Causes and classification of EMD mode mixing

At present, the lack of insight into the problem of mode mixing in Empirical Mode Decomposition (EMD) hinders the development of solutions to the problem. Starting with the phenomenon that the EMD decomposition cannot be accomplished when the number of signal extrema is abnormal, the causes of mode mixing were investigated and the conclusion was reached that there are only two basic types of mode mixing. In light of this finding, the mechanisms of the three typical mode mixing solutions and their limitations were analyzed. It was found from the analysis process and results that the findings of this study regarding the causes and types of mode mixing were correct

Secure Split Learning against Property Inference, Data Reconstruction, and Feature Space Hijacking Attacks

Split learning of deep neural networks (SplitNN) has provided a promising solution to learning jointly for the mutual interest of a guest and a host, which may come from different backgrounds, holding features partitioned vertically. However, SplitNN creates a new attack surface for the adversarial participant, holding back its practical use in the real world. By investigating the adversarial effects of highly threatening attacks, including property inference, data reconstruction, and feature hijacking attacks, we identify the underlying vulnerability of SplitNN and propose a countermeasure. To prevent potential threats and ensure the learning guarantees of SplitNN, we design a privacy-preserving tunnel for information exchange between the guest and the host. The intuition is to perturb the propagation of knowledge in each direction with a controllable unified solution. To this end, we propose a new activation function named R3eLU, transferring private smashed data and partial loss into randomized responses in forward and backward propagations, respectively. We give the first attempt to secure split learning against three threatening attacks and present a fine-grained privacy budget allocation scheme. The analysis proves that our privacy-preserving SplitNN solution provides a tight privacy budget, while the experimental results show that our solution performs better than existing solutions in most cases and achieves a good tradeoff between defense and model usability.Comment: 23 page

The correlation between serum calcium levels and prognosis in patients with severe acute osteomyelitis

ObjectiveTo explore the relationship between serum calcium levels and the prognosis of severe acute osteomyelitis, and to assess the effectiveness of calcium levels in prognostic evaluation.MethodsRelevant patient records of individuals diagnosed with severe acute osteomyelitis were obtained for this retrospective study from the Medical Information Mart for Intensive Care (MIMIC-IV). The study aimed to assess the impact of different indicators on prognosis by utilizing COX regression analysis. To enhance prognostic prediction for critically ill patients, a nomogram was developed. The discriminatory capacity of the nomogram was evaluated using the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve, in addition to the calibration curve.ResultThe study analyzed a total of 1,133 cases of severe acute osteomyelitis, divided into the survivor group (1,025 cases) and the non-survivor group (108 cases). Significant differences were observed between the two groups in terms of age, hypertension, sepsis, renal injury, and various laboratory indicators, including WBC, PLT, Ca2+, CRP, hemoglobin, albumin, and creatinine (P<0.05). However, no significant differences were found in race, gender, marital status, detection of wound microbiota, blood sugar, lactate, and ALP levels. A multivariate COX proportional hazards model was constructed using age, hypertension, sepsis, Ca2+, creatinine, albumin, and hemoglobin as variables. The results revealed that hypertension and sepsis had a significant impact on survival time (HR=0.514, 95% CI 0.339–0.779, P=0.002; HR=1.696, 95% CI 1.056–2.723, P=0.029). Age, hemoglobin, Ca2+, albumin, and creatinine also showed significant effects on survival time (P<0.05). However, no statistically significant impact on survival time was observed for the other variables (P>0.05). To predict the survival time, a nomogram was developed using the aforementioned indicators and achieved an AUC of 0.841. The accuracy of the nomogram was further confirmed by the ROC curve and calibration curve.ConclusionAccording to the findings, this study establishes that a reduction in serum calcium levels serves as a distinct and standalone predictor of mortality among individuals diagnosed with severe acute osteomyelitis during their stay in the Intensive Care Unit (ICU) within a span of two years

Elastic stable intramedullary nail combined with Kirschner wire (E-K) technique for treating pediatric distal tibial diaphyseal metaphyseal junction (DTDMJ) fractures

ObjectiveElastic stable intramedullary nail (ESIN) is a commonly used method for treating diaphyseal fractures of the tibia, but its application in Distal Tibial Diaphyseal Metaphyseal Junction (DTDMJ) fractures has been a subject of controversy. This study aims to evaluate the clinical efficacy of the Elastic stable intramedullary nail-Kirschner wire (E-K) technique in treating pediatric DTDMJ fractures, providing better clinical decision-making for clinicians in diagnosing and treating such fractures.MethodsWe conducted a retrospective analysis of patients aged 3–9 years who received treatment at our hospital from January 2019–January 2021 for distal tibial diaphyseal metaphyseal junction (DTDMJ) fractures. Based on their surgical procedures, they were categorized into the Elastic Stable Intramedullary Nail—Kirschner wire group (E-K) and the ESIN group. Demographic data, surgical duration, clinical outcomes, complications, and imaging data were recorded.ResultsThe study included a total of 57 patients, with 24 cases in the E-K group and 33 cases in the ESIN group. There were 30 males and 27 females. The average age was (6.25 ± 1.59) years in the E-K group and (6.27 ± 1.48) years in the ESIN group. There were no significant differences between the two groups in terms of gender, age, weight, time from injury to surgery, follow-up time, side of injury, associated injuries, nail site infection, deep infection, and nail removal time (P > 0.05). Neither group experienced nonunion or refracture. The E-K group exhibited significantly lower coronal and sagittal plane angular values at the final follow-up compared to the ESIN group (P < 0.001). In the E-K group, the final follow-up coronal plane angle was 2.67 (1.09)°, while in the ESIN group, it was 6.55 (2.05)°. The final follow-up sagittal plane angle was 3.12 (1.54)° in the E-K group and 7.58 (1.48)° in the ESIN group. Both groups showed good alignment in the initial postoperative x-rays, with no statistically significant differences. However, during clinical healing, the ESIN group exhibited significant displacement, whereas the E-K group had minimal displacement, demonstrating a significant statistical difference (P < 0.001). There was a statistically significant difference in the AOFAS joint function assessment between the two groups (P = 0.027).ConclusionThe E-K technique is a viable option for treating DTDMJ fractures in pediatric patients, with well-established clinical efficacy. Its advantages include a straightforward surgical procedure, safety, and a low incidence of severe complications

Cavity locking with spatial modulation of optical phase front for laser stabilization

We study optical cavity locking for laser stabilization through spatial modulation of the phase front of a light beam. A theoretical description of the underlying principle is developed for this method and special attention is paid to residual amplitude modulation (RAM) caused by experimental imperfections, especially the manufacture errors of the spatial phase modulator. The studied locking method owns the common advantages of the Pound-Drever-Hall method and the tilt-locking one, and it can provide a more artful way to eliminate RAM noise in phase modulation for the ultimate stability of lasers. In situations where cost and portability are a practical issue, the studied method allows one to realize compact laser stabilization systems locked to Fabry-P\acute{\mbox{e}}rot cavities without use of expensive bulky devices, such as signal generators and electro-optic modulators.Comment: 3 figure

Validation and Utilization of a Clinical Next-Generation Sequencing Panel for Selected Cardiovascular Disorders

The development of high-throughput technologies such as next-generation sequencing (NGS) has allowed for thousands of DNA loci to be interrogated simultaneously in a fast and economical method for the detection of clinically deleterious variants. Whenever a clinical diagnosis is known, a targeted NGS approach involving the use of disease-specific gene panels can be employed. This approach is often valuable as it allows for a more specific and clinically relevant interpretation of results. Here, we describe the customization, validation, and utilization of a commercially available targeted enrichment platform for the scalability of clinical diagnostic cardiovascular genetic tests, including the design of the gene panels, the technical parameters for the quality assurance and quality control, the customization of the bioinformatics pipeline, and the post-bioinformatics analysis procedures. Regions of poor base coverage were detected and targeted by Sanger sequencing as needed. All panels were successfully validated using genotype-known DNA samples either commercially available or from research subjects previously tested in outside clinical laboratories. In our experience, utilizing several of the sub-panels in a clinical setting with 33 real-life cardiovascular patients, we found that 20% of tests requested were reported to have at least one pathogenic or likely pathogenic variant that could explain the patient phenotype. For each of these patients, the positive results may aid the clinical team and the patients in best developing a disease management plan and in identifying relatives at risk

Optical surface waves over metallo-dielectric nanostructures: Sommerfeld integrals revisited

The asymptotic closed-form solution to the fundamental diffraction problem of a linear horizontal Hertzian dipole radiating over the metallo-dielectric interface is provided. For observation points just above the interface, we confirm that the total surface near-field is the sum of two components: a long-range surface plasmon polariton and a short-range radiative cylindrical wave. The relative phases, amplitudes and damping functions of each component are quantitatively elucidated through simple analytic expressions for the entire range of propagation: near and asymptotic. Validation of the analytic solution is performed by comparing the predictions of a dipolar model with recently published dataComment: 13 pages, 7 figures. To appear in Optics Express Vol. 16, No. 1

Normal Breast-Derived Epithelial Cells with Luminal and Intrinsic Subtype-Enriched Gene Expression Document Interindividual Differences in Their Differentiation Cascade

Cell-type origin is one of the factors that determine molecular features of tumors, but resources to validate this concept are scarce because of technical difficulties in propagating major cell types of adult organs. Previous attempts to generate such resources to study breast cancer have yielded predominantly basal-type cell lines. We have created a panel of immortalized cell lines from core breast biopsies of ancestry-mapped healthy women that form ductal structures similar to normal breast in 3D cultures and expressed markers of major cell types, including the luminal-differentiated cell-enriched ERα-FOXA1-GATA3 transcription factor network. We have also created cell lines from PROCR (CD201)+/EpCAM- cells that are likely the "normal" counterpart of the claudin-low subtype of breast cancers. RNA-seq and PAM50-intrinsic subtype clustering identified these cell lines as the "normal" counterparts of luminal A, basal, and normal-like subtypes and validated via immunostaining with basal-enriched KRT14 and luminal-enriched KRT19. We further characterized these cell lines by flow cytometry for distribution patterns of stem/basal, luminal-progenitor, mature/differentiated, multipotent PROCR+ cells, and organogenesis-enriched epithelial/mesenchymal hybrid cells using CD44/CD24, CD49f/EpCAM, CD271/EpCAM, CD201/EpCAM, and ALDEFLUOR assays and E-cadherin/vimentin double staining. These cell lines showed interindividual heterogeneity in stemness/differentiation capabilities and baseline activity of signaling molecules such as NF-κB, AKT2, pERK, and BRD4. These resources can be used to test the emerging concept that genetic variations in regulatory regions contribute to widespread differences in gene expression in "normal" conditions among the general population and can delineate the impact of cell-type origin on tumor progression.Significance: In addition to providing a valuable resource for the breast cancer research community to investigate cell-type origin of different subtypes of breast cancer, this study highlights interindividual differences in normal breast, emphasizing the need to use "normal" cells from multiple sources as controls to decipher the effects of cancer-specific genomic aberrations

Genome-wide studies reveal the essential and opposite roles of ARID1A in controlling human cardiogenesis and neurogenesis from pluripotent stem cells

Background Early human heart and brain development simultaneously occur during embryogenesis. Notably, in human newborns, congenital heart defects strongly associate with neurodevelopmental abnormalities, suggesting a common gene or complex underlying both cardiogenesis and neurogenesis. However, due to lack of in vivo studies, the molecular mechanisms that govern both early human heart and brain development remain elusive. Results Here, we report ARID1A, a DNA-binding subunit of the SWI/SNF epigenetic complex, controls both neurogenesis and cardiogenesis from human embryonic stem cells (hESCs) through distinct mechanisms. Knockout-of-ARID1A (ARID1A−/−) leads to spontaneous differentiation of neural cells together with globally enhanced expression of neurogenic genes in undifferentiated hESCs. Additionally, when compared with WT hESCs, cardiac differentiation from ARID1A −/− hESCs is prominently suppressed, whereas neural differentiation is significantly promoted. Whole genome-wide scRNA-seq, ATAC-seq, and ChIP-seq analyses reveal that ARID1A is required to open chromatin accessibility on promoters of essential cardiogenic genes, and temporally associated with key cardiogenic transcriptional factors T and MEF2C during early cardiac development. However, during early neural development, transcription of most essential neurogenic genes is dependent on ARID1A, which can interact with a known neural restrictive silencer factor REST/NRSF. Conclusions We uncover the opposite roles by ARID1A to govern both early cardiac and neural development from pluripotent stem cells. Global chromatin accessibility on cardiogenic genes is dependent on ARID1A, whereas transcriptional activity of neurogenic genes is under control by ARID1A, possibly through ARID1A-REST/NRSF interaction

Dependence receptor UNC5A restricts luminal to basal breast cancer plasticity and metastasis

BACKGROUND: The majority of estrogen receptor-positive (ERα+) breast cancers respond to endocrine therapies. However, resistance to endocrine therapies is common in 30% of cases, which may be due to altered ERα signaling and/or enhanced plasticity of cancer cells leading to breast cancer subtype conversion. The mechanisms leading to enhanced plasticity of ERα-positive cancer cells are unknown. METHODS: We used short hairpin (sh)RNA and/or the CRISPR/Cas9 system to knockdown the expression of the dependence receptor UNC5A in ERα+ MCF7 and T-47D cell lines. RNA-seq, quantitative reverse transcription polymerase chain reaction, chromatin immunoprecipitation, and Western blotting were used to measure the effect of UNC5A knockdown on basal and estradiol (E2)-regulated gene expression. Mammosphere assay, flow cytometry, and immunofluorescence were used to determine the role of UNC5A in restricting plasticity. Xenograft models were used to measure the effect of UNC5A knockdown on tumor growth and metastasis. Tissue microarray and immunohistochemistry were utilized to determine the prognostic value of UNC5A in breast cancer. Log-rank test, one-way, and two-way analysis of variance (ANOVA) were used for statistical analyses. RESULTS: Knockdown of the E2-inducible UNC5A resulted in altered basal gene expression affecting plasma membrane integrity and ERα signaling, as evident from ligand-independent activity of ERα, altered turnover of phosphorylated ERα, unique E2-dependent expression of genes effecting histone demethylase activity, enhanced upregulation of E2-inducible genes such as BCL2, and E2-independent tumorigenesis accompanied by multiorgan metastases. UNC5A depletion led to the appearance of a luminal/basal hybrid phenotype supported by elevated expression of basal/stem cell-enriched ∆Np63, CD44, CD49f, epidermal growth factor receptor (EGFR), and the lymphatic vessel permeability factor NTN4, but lower expression of luminal/alveolar differentiation-associated ELF5 while maintaining functional ERα. In addition, UNC5A-depleted cells acquired bipotent luminal progenitor characteristics based on KRT14+/KRT19+ and CD49f+/EpCAM+ phenotype. Consistent with in vitro results, UNC5A expression negatively correlated with EGFR expression in breast tumors, and lower expression of UNC5A, particularly in ERα+/PR+/HER2- tumors, was associated with poor outcome. CONCLUSION: These studies reveal an unexpected role of the axon guidance receptor UNC5A in fine-tuning ERα and EGFR signaling and the luminal progenitor status of hormone-sensitive breast cancers. Furthermore, UNC5A knockdown cells provide an ideal model system to investigate metastasis of ERα+ breast cancers