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Abstract Enhancing efficiency and productivity in countries’ healthcare systems is a global challenge. The Chinese government invested huge resources to improve the efficiency and productivity of the healthcare system across the country. To assess the success of the mission above, this research utilized DEA-SBM Meta frontier analysis alongside the Malmquist Productivity Index. These methodologies were employed to gauge Efficiency, production technology heterogeneity, and productivity of healthcare systems change across 31 mainland Chinese provinces and four distinct geographical regions throughout the study period spanning from 1997 to 2022. Results revealed that the mean efficiency score of China’s healthcare system is 0.7672. It indicates a growth potential of 23.28 percent in the operational efficiency of healthcare systems. The eastern region’s efficiency level (0.86917) is higher among all four regions. Zhejiang, Shandong, and Guangdong are the top three healthcare-efficiency performers. The technology gap ratio indicates that eastern regions witnessed a high TGR (0.9909), showing the country’s attainment of superior healthcare technologies. Beijing, Guangdong, Shanghai, Tianjin, and Zhejiang witnessed higher TGR values among all 31 mainland Chinese provinces. The total factor productivity index of the healthcare system witnessed a slight growth of 0.33%, with an average MI score of 1.0033. Efficiency change (EC) was found to be the main determinant of TFPC as technology change TC is less than EC. Moreover, the MI score of the Western region (1.033) is higher than the corresponding Eastern, northeastern, and central regions. Guizhou, Anhui, and Yunnan were found to be the top three performers in TFPC growth. Finally, the Kruskal–Wallis test confirmed the statistically significant difference among 4 Chinese regions for the healthcare system’s efficiency, TFPC, and TGR.

Abstract Background The soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) is considered a biomarker of microglia activity. The objective of this study was to investigate the trajectory of CSF sTREM2 levels over time and examine its association with sex. Methods A total of 1,017 participants from the Alzheimer’s Disease Neuroimaging Initiative Study (ADNI) with at least one CSF sTREM2 record were included. The trajectory of CSF sTREM2 was analyzed using a growth curve model. The association between CSF sTREM2 levels and sex was assessed using linear mixed-effect models. Results CSF sTREM2 levels were increased with age over time (P

Abstract This study investigates the longitudinal dynamic changes in immune cells in COVID-19 patients over an extended period after recovery, as well as the interplay between immune cells and antibodies. Leveraging single-cell mass spectrometry, we selected six COVID-19 patients and four healthy controls, dissecting the evolving landscape within six months post-viral RNA clearance, alongside the levels of anti-spike protein antibodies. The T cell immunophenotype ascertained via single-cell mass spectrometry underwent validation through flow cytometry in 37 samples. Our findings illuminate that CD8 + T cells, gamma-delta (gd) T cells, and NK cells witnessed an increase, in contrast to the reduction observed in monocytes, B cells, and double-negative T (DNT) cells over time. The proportion of monocytes remained significantly elevated in COVID-19 patients compared to controls even after six-month. Subpopulation-wise, an upsurge manifested within various T effector memory subsets, CD45RA + T effector memory, gdT, and NK cells, whereas declines marked the populations of DNT, naive and memory B cells, and classical as well as non-classical monocytes. Noteworthy associations surfaced between DNT, gdT, CD4 + T, NK cells, and the anti-S antibody titer. This study reveals the changes in peripheral blood mononuclear cells of COVID-19 patients within 6 months after viral RNA clearance and sheds light on the interactions between immune cells and antibodies. The findings from this research contribute to a better understanding of immune transformations during the recovery from COVID-19 and offer guidance for protective measures against reinfection in the context of viral variants.

Abstract Background Inappropriate eating behaviors, particularly a lack of food diversity and poor diet quality, have a significant impact on the prognosis of certain chronic conditions and exacerbate these conditions in the community-dwelling elderly population. Current dietary interventions for the elderly have not adequately considered the nutritional needs associated with multiple chronic conditions and personal dietary preferences of elderly individuals. A personalized recommendation system has been recognized as a promising approach to address this gap. However, its effectiveness as a component of an elderly-targeted dietary intervention in real-world settings remains unknown. Additionally, it is unclear whether this intervention approach will be user-friendly for the elderly. Therefore, this study aims to examine the effectiveness of a personalized meal recommendation system designed to improve dietary behavior in community-dwelling elders. The implementation process in terms of System usability and satisfaction will also be assessed. Methods The trial has been designed as a 6-month, non-blinded, parallel two-arm trial. One hundred fifty community-dwelling elders who meet the eligibility criteria will be enrolled. Subjects will be allocated to either the intervention group, receiving personalized meal recommendations and access to corresponding food provided as one component of the intervention, as well as health education on elder nutrition topics, or the control group, which will receive nutritional health education lectures. Outcomes will be measured at three time points: baseline at 0 months, 3 months, and 6 months. The primary outcomes will include dietary diversity (DDS) and diet quality (CDGI-E) of enrolled community-dwelling elders, representing their dietary behavior improvement, along with dietary behavior adherence to recommended meals. Secondary outcomes will measure the perceived acceptability and usability of the personalized meal recommendation system for the intervention group. Exploratory outcomes will include changes in the nutritional status and anthropometric measurements of the community-dwelling elders. Discussion This study aims to examine the effectiveness, acceptability, and usability of a personalized meal recommendation system as a data-driven dietary intervention to benefit community-dwelling elders. The successful implementation will inform the future development and integration of digital health strategies in daily nutrition support for the elderly. Trial registration Chinese Clinical Trial Registry ChiCTR2300074912. Registered on August 20, 2023, https://www.chictr.org.cn/showproj.html?proj=127583

Abstract With the development of distributed power sources in the distribution network, the algorithm of distribution network reconfiguration is gaining attention from experts and scholars. Its goal is to reduce the power loss during power transmission, so as to reduce the power grid loss during power transmission. And weaken the electric heating effect in the process of electric energy transmission, thus maintaining the safety of the surrounding residents. Due to the wire impedance effect, a lot of electric energy of the circuit is lost to electric heating, which is easy to cause local overheating and lead to fire. This will not only cause power loss, but also endanger the safety of surrounding residents. To address the issue, experiments on distribution grid reconstruction are performed using the enhanced particle swarm-fish swarm algorithm with the Elecgrid self-constructed dataset. Initially, low-voltage distributed power sources in parallel are connected to the circuit, thereby decreasing internal resistance and electrical heat. Then, by controlling the circuit in the system, the double separation relay adjusts the inductance and capacitance of the conductor, thus reducing the reactance length. Additionally, particle swarm particles are mutated to enable them to jump out of the local optimum, and elite fish approach is used to expand the search area. Finally, the proposed fusion algorithm is applied to the self-built data set of Elecgrid and compared with the other three algorithms. The fusion algorithm serves as the standard test system for this comparison. The active power loss of the hybrid algorithm is 63 kW at an operating voltage of 0.74 V. The loss work of the other three algorithms is 74 kW, 97 kW and 109 kW respectively. The mixed algorithm has the lowest loss among the four algorithms. The experiments are repeated for six times, and the linear fitting degrees of the four algorithms are 0.9804, 0.9527, 0.9612 and 0.9503, respectively. The experimental results show that the application of this algorithm can effectively reduce the active loss in the process of distribution network reconfiguration, thus reducing energy consumption; At the same time, it can reduce the electric heating in the process of electric energy transmission, and then prevent the occurrence of fire. There are three main contributions of this study. Firstly, the resistance in the transmission path is reduced by using this algorithm, so that the power transmission efficiency can be analyzed more accurately. Secondly, the new algorithm enriches the power safety maintenance method; Finally, the fire caused by local overheating of the line is reduced by fusion algorithm.

Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disease prominently characterized by slowly progressive lower limb weakness and spasticity. The significant genotypic and phenotypic heterogeneity of this disease makes its accurate diagnosis challenging. In this study, we identified the NM_001168272: c.2714A > G (chr3.hg19: g.4716912A > G, N905S) variant in the ITPR1 gene in a three-generation Chinese family with multiple individuals affected by HSP, which we believed to be associated with HSP pathogenesis. To confirm, we performed whole exome sequencing, copy number variant assays, dynamic mutation analysis of the entire family, and protein structure prediction. The variant identified in this study was in the coupling domain, and this is the first corroborated report assigning ITPR1 variants to HSP. These findings expand the clinical and genetic spectrum of HSP and provide important data for its genetic analysis and diagnosis.

Cancer is one of the top 10 fatal diseases worldwide, among which advanced metastatic carcinoma has the highest mortality rate. Sunitinib and immune checkpoint blockers are commonly used to treat metastatic renal carcinoma with limited efficacy. Therefore, there is an urgent need to develop novel targeted therapies for metastatic renal cancer. In this study, we designed an antibody fusion protein, 57103, that simultaneously targeted the cluster of differentiation 24 (CD24), interleukin 4 receptor (IL-4R), and integrin receptors αvβ3 and α5β1. In vitro assays showed that 57103 significantly suppressed the proliferation, migration, invasion, colony formation, and adhesion abilities of renal cancer cells, resulting in a comprehensive and significant antitumor effect. Furthermore, 57103 inhibited angiogenesis, promoted THP1-derived M0-type macrophage phagocytosis, and enhanced the antibody-dependent cellular cytotoxicity of peripheral blood mononuclear and NK92MI-CD16a cells. In vivo experiments revealed significant inhibition of tumor growth in ACHN cell xenograft nude mice and an MC38-hCD24 tumor-bearing mouse model. Immunohistochemical analysis showed that 57103 decreased the proliferation and induced the apoptosis of renal cancer cells, while inhibiting angiogenesis. The MC38-hPDL1 and MC38-hCD24-hPDL1 tumor-bearing mouse models further offer the possibility of combining 57103 with the PDL1 antagonist atezolizumab. In conclusion, 57103 is a potential candidate drug for the treatment of metastatic renal carcinoma or PDL1-overexpressing cancer.

To grasp the hydraulic performance and abrasion characteristics of a particular model pump before manufacture, this paper firstly numerically calculates the three-dimensional viscous steady incompressible flow of a solid-liquid two-phase flow centrifugal pump with specific speed n $_{\mathrm {s}}=93$ based on the Mixture model and obtains the influences of the three typical particle attributes (particle diameter, solid-phase concentration, and solid-phase density) on the hydraulic performance of the calculation model pump. Subsequently, numerical prediction of the abrasion of major overflow parts due to particle collision impacts was carried out based on the DPM model. The results show that the solid-phase concentration has the most significant effect on the hydraulic performance of solid-liquid two-phase flow pumps, and the diameter of solid-phase particles has the most minor effect. With the increase of particle diameter and solid-phase concentration, head and efficiency are gradually reduced. In contrast, with the increase of solid-phase density, head and efficiency show a trend of increasing and decreasing. The most severe decrease in hydraulic performance occurs at a Cv of 30%, where the head decreases to 20.19m, and the efficiency decreases to 66.90%. With the increase of the three typical solid-phase properties, the abrasion in the overflow inner wall surface of the solid-liquid two-phase flow centrifugal pump shows different degrees of deterioration, and the maximum degree of wear of about 0.0010kg/m2s.

Abstract Premature ovarian failure (POF) is a leading cause of women’s infertility without effective treatment. The purpose of this study was to investigate the protective effects of Luffa cylindrica fermentation liquid (LF) on cyclophosphamide (CTX) -induced POF in mice and to preliminarily investigate the underlying mechanisms. Thirty-two Balb/c mice were divided into four groups randomly. One group served as the control, while the other three received CTX injections to establish POF models. A 14-day gavage of either 5 or 10 μL/g LF was administered to two LF pretreatment groups. To analyze the effects of LF, the ovarian index, follicle number, the levels of serum sex hormones, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), inflammatory factors, and apoptosis of the ovarian cells were measured. The effects of LF pretreatment on the expression of TLR4/NF-κB and apoptosis pathways were also evaluated. We found that LF pretreatment increased the ovarian index and the number of primordial and antral follicles while decreasing those of atretic follicles. LF pretreatment also increased the serum levels of estradiol (E2) and anti-Müllerian hormone (AMH), while decreasing those of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Furthermore, LF pretreatment increased the levels of SOD and GSH in the ovaries, while decreasing those of MDA, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). LF administration reduced the amount of TUNEL+ ovarian cells and the levels of TLR4 and NF-κB P65 protein expression. In conclusion, LF has antioxidant, anti-inflammatory as well as anti-apoptotic effects against CTX-induced POF, and the inhibition of TLR4/NF-κB and apoptosis pathways may be involved in its mechanisms. Graphical Abstract

BackgroundChina’s older population is facing serious health challenges, including malnutrition and multiple chronic conditions. There is a critical need for tailored food recommendation systems. Knowledge graph–based food recommendations offer considerable promise in delivering personalized nutritional support. However, the integration of disease-based nutritional principles and preference-related requirements needs to be optimized in current recommendation processes. ObjectiveThis study aims to develop a knowledge graph–based personalized meal recommendation system for community-dwelling older adults and to conduct preliminary effectiveness testing. MethodsWe developed ElCombo, a personalized meal recommendation system driven by user profiles and food knowledge graphs. User profiles were established from a survey of 96 community-dwelling older adults. Food knowledge graphs were supported by data from websites of Chinese cuisine recipes and eating history, consisting of 5 entity classes: dishes, ingredients, category of ingredients, nutrients, and diseases, along with their attributes and interrelations. A personalized meal recommendation algorithm was then developed to synthesize this information to generate packaged meals as outputs, considering disease-related nutritional constraints and personal dietary preferences. Furthermore, a validation study using a real-world data set collected from 96 community-dwelling older adults was conducted to assess ElCombo’s effectiveness in modifying their dietary habits over a 1-month intervention, using simulated data for impact analysis. ResultsOur recommendation system, ElCombo, was evaluated by comparing the dietary diversity and diet quality of its recommended meals with those of the autonomous choices of 96 eligible community-dwelling older adults. Participants were grouped based on whether they had a recorded eating history, with 34 (35%) having and 62 (65%) lacking such data. Simulation experiments based on retrospective data over a 30-day evaluation revealed that ElCombo’s meal recommendations consistently had significantly higher diet quality and dietary diversity compared to the older adults’ own selections (P

The stability of the surrounding rock in the inclined coal seam stope is crucial for the safety of the gob-side entry. In this article, we systematically analyze the surrounding rock stability of the gob-side entry formed by roof-cutting (GEFR) in an inclined coal seam. We identify three forms of roof structure evolution in the formation process of GEFR and analyze the two main modules affecting the deformation of the surrounding rock structure. We determine the critical elements of surrounding rock deformation in different stages of the GEFR retaining process. Further, we propose a classification of the deformation of the surrounding rock structure of GEFR into stress and structural types during stabilization. We analyze the length of the gangue side's bearing area and calculate the lateral gangue's impact energy. We establish three instability modes of the roof based on the fractured state of the roof structure of the GEFR and provide a mechanical criterion of instability. Finally, based on the results of our theoretical analysis, we propose a control principle for the surrounding rock deformation of GEFR and establish countermeasures for controlling the roof-cutting angle and an asymmetric coupling support system. A field case study was conducted under conditions involving an inclined thick coal seam to investigate the surrounding rock deformation and overburden stress evolution using field monitoring data. The field test results confirm that the control measures of the control roof-cutting angle and the asymmetric coupling support system positively impact the stability of the surrounding rock of the roof-cutting entry in an inclined coal seam.

In this work, a cost-effective organic package substrate embedded coupled magnetic core inductor technology is proposed and demonstrated for power supply in package applications. Based on a novel lithographic via process, it involves a solid copper pillar electroplating step for creating a groove and integration of the vertical interconnects of the inductor. The primary and secondary windings of the coupled inductor are interleaved on the rectangular magnetic composite core which is accommodated within the groove. The coupled inductor combines solid vertical interconnecting with low loss magnetic composite core, therefore bringing together tight process tolerances and superior current capability. Experimental results show that the 2.9-mm2 coupled inductor achieves a high inductance to resistance ratio of 0.28 nH/mΩ, and a coupling factor of 0.57. In addition, the proposed inductor achieves an ultra-high saturation current of 16.52 A that is the highest reported value for a high-frequency integrated magnetic core inductor to the best of our knowledge. The performance of the coupled inductor has been calculated for a standard 1.8 to 1 V interleaved converter. Notably, it demonstrated a remarkable efficiency exceeding 95% across a wide range of phase currents between 0.11 and 2.32 A.

Abstract This work aims to explore the long‐term prognosis of hepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF). In this prospective study, eligible inpatients with HBV‐ACLF are enrolled and followed up from December 2012 to February 2023, for clinical events, laboratory tests at least every 6 months. Overall, the survival rates at 28 days, 90 days, 1 year, 5 years, and 8 years are 64.7%, 48.8%, 46.1%, 43.8%, and 42.2%, respectively. Among the 8‐year mortality and liver transplant cases, ACLF survivors (who survived over 90 days) accounted for 7.8% (9/115). Among 101 patients who survived for more than 90 days, 97.9% of patients achieve virologic response at 1 year. For HBeAg‐positive patients, the HBeAg seroconversion are 25.5%, 63.6%, and 76.9% at 1, 5, and 8 years, respectively. Alanine aminotransferase, aspartate aminotransferase, total bilirubin, INR, white blood cell count, and albumin levels gradually improve within the first year. Fibrosis biomarkers APRI, FIB‐4 and Chitinase‐3‐like protein 1 (CHI3L1) levels decreases within the first 5 years. The Cox proportional hazards regression reveal that high total bilirubin (HR = 1.008, p = 0.021) is the independent risk factor for 8‐year survival of ALCF survivors. The 90‐day period following of HBV‐ACLF represented a critical juncture for long‐term prognosis, revealing favorable outcomes beyond this timeframe.

As the manufacturing industry is the foundation of the national economy, many countries have made concerted efforts to promote the transition upgrading of manufacturing enterprises from political, industrial, and academic circles. This study employed content analysis to explore the transition upgrading factors for manufacturing enterprises from an energy source perspective. With the help of FsQCA (Fuzzy-sets qualitative comparative analysis), which can mine multivariate combination relationships using a small number of samples, this study quantitatively calculated the transition paths and energy source combinations of manufacturing enterprises. Three transition upgrading paths were proposed, including an innovation-oriented path, a business-oriented path, and an efficiency-oriented path. The results indicate that manufacturing enterprises can realize transition upgrading based on three key methods, including innovation resources and innovation activities, strategic layout, and production operation + network relationship (peripheral). Such a finding validated the rationality of the theoretical path design and improved the research depth and precision. Multiple case analyses of Huawei, Haier, and Lenovo reveal that manufacturing enterprises used three ways to promote transition upgrading: the joint action of innovation activities and innovation resources; the uni-directional causal effect of strategic layout adjustment to increase market value; and the coordination and matching role of network relations dominated by production and operation. We conclude that this study provides an effective decision-making basis and management reference for manufacturing enterprises, so that enterprises can choose an appropriate energy accumulation method and scientifically realize the transition upgrading.

In recent years, the concept of despotic leadership has garnered considerable attention in sports. Despotic leadership significantly reflecting leaders' deviant behavior has today heightened the risk of health hazards in the workplace. In addition, the perceived organizational politics have also yielded a deleterious result on employees’ well-being. In the dynamic landscape of healthcare, understanding the implications of organizational behavior on well-being is paramount for risk management. This study elucidates the relationships between despotic leadership, perceived organizational politics, workplace incivility, emotional exhaustion, person-organization unfit, and health harm, which can pose significant risks in a healthcare setting. The quantitative study was conducted using an empirical survey with respondents representing sports organizations. A Partial Least Squares Structural Equation Model (PLS-SEM) was used to analyze data from 429 participants using Smart PLS. The study findings suggest that despotic leadership and perceived organizational politics can lead to increased risks, manifested as workplace incivility, emotional exhaustion, and person-organization unfit. These organizational risks subsequently translate to tangible health harm for employees. Mediation analyses revealed that workplace incivility, emotional exhaustion, and person-organization unfit mediate the detrimental health outcomes rooted in leadership and organizational politics. The study underscores the urgent need for risk management strategies to foster a healthier organizational culture and leadership approach in healthcare settings. This will ensure enhanced employee well-being and a reduction in associated health risks, thus aligning with best practices in healthcare policy.

BackgroundVentricular tachycardia (VT) diagnosis is challenging due to the similarity between VT and some forms of supraventricular tachycardia, complexity of clinical manifestations, heterogeneity of underlying diseases, and potential for life-threatening hemodynamic instability. Clinical decision support systems (CDSSs) have emerged as promising tools to augment the diagnostic capabilities of cardiologists. However, a requirements analysis is acknowledged to be vital for the success of a CDSS, especially for complex clinical tasks such as VT diagnosis. ObjectiveThe aims of this study were to analyze the requirements for a VT diagnosis CDSS within the frameworks of knowledge and practice and to determine the clinical decision support (CDS) needs. MethodsOur multidisciplinary team first conducted semistructured interviews with seven cardiologists related to the clinical challenges of VT and expected decision support. A questionnaire was designed by the multidisciplinary team based on the results of interviews. The questionnaire was divided into four sections: demographic information, knowledge assessment, practice assessment, and CDS needs. The practice section consisted of two simulated cases for a total score of 10 marks. Online questionnaires were disseminated to registered cardiologists across China from December 2022 to February 2023. The scores for the practice section were summarized as continuous variables, using the mean, median, and range. The knowledge and CDS needs sections were assessed using a 4-point Likert scale without a neutral option. Kruskal-Wallis tests were performed to investigate the relationship between scores and practice years or specialty. ResultsOf the 687 cardiologists who completed the questionnaire, 567 responses were eligible for further analysis. The results of the knowledge assessment showed that 383 cardiologists (68%) lacked knowledge in diagnostic evaluation. The overall average score of the practice assessment was 6.11 (SD 0.55); the etiological diagnosis section had the highest overall scores (mean 6.74, SD 1.75), whereas the diagnostic evaluation section had the lowest scores (mean 5.78, SD 1.19). A majority of cardiologists (344/567, 60.7%) reported the need for a CDSS. There was a significant difference in practice competency scores between general cardiologists and arrhythmia specialists (P=.02). ConclusionsThere was a notable deficiency in the knowledge and practice of VT among Chinese cardiologists. Specific knowledge and practice support requirements were identified, which provide a foundation for further development and optimization of a CDSS. Moreover, it is important to consider clinicians’ specialization levels and years of practice for effective and personalized support.

Objectives: Methylmalonic acidemia (MMA) is a rare inborn genetic disorder that is characterized by increased levels of methylmalonic acid in blood plasma and urine. Isolated methylmalonic acidemia is one of the most common types of MMA and is caused by mutations in the gene encoding methyl-malonyl coenzyme A mutase (MMUT). In this study, we investigated the possible mechanisms underlying the symptoms of isolated MMA in a patient by molecular analysis. Methods: PCR amplification and Sanger sequencing analysis was performed to identify variants in the MMUT gene in the proband and his family. Furthermore, minigene constructs were generated to validate the splicing defects in the MMUT gene variant identified in the proband. Results: The 3-year-old patient was admitted to the hospital with symptoms of MMA, including fever, convulsions, and vomiting. He showed metabolic acidosis, high levels of methylmalonic acid in blood and urine, and normal blood homocysteine levels. Genetic analysis demonstrated that the patient was a compound heterozygous carrier of two variants in the MMUT gene: a missense c.278G > A variant that has already been reported in a patient with the severe mut⁰ phenotype; and a novel splice site variant c.2125-2A > G. RT-PCR analysis showed that, while the novel variant clearly alters splicing, a minor amount of a full-length transcript is generated, suggesting that a wild-type protein may be produced although at a lower quantitative level. The patient's condition improved after treatment with vitamin B12. Serious complications were not reported during follow-up at age 5. Conclusions: We identified a novel splice site variant that partially disrupts normal splicing of the MMUT pre-mRNA. Production of a reduced amount of full-length transcript is responsible for the mild clinical phenotype observed in this patient. Functional studies have proven useful in exploring the genotype‐phenotype association and in providing guidance for the genetic diagnosis of MMA.

Despite China's heavy investment in sports infrastructure development in the last decades, the financial resources utilization efficiency (FRUE), regional technological gap (TGR), and total factor productivity change (TFPC) in sports infrastructure development are undiscovered and worth investigating. To this end, this study employed DEA-SBM, Meta-frontier analysis, and Malmquist productivity index on the data set of 31 Chinese provinces and 3 regions for the years 2014–2021 to gauge the FRUE, TGR, and TFPC in sports infrastructure development. The results indicate that the average FRUE is 0.4859, with a growth potential of 51.41% in financial resource utilization efficiency for sports infrastructure development. Further Eastern region is more efficient as compared to the Central and western regions. Beijing, Shanghai, Tibet, Hainan, and Guangdong are top performers in FRUE. Further, the value of TGR in the East is 0.9787 which is higher than in Central (0.4977), and Western (0.5821) regions. It indicates that the eastern region contains superior production technology in the development of the sports infrastructure in China. Moreover, the average TFPC value is 1.035 witnessed a 3.5% growth, primarily determined by technological change (TC). As TC = 1.0273 is higher than efficiency change EC = 0.997. The eastern region has a higher average TFPC of 1.048, indicating higher total factor productivity growth in sports infrastructure development. Beijing, Liaoning, Tianjin, Shanghai, and Zhejiang are the top performers in the TFP growth over the study period. Finally, the Kruskal-Wallis test proved the statistically significant difference in three regions of China for FRUE, TGR, and TFPC in sports infrastructure development.

Abstract Objectives Abdominal palpation is an essential examination to diagnose various digestive system diseases. This study aimed to develop an objective and standardized test based on abdominal palpation simulators, and establish a credible pass/fail standard of basic competency. Methods Two tests were designed using the newly developed Jucheng abdominal palpation simulator (test 1) and the AbSim simulator (test 2), respectively. Validity evidence for both tests was gathered according to Messick’s contemporary framework by using experts to define test content and then administering the tests in a highly standardized way to participants of different experience. Different simulator setups modified by the built-in software were selected from hepatomegaly, splenomegaly, positive McBurney’s sign plus rebound tenderness, gallbladder tenderness (Murphy’s sign), pancreas tenderness, and a normal setup without pathologies, with six sets used in test 1 and five sets used in test 2. Different novices and experienced were included in the tests, and test 1 was also administered to an intermediate group. Scores and test time were collected and analyzed statistically. Results The internal consistency reliability of test 1 and test 2 showed low Cronbach’s alphas of 0.35 and -0.41, respectively. Cronbach’s alpha for palpation time across cases were 0.65 for test 1 and 0.76 for test 2. There was no statistical difference in total time spent and total scores among the three groups in test 1 (P-values (ANOVA) were 0.53 and 0.35 respectively), nor between novices and experienced groups in test 2 (P-values (t-test) were 0.13 and 1.0 respectively). It was not relevant to try to establish pass/fail standards due to the low reliability and lack of discriminatory ability of the tests. Conclusions It was not possible to measure abdominal palpation skills in a valid way using either of the two standardized, simulation-based tests in our study. Assessment of the patient’s abdomen using palpation is a challenging clinical skill that is difficult to simulate as it highly relies on tactile sensations and adequate responsiveness from the patients.

IntroductionIn the Dongting water system, the Carassius auratus (Crucian carp) complex is characterized by the coexistence of diploid forms (2n=100, 2nCC) and polyploidy forms. The diploid (2nCC) and triploid C.auratus (3n=150, 3nCC) had the same fertility levels, reaching sexual maturity at one year. MethodsThe nucleotide sequence, gene expression, methylation, and immunofluorescence of the gonadotropin releasing hormone 2(Gnrh2), Gonadotropin hormone beta(Gthβ), and Gonadotropin-releasing hormone receptor(Gthr) genes pivotal genes of the hypothalamic-pituitary-gonadal (HPG) axis were analyzed. ResultsThe analysis results indicated that Gnrh2, follicle-stimulating hormone receptor(Fshr), and Lethal hybrid rescue(Lhr) genes increased the copy number and distinct structural differentiation in 3nCC compared to that in 2nCC. The transcript levels of HPG axis genes in 3nCC were higher than 2nCC (P

In the context of innovative enterprises in China, the significance of sleep quality for employees' physical and mental well-being cannot be understated. This study explores the complex relationship between Mindfulness and sleep quality and examines the potential interaction between Social Interaction Anxiety and prolonged sleep behavior. To this end, a thorough evaluation involving the administration of the Mindfulness scale, Social Interaction Anxiety scale, sleep delay scale, and the Pittsburgh Sleep Quality Index (PSQI) was conducted among a significant sample of innovative enterprise employees (N = 1648). The findings reveal that a notable proportion of these employees, 31.1% to be precise (as per PSQI 8), grapple with compromised sleep quality. Subsequent analyses shed light on compelling patterns, underscoring a robust negative correlation between Mindfulness and factors like Social Interaction Anxiety, sleep delay, and sleep quality (β = -0.71, -0.37, -0.35; P < 0.01). Conversely, a significant positive correlation emerges connecting Social Interaction Anxiety, sleep delay, and sleep quality (β = 0.23, 0.37, 0.32; P < 0.01). Interestingly, mediation analysis demonstrates that Mindfulness significantly negatively influences sleep quality, independent of demographic factors such as sex and age. This impact is mediated by sleep delay, which also interacts with Social Interaction Anxiety. In summary, the research emphasizes the predictive function of Mindfulness in improving sleep quality among employees in innovative enterprises, achieved through its reduction of Social Interaction Anxiety and bedtime procrastination tendencies.

Muscle strength (MS) is related to our neural and muscle systems, essential for clinical diagnosis and rehabilitation evaluation. Although emerging wearable technology seems promising for MS assessment, problems still exist, including inaccuracy, spatiotemporal differences, and analyzing methods. In this study, we propose a wearable device consisting of myoelectric and strain sensors, synchronously acquiring surface electromyography and mechanical signals at the same spot during muscle activities, and then employ a deep learning model based on temporal convolutional network (TCN) + Transformer (Tcnformer), achieving accurate grading and prediction of MS. Moreover, by combining with deep clustering, named Tcnformer deep cluster (TDC), we further obtain a 25-level classification for MS assessment, refining the conventional 5 levels. Quantification and validation showcase a patient’s postoperative recovery from level 3.2 to level 3.6 in the first few days after surgery. We anticipate that this system will importantly advance precise MS assessment, potentially improving relevant clinical diagnosis and rehabilitation outcomes.

BackgroundPregnancy is a pivotal phase in a woman’s life, demanding special attention to ensure maternal and fetal health. Prenatal education plays a vital role in promoting healthy pregnancies and reducing adverse outcomes for pregnant women. Mobile prenatal education programs have gained traction due to their accessibility and timeliness, especially in light of finite health care resources and the constraints imposed by the COVID-19 pandemic. ObjectiveThis study aims to develop and evaluate the effectiveness of a mobile-based prenatal education program in improving pregnancy outcomes. MethodsWe developed a mobile-based prenatal education curriculum in collaboration with a multidisciplinary maternal care team from Peking Union Medical College Hospital (PUMCH) in Beijing, China. Data were retrospectively collected from 1941 pregnant women who had registered for the PUMCH mobile prenatal education program and subsequently delivered at PUMCH between May 2021 and August 2022. The study compared pregnancy outcomes between the completing group, which were pregnant women who had completed at least 1 course, and the noncompleting group. We also analyzed differences among course topics within the completing group and assessed course topic popularity among pregnant women. ResultsThe PUMCH mobile prenatal education curriculum consists of 436 courses across 9 topics. Out of the participants, a total of 1521 did not complete any courses, while 420 completed at least 1 course. Compared with the noncompleting group, pregnant women who completed courses exhibited a significant reduction in the risk of gestational diabetes mellitus, induced abortion, postpartum infection, fetal intrauterine distress, and neonatal malformation. Among those in the completing group, a total of 86% (361/420) started course completion during the first and second trimesters. Furthermore, completing courses related to topics of pregnancy psychology and pregnancy nutrition was associated with reduced risks of premature rupture of membranes and small for gestational age infants, respectively. Pregnancy psychology and postpartum recovery were the preferred topics among pregnant women. ConclusionsThe study demonstrates the potential of mobile-based prenatal education programs in improving pregnancy outcomes and supporting health care providers in delivering effective prenatal education. The rise of mobile prenatal education presents an opportunity to improve maternal and child health outcomes. Further research and broader implementation of such programs are warranted to continually improve maternal and child health.

Abstract Introduction Unbiased metagenomic next-generation sequencing (mNGS) has been used for infection diagnosis. In this study, we explored the clinical diagnosis value of mNGS for pulmonary complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods From August 2019 to June 2021, a prospective study was performed to comparatively analyze the pathogenic results of mNGS and conventional tests for bronchoalveolar lavage fluid (BALF) from 134 cases involving 101 patients with pulmonary complications after allo-HSCT. Results More pathogens were identified by mNGS than with conventional tests (226 vs 120). For bacteria, the diagnostic sensitivity (P = 0.144) and specificity (P = 0.687) were similar between the two methods. For fungus except Pneumocystis jirovecii (PJ), conventional tests had a significantly higher sensitivity (P = 0.013) with a similarly high specificity (P = 0.109). The sensitivities for bacteria and fungi could be increased with the combination of the two methods. As for PJ, both the sensitivity (100%) and specificity (99.12%) of mNGS were very high. For viruses, the sensitivity of mNGS was significantly higher (P = 0.021) and the negative predictive value (NPV) was 95.74% (84.27–99.26%). Pulmonary infection complications accounted for 90.30% and bacterium was the most common pathogen whether in single infection (63.43%) or mixed infection (81.08%). The 6-month overall survival (OS) of 88.89% in the early group (mNGS ≤ 7 days) was significantly higher than that of 65.52% (HR 0.287, 95% CI 0.101–0.819, P = 0.006) in the late group (mNGS > 7 days). Conclusions mNGS for BALF could facilitate accurate and fast diagnosis for pulmonary complications. Early mNGS could improve the prognosis of patients with pulmonary complications after allo-HSCT. Trial Registration ClinicalTrials.gov identifier, NCT 04051372.

Transjugular intrahepatic portosystemic shunt (TIPS) is an essential procedure for the treatment of portal hypertension but can result in hepatic encephalopathy (HE), a serious complication that worsens patient outcomes. Investigating predictors of HE after TIPS is essential to improve prognosis. This review analyzes risk factors and compares predictive models, weighing traditional scores such as Child-Pugh, Model for End-Stage Liver Disease (MELD), and albumin-bilirubin (ALBI) against emerging artificial intelligence (AI) techniques. While traditional scores provide initial insights into HE risk, they have limitations in dealing with clinical complexity. Advances in machine learning (ML), particularly when integrated with imaging and clinical data, offer refined assessments. These innovations suggest the potential for AI to significantly improve the prediction of post-TIPS HE. The study provides clinicians with a comprehensive overview of current prediction methods, while advocating for the integration of AI to increase the accuracy of post-TIPS HE assessments. By harnessing the power of AI, clinicians can better manage the risks associated with TIPS and tailor interventions to individual patient needs. Future research should therefore prioritize the development of advanced AI frameworks that can assimilate diverse data streams to support clinical decision-making. The goal is not only to more accurately predict HE, but also to improve overall patient care and quality of life.

Accurate and comprehensive detection of pavement cracks is important for maintaining road quality and ensuring traffic safety. However, the complexity of road surfaces and the diversity of cracks make it difficult for existing methods to accomplish this challenging task. This paper proposes a novel network named the global graph multiscale network (GGMNet) for automated pixel-level detection of pavement cracks. The GGMNet network has several innovations compared with the mainstream road crack detection network: (1) a global contextual Res-block (GC-Resblock) is proposed to guide the network to emphasize the identities of cracks while suppressing background noises; (2) a graph pyramid pooling module (GPPM) is designed to aggregate the multi-scale features and capture the long-range dependencies of cracks; (3) a multi-scale features fusion module (MFF) is established to efficiently represent and deeply fuse multi-scale features. We carried out extensive experiments on three pavement crack datasets. These were DeepCrack dataset, with complex background noises; the CrackTree260 dataset, with various crack structures; and the Aerial Track Detection dataset, with a drone’s perspective. The experimental results demonstrate that GGMNet has excellent performance, high accuracy, and strong robustness. In conclusion, this paper provides support for accurate and timely road maintenance and has important reference values and enlightening implications for further linear feature extraction research.

Abstract Congenital heart disease (CHD) is one of the leading causes of mortality among birth defects, and due to significant variations in the whole heart and great vessel, automatic CHD segmentation using CT images has been always under-researched. Even though some segmentation algorithms have been developed in the literature, none perform very well under the complex structure of CHD. To deal with the challenges, we take advantage of deep learning in processing regular structures and graph algorithms in dealing with large variations and propose a framework combining both the whole heart and great vessel segmentation in complex CHD. We benefit from deep learning in segmenting the four chambers and myocardium based on the blood pool, and then we extract the connection information and apply graph matching to determine the categories of all the vessels. Experimental results on 68 3D CT images covering 14 types of CHD illustrate our framework can increase the Dice score by 12% on average compared with the state-of-the-art whole heart and great vessel segmentation method in normal anatomy. We further introduce two cardiovascular imaging specialists to evaluate our results in the standard of the Van Praagh classification system, and achieves well performance in clinical evaluation. All these results may pave the way for the clinical use of our method in the incoming future.

Summary: By sorting receptor tyrosine kinases into endolysosomes, the endosomal sorting complexes required for transport (ESCRTs) are thought to attenuate oncogenic signaling in tumor cells. Paradoxically, ESCRT members are upregulated in tumors. Here, we show that disruption of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), a pivotal ESCRT component, inhibited tumor growth by promoting CD8+ T cell infiltration in melanoma and colon cancer mouse models. HRS ablation led to misfolded protein accumulation and triggered endoplasmic reticulum (ER) stress, resulting in the activation of the type I interferon pathway in an inositol-requiring enzyme-1α (IRE1α)/X-box binding protein 1 (XBP1)-dependent manner. HRS was upregulated in tumor cells with high tumor mutational burden (TMB). HRS expression associates with the response to PD-L1/PD-1 blockade therapy in melanoma patients with high TMB tumors. HRS ablation sensitized anti-PD-1 treatment in mouse melanoma models. Our study shows a mechanism by which tumor cells with high TMB evade immune surveillance and suggests HRS as a promising target to improve immunotherapy.

Despite the large demand for dental restoration each year, the design of crown restorations is mainly performed via manual software operation, which is tedious and subjective. Moreover, the current design process lacks biomechanics optimization, leading to localized stress concentration and reduced working life. To tackle these challenges, we develop a fully automated algorithm for crown restoration based on deformable model fitting and biomechanical optimization. From a library of dental oral scans, a conditional shape model (CSM) is constructed to represent the inter-teeth shape correlation. By matching the CSM to the patient’s oral scan, the optimal crown shape is estimated to coincide with the surrounding teeth. Next, the crown is seamlessly integrated into the finish line of preparation via a surface warping step. Finally, porous internal supporting structures of the crown are generated to avoid excessive localized stresses. This algorithm is validated on clinical oral scan data and achieved less than 2 mm mean surface distance as compared to the manual designs of experienced human operators. The mechanical simulation was conducted to prove that the internal supporting structures lead to uniform stress distribution all over the model.

The COVID‐19 pandemic exacerbates challenges faced by human immunodeficiency virus patients, who are at heightened risk for infection due to compromised immune systems. This study aims to develop a reliable, home‐based point‐of‐care testing (POCT) tool for early screening of acquired immunodeficiency syndrome (AIDS) coinfected with Talaromyces marneffei infection. Employing a “From weak to strong” deduction strategy for feature selection, data from 464 AIDS patients across four cohorts between February 5th, 2014, and January 8th, 2022, are analyzed. The top three features consistently observed are D‐dimer, cluster of differentiation 4+, and aspartate transaminase. Based on these features, the simplest risk‐scoring model is constructed, with the area under the receiver operating characteristic curve values of 0.91, 0.80, and 0.69 in the hold‐out cohort, external cohort 1, and external cohort 2, respectively. This “From weak to strong” deduction strategy identifies advantageous clinical features, enabling the development of simplified clinical risk scores with multiple biomarkers. To facilitate practical implementation, enhanced POCT tools are introduced, specifically a strip with segmented testing capabilities that demonstrates sensitivity and strong correlation with clinical scoring models. Furthermore, an open‐access website and a free Android mobile app are created to support community utilization. The findings underscore the effectiveness of the innovative deduction strategy and enhanced test strips, which enable bedside measurements without laboratory dependency.

Abstract Extracellular vesicles (EVs) have emerged as a promising source of biomarkers for disease diagnosis. However, current diagnostic methods for EVs present formidable challenges, given the low expression levels of biomarkers carried by EV samples, as well as their complex physical and biological properties. Herein, a highly sensitive double digital assay is developed that allows for the absolute quantification of individual molecules from a single EV. Because the relative abundance of proteins is low for a single EV, tyramide signal amplification (TSA) is integrated to increase the fluorescent signal readout for evaluation. With the integrative microfluidic technology, the technology's ability to compartmentalize single EVs is successfully demonstrated, proving the technology's digital partitioning capacity. Then the device is applied to detect single PD‐L1 proteins from single EVs derived from a melanoma cell line and it is discovered that there are ≈2.7 molecules expressed per EV, demonstrating the applicability of the system for profiling important prognostic and diagnostic cancer biomarkers for therapy response, metastatic status, and tumor progression. The ability to accurately quantify protein molecules of rare abundance from individual EVs will shed light on the understanding of EV heterogeneity and discovery of EV subtypes as new biomarkers.

Water stress is an important factor affecting herb quality and yield and exogenous spermidine (Spd) addition can enhance dehydration tolerance of plants. Anoectochilus roxburghii (Wall.) Lindl is a perennial herb widely used in medicine, health care, and beauty industry, yet, its dehydration resistance remains largely unknown. In this view, the current research aimed at elucidating the drought resistance mechanism of A. roxburghii under PEG-induced water stress at different levels (10%, 20%, and 30% PEG6000). In particular, the morphological, physiological, and biochemical changes occurring in leaves treated with (0.5 mM, 5 mM) or without Spd were discussed under moderate water stress (20% PEG6000). Results showed that water stress significantly inhibited the growth of A. roxburghii by decreasing the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), arginine decarboxylase (ADC), S-adenosylmethionine decarboxylase (SAMDC), and polyamine oxidase (PAO). The contents of soluble protein, soluble proline, hydrogen peroxide (H2O2), malondialdehyde (MDA), and the relative conductivity (REC) of leaves increased by 27.32%, 31.37%, 68.84%, 103.61%, and 63.64%, respectively. Under dehydration condition, foliar spraying Spd effectively improved plant growth with the contents of soluble protein and soluble proline increased, while the H2O2, REC, and MDA contents decreased. The SOD activity of 0.5 mM and 5 mM treatments were 1.13 and 1.01 times higher than only 20% PEG treatment, respectively. Similarly, the POD activity of 0.5 mM and 5 mM treatments increased by 52.82% and 34.11%, while the CAT activity of 0.5 mM and 5 mM treatments increased by 34.39 and 33.15 U/mgprot, respectively. In addition, exogenous Spd application significantly increased the key enzyme activities of polyamine metabolism (ADC, SAMDC, and PAO) under moderate water stress. In conclusion, exogenous Spd addition with low concentration (0.5 mM) improved the resistance of A. roxburghii against water stress by increasing the antioxidant enzymes activities and endogenous polyamines contents. This study helps to the understanding of dehydration resistance of A. roxburghii and provide guidelines for its cultivation under water deficit condition.

The unfolded protein response (UPR) is a cell-designated strategy that maintains the balance of protein folding in the endoplasmic reticulum (ER). UPR features a network of signal transduction pathways that reprogram the transcription, mRNA translation, and protein post-translational modification to relieve the ER stresses from unfolded/misfolded proteins. Infection with plant viruses can induce the UPR, and activated UPR often promotes plant viral infections in turn. However, the mechanism used by plant viruses to balance UPR and achieve robust infection remain largely unknown. In this study, P1SCSMV was identified as a virus-encoded RNA silencing suppressor (VSR). Heterologous overexpression of P1SCSMV via potato virus X (PVX) was found lead to programmed cell death (PCD) in Nicotiana benthamiana. Furthermore, P1SCSMV was also found to inhibit the PVX infection-triggered UPR by downregulating UPR-related genes and directly induced the distortion and collapse of the ER polygonal meshes on PVX-P1SCSMV infected N. benthamiana. Moreover, self-interaction, VSR activity, UPR inhibition, and cell death phenotype of P1SCSMV were also found to be dependent on its bipartite nuclear localization signal (NLS) (251RKRKLFPRIPLK262). P1SCSMV was found to directly bind to the stem-loop region of NbbZIP60U via its NLS and inhibit the UPR pathways, ultimately resulting in a PCD phenotype in PVX-P1SCSMV infected N. benthamiana leaves. This study also revealed the balancing role of potyviruses encoded P1SCSMV in the UPR pathway to achieve robust viral infection. This may represent a novel virulence strategy for plant viruses.

Background Dietary monitoring is critical to maintaining human health. Social media platforms are widely used for daily recording and communication for individuals’ diets and activities. The textual content shared on social media offers valuable resources for dietary monitoring. Objective This study aims to describe the development of iFood, an applet providing personal dietary monitoring based on social media content, and validate its usability, which will enable efficient personal dietary monitoring. Methods The process of the development and validation of iFood is divided into four steps: Diet datasets construction, diet record and analysis, diet monitoring applet design, and diet monitoring applet usability assessment. The diet datasets were constructed with the data collected from Weibo, Meishijie, and diet guidelines, which will be used as the basic knowledge for further model training in the phase of diet record and analysis. Then, the friendly user interface was designed to link users with backend functions. Finally, the applet was deployed as a WeChat applet and 10 users from the Beijing Union Medical College have been recruited to validate the usability of iFood. Results Three dietary datasets, including User Visual-Textual Dataset, Dietary Information Expansion Dataset, and Diet Recipe Dataset have been constructed. The performance of 4 models for recognizing diet and fusing unimodality data was 40.43%(dictionary-based model), 18.45%(rule-based model), 59.95%(Inception-ResNet-v2), and 51.38% (K-nearest neighbor), respectively. Furthermore, we have designed a user-friendly interface for the iFood applet and conducted a usability assessment, which resulted in an above-average usability score. Conclusions iFood is effective for managing individual dietary behaviors through its seamless integration with social media data. This study suggests that future products could utilize social media data to promote healthy lifestyles.

IntroductionThe novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined.MethodsWe performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis.ResultsThe study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid malignancies. The median follow-up time was 27.0 months. For the entire cohort, the cumulative incidences (CIs) of grade II-IV and III-IV acute GVHD (aGVHD) by 180 days were 13.46% (95% CI, 9.64%-17.92%) and 5.77% (95% CI, 3.37%-9.07%); while total and moderate/severe chronic GVHD (cGVHD) by 2 years were 30.97% (95% CI, 25.43%-36.66%) and 18.08% (95% CI, 13.68%-22.98%), respectively. The 2-year overall survival (OS), relapse-free survival (RFS), GVHD-free, relapse-free survival (GRFS), non-relapse mortality (NRM), and CIs of relapse were 60.7% (95% CI, 54.8%-67.10%), 58.1% (95% CI, 52.2%-64.5%), 50.6% (95% CI, 44.8-57.1%), 23.04% (95% CI, 18.06%-28.40%), and 18.09% (95% CI, 14.33%-23.97%, respectively. The 1-year CIs of cytomegalovirus (CMV) and Epstein–Barr virus (EBV) reactivation were 43.46% (95% CI, 37.39%-49.37%) and 18.08% (95% CI, 13.68%-22.98%), respectively. In multivariate analysis, the disease status at transplantation was associated with inferior survivor outcomes for all patients and myeloid and lymphoid malignancies, while cGVHD had superior outcomes for all patients and myeloid malignancies, but not for lymphoid malignancies.DiscussionThe results demonstrated that the novel regimen could effectively prevent the occurrence of aGVHD in haplo-PBSCT.

Abstract Background Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder caused by the loss of paternally expressed genes in the human chromosome region 15q11.2-q13. It is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity. Motor milestones and language development are delayed and most patients have intellectual disability. Case presentation Here we describe a rare PWS case caused by mosaic imprinting defect in the region 15q11.2-q13 of paternal origin. The proband was a male child with a clinical presentation of global developmental delay and hypotonia with specific facial features. Karyotype of the child was noted as mosaic: 45XY,der(15)?t(15;21),-21[26]/46,XY[24]. Whole-exome sequencing (WES) identified a deletion of 22.7 Mb in size at chr15q11.2q21.1 region and a deletion of 2.1 Mb in size at chr21q22.3 region. The Methylation-specific multiplex ligation-dependent probe amplification(MS-MLPA) of the 15q11.2-q13 region showed that the loading ratio of methylated alleles was 70% and that of unmethylated alleles was 30%(50% normal), which confirmed that the loss of mosaic imprinted defects in the paternal allele led to the diagnosis of PWS. Conclusions We propose that complete clinical criteria for PWS should not be considered sensitive in diagnosing partial atypical PWS due to mosaic imprinting defects. In contrast, clinical suspicion based on less restrictive criteria followed by multiple techniques is a more powerful approach.

The power conversion efficiency (PCE) of single-junction perovskite solar cells (PSCs) has reached 26.1% in small-scale devices. However, defects at the bulk, surface, grain boundaries, and interfaces act as non-radiative recombination centers for photogenerated electron-hole pairs, limiting the open-circuit voltage and PCE below the Shockley–Queisser limit. These defect states also induce ion migration towards interfaces and contribute to intrinsic instability in PSCs, reducing the quasi-Fermi level splitting and causing anomalous hysteresis in the device. The influence of defects becomes more prominent in large-area devices, demonstrating much lower PCE than the lab-scale devices. Therefore, commercializing PSCs faces a big challenge in terms of rapid decline in working performance due to these intrinsic structural defects. This paper provides a comprehensive review of recent advances in understanding the nature and the classification of defects, their impact on voltage losses, device parameters, intrinsic stability, and defect quantification and characterization techniques. Novel defect passivation techniques such as compositional engineering, additive engineering, post-treatments, dimensionality engineering, and interlayer engineering are also reviewed, along with the improvements in PCE and stability based on these techniques for both small-area devices and large-area roll-to-roll coated devices.

Abstract Echocardiography, a simple and noninvasive tool, is the first choice for screening pulmonary hypertension (PH). However, accurate assessment of PH, incorporating both the pulmonary artery pressures and additional signs for PH remained unsatisfied. Thus, this study aimed to develop a machine learning (ML) model that can automatically evaluate the probability of PH. This cohort included data from 346 (275 for training set and internal validation set and 71 for external validation set) patients with suspected PH patients and receiving right heart catheterization. Echocardiographic images on parasternal short axis‐papillary muscle level (PSAX‐PML) view from all patients were collected, labeled, and preprocessed. Local features from each image were extracted and subsequently integrated to build a ML model. By adjusting the parameters of the model, the model with the best prediction effect is finally constructed. We used receiver‐operating characteristic analysis to evaluate model performance and compared the ML model with the traditional methods. The accuracy of the ML model for diagnosis of PH was significantly higher than the traditional method (0.945 vs. 0.892, p = 0.027 [area under the curve [AUC]]). Similar findings were observed in subgroup analysis and validated in the external validation set (AUC = 0.950 [95% CI: 0.897−1.000]). In summary, ML methods could automatically extract features from traditional PSAX‐PML view and automatically assess the probability of PH, which were found to outperform traditional echocardiographic assessments.

Helminth derived excretory/secretory molecules have shown efficacy in the treatment of allergic asthma in mice, but their roles in allergic rhinitis (AR) are little known. In this study, we aimed to determine the intervention effect of SJMHE1, a Schistosoma japonicum derived small molecular peptide, on ovalbumin (OVA)-induced AR mice and investigate its possible mechanism. AR was induced in BALB/c mice, following which the mice were treated with phosphate-buffered saline (PBS), OVA323-339 and SJMHE1 respectively. SJMHE1 treatment improved clinical symptoms (rubbing and sneezing), suppressed infiltrates of inflammatory cells and eosinophils in nasal mucosa, modulated the production of type-2 (IL-4 and IL-13) and anti-inflammatory (IL-10) cytokines in the nasal lavage fluids (NLF), spleen, and serum. To investigate the underlying mechanism, fluorescein isothiocyanate (FITC)-labeled SJMHE1 was subcutaneously injected into AR mice, and we found that the FITC-SJMHE1 could accumulate in spleen, but not in nasal mucosa. FITC-SJMHE1 mainly bound to CD19 positive cells (B cells), and the SJMHE1 treatment significantly increased the proportion of regulatory B cells (Bregs) and B10 cells, along with the enhancement of PR domain containing protein 1 (Prdm1) protein levels. SJMHE1 may alleviate AR by upregulating Bregs, and has great potential as a new avenue for the AR treatment.

Summary: Background: Only a minority of melanoma patients experience durable responses to immunotherapies due to inter- and intra-tumoral heterogeneity in melanoma. As a result, there is a pressing need for suitable preclinical models to investigate resistance mechanisms and enhance treatment efficacy. Methods: Here, we report two different methods for generating melanoma patient-derived organoids (MPDOs), one is embedded in collagen gel, and the other is inlaid in Matrigel. MPDOs in Matrigel are used for assessing the therapeutic effects of anti-PD-1 antibodies (αPD-1), autochthonous tumor infiltrating lymphocytes (TILs), and small molecule compounds. MPDOs in collagen gel are used for evaluating the chemotaxis and migratory capacity of TILs. Finding: The MPDOs in collagen gel and Matrigel have similar morphology and immune cell composition to their parental melanoma tissues. MPDOs show inter- and intra-tumoral heterogeneity and contain diverse immune cells such as CD4+, CD8+ T, Treg, CD14+ monocytic, CD15+, and CD11b+ myeloid cells. The tumor microenvironment (TME) in MPDOs is highly immunosuppressive, and the lymphoid and myeloid lineages express similar levels of PD-1, PD-L1, and CTLA-4 as their parental melanoma tissues. Anti-PD-1 antibodies (αPD-1) reinvigorate CD8+ T cells and induce melanoma cell death in the MPDOs. TILs expanded by IL-2 and αPD-1 show significantly lower expression of TIM-3, better migratory capacity and infiltration of autochthonous MPDOs, and more effective killing of melanoma cells than TILs expanded by IL-2 alone or IL-2 with αCD3. A small molecule screen discovers that Navitoclax increases the cytotoxicity of TIL therapy. Interpretation: MPDOs may be used to test immune checkpoint inhibitors and cellular and targeted therapies. Funding: This work was supported by the NIH grants CA114046, CA261608, CA258113, and the Tara Miller Melanoma Foundation.

The harsh environment of high alkalinity inhibits the effective induction of calcium carbonate precipitation by microorganisms within concrete. In this study, a gradient domestication method was employed to enhance the alkali tolerance of Sporosarcina pasteurii, and various activity parameters (OD600, conductivity, urease activity, and calcium carbonate content) were assessed in an alkaline cultivation setting. Subsequently, a comprehensive evaluation was conducted to compare the impact of domesticated microorganisms on the mechanical properties, impermeability, and self-healing capacity of concrete. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques were employed to characterize the morphology and composition of mineralization products. The results demonstrate that gradient domestication techniques effectively enhance the activity of microorganisms in highly alkaline environments and confirmed that enhanced alkalinity tolerance possesses the potential for multigenerational retention. In comparison to the undomesticated microbial samples at 28 d, concrete incorporating domesticated microorganisms exhibited a 16.59 % increase in compressive strength, a 37.74 % reduction in sorption, and a 23.08 % decrease in permeability. Additionally, the maximum closed crack width measured 0.57 mm, exceeding the 0.44 mm observed in the non-domesticated bacterial group. This study offers a promising strategy for improving the efficiency of microbial-induced calcium carbonate precipitation in concrete.

Rapid drying of peanut is very important to maintain quality and reduce the risk of mildew, especially for peanut harvested in high moisture content in China. The modified mixed-flow dryer can dry freshly harvested peanut efficiently and evenly which is not available for traditional fixed-bed drying. However, the performances of energy and exergy of peanut drying using modified mixed-flow dryer are not clear, lacking of relevant data for equipment improvement and process formulation. Therefore the relevant investigation was carried out to evaluate the performance of fresh harvested peanut drying using industrial mixed-flow dryer with heat-pump full power heating and waste heat recovery The results show that the energy consumption is mainly consumed by heat-pump and centrifugal fan, accounting for 73.5% and 24.2% of all energy consumed respectively. The overall specific energy consumption and specific heat consumption are 1494.5 kJ/kg and 4706.1 kJ/kg respectively. The thermal efficiency and the energy efficiency are affected by the change of the temperature of airflow entering the drying chamber, both fluctuate over time, increase earlier then decrease later and rise again until the material temperature reach to a relatively steady temperature. And the energy efficiency of dryer (178.9%) is approximately triple of thermal efficiencies of drying chamber (56.1%) and dryer (59.4%) for the overall drying. The heat utilization ratio decreases gradually over drying time, with the overall value of 50.0% for drying chamber and 52.9% for dryer. The exergy efficiency of drying process earlier increases then decreases in the overall trend with the overall value of 51.3%. The exergy efficiencies of the drying chamber and whole dryer are both increased gradually with the overall value of 34.5% and 31.8% respectively. However, the variation tendencies of energy improvement potential rates are opposite to exergy efficiencies.

Abstract Background Medical imaging reports play an important role in communication of diagnostic information between radiologists and clinicians. Head magnetic resonance imaging (MRI) reports can provide evidence that is widely used in the diagnosis and treatment of ischaemic stroke. The high-signal regions of diffusion-weighted imaging (DWI) images in MRI reports are key evidence. Correctly identifying high-signal regions of DWI images is helpful for the treatment of ischaemic stroke patients. Since most of the multiple signals recorded in head MRI reports appear in the same part, it is challenging to identify high-signal regions of DWI images from MRI reports. Methods We developed a deep learning model to automatically identify high-signal regions of DWI images from head MRI reports. We proposed a fine-grained entity typing model based on machine reading comprehension that transformed the traditional two-step fine-grained entity typing task into a question-answering task. Results To prove the validity of the model proposed, we compared it with the fine-grained entity typing model, of which the F1 measure was 5.9% and 3.2% higher than the F1 measures of the models based on LSTM and BERT, respectively. Conclusion In this study, we explore the automatic identification of high-signal regions of DWI images from the description part of a head MRI report. We transformed the identification of high-signal regions of DWI images to an FET task and proposed an MRC-FET model. Compared with the traditional two-step FET method, the model we proposed not only simplifies the task but also has better performance. The comparable result shows that the work in this study can contribute to improving the clinical decision support system.

Abstract Background Patients may be endangered if new graduate nurses cannot recognize and manage anaphylactic shock. Consequently, enhancing the new graduate nurses’ understanding of their roles and responsibilities during the rescue of a patient with anaphylactic shock is important. However, due to its inherent limitations, traditional classroom-based teaching makes it difficult to explore the potential of the students. Although popular simulation teaching has several notable advantages, it has not been proven to be effective in training inexperienced nurses on anaphylactic shock. We investigated the effect of a standardized patient-based simulation on the behaviors of new graduate nurses’ during anaphylactic shock rescue to identify an effective and safe method for contemporary nursing education. Methods Except for the ill or pregnant, all the new graduate nurses were included in the study as students to undergo a standardized patient-based simulation conducted in the clinical skills center of a general hospital. The simulation training was designed to teach students to recognize the signs and symptoms of anaphylactic shock, place the patient in the correct position, stop the ongoing intravenous infusion of the antibiotic which triggers the anaphylactic shock, restart an intravenous infusion on a new infusion apparatus, give 100% oxygen via a nasal cannula or mask, preserve airway patency, call the rapid response team, and correctly administer the medications prescribed by the clinicians. Before and after the training, the instructors evaluated each student’s skills and behaviors using a clinical competency evaluation list. After the training, all students completed the Chinese version of the Simulation Design Scale (SDS) to demonstrate their satisfaction with the program and then participated in semi-structured interviews with their instructors. Results All 104 graduate nurses had a significant improvement on the 6 competencies of the clinical competency evaluation list after the simulation training (P

Abstract Background Trimethylamine N-oxide (TMAO)-related metabolites are associated with the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) and are known to disrupt lipid metabolism. The aims of this study were to evaluate the associations between TMAO-related metabolites and blood lipids and determine how lowering the lipid profile via rosuvastatin therapy influences TMAO-related metabolites. Methods A total of 112 patients with suspected ASCVD were enrolled in this study. The levels of plasma TMAO-related metabolites, including TMAO, choline, carnitine, betaine, and γ-butyrobetaine (GBB), were analyzed by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC/MS/MS) before and after rosuvastatin therapy in all patients. Statistical methods were used to detect the associations between TMAO-related metabolites and blood lipids and determine how rosuvastatin therapy alters the levels of these metabolites. Results A significant positive correlation was found between TMAO and triglycerides (TG) (r = 0.303, P 0.05). However, a significantly positive association between carnitine and TC and a negative association between carnitine and LDL-c or between betaine and TG were found after adjustment for sex, age, body mass index (BMI) and lipids (P