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To establish a risk prediction model and make individualized assessment for the susceptible diabetic retinopathy (DR) population in type 2 diabetic mellitus (T2DM) patients. According to the retrieval strategy, inclusion and exclusion criteria, the relevant meta-analyses on DR risk factors were searched and evaluated. The pooled odds ratio (OR) or relative risk (RR) of each risk factor was obtained and calculated for β coefficients using logistic regression (LR) model. Besides, an electronic patient-reported outcome questionnaire was developed and 60 cases of DR and non-DR T2DM patients were investigated to validate the developed model. Receiver operating characteristic curve (ROC) was drawn to verify the prediction accuracy of the model. After retrieving, eight meta-analyses with a total of 15,654 cases and 12 risk factors associated with the onset of DR in T2DM, including weight loss surgery, myopia, lipid-lowing drugs, intensive glucose control, course of T2DM, glycated hemoglobin (HbA1c), fasting plasma glucose, hypertension, gender, insulin treatment, residence, and smoking were included for LR modeling. These factors, followed by the respective β coefficient was bariatric surgery (− 0.942), myopia (− 0.357), lipid-lowering drug follow-up < 3y (− 0.994), lipid-lowering drug follow-up > 3y (− 0.223), course of T2DM (0.174), HbA1c (0.372), fasting plasma glucose (0.223), insulin therapy (0.688), rural residence (0.199), smoking (− 0.083), hypertension (0.405), male (0.548), intensive glycemic control (− 0.400) with constant term α (− 0.949) in the constructed model. The area under receiver operating characteristic curve (AUC) of the model in the external validation was 0.912. An application was presented as an example of use. In conclusion, the risk prediction model of DR is developed, which makes individualized assessment for the susceptible DR population feasible and needs to be further verified with large sample size application. [ABSTRACT FROM AUTHOR]

Realizing high thermoelectric performance in CoSb3 skutterudite‐based thin films and their devices is historically challenging, especially due to the lack of high‐performing thin‐film‐based device working at medium‐to‐high temperatures. Here, a record‐high ZT of 1.1 is achieved at 683 K in an n‐type Ce0.3Ni1.5Co2.5Sb12 thin film, fabricated from a self‐designed target via advanced pulsed laser deposition. Both experimental and computational results confirm that the Ce‐filling and metal‐featured nanoinclusions such as CeSb contribute to high electrical conductivity, while the Ni‐doping and significantly strengthen the energy filtering effect that occurs at the dense interfaces between the Ce0.3Ni1.5Co2.5Sb12 matrix and the nanoinclusions which leads to a large Seebeck coefficient, giving rise to such a high ZT. In addition, a new‐type CoSb3 thin‐film‐based device is successfully fabricated, which exhibits a high output power density of 8.25 mW cm−2 at a temperature difference of 140 K and a cold‐side temperature of 573 K, indicating the potential for application to medium‐to‐high‐temperature power generation scenarios. [ABSTRACT FROM AUTHOR]

In this study, the effects of solution treatment (ST) on the microstructure and anisotropic mechanical properties of Hastelloy X fabricated by laser directed energy deposition (L-DED) were investigated. The microstructure of the as-deposited (AD) sample presented coarse granular grains aligned with the deposition direction. Due to the segregation of Mo and Cr elements, a special cellular-structure was formed in the inter-dendritic region, along with the strip-like carbides consisting of both M 23 C 6 and M 6 C carbides. The cellular-structure homogenized rapidly after the ST. In detail, as the ST temperature increased, recrystallization generally occurred. Meanwhile, the strip carbides began to gradually dissolve and dissociate into dispersed particles which led to a drop in microhardness from 220 HV to 161 HV. The room temperature tensile results showed that the yield strength in the transversal direction (TD) and longitudinal direction (LD) decreased with the increase of ST temperature, reaching a minimum value of 285 MPa after the ST at 1175 °C. In addition, the ultimate tensile strength of the LD and TD samples reached maximum values of 693 MPa and 703 MPa at 1150 °C, respectively. It should be noted that the elongation of the low ductile TD sample can be improved significantly from 30% to 75% after the ST at 1175 °C. Therefore, it can be concluded that the anisotropy within the TD and LD samples can be effectively eliminated by controlling the cellular-structure, grain-structure, and carbide morphology during ST. • Cellular-structure is the major reason for anisotropic yield strength of as-deposited Hastelloy X. • Recrystallization during solution treatment could improve the anisotropic mechanical properties. • The dissolution of strip-like carbides benefits for enhancing the elongation of as-deposited Hastelloy X. [ABSTRACT FROM AUTHOR]

In this study, the laser repairing (LR) method is applied to 12Cr12Mo stainless steel, and the corresponding microstructural evolution, texture characteristic, and hardness variation are investigated. A 50/50 uniaxial tensile-test is conducted, and the mechanical failure mechanism is investigated using scanning electron microscope and transmission electron microscopy. The results show that the microstructure consists mainly of martensite and tiny M 23 C 6 carbide particles in the deposited zone (DZ), while the substrate contains tempered martensite and coarse M 23 C 6 carbide. The high laser-power generates a cubic texture in the DZ, while the substrate maintains a texture-free matrix. From the substrate to the DZ, the hardness increases sharply at the fusion line and then decreases gradually along the building direction. The tensile-test result indicates that the overall mechanical properties of LRed 12Cr12Mo stainless steel are comparable to wrought parts. Moreover, the microvoid-coalescence fracture indicates good plasticity of the LRed samples. Using this approach, we successfully repaired a 17th-stage stator cascade of a gas turbine, which indicates that LR can be used for the type of steel investigated in this study. • A defect-free metallurgical bonding could be obtained under both argon and air atmosphere during laser repairing. • The mechanical properties of laser repaired samples were comparable with those of the wrought substrate. • The 17th stage stator cascade of a gas turbine made from 12Cr12Mo steel was successfully repaired by laser repairing. [ABSTRACT FROM AUTHOR]

Objective: The post-hoc analysis aimed to explore the effect of ticagrelor plus aspirin (T+A) or ticagrelor alone (T) vs aspirin alone (A) on saphenous vein (SV) graft patency 1 year after coronary-artery bypass grafting (CABG) under different baseline levels of low-density lipoprotein cholesterol (LDL-C). Methods: All the 500 patients with 1460 SV grafts from the DACAB trial (NCT02201771) were stratified into subgroup LDL-Low (baseline LDL-C<1.8mmol/L, 148 patients with 430 SV grafts) & subgroup LDL-High (baseline LDL-C≥ 1.8mmol/L, 352 patients with 1030 SV grafts). The primary outcome was the 1-year SV graft patency (Fitzgibbon grade A). The generalized estimating equation model was applied in grafts outcome analyses. Results: The mean baseline LDL-C were 1.4mmol/L and 2.6mmol/L while mean follow-up LDL-C were 1.6mmol/L and 2.3mmol/L for subgroup LDL-Low and subgroup LDL-High, respectively. The baseline and 1-year statin use were comparable between the two subgroups (baseline, LDL-Low: 94.6% [140 of 148 patients], LDL-High: 93.5% [329 of 352 patients], P=0.633; 1-year, LDL-Low: 96.0% [142 of 148 patients], LDL-High: 95.7% [337 of 352 patients], P=0.916).For subgroup LDL-Low and subgroup LDL-High, the 1-year SV graft patency rates were constant significant higher with T+A vs A (LDL-Low: adjusted OR=0.41 [95%CI, 0.17 to 0.97]; LDL-High: adjusted OR=0.38 [95%CI, 0.20 to 0.71]; Inter P=0.679), but may not with T vs A (LDL-Low: adjusted OR=0.24 [95%CI, 0.08 to 0.67]; LDL-High: adjusted OR=0.93 [95%CI, 0.53 to 1.63]; Inter P=0.030). The 1-year SV graft patency were 83.8% (359 of 430 grafts) in subgroup LDL-Low and 82.3% (848 of 1030 grafts) in subgroup LDL-High. No statistically significant difference was observed between the two subgroups (adjusted OR=0.96 [95%CI, 0.62 to 1.50], P=0.857). Conclusion: For 1-year SV graft patency post-CABG, T+A was more effective than A alone in both subgroup LDL-Low and LDL-High; T alone might be more effective than A alone in subgroup LDL-Low. No statistically significant difference of 1-year SV graft patency were observed between subgroup LDL-Low and LDL-High in the DACAB trial. [ABSTRACT FROM AUTHOR]

As a most promising mid‐temperature thermoelectric material, CoSb3‐based bulk material exhibits an applicable figure‐of‐merit (ZT) of more than one. However, their fabrication is historically time‐consuming due to the long‐time solid‐state phase transitions from CoSb2 to CoSb3. To overcome this challenge, here, a fast one‐step process is developed to fabricate n‐type Yb‐doped CoSb3 with stable ZT of 1.12 at 765 K in <5 h. Experiments confirm Yb promotes peritectic reactions of CoSb + Liquid → CoSb2 and CoSb2 + Liquid → CoSb3, optimizes power factor, and suppresses thermal conductivity. Moreover, the dense grains, induced by the one‐step crystallization, result in outstanding mechanical properties with a Young's modulus of 171.4 GPa and a hardness of 8.8 GPa in the Yb‐doped CoSb3. This study indicates that the fast one‐step fabrication route can effectively promote the practical applications of CoSb3‐based thermoelectrics and provide guidance for thermoelectric fabrication via rational phase design. [ABSTRACT FROM AUTHOR]

• Proposed plant point cloud segmentation combining deep learning and clustering. • Improved ASAP-PointNet model for superior semantic segmentation on cabbage dataset. • Optimized DBSCAN algorithm for enhanced organ-level segmentation. • Automated data analysis from 3D point clouds to phenotypic parameters. Plant phenotyping is essential for understanding and managing plant growth and development. 3D point clouds provide a better understanding of plant 3D structures. Point cloud segmentation is the basis for studying the 3D structure of plants through 3D point clouds, and accurate point cloud segmentation is crucial for extracting relevant phenotypic parameters. In this study, cabbage was used as an example, and a plant point cloud segmentation method combining deep learning algorithms and clustering algorithms was proposed. Specifically, a cabbage point cloud dataset was constructed using a 3D scanning platform. The ASAP attention module was incorporated into the PointNet++ model, resulting in the improved ASAP-PointNet model. Superior semantic segmentation performance on the cabbage point cloud dataset was demonstrated by this model. The workflow of the DBSCAN algorithm was also optimized, which exhibited enhanced performance in organ-level plant point cloud segmentation experiments. Subsequently, five phenotypic features were extracted. The experimental results revealed that an accuracy of 0.95 and an intersection over union (IoU) of 0.86 for semantic segmentation were achieved by the ASAP-PointNet model. The correlation coefficients between the four phenotype parameters (plant height, leaf length, leaf width, and leaf area) and their corresponding measured values were 0.96, 0.91, 0.95, and 0.94, respectively. An automated data analysis, from plant 3D point clouds to phenotypic parameters, is enabled by the proposed method, which serves as a valuable reference for plant phenotype research. [ABSTRACT FROM AUTHOR]

Brigatinib is a next‐generation anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of patients with ALK‐positive (ALK+) non–small cell lung cancer (NSCLC). A phase 1 drug‐drug interaction study was conducted to evaluate the effect of multiple‐dose administration of brigatinib on the single‐dose pharmacokinetics of midazolam, a sensitive cytochrome P450 3A substrate. In cycle 1, patients with ALK+ or ROS1+ solid tumors, including NSCLC, received a single 3‐mg dose of midazolam as an oral solution alone on day 1 and then coadministered with brigatinib on day 21 (brigatinib 90 mg once daily on days 2‐8; 180 mg once daily on days 9‐28). After cycle 1, patients could continue to receive brigatinib in 28‐day treatment cycles. The primary study objective was to characterize the effect of brigatinib 180 mg once daily on midazolam pharmacokinetics. The secondary objective was to assess safety. Exploratory efficacy endpoints included objective response rate and progression‐free survival. Brigatinib was generally well tolerated, and safety data were consistent with the known safety profile. Among the 10 patients with ALK+ NSCLC, the confirmed objective response rate was 30% and median progression‐free survival was 7.2 months. Coadministration of brigatinib reduced midazolam maximum observed plasma concentration by ≈16% (geometric least‐squares mean ratio, 0.836 [90%CI, 0.662‐1.056]) and area under the plasma concentration–time curve from time 0 to infinity by ≈26% (geometric least‐squares mean ratio, 0.741 [90%CI, 0.600‐0.915]). Thus, brigatinib is a weak inducer of cytochrome P450 3A in vivo. [ABSTRACT FROM AUTHOR]

Glaucoma is characterized by pathological elevation of intraocular pressure (IOP) due to dysfunctional trabecular meshwork (TM), which is the primary cause of irreversible vision loss. There are currently no effective treatment strategies for glaucoma. Mitochondrial function plays a crucial role in regulating IOP within the TM. In this study, primary TM cells treated with dexamethasone were used to simulate glaucomatous changes, showing abnormal cellular cytoskeleton, increased expression of extracellular matrix, and disrupted mitochondrial fusion and fission dynamics. Furthermore, glaucomatous TM cell line GTM3 exhibited impaired mitochondrial membrane potential and phagocytic function, accompanied by decreased oxidative respiratory levels as compared to normal TM cells iHTM. Mechanistically, lower NAD + levels in GTM3, possibly associated with increased expression of key enzymes CD38 and PARP1 related to NAD + consumption, were observed. Supplementation of NAD + restored mitochondrial function and cellular viability in GTM3 cells. Therefore, we propose that the aberrant mitochondrial function in glaucomatous TM cells may be attributed to increased NAD + consumption dependent on CD38 and PARP1, and NAD + supplementation could effectively ameliorate mitochondrial function and improve TM function, providing a novel alternative approach for glaucoma treatment. • Human glaucomatous TM cells GTM 3 exhibited mitochondrial dysfunction and NAD + deficiency. • The excessive NAD+ consumption of PARP1 and CD38 was the main cause of NAD+ deficiency. • NAD+ supplementation improved the mitochondrial and cellular function of glaucomatous TM cells. [ABSTRACT FROM AUTHOR]

Solid-state refrigeration is considered a promising alternative to traditional vapor compression refrigeration technology. Researchers demonstrated that Ni–Mn–Ti alloys have a remarkable elastocaloric effect. However, the Ni–Mn–Ti alloy can only operate under a uniaxial stress field due to its antiferromagnetic austenite, which narrows its range of refrigeration temperatures. Here, we activated the magnetism of the alloy by replacing some Ni atoms with Co atoms. The Ni–Co–Mn–Ti–B alloy demonstrates a reversible maximum magnetic entropy change(Δ S m) of 24.9 J kg−1 K−1 and achieves an adiabatic temperature change of 7.8 K under a 7 T magnetic field. Additionally, we demonstrate that adding boron (0.2%) can improve the mechanical properties and cyclic stability in Ni–Mn–Ti alloys. The elastocaloric effect of 21.3 K with high cycle stability (1013 cycles) were successfully achieved in the directionally solidified (Ni 35 Co 15 Mn 35 Ti 15) 99.8 B 0.2 alloy. Furthermore, we have demonstrated that the magnetoelastic coupling effect can effectively extend the refrigeration temperature range. The alloys achieved large caloric effects in the temperature range of 240 K–340 K. This provides a new strategy for designing high-performance materials for wide-temperature-domain refrigeration. • The addition of Co activates the magnetic structure coupling of Ni–Mn–Ti alloy. The alloy exhibits a reversible maximum magnetic entropy change Δ S m of 24.9 Jkg −1 K −1 and achieves an adiabatic temperature change of 7.8 K under a 7 T magnetic field. • The addition of B can effectively improve the strength and ductility of the alloy. The material shows a highly stable (1013 cycles) elastocaloric effect of 21.3K. • The material can achieve a continuous refrigerable operating temperature range from 240 K to 340 K by combining elastocaloric, magnetocaloric and magnetoelastic coupling effects. • The stress-assisted method can not only improve the reversibility of caloric effect , but also broaden the temperature range of reversible caloric effect and improve the refrigeration performance of the active refrigerator. [ABSTRACT FROM AUTHOR]

This study examined various parental racial socialization messages as mediators between school‐based racial discrimination and racial identity formation over 4 years for African American boys (N = 639) and African American girls (N = 711). Findings indicated that school‐based racial discrimination was associated with racial identity beliefs. For African American boys, behavioral racial socialization messages mediated the relation between school‐based racial discrimination and racial centrality over time. Mediation also resulted for African American girls, but for a different set of race‐related messages (negative messages and racial barriers) and racial identity beliefs. The developmental significance of the findings and implications for future research are discussed. [ABSTRACT FROM AUTHOR]

Chronic stress is associated with impairment of synapse plasticity in hippocampus and cognitive dysfunction in rodent and human. Notably, corticosterone (CORT) is believed to take responsibility for dendritic atrophy and reduction of spine number induced by chronic stress in hippocampus. But little is known about the molecular mechanisms underlying CORT induced abnormal synapse plasticity and cognitive dysfunction. Drebrin is an F-actin binding protein that modulates memory formation and maintenance by controlling the genesis and morphology of dendritic spines. In addition, miRNAs have been reported to participate in the negative regulation of protein-coding genes. In this study, five miRNAs capable of targeting Drebrin were selected by searching miRNA databases. One of these miRNAs, miR-19b-3p, was found to be upregulated in the hippocampal neurons of mice with chronic restraint stress (CRS). Luciferase reporter assay and Fluorescence in situ hybridization (FISH) were employed to identify the interaction between miR-19b-3p and Drebrin. In addition, silencing miR-19b-3p expression in vivo using an antagomir or in vitro using an inhibitor increased Drebrin expression, ameliorated the abnormal dendritic structure and upregulated the spine density in hippocampal CA1 pyramidal neurons of CRS mice and primary hippocampal neurons cultured under CORT stimulation, respectively. Electrophysiological analysis revealed that inhibition of miR-19b-3p rescued the limited synaptic transmission and synaptic plasticity in hippocampal neurons. Moreover, blocking miR-19b-3p drastically protected against cognitive deficits in CRS mice. These in vivo and in vitro findings indicate that the upregulation of miR-19b-3p exacerbates CRS-induced abnormal synaptic plasticity and cognitive impairment by targeting Drebrin. • CRS stimulation was able to up-regulate miR-19b-3p and down-regulate Drebrin in hippocampal neurons. • CORT mediated miR-19b-3p/Drebrin axis under CRS stimulation. • Inhibition of miR-19b-3p rescued abnormal synaptic plasticity and cognitive deficits by targeting Drebrin in CRS mice. [ABSTRACT FROM AUTHOR]

BMT CTN 1401 is an academically led randomized study of a personalized cancer vaccine in which the combination of DC/MM fusion vaccine and lenalidomide maintenance after autoHCT is compared with maintenance alone as upfront treatment of MM (NCT#02728102). Assessment of the percentage of patients achieving CR and therapy-induced changes in MM-specific immunity are the primary clinical and immunologic endpoints, respectively. The protocol represents a transformative open source approach to cell therapy in MM and required collection of tumor cells prior to treatment initiation and vaccine production at day 60 after autoHCT. The process featured a multi-step approach of procedural standardization, training, and centralized verification of manufactured product/release criteria. Here we present initial analysis of accrual and vaccine manufacturing. Enrollment of 203 patients completed within 26 months with 140 patients randomized. Drop-out rate from enrollment to randomization was 31% (expected 30%). Sixty-eight patients were randomized to the DC/MM fusion vaccine arm, with 63 having products successfully manufactured and approved for release at 14 manufacturing sites. Vaccine products for 5 patients were not approved for release for the following reasons: final TC/DC viability did not meet release criteria (n = 3), product failed to meet sterility release criteria (n = 1), and disease progression prior to manufacture (n = 1). Among 63 participants who received vaccine, mean DC viability and CD86 expression was 79.3% (Standard Deviation = 11.3) and 80.6% (SD = 12.9), respectively. Mean viability and percent cells co-expressing DC and tumor antigens was 78.6% (SD = 13.0) and 47.9% (SD = 11.4), respectively. The process devised for BMT CTN 1401 led to rapid patient accrual and successful point-of-care DC/MM fusion vaccine generation. Feasibility of serial sample collection and performance of immunologic correlates were demonstrated. This multi-center collaboration highlights the development of a personalized tumor vaccine platform that serves as a model for future immunotherapy trials in MM. [ABSTRACT FROM AUTHOR]