Background:Ambient ozone (O3) exposure has been found to be associated with gestational hypertension, which, in turn, increases the risk of term low birth weight (LBW). As such, gestational hypertension acts as a potential mechanism mediating restricted fetal growth; however, few epidemiological studies have quantified this specific mediation pathway. Objective:This study aims to examine whether gestational hypertension serves as a mediator of the association between prenatal O3 exposure and term LBW. Methods:We conducted a population-based cohort study using the Cheeloo Lifespan Electronic Health Research Data-library, including 3,394,739 singleton term live births in Shandong Province, China, from January 1, 2016, to December 31, 2022. We used high-resolution spatiotemporal models based on residential addresses for exposure assessment. In addition to term LBW, we examined term small for gestational age (SGA) to capture fetal growth restriction while accounting for gestational age at birth. Given the low prevalence of these outcomes, we used logistic regression models where odds ratios approximated relative risks. A 4-step mediation analysis using logistic regression was conducted, followed by a counterfactual-based causal mediation analysis, to test the mediating role of gestational hypertension. Results:The mean (SD) O3 concentration was 113.90 (13.03) μg m-3. Each IQR increase in O3 was positively associated with the risks of term LBW (relative risk 1.055, 95% CI 1.034-1.077) and term SGA (relative risk 1.037, 95% CI 1.026-1.048). Using the traditional approach, gestational hypertension mediated 19.94% of the risk for term LBW and 13.41% for term SGA. Under the counterfactual framework, the contribution rates were 38.82% (term LBW) and 19.96% (term SGA) when excluding exposure-mediator interaction, and 35.15% (term LBW) and 18.82% (term SGA) when accounting for such interaction. Conclusions:Our findings showed that gestational hypertension was a significant mediator of the association between O3 exposure and risks of term LBW. Consequently, a multitiered strategy-encompassing stricter air quality standards, integrating O3 risk education into routine prenatal care, and taking proactive measures to minimize personal exposure-is essential to prevent potential adverse impacts on developing fetuses and mothers.

Deep networks trained on noisy labels simultaneously generalize on clean data and memorize flipped labels. These are usually conflated as pressures on one capacity. We present Topo^2, a measurement framework that makes them causally separable, measurable, and law-governed. Persistent-homology H1 structure of the representation space separates into a within-class manifold channel (a function of the training stopping point) and a cross-class channel (a monotone readout of memorized flipped samples). An intervention, the FM0 prescription (zero loss on flipped samples from epoch 0), reaches each setting's generalization ceiling while memorizing essentially nothing. Within the framework we establish a law set with graded evidence: (L2) FM0 separation prescription (9/9); (L1) the within-channel as a training-position function (mid-rise 6/6; convergence-back CIFAR 3/3, SVHN 2/3); (L3) a ring-construction identity (definitional, not a law); and TLS (memory-generalization topological layering): memory is causally additive, anchored (silencing clean collapses the representation), invertible (stripping memory restores near-ceiling generalization), and quantitatively billable (the memorization cost law, effective slope coefficient C 0.38 at the reference capacity: CIFAR-10 0.3801 / SVHN 0.3806 / CIFAR-100 0.384 / VGG 0.3715, capacity-dependent in general and traced to clean-sample feature displacement). We also publish the framework's boundaries: a falsification ledger of nine dead ends, and an instrument-vindication section that excludes six families of global statistics as explanations of the within-channel. The framework turns "memorization" from an ill-defined capacity into a measurable, separable, invertible topological layer.

Background: This study investigates the correlation between the weight-adjusted waist index (WWI) and cognitive performance in the senior American population, focusing on those without diabetes from 2011 to 2014. Methods: We analyzed data from the 2011-2012 and 2013-2014 National Health and Nutrition Examination Surveys (NHANES), focusing on non-diabetic participants aged 60 and older who completed cognitive tests: Establish a Registry for Alzheimer's disease (CERAD), the Animal Fluency test (AFT), and Digit Symbol Substitution test (DSST). WWI was calculated using waist circumference divided by the square root of body weight. We employed linear univariate and multivariate analyses, along with curve fitting, we conducted subgroup and interaction analyses to elucidate the relationships under investigation. Results: The study incorporated a cohort of 1649 participants aged 60 years and older, each with a complete set of data, enabling a thorough analysis. After adjusting for confounding factors, significant negative correlations were found between WWI and both CERAD ((3: -0.48; 95% CI: -0.92 to -0.05; P=0.03) and DSST ((3: -1.15; 95% CI: -2.09 to -0.21; P=0.017) scores, suggesting a link to cognitive decline. No association was found with AFT scores. The relationship between WWI and DSST was found to be nonlinear (P for non-linearity=0.022). Additionally, the association between WWI and CERAD was also observed (P for non-linearity=0.042). However, linear relationships were observed between WWI and AFT (P for non-linearity=0.418). The subgroup analysis was overall stable. Conclusion: Our cross-sectional study indicates a strong link between a high WWI and reduced cognitive function in non-diabetic older Americans, as shown by CERAD and DSST scores. Attaining an optimal WWI may be vital for cognitive decline, highlighting its role in a potential preventative approach. Clinical Trial Registry Number and Website Where It Was Obtained: The study design and data are publicly accessible at www.cdc.gov/nchs/nhanes/.

BACKGROUND:Cefoperazone/sulbactam (CPZ/SAM) is a first-line antibacterial drug in clinical practice. METHODS:This article reports a case of extreme elevation of INR due to the use of CPZ/SAM four days. After drug withdrawal and administration of fresh frozen plasma, the coagulation function returned to normal. RESULTS:The INR results were extremely elevated, which is believed to be caused by taking CPZ/SAM. CONCLUSIONS:When patients take CPZ/SAM anti-infection therapy, the patient's coagulation function should be closely monitored for the prevention of the occurrence of adverse reactions.

Objective To explore the value of amide proton transfer-weighted imaging(APTw) and T2 mapping in assessing microsatellite instability(MSI) in endometrial adenocarcinoma. Methods The patients with clinically suspected endometrial cancer were prospectively enrolled and underwent APTw and T2 mapping before operation.Two radiologists independently outlined the regions of interest and measured the quantitative parameters.The intragroup correlation coefficients were calculated to assess the agreement of MRI parameters measured by the two radiologists.The independent samples t-test and Mann-Whitney U test were conducted to compare quantitative variables between the MSI and microsatellite stability(MSS) groups.The receiver operator characteristic curve was established to evaluate the prediction performance of different parameters.The DeLong test was implemented to compare the area under the curve(AUC) between single parameters and their combination. Results Twenty-one patients in the MSI group and 37 patients in the MSS group were finally enrolled in this study.The results showed excellent agreement between two radiologists in assessing MRI parameters.The MSI group had higher APTw values[(2.72±0.52)% vs.(2.08±0.39)%,P<0.001]and lower T2 values[92.25(90.82,99.91) ms vs.101.80(96.15,112.13) ms,P<0.001]than the MSS group.The receiver operating characteristic curve showed that the AUC of APTw and T2 values were 0.821(95%CI=0.698-0.909) and 0.793(95%CI=0.666-0.888),respectively.No significant difference in diagnostic efficacy was observed between the two sequences(P=0.692).The combination of APTw and T2 mapping yielded the highest AUC of 0.897(95%CI=0.789-0.961),which was higher than that of APTw and T2 mapping alone(P=0.042,P=0.025,respectively). Conclusions APTw and T2 mapping are valuable in assessing the MSI of endometrial adenocarcinoma,and the combination of the two demonstrates higher diagnostic efficacy,thus providing a basis for the selection of preoperative therapeutic modalities for the patients.

Differentiating between pyogenic (PS) and brucellar (BS) spondylitis is clinically challenging due to their similar clinical symptoms, with delayed diagnosis or misdiagnosis common, causing trouble for surgeons in selecting appropriate treatment strategies. Currently, radiology-based diagnostic models for PS and BS are lacking. This study aimed to combine magnetic resonance (MR) and radiographic imaging to elucidate the differences between PS and BS and develop a novel diagnostic model for differential diagnosis. We collected and analyzed the differences between MR and radiological images of patients with PS and BS from two medical institutions. A nomogram was constructed using least absolute shrinkage and selection operator (LASSO) regression, alongside univariate and multivariate analyses to select the best features of the predictive model. Model discrimination, calibration, and clinical utility were assessed using receiver operating characteristic, calibration, and decision curve analyses. Among the enrolled 342 patients with PS (n = 167) or BS (n = 175), we found significant differences in MR and radiological characteristics between the two groups. LASSO regression analysis revealed that thoracic involvement, involved vertebrae number, parrot beak osteophyte presence, endplate destruction, and intervertebral disc signal strength on T1-weighted sequences were independent predictive factors for differentiating between PS and BS. The imaging-based clinical prediction model showed high accuracy in the training and validation sets, with the area under the curve achieving 0.861 and 0.908, respectively, and a significant net benefit in the threshold probability, indicating high clinical potential of the model. This imaging-based model offers a useful tool for efficiently differentiating PS and BS, facilitating prompt diagnosis and treatment and mitigating incorrect or delayed diagnosis.

PURPOSE:In clinical practice, fetal gastrointestinal magnetic resonance imaging (MRI) encounters significant challenges. T1-weighted images are particularly susceptible to the effects of fetal and maternal movements compared to other weighted images, complicating the acquisition of satisfactory results. This study aimed to compare three fast 3D-T1 weighted gradient echo (GRE) sequences-free-breathing stack-of-stars VIBE (STAR-VIBE), breath-hold VIBE (BH-VIBE), and free-breathing multi-average VIBE (MA-VIBE)-for fetal gastrointestinal MRI in fetuses with both normal and abnormal gastrointestinal tracts between 21 and 36 weeks of gestation. METHODS:This study enrolled 67 pregnant women who underwent fetal abdominal MRI at our hospital between October 2022 and October 2023, during their gestational period of 21-36 weeks. Among these participants, 22 were suspected of having fetal gastrointestinal anomalies based on ultrasound findings, while the remaining 45 were considered to have normal fetal gastrointestinal development. All subjects underwent True fast imaging with steady-state precession sequence scanning along with three T1-weighted imaging techniques on a Siemens 1.5-T Aera scanner: STAR-VIBE, BH-VIBE, and MA-VIBE. Two radiologists evaluated image quality, intestinal clarity, and lesion conspicuity using a five-point scale where higher scores indicated superior performance for each technique; they were blinded to the acquisition schemes used. Interobserver variability assessments were also conducted. RESULTS:The free-breathing MA-VIBE sequence demonstrated significantly better performance than both STAR-VIBE and BH-VIBE in terms of fetal gastrointestinal MRI quality (3.81 ± 0.40 vs. 3.35 ± 0.70 vs. 2.90 ± 0.64; p < .05). The STAR-VIBE and BH-VIBE sequences exhibited moderate consistency (kappa = 0.586 and kappa = 0.527 respectively; P < .05), whereas the MA-VIBE sequence showed higher consistency (kappa = 0.712; P < .05). CONCLUSION:The free-breathing MA-VIBE sequence provided superior visualization for assessing fetal intestinal conditions compared to other methods employed in this study. On a 1.5 T MRI device, T1-weighted images based on the free-breathing MA-VIBE sequence can effectively overcome motion artifacts and compensate for the reduced signal-to-noise ratio caused by the application of acceleration techniques, thus significantly improving the quality of T1-weighted images.

Rationale and Objectives: To investigate the predictive value of intravoxel incoherent motion (IVIM) combined with amide proton transfer-weighted (APTw) imaging for the preoperative grading of bladder cancer (BC). Materials and Methods: A total of 69 patients with histopathologically confirmed BC underwent diffusion-weighted imaging (DWI), IVIM, and APTw imaging at 3.0 T MRI. Two radiologists independently measured the mean apparent diffusion coefficient (ADC) in DWI, true diffusion coefficient (D), perfusion-related pseudo-diffusion coefficient (D*), and perfusion fraction (f) in IVIM, and APTw values, respectively. The areas under the receiver operating characteristic curves (AUCs) were utilized to compare the diagnostic efficacy of these single and combined quantitative parameters. Results: ADC and D values of low-grade BC were significantly higher than those of high-grade BC ([1.42 +/- 0.20 x10(-3) mm(2)/s] vs. [1.09 +/- 0.25 x10(-3) mm(2)/s] and [1.24 +/- 0.24 x10(-3) mm(2)/s] vs. [0.89 +/- 0.18 x10(-3) mm(2)/s], respectively; all P < 0.001). Opposite patterns were found for APTw ( [1.53 +/- 0.42]% vs. [2.38 +/- 0.71]%, P < 0.001). The ROC curves indicated that the combination of D and APTw values could distinguish low- from high-grades of BC with the highest predictive efficacy (AUC = 0.96), as well as a significant difference compared to those by ADC, D, and APTw values separately (AUC = 0.84, 0.88, 0.85, respectively; all P < 0.05). Conclusion: IVIM combined with APTw imaging significantly improved the predictive efficacy of assessing low- and high-grade BC compared to the individual parameters on their own, providing an effective non-invasive method for clinical preoperative prediction of BC grading.

OBJECTIVE:To report a statistical evaluation of symptomatology based on 56 cases of SAPHO syndrome and 352 non-SAPHO involvement cases, to propose a symptomatic scoring system in consideration of early warning for SAPHO syndrome.METHODS:A cohort comprising 56 subjects diagnosed with SAPHO syndrome was reported, as well as 352 non-SAPHO involvement cases, including their chief complaints, skin manifestations, radiological findings, and laboratory tests. We systematically reviewed previous published five representative huge cohorts from different countries to conclude several specific features of SAPHO by comparing with our case series. The score of each specific index is based on respective incidence and comparison of two cohorts was performed.RESULT:In terms of complaint rates, all subjects of two cohorts suffered from osseous pain, which appeared in the anterior chest wall, spine, and limb which were calculated. In respect to dermatological lesions, SAPHO patients suffered from severe acne, and other patients (82.14%) accompanied with palmoplantar pustulosis. Having received radiological examinations, most SAPHO subjects rather than non-SAPHO involvement cases showed abnormal osteoarticular lesions under CT scanning and more detailed information under whole-body bone scintigraphy. Differences also emerged in elevation of inflammation values and rheumatic markers like HLA-B27. Based on our cases and huge cohorts documented, the early warning standard is set to be 5 scores.CONCLUSIONS:SAPHO syndrome case series with 56 subjects were reported and an accumulative scoring system for the early reminder on SAPHO syndrome was proposed. The threshold of this system is set to be 5 points. Key Points • Fifty-six patients diagnosed by SAPHO syndrome with detailed symptoms and radiological findings were reported. • Comparison was made between the 56 SAPHO patients and 352 non-SAPHO involvement cases. • An accumulative scoring system for the early reminder on SAPHO syndrome was proposed and the threshold of this system is set to be five points.

To evaluate the diagnostic value of luteinizing hormone (LH) and LH/follicle stimulating hormone (FSH) ratio at 60 min after gonadotropin-releasing hormone analogs (GnRHa) stimulation test for central precocious puberty (CPP) in girls. Two hundred and fifty-seven girls, aged 3 to 7.5 y, suspected of precocious puberty at authors’ hospital from April 2020 through November 2023 were enrolled in the study. The blood was taken at 0, 30, 60 min after GnRHa stimulation test, and LH and LH/FSH were detected by chemiluminescence assay. The diagnostic efficacy was analysed by Mann–Whitney U test, spearman’s correlation analysis and receiver operating characteristic (ROC) analysis. The proportion of obesity was analysed by Chi-square test. LH and LH/FSH at different times were statistically significantly different (P <0.05) between the CPP and non-CPP groups. Spearman’s correlation analysis showed that the level of LH and LH/FSH at 60 min had the strongest consistency with the peak of LH (r = 0.9988, P <0.001) and LH/FSH (r = 0.9981, P <0.001). ROC curve analysis showed that the area under the ROC curves at 60 min of LH and LH/FSH were 0.975 and 0.997 with a cut-off value of 5.70 IU/L and 0.609, respectively. The peak of LH and LH/FSH in the diagnosis of CPP can be determined by LH and LH/FSH at 60 min after the triptorelin acetate is injected. This will reduce the number of blood draws required compared with the traditional stimulation test, which is more effective and acceptable for children.

BACKGROUND CONTEXT: A high-riding vertebral artery (HRVA) can deviate too medially, too posteriorly, or too superiorly to allow the safe insertion of screws. However, it is unknown whether the presence of a HRVA is associated with morphological changes of the atlantoaxial joint.PURPOSE: To investigate the association between HRVA and atlantoaxial joint morphology in patients with and without HRVA.STUDY DESIGN: A retrospective case-control study and finite element (FE) analysis.PATIENT SAMPLE: A total of 396 patients with cervical spondylosis underwent multi-slice spi-ral computed tomography (MSCT) of cervical spine at our institutions from 2020 to 2022.OUTCOME MEASURES: A series of atlantoaxial joint morphological parameters, including C2 lateral mass settlement (C2 LMS), C1-2 sagittal joint inclination (C1-2 SI), C1-2 coronal joint inclination (C1-2 CI), atlanto-dental interval (ADI), lateral atlanto-dental interval (LADI), and C1 -2 relative rotation angle (C1-2 RRA) were measured, and lateral atlantoaxial joints osteoarthritis (LAJs-OA) was recorded. The stress distribution on the C2 facet surface under different torques of flexion-extension, lateral bending, and axial rotation was analyzed by FE models. A 2-Nm moment was applied to all models to determine the range of motion (ROM).METHODS: A total of 132 consecutive cervical spondylosis patients with unilateral HRVA were enrolled in the HRVA group, and 264 patients without HRVA matched for age and sex were enrolled in the normal (NL) group. Atlantoaxial joint morphological parameters were compared between two sides of C2 lateral mass within HRVA or NL group, and between HRVA and NL groups. A 48-year-old woman with cervical spondylosis without HRVA was selected for cervical MSCT. A three-dimensional (3D) FE intact model of the normal upper cervical spine (C0-C2) was created. We established the HRVA model by simulating atlantoaxial morphological changes of uni-lateral HRVA with FE method.RESULTS: The C2 LMS was significantly smaller on the HRVA side than that on the non-HRVA side in the HRVA group, but C1-2 SI, C1-2 CI, and LADI on HRVA side were significantly larger than those on non-HRVA side. There was no significant difference between left and right sides in the NL group. The difference in C2 LMS (d-C2 LMS) between HRVA side and non-HRVA side in the HRVA group was larger than that in the NL group (P < 0.05). Meanwhile, the differences in C1-2 SI (d-C1/2 SI), C1-2 CI (d-C1/2 CI), and LADI (d-LADI) in the HRVA group were significantly larger than those in the NL group. The C1-2 RRA in the HRVA group was significantly larger than that in the NL group. Pearson correlations showed that d-C1/2 SI, d -C1/2 CI, and d-LADI were positively associated with d-C2 LMS (r=0.428, 0.649, 0.498, respec-tively, p<.05 for all). The incidence of LAJs-OA in the HRVA group (27.3%) was significantly larger than that in the NL group (11.7%). Compared with the normal model, the ROM of C1-2 seg-ment declined in all postures of the HRVA FE model. We found a larger distribution of stress on the C2 lateral mass surface of the HRVA side under different moment conditions.CONCLUSIONS: We suggest that HRVA affects the integrity of the C2 lateral mass. This change in patients with unilateral HRVA is associated with the nonuniform settlement of the lateral mass and an increase in the lateral mass inclination, which may further affect the degeneration of the atlantoaxial joint because of the stress concentration on the C2 lateral mass surface. & COPY; 2023 Elsevier Inc. All rights reserved.

Accurate identification of lesions is a key step in surgical planning. However, this task mainly exists two challenges: 1) Due to the complex anatomical shapes of different lesions, most segmentation methods only achieve outstanding performance for a specific structure, rather than other lesions with location differences. 2) The huge number of parameters limits existing transformer-based segmentation models. To overcome these problems, we propose a novel slight dual-path network (SDPN) to segment variable location lesions or organs with significant differences accurately. First, we design a dual-path module to integrate local with global features without obvious memory consumption. Second, a novel Multi-spectrum attention module is proposed to pay further attention to detailed information, which can automatically adapt to the variable segmentation target. Then, the compression module based on tensor ring decomposition is designed to compress convolutional and transformer structures. In the experiment, four datasets, including three benchmark datasets and a clinical dataset, are used to evaluate SDPN. Results of the experiments show that SDPN performs better than other start-of-the-art methods for brain tumor, liver tumor, endometrial tumor and cardiac segmentation. To ensure the generalizability, we train the network on Kvasir-SEG and test on CVC-ClinicDB which collected from a different institution. The quantitative analysis shows that the clinical evaluation results are consistent with the experts. Therefore, this model may be a potential candidate for the segmentation of lesions and organs segmentation with variable locations in clinical applications.

Background: An understanding of the associations between midregion fat depots and systemic hormone levels will be crucial for developing health-promotion messages aimed at overweight or obese women. However, related research in this area is rare. The present study was performed to identify and quantify fat related reproduction pituitary and ovarian hormones in overweight or obese women.Methods: A total of 250 eligible overweight or obese women scheduled to undergo laparoscopic sleeve gastrectomy (LSG) from a single center were retrospectively included in this study. Computed tomography (CT) images at the level of the umbilicus were selected, and abdominal fat areas were measured and calculated. The reproduction-related pituitary and ovarian hormones were also measured. The correlations among the parameters were examined using Spearman correlation test. Multiple linear regression analysis was performed after log and 0-transformation of the hormone levels and fat area-related variables.Results: Positive correlations were detected for prolactin (PRL) with total fat area (TFA) [0=0.045; P=0.029; 95% confidence interval (CI): 0.004-0.085] and subcutaneous fat area (SFA) (0=0.066; P=0.023; 95% CI: 0.009-0.123), whereas estradiol showed a negative correlation with visceral fat area (VFA) (0=-0.056, P=0.005; 95% CI: -0.096 to -0.017) and relative VFA (rVFA) (0 =-0.068; P=0.001; 95% CI: -0.109 to -0.027) and a positive correlation with SFA (13=0.036; P=0.042; 95% CI: 0.001-0.071). Progesterone (PROG) was negatively correlated with both VFA (13=-0.037; P=0.002; 95% CI: -0.061 to -0.013) and rVFA (13=-0.039; P=0.002; 95% CI: -0.063 to -0.014). The final results revealed that TFA was increased by 3.1% and SFA was increased by 4.7% with a doubling of PRL concentration; VFA was reduced by 2.5% and rVFA was reduced by 2.6% with a doubling of PROG concentration; and VFA was reduced by 3.8%, rVFA was reduced by 4.6%, and SFA was increased by 2.5% with a doubling of estradiol concentration.Conclusions: There exist certain associations between some reproduction-related pituitary and ovarian hormones and fat areas. Our findings provide new insights into the associations between midregion fat depots and systemic hormone levels in overweight or obese women.

Verifiable symmetric searchable encryption is a keyword search technology that supports verification of search results. Many schemes improve search performance by dividing each keyword label into segments and storing them in a Trie-tree at the expense of high storage. And the index will degenerate into a linear linked list when all keyword labels have the same prefix except for the last segment. But it will greatly affect the search efficiency. In this paper, we propose a verifiable symmetric searchable encryption scheme based on the AVL Tree (abbreviated as VSSE-AVL), which uses complete keyword labels to build the index. Compared with the Trie-tree index, VSSE-AVL not only balances storage and search performance, but also avoids degradation. To verify the correctness and completeness of empty search results, we store path information in each leaf node and node with only one child node. Considering the substitution attack, we bind the file identifier and the file so that the client will find out once the server returns inconsistent search results. Rigorous security analysis shows VSSE-AVL satisfies privacy and verifiability. Compared with the verifiable SSE-2 with the same security, the experimental evaluation shows that our proposed scheme performs better on storage, search and verification.

Covalent inhibitors of Bruton tyrosine kinase (BTK) have transformed the therapy of chronic lymphocytic leukemia (CLL), but continuous therapy has been complicated by the development of resistance. The most common resistance mechanism in patients whose disease progresses on covalent BTK inhibitors (BTKis) is a mutation in the BTK 481 cysteine residue to which the inhibitors bind covalently. Pirtobrutinib is a highly selective, noncovalent BTKi with substantial clinical activity in patients whose disease has progressed on covalent BTKi, regardless of BTK mutation status. Using in vitro ibrutinib-resistant models and cells from patients with CLL, we show that pirtobrutinib potently inhibits BTK-mediated functions including B-cell receptor (BCR) signaling, cell viability, and CCL3/CCL4 chemokine production in both BTK wild-type and C481S mutant CLL cells. We demonstrate that primary CLL cells from responding patients on the pirtobrutinib trial show reduced BCR signaling, cell survival, and CCL3/CCL4 chemokine secretion. At time of progression, these primary CLL cells show increasing resistance to pirtobrutinib in signaling inhibition, cell viability, and cytokine production. We employed longitudinal whole-exome sequencing on 2 patients whose disease progressed on pirtobrutinib and identified selection of alternative-site BTK mutations, providing clinical evidence that secondary BTK mutations lead to resistance to noncovalent BTKis.

Accurate segmentation of organs, tissues and lesions is essential for computer-assisted diagnosis. Previous works have achieved success in the field of automatic segmentation. However, there exists two limitations. (1) They are remain challenged by complex conditions, such as segmentation target is variable in location, size and shape, especially for different imaging modalities. (2) Existing transformer-based networks suffer from a high parametric complexity. To solve these limitations, we propose a new Tensorized Transformer Network (TT-Net). In this paper, (1) Multi-scale transformer with layers-fusion is proposed to faithfully capture context interaction information. (2) Cross Shared Attention (CSA) module that based on pHash similarity fusion (pSF) is well-designed to extract the global multi-variate dependency features. (3) Tensorized Self-Attention (TSA) module is proposed to deal with the large number of parameters, which can also be easily embedded into other models. In addition, TT-Net gains a good explainability through visualizing the transformer layers. The proposed method is evaluated on three widely accepted public datasets and one clinical dataset, which contains different imaging modalities. Comprehensive results show that TT-Net outperforms other state-of-the-art methods for the four different segmentation tasks. Besides, the compression module which can be easily embedded into other transformer-based methods achieves lower computation with comparable segmentation performance.

Objective To explore the network structure underlying the symptoms of menopausal syndrome and to identify the central and bridge symptoms of menopause among middle-aged women. Methods This is a cross-sectional survey study conducted in the Chinese community with a total of 1829 women aged 40-65 years. The Menopause Rating Scale (MRS) was used to assess the menopausal syndrome, including somato-vegetative, psychological, and urogenital subdomains. The network analysis was performed to determine the central and bridge symptoms of menopause. Results In the network of menopausal symptoms, anxiety, vaginal dryness, depressive mood, and irritability were the most central symptoms. Depressive mood, anxiety, and vaginal dryness were also detected as the bridge symptoms. The estimated network between the symptoms had good stability (CS-strength = 0.75 and CS-edge = 0.75). Conclusion The present network analysis provided unique insights into the inner structure of menopausal symptoms. Psychological symptoms should be considered as the core symptoms in developing relevant interventions to improve the health and well-being of middle-aged women.

Aqueous redox flow batteries (ARFBs) are a promising technology for grid-scale energy storage, however, their commercial success relies on redox-active materials (RAM) with high electron storage capacity and cost competitiveness. Herein, a redox-active material lithium ferrocyanide (Li-4[Fe(CN)(6)]) is designed. Li+ ions not only greatly boost the solubility of [Fe(CN)(6)](4-) to 2.32 M at room temperature due to weak intermolecular interactions, but also improves the electrochemical performance of [Fe(CN)(6)](4-/3-). By coupling with Zn, ZIRFBs were built, and the capacity of the batteries was as high as 61.64 Ah L-1 (pH-neutral) and 56.28 Ah L-1 (alkaline) at a [Fe(CN)(6)](4-) concentration of 2.30 M and 2.10 M. These represent unprecedentedly high [Fe(CN)(6)](4-) concentrations and battery energy densities reported to date. Moreover, benefiting from the low cost of Li-4[Fe(CN)(6)], the overall chemical cost of alkaline ZIRFB is as low as $11 per kWh, which is one-twentieth that of the state-of-the-art VFB ($211.54 per kWh). This work breaks through the limitations of traditional electrolyte composition optimization and will strongly promote the development of economical [Fe(CN)(6)](4-/3-)-based RFBs in the future.

We report the generation of high-order transverse modes from a Kerr-lens mode-locked femtosecond laser. Two different orders of Hermite-Gaussian modes were realized by non-collinear pumping, which were converted into the corresponding Laguerre-Gaussian vortex modes using a cylindrical lens mode converter. The mode-locked vortex beams, with an average power of 1.4 W and 0.8 W, contained pulses as short as 126 fs and 170 fs at the first and second Hermite-Gaussian mode orders, respectively. This work demonstrates the possibility of developing Kerr-lens mode-locked bulk lasers with various pure high-order modes and paves the way for generating ultrashort vortex beams.

Mammalian haploid cells are important resources for forward genetic screening and are important in genetic medicine and drug development. However, the self-diploidization of murine haploid embryonic stem cells (haESCs) during daily culture or differentiation jeopardizes their use in genetic approaches. Here, we show that overexpression (OE) of an antiapoptosis gene, BCL2, in haESCs robustly ensures their haploidy maintenance in various situations, even under strict differentiation in vivo (embryonic 10.5 chimeric fetus or 21-day teratoma). Haploid cell lines of many lineages, including epiblasts, trophectodermal lineages, and neuroectodermal lineages, can be easily derived by the differentiation of BCL2-OE haESCs in vitro. Transcriptome analysis revealed that BCL2-OE activates another regulatory gene, Has2, which is also sufficient for haploidy maintenance. Together, our findings provide an effective and secure strategy to reduce diploidization during differentiation, which will contribute to the generation of haploid cell lines of the desired lineage and related genetic screening.