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Abstract We have developed a digital twin-based CKD identification and prediction model that leverages generalized metabolic fluxes (GMF) for patients with Type 2 Diabetes Mellitus (T2DM). GMF digital twins utilized basic clinical and physiological biomarkers as inputs for identification and prediction of CKD. We employed four diverse multi-ethnic cohorts (n = 7072): a Singaporean cohort (EVAS, n = 289) and a North American cohort (NHANES, n = 1044) for baseline CKD identification, and two multi-center Singaporean cohorts (CDMD, n = 2119 and SDR, n = 3627) for 3-year CKD prediction and risk stratification. We subsequently conducted a comprehensive study utilizing a single dataset to evaluate the clinical utility of GMF for CKD prediction. The GMF-based identification model performed strongly, achieving an AUC between 0.80 and 0.82. In prediction, the GMF generated with complete parameters attained high performance with an AUC of 0.86, while with incomplete parameters, it achieved an AUC of 0.75. The GMF-based prediction model utilizing complete inputs is the standard implementation of our algorithm: HealthVector Diabetes®. We have established the GMF digital twin-based model as a robust clinical tool capable of predicting and stratifying the risk of future CKD within a 3-year time horizon. We report the correlation of GMF with basic input parameters, their ability to differentiate between future health states and medication status at baseline, and their capability to quantify CKD progression rates. This holistic methodology provides insights into patients’ health states and CKD progression rates based on GMF metabolic profile differences, enabling personalized care plans.

Electric vehicles (EVs) have been widely considered an essential element to contribute to green and smart transportation, which will further enhance the development of smart cities. Hong Kong, as one of the largest metropolises in the world, has promoted the deployment of EVs for both the private and public transportation sectors over the past decade, with substantial financial subsidies and encouraging policy incentives. With the rapid penetration of EVs, especially in the market of private passenger cars, Hong Kong may face the challenge of insufficient charging facilities in the next few years. As such, the research study aims to develop a mathematical model using a topological method to map out feasible locations for new EV charging facilities on Ap Lei Chau Island, to construct a small Python program to optimize the mapping process of these feasible locations, and to estimate energy consumption and associated economic analysis to foster the spatial planning of EV charging facility networks. In conclusion, optimal locations for new charging facilities for EVs have been revealed to match the rapid growth of EV usage and facilitate the emergence of green and smart transportation.

Abstract Background To evaluate the degeneration of the corticospinal tract (CST) and corpus callosum (CC) in patients with motor neuron disease and upper motor neuron (UMN) dysfunction using diffusion kurtosis imaging (DKI). Methods Twenty‐seven patients and 33 healthy controls underwent magnetic resonance imaging along with clinical and neuropsychological testing. Tractography of diffusion tensor images was performed to extract tracts of the bilateral CST and CC. Group mean differences both across the entire averaged tract and along each tract were assessed, including correlations between diffusion metrics and clinical measures. Tract‐based spatial statistics (TBSS) was performed to evaluate the spatial distribution of whole‐brain microstructural abnormalities in patients. Results In comparison to controls, patients had significantly higher mean and radial diffusivity and lower fractional anisotropy (FA), kurtosis anisotropy, mean kurtosis (MK), and radial kurtosis (RK) in the CST and CC (p

Background. Linear scleroderma is one of the five forms of scleroderma, but it is the most common form of localized scleroderma in childhood. If left untreated, it can lead to severe disfigurement and functional impairment. The typical appearance is a linear streak with cutaneous induration on the face or head in association with various ophthalmological and neurological signs and symptoms. Treatment typically includes corticosteroids and/or methotrexate with life-long monitoring for recurrence. Case Presentation. A 12-year-old girl presented to our clinic in northern rural Cambodia with a history of a linear streak on her forehead that was growing down her nasal bridge. She denied any tenderness or family history of rheumatic disease. Her history was significant for strabismus as a child. A visiting pediatric rheumatologist assisted us with the appropriate diagnosis and treatment plan. Conclusion. In our case report, we present a child with linear scleroderma who fortunately came to medical attention early and received appropriate treatment before the onset of complications. She was treated with systemic immunosuppression as well as topical steroids. After treatment, she had no further progression on her face and continued to follow up with us to monitor for disease activity. To summarize, linear scleroderma is an uncommon diagnosis for general pediatricians and should be recognized early to provide appropriate treatment and follow-up.

Hypothermia (axillary temperature less than 36.5°) is a major source of neonatal morbidity and mortality, with a disproportionate burden of disease in low- and middle-income countries. Despite the importance of thermoregulation on newborn outcomes, the global epidemiologic landscape of neonatal hypothermia is poorly characterized. Clinical decision support (CDS) software provides point-of-care recommendations to guide clinical management and may support data capture in settings with limited informatics infrastructure. Towards this end, we conducted a prospective observational study of the NoviGuide, a novel CDS platform for newborn care, at four health facilities in Uganda between September 2022 to May 2021. Data were extracted from clinical information (e.g. axillary temperature, birth weight, gestational age) entered into the NoviGuide by nurses and midwives on newborns within 24 hours of delivery. Descriptive statistics and multivariable logistic regression were used to evaluate neonatal temperature profiles and the association between hypothermia and clinical features. Among 1,027 completed assessments, 30.5% of entries had neonatal hypothermia with significant variation across study sites. On multivariable logistic regression analysis, we found that hypothermia was independently associated with pre-term birth (Adjusted Odd's Ratio [aOR] 2.62, 95% Confidence interval [CI] 1.38-4.98), sepsis/concern for sepsis (aOR 2.73, 95% CI 2.90-3.94), and hypoglycemia/concern for hypoglycemia (aOR 1.78, 95% CI 1.17-2.72). Altogether, neonatal hypothermia was commonly entered into the NoviGuide and associated clinical characteristics aligned with previous studies based on conventional data collection instruments. Our results should be contextualized within unique technical and operational features of CDS tools, including a bias towards acutely ill patients and limited quality control. Nonetheless, this study demonstrates that a CDS used voluntarily by clinicians has the potential to fill key data gaps and drive quality improvement towards reducing neonatal hypothermia in low resource settings.

Respiratory disease is a leading cause of death in children under 5 years of age worldwide, and most of these deaths occur in low- to middle-income countries (LMICs) where advanced respiratory care technology is often limited. Much of the equipment required to provide advanced respiratory care is unavailable in these areas due to high costs, the need for specialty trained personnel, and myriad other resource constraints that limit uptake and sustainable use of these devices, including reliable access to electricity, sensitive equipment needing frequent maintenance, single-patient-use supplies, and lack of access to sterilization equipment. Compounding the problem, pediatrics is uniquely challenging in that one size does not fit all, or even most patients. Despite these substantial barriers, numerous innovations in respiratory care technology have been made in recent years that have brought increasing access to high quality respiratory care in some of the most remote areas of the world. In this article, we intend to review the global burden of respiratory diseases for children, highlight the prototypical innovations that have been made in bringing respiratory care to LMICs, spotlight some of the technologies being actively developed to improve respiratory care in resource-constrained settings, and conclude with a discussion highlighting areas where further innovation is still needed.

The electric vehicle (EV) has proven to be a workable solution to minimizing environmental pollution. The EV has generally received substantial attention from both individual customers and corporate users. The EV has transformed remarkably and in recent years emerged as the most quickly developing section of the automobile industry. China has proven to be an outstanding country in enhancing the manufacture and marketing of EVs. Nevertheless, green environment, charging infrastructure and technology are the three main challenges leading to slowing down the penetration progress of EVs into the Greater Bay Area (GBA) of China. This study aims to report the existing development of the EV industry in China. Then, it elaborates on national policies to facilitate the enlargement of charging infrastructures, explains how to stimulate the development of charging infrastructure at the national level, discusses the implementation dilemma at the provincial and city levels, and highlights the challenges and policy gaps. Finally, it addresses some issues, challenges, progress and implications for improving the EV penetration in the GBA in the forthcoming years.

Despite the development of therapeutic agents that selectively target cancer cells, relapse driven by acquired drug resistance and resulting treatment failure remains a significant issue. The highly conserved Hedgehog (HH) signaling pathway performs multiple roles in both development and tissue homeostasis, and its aberrant regulation is known to drive the pathogenesis of numerous human malignancies. However, the role of HH signaling in mediating disease progression and drug resistance remains unclear. This is especially true for myeloid malignancies. The HH pathway, and in particular the protein Smoothened (SMO), has been shown to be essential for regulating stem cell fate in chronic myeloid leukemia (CML). Evidence suggests that HH pathway activity is critical for maintaining the drug-resistant properties and survival of CML leukemic stem cells (LSCs), and that dual inhibition of BCR-ABL1 and SMO may comprise an effective therapeutic strategy for the eradication of these cells in patients. This review will explore the evolutionary origins of HH signaling, highlighting its roles in development and disease, which are mediated by canonical and non-canonical HH signaling. Development of small molecule inhibitors of HH signaling and clinical trials using these inhibitors as therapeutic agents in cancer and their potential resistance mechanisms, are also discussed, with a focus on CML.

Building a new type of power system is an important guarantee to support China’s “dual carbon” goal. Due to the inseparable relationship between industrial and agricultural production and electric energy utilization, there must be interdisciplinary integration to achieve the goal of “dual carbon”. The disciplines of horticulture and electric power are taken as examples in this paper to analyze the feasibility of carbon emission reduction through coordinating agricultural photovoltaic (PV) greenhouse and electric vehicle (EV) energy storage. Firstly, the mechanism of carbon emission difference caused by electric energy supplementing during EV charging is analyzed. Secondly, in the context of the contradiction between the reduction of battery life caused by discharging (increasing carbon emission) and the increase in PV output consumption by orderly charging and discharging (reducing carbon emission), an optimization model for the synergistic operation of EV clusters and greenhouse PVs (with the objective of minimizing carbon emissions) is proposed. Finally, the effectiveness of the proposed model is verified through simulation cases. The energy storage characteristics of EVs is capable of realizing the transfer of PV power generation in the time dimension, and the coordinated operation of greenhouse PVs and EVs’ charging and discharging can effectively reduce carbon emission during the EV operation period. In a typical summer scenario of PV output, the carbon emission of EVs in V2G (vehicle to grid) mode was reduced by 69.13% compared to disorderly charging. It is shown that the adequacy of PV generation and the orderly dispatching of the charging and discharging of EVs are the key factors in reducing carbon emission throughout the life cycle of EVs.

In 2013, the first electric taxis were launched in Hong Kong. In 2021, the HKSAR government announced that no new registration of fuel-propelled private cars, including hybrid vehicles, will be granted by the year 2035. Local public policies have shown a breakthrough milestone in the passenger transport sector and fostered the development of a smart city in Hong Kong as an international metropolis. This paper aims to study the feasibility of gradually introducing electric vehicles (EVs) in the Hong Kong taxi industry in the next decade. In particular, taxi license owners’ intentions of purchasing electric vehicles for operational use and the driving behavior of taxi drivers in Hong Kong are investigated. Multiagent modelling with an integrated behavioral model is then adopted to analyze the survey data collected from 250 taxi drivers in Hong Kong, followed by interviews with industrial experts. The implications for future public policies are then discussed. To achieve emission reduction, the paper suggests a gradual, step-by-step promotion and transfer from conventional taxis to electric taxis in Hong Kong, with consideration of various factors and the interests of different stakeholders in the community.

BackgroundBurnout interventions are limited by low use. Understanding resident physician preferences for burnout interventions may increase utilization and improve the assessment of these interventions. ObjectiveThis study aims to use an econometric best-worst scaling (BWS) framework to survey internal medicine resident physicians to establish help-seeking preferences for burnout and barriers to using wellness supports by quantifying selections for 7 wellness support options and 7 barriers. MethodsInternal medicine resident physicians at our institution completed an anonymous web-based BWS survey during the 2020-2021 academic year. This cross-sectional study was analyzed with multinomial logistic regression and latent class modeling to determine the relative rank ordering of factors for seeking support for burnout and barriers to using wellness supports. Analysis of variance with Tukey honest significant difference posthoc test was used to analyze differences in mean utility scores representing choice for barriers and support options. ResultsOf the 163 invited residents, 77 (47.2% response rate) completed the survey. Top-ranking factors for seeking wellness supports included seeking informal peer support (best: 71%; worst: 0.6%) and support from friends and family (best: 70%; worst: 1.6%). Top-ranking barriers to seeking counseling included time (best: 75%; worst: 5%) and money (best: 35%; worst: 21%). ConclusionsOverall, our findings suggest that low utilization of formal mental health support is reflective of resident preferences to seek help informally and that increasing utilization will require addressing pragmatic barriers of time and cost. Assessing physician preferences for wellness-related initiatives may contribute to understanding the low utilization of formal mental health services among physicians, which can be determined using a BWS framework.

With the dynamic development of renewable energies, energy storage devices, and electric vehicles, microgrids have been playing an increasingly vital role in smart power grids. Under the recent development of carbon neutralisation, microgrid systems containing multiple clean energy sources have become significant modules for energy conservation and emission reduction. Considering technological and environmental elements, we investigated the economic operation of microgrids with the integration of electric vehicles. In this paper, carbon trading mechanisms and operation scheduling strategies are analysed in the simulation models. Then, transaction costs and power balance are discussed. Industrial applications and policy implications are also presented.

OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 μg/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 μm thick sagittal sections from each joint, 50 μm apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.

The ESS is designed as a suite of components that enable and facilitate sensor networks, their deployment, management, and usage. In meeting its charter, the ESS spans a comprehensive set of platforms and operates in a diverse set of environments. It is, therefore, based on a tiered architecture comprised of; motes (mica2, tos, chipcon, sensor interface board), microservers (strongarm/xscale, linux, motenic, 802.11), commodity platforms (x86, linux, 802.11) platforms, and enterprise platforms (such as solaris and oracle)...

Current developments in sensing technology will allow sensor networks to be embedded in diverse environments to allow for the collection, manipulation, and transmission of experimental data. One such application of this technology is the Extensible Sensing System, which is designed to be the testbed for sensors and user interfaces to be used in environment sensing...

Calcium silicate (CS) cements have excellent bioactivity and can induce the bone-like apatite formation. They are good biomaterials for bone tissue engineering and bone regenerative medicine. However, they have degradability and the dissolved CS can cause the inflammatory response at the early post-implantation stage. The purpose of this study was to design and prepare the curcumin-loaded mesoporous CS (MesoCS/curcumin) cements as a strategy to reduce the inflammatory reaction after implantation. Methods: The MesoCS/curcumin cements were designed and prepared. The characteristics of MesoCS/curcumin specimens were examined by transmission electron microscopy (TEM), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Their physical properties, biocompatibility, and anti-inflammatory ability were also evaluated. Results: The MesoCS/curcumin cements displayed excellent biocompatibility and physical properties. Their crystalline characterizations were very similar with MesoCS cements. After soaking in simulated body fluid, the bone-like apatite layer of the MesoCS/curcumin cements could be formed. In addition, it could inhibit the expression of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) after inflammation reaction induced by lipopolysaccharides and had good anti-inflammatory ability. Conclusion: Adding curcumin in MesoCS cements can reduce the inflammatory reaction, but does not affect the original biological activity and properties of MesoCS cements. It can provide a good strategy to inhibit the inflammatory reaction after implantation for bone tissue engineering and bone regenerative medicine.

ObjectivesWe aimed to study the prevalence of CTCs in breast cancer (BC) patients undergoing neoadjuvant or palliative therapy with a label-free microfluidic platform (ClearCell FX), and its prognostic relevance in metastatic BC (mBC).Materials and methodsPeripheral blood samples were collected from 108 BC patients before starting a new line of treatment ("baseline"), majority of whom had mBC (76/108; 70.4%). CTCs were retrieved by dean flow fractionation that enriched for larger cells, and enumerated using immunofluorescence-based staining. Progression-free survival (PFS) in mBC patients was analysed using Kaplan-Meier method; cox proportional hazard models were used for univariable and multivariable analyses.ResultsThe detection rate of CTCs before starting a new line of treatment was 75.9% (n = 108; median: 8 CTCs/7.5 ml blood) at a cut off of ≥2 CTCs. PFS was inferior for mBC patients with baseline CTC count ≥5 CTCs/7.5 ml blood vs. those with < 5 CTCs/7.5 ml blood (median PFS: 4.3 vs. 7.0 months; p-value: 0.037). The prognostic relevance of CTCs was most significant in patients with HER2- mBC (median PFS: 4.1 vs. 8.3 months; p-value: 0.032), luminal (HR+HER2-) subtype (median PFS: 4.2 vs. 8.3 months; p-value: 0.048), and patients who had one or more prior treatments (median PFS: 4.2 vs. 7.0 months; p-value: 0.02). On multivariable analysis, baseline CTC level (hazard ratio (HR): 1.84, p-value: 0.02) and pre-treatment status (HR: 1.87, p-value: 0.05) were independent predictors of PFS.ConclusionsThis work demonstrates the prognostic significance of CTCs in mBC detected using a label-free size-based enrichment platform.