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Hydrogen persulfide (H2S2) is an important sulfur-containing signaling molecule that plays a crucial role in the homeostasis of various organ systems, such as the renal, cardiovascular, liver, and gastrointestinal systems. However, research on H2S2in biological settings is still challenging due to its instability and high reactivity. Compounds that can controllably release H2S2(also known as donors) are thus crucial research tools. Currently, available H2S2donors are still very limited, with most of them relying on modified disulfide templates. These templates possess an unavoidable limitation of being susceptible to cellular disulfide exchange which can compromise their efficacy. In this work, we explored nondisulfide-based and nonoxidation-dependent templates for the design of H2S2donors. We found that tertiary naphthacyl thiols could undergo phototriggered C–S homolytic cleavage to form H2S2via hydrosulfide (HS) radicals. In addition, the release of H2S2was associated with the formation of a product with strong blue fluorescence, which allowed for real-time monitoring of the release process. This reaction was demonstrated to proceed effectively in both buffers and cells, with the ability to enhance intracellular production of persulfides, including GSSH, CysSSH, H2S2, H2S3, etc. It provides a unique photocontrolled H2S2donor system with distinct advantages compared to known H2S2donors due to its good stability and spatiotemporal control ability.

IMPORTANCE: Nearly 6 million children in the US have asthma, and over one-third of US children are insured by Medicaid. Although 23 state Medicaid programs have experimented with accountable care organizations (ACOs), little is known about ACOs’ effects on longstanding insurance-based disparities in pediatric asthma care and outcomes. OBJECTIVE: To determine associations between Massachusetts Medicaid ACO implementation in March 2018 and changes in care quality and use for children with asthma. DESIGN, SETTING, AND PARTICIPANTS: Using data from the Massachusetts All Payer Claims Database from January 1, 2014, to December 31, 2020, we determined child-years with asthma and used difference-in-differences (DiD) estimates to compare asthma quality of care and emergency department (ED) or hospital use for child-years with Medicaid vs private insurance for 3 year periods before and after ACO implementation for children aged 2 to 17 years. Regression models accounted for demographic and community characteristics and health status. Data analysis was conducted between January 2022 and June 2024. EXPOSURE: Massachusetts Medicaid ACO implementation. MAIN OUTCOMES AND MEASURES: Primary outcomes were binary measures in a calendar year of (1) any routine outpatient asthma visit, (2) asthma medication ratio (AMR) greater than 0.5, and (3) any ED or hospital use with asthma. To determine the statistical significance of differences in descriptive statistics between groups, χ2 and t tests were used. RESULTS: Among 376 509 child-year observations, 268 338 (71.27%) were insured by Medicaid and 73 633 (19.56%) had persistent asthma. There was no significant change in rates of routine asthma visits for Medicaid-insured child-years vs privately insured child-years post-ACO implementation (DiD, −0.4 percentage points [pp]; 95% CI, −1.4 to 0.6 pp). There was an increase in the proportion with AMR greater than 0.5 for Medicaid-insured child-years vs privately insured in the postimplementation period (DiD, 3.7 pp; 95% CI, 2.0-5.4 pp), with absolute declines in both groups postimplementation. There was an increase in any ED or hospital use for Medicaid-insured child-years vs privately insured postimplementation (DiD, 2.1 pp; 95% CI, 1.2-3.0 pp), an 8% increase from the preperiod Medicaid use rate. CONCLUSIONS AND RELEVANCE: Introduction of Massachusetts Medicaid ACOs was associated with persistent insurance-based disparities in routine asthma visit rates; a narrowing in disparities in appropriate AMR rates due to reductions in appropriate rates among those with private insurance; and worsening disparities in any ED or hospital use for Medicaid-insured children with asthma compared to children with private insurance. Continued study of changes in pediatric asthma care delivery is warranted in relation to major Medicaid financing and delivery system reforms.

In this letter, for the first time, a novel 100G pre-amplified self-coherent passive optical network (SC-PON) architecture is proposed and experimentally verified. To mitigate the reduction in receiver sensitivity resulting from co-transmitted carriers in self-coherent systems, a semiconductor optical amplifier (SOA) was deployed for pre-amplification with a noise figure of 7.5dB and a small-signal gain of 30dB. As a proof-of-concept, a system experiment of pre-amplified 25-GBaud 16-QAM SC-PON is demonstrated in the downstream, achieving a data rate of 100 Gb/s/ $\lambda $ over 20-km single-mode fiber (SMF) with a receiver sensitivity of -22dBm. We achieve a power budget beyond 33.6 dB under the 15% SD-FEC threshold of $2\times 10 ^{-2}$ , surpassing the power budget specified by ITU-T class N1 and IEEE class PR(X). The results indicate that the proposed SC-PON has the potential applicability for next-generation beyond 100G access systems.

Guidelines recommend low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs) rather than unfractionated heparin (UFH) for treatment of acute pulmonary embolism (PE) given their efficacy and reduced risk of bleeding. Using data from a large consortium of US hospitals, we examined trends in initial anticoagulation among hospitalized patients diagnosed with acute PE.

Psychiatric disorders are highly heritable yet polygenic, potentially involving hundreds of risk genes. Genome-wide association studies have identified hundreds of genomic susceptibility loci with susceptibility to psychiatric disorders; however, the contribution of these loci to the underlying psychopathology and etiology remains elusive. Here we generated deep human brain proteomics data by quantifying 11,608 proteins across 268 subjects using 11-plex tandem mass tag coupled with two-dimensional liquid chromatography-tandem mass spectrometry. Our analysis revealed 788 cis-acting protein quantitative trait loci associated with the expression of 883 proteins at a genome-wide false discovery rate <5%. In contrast to expression at the transcript level and complex diseases that are found to be mainly influenced by noncoding variants, we found protein expression level tends to be regulated by non-synonymous variants. We also provided evidence of 76 shared regulatory signals between gene expression and protein abundance. Mediation analysis revealed that for most (88%) of the colocalized genes, the expression levels of their corresponding proteins are regulated by cis-pQTLs via gene transcription. Using summary data-based Mendelian randomization analysis, we identified 4 proteins and 19 genes that are causally associated with schizophrenia. We further integrated multiple omics data with network analysis to prioritize candidate genes for schizophrenia risk loci. Collectively, our findings underscore the potential of proteome-wide linkage analysis in gaining mechanistic insights into the pathogenesis of psychiatric disorders.

Microcin J25 (MccJ25), a lasso peptide antibiotic with a unique structure that resembles the lariat knot, has been a topic of intense interest since its discovery in 1992. The precursor (McjA) contains a leader and a core segment. McjB is a protease activated upon binding to the leader, and McjC converts the core segment into the mature MccJ25. Previous studies suggested that these biosynthetic steps likely proceed in a (nearly) concerted fashion; however, there is only limited information regarding the structural and molecular intricacies of MccJ25 biosynthesis. To close this knowledge gap, we used AlphaFold2 to predict the structure of the precursor (McjA) in complex with its biosynthetic enzymes (McjB and McjC) and queried the critical predicted features by protein engineering. Based on the predicted structure, we designed protein variants to show that McjB can still be functional and form a proficient biosynthetic complex with McjC when its recognition and protease domains were circularly permutated or split into separate proteins. Specific residues important for McjA recognition were also identified, which permitted us to pinpoint a compensatory mutation (McjBM108T) to restore McjA/McjB interaction that rescued an otherwise nearly nonproductive precursor variant (McjAT–2M). Studies of McjA, McjB, and McjC have long been mired by them being extremely difficult to handle experimentally, and our results suggest that the AF2 predicted ternary complex structure may serve as a reasonable starting point for understanding MccJ25 biosynthesis. The prediction-validation workflow presented herein combined artificial intelligence and laboratory experiments constructively to gain new insights.

This study unveils the “green” metal–organic framework (MOF) structuring mechanism by decoding proton transfer in water during ZIF-8 synthesis. Combining in situsmall- to wide-angle X-ray scattering, multiscale simulations, and quantum calculations, we reveal that the ZIF-8 early-stage nucleation and crystallization process in aqueous solution unfolds in three distinct stages. In stage I, imidazole ligands replace water in zinc–water cages, triggering an “acidity flip” that promotes proton transfer. This leads to the assembly of structures from single zinc ions to 3D amorphous cluster nuclei. In stage II, amorphous nuclei undergo a critical transformation, evolving into crystalline nuclei and subsequently forming mesoscale-ordered structures and crystallites. The process proceeds until the amorphous precursors are completely consumed, with the transformation kinetics governed by an energy barrier that determines the rate-limiting step. In stage III, stable crystallite nanoparticles form in solution, characterized by a temperature-dependent thermal equilibrium of molecular interactions at the crystal–solution interface. Beyond these core advancements, we explore the influence of encapsulated pepsin and nonencapsulated lysozyme on ZIF-8 formation, finding that their amino acid proton transfer capacity and concentration influence the resulting biomolecule-MOF composite’s shape and encapsulation efficiency. The findings contribute to understanding the molecular mechanisms behind biomimetic mineralization and have potential implications for engineering proteins within amorphous MOF nuclei as protein embryo growth sites.

Obesity and colorectal cancer are global public health issues, with the prevalence of both conditions increasing over the last 4 decades. In the United States alone, the prevalence of obesity is greater than 40%, and this percentage is projected to increase past 50% by 2030. This review focuses on understanding the association between obesity and the risk of colorectal cancer while also highlighting hypotheses about molecular mechanisms underlying the link between these disease processes. We also consider whether those linkages can be disrupted via weight loss therapies, including lifestyle modifications, pharmacotherapy, bariatric surgery, and endobariatrics.

Myhre syndrome (MS, MIM 139210) is a rare multisystemic disorder caused by recurrent pathogenic missense variants in SMAD4. The clinical features have been mainly documented in childhood and comprise variable neurocognitive development, recognizable craniofacial features, a short stature with a pseudo-muscular build, hearing loss, thickened skin, joint limitations, diverse cardiovascular and airway manifestations, and increased fibrosis often following trauma or surgery. In contrast, adults with MS are underreported obscuring potential clinical variability. Here, we describe 24 adults with MS, including 17 diagnosed after the age of 18 years old, and we review the literature on adults with MS. Overall, our cohort shows a milder phenotype as well as lower mortality rates compared to what has been published in literature. Individuals with a codon 500 variant in SMAD4present with a more pronounced neurodevelopmental and systemic phenotype. However, in contrast to the literature, we observe cardiovascular abnormalities in individuals with the p.(Arg496Cys) variant. In addition, we describe scoliosis as a new manifestation and we report fertility in two additional males with the p.(Arg496Cys). In conclusion, our study contributes novel insights into the clinical variability of MS and underscores the importance of variant-specific considerations, and we provide recommendations for the management of MS in adulthood.

Purpose: Surface-enhanced Raman scattering (SERS) is a technique for trace analysis detection based on the interaction of light with matter and between materials. In the past development of SERS, precious metals were primarily chosen as substrates due to their high electromagnetic effect, which leads to significantly enhanced SERS signals. However, the effect of using only precious metals is limited. Therefore, this study utilizes the characteristic micro-nano V-shaped pits that appear on the surface of c-plane GaN after wet etching. By depositing a gold film of various thicknesses, we aim to increase the contact area with the target molecule Rhodamine 6G (R6G), thereby further enhancing the sensitivity of SERS detection. Methods: After fabricating pitted c-plane GaN using chemical etching techniques, we analyzed the sample surface with a scanning electron microscope and assessed the impact of different gold film thicknesses on the SERS intensity of R6G using Raman spectroscopy. The comprehensive biomedical detection effectiveness was also evaluated using contact angle measurement, and fluorescence microscopy. Results: For the target molecule R6G, after depositing a 25 nm gold film, the enhancement factor of the substrate for detection reached 2.21×108, and the limit of detection was achieved at a concentration of 10− 10M. Conclusion: This study confirms the feasibility of using wet etching techniques on hexagonal materials like GaN for SERS applications. The GaN substrate with V-shaped pits provides an increased surface area, effectively enhancing SERS signal strength. This offers different choices and perspectives for SERS substrate selection in the detection of various target molecules.

This study aimed to investigate the contribution of myeloid differentiation primary‐response gene 88 (MyD88) on the differentiation of T helper type 17 (Th17) and regulatory T (Treg) cells and the emerging subgingival microbiota dysbiosis in Porphyromonas gingivalis‐induced experimental periodontitis. Alveolar bone loss, infiltrated inflammatory cells, immunostained cells for tartrate‐resistant acid phosphatase (TRAP), the receptor activator of nuclear factor‐kB ligand (RANKL), and osteoprotegerin (OPG) were quantified by microcomputerized tomography and histological staining between age‐ and sex‐matched homozygous littermates (wild‐type [WT, Myd88+/+] and Myd88−/−on C57BL/6 background). The frequencies of Th17 and Treg cells in cervical lymph nodes (CLNs) and spleen were determined by flow cytometry. Cytokine expression in gingival tissues, CLNs, and spleens were studied by quantitative polymerase chain reaction (qPCR). Analysis of the composition of the subgingival microbiome and functional annotation of prokaryotic taxa (FAPROTAX) analysis were performed. P. gingivalis‐infected Myd88−/−mice showed alleviated bone loss, TRAP+osteoclasts, and RANKL/OPG ratio compared to WT mice. A significantly higher percentage of Foxp3+CD4+T cells in infected Myd88−/−CLNs and a higher frequency of RORγt+CD4+T cells in infected WT mice was noted. Increased IL‐10and IL‐17aexpressions in gingival tissue at D14–D28 then declined in WT mice, whereas an opposite pattern was observed in Myd88−/−mice. The Myd88−/−mice exhibited characteristic increases in gram‐positive species and species having probiotic properties, while gram‐negative, anaerobic species were noted in WT mice. FAPROTAX analysis revealed increased aerobic chemoheterotrophy in Myd88−/−mice, whereas anaerobic chemoheterotrophy was noted in WT mice after P. gingivalisinfection. MyD88 plays an important role in inflammation‐induced bone loss by modulating the dynamic equilibrium between Th17/Treg cells and dysbiosis in P. gingivalis‐induced experimental periodontitis.

Oncolytic adenoviruses have emerged as a promising therapeutic approach for cancer therapy. However, systemic delivery of the viruses to metastatic tumors remains a major challenge. Mesenchymal stem cells (MSCs) possess tumor tropism property and can be used as cellular vehicles for delivering oncolytic adenoviruses to tumor sites. Since telomerase activity is found in ~90% of human carcinomas, but undetected in normal adult cells, the human telomerase reverse transcriptase gene (TERT) promoter can be exploited for regulating the replication of oncolytic adenoviruses. Here, we evaluated the antitumor effects of syngeneic murine MSCs loaded with the luciferase-expressing, telomerase-dependent oncolytic adenovirus Ad.GS2 (MSC-Ad.GS2) and Ad.GS2 alone on metastatic MBT-2 bladder tumors. MSCs supported a low degree of Ad.GS2 replication, which could be augmented by coculture with MBT-2 cells or tumor-conditioned medium (TCM), suggesting that viral replication is increased when MSC-Ad.GS2 migrates to tumor sites. MBT-2 cells and TCM enhanced viral replication in Ad.GS2-infected MSCs. SDF-1 is a stem cell homing factor. Our results suggest that the SDF-1/STAT3/TERT signaling axis in MSCs in response to the tumor microenvironment may contribute to the enhanced replication of Ad.GS2 carried by MSCs. Notably, we demonstrate the potent therapeutic efficacy of systemically delivered MSC-Ad.GS2 in pleural disseminated tumor and experimental metastasis models using intrapleural and tail vein injection of MBT-2 cells, respectively. Treatment with MSC-Ad.GS2 significantly reduced tumor growth and prolonged the survival of mice bearing metastatic bladder tumors. Since telomerase is expressed in a broad spectrum of cancers, this therapeutic strategy may be broadly applicable.Graphical Abstract

Rapidly growing data traffic drives the development of next-generation short-reach optical interconnects technology. Coherent detection has high-spectral efficiency, which is considered as a potential solution to break through the data-rate limitation of short-reach optical communication systems. Here, we introduce the concept of quasi frequency-synchronous optical network (FSON) architecture for short-reach optical communication in order to simplify coherent optical detection. We also demonstrate a novel optical carrier phase recovery scheme based on OPLL in FSON. In the OPLL, an acoustic optical modulator (AOM) is used as a feedback actuator to compensate for both the frequency offset and phase fluctuation introduced by the fiber link. In so doing, coherent detection requires neither MIMO nor carrier phase recovery DSP. We next present the world-first polarization and phase demultiplexing of DP-QPSK signals in optical domain without employing electronic DSP. The four tributaries of 100-Gb/s DP-QPSK signals are recovered below 3.8 × 10–3 BER threshold at −30-dBm receiver optical power. Our proposed DSP-free coherent detection provides an attractive solution for next generation datacenter transport with low cost and power consumption.

ABSTRACTWith value pegged to fiat currencies, stablecoins can mediate the price volatility of cryptocurrencies. And yet, the concept of stablecoin and its impact on fostering individuals’ cryptocurrency adoptions remain unclear. To explore stablecoin’s role in a contextualized way, we adopted the Push-Pull-Mooring (PPM) model as the theoretical foundations. PPM Framework is especially suitable for our study because it allows us to use a pretest-posttest approach to study the changes of different factors created by introducing stablecoins and the impact of these factors on the continuous intention (CI) of adopting cryptocurrency exchanges. Our results suggested that less experienced cryptocurrency users might not understand immediately upon learning about stablecoins. They may even feel confused and become less motivated to adopt cryptocurrencies. Conversely, more experienced users may recognize the importance of stablecoins. Moreover, after the introduction of stablecoins, the power of different factors on CI has also changed. Therefore, cryptocurrency exchanges need to adopt more diversified strategies to engage users of varying experience levels.

IMPORTANCE: Inpatient clinical deterioration is associated with substantial morbidity and mortality but may be easily missed by clinicians. Early warning scores have been developed to alert clinicians to patients at high risk of clinical deterioration, but there is limited evidence for their effectiveness. OBJECTIVE: To evaluate the effectiveness of an artificial intelligence deterioration model–enabled intervention to reduce the risk of escalations in care among hospitalized patients using a study design that facilitates stronger causal inference. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a regression discontinuity design that controlled for confounding and was based on Epic Deterioration Index (EDI; Epic Systems Corporation) prediction model scores. Compared with other observational research, the regression discontinuity design facilitates causal analysis. Hospitalized adults were included from 4 general internal medicine units in 1 academic hospital from January 17, 2021, through November 16, 2022. EXPOSURE: An artificial intelligence deterioration model–enabled intervention, consisting of alerts based on an EDI score threshold with an associated collaborative workflow among nurses and physicians. MAIN OUTCOMES AND MEASURES: The primary outcome was escalations in care, including rapid response team activation, transfer to the intensive care unit, or cardiopulmonary arrest during hospitalization. RESULTS: During the study, 9938 patients were admitted to 1 of the 4 units, with 963 patients (median [IQR] age, 76.1 [64.2-86.2] years; 498 males [52.3%]) included within the primary regression discontinuity analysis. The median (IQR) Elixhauser Comorbidity Index score in the primary analysis cohort was 10 (0-24). The intervention was associated with a −10.4–percentage point (95% CI, −20.1 to −0.8 percentage points; P = .03) absolute risk reduction in the primary outcome for patients at the EDI score threshold. There was no evidence of a discontinuity in measured confounders at the EDI score threshold. CONCLUSIONS AND RELEVANCE: Using a regression discontinuity design, this cohort study found that the implementation of an artificial intelligence deterioration model–enabled intervention was associated with a significantly decreased risk of escalations in care among inpatients. These results provide evidence for the effectiveness of this intervention and support its further expansion and testing in other care settings.

Background: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing outcomes and providing information for a larger number and broader range of SMA patients than included in clinical trials.Objective: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting.Methods: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources.Results: Recruitment started in September 2018. As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial SMA diagnosis was 1 (0–6) month and at onasemnogene abeparvovec infusion was 3 (1–10) months. Eighty patients (47.6%) had two and 70 (41.7%) had three copies of SMN2, and 98 (58.3%) were identified by newborn screening. Infants identified by newborn screening had a lower age at final assessment (mean age 11.5 months) and greater mean final (SD) CHOP INTEND score (57.0 [10.0] points) compared with clinically diagnosed patients (23.1 months; 52.1 [8.0] points). All patients maintained/achieved motor milestones. 48.5% (n?=?81/167) experienced at least one treatment-emergent adverse event (AE), and 31/167 patients (18.6%) experienced at least one serious AE, of which 8/31 were considered treatment-related.Conclusion: These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient population, which was consistent with initial clinical data and published 5-year follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec.

Background: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that affects ambulatory function. Quantitative ultrasound (QUS) imaging, utilizing envelope statistics, has proven effective in diagnosing DMD. Radiomics enables the extraction of detailed features from QUS images. This study further proposes a hybrid QUS radiomics and explores its value in characterizing DMD. Methods: Patients (n = 85) underwent ultrasound examinations of gastrocnemius through Nakagami, homodyned K (HK), and information entropy imaging. The hybrid QUS radiomics extracted, selected, and integrated the retained features derived from each QUS image for classification of ambulatory function using support vector machine. Nested five fold cross-validation of the data was conducted, with the rotational process repeated 50 times. The performance was assessed by averaging the areas under the receiver operating characteristic curve (AUROC). Results: Radiomics enhanced the average AUROC of B-scan, Nakagami, HK, and entropy imaging to 0.790, 0.911, 0.869, and 0.890, respectively. By contrast, the hybrid QUS radiomics using HK and entropy images for diagnosing ambulatory function in DMD patients achieved a superior average AUROC of 0.971 (p &lt; 0.001 compared with conventional radiomics analysis). Conclusions: The proposed hybrid QUS radiomics incorporates microstructure-related backscattering information from various envelope statistics models to effectively enhance the performance of DMD assessment.

Purpose: As a smart service, location-based advertising (LBA) integrates advanced technologies to deliver personalized messages based on a user’s real-time geographic location and needs. However, research has shown that privacy concerns threaten the diffusion of LBA. This research investigates how privacy-related factors (i.e. LBA type, privacy self-efficacy (PSE) and consumer generation) impact consumers’ value-in-use and their intention to use LBA. Design/methodology/approach: This study developed and examined an LBA value-in-use framework that integrates the role of LBA type, consumers’ PSE and consumer generation into the technology acceptance model (TAM). Data were collected through two experiments in the field with a total of 374 consumers. The proposed relationships were tested using PROCESS modeling. Findings: The results reveal that pull (vs push) LBA causes higher value-in-use in terms of perceived usefulness and perceived ease of use, leading to greater usage intention. Further, the differences in the mediated relationship between pull- and push-LBA are larger among consumers of low PSE (vs high PSE) and Generation Z (vs other generations). The findings suggest that the consumer value-in-use brought about by LBA diminishes when using push-LBA for low PSE and Generation Z consumers. Originality/value: This research is the first to integrate the privacy-related interactions of LBA type and consumer characteristics into TAM to develop a TAM-based LBA value-in-use framework. This study contributes to the literature on service value-in-use, smart services and LBA by clarifying the boundary conditions that determine the effectiveness of LBA in enhancing consumers’ value-in-use.

Traditional comparisons of slope coefficients and mean responses in linear regression analysis mainly focus on the significant difference rather than the practical equivalence. There has been a growing awareness and demand for appropriate techniques for assessing similarity and comparability in applied research. Because of the simplicity of the two one-sided tests of mean equivalence, this study describes the corresponding extensions for appraising slope coefficients and mean responses in one and two linear regression lines. The equivalence tests can help assess the negligible trends and similar responses in a single regression line and evaluate the unimportant interaction-moderation effects and comparable simple effects between two linear regression lines. Exact power and sample size formulas are also derived for design planning, and the proposed procedures have the distinct property of accommodating the random properties of both the response and predictor variables. Their usage and validity are illustrated and justified through numerical illustrations and simulation assessments.

This study aims to explore the impact of perceived value, individual differences and self-efficacy of consumers towards their intention of using mobile during COVID-19. This study adopts the technology acceptance model (TAM) with individual differences and self-efficacy factors affecting consumers' intentions towards using mobile payment and employs structural equation modelling to analyse. A convenient sampling technique is used to gather data from a self-administered questionnaire. The results confirm that consumers' intention of using mobile payment was influenced by their perceived value, individual differences and self-efficacy. Perceived convenience and perceived enjoyment positively affect intention to use; however, perceived fees and perceived risk negatively influence intention to use. Moreover, this study demonstrates that innovativeness and knowledge of mobile payment both have positive effects on intention to use. Self-efficacy influences the intention to use positively as well. The current study offers a holistic understanding of significant factors influencing Taiwan consumers' intention of using mobile payment.

In autonomous driving systems, the monocular 3D object detection algorithm is a crucial component. The safety of autonomous vehicles heavily depends on a well-designed detection system. Therefore, developing a robust and efficient 3D object detection algorithm is a major goal for institutes and researchers. Having a 3D sense is essential in autonomous vehicles and robotics, as it allows the system to understand its surroundings and react accordingly. Compared with stereo-based and Lidar-based methods, monocular 3D Object detection is a challenging task as it only utilizes 2D information to generate complex 3D features, making it low-cost, less computationally intensive, and with great potential. However, the performance of monocular methods is impaired due to the lack of depth information. In this paper, we propose a simple, end-to-end, and effective network for monocular 3D object detection without the use of external training data. Our work is inspired by auxiliary learning, in which we use a robust feature extractor as our backbone and multiple regression heads to learn auxiliary knowledge. These auxiliary regression heads will be discarded after training for improved inference efficiency, allowing us to take advantage of auxiliary learning and enabling the model to learn critical information more conceptually. The proposed method achieves 17.28% and 20.10% for the moderate level of the Car category on the KITTI benchmark test set and validation set, respectively, which outperforms the previous monocular 3D object detection approaches.

Objective: The conventional approach to the analysis of dynamic PET data can be described as a two-stage approach. In Stage 1, each individual's kinetic parameter estimates are obtained by modeling their PET data. Then in Stage 2, those parameter estimates are treated as though they are the observed data and compared across subjects and groups using standard statistical analyses. In this context, we explore the application of nonlinear mixed-effects (NLME) model under the assumptions of simplified reference tissue model. Methods: In the NLME framework, all subject's PET data are modeled simultaneously and the estimation of kinetic parameters and statistical inference across subjects are performed jointly. Results: In simulated [${}^{11}$C]WAY100635 data, this NLME approach shows improved power (6–27% increase) for detecting group differences and greater consistency of population (1.13–1.44 times greater) and individual-level parameter estimation compared to the two-stage approach applying simplified reference tissue model for pharmacokinetic modeling of PET data. We applied our NLME approach to clinical PET data and observed shrinkage of individual-level parameters that is inherent in this modeling structure. Conclusion: The proposed approach is more powerful and accurate than the two-stage approach under the assumptions of simplified reference tissue model in PET data. Significance: The stability of the NLME approach not only improves the efficiency of collected data, but also comes with no additional financial cost and negligible computation cost.

The partial inverse problem for differential pencils on a star-shaped graph is studied from mixed spectral data. More precisely, we show that if the potentials on all edges on the star-shaped graph but one are known a priori then the unknown potential on the remaining edge can be uniquely determined by partial information on the potential and a part of eigenvalues.

Obesity is endemic to many developed countries. Overweight or obesity is associated with an increased risk of developing cancer. Dysfunctional adipose tissue alters cancer cell proliferation and migration; however, whether and how neoplastic epithelial cells communicate with adipose tissue and the underlying mechanism are less clear. BTG3 is a member of the anti-proliferative BTG/Tob family and functions as a tumor suppressor. Here, we demonstrated that BTG3 levels are downregulated in basal cell carcinoma and squamous cell carcinoma compared to normal skin tissue, and Btg3knockout in mice augmented the development of papilloma in a mouse model of DMBA/TPA-induced skin carcinogenesis. Mechanistically, BTG3-knockout keratinocytes promoted adipocyte differentiation mainly through the release of IL1α, IL10, and CCL4, as a result of elevated NF-κB activity. These adipocytes produced CCL20 and FGF7 in a feedback loop to promote keratinocyte migration. Thus, our findings showcased the role of BTG3 in guarding the interplay between keratinocytes and adjacent adipocytes, and identified the underlying neoplastic molecular mediators that may serve as possible targets in the treatment of skin cancer.

In recent years, due to the impact of the COVID-19 pandemic, enterprises have been forced to adapt their operation patterns to ensure resilience, transitioning from traditional office-based work to remote work from home. However, this sudden and unforeseen change has made enterprises unprepared, resulting in a dramatic increase in cybersecurity threats. The most significant challenge arises from the adjustment from working in previously trusted areas to that beyond the boundaries of protection. While employees used to work within the company's defense perimeter, malicious attacks were blocked and detected by boundary security gateways. Shifting to remote work moves employees out of the protective environment, thereby their devices connecting to the internal resources of a company become exploitable targets for threat actors, and weaknesses in the internal authentication, authorization, and access control mechanisms become evident. The zero trust architecture (ZTA) approach is primarily focused on resource protection. When users or services attempt to access resources, ZTA requires precise authentication, minimal authorization, and continuous verification (trust inference) to ensure legitimacy and authorization of the resource usage, eliminating any space for assumed or inherited trust. In this article, we will address the challenges in handling the threats and propose the strategies, implementation, and limitation of ZTA, aiming to shed light on its effectiveness and applicability in mitigating cybersecurity risks.

Seventy-five years ago, visionaries in the field of reliability engineering came together to establish the IEEE Reliability Society, marking the commencement of a remarkable journey toward enhancing the dependability, resilience, and security of technological systems. As we celebrate this significant milestone, it is an opportune moment to reflect on the society's illustrious history, achievements, and the enduring impact it has had on the world of technology.

The convergence of technologies is happening across various aspects, such as communication, computing, medicine, and transportation. The smartphone is a perfect example of convergence, packing features, such as a camera, GPS, artificial intelligence, and Internet connectivity into one sleek device. Autonomous driving is another good example. In a time of rapidly converging technologies, reliability engineering must take into account the potential for cyber threats, the need for cyber trust, the importance of cyber security, and the criticality of cyber resilience. In this way, reliability engineers can ensure the confidentiality, integrity, and availability of computer systems and networks in the face of evolving threats and changing technologies. In this article, we introduce the challenges and current progress of reliability engineering in emerging technologies, including practices and applications of cyber trust and security, AI-empowered autonomous driving systems, modern mobile networks, blockchains and distributed ledger technologies, prognostic and health management, integrated circuit and hardware, and enterprise cybersecurity and threat hunting.

The competition between hackers and defenders is the game of spear and shield in cybersecurity. The field of cybersecurity has been studied for decades, yet it remains a severe and critical topic. One of the main reasons is the fast evolution of hacking techniques. To stay stealthy in the compromised network environment, hackers tend to use system built-in tools and legitimate software to launch the attack by imitating normal activities. These behaviors are seemingly normal but malicious, making it difficult to distinguish them from legitimate activities and leading to a high volume of false alarms raised by detection tools. Countless approaches have been proposed to address these problems. However, conventional evaluation methods for detection approaches have limited capability of handling evolving hacking techniques, thereby hindering the evaluation effectiveness in real-world network environments. The gap between the lab evaluation and real-world practice is significant and should not be overlooked. In this article, the competition between cybersecurity attacks and defenses will be introduced. The current state, approaches, and challenges from both sides will be included to illustrate the gap. Finally, research opportunities for the next era of the game of spear and shield will be proposed.

This article presents a prioritization scheme aimed at assisting enterprises in strengthening their cybersecurity posture by efficiently addressing cyberthreat intelligence and common vulnerabilities and exposures aligned with their specific risk landscape.

The advancement of next-generation fiber-optic transmission requires higher-speed transceivers where cost, footprint and power consumption are of critical consideration. Photonic integration provides an effective solution to reduce the cost and footprint of the transceivers by integrating diverse optoelectronic devices on chips. In particular, complementary metal–oxide–semiconductor (CMOS)-compatible silicon photonics (SiP) has been considered as a promising platform with high integration density and high yield. Since a coherent receiver relies on a local laser based on heterogeneous III-V materials, it is highly desired to eliminate the laser by developing integrated SiP DD receivers. In this paper, by leveraging the polarization diversity technique, we demonstrate the first four-dimensional (I, Q, X, Y) integrated dual-polarization (DP) direct detection (DD) receiver with an automated silicon polarization controller followed by two SiP single-polarization carrier-assisted differential detection (CADD) receivers. A 528-Gb/s polarization-division multiplexing 16-QAM OFDM signal was transmitted over an 80-km single-mode fiber (SMF) link and detected using the integrated SiP DP-CADD receiver, with a bit error ratio below the 24% soft-decision forward error correction threshold. To the best of our knowledge, we achieved a record 426-Gb/s net capacity and 11.83-b/s/Hz net ESE for an integrated DD receiver.

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific SPTLC1variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in SPTLC2c.778G>A [p.Glu260Lys] manifesting with juvenile ALS.MethodsClinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients’ blood and fibroblasts, was performed.ResultsAll patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction studies and electromyography, muscle biopsies and muscle ultrasound studies. Biochemical investigations in plasma and fibroblasts showed elevated levels of ceramides and unrestrained de novo sphingolipid synthesis. Our studies indicate that SPTLC2variant [c.778G>A, p.Glu260Lys] acts distinctly from hereditary sensory and autonomic neuropathy (HSAN)-causing SPTLC2variants by causing excess canonical sphingolipid biosynthesis, similar to the recently reported SPTLC1ALS associated pathogenic variants. Our studies also indicate that serine supplementation, which is a therapeutic in SPTLC1and SPTCL2-associated HSAN, is expected to exacerbate the excess sphingolipid synthesis in serine palmitoyltransferase (SPT)-associated ALS.ConclusionsSPTLC2is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further.

Spinal muscular atrophy (SMA) is a neuromuscular disorder arising from biallelic non-functional survival motor neuron 1(SMN1) genes with variable copies of partially functional SMN2gene. Intrathecal onasemnogene abeparvovec administration, at fixed, low doses, may enable treatment of heavier patients ineligible for weight-based intravenous dosing. STRONG (NCT03381729) assessed the safety/tolerability and efficacy of intrathecal onasemnogene abeparvovec for sitting, nonambulatory SMA patients. Sitting, nonambulatory SMA patients (biallelic SMN1loss, three SMN2copies, aged 6–<60 months) received a single dose of intrathecal onasemnogene abeparvovec. Patients were enrolled sequentially into one of three (low, medium, and high) dose cohorts and stratified into two groups by age at dosing: younger (6–<24 months) and older (24–<60 months). Primary endpoints included safety/tolerability, independent standing ≥3 seconds (younger group), and change in Hammersmith Functional Motor Scale Expanded (HFMSE) from baseline (older group) compared with historic controls. Thirty-two patients were enrolled and completed the study (medium dose, n = 25). All patients had one or more treatment-emergent adverse events, with one serious and related to treatment (transaminase elevations). No deaths were reported. One of 13 patients (7.7%) in the younger group treated with the medium dose achieved independent standing. At Month 12 for the older group receiving the medium dose, change from baseline in HFMSE was significantly improved compared with the SMA historic control population (P < 0.01). Intrathecal onasemnogene abeparvovec was safe and well-tolerated. Older patients treated with the medium dose demonstrated increases in HFMSE score greater than commonly observed in natural history.

The peak age-of-information (AoI) performance in irregular repetition slotted ALOHA (IRSA) is revisited in this paper with a particular focus on heterogeneous networks, where types of users may have different numbers of users, active probabilities, and sensitivities to AoI. A distributed scheduling framework that is both conceptually and practically simple is proposed. A series of analyses and approximations are conducted, which lead to a closed-form approximation of the best scheduling policy within the proposed framework. Extensive simulations are provided to confirm that in spite of being extremely low complex, the proposed policy can significantly reduce the weighted average peak AoI, especially for heavily overloaded scenarios.

In today's digital environment, nearly every industry faces challenges concerning reliability, security, and trust. Ensuring that systems persist in operation despite hacker threats and that enterprises can effectively safeguard their assets are paramount concerns.

Thermosets present sustainability challenges that could potentially be addressed through the design of deconstructable variants with tunable properties; however, the combinatorial space of possible thermoset molecular building blocks (e.g., monomers, cross-linkers, and additives) and manufacturing conditions is vast, and predictive knowledge for how combinations of these molecular components translate to bulk thermoset properties is lacking. Data science could overcome these problems, but computational methods are difficult to apply to multicomponent, amorphous, statistical copolymer materials for which little data exist. Here, leveraging a data set with 101 examples, we introduce a closed-loop experimental, machine learning (ML), and virtual screening strategy to enable predictions of the glass transition temperature (Tg) of polydicyclopentadiene (pDCPD) thermosets containing cleavable bifunctional silyl ether (BSE) comonomers and/or cross-linkers with varied compositions and loadings. Molecular features and formulation variables are used as model inputs, and uncertainty is quantified through model ensembling, which together with heavy regularization helps to avoid overfitting and ultimately achieves predictions within <15 °C for thermosets with compositionally diverse BSEs. This work offers a path to predicting the properties of thermosets based on their molecular building blocks, which may accelerate the discovery of promising plastics, rubbers, and composites with improved functionality and controlled deconstructability.

Complex-valued double-sideband (CV-DSB) direct detection (DD) is a promising solution for high capacity and cost-sensitive data center interconnects, since it can reconstruct the optical field as a homodyne coherent receiver while does not require a costly local oscillator laser. In a carrier-assisted CV-DSB DD system, the carrier occupies a large proportion of the total optical signal power but bears no information. Reducing the carrier to signal power ratio (CSPR) can improve the information-bearing signal power and thus maximize the achievable system performance. Recently, we have proposed and demonstrated a deep-learning-enabled DD (DLEDD) scheme to reconstruct the full-field of the CV-DSB signal. In the DLEDD scheme, the optical CV-DSB signal was detected by a dispersion-diversity receiver and then recovered by a deep convolutional neural network (CNN). Nevertheless, the computational complexity of the deep CNN is the main obstacle to the application of the DLEDD scheme. In this paper, we demonstrate a 50-GBaud CV-DSB 32-ary quadrature amplitude modulation (32-QAM) signal transmission over 80-km single-mode fiber with ∼64% computational-budget reduction in the field reconstruction. This is achieved by using 1×1 convolutions to attain a sparse dimensionality (in particular the number of channels) of the deep CNN. To the best of our knowledge, we achieve the highest electrical spectral efficiency of 7.07 b/s/Hz per polarization per wavelength for a CV-DSB DD receiver without requiring a sharp-roll-off optical filter.

This paper is focused on the pulse-and-glide (PnG) control for a parallel hybrid electric vehicle (HEV) in car-following. PnG is an eco-driving technique that alternately turns on and off the engine to save fuel. For HEVs, the ride comfort concerns by PnG in conventional vehicles can be alleviated by oscillating the battery state of charge (SOC), instead of the vehicle speed. However, due to the ohmic losses during the battery charging and discharging process, the fuel saving potential is much reduced. In order to reach a balance between ride comfort and fuel economy, a control method is proposed to utilize both the vehicle body and the battery as the energy buffers simultaneously in the PnG operation. In particular, two minimum-time control problems, one for the pulsing phase and another for the gliding phase, are formulated and implemented as model predictive control (MPC). With the applications of a series of approximations and sparsity optimization techniques, these two control problems become quadratic programming (QP) problems after the application of the pseudo-spectral (PS) method. The online implementability is thus ensured. Numerical simulations using naturalistic driving data show on average 17.1% and 5.1% improvements of fuel economy for local and highway speeds, respectively. It is shown that the proposed method is able to improve the fuel economy while maintaining both ride comfort and SOC sustenance.

IMPORTANCE: The ability to provide invasive mechanical ventilation (IMV) is a mainstay of modern intensive care; however, whether rates of IMV vary among countries is unclear. OBJECTIVE: To estimate the per capita rates of IMV in adults across 3 high-income countries with large variation in per capita intensive care unit (ICU) bed availability. DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined 2018 data of patients aged 20 years or older who received IMV in England, Canada, and the US. EXPOSURE: The country in which IMV was received. MAIN OUTCOMES AND MEASURES: The main outcome was the age-standardized rate of IMV and ICU admissions in each country. Rates were stratified by age, specific diagnoses (acute myocardial infarction, pulmonary embolus, upper gastrointestinal bleed), and comorbidities (dementia, dialysis dependence). Data analyses were conducted between January 1, 2021, and December 1, 2022. RESULTS: The study included 59 873 hospital admissions with IMV in England (median [IQR] patient age, 61 [47-72] years; 59% men, 41% women), 70 250 in Canada (median [IQR] patient age, 65 [54-74] years; 64% men, 36% women), and 1 614 768 in the US (median [IQR] patient age, 65 [54-74] years; 57% men, 43% women). The age-standardized rate per 100 000 population of IMV was the lowest in England (131; 95% CI, 130-132) compared with Canada (290; 95% CI, 288-292) and the US (614; 95% CI, 614-615). Stratified by age, per capita rates of IMV were more similar across countries among younger patients and diverged markedly in older patients. Among patients aged 80 years or older, the crude rate of IMV per 100 000 population was highest in the US (1788; 95% CI, 1781-1796) compared with Canada (694; 95% CI, 679-709) and England (209; 95% CI, 203-214). Concerning measured comorbidities, 6.3% of admitted patients who received IMV in the US had a diagnosis of dementia (vs 1.4% in England and 1.3% in Canada). Similarly, 5.6% of admitted patients in the US were dependent on dialysis prior to receiving IMV (vs 1.3% in England and 0.3% in Canada). CONCLUSIONS AND RELEVANCE: This cohort study found that patients in the US received IMV at a rate 4 times higher than in England and twice that in Canada in 2018. The greatest divergence was in the use of IMV among older adults, and patient characteristics among those who received IMV varied markedly. The differences in overall use of IMV among these countries highlight the need to better understand patient-, clinician-, and systems-level choices associated with the varied use of a limited and expensive resource.

MB-102 is a novel fluorescent tracer agent that is exclusively removed from the body by glomerular filtration. This agent can be detected transdermally to provide a real-time measurement of glomerular filtration rate at the point-of-care and is currently in clinical studies for such. MB-102 clearance during continuous renal replacement therapy (CRRT) is unknown. Its plasma protein binding (~0%), molecular weight (~372 Da) and volume of distribution (15–20 L) suggest that it may be removed by renal replacement therapies. To determine the disposition of MB-102 during CRRT, an in vitrostudy assessing the transmembrane clearance (CLTM) and adsorptive clearance of MB-102 was conducted. A validated in vitrobovine blood continuous hemofiltration (HF) and continuous hemodialysis (HD) models were performed using two types of hemodiafilters to evaluate CLTMof MB-102. For HF, three different ultrafiltration rates were evaluated. For HD, four different dialysate flow rates were evaluated. Urea was used as a control. No MB-102 adsorption to the CRRT apparatus or either of hemodiafilters was observed. MB-102 is readily removed by HF and HD. Dialysate and ultrafiltrate flow rates directly influence MB-102 CLTM. Hence MB-102 CLTM should be measurable for critically ill patients receiving CRRT.

Critically ill patients undergoing continuous renal replacement therapy (CRRT) have medical conditions requiring extensive pharmacotherapy. Continuous renal replacement therapy impacts drug disposition. Few data exist regarding drug dosing requirements with contemporary CRRT modalities and effluent rates. The practical limitations of pharmacokinetic studies requiring numerous plasma and effluent samples, and lack of generalizability of observations from specific CRRT prescriptions, highlight gaps in bedside assessment of CRRT drug elimination and individualized dosing needs. We employed a porcine model using transdermal fluorescence detection of the glomerular filtration rate fluorescent tracer agent MB-102, with the aim to assess the relationship between systemic exposure of MB-102 and meropenem during CRRT. Animals underwent bilateral nephrectomies and received intravenous bolus doses of MB-102 and meropenem. Once MB-102 equilibrated in the animal, CRRT was initiated. Continuous renal replacement therapy prescriptions comprised four combinations of blood pump (low versushigh) and effluent (low versushigh) flow rates. Changes in transdermal detected MB-102 clearance occurred immediately with a change in CRRT rates. Blood side meropenem clearance mirrored transdermal MB-102 clearance (r2: 0.95–0.97, pvalue all <0.001). We suggest transdermal MB-102 clearance provides real-time personalized assessment of drug elimination and could optimize prescription of drugs for critically ill patients requiring CRRT.