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Abstract Background To investigate the risk factors and prognosis of clinical pseudophakic cystoid macular edema (PCME) after uneventful phacoemulsification surgery in patients without pre-existing fundus diseases. Methods This was a retrospective case-control study. Medical records between August 2020 and August 2023 were reviewed for patients who had no previous fundus diseases and developed clinical PCME. A control group was randomly chosen and the risk factors for PCME was analyzed by binary logistic regression. Structure and visual prognosis of the PCME cohort were observed and compared among subgroups undergoing different treatment measures. Results Forty-seven eyes of 47 patients with PCME were included. The development of PCME was associated with higher systolic blood pressure (OR, 1.048; 95%CI 1.002, 1.097; P = .042), no posterior vitreous detachment (OR, 0.215; 95%CI: 0.553, 0.887; P = .032) and shorter axial lengths (OR, 0.401; 95%CI 0.161, 0.997; P = .049) compared to controls. During a mean follow-up of 8.26 months, 36 eyes (76.6%) showed visual improvement with decreased macular thickness. Different treatment modalities, including observation, topical NSAIDs, and intervention therapy, have no significant differences on the visual prognosis (P = 1.000). However, the intervention group had a shorter recovery time compared to the observation group (28.6 vs. 45.9 days, P = .037). Conclusion PCME remains an encountered morbidity in patients without pre-existing fundus diseases. Shorter axial lengths, absence of posterior vitreous detachment, and higher systolic blood pressure are risk factors of PCME. Active intervention failed to improve the prognosis of PCME but could shorten the recovery time.

The epidermal growth factor receptor (EGFR) plays a pivotal role in tumor progression and is an essential therapeutic target for treating malignant gliomas. Small interfering RNA (siRNA) has the potential to selectively degrade EGFR mRNA, yet its clinical utilization is impeded by various challenges, such as inefficient targeting and limited escape from lysosomes. Our research introduces polyethylene glycol (PEG) and endoplasmic reticulum membrane-coated siEGFR nanoplexes (PEhCv/siEGFR NPs) as an innovative approach to brain glioma therapy by overcoming several obstacles: 1) Tumor-derived endoplasmic reticulum membrane modifications provide a homing effect, facilitating targeted accumulation and cellular uptake; 2) Endoplasmic reticulum membrane proteins mediate a non-degradable ''endosome-Golgi-endoplasmic reticulum'' transport pathway, circumventing lysosomal degradation. These nanoplexes demonstrated significantly enhanced siEGFR gene silencing in both in vitro and in vivo U87 glioma models. The findings of this study pave the way for the advanced design and effective application of nucleic acid-based therapeutic nanocarriers.

In December 2021, WHO’s 194 member states began reaching a consensus to start the process of drafting and negotiating a pandemic treaty under the WHO Act. Although there is already a PHEIC system to deal with sudden public health events such as pandemics, the system is not sufficient to deal with global pandemic events. The draft WHO Pandemic Agreement reflects the negotiating process until 24 May 2024. The negotiating team is faced with legal issues such as the treatment of the relationship between the pandemic treaty and the International Health Regulations, the determination of the contracting model, the attribution of the pandemic definition power and the construction of the dispute settlement mechanism. Through a study of the articles of the current draft and a comparative analysis with other treaties, this paper discusses the need to distinguish the functions of the pandemic treaty and the International Health Regulations (IHR), adopt a soft and hard contracting model, establish an open and transparent pandemic determination mechanism, reform the institutional functions of WHO, and establish an effective dispute settlement mechanism in order to solve the above problems. Ultimately, fairness and justice in international public health governance will be achieved.

Abstract Background This study aimed to investigate the functional and anatomical outcomes of subthreshold micropulse laser (SMPL) therapy in eyes with early postoperative macular thickening after idiopathic epiretinal membrane (iERM) removal. Methods This was a prospective and interventional study. Forty-eight eyes from 48 patients with macular edema at 1 month after iERM removal were randomly divided into two groups. Patients in the SMPL group (n = 24) received SMPL therapy while no special intervention was used for the observation group (n = 24). Baseline demographic data and clinical findings before and at 1 and 3 months after SMPL treatment or observation, including best-corrected visual acuity (BCVA) and the changes in central subfield thickness (CST) and average macular thickness (AMT), were analyzed. Results An improvement in BCVA with a decrease in CST and AMT from baseline to the 3-month follow-ups were observed in both SMPL and observation groups. No significant difference in BCVA was observed between the SMPL group and observation group either in the 1-month (0.26 [0.15, 0.52] vs. 0.26 [0.15, 0.39], P = 0.852) or the 3-month (0.15 [0.10, 0.30] vs. 0.23 [0.15, 0.30], P = 0.329) follow-up. There was a greater reduction in CST in the SMPL group versus observation group between baseline and the 3-month follow-up (-77.8 ± 72.3 μm vs. -45.0 ± 46.9 μm, P = 0.049). The alteration in AMT did not differ between the two groups in either 1-month (-16.5 ± 20.1 μm vs. -19.7 ± 16.3 μm, P = 0.547) or 3-month (-36.9 ± 26.9 μm vs. -34.0 ± 20.1 μm, P = 0.678) follow-up. Conclusions SMPL therapy led to a significant decrease in CST at the 3-month follow-up while did not significantly improve the visual acuity in patients with postoperative macular thickening following iERM surgery. Trial registration The study was registered on Aug 27, 2020 (Trial Registration Number: ChiCTR 2000037227).

Under the new coronavirus epidemic, the implementation of public health measures has generated some resistance in countries around the world. The essence of examining the human rights claims of those who oppose the epidemic is that they have a too narrow understanding of individual human rights and ignore the obligation implications of human rights itself. From the historical point of view, health and epidemic prevention is the objective necessity of the survival and development of human society; From the ethical point of view, the joint fight against the epidemic is the moral obligation of the coordinated development of individuals and society. From the normative point of view, the management of infectious diseases is the basic consensus established by many international conventions. To correct the narrow understanding of individual human rights concept, the global human rights concept should be established in pandemic governance, and the concept of human health community should be shaped in the pandemic convention to build governance consensus, implement the same health concept to clarify the scope of governance, implement the principle of common but differentiated responsibilities, and strengthen the participation of individuals and communities in public health governance to improve governance paths. To shape a more reasonable and effective pandemic governance order.

We examined healthcare costs at HonorHealth, a community-based academic health center comprised of 5 hospitals and numerous ambulatory care facilities. Patient encounters that resulted in admission in 2019 were included in the study. Mean costs in 2019 for high costs and high needs (HCHN) patients were compared with all remaining patients using a framework developed by the National Academy of Medicine. HCHN patients were older (71 vs 52 years), with a lower percentage of females (41.7% vs 59.8%), more frequently White (90.1% vs 87.5%), less frequently married (52.4% vs 54.5%), with a longer length of stay (6.5 vs 3.0 days) and higher mean charges ($134 743 vs $16 414). The mean cost per patient in the HCHN group decreased by age group ($192, 963, $165 200, $144 584, $134 795, and $108 356) for 0 to 18, 19 to 44, 45 to 64, 65 to 84, and 85+ years, respectively. HCHN patients were more publicly insured (49% vs 38%). Targeted interventions to treat HCHN may lead to lower healthcare costs and improved health outcomes within this system.

Abstract Aims Diabetic retinopathy (DR) is a significant global public health concern. Alternative, safe, and cost‐effective pharmacologic approaches are warranted. We aimed to investigate the therapeutic potential of nattokinase (NK) for early DR and the underlying molecular mechanism. Methods A mouse model of diabetes induced by streptozotocin was utilized and NK was administered via intravitreal injection. Microvascular abnormities were evaluated by examining the leakage from blood–retinal barrier dysfunction and loss of pericytes. Retinal neuroinflammation was examined through the assessment of glial activation and leukostasis. The level of high mobility group box 1 (HMGB1) and its downstream signaling molecules was evaluated following NK treatment. Results NK administration significantly improved the blood–retinal barrier function and rescued pericyte loss in the diabetic retinas. Additionally, NK treatment inhibited diabetes‐induced gliosis and inflammatory response and protected retinal neurons from diabetes‐induced injury. NK also improved high glucose‐induced dysfunction in cultured human retinal micrangium endothelial cells. Mechanistically, NK regulated diabetes‐induced inflammation partially by modulating HMGB1 signaling in the activated microglia. Conclusions This study demonstrated the protective effects of NK against microvascular damages and neuroinflammation in the streptozotocin‐induced DR model, suggesting that NK could be a potential pharmaceutical agent for the treatment of DR.

Conclusions: Intravitreal conbercept injection presents dual effects of antiangiogenesis and anti-inflammation and can be served as an adjuvant treatment to vitrectomy for PDR patients.

Abstract Diabetic retinopathy (DR) is a leading cause of blindness that poses significant public health concerns worldwide. Increasing evidence suggests that neuroinflammation plays a key role in the early stages of DR. Microglia, long-lived immune cells in the central nervous system, can become activated in response to pathological insults and contribute to retinal neuroinflammation. However, the molecular mechanisms of microglial activation during the early stages of DR are not fully understood. In this study, we used in vivo and in vitro assays to investigate the role of microglial activation in the early pathogenesis of DR. We found that activated microglia triggered an inflammatory cascade through a process called necroptosis, a newly discovered pathway of regulated cell death. In the diabetic retina, key components of the necroptotic machinery, including RIP1, RIP3, and MLKL, were highly expressed and mainly localized in activated microglia. Knockdown of RIP3 in DR mice reduced microglial necroptosis and decreased pro-inflammatory cytokines. Additionally, blocking necroptosis with the specific inhibitor GSK-872 improved retinal neuroinflammation and neurodegeneration, as well as visual function in diabetic mice. RIP3-mediated necroptosis was activated and contributed to inflammation in BV2 microglia under hyperglycaemic conditions. Our data demonstrate the importance of microglial necroptosis in retinal neuroinflammation related to diabetes and suggest that targeting necroptosis in microglia may be a promising therapeutic strategy for the early stages of DR.

Due to the space–time coupling access, we find that anti-eavesdropping opportunities exist in underwater acoustic networks (UANs), where packets can be successfully received only by the intended receiver, but collide at the unintended receivers. These opportunities are highly spatially dependent, and this paper studies the case that linearly deployed sensor nodes directly report data toward a single collector. We found an eavesdropping ring centered around these linearly deployed sensor nodes, where the eavesdropper could steal all the reported data. Since the typical receiving-alignment-based scheduling MAC (TRAS-MAC) will expose the relative spatial information among the sensor nodes with the collector, the eavesdropper can locate the eavesdropping ring. Although moving the collector into the one-dimensional sensor node chain can degrade the eavesdropping ring to a point that constrains the eavesdropping risk, the collector’s location will be subsequently exposed to the eavesdropper. To efficiently protect the reported data and prevent the exposure of the collector’s location, we designed a slotted- and receiving-alignment-based scheduling MAC (SRAS-MAC). The NS-3 simulation results showed the effectiveness of the SRAS-MAC and the TRAS-MAC in protecting data from eavesdropping, which protect 90% of the data from eavesdropping in the one-eavesdropper case and up to 80% of data from eavesdropping in ten-eavesdropper cases. Moreover, unlike TRAS-MAC, which will expose the collector’s location, SRAS-MAC provides multiple positions for the collector to hide, and the eavesdropper cannot distinguish where it is.

Variation in hydrological connectivity (HC) between rivers and lakes gives rise to periodic large water level fluctuation (WLF) in river-connected lakes (RCL). However, how WLF shapes the material cycling and concomitant trophodynamics of RCL remain unclear. Here we evaluated the resource availability, relative contributions of autochthonous and allochthonous carbon sources (by Bayesian mixing models) and trophic structure (using δ13C and δ15N) of Lake Poyang, the largest freshwater lake in China, during different hydrological periods. Terrestrial C3 plants in the aquatic/terrestrial transition zones (ATTZ) were the main supporter of aquatic consumers all year round. Compared with historical data, the contributions of autochthonous production to aquatic food webs were low. This is primarily ascribed to the influences of hydrological regimes in that the operation of Three Gorges Dam and HC changed the rhythm of WLF in Lake Poyang, restricting the production of aquatic vegetation and epiphytic algae. Most common fish species indicated higher trophic positions (TPs) during the dry than wet season, but only eleven of thirty-six common species showed a statistically significant increase (p

Abstract Background Vitrectomy and peeling of the internal limiting membrane (ILM) was an effective therapeutic approach for myopic foveoschisis with progressive visual loss. This study investigated the anatomical and visual outcomes of fovea-sparing ILM peeling with or without the inverted flap technique for patients with symptomatic myopic foveoschisis (MF). Methods We retrospectively reviewed the clinical data of patients with MF. Vitrectomy with fovea-sparing ILM peeling and air tamponade was performed in all patients. The primary outcome measures included best-corrected visual acuity (BCVA), mean macular thickness (MMT), and central foveal thickness (CFT). Depending on whether an inverted ILM flap technique was utilized, further subgroup comparisons between the inverted flap group and the non-inverted flap group were conducted. Results Twenty-six eyes of 22 patients were included. Fifteen eyes were underwent fovea-sparing ILM peeling without inverted ILM flap and 11 of the 26 eyes were treated with fovea-sparing ILM peeling and an inverted ILM flap technique. In the mean follow-up period of 10.74 ± 4.58 months, a significant improvement in BCVA was observed from 0.97 ± 0.45 logMAR to 0.58 ± 0.51 logMAR (P 0.05). Conclusion Fovea-sparing ILM peeling with or without inverted flap technique resulted in favorable visual and anatomical outcomes for the treatment of MF. An important factor affecting the postoperative visual outcome was the preoperative visual acuity. Our study found no significant difference between the presence and absence of the inverted ILM flap.

In humans, germline TP53 mutations predispose carriers to a wide spectrum of cancers, which is known as Li–Fraumeni syndrome (LFS). To date, the association of melanomas with LFS remains unestablished. No melanomas have been reported in any P53‐modified mouse models either. In this study, we show that targeted disruption of P53 at the DNA‐binding domain in Xenopus tropicalis recapitulates LFS, with the formation of soft‐tissue sarcomas and pancreatic ductal adenocarcinoma. Interestingly, 19% of the 14‐month‐old tp53Δ7/Δ7 homozygotes and 18% of tp53+/Δ7 heterozygotes spontaneously developed small nevi and non‐invasive melanomas. Large invasive melanomas were also observed in other older homozygous mutants, with about 7.9% penetrance. Our data suggest that more dermatologic investigation of LFS patients should be able to settle the association of melanoma with LFS in epidemiology. Our model is also valuable for further investigation of the molecular mechanism underlying melanoma progression upon germline alteration of the tp53 locus.

Abstract Background Capillary non-perfusion is an important characteristic for diabetic retinopathy (DR) indicating microvascular damage and ischemia. Data on the description and treatment outcomes of DR with large area of non-perfusion are lacking to date. We aim to describe the characteristics and treatment outcomes in a series of patients with DR who presented extensively large area of capillary non-perfusion (LACNP). Methods Fundus fluorescein angiograms from medical charts in patients diagnosed with DR between Jan 2017 and Dec 2019 were retrospectively reviewed. Clinical data in eyes with LACNP including imaging and laboratory findings at the first presentation were analyzed. The LACNP was defined as over 70% area of capillary non-perfusion throughout the whole image retina. The mean follow-up duration was 12.4 ± 16.7 months. Follow-up data including extensive pan-retinal photocoagulation and surgical intervention and treatment outcomes were evaluated. Results A total of 43 eyes in 24 patients with LACNP were included, accounting for 3.3% of DR populations in the same period. The overall percentage of non-perfusion area was 79.1 ± 8.1%. All patients received proper control of diabetes and hypertension, and extensive pan-retinal laser photocoagulation. During the follow-up periods, 20 eyes (46.5%) developed severe neovascular complications, of which 15 eyes (34.9%) underwent vitrectomy and/or anti-glaucoma surgeries. Conservative therapies including glycemic control and supplemental laser photocoagulation were conducted in 23 eyes (53.5%) without neovascular complications. In the final follow-up, best corrected visual acuity improved or maintained stable in 19 eyes (44.2%) while deteriorated in 24 eyes (55.8%). Conclusions The presence of LACNP is the hallmark of advanced DR and often indicates a poor visual outcome, although aggressive treatments may slow DR progression and maintain central vision for some time.

In this study, we explored the relationship between the platelet endothelial aggregation receptor 1 (PEAR1) polymorphisms, platelet reactivity, and clinical outcomes in patients with minor stroke or transient ischemic attack (TIA). Randomized controlled trial subgroups were assessed, wherein patients received dual antiplatelet therapy for at least 21 days. Platelet reactivity was measured at different time intervals. Genotypes were categorized as wild-type, mutant heterozygous, and mutant homozygous. Clinical outcomes were evaluated after 90 days. The rs12041331 polymorphism predominantly influenced adenosine diphosphate channel platelet activity, with the AA genotype displaying significantly lower residual platelet activity to the P2Y12 response unit (p < 0.01). This effect was more evident after 7 days of dual antiplatelet treatment (p = 0.016). Mutant A allele carriers had decreased rates of recurrent stroke and complex endpoint events but were more prone to bleeding (p = 0.015). The rs2768759 polymorphism majorly impacted arachidonic acid (AA) channel platelet activity, which was particularly noticeable in the C allele carriers. Our regression analysis demonstrated that rs12041331 AA + GA and rs2768759 CA predicted 90-day post-stroke bleeding. In conclusion, the PEAR1 polymorphisms rs12041331 and rs2768759 interfere with platelet aggregation and the performance of antiplatelet drugs. These genetic variations may contribute to bleeding events associated with minor stroke and TIA.

Summary: Accurate prediction of protein–ligand binding affinity is crucial in structure-based drug design but remains some challenges even with recent advances in deep learning: (1) Existing methods neglect the edge information in protein and ligand structure data; (2) current attention mechanisms struggle to capture true binding interactions in the small dataset. Herein, we proposed SEGSA_DTA, a SuperEdge Graph convolution-based and Supervised Attention-based Drug–Target Affinity prediction method, where the super edge graph convolution can comprehensively utilize node and edge information and the multi-supervised attention module can efficiently learn the attention distribution consistent with real protein-ligand interactions. Results on the multiple datasets show that SEGSA_DTA outperforms current state-of-the-art methods. We also applied SEGSA_DTA in repurposing FDA-approved drugs to identify potential coronavirus disease 2019 (COVID-19) treatments. Besides, by using SHapley Additive exPlanations (SHAP), we found that SEGSA_DTA is interpretable and further provides a new quantitative analytical solution for structure-based lead optimization.

BackgroundClinical prediction models suffer from performance drift as the patient population shifts over time. There is a great need for model updating approaches or modeling frameworks that can effectively use the old and new data. ObjectiveBased on the paradigm of transfer learning, we aimed to develop a novel modeling framework that transfers old knowledge to the new environment for prediction tasks, and contributes to performance drift correction. MethodsThe proposed predictive modeling framework maintains a logistic regression–based stacking ensemble of 2 gradient boosting machine (GBM) models representing old and new knowledge learned from old and new data, respectively (referred to as transfer learning gradient boosting machine [TransferGBM]). The ensemble learning procedure can dynamically balance the old and new knowledge. Using 2010-2017 electronic health record data on a retrospective cohort of 141,696 patients, we validated TransferGBM for hospital-acquired acute kidney injury prediction. ResultsThe baseline models (ie, transported models) that were trained on 2010 and 2011 data showed significant performance drift in the temporal validation with 2012-2017 data. Refitting these models using updated samples resulted in performance gains in nearly all cases. The proposed TransferGBM model succeeded in achieving uniformly better performance than the refitted models. ConclusionsUnder the scenario of population shift, incorporating new knowledge while preserving old knowledge is essential for maintaining stable performance. Transfer learning combined with stacking ensemble learning can help achieve a balance of old and new knowledge in a flexible and adaptive way, even in the case of insufficient new data.

Systems for automatic detection of a single disease may miss other important conditions. Here, the authors show a deep learning platform can detect 39 common retinal diseases and conditions.

The psychological problems and employment problems of college students have always been the focus of attention of all sectors of society. The COVID-19 epidemic has a great impact on the mental health and employment of Chinese college students. Under this background, this study discusses how epidemic anxiety affects the employment confidence and perception of employment situation of Chinese college students. Through the online questionnaire survey of 1,132 college students nationwide, and the ordinal logistic regression analysis of the survey data using Stata 16.0 software, the results show that: (1) Epidemic anxiety negatively affects Chinese college students' employment confidence and employment situation perception, and has a significant impact on employment confidence. The three control variables of employment guidance, older age and higher education have a significant positive impact on college students' employment confidence and employment situation perception. College students in the eastern region have stronger employment confidence and more optimistic employment situation perception. But the expected monthly salary is negatively correlated with employment confidence. (2) Male college students and Science and Engineering students' epidemic anxiety have a stronger negative impact on employment confidence and employment situation perception. (3) Employment guidance has a moderating effect on the relationship between epidemic anxiety, employment confidence and employment situation perception. Employment guidance can enhance college students' employment confidence and reduce their sense of employment crisis by alleviating epidemic anxiety. Combined with the research conclusions, it is proposed that the state and schools should pay attention to the psychological counseling of college students, strengthen the employment guidance of colleges and universities, vigorously support the development of small, medium-sized and micro enterprises, and improve the employment and entrepreneurship service system of college students, so as to promote the employment of college students.

Arctic navigation research will be more urgent as it is predicted that 4.7% of the shipping trade will be deployed in the Arctic region by 2030. This paper presents a multi-objective path optimization algorithm based on the field theory to investigate Arctic shipping route design and navigation strategies that take safety, economy and environmental protection as factors. The algorithm considers the ice conditions in Arctic waters throughout the year, the energy consumption of ships with different ice classes and carbon emissions. The sea environment is initially modeled using the potential field method, incorporating the ice condition field, fuel consumption, emission field and directional field. The navigable area is defined based on the ship navigability, and path optimization is conducted using the principle of gradient descent between the departure point and destination. The experimental results show that the cost of carbon emissions and fuel consumption varies for each class of ship on the planned path in different months. Therefore, by combining different classes of ships and months, we obtain an Arctic navigation strategy with a consideration of the best cost and environmental protection for each month. The path planning and navigation strategy decision method proposed in this paper can provide a reference for an Arctic route design, navigation month and vessel selection, which is beneficial to the sustainable development of Arctic shipping.

Deep network models rely on sufficient training samples to perform reasonably well, which has inevitably constrained their application in classification of hyperspectral images (HSIs) due to the limited availability of labeled data. To tackle this particular challenge, we propose a hybrid relation network, H-RNet, by combining three-dimensional (3-D) convolution neural networks (CNN) and two-dimensional (2-D) CNN to extract the spectral–spatial features whilst reducing the complexity of the network. In an end-to-end relation learning module, the sample pairing approach can effectively alleviate the problem of few labeled samples and learn correlations between samples more accurately for more effective classification. Experimental results on three publicly available datasets have fully demonstrated the superior performance of the proposed model in comparison to a few state-of-the-art methods.

BackgroundObservational studies indicated that cholesterol efflux capacity (CEC) of high-density lipoprotein (HDL) is inversely associated with cardiovascular events, independently of the HDL cholesterol concentration. The aim of the study is to examine the casual relevance of CEC for coronary artery disease (CAD) and myocardial infarction (MI), and compare it with that for ischemic stroke and its subtypes using a Mendelian randomization approach.MethodsWe performed a 2-sample Mendelian randomization to estimate the casual relationship of CEC with the risk of CAD, MI, and ischemic stroke. A CEC-related genetic variant (rs141622900) and other five genetic variants were used as the instrumental variables. Association of genetic variants with CAD were estimated in a GWAS involving 60,801 CAD cases and 123,504 controls. They were then compared with the associations of these variants with ischemic stroke and its subtypes (large vessel, small vessel, and cardioembolic) involving 40,585 ischemic stroke cases and 406,111 controls.ResultsUsing the SNP of rs141622900 as the instrument, a 1-SD increase in CEC was associated with 45% lower risk for CAD (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.44–0.69, p < 0.001) and 33% lower risk for MI (odds ratio [OR] 0.67, 95% CI 0.52–0.87, p = 0.002). By contrast, the causal effect of CEC was much weaker for ischemic stroke (odds ratio [OR] 0.79, 95% CI 0.64–0.97, p = 0.02; p for heterogeneity = 0.03) and, in particular, for cardioembolic stroke (p for heterogeneity = 0.006) when compared with that for CAD. Results using five genetic variants as the instrument also indicated consistently weaker effects on ischemic stroke than on CAD.ConclusionGenetic predicted higher CEC may be associated with decreased risk of CAD. However, the casual association of CEC with ischemic stroke and specific subtypes would need to be validated in further Mendelian randomization studies.

Purple-stem Brassica napus (B. napus) is a phenotype with unique color because of its high anthocyanins content. Anthocyanins are naturally occurring plant pigments that have antioxidants activity and play important role in plant defense against abiotic and biotic stresses. In the present study, drought induced effects on plants were investigated in hydroponically grown seedlings of green stem (GS) and purple stem (PS) genotypes of B. napus. The results of this study showed that the major function of anthocyanins accumulation during drought was to enhance the antioxidant capability and stress tolerance in B. napus plants. Our results showed that drought significantly inhibited the plant growth in terms of decreased biomass accumulation in both genotypes, although marked decline was observed in GS genotype. The reduction in photosynthetic attributes was more noticeable in the GS genotype, whereas the PS genotype showed better performance under drought stress. Under stressful conditions, both the genotype showed excessive accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher levels of antioxidant enzymes activities. Under drought conditions, the GS genotype showed apparent damages on chloroplast deformation like in thylakoid membrane and grana structural distortion and fewer starch grains and bigger plastoglobuli. Moreover, during drought stress, the PS genotype exhibited maximum expression levels of anthocyanins biosynthesis genes and antioxidant enzymes accompanied by higher stress tolerance relative to GS genotype. Based on these findings, it can be concluded that GS genotype found more sensitive to drought stress than the PS genotype. Furthermore this research paper also provides practical guidance for plant biologists who are developing stress-tolerant crops by using anthocyanin biosynthesis or regulatory genes.

Objective To develop and validate a real-world screening, guideline-based deep learning (DL) system for referable diabetic retinopathy (DR) detection.Design This is a multicentre platform development study based on retrospective, cross-sectional data sets. Images were labelled by two-level certificated graders as the ground truth. According to the UK DR screening guideline, a DL model based on colour retinal images with five-dimensional classifiers, namely image quality, retinopathy, maculopathy gradability, maculopathy and photocoagulation, was developed. Referable decisions were generated by integrating the output of all classifiers and reported at the image, eye and patient level. The performance of the DL was compared with DR experts.Setting DR screening programmes from three hospitals and the Lifeline Express Diabetic Retinopathy Screening Program in China.Participants 83 465 images of 39 836 eyes from 21 716 patients were annotated, of which 53 211 images were used as the development set and 30 254 images were used as the external validation set, split based on centre and period.Main outcomes Accuracy, F1 score, sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), Cohen’s unweighted κ and Gwet’s AC1 were calculated to evaluate the performance of the DL algorithm.Results In the external validation set, the five classifiers achieved an accuracy of 0.915–0.980, F1 score of 0.682–0.966, sensitivity of 0.917–0.978, specificity of 0.907–0.981, AUROC of 0.9639–0.9944 and AUPRC of 0.7504–0.9949. Referable DR at three levels was detected with an accuracy of 0.918–0.967, F1 score of 0.822–0.918, sensitivity of 0.970–0.971, specificity of 0.905–0.967, AUROC of 0.9848–0.9931 and AUPRC of 0.9527–0.9760. With reference to the ground truth, the DL system showed comparable performance (Cohen’s κ: 0.86–0.93; Gwet’s AC1: 0.89–0.94) with three DR experts (Cohen’s κ: 0.89–0.96; Gwet’s AC1: 0.91–0.97) in detecting referable lesions.Conclusions The automatic DL system for detection of referable DR based on the UK guideline could achieve high accuracy in multidimensional classifications. It is suitable for large-scale, real-world DR screening.

Inorganic and organic nitrates are present in vivo and in vitro. Inorganic nitrate is considered a pool of nitric oxide (NO), but it can be converted into nitrite and NO through various mechanisms. It plays an important role in the regulation of complex physiological and biochemical reactions, such as anti-inflammatory processes and the inhibition of platelet aggregation, which are closely related to the pathology and treatment of cerebrovascular disease. Ischemic cerebrovascular disease is characterized by high incidence, recurrence, and disability rates. Nitrate, nitrite, and NO were recently found to be involved in cerebrovascular disease. In this review, we describe the relationship between cerebrovascular disease and nitrate metabolism to provide a basis for further advances in laboratory and clinical medicine.

Abstract Background Likelihood of developing acute kidney injury (AKI) increases with age. We aimed to explore whether the predictability of AKI varies between age groups and assess the volatility of risk factors using electronic medical records (EMR). Methods We constructed a retrospective cohort of adult patients from all inpatient units of a tertiary care academic hospital and stratified it into four age groups: 18–35, 36–55, 56–65, and > 65. Potential risk factors collected from EMR for the study cohort included demographics, vital signs, medications, laboratory values, past medical diagnoses, and admission diagnoses. AKI was defined based on the Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria. We analyzed relative importance of the risk factors in predicting AKI using Gradient Boosting Machine algorithm and explored the predictability of AKI across age groups using multiple machine learning models. Results In our cohort, older patients showed a significantly higher incidence of AKI than younger adults: 18–35 (7.29%), 36–55 (8.82%), 56–65 (10.53%), and > 65 (10.55%) (p 65 were 0.784 (95% CI, 0.769–0.800), 0.766 (95% CI, 0.754–0.777), 0.754 (95% CI, 0.741–0.768), and 0.725 (95% CI, 0.709–0.737), respectively. We also observed that the relative risk of AKI predictors fluctuated between age groups. Conclusions As complexity of the cases increases with age, it is more difficult to quantify AKI risk for older adults in inpatient population.

Background Obstructive sleep apnea (OSA) has shown to be associated with an increased risk of atrial fibrillation in observational studies. Whether this association reflect causal effect is still unclear. The aim of this study was to evaluate the causal effect of OSA on atrial fibrillation. Methods and Results We used a 2‐sample Mendelian randomization (MR) method to evaluate the causal effect of OSA on atrial fibrillation. Summary data on genetic variant‐OSA association were obtained from a recently published genome‐wide association studies with up to 217 955 individuals and data on variant‐atrial fibrillation association from another genome‐wide association study with up to 1 030 836 individuals. Effect estimates were evaluated using inverse‐variance weighted method. Other MR analyses, including penalized inverse‐variance weighted, penalized robust inverse‐variance weighted, MR‐Egger, simple median, weighted median, weighted mode‐based estimate and Mendelian Randomization Pleiotropy Residual Sum and Outlier methods were performed in sensitivity analyses. The MR analyses in both the fixed‐effect and random‐effect inverse‐variance weighted models showed that genetically predicted OSA was associated with an increased risk of atrial fibrillation (odds ratio [OR], 1.21; 95% CI, 1.12–1.31, P

In order to improve the combustion performance of a ramjet under low temperature and pressure, a gliding arc plasma actuator was designed based on a typical evaporation flameholder. The discharge characteristics, as well as the activating effect of single-channel and three-channel gliding arc plasma under different carrier gas flow rates, were studied. Results show that with the increase in the carrier gas flow rate, the average duration of the gliding arc discharge becomes shorter, while the average power increases, and the specific input energy decreases. Compared with single-channel discharge, three-channel discharge has higher discharge power and energy injection rate, which makes a bigger actuated space. Through gliding arc plasma, the kerosene is cracked and H2, CH4, C2H2, C2H4, C3H6 and other small molecule components are produced. For three-channel gliding arc discharge, the effective cracking rate and the production rate of each component are higher than those of the single-channel discharge; both of them gradually increase with the increase in the carrier gas flow rate. The experiment results indicate that three-channel gliding arc plasma can effectively widen the ignition boundary and improve the combustion efficiency of ramjet combustion. The ignition pressure boundary is expanded from 60 kPa to 50 kPa under 390 K; the combustion efficiency is increased from 76% to 82%.

Abstract This paper studies the rate control algorithm to improve the performance of semi-TCP, which adopts a buffer-based hop-by-hop congestion control mechanism. By analyzing the impact of the buffer-based sending strategy on the medium contention and interference, we find that this sending strategy is too aggressive to increase the throughput, which leads to severe contention and interference in the channel. Extensive simulations are then carried out and reveal the significance of the channel status of the first hop in rate control. Based on the findings in the simulations, we propose a binary search-based rate control to improve semi-TCP using only local information. The proposed rate control relies on the media status in the first hop to adjust the source rate to approach the peak throughput, without the assistance of end-to-end feedback. Simulation results show the effectiveness of the proposed algorithm in improving the end-to-end throughput and delay.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9), a pivotal protein in low-density lipoprotein cholesterol metabolism, has been validated to be an established target for cardiovascular (CV) risk reduction. Nevertheless, prospective studies concerning the associations between circulating PCSK9 and the risk of CV events and mortality have yielded, so far, inconsistent results. Herein, we conducted a meta-analysis to evaluate the association systemically.Methods: Pertinent studies were identified from PubMed, EMBASE, and Cochrane Library database through July 2020. Longitudinal studies investigating the value of circulating PCSK9 for predicting major adverse cardiovascular events (MACEs) or stroke or all-cause mortally with risk estimates and 95% confidence intervals (CI) were included in the analyses. Dose-response meta-analysis was also applied to evaluate circulating PCSK9 and risk of MACEs in this study.Results: A total of 22 eligible cohorts comprising 28,319 participants from 20 eligible articles were finally included in the study. The pooled relative risk (RR) of MACEs for one standard deviation increase in baseline PCSK9 was 1.120 (95% CI, 1.056–1.189). When categorizing subjects into tertiles, the pooled RR for the highest tertile of baseline PCSK9 was 1.252 (95% CI, 1.104–1.420) compared with the lowest category. This positive association between PCSK9 level and risk of MACEs persisted in sensitivity and most of the subgroup analyses. Twelve studies were included in dose-response meta-analysis, and a linear association between PCSK9 concentration and risk of MACEs was observed (x2 test for non-linearity = 0.31, P non-linearity = 0.575). No significant correlation was found either on stroke or all-cause mortality.Conclusion: This meta-analysis added further evidence that high circulating PCSK9 concentration significantly associated with increased risk of MACEs, and a linear dose-response association was observed. However, available data did not suggest significant association either on stroke or all-cause mortality. Additional well-designed studies are warranted to further investigate the correlations between PCSK9 concentration and stroke and mortality.

Background and purpose Transient ischaemic attack (TIA), transient symptoms with infarction (TSI) and diffusion-weighted imaging (DWI)-negative acute ischaemic stroke (AIS) share similar aetiologies but are considered to have a rather benign prognosis. We intended to investigate the association between intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and the prognosis of patients with TIA, TSI and DWI-negative AIS.Methods Clinical and imaging data of eligible participants were derived from the Chinese Intracranial Atherosclerosis study, according to symptom duration, acute infarction on DWI and discharge diagnosis. Based on the severity and location of arterial atherosclerosis, we categorised the study population into four groups: no or

Background and Purpose: Early age exposure to the Chinese Great Leap Forward famine (1959–1961) is associated with the incidence of risk factors for ischemic stroke. This study aims to examine the relationship between early age famine exposure and 12-month stroke recurrence. We sought to explore the interaction between famine exposure status and metabolic phenotypes on stroke recurrence and how the adherence of crucial evidence-based key performance indicators (KPI) would modify this interaction.Methods: We analyzed data of patients who were born between 1953 and 1964 in the China National Stroke Registry II (CNSR-II). The study population was further divided into five subgroups for comparing 12-month stroke recurrence. A multivariate Cox proportional hazard regression model was used in analyzing the impact of the concurrence of metabolic phenotypes—type 2 diabetes (T2D) or metabolic syndrome (MetS)—and early-age famine exposure on recurrent risk. The influence of the adherence to predefined KPI and concurrency of metabolic phenotype was also evaluated.Results: Concurrent T2D and early age famine exposure was associated with an increased recurrence risk of ischemic stroke with 12 months [adjusted hazard ratio (HR): 1.63, 95% confidence interval (CI) 1.28–2.07]. Optimal adherence to KPI was not associated with significantly reduced risk of 12-month stroke recurrence (adjusted HR: 0.80, 95% CI: 0.51–1.26).Conclusions: Concurrency of early-age famine exposure and diabetes mellitus was associated with a higher risk of stroke recurrence within 12 months, and adherence to evidence-based KPI did not reduce the risk significantly.

Aim: Early detection of coronavirus disease 2019 (COVID-19) patients who are likely to develop worse outcomes is of great importance, which may help select patients at risk of rapid deterioration who should require high-level monitoring and more aggressive treatment. We aimed to develop and validate a nomogram for predicting 30-days poor outcome of patients with COVID-19.Methods: The prediction model was developed in a primary cohort consisting of 233 patients with laboratory-confirmed COVID-19, and data were collected from January 3 to March 20, 2020. We identified and integrated significant prognostic factors for 30-days poor outcome to construct a nomogram. The model was subjected to internal validation and to external validation with two separate cohorts of 110 and 118 cases, respectively. The performance of the nomogram was assessed with respect to its predictive accuracy, discriminative ability, and clinical usefulness.Results: In the primary cohort, the mean age of patients was 55.4 years and 129 (55.4%) were male. Prognostic factors contained in the clinical nomogram were age, lactic dehydrogenase, aspartate aminotransferase, prothrombin time, serum creatinine, serum sodium, fasting blood glucose, and D-dimer. The model was externally validated in two cohorts achieving an AUC of 0.946 and 0.878, sensitivity of 100 and 79%, and specificity of 76.5 and 83.8%, respectively. Although adding CT score to the clinical nomogram (clinical-CT nomogram) did not yield better predictive performance, decision curve analysis showed that the clinical-CT nomogram provided better clinical utility than the clinical nomogram.Conclusions: We established and validated a nomogram that can provide an individual prediction of 30-days poor outcome for COVID-19 patients. This practical prognostic model may help clinicians in decision making and reduce mortality.

A new method is proposed in this paper to detect airborne nanoparticles, detecting the light scattering caused by both the particle and the surrounding molecules, which can surpass the limitations of conventional laser optical methods while maintaining simplicity and cost-effectiveness. This method is derived from a mathematical analysis that describes the particle light scattering phenomenon more exactly by including the influence of light scattered from surrounding gas molecules. The analysis shows that it is often too much of a simplification to consider only light scattering from the detected nanoparticle, because light scattering from the surrounding gas molecules, whether visible or invisible to the sensor, is important for nanoparticle detection. An image detection approach utilizing the light scattering from surrounding air molecules is described for the detection of airborne nanoparticles. Tests using monodisperse nanoparticles confirm that airborne particles of around 50 nm in size can even be detected using a low-cost testing device. This shows further that even when using a simple image processing code, captured particle light scattering images can be converted digitally into instantaneous particle counts or concentrations. The factors limiting conventional pulse detection are further discussed. This new method utilizes a simple static light scattering (SLS) approach to enable the development of new devices with better detection capabilities, paving the way for the further development of nanoparticle detection technology.

Aim Stroke is the leading cause of disability and death in China. Ischaemic stroke accounts for about 60%–80% of all strokes. It is of considerable significance to carry out multidimensional management of ischaemic cerebrovascular diseases. This evidence-based guideline aims to provide the latest detailed and comprehensive recommendations on the diagnosis, treatment and secondary prevention of ischaemic cerebrovascular diseases.Methods We had performed comprehensive searches of MEDLINE (via PubMed) (before 30 June 2019), and integrated the relevant information into charts and distributed to the writing group. Writing group members discussed and determined the recommendations through teleconference. We used the level of evidence grading algorithm of Chinese Stroke Association to grade each recommendation. The draft was reviewed by the Guideline Writing Committee of Chinese Stroke Association Stroke and finalised. This guideline is fully updated every 3 years.Results This evidence-based guideline is based on the treatment, care and prevention of ischaemic cerebrovascular diseases, which emphasises on pathogenesis evaluation, intravenous thrombolysis, endovascular therapy, antiplatelet therapy, prevention and treatment of complications, and risk factor management.Conclusions This updated guideline presents a framework for the management of ischaemic cerebrovascular diseases. Timely first-aid measures, professional care in the acute stage, and proactive secondary prevention will be helpful to patients.

Background: The combination of clopidogrel and aspirin is recommended for the treatment of patients with acute minor stroke or transient ischemic attack (TIA). However, with varied clopidogrel resistance (often due to CYP2C19 loss-of-function (LOF) alleles), alternatives like ticagrelor have been suggested. Previous studies showed that ticagrelor had a lower platelet reactivity assessed by VerifyNow P2Y12 assay than clopidogrel. We aimed to compare the effect of ticagrelor vs. clopidogrel on platelet reactivity assessed by a different method (Aggrestar platelet function analyzer) and analyze whether CYP2C19 genotypes were involved.Methods: A pre-specified subgroup analysis of a randomized controlled trial- Platelet Reactivity in Acute Non-disabling Cerebrovascular Events (PRINCE) was conducted. Patients with minor stroke or TIA were randomized for treatment with ticagrelor plus aspirin or clopidogrel plus aspirin. Platelet reactivity was assessed by Aggrestar (PL) platelet function analyzer and high on-treatment platelet reactivity (HOPR) on ticagrelor or clopidogrel was compared. Clinical outcomes included any stroke, composite vascular events and bleeding events within 90 days. Patients were categorized into carriers and non-carriers according to the carrier status of CYP2C19 LOF alleles.Results: Among 675 patients enrolled in the PRINCE trial, 387 patients were included in this subgroup: 197 were randomized to ticagrelor plus aspirin and 190 to clopidogrel plus aspirin. At 90 ± 7 days, compared with clopidogrel/aspirin group, the proportion of HOPR in ticagrelor/aspirin group was significantly lower (19.6 vs. 40.8%, P < 0.001). No significant treatment-by-genotype interactions were found (P for interaction = 0.12). Within 90 days, a trend toward a lower risk of new stroke in ticagrelor/aspirin compared to clopidogrel/aspirin was observed (4.6 vs. 9.5%, HR 0.47, 95% CI 0.21-1.05, P = 0.06).Conclusions: Ticagrelor is superior to clopidogrel in inhibiting platelet reactivity measured by the PL platelet function analyzer among patients with acute minor stroke or TIA. Our study confirmed the finding of the main analysis of PRINCE trial in a different assay. Large randomized controlled trials are needed to evaluate our findings.Clinical Trial Registration:Clinicaltrials.gov NCT02506140.

Objective Some patients have been found to develop intraoperative amaurosis under sub-Tenon’s anesthesia. We explored whether these patients have poor surgical outcomes during mid- to long-term postoperative follow-up. Methods In this case series, 74 of 85 patients with macular diseases who underwent phacoemulsification combined with vitrectomy under sub-Tenon’s anesthesia developed intraoperative amaurosis. The surgical outcomes at the 2- and 4-month follow-ups in these patients were investigated and compared with the outcomes in patients without amaurosis using best-corrected visual acuity (BCVA), optical coherence tomography (OCT), and pattern visual evoked potential (PVEP). Results Both BCVA and the OCT-based macular structure in patients with intraoperative amaurosis showed significant postoperative improvement comparable with that of patients without amaurosis. The presence of intraoperative amaurosis was not associated with either macular hole closure or macular edema regression. PVEP revealed no significant changes in the wave latency or amplitude before and after surgery. Conclusion Intraoperative amaurosis following sub-Tenon’s block is commonly seen but does not predict a poor surgical prognosis. When a patient develops amaurosis during surgery, the surgeon should increase patient comfort through verbal communication rather than perform an additional intervention to help relieve the patient’s anxiety.

Ischemic stroke is a life-threatening cerebral vascular disease and accounts for high disability and mortality worldwide. Currently, no efficient therapeutic strategies are available for promoting neurological recovery in clinical practice, except rehabilitation. The majority of neuroprotective drugs showed positive impact in pre-clinical studies but failed in clinical trials. Therefore, there is an urgent demand for new promising therapeutic approaches for ischemic stroke treatment. Emerging evidence suggests that exosomes mediate communication between cells in both physiological and pathological conditions. Exosomes have received extensive attention for therapy following a stroke, because of their unique characteristics, such as the ability to cross the blood brain–barrier, low immunogenicity, and low toxicity. An increasing number of studies have demonstrated positively neurorestorative effects of exosome-based therapy, which are largely mediated by the microRNA cargo. Herein, we review the current knowledge of exosomes, the relationships between exosomes and stroke, and the therapeutic effects of exosome-based treatments in neurovascular remodeling processes after stroke. Exosomes provide a viable and prospective treatment strategy for ischemic stroke patients.

The transmissions of ocean information have to cross the water-air interface.In this case,the information transmission network architecture requires the efficient integration of the underwater acoustic network and the radio network.However,the performance of the underwater acoustic link lags far behind the radio link,and becomes a bottleneck that restricts the performance of marine information networks.An acoustic-radio cooperative marine information network was proposed,which exploited the cooperation of acoustic and radio links to improve network performance.After demonstrating the advantages of acoustic-radio cooperation through three application scenarios,the network architecture and protocols,as well as the challenges for the acoustic-radio cooperative maritime information network were discussed.Acoustic-radio cooperation was not only an effective method for realizing the integration of air-water networks,but also an important method for realizing the integration of network communications,computing,and storage in marine information networks.

Abstract Background Acute kidney injury (AKI), characterized by abrupt deterioration of renal function, is a common clinical event among hospitalized patients and it is associated with high morbidity and mortality. AKI is defined in three stages with stage-3 being the most severe phase which is irreversible. It is important to effectively discover the true risk factors in order to identify high-risk AKI patients and allow better targeting of tailored interventions. However, Stage-3 AKI patients are very rare (only 0.2% of AKI patients) with a large scale of features available in EHR (1917 potential risk features), yielding a scenario unfeasible for any correlation-based feature selection or modeling method. This study aims to discover the key factors and improve the detection of Stage-3 AKI. Methods A causal discovery method (McDSL) is adopted for causal discovery to infer true causal relationship between information buried in EHR (such as medication, diagnosis, laboratory tests, comorbidities and etc.) and Stage-3 AKI risk. The research approach comprised two major phases: data collection, and causal discovery. The first phase is propose to collect the data from HER (includes 358 encounters and 891 risk factors). Finally, McDSL is employed to discover the causal risk factors of Stage-3 AKI, and five well-known machine learning models are built for predicting Stage-3 AKI with 10-fold cross-validation (predictive accuracy were measured by AUC, precision, recall and F-score). Results McDSL is useful for further research of EHR. It is able to discover four causal features, all selected features are medications that are modifiable. The latest research of machine learning is employed to compare the performance of prediction, and the experimental result has verified the selected features are pivotal. Conclusions The features selected by McDSL, which enable us to achieve significant dimension reduction without sacrificing prediction accuracy, suggesting potential clinical use such as helping physicians develop better prevention and treatment strategies.

The redundant design of communication networks leads to under-utilization of idle devices, which have been reported to consume a significant portion of energy. Thus, it demands a sleep scheduling scheme to improve energy efficiency of communication networks. In this paper, we formulate the optimal sleep scheduling problem from the perspective of routing, which aggregates the traffic loads to fewer active devices by route selection and put the idle devices into sleep to save energy. We then design a genetic algorithm to find out near-optimal sleep scheduling solution, which facilitates the implementation in software-defined networks. Simulation results over network instants from the online database survivable network design library show that our proposed genetic sleep scheduling algorithm outperforms the existing schemes in saving energy.

Abstract Thrombolysis treatment for patients with mild stroke is controversial. The aim of our study was to investigate whether patients with mild stroke or its specific etiologic subtype might benefit from rt-PA therapy. Data were derived from two cohorts of patients with and without rt-PA treatment: (1) the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) and (2) the China National Stroke Registry (CNSR) database. Patients with mild stroke (defined as National Institutes of Health Stroke Scale ≤5) receiving the rt-PA therapy and without rt-PA therapy were matched in 1:2 for age, sex, stroke severity and etiologic subtype. A total of 134 rt-PA-treated patients were matched to 249 non-rt-PA-treated patients in the study. Among them, 104 (76%) rt-PA-treated patients with mild stroke had good outcome after 3 months compared with 173 (69.5%) non-rt-PA-treated matching cases (odds ratio [OR], 1.48; 95% confidence interval [CI], 0.91–2.43; P = 0.12). Compared with non-rt-PA-treated group, rt-PA-treated patients had good outcome after 3 months in those with stroke subtype of large-artery atherosclerosis (LAA) (80.5% vs 65.1%; OR, 2.19; 95%CI, 1.14–4.21; P = 0.02). For patients with mild stroke, intravenous rt-PA treatment may be effective. Patients with stroke subtype of LAA might benefit more from rt-PA treatment.

To assess targeting of an epothilone folate conjugate (BMS-753493) to the folate receptor (FR)-overexpressed tumor in mice bearing both FR+ and FR– tumors, a series of experiments were conducted by quantitative whole-body autoradiography (QWBA) and LC–MS/MS following i.v. administration of BMS-753493 or its active moiety, BMS-748285 in mice bearing FR+ (98M109) and FR– (M109) tumors. QWBA showed [3H]BMS-753493–derived radioactivity was extensively distributed to various tissues. The FR over-expressing 98M109 tumors showed consistently higher level of radioactivity than FR-negative tumors (i.e., M109 tumors) up to 48 h post dose of [3H]BMS-753493, despite the magnitude of difference between the tumors is relatively small (generally 3~5-fold). The radioactivity level in 98M109 tumors was 2~12-fold of normal tissues except intestine/content at 48 h post dose. No selective radioactivity uptake into 98M109 tumors over M109 or normal tissues was observed after i.v. administration of the active epothilone, [3H]BMS-748285. LC–MS/MS measurements demonstrated that the concentrations of BMS-748285, presumably from hydrolysis of the folate conjugate, in 98M109 tumors were greater than those in M109 tumors after i.v. administration of BMS-753493 (2–3-fold) whereas no differential uptake in the tumors following BMS-748285 administration. Those data were consistent with radioactivity determinations. Those results demonstrated that the folate conjugation in BMS-753493 enabled moderately preferential distribution of the active epothilone to FR over-expressing 98M109 tumors, thereby supporting targeted delivery of cytotoxics through the folate receptor.

Grounded in social network theory and a risk-buffering model, this study examined whether delinquent peer affiliation mediated the association between peer victimization and adolescent aggressive behavior and whether this mediating process was moderated by parental knowledge. A total of 4,209 Chinese adolescents (48.47% male, Mage = 13.68) completed questionnaires on peer victimization, parental knowledge, delinquent peer affiliation, and adolescent aggressive behavior. Path analyses showed that delinquent peer affiliation partially mediated the relationship between peer victimization and aggressive behavior. Moreover, parental knowledge had a protective effect of buffering the adverse influence of peer victimization on aggressive behavior. This indirect link was stronger for adolescents with low parental knowledge than for those with high parental knowledge. This finding highlights delinquent peer affiliation as a potential link between peer victimization and aggressive behavior and provides an effective intervention for addressing the adverse effects of peer victimization.

BackgroundWe aimed to determine the risk conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent stroke in patients with minor ischemic stroke or transient ischemic attack from the CHANCE (Clopidogrel in High‐risk patients with Acute Non‐disabling Cerebrovascular Events) trial. Methods and ResultsIn total, 3044 patients were included. Patients were stratified into 4 groups: neither, METS only, DM only, or both. METS was defined using the Chinese Diabetes Society (CDS) and International Diabetes Foundation (IDF) definitions. The primary outcome was new stroke (including ischemic and hemorrhagic) at 90 days. A multivariable Cox regression model was used to assess the relationship of METS and DM status to the risk of recurrent stroke adjusted for potential covariates. Using the CDS criteria of METS, 53.2%, 17.2%, 19.8%, and 9.8% of patients were diagnosed as neither, METS only, DM only, and both, respectively. After 90 days of follow‐up, there were 299 new strokes (293 ischemic, 6 hemorrhagic). Patients with DM only (16.1% versus 6.8%; adjusted hazard ratio 2.50, 95% CI 1.89–3.39) and both (17.1% versus 6.8%; adjusted hazard ratio 2.76, 95% CI 1.98–3.86) had significantly increased rates of recurrent stroke. No interaction effect of antiplatelet therapy by different METS or DM status for the risk of recurrent stroke (P=0.82 for interaction in the fully adjusted model of CDS) was observed. Using the METS (IDF) criteria demonstrated similar results. ConclusionsConcurrent METS and DM was associated with an increased risk of recurrent stroke in patients with minor stroke and transient ischemic attack.

BackgroundInsulin resistance is associated with an increased risk of cardiovascular events in the general population. This study aimed to estimate the association between post–glucose load measures of insulin resistance and prognosis of nondiabetic patients with ischemic stroke. Methods and ResultsData were derived from the ACROSS‐China (Abnormal Glucose Regulation in Patients with Acute Stroke across China) registry. Patients with ischemic stroke without a history of diabetes mellitus were included. Two post–glucose load measures of insulin sensitivity, the insulin sensitivity indices ISI(composite) and the ISI0,120, were calculated. Outcomes included stroke recurrence, all‐cause death, and poor functional outcome at 12 months. Among 1203 patients, 63.3% were male with an average age of 62.1 years. At 12 months, 168 (14.4%) patients had recurrent stroke, 111 (9.2%) had died, and 288 (24.4%) had poor outcome. After adjustment for potential covariates, the first quartile of the ISI(composite) was associated with increased 12‐month stroke recurrence (adjusted hazard ratio 2.02, 95% CI 1.28–3.18, P=0.003), death (adjusted hazard ratio 2.78, 95% CI 1.59–4.86, P

To investigate the optical intensity in different compartments of subretinal fluid in acute Vogt-Koyanagi-Harada (VKH) disease by using spectral domain optical coherence tomography (SD-OCT).Fifty acute VKH eyes and 25 cases with acute central serous chorioretinopathy (CSCR) were included in this retrospective comparative study. The optical intensities of subretinal fluid, vitreous humour and the entire scanned region displayed by SD-OCT were measured with Image J by three independent readers. In the VKH eyes with subretinal septa, the subretinal fluid was segmented into two types of compartments, supra-septa space and sub-septa space. Optical intensity ratios of different compartments of subretinal fluids divided by vitreous humour or the entire scanned region were compared.The measurement of optical intensity was highly reproducible (intraclass correlation coefficient> 0.9). The optical intensity of the supra-septa space divided by the vitreous humour was significantly higher compared to that of sub-septa space in VKH (mean difference = 4.27 ± 5.15, p