instagram account of the luxury fashion brand for at least 1 year, with a total of 582 valid samples. Structural equation modeling (SEM) is used to test the model. Findings: All except for one of the hypotheses are supported, and the theoretical model exhibits acceptable goodness-of-fit. The strongest effect is that of brand community identification on affective brand commitment, followed by that of online co-creation on community citizenship behavior and that of brand commitment on community citizenship behavior. Originality/value: SIT was used as the basis and extended to the TSSC to integrate the theoretical perspectives. This study identifies the online brand relationship between service providers and consumers, explores possible causes and consequences from multiple perspectives and proposes conclusions and practical management implications as references for marketing personnel. [ABSTRACT FROM AUTHOR]

Light-triggered molecular switches are extensively researched for their applications in medicine, chemistry and material science and, if combined, particularly for their use in multifunctional smart materials, for which orthogonally, i.e. individually, addressable photoswitches are needed. In such a multifunctional mixture, the switching properties, efficiencies and the overall performance may be impaired by undesired mutual dependences of the photoswitches on each other. Within this study, we compare the performance of the pure photoswitches, namely an azobenzene derivative (Azo) and a donor–acceptor Stenhouse adduct (DASA), with the switching properties of their mixture using time-resolved temperature-dependent UV/VIS absorption spectroscopy, time-resolved IR absorption spectroscopy at room temperature and quantum mechanical calculations to determine effective cross sections, switching kinetics as well as activation energies of thermally induced steps. We find slightly improved effective cross sections, percentages of switched molecules and no increased activation barriers of the equimolar mixture compared to the single compounds. Thus, the studied mixture Azo + DASA is very promising for future applications in multifunctional smart materials. [ABSTRACT FROM AUTHOR]

Live streaming has become the new trend in social media. Using trust transfer theory as the basis for model building, this study examined how the source credibility of live streamers affects their followers' trust in the live stream and in the product, and, by extension, the relationship context that influences viewers' behavioral intentions. This study recruited customers who had viewed a Facebook live stream and purchased the advertised product within the past 6 months; 567 valid questionnaire surveys were collected and tested using Structural Equation Modeling (SEM). The results indicated that two types of trust play a mediating role in online live stream environments. The source credibility of live streamers is an antecedent for establishing mutual trust. In the trust transfer mechanism, trust in product is the key to developing trust in a live streamer. Trust in live streamers is more influenced by trust in product (coefficient = 0.645) than by the live streamer's source credibility (coefficient = 0.33). To trigger the purchase intention of a live streaming audience, live streamers must first induce a continuous watching intention in the audience to increase the likelihood of the audience purchasing products sold during live streams. The results of the multi-group analysis were consistent with the model results, demonstrating their generalizability. Specifically, in the social media live stream environment, high levels of customer engagement played a major moderating role in both establishing viewers' continuous watching intention and purchase intention. Finally, this study provides live streaming marketers with concrete managerial and practical suggestions for implementing effective live streaming strategies. [ABSTRACT FROM AUTHOR]

Nasal obstruction exerts considerable physiological effects on the respiratory system and craniofacial morphology during the developmental stage. This study used MMP-3-LUC transgenic rats for in vivo tracking of long-term expression in the rat nasal region after unilateral nasal obstruction. Skeletal changes of the craniofacial, nasal, and sinus regions were measured through micro-computed tomography examination and analysis with 3D image processing and calculation. Matrix metalloproteinase-3 and olfactory marker protein expression were also investigated through immunohistochemistry (IHC). Unilateral nasal obstruction significantly reduced the MMP-3 signal in the nasal region of MMP-3-LUC transgenic rats, which was mainly expressed in the respiratory epithelium. Long-term obstruction also caused morphological changes of the craniofacial hard tissue, such as nasal septal deviation, longer inter-jaw distance, and increased maxillary molar dental height. It also caused compensatory growth in olfactory nerve bundles and the olfactory epithelium, as confirmed by IHC. In our study, long-term unilateral nasal obstruction caused nasal septal deviation toward the unobstructed side, hyper divergent facial development including longer molar dental height, and reduced MMP-3 production. However, further investigation is necessary to explore the mechanism in depth. [ABSTRACT FROM AUTHOR]

Background Transcriptome-wide association studies have been successful in identifying candidate susceptibility genes for colorectal cancer (CRC). To strengthen susceptibility gene discovery, we conducted a large transcriptome-wide association study and an alternative splicing transcriptome-wide association study in CRC using improved genetic prediction models and performed in-depth functional investigations. Methods We analyzed RNA-sequencing data from normal colon tissues and genotype data from 423 European descendants to build genetic prediction models of gene expression and alternative splicing and evaluated model performance using independent RNA-sequencing data from normal colon tissues of the Genotype-Tissue Expression Project. We applied the verified models to genome-wide association studies (GWAS) summary statistics among 58 131 CRC cases and 67 347 controls of European ancestry to evaluate associations of genetically predicted gene expression and alternative splicing with CRC risk. We performed in vitro functional assays for 3 selected genes in multiple CRC cell lines. Results We identified 57 putative CRC susceptibility genes, which included the 48 genes from transcriptome-wide association studies and 15 genes from splicing transcriptome-wide association studies, at a Bonferroni-corrected P  value less than  .05. Of these, 16 genes were not previously implicated in CRC susceptibility, including a gene PDE7B (6q23.3) at locus previously not reported by CRC GWAS. Gene knockdown experiments confirmed the oncogenic roles for 2 unreported genes, TRPS1 and METRNL , and a recently reported gene, C14orf166. Conclusion This study discovered new putative susceptibility genes of CRC and provided novel insights into the biological mechanisms underlying CRC development. [ABSTRACT FROM AUTHOR]

Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN), is located on chromosome 4q22.1. This multifunctional secreted acidic glycoprotein is expressed intracellularly and extracellularly in various tissues, where it interacts with regulatory proteins and pro-inflammatory immune chemokines, contributing to the pathogenesis of multiple diseases. Nevertheless, the intricate genetic connections between SPP1 and ovarian aging remain largely unexplored. This study aims to bridge this knowledge gap by delving into ovarian aging and its associations with SPP1 using multi-omics data analysis. Our findings indicate that SPP1 is a potential gene related to ovarian aging. To comprehend the role of SPP1, we conducted spatial transcriptomic analyses on young and aged female mouse ovaries, revealing a significant decline in SPP1 expression in the aging group compared to the young group. Similarly, a significantly low level of SPP1 was found in the 73-year-old sample. Additionally, in-depth single-cell RNA-sequencing analysis identified associations between SPP1 and ITGAV, ITGB1, CD44, MMP3, and FN1. Notably, co-expression analysis highlighted a strong correlation between SPP1 and ITGB1. In summary, this study pioneers the identification of SPP1 as a gene implicated in ovarian aging. Further research into the role of SPP1 has the potential to advance precision medicine and improve treatment strategies for ovarian aging-related conditions. [ABSTRACT FROM AUTHOR]

Global navigation satellite systems (GNSSs) applied to intelligent transport systems in urban areas suffer from multipath and non-line-of-sight (NLOS) effects due to the signal reflections from high-rise buildings, which seriously degrade the accuracy and reliability of vehicles in real-time applications. Accordingly, the integration between GNSS and inertial navigation systems (INSs) could be utilized to improve positioning performance. However, the fixed GNSS solution uncertainty of the conventional integration method cannot determine the fluctuating GNSS reliability in fast-changing urban environments. This weakness becomes solvable using a deep learning model for sensing the ambient environment intelligently, and it can be further mitigated using factor graph optimization (FGO), which is capable of generating robust solutions based on historical data. This paper mainly develops the adaptive GNSS/INS loosely coupled system on FGO, along with the fixed-gain Kalman filter (KF) and adaptive KF (AKF) being taken as comparisons. The adaptation is aided by a convolutional neural network (CNN), and the feasibility is verified using data from different grades of receivers. Compared with the integration using fixed-gain KF, the proposed adaptive FGO (AFGO) maintains the 100% positioning availability and reduces the overall 2D positioning error by up to 70% in the aspects of both root mean square error (RMSE) and standard deviation (STD). [ABSTRACT FROM AUTHOR]

Organic–inorganic hybrid perovskites have garnered significant attention in optoelectronics owing to their outstanding tunable optical characteristics. Controlled growth of perovskite nanocrystals from solutions is key for controlling the emission intensity and photoluminescence lifetime of perovskites. In particular, most studies have focused on controlling the crystallization of perovskite through chemical treatment using chelating ligands or physical treatment via antisolvent diffusion, and there exists a trade‐off between the photoluminescence intensity and lifetime of perovskites. Herein, a selective solvent vapor‐assisted crystallization with the aid of a functional polymer, which nanoscale perovskite crystals are grown andante from precursor solution, is presented for tuning the crystallization and optical properties of a common halide perovskite, methylammonium lead bromide (MAPbBr3). The proposed method here produces perovskite nanocrystals in the range of 200–300 nm. The spin‐coated thin film formed from the perovskite solution exhibits strong green photoluminescence with a long lifetime. The effects of the functional group and polymer dosage on the crystallization of MAPbBr3 are systematically investigated, and the crystallization mechanism is explained based on a modified LaMer model. This study provides an advanced solution process for precisely controlling perovskite crystallization to enhance their optical properties for next‐generation optoelectronic devices. [ABSTRACT FROM AUTHOR]

Advances in soft robotics strongly rely on the development and manufacturing of new responsive soft materials. In particular, light‐based 3D printing techniques, and especially, digital light processing (DLP), offer a versatile platform for the fast manufacturing of complex 3D/4D structures with a high spatial resolution. In this work, DLP all‐printed bilayered structures exhibiting reversible and multi‐responsive behavior are presented for the first time. For this purpose, liquid crystal elastomers (LCEs) are used as active layers and combined with a printable non‐responsive elastomer acting as a passive layer. Furthermore, selective light response is incorporated by embedding various organic dyes absorbing light at different regimes in the active layers. An in‐depth characterization of the single materials and printed bilayers demonstrates a reversible and selective response. Last, the versatility of the approach is shown by DLP printing a bilayered complex 3D structure consisting of four different materials (a passive and three different LCE active materials), which exhibit different actuation patterns when irradiated with different wavelengths of light. [ABSTRACT FROM AUTHOR]

Current noninvasive estimation of right atrial pressure (RAP) by inferior vena cava (IVC) measurement during echocardiography may have significant inter-rater variability due to different levels of observers' experience. Therefore, there is a need to develop new approaches to decrease the variability of IVC analysis and RAP estimation. This study aims to develop a fully automated artificial intelligence (AI)-based system for automated IVC analysis and RAP estimation. We presented a multi-stage AI system to identify the IVC view, select good quality images, delineate the IVC region and quantify its thickness, enabling temporal tracking of its diameter and collapsibility changes. The automated system was trained and tested on expert manual IVC and RAP reference measurements obtained from 255 patients during routine clinical workflow. The performance was evaluated using Pearson correlation and Bland-Altman analysis for IVC values, as well as macro accuracy and chi-square test for RAP values. Our results show an excellent agreement (r=0.96) between automatically computed versus manually measured IVC values, and Bland-Altman analysis showed a small bias of - 0.33 mm. Further, there is an excellent agreement ( (p < 0.01 ) between automatically estimated versus manually derived RAP values with a macro accuracy of 0.85. The proposed AI-based system accurately quantified IVC diameter, collapsibility index, both are used for RAP estimation. This automated system could serve as a paradigm to perform IVC analysis in routine echocardiography and support various cardiac diagnostic applications. [ABSTRACT FROM AUTHOR]

Background: Non-surgical mini-implant assisted rapid palatal expansion, or midfacial skeletal expansion, is a paradigm-shifting concept that in recent years has expanded the envelope of orthopedic movement in the transverse direction for adult patients. Although adding mini-screws to a rapid palatal expander is not complicated, accurate and successful expansion strongly depends on the device's position and its relation to the resisting structures of the maxillofacial complex. Case presentation: This article presents a digital workflow to locate the optimal position of the Midfacial Skeletal Expander (MSE) device in a CBCT-combined intraoral scan file and describes how to transfer the MSE position intra-orally with properly sized bands during the device fabrication. The complete digital workflow of MSE fabrication and its application for a Class III orthognathic surgical case is presented in detail. Conclusions: This report describes a completely digital process that can accurately position the MSE device according to the orientation and morphology of maxillary basal bone, which is crucial in adult cases demand maxillary expansion. [ABSTRACT FROM AUTHOR]

Induction of DNA damage response (DDR) to ensure accurate duplication of genetic information is crucial for maintaining genome integrity during DNA replication. Cellular senescence is a DDR mechanism that prevents the proliferation of cells with damaged DNA to avoid mitotic anomalies and inheritance of the damage over cell generations. Human WWOX gene resides within a common fragile site FRA16D that is preferentially prone to form breaks on metaphase chromosome upon replication stress. We report here that primary Wwox knockout (Wwox−/−) mouse embryonic fibroblasts (MEFs) and WWOX-knockdown human dermal fibroblasts failed to undergo replication-induced cellular senescence after multiple passages in vitro. Strikingly, by greater than 20 passages, accelerated cell cycle progression and increased apoptosis occurred in these late-passage Wwox−/− MEFs. These cells exhibited γH2AX upregulation and microsatellite instability, indicating massive accumulation of nuclear DNA lesions. Ultraviolet radiation-induced premature senescence was also blocked by WWOX knockdown in human HEK293T cells. Mechanistically, overproduction of cytosolic reactive oxygen species caused p16Ink4a promoter hypermethylation, aberrant p53/p21Cip1/Waf1 signaling axis and accelerated p27Kip1 protein degradation, thereby leading to the failure of senescence induction in Wwox-deficient cells after serial passage in culture. We determined that significantly reduced protein stability or loss-of-function A135P/V213G mutations in the DNA-binding domain of p53 caused defective induction of p21Cip1/Waf1 in late-passage Wwox−/− MEFs. Treatment of N-acetyl-l-cysteine prevented downregulation of cyclin-dependent kinase inhibitors and induced senescence in Wwox−/− MEFs. Our findings support an important role for fragile WWOX gene in inducing cellular senescence for maintaining genome integrity during DDR through alleviating oxidative stress. [ABSTRACT FROM AUTHOR]

Candidiasis is one of the most important fungal diseases and generally refers to diseases of the skin or mucosal tissues caused by Candida species. Candida glabrata is an opportunistic human fungal pathogen. Infection with C. glabrata has significantly increased due to innate antifungal drug tolerance and the ability to adhere to mucocutaneous surfaces. Spt-Ada-Gcn5 acetyltransferase complex contains two different post-translational modifications, histone acetylation (HAT) module and deubiquitination (DUB) module, which are decisive in gene regulation and highly conserved in eukaryotes. Previous research in our laboratory found that the HAT module ADA2 could regulate C. glabrata oxidative stress tolerance, drug tolerance, cell wall integrity, and virulence. However, the roles of the DUB module that is comprised of UBP8, SGF11, SGF73 , and SUS1 genes in those phenotypes are not yet understood. In this study, we found that DUB module genes UBP8, SGF11 , and SUS1 , but not SGF73 positively regulate histone H2B DUB. Furthermore, ubp8, sgf11 , and sus1 mutants exhibited decreased biofilm formation and sensitivity to cell wall-perturbing agent sodium dodecyl sulfate and antifungal drug amphotericin B. In addition, the sgf73 mutant showed increased biofilm formation but was susceptible to oxidative stresses, antifungal drugs, and cell wall perturbing agents. The ubp8, sgf11 , and sus1 mutants showed marginal hypovirulence, whereas the sgf73 mutant exhibited virulence similar to the wild type in a murine systemic infection model. In conclusion, the C. glabrata DUB module plays distinct roles in H2B ubiquitination, oxidative stress response, biofilm formation, cell wall integrity, and drug tolerance, but exhibits minor roles in virulence. [ABSTRACT FROM AUTHOR]

Background: Genetic testing can identify cancer risk early, enabling prevention and early detection. We describe use of risk management interventions following genetic testing in the Cancer Health Assessment Reaching Many (CHARM) study. CHARM assessed risk and provided genetic testing to low income, low literacy, and other underserved populations that historically face barriers to accessing cancer genetic services. Methods: CHARM was implemented in Kaiser Permanente Northwest (KPNW) and Denver Health (DH) between 2018 and 2020. We identified post‐testing screening (mammography, breast MRI, colonoscopy) and surgical (mastectomy, oophorectomy) procedures using electronic health records. We examined utilization in participants who did and did not receive actionable risk management recommendations from study genetic counselors following national guidelines. Results: CHARM participants were followed for an average of 15.4 months (range: 0.4–27.8 months) after results disclosure. Less than 2% (11/680) received actionable risk management recommendations (i.e., could be completed in the initial years following testing) based on their test result. Among those who received actionable recommendations, risk management utilization was moderate (54.5%, 6/11 completed any procedure) and varied by procedure (mammogram: 0/3; MRI: 2/4; colonoscopy: 4/5; mastectomy: 1/5; oophorectomy: 0/3). Cancer screening and surgery procedures were rare in participants without actionable recommendations. Conclusion: Though the number of participants who received actionable risk management recommendations was small, our results suggest that implementing CHARM's risk assessment and testing model increased access to evidence‐based genetic services and provided opportunities for patients to engage in recommended preventive care, without encouraging risk management overuse. [ABSTRACT FROM AUTHOR]

Somatic mutations in cancer patients are inherently sparse and potentially high dimensional. Cancer patients may share the same set of deregulated biological processes perturbed by different sets of somatically mutated genes. Therefore, when assessing the associations between somatic mutations and clinical outcomes, gene‐by‐gene analysis is often under‐powered because it does not capture the complex disease mechanisms shared across cancer patients. Rather than testing genes one by one, an intuitive approach is to aggregate somatic mutation data of multiple genes to assess their joint association with clinical outcomes. The challenge is how to aggregate such information. Building on the optimal transport method, we propose a principled approach to estimate the similarity of somatic mutation profiles of multiple genes between tumor samples, while accounting for gene–gene similarities defined by gene annotations or empirical mutational patterns. Using such similarities, we can assess the associations between somatic mutations and clinical outcomes by kernel regression. We have applied our method to analyze somatic mutation data of 17 cancer types and identified at least five cancer types, where somatic mutations are associated with overall survival, progression‐free interval, or cytolytic activity. [ABSTRACT FROM AUTHOR]

The global public health threat of antimicrobial resistance (AMR) has been accelerated by many interrelated factors spanning across One Health—human health, animal health, and the environment. Singapore launched its own National Strategic Action Plan (NSAP) on AMR in November 2017 with the aim of tackling the growing threat of AMR in Singapore through coordinated approaches. However, little is known about the policy process and development of the NSAP in Singapore. In this study, we analysed these aspects using an AMR governance framework. In-depth interviews were conducted with 20 participants across the One Health spectrum. The interviews were transcribed verbatim and analysed thematically. Areas that were well executed included (1) good coordination across various agencies, (2) a dedicated office to coordinate the work on the NSAP, and (3) a high level of governmental support. Areas that were lacking included (1) a lack of participation from certain sectors, (2) insufficient awareness around the AMR issue, (3) constraints in information sharing, and (4) a lack of ideal indicators to track the progress in addressing AMR. Improvements in these areas will provide a more holistic One Health engagement in support of the effective planning and implementation of the NSAP. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a global public health threat that affects humans, animals, and the environment across the One Health spectrum. Singapore launched its own National Strategic Action Plan (NSAP) on AMR in 2017 with the aim of tackling the growing threat of AMR in Singapore through coordinated approaches. However, little is known about the implementation of the NSAP. In this study, we analysed the implementation of the NSAP with guidance from an AMR governance framework. We conducted in-depth interviews with 20 participants across the One Health spectrum. The interviews were transcribed verbatim and analysed thematically. Overall, the implementation of activities against AMR was more advanced with respect to human health compared to other sectors such as (1) AMR and antimicrobial use (AMU) surveillance systems in hospitals; (2) the hospital antimicrobial stewardship (AMS) service and legislation to optimise AMU; (3) the national children and adults vaccination programme for IPC; (4) multiple avenues for education and awareness for both professionals and public; and (5) extensive research and collaboration networks with many sources of funding. Areas that were lacking presented problems including (1) an incomplete surveillance system for AMR and AMU across all sectors; (2) the need for better AMS and legislation in some sectors; (3) insufficient innovation in education for sustained behavioural modification; and (4) the need for more open research collaborations and the translation of research into policy outcomes. Improvements in these areas will enhance the overall implementation of the NSAP through a more holistic One Health approach. [ABSTRACT FROM AUTHOR]

Brain wiring redundancy counteracts aging‐related cognitive decline by reserving additional communication channels as a neuroprotective mechanism. Such a mechanism plays a potentially important role in maintaining cognitive function during the early stages of neurodegenerative disorders such as Alzheimer's disease (AD). AD is characterized by severe cognitive decline and involves a long prodromal stage of mild cognitive impairment (MCI). Since MCI subjects are at high risk of converting to AD, identifying MCI individuals is essential for early intervention. To delineate the redundancy profile during AD progression and enable better MCI diagnosis, we define a metric that reflects redundant disjoint connections between brain regions and extract redundancy features in three high‐order brain networks—medial frontal, frontoparietal, and default mode networks—based on dynamic functional connectivity (dFC) captured by resting‐state functional magnetic resonance imaging (rs‐fMRI). We show that redundancy increases significantly from normal control (NC) to MCI individuals and decreases slightly from MCI to AD individuals. We further demonstrate that statistical features of redundancy are highly discriminative and yield state‐of‐the‐art accuracy of up to 96.8 ± 1.0% in support vector machine (SVM) classification between NC and MCI individuals. This study provides evidence supporting the notion that redundancy serves as a crucial neuroprotective mechanism in MCI. [ABSTRACT FROM AUTHOR]

Purpose: Reliable and objective measures of abdominal fat distribution across imaging modalities are essential for various clinical and research scenarios, such as assessing cardiometabolic disease risk due to obesity. We aimed to compare quantitative measures of subcutaneous (SAT) and visceral (VAT) adipose tissues in the abdomen between computed tomography (CT) and Dixon-based magnetic resonance (MR) images using a unified computer-assisted software framework. Materials and Methods: This study included 21 subjects who underwent abdominal CT and Dixon MR imaging on the same day. For each subject, two matched axial CT and fat-only MR images at the L2-L3 and the L4-L5 intervertebral levels were selected for fat quantification. For each image, an outer and an inner abdominal wall regions as well as SAT and VAT pixel masks were automatically generated by our software. The computer-generated results were then inspected and corrected by an expert reader. Results: There were excellent agreements for both abdominal wall segmentation and adipose tissue quantification between matched CT and MR images. Pearson coefficients were 0.97 for both outer and inner region segmentation, 0.99 for SAT, and 0.97 for VAT quantification. Bland–Altman analyses indicated minimum biases in all comparisons. Conclusion: We showed that abdominal adipose tissue can be reliably quantified from both CT and Dixon MR images using a unified computer-assisted software framework. This flexible framework has a simple-to-use workflow to measure SAT and VAT from both modalities to support various clinical research applications. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests the involvement of tumor-derived exosomes in the development and recurrence of hepatocellular carcinoma (HCC). We previously identified miR-4669 as a highly expressed microRNA in circulating exosomes obtained from patients with post-transplant HCC recurrence. This study aimed to explore how overexpression of miR-4669 affects HCC development and recurrence. The impact of miR-4669 overexpression in Hep3B cells on tumor cell behavior and the tumor microenvironment was evaluated in vitro. In addition, the clinical value of exosomal miR-4669 for the prediction of treatment response to HCC downstaging therapies and following post-transplant HCC recurrence was explored. Overexpression of miR-4669 enhanced migration ability and led to acquired sorafenib resistance with an elevation of sirtuin 1 and long noncoding RNA associated with microvascular invasion. Active release of tumor-derived exosomes and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) contributed to generating an immunosuppressive tumor microenvironment through the induction of M2 macrophage polarization. The retrospective analysis demonstrated the clinical value of exosomal miR-4669 for predicting treatment response to HCC downstaging therapies and for risk assessment of post-transplant HCC recurrence. In summary, the present data demonstrate the impact of exosomal miR-4669 on HCC recurrence through the enhancement of tumor aggressiveness and generation of an immunosuppressive tumor microenvironment. [ABSTRACT FROM AUTHOR]

This study sought to assess the interdecadal and interannual variability of autumn extreme rainfall (ER) in Taiwan from 1979 to 2019. Three types of ER events were identified based on a clustering analysis augmented by a deep autoencoder-based neural network model. This method outperforms other methods in obtaining the optimal number of clusters by extracting the synoptic features in advance. The patterns associated with these three types include a tropical cyclone covering Taiwan (TC), a TC-like circulation in the South China Sea (SCS) accompanied by northeasterly near northern Taiwan (TC-NE), and northeasterly near northern Taiwan (NE). The differences in the rainfall pattern caused by the three types were discernable over Taiwan. How the PDO or ENSO modulates the regional large-scale environment to favor the occurrence of these ER events was investigated. The occurrence of TC-NE events was simultaneously correlated with the negative phases of PDO/ENSO in the interdecadal/interannual scale. In the negative phases of PDO/ENSO, a low-level anomalous cyclone over SCS accompanied by background northeasterly favored the regional TC activities and may cause more TC-NE events. The occurrence of NE events is simultaneously correlated with the cold phase of ENSO. An anomalous low-level anticyclone in Northeast Asia strengthened the northeasterly toward northern Taiwan, and with the seasonal background moisture, provided favorable conditions for the occurrence of the NE events. Overall, the occurrence of the TC events did not correlate with the PDO or ENSO signals; the reasons for the lack of correlation were discussed herein. [ABSTRACT FROM AUTHOR]

Children and adolescents are vulnerable to non-accidental injury. Early identification and prevention rely on detailed epidemiological studies, which are limited in Asia. This retrospective study used the registry data of Pan-Asian Trauma Outcome Study (PATOS) from October 1, 2015 to December, 31, 2020. Pediatric patients (aged < 20 years) with non-accidental injuries were enrolled, which were divided by age into preschool (0–6 years), child (7–12 years), and adolescent (13–19 years) groups. Baseline characteristics, injury epidemiology, and excess mortality ratio-adjusted injury severity score (EMR-ISS) were collected. Major trauma was defined as an EMR-ISS score > 24. The study enrolled 451 patients with non-accidental injuries, accounting for 2.81% of pediatric trauma events presented to an emergency department in the PATOS registry. The overall mortality rate was 0.9%, similar to those in Western countries. Mortality rate was high in preschool children (8.7%, p = 0.017) than in other age groups. The sex-specific incidence was higher in boys (3.10% vs. 2.13%, p = 0.001). In adolescents, more events occurred on the street (25.9%), whereas home remained the most common locale in girls of all ages. In the multivariable regression analysis, abdominal and multiple injuries were risk factors for major trauma. [ABSTRACT FROM AUTHOR]

Background: Antibiotic prescription practices in primary care in Singapore have received little scholarly attention. In this study, we ascertained prescription prevalence and identified care gaps and predisposing factors. Methods: A retrospective study was conducted on adults (>21 years old) at six public primary care clinics in Singapore. Prescriptions >14 days were excluded. Descriptive statistics were used to showcase the prevalence data. We used chi-square and logistic regression analyses to identify the factors affecting care gaps. Results: A total of 141,944 (4.33%) oral and 108,357 (3.31%) topical antibiotics were prescribed for 3,278,562 visits from 2018 to 2021. There was a significant reduction in prescriptions (p < 0.01) before and after the pandemic, which was attributed to the 84% reduction in prescriptions for respiratory conditions. In 2020 to 2021, oral antibiotics were most prescribed for skin (37.7%), genitourinary (20.2%), and respiratory conditions (10.8%). Antibiotic use in the "Access" group (WHO AWaRe classification) improved from 85.6% (2018) to 92.1% (2021). Areas of improvement included a lack of documentation of reasons for antibiotic use, as well as inappropriate antibiotic prescription for skin conditions. Conclusion: There was a marked reduction in antibiotic prescriptions associated with the onset of the COVID-19 pandemic. Further studies could address the gaps identified here and evaluate private-sector primary care to inform antibiotic guidelines and the local development of stewardship programs. [ABSTRACT FROM AUTHOR]

Background: Although jaw asymmetry is commonly seen in skeletal Class III patients, its correlation with occlusal function and masticatory muscle activity has not been fully elucidated. Objectives: The purpose of this study was to investigate the occlusal function and masticatory muscle activity in skeletal Class III patients with various patterns of mandibular asymmetry. Methods: Forty‐two patients and 10 normal participants were examined. The patients were categorised into three groups. Groups 1 and 2 exhibited menton and ramus deviation to the same side. Menton deviation was larger than ramus deviation in Group 1, whereas Group 2 showed the inverse relation. Group 3 patients showed menton and ramus deviation in opposite directions. Occlusal contact area (OCA), relative bite force (RBF), and temporalis anterior (TA) and masseter muscle (MM) activity at maximum clenching were measured using T‐Scan Novus system and Bio‐EMG‐III. Statistical analysis was performed using the t‐test, one‐way analysis of variance with Bonferroni correction and Spearman correlation (α =.05). Results: Compared with normal participants, the patients had smaller OCA and greater asymmetry in the distribution of masticatory muscle activity. Greater ramus deviation was associated with smaller OCA in Group 1 but with larger OCA in Group 3. In Group 1, greater menton deviation was related to stronger TA activity on the non‐deviation side. In Group 2, greater ramus deviation was related to stronger MM activity on the deviation side. Conclusion: Deviation of the menton and ramus was individually related to OCA and masticatory muscle activity, and this relationship varied according to the pattern of mandibular asymmetry. [ABSTRACT FROM AUTHOR]

In-service education for oncology nurses usually adopts didactic teaching. This study investigated the effects of virtual reality (VR) and a digital learning-based Port-A-catheter educational course for oncology nurses. A mixed-methods research design was employed, with a convenience sample of 43 nurses from a regional teaching hospital in Taiwan participating. Measurements were taken at three time points: pre-test, 1st post-test, and 2nd post-test. The data was analyzed using descriptive statistics and repeated ANOVA tests. Results showed significant improvement in Port-A-catheter knowledge and skill levels (p < 0.0001) and high learning attitude and satisfaction scores of 4.29 ± 0.46 and 4.31 ± 0.58 points, respectively. Five qualitative themes emerged, highlighting the realistic VR scenarios, VR practice's usefulness, willingness to learn with VR, VR system limitations, and the potential for future courses. The study concluded that a VR-based educational course effectively enhanced nurses' knowledge, skills, learning attitude, and satisfaction, recommending the inclusion of diverse clinical scenarios for practical learning. [ABSTRACT FROM AUTHOR]