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Objective To describe the health care resource use (HCRU) and costs of patients with systemic sclerosis (SSc) prior to and after diagnosis. Methods This retrospective study used a claims data set (Merative MarketScan; 2015‐2019). Eligible patients with SSc were identified by diagnosis codes and required at least 24 months of enrollment without an SSc diagnosis before their first SSc claim and at least 12 months of enrollment thereafter. Total HCRU and costs were reported for three intervals: 2 years and 1 year before and 1 year after index diagnosis. A general population cohort without SSc was matched 1:1 to the SSC cohort on age and sex for comparison. Results Eligibility criteria identified 902 patients with SSc (mean age: 54 years old; 85% female). Mean per‐member per year costs increased each year from $22,383 to $29,708 to $47,095, 2 years before, 1 year before, and 1 year after index diagnosis versus $10,232 to $9656 to $9714 in the general population cohort. Outpatient settings represented the largest proportion of cost 1 year after SSc diagnosis ($16,392), followed by prescription drugs ($10,692), physician office ($10,523), and inpatient ($9448) settings. Conclusion Patients with SSC accrued greater costs and required more services than a general population cohort. These elevated expenditures and HCRU were observed at least 2 years before an SSc diagnosis and increased over time, reflecting both the progressive, multisystem nature of SSc and potential challenges in diagnosis. These findings suggest that SSc poses a substantial burden on the US health care system and highlights the need for early diagnosis and effective therapies.

Abstract Background Genetic disorders ascribe to half of cases of congenital hearing loss. Hearing screening is significant in detecting hearing loss (HL) but weak at diagnosis, which can be complemented by genetic screening. Methods To find a feasible method to accomplish genetic screening and evaluate its advantage when combined with hearing screening, between 1 January 2022, and 10 December 2023, we performed an observational cohort study based on 2488 neonates from the Han population at three hospitals in Jiangsu province. Genetic screening for 20 variants in four common HL‐associated genes by multicolor melting curve analysis (MMCA) and hearing screening were offered concurrently to all participants. Results In total, 170 (6.8%) of 2488 eligible neonates were detected at least one variant and among them, the proportion of referral was higher (p

The convergence of software-defined networking (SDN) and the Internet of Things (IoT) provides a scalable method for handling the considerable volumes of data produced by IoT devices. However, the lack of appropriate security measures can lead to unauthorized access to sensitive data, potential breaches, and privacy violations, as well as time-consuming and inefficient data retrieval methods in SDN-IoT systems that require decrypting the entire dataset. To address these challenges, this article proposes the time-attribute-based access control scheme in SDN-IoT (TAAC). The TAAC scheme combines ciphertext-policy attribute-based encryption with a novel time-attribute-based access tree to ensure fine-grained access control on time and attributes, enabling secure ciphertext interaction and information sharing across domains. Furthermore, the TAAC scheme also incorporates searchable encryption, which enhances the efficiency of data retrieval. By implementing searchable encryption techniques, the data receiver can generate trapdoors to search and retrieve specific encrypted data without the need to decrypt the entire dataset. In summary, the TAAC scheme improves storage efficiency and computation, enhances scalability, and provides robust security, offering an efficient and secure solution for ciphertext sharing in SDN-IoT environments. Experimental results have demonstrated that the TAAC scheme shows excellent performance and outperforms other attribute-based searchable encryption algorithms.

Abstract Preeclampsia (PE) is a multisystemic and placental inflammatory disease that causes maternal and infant health issues. As one of the active components in peony root extract, paeonol (Pae) exerts anti‐apoptosis and anti‐inflammatory effects. Nonetheless, the protective role of Pae in PE has not yet been characterized. A mouse model of PE was constructed through tail vein injection of 1 mg/d phosphatidylserine/dioleoyl‐phosphatidycholine suspension. The levels of inflammatory cytokines in the placenta were examined via enzyme‐linked immunosorbent assay (ELISA). The mRNA levels of inflammatory cytokines (TNF‐α, IL‐6, IFN‐γ, and IL‐4) and apoptosis markers (Bax, Bcl‐2, and caspase‐3) were tested using quantitative reverse transcription‐polymerase chain reaction (qRT–PCR). Western blot analysis was performed to detect the protein levels of apoptosis markers and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway‐related molecules. Here, Pae repressed the inflammatory response in the placenta of PE‐like mouse models, as demonstrated by the decreased concentrations and mRNA levels of TNF‐α, IL‐6, and IFN‐γ and the increased concentrations and mRNA levels of IL‐4. Apoptosis in the placentas of PE‐like mouse models was attenuated by Pae, as manifested by the downregulated mRNA and protein levels of Bax and cleaved‐caspase‐3 and the upregulated Bcl‐2. Administration of Pae inhibited the phosphorylation of JAK2 and STAT3 in the placental tissues of PE mice. The JAK2/STAT3 pathway agonist (SC‐39100) reversed Pae treatment‐mediated suppression of placental inflammation and apoptosis in PE mice. Overall, Pae inhibits the JAK2/STAT3 signaling pathway to attenuate placental inflammation and apoptosis in PE mice.

Introduction Mesenteric lymph nodes (MLNs) are central in immune anatomy. MLNs are associated with the composition of gut microbiota, affecting the central system and immune system. Gut microbiota was found to differ among individuals of different social hierarchies. Nowadays, excision of MLNs is more frequently involved in gastrointestinal surgery; however, the potential side effects of excision of MLNs on social dominance are still unknown. Methods MLNs were removed from male mice (7–8 weeks old). Four weeks after MLN removal, social dominance test was performed to investigate social dominance; hippocampal and serum interleukin (IL)‐1β, IL‐10, and tumor necrosis factor‐alpha (TNF‐α) were investigated; and histopathology was used to evaluate local inflammation of the ileum. The composition of the gut microbiota was then examined to understand the possible mechanism, and finally intraperitoneal injection of IL‐10 was used to validate the effect of IL‐10 on social dominance. Results There was a decrease in social dominance in the operation group compared to the control group, as well as a decrease in serum and hippocampal IL‐10 levels, but no difference in serum and hippocampal IL‐1β and TNF‐α levels, and no local inflammation of the ileum after MLN removal. 16S rRNA sequencing analysis showed that the relative abundance of the class Clostridia was decreased in the operation group. This decrease was positively associated with serum IL‐10 levels. Furthermore, intraperitoneal injection of IL‐10 in a subset of mice increased social dominance. Conclusions Our findings suggested that MLNs contributed to maintaining social dominance, which might be associated with reduced IL‐10 and the imbalance of specific flora in gut microbiota.

Abstract Fluorescent probes for detection of CN− still have many limitations, such as small Stokes shift, irreversible, and background interference, which hamper their applications for on‐site detection and bioimaging of CN−. In this work, we design a new CN−‐activatable fluorescent probe (named AHMM) containing an ESIPT (excited‐state intramolecular proton transfer) and hydrogen bond features, which show a large Stokes shift (225 nm) and molecular structural reversible detection. The probe AHMM exhibits an excellent selectivity for CN− without any interference from other anions in aqueous DMSO system. Furthermore, the mechanism of the interaction of AHMM with CN− is concluded by various experiments. The limit of detection of AHMM for CN− is calculated as low as 4.47 × 10−8 M, lower than the concentration of CN− deemed acceptable by WHO (World Health Organization). AHMM can recognize CN− in tap water quantitatively and on‐site by a smartphone APP. Moreover, food samples such as almond and cassava including CN− are visualized by fluorescence imaging. In addition, the probe shows practical applications of CN− imaging in cells and mice. This concept can be applied for designing multifunctional fluorescent probes with ESIPT and reversible characteristics for detection of CN−.

Abstract Background Kidney cancer is one of the most common solid tumors. The advancement of human kidney cancer research and treatment has been hindered by a lack of research models that faithfully recapitulate the diversity of the disease. Methods We established an effective three‐dimensional culture system for generating kidney cancer organoids from clinical renal cell carcinoma samples. Renal cell carcinoma (RCC) organoids were characterized by H&E staining, immunofluorescence, whole‐exome sequencing, RNA sequencing and single‐cell RNA sequencing. The use of RCC organoids in personalized cancer therapy was assessed by testing their responses to treatment drugs and chimeric antigen receptor T cells. Results Using this organoid culture system, 33 kidney cancer organoid lines from common kidney cancer subtypes, including clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and chromophobe renal cell carcinoma (chRCC), were generated. RCC organoids preserved the histological architectures, mutational landscapes, and transcriptional profile of the parental tumor tissues. Single‐cell RNA‐sequencing revealed inter‐ and intra‐tumoral heterogeneity in RCC organoids. RCC organoids allowed for in vitro drug screening and provided a tool for assessing the efficacy of chimeric antigen receptor T cells. Conclusions Patient‐derived RCC organoids are valuable pre‐clinical models for academic research and personalized medicine.

Abstract Conventional antiplatelet agents indiscriminately inhibit both thrombosis and hemostasis, and the increased bleeding risk thus hampers their use at more aggressive dosages to achieve adequate effect. Blocking integrin αIIbβ3 outside‐in signaling by separating the β3/Src interaction, yet to be proven in vivo, may nonetheless resolve this dilemma. Identification of a specific druggable target for this strategy remains a fundamental challenge as Src SH3 is known to be responsible for binding to not only integrin β3 but also the proteins containing the PXXP motif. In vitro and in vivo mutational analyses show that the residues, especially E97, in the RT loop of Src SH3 are critical for interacting with β3. DCDBS84, a small molecule resulting from structure‐based virtual screening, is structurally validated to be directed toward the projected target. It specifically disrupts β3/Src interaction without affecting canonical PXXP binding and thus inhibits the outside‐in signaling‐regulated platelet functions. Treatment of mice with DCDBS84 causes a profound inhibition of thrombosis, equivalent to that induced by extremely high doses of αIIbβ3 antagonist, but does not compromise primary hemostasis. Specific targets are revealed for a preferential inhibition of thrombosis that may lead to new classes of potent antithrombotics without hemorrhagic side effects.

With the globalization of network education and the design and construction of all aspects of engineering, network science education is playing an increasingly important role in higher education and even the lifelong education system of college students. The purpose of this article is to study emotional interaction in deep learning network education and analyze the status quo of its behavioral decision-making mechanism. It uses research literature method, algorithmic statistical method, and questionnaire survey method to investigate specific groups of people; analyzes the status quo of emotional interaction and behavioral decision-making mechanism; improves statistical algorithms; and explores an old style emotional cognitive decision-making model. In this paper, a questionnaire survey of a university shows that the proportion of students whose online learning time is 1.5–2 hours is about 10.3% and the proportion of 1–1.5 hours is about 6.8%. The study time of students’ online courses is mainly concentrated. The study time between 0.5 and 1 hour accounts for about 83.2%; about 2.3% of learners rarely use the Internet, less than 0.5 hour; and 1% of students hardly use online courses and may rely more on traditional classroom teaching. Further research showed the behavior of their emotional interaction: interactive teaching network in six modules reached the upper level, the peak value of the curve was 0.737, the bottom value was 0.115, and the transitivity was above 0.115. From deep statistical learning algorithms to completing network science education, designing or modifying more comprehensive and faster bpq-l learning algorithms based on traditional learning algorithms can allow us to find target sentiments.

Purpose. To characterize cataract patients and postoperative outcomes in the Medicare fee-for-service (FFS) population. Design. A retrospective observational cohort study. Methods. Medicare fee-for-service (A&B) databases were queried from October 2015 to December 2017. Patients with procedural claims using CPT codes (66982 or 66984) and with 1–12 months of postcataract follow-up data were included in the analysis. Results. 133,896 records of 82,246 CMS FFS claims were included in the analysis. The average patient age was 73.8, and 58.2% were females. The cataract surgery setting was ASC (71.3%) followed by HOPD (27.6%). The median time between first and second surgery was 15 days. The most common comorbidities included diabetes (28.6%), glaucoma (22.1%), and macular degeneration (21.7%). Posterior capsule rupture occurred in 0.2% of cases. The

It is difficult to predict tight sandstone gas in continental rift basin because of complex deep structure, fast transformation of sedimentary facies, large lateral variation of reservoir thickness, and tight and strong heterogeneity. Based on the petrophysical analysis of logging data, this paper improved the traditional low-frequency establishment method of prestack synchronous inversion which is under the constraints of fine isochronal sequence stratigraphy framework. The prestack AVO has attributed as covariate, and Bayes kriging method has applied to establish low-frequency model. Then, the relationship between density and P-wave and S-wave impedance has been introduced. The results show that the stability of density parameters has been improved, and the facies controlled prestack inversion with drilling verification has been realized which the number of layers with thickness error less than 20% accounts for 75.2%. Exploration practice shows that the facies controlled prestack inversion technology has important reference significance for other deep continental fault basins.

The microstructure, mechanical properties, oxidation, and corrosion resistance of 2205 stainless steels without and with Al in a range of 0.5 to 2.5 wt.% were investigated in this paper. The results showed that the matrix phase transformed from austenite to ferrite. The volume fraction of the ferrite in the steels decreased at first and then increased and was the lowest in the steel with 0.5 wt.% Al. Most of the Al was dissolved in the ferrite and austenite phases in the steels. The ultimate tensile strength and elongation rate of the steels increased at first and then decreased with the increasing Al content, with the highest values in the steel with 0.5 wt.% Al. The yield strength of the steels slightly increased from 544 to 607 MPa due to the addition of Al. The oxidation rates of the steels with Al were much lower than that of the steel without Al, and the rate of the steel with 1.5 wt.% Al was the lowest, approximately 10 times lower than that of the steel without Al. The corrosion rates of the steels with 0.5 and 1.0 wt.% Al were slightly higher than that of the alloy without Al. In general, the steel with 1 wt.% Al had optimal properties.

Objectives. Gestational diabetes mellitus (GDM) leads to an abnormal placental environment which may cause some structural alterations of placenta and affect placental development and function. In this study, the ultrastructural appearances of term placentas from women with GDM and normal pregnancy were meticulously compared. Materials and Methods. The placenta tissues of term birth from 10 women with GDM and 10 women with normal pregnancy were applied with the signed informed consent. The morphology of fetomaternal interface of placenta was examined using light microscopy (LM) and transmission electron microscopy (TEM). Results. On LM, the following morphological changes in villous tissues were found in the GDM placentas when compared with the control placentas: edematous stroma, apparent increase in the number of syncytial knots, and perivillous fibrin deposition. On TEM, the distinct ultrastructural alterations indicating the degeneration of terminal villi were found in the GDM placentas as follows: thickening of the basal membrane (BM) of vasculosyncytial membrane (VSM) and the VSM itself, significantly fewer or even absent syncytiotrophoblastic microvilli, swollen or completely destroyed mitochondria and endoplasmic reticulum, and syncytiotrophoblasts with multiple vacuoles. Conclusion. Ultrastructural differences exist between GDM and control placentas. The differences of placenta ultrastructure are likely responsible for the impairment of placental barrier and function in GDM.