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To characterize quick contrast sensitivity function (qCSF) in keratoconus and its correlation with corneal topographic parameters.Patients with keratoconus (n = 120) who visited the Fudan Eye and ENT Hospital between April and June 2021 were enrolled in our study. A total of 215 eyes were subdivided into three groups according to maximum keratometry (KSignificant differences in the area under the log CSF (AULCSF) and CSF Acuity among the three groups were found, which decreased with an increase in KThe use of qCSF test can serve as a feasible tool to evaluate visual quality and severity of keratoconus, since changes in CS significantly correlated with keratoconus severity.

Markers are needed to increase the diagnostic accuracy of prostate-specific antigen (PSA) in prostate cancer (PCa) screening. Mounting evidence has shown that plasma proteins can be hopeful biomarkers for cancer diagnosis.Tandem mass tag (TMT)-based proteomics and parallel reaction monitoring (PRM) analysis were used to screen the differential proteins and further validated in other independent studies (n = 539). Receiver-operating characteristic (ROC), decision curves and nomograms were applied to assess the diagnostic accuracy of biomarkers.Three candidate proteins (DBP, LCAT and ORM2) were preliminarily screened. Subsequent validation studies revealed significant upregulation of ORM2 in PCa patients across other independent cohorts. ORM2 yielded excellent discriminative power for PCa from benign prostatic hyperplasia (BPH) patients (AUC = 0.861 and 0.814 in validation phases 2a and 2b, respectively). Importantly, the combination of ORM2 and PSA gave better predictive accuracy than PSA alone. We incorporated age, PSA and ORM2 into a nomogram, which yielded C-index of 0.883 in validation phase 2a. A similar C-index of 0.879 was obtained in external validation phase 2b.In summary, our study suggests that ORM2 could be treated as a complementary biomarker for PSA in distinguishing PCa from BPH.

The fast development of mid-wave infrared photonics has increased the demand for high-performance photodetectors that operate in this spectral range. However, the signal-to-noise ratio, regarded as a primary figure of merit for mid-wave infrared detection, is strongly limited by the high dark current in narrow-bandgap materials. Therefore, conventional mid-wave infrared photodetectors such as HgCdTe require cryogenic temperatures to avoid excessively high dark current. To address this challenge, we report an avalanche photodiode design using photon-trapping structures to enhance the quantum efficiency and minimize the absorber thickness to suppress the dark current. The device exhibits high quantum efficiency and dark current density that is nearly three orders of magnitude lower than that of the state-of-the-art HgCdTe avalanche photodiodes and nearly two orders lower than that of previously reported AlInAsSb avalanche photodiodes that operate at 2 µm. Additionally, the bandwidth of these avalanche photodiodes reaches ~7 GHz, and the gain–bandwidth product is over 200 GHz; both are more than four times those of previously reported 2 µm avalanche photodiodes.

Objective This study evaluated the identification efficiency of contrast-enhanced ultrasound (CEUS) for sentinel lymph nodes (SLN) to accurately represent the axillary node status in early-stage breast cancer. Method In total, 109 consecutive consenting patients with clinically node-negative and T1-2 breast cancer were included in this study. All patients received CEUS to identify SLN before surgery, and a guidewire was deployed to locate SLN in those who were successfully explored by CEUS. The patients underwent sentinel lymph node biopsy (SLNB), and the blue dye was used to trace SLN during the surgery. The decision to perform axillary lymph node dissection (ALND) depended on the intraoperative pathological identification of SLN by CEUS (CE-SLN). The concordance rate of pathological status between CE-SLN and dyed SLN was calculated. Result The CEUS detection rate was 96.3%; CE-SLN failed in 4 patients. Among the remaining 105 successful identifications, 18 were CE-SLN positive by intraoperative frozen section, and one with CE-SLN micrometastasis was diagnosed by paraffin section. No additional lymph node metastases were found in CE-SLN-negative patients. The concordance rate of pathological status between CE-SLN and dyed SLN was 100%. Conclusion CEUS can accurately represent the status of axillary lymph nodes in patients with clinically node-negative and small tumor burden breast cancer. Graphical Abstract

Telomeres, at the ends of chromosomes, protect chromosomes from fusion and preserve genomic stability. However, the molecular mechanisms underlying telomere attrition-induced genome instability remain to be understood. We systematically analyzed the expression of retrotransposons and performed genomic sequencing of different cell and tissue types with telomeres of varying lengths due to telomerase deficiency. We found that critically short telomeres altered retrotransposon activity to promote genomic instability in mouse embryonic stem cells, as evidenced by elevated numbers of single nucleotide variants, indels and copy number variations (CNVs). Transpositions of retrotransposons such as LINE1 resulting from the short telomeres can also be found in these genomes with elevated number of mutations and CNVs. Retrotransposon activation is linked to increased chromatin accessibility, and reduced heterochromatin abundance correlates with short telomeres. Re-elongation of telomeres upon recovery of telomerase partly represses retrotransposons and heterochromatin accumulation. Together, our findings suggest a potential mechanism by which telomeres maintain genomic stability by suppressing chromatin accessibility and retrotransposon activity.

Background Implantable collamer lens (ICL) has been widely accepted for its excellent visual outcomes for myopia correction. It is a new challenge in phakic IOL power calculation, especially for those with low and moderate myopia. This study aimed to establish a novel stacking machine learning (ML) model for predicting postoperative refraction errors and calculating EVO-ICL lens power. Methods We enrolled 2767 eyes of 1678 patients (age: 27.5 ± 6.33 years, 18–54 years) who underwent non-toric (NT)-ICL or toric-ICL (TICL) implantation during 2014 to 2021. The postoperative spherical equivalent (SE) and sphere were predicted using stacking ML models [support vector regression (SVR), LASSO, random forest, and XGBoost] and training based on ocular dimensional parameters from NT-ICL and TICL cases, respectively. The accuracy of the stacking ML models was compared with that of the modified vergence formula (MVF) based on the mean absolute error (MAE), median absolute error (MedAE), and percentages of eyes within ± 0.25, ± 0.50, and ± 0.75 diopters (D) and Bland-Altman analyses. In addition, the recommended spheric lens power was calculated with 0.25 D intervals and targeting emmetropia. Results After NT-ICL implantation, the random forest model demonstrated the lowest MAE (0.339 D) for predicting SE. Contrarily, the SVR model showed the lowest MAE (0.386 D) for predicting the sphere. After TICL implantation, the XGBoost model showed the lowest MAE for predicting both SE (0.325 D) and sphere (0.308 D). Compared with MVF, ML models had numerically lower values of standard deviation, MAE, and MedAE and comparable percentages of eyes within ± 0.25 D, ± 0.50 D, and ± 0.75 D prediction errors. The difference between MVF and ML models was larger in eyes with low-to-moderate myopia (preoperative SE > − 6.00 D). Our final optimal stacking ML models showed strong agreement between the predictive values of MVF by Bland-Altman plots. Conclusion With various ocular dimensional parameters, ML models demonstrate comparable accuracy than existing MVF models and potential advantages in low-to-moderate myopia, and thus provide a novel nomogram for postoperative refractive error prediction and lens power calculation.

Vehicle Logo Detection (VLD) is of great significance to Intelligent Transportation Systems (ITS). Although many methods have been proposed for VLD, it remains a challenging problem. To improve the VLD accuracy, an Intersection over Average (IoAverage) loss is proposed for enhancing the bounding box regression. The IoAverage loss accelerates the convergence of bounding box regression than using the Intersection over Union (IoU) loss. In the experiments, IoAverage loss has been incorporated into the state-of-the-art object detection framework YOLOV5s, namely YOLOV5s-IoAv in this paper. The advantages of the IoAverage loss are verified on the PASCAL VOC2007 datasets. The results of using the IoAverage loss show performance gains of + 15.27% mAP0.5 and + 30.87% mAP0.5:0.95 higher than that of the Complete IoU (CIoU) loss. The application of YOLOV5s-IoAv is implemented to VLD on dataset VLD100K-61. VLD100K-61 is a self-collected dataset containing 100,041 images supplied by traffic surveillance cameras in the real world from 61 categories. YOLOV5s-IoAv achieves performance gains as + 15.27% mAP0.5:0.95 for VLD than YOLOV5s-CIoU. The proposed method yields the mAP0.5 value of up to 0.992 on the dataset VLD100K-61, providing a promising solution to vehicle logo recognition applications.

Purpose To investigate the morphological changes of concave iris in myopic patients after EVO implantable collamer lens (ICL) implantation. Methods EVO ICL candidates with posterior bowing iris were observed using ultrasound biometric microscopy (UBM) in this prospective nonrandomized observational study. Forty patients were enrolled, with 20 patients in the concave iris group and the other 20 patients in the control group. None of the patients underwent laser peripheral iridotomy. All patients received preoperative and postoperative examinations, which included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), subjective manifest refraction and intraocular pressure. UBM was used to observe iris curvature (IC), irido-corneal angle (ICA), posterior chamber angle (PCA), iris-lens contact distance (ILCD), iris-zonule distance (IZD) and ciliary process length (CPL). Anterior chamber angle pigment was observed by gonioscopy. The preoperative and postoperative data were analyzed using SPSS. Results The average follow-up period was 13.3 ± 5.3 months. The mean efficacy indices were 1.10 ± 0.13 and 1.07 ± 0.11 (P = 0.58), and the safety indices were 1.19 ± 0.09 and 1.18 ± 0.17 in the control group and the concave iris group (P = 0.93), respectively. The IOP postoperatively were 14.13 ± 2.02 mmHg and 14.69 ± 1.59 mmHg in control and concave iris groups (P = 0.37). Preoperatively, the concave iris group was presented with greater IC (P P P = 0.004), narrower PCA (P = 0.01), and shorter IZD (P = 0.03) than the control group. In the concave iris group, IC, ILCD and ICA were significantly decreased after ICL implantation (P P = 0.03 and P = 0.04, respectively). Postoperative IC, ILCD, ICA, PCA and IZD were not statistically different between groups (P > 0.05). There was no significant difference in pigment deposition grades between the two groups (P = 0.37). Conclusion After EVO ICL implantation, the morphology of concave iris was significantly improved, which may reduce the risk of intraocular pigment dissemination caused by iris concavity. The concave iris has no impact on the safety of EVO ICL surgery during the follow-up.

With the rapid development of two-phase heat exchangers, the further improvement of the capillary performance of their internal wick faces a great challenge. As an important technology in the surface treatment of aluminum alloys, anodic oxidation has been widely used to develop various functional nanostructures. In this study, nanopores with diameters of 30–40 nm were fabricated on the surface of aluminum fibers through anodic oxidation under an oxalic acid system. Results showed that anodizing increased the specific surface area of the aluminum braid by 163 times, and changed its surface wettability from hydrophobic to superhydrophilic. A significant reduction in the effective capillary radius can substantially increase the capillary force of aluminum braids on the basis of capillary theory. Therefore, the nanoporous aluminum braids can be used as a novel wick in the vapor chamber to improve its capillary performance. Capillary rate-of-rise tests with ethanol and acetone were performed to characterize the capillary of this novel wick structure. Infrared thermal imaging was utilized to monitor the capillary rise of aluminum braided wicks. The capillary force of the anodized wicks was greater than that of a normal wick, and the maximum capillary rise height was 81 mm. The nanoporous aluminum braided wicks prepared by anodizing could be applied in heat transfer.

Background Preoperative analgesia of hip fracture in elderly patients is important, but it is also lacking. In particular, nerve block was not provided in time. In order to provide more effective analgesia, we designed a multimodal pain management mode based on instant messaging software. Methods From May to September 2022, a total of 100 patients with unilateral hip fracture aged over 65 were randomly divided into the test group and the control group. Finally, 44 patients in each group completed the result analysis. A new pain management mode was used in the test group. This mode focuses on the full information exchange between medical personnel in different departments, early fascia iliaca compartment block (FICB), and closed-loop pain management. Outcomes include the time when FICB is completed for the first time; The number of cases of FICB completed by emergency doctors; Patients' pain score, pain duration. Results The time for patients in the test group to complete FICB for the first time was 3.0 [1.925–3.475] h, which was less than the time for patients in the control group (4.0 [3.300–5.275] h). The difference was statistically significant (P P = 0.087). The test group was superior to the control group in the highest NRS score (4.00 [3.00–4.00] vs 5.00 [4.00–5.75]), the duration of the highest NRS score (20.00 [20.00–25.00] mins vs 40.00 [30.00–48.75] mins), and the NRS > 3 time (35.00 [20.00–45.00] mins vs 72.50 [60.00–45.00] mins). The analgesic satisfaction of patients in the test group (5.00 [4.00–5.00]) was also significantly higher than that of the control group (3.00 [3.00–4.00]). The above four indexes were different between the two groups (P Conclusions Using instant messaging software, the new model of pain management can enable patients to receive FICB as soon as possible and improve the timeliness and effectiveness of analgesia. Trial registration Chinese Clinical Registry Center, ChiCTR2200059013, 23/04/2022.

Objective Currently, the association between smoking, alcohol, and coffee intake and the risk of ovarian cancer (OC) remains conflicting. In this study, we used a two-sample mendelian randomization (MR) method to evaluate the association of smoking, drinking and coffee consumption with the risk of OC and prognosis. Methods Five risk factors related to lifestyles (cigarettes per day, smoking initiation, smoking cessation, alcohol consumption and coffee consumption) were chosen from the Genome-Wide Association Study, and 28, 105, 10, 36 and 36 single-nucleotide polymorphisms (SNPs) were obtained as instrumental variables (IVs). Outcome variables were achieved from the Ovarian Cancer Association Consortium. Inverse-variance-weighted method was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). Results The two-sample MR analysis supported the causal association of genetically predicted smoking initiation (OR: 1.15 per SD, 95%CI: 1.02–1.29, P = 0.027) and coffee consumption (OR: 1.40 per 50% increase, 95%CI: 1.02–1.93, P = 0.040) with the risk of OC, but not cigarettes per day, smoking cessation, and alcohol consumption. Subgroup analysis based on histological subtypes revealed a positive genetical predictive association between coffee consumption and endometrioid OC (OR: 3.01, 95%CI: 1.50–6.04, P = 0.002). Several smoking initiation-related SNPs (rs7585579, rs7929518, rs2378662, rs10001365, rs11078713, rs7929518, and rs62098013), and coffee consumption-related SNPs (rs4410790, and rs1057868) were all associated with overall survival and cancer-specific survival in OC. Conclusion Our findings provide the evidence for a favorable causal association of genetically predicted smoking initiation and coffee consumption with OC risk, and coffee consumption is linked to a greater risk of endometrioid OC.

Background For elderly adults undergoing hip arthroplasty, fascia iliaca compartment block (FICB) is often used before spinal anesthesia to reduce the pain of posture placement. However, the impact of FICB within 48 h needs further study. Methods 89 elderly adults scheduled to undergo arthroplasty for hip fracture were enrolled and randomized into the FICB group (n = 45) and the control group (n = 44). The fascia iliaca on the operated side was located using ultrasound, and a puncture needle was placed under the fascia iliaca. The FICB group was injected with 40 ml of 0.5% ropivacaine, and the control group was injected with 40 ml of normal saline. Spinal anesthesia was performed after 20 min. Our primary outcome measures were: duration of analgesia, muscle strength, and Quality of Recovery (QoR). Results The duration of analgesia in the FICB group was 403.5 ± 39.6 min, which was longer than that (357.5 ± 35.9 min) of the control group (P = 0.012). There were 19 (42.2%) patients with muscle strength of grade 4 in the FICB group and 36 (81.8%) patients with muscle strength of grade 4 in the control group. FICB group was lower (P P P = 0.232). Conclusions For elderly adults with hip fractures, FICB provided longer analgesia and improved 24-h QoR, but reduced postoperative muscle strength. Trail registration Chinese Clinical Registry Center, ChiCTR2200056937, 23/02/2022.

Background To compare the characteristics of corneal thickness measurements among the RTVue, Casia-2, and Pentacam in patients with mild-to-moderate keratoconus. Methods We recruited 46 eyes of 46 patients diagnosed with mild-to-moderate keratoconus at our hospital between January and March 2022. The central corneal thickness (CCT) and thinnest corneal thickness (TCT) were measured using two optical coherence tomography (OCT) instruments (RTVue and Casia-2) and the more conventional Pentacam. Differences and correlations between the CCTs and TCTs, based on the device and influencing factors, were explored. Results The CCTs were highly consistent among the groups (p = 0.434) and correlated with one another (p p p p p = 0.633) and thinnest point location measurement (p > 0.05). Multivariate analysis identified that the TCT measurement difference between the RTVue and Pentacam was related to the difference between the CCT and TCT (b = 0.490, 95% confidence interval [CI]: 0.033 to 0.948, p = 0.036), whereas the difference between the Casia-2 and Pentacam was related to the anterior radius for curvature (A) grade (b = 3.9, 95% CI: 1.753 to 6.074, p = 0.001), corneal pachymetry at the thinnest (C) grade (b = − 7.875, 95% CI: − 11.404 to − 4.346, p p = 0.012). Conclusions CCTs in patients with mild-to-moderate keratoconus were similar among all three devices, but the TCTs and the thinnest point locations were not. Furthermore, the TCT measurement differences between the OCT devices and the Pentacam were more pronounced in keratoconus cases with a steeper anterior surface, thicker TCTs, and a larger difference between the CCT and TCT. Trial registration Number: 2021118–1. Retrospectively registered: September 01, 2021.

Background Gilteritinib is the only drug approved as monotherapy for acute myeloid leukemia (AML) patients harboring FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation throughout the world. However, drug resistance inevitably develops in clinical. Sitravatinib is a multi-kinase inhibitor under evaluation in clinical trials of various solid tumors. In this study, we explored the antitumor activity of sitravatinib against FLT3-ITD and clinically-relevant drug resistance in FLT3 mutant AML. Methods Growth inhibitory assays were performed in AML cell lines and BaF3 cells expressing various FLT3 mutants to evaluate the antitumor activity of sitravatinib in vitro. Immunoblotting was used to examine the activity of FLT3 and its downstream pathways. Molecular docking was performed to predict the binding sites of FLT3 to sitravatinib. The survival benefit of sitravatinib in vivo was assessed in MOLM13 xenograft mouse models and mouse models of transformed BaF3 cells harboring different FLT3 mutants. Primary patient samples and a patient-derived xenograft (PDX) model were also used to determine the efficacy of sitravatinib. Results Sitravatinib inhibited cell proliferation, induced cell cycle arrest and apoptosis in FLT3-ITD AML cell lines. In vivo studies showed that sitravatinib exhibited a better therapeutic effect than gilteritinib in MOLM13 xenograft model and BaF3-FLT3-ITD model. Unlike gilteritinib, the predicted binding sites of sitravatinib to FLT3 did not include F691 residue. Sitravatinib displayed a potent inhibitory effect on FLT3-ITD-F691L mutation which conferred resistance to gilteritinib and all other FLT3 inhibitors available, both in vitro and in vivo. Compared with gilteritinib, sitravatinib retained effective activity against FLT3 mutation in the presence of cytokines through the more potent and steady inhibition of p-ERK and p-AKT. Furthermore, patient blasts harboring FLT3-ITD were more sensitive to sitravatinib than to gilteritinib in vitro and in the PDX model. Conclusions Our study reveals the potential therapeutic role of sitravatinib in FLT3 mutant AML and provides an alternative inhibitor for the treatment of AML patients who are resistant to current FLT3 inhibitors.

Background Type 2 innate lymphoid cells (ILC2) are upregulated in childhood allergic rhinitis (AR) and are associated with AR severity. This study aimed to investigate changes in the ILC2 milieu in pediatric patients with AR after sublingual immunotherapy (SLIT). Methods Forty- pediatric patients with AR received house dust mite (HDM) allergen extract for SLIT group and thirty pediatric patients received placebo in the study, respectively. The levels of ILC2, ILC2-related cytokines (IL-5/IL-13) and their transcription factors (GATA binding protein 3, retinoic acid-related orphan receptor α) in the circulation were assessed after 1- and 2-year SLIT. Moreover, peripheral blood mononuclear cells (PBMCs) in patients were prepared and stimulated by recombinant thymic stromal lymphopoietin, IL-25, and IL-33 after 2-year SLIT. Subsequently, the levels of ILC2, IL-5, and IL-13 were tested. Results The frequency of ILC2 and the levels of their transcription factors in the circulation were significantly decreased after SLIT in the SLIT group. The levels of ILC2-related cytokines in the SLIT group showed the same trend. The frequency of ILC2 was positively correlated with transcription factors and cytokines after SLIT. SLIT was observed to reduce the ability of HDM sensitization to generate the ILC2 milieu in PBMCs. Conclusions Changes in the ILC2 milieu may be correlated with the curative effect and immune regulation function of SLIT. Our results suggested that the regulatory effect on ILC2 is part of the therapeutic mechanism of SLIT.

Developmental dysplasia of the hip (DDH) is a debilitating condition that affects 1–7% of newborns. Children with DDH, not treated early and effectively, will easily lead to disability. A better understanding of the biology of DDH is critical to the development of prognostic biomarkers and novel therapies. The purpose of this study was to establish a biobank of DDH genetic resources, to facilitate clinical and basic scientific research. The biological specimen and clinical data of DDH were collected in Shanghai Children’s Hospital from 2014 to 2021. The collection of blood samples was performed at definitive diagnosis and review, tissue specimens were performed at definitive surgery. The clinical data was collected at the whole stage of DDH patients at diagnosis, treatment and follow-up. A total of 528 patients with DDH were enrolled in this study, 90 were men and 438 were women, with the mean age of 4.67 years. The numbers of tissue and blood specimens reached 2172 and 1490, respectively. The quality test results showed that the DNA concentration decreased slightly with the extension of storage time, but the DNA purity did not change. Meanwhile, the extension of storage time slightly affected the stability of protein of tissue samples but did not affect the expression of the housekeeping gene. The DDH biobank built has the potential of monitoring disease pathogenesis and progress, which could provide specimens to the researchers improving the biological understanding and provide guidance of clinical treatment of this disease to clinicians.

CD8+CD103+ tissue-resident memory T cells (TRMs) are involved in tumor immune response and linked to favorable clinical outcome in human cancer. However, the distribution, phenotype, functional properties and clinical relevance of these cells in gastric cancer (GC) remain elusive. Here, our data show that, in comparison to non-tumor tissues, the percentages of CD8+CD103+ TRMs in tumors are significantly decreased. Most tumor-infiltrating CD8+CD103+ TRMs are CD45RA−CCR7− effector-memory cells with higher PD-1 and 4-1BB expression than those from non-tumor tissues. Further, tumor-infiltrating CD8+CD103+ TRMs show impaired cytolytic capacity due to decreased granzyme B and perforin expression. Moreover, ex vivo PD-1 blockade could restore the cytolytic capacity of tumor-infiltrating CD8+CD103+ TRMs, and such anti-PD-1-mediated reinvigoration of CD8+CD103+ TRMs could be further enhanced by 4-1BB co-stimulation. Finally, lower levels of Tumor-infiltrating CD8+CD103+ TRMs are positively correlated with GC progression and poor patients’ survival. Our data suggest that restoring CD8+CD103+ TRM function by combining PD-1 blockade and 4-1BB co-stimulation may be a promising strategy for treating GC.

Accurate and credible displacement prediction is essential to dam safety monitoring. However, due to the inherent uncertainties involved in dam systems, errors of conventional deterministic point predictions are inevitable and sometimes large. In this paper, prediction intervals (PIs) are used instead of deterministic values to quantify the associated uncertainties and improve the reliability of dam displacement prediction. A hybrid modeling approach is proposed to synthetically evaluate the aleatoric and epistemic uncertainties through PI construction, which integrates the non-parametric bootstrap, least squares support vector machine (LSSVM), and artificial neural network (ANN) algorithms. Specifically, the PIs of dam displacement are constructed in two stages. In the first stage, multiple bootstrap-based LSSVMs are utilized to estimate the true regression means of future displacements and the variance of model uncertainty. In the second stage, a modified ANN (MANN) is developed and applied to estimate the variance of data noise. The final PIs are calculated by combining the true regression means and the variances of model uncertainty and data noise. The performance of the bootstrap-LSSVM–MANN model is verified using monitoring data from a real concrete dam. The results show that the proposed method can generate computationally efficient high-quality PIs and can effectively deal with multiple uncertainties in data-driven modeling and prediction. The novel approach has great potential to support the decision-making activities in an environment characterized by uncertainties and risks.