Lightweight Low-Rank Adaptation Vision Transformer Framework for Cervical Cancer Detection and Cervix Type Classification.

Cervical cancer is a major health concern worldwide, highlighting the urgent need for better early detection methods to improve outcomes for patients. In this study, we present a novel digital pathology classification approach that combines Low-Rank Adaptation (LoRA) with the Vision Transformer (ViT) model. This method is aimed at making cervix type classification more efficient through a deep learning classifier that does not require as much data. The key innovation is the use of LoRA, which allows for the effective training of the model with smaller datasets, making the most of the ability of ViT to represent visual information. This approach performs better than traditional Convolutional Neural Network (CNN) models, including Residual Networks (ResNets), especially when it comes to performance and the ability to generalize in situations where data are limited. Through thorough experiments and analysis on various dataset sizes, we found that our more streamlined classifier is highly accurate in spotting various cervical anomalies across several cases. This work advances the development of sophisticated computer-aided diagnostic systems, facilitating more rapid and accurate detection of cervical cancer, thereby significantly enhancing patient care outcomes.

Incidence of dreaming during ciprofol anesthesia for painless gastroscopy.

BACKGROUND: Dreaming is often reported by patients who undergo propofol-based sedation, but there have not been any studies to date focused on the incidence of dreaming and factors associated therewith following the administration of ciprofol anesthesia in patients undergoing painless gastroscopy. The present study was thus developed with the goal of assessing the incidence of dreaming. METHODS: In total, this study enrolled 200 patients undergoing painless gastroscopy. During the procedure, patients' electroencephalographic Bispectral Index (BIS), blood pressure (BP), heart rate (HR), blood oxygen saturation (SpO2), and PETCO2 were monitored. When their MOAA/S score reached five after the procedure, patients were administered questionnaires including the Brice questionnaire and a five-point Likert Scale, and the content of any recalled dreams was also recorded. RESULTS: Overall, 27.5% of the participants in this study reported dreaming during the procedure, with most having experienced simple, pleasant dreams about everyday life. Identified predictors of dreaming during painless gastroscopy included lower ASA grade, preoperative knowledge of painless examination, a higher frequency of dreams in the month before the procedure, poor sleep quality during the month before the procedure, and shorter awakening time. Dreamers showed significantly lower BIS values at 2 min after endoscope insertion and following endoscope removal, and also showed lower minimum BIS values compared with non-dreamers. CONCLUSIONS: The postoperative dream recall incidence in this study was 27.5% among patients undergoing painless gastroscopy under ciprofol sedation anesthesia.

Unveiling new horizons in heart research: the promise of multi-chamber cardiac organoids.

Human cardiac and other organoids have recently emerged as a groundbreaking tool for advancing our understanding the developmental biology of human organs. A recent paper from Sasha Mendjan's laboratory published in the journal Cell on December 7, 2023, reported the generation of multi-chamber cardioids from human pluripotent stem cells, a transformative technology in the field of cardiology. In this short highlight paper, we summarize their findings. Their cardioids remarkably recapitulate the complexity of the human embryonic heart, including tissue architecture, cellular diversity, and functionality providing an excellent in vitro model for investigation of human heart development, disease modeling, precision medicine, and regenerative medicine. Thus, generating cardioids is an important step forward for understanding human heart development and developing potential therapies for heart diseases.

Effect of subclavian vein diameter combined with perioperative fluid therapy on preventing post-induction hypotension in patients with ASA status I or II.

BACKGROUND: Perioperative hypotension is frequently observed following the initiation of general anesthesia administration, often associated with adverse outcomes. This study assessed the effect of subclavian vein (SCV) diameter combined with perioperative fluid therapy on preventing post-induction hypotension (PIH) in patients with lower ASA status. METHODS: This two-part study included patients aged 18 to 65 years, classified as ASA physical status I or II, and scheduled for elective surgery. The first part (Part I) included 146 adult patients, where maximum SCV diameter (dSCVmax), minimum SCV diameter (dSCVmin), SCV collapsibility index (SCVCI) and SCV variability (SCVvariability) assessed using ultrasound. PIH was determined by reduction in mean arterial pressure (MAP) exceeding 30% from baseline measurement or any instance of MAP < falling below 65 mmHg for ≥ a duration of at least 1 min during the period from induction to 10 min after intubation. Receiver Operating Characteristic (ROC) curve analysis was employed to determine the predictive values of subclavian vein diameter and other relevant parameters. The second part comprised 124 adult patients, where patients with SCV diameter above the optimal cutoff value, as determined in Part I study, received 6 ml/kg of colloid solution within 20 min before induction. The study evaluated the impact of subclavian vein diameter combined with perioperative fluid therapy by comparing the observed incidence of PIH after induction of anesthesia. RESULTS: The areas under the curves (with 95% confidence intervals) for SCVCI and SCVvariability were both 0.819 (0.744-0.893). The optimal cutoff values were determined to be 45.4% and 14.7% (with sensitivity of 76.1% and specificity of 86.7%), respectively. Logistic regression analysis, after adjusting for confounding factors, demonstrated that both SCVCI and SCVvariability were significant predictors of PIH. A threshold of 45.4% for SCVCI was chosen as the grouping criterion. The incidence of PIH in patients receiving fluid therapy was significantly lower in the SCVCI ≥ 45.4% group compared to the SCVCI < 45.4% group. CONCLUSIONS: Both SCVCI and SCVvariability are noninvasive parameters capable of predicting PIH, and their combination with perioperative fluid therapy can reduce the incidence of PIH.

ERK signaling waves via body-wall muscles guide planarian whole-body regeneration across long distances.

Whole-body regeneration is a multifaceted process that reinstates a body to its initial three-dimension size and structure after resection injury. It is well-known that signaling waves such as calcium and extracellular signal-related kinase (ERK) signaling waves can efficiently transmit information between tissues or cells. However, the mechanisms responsible for coordinating wound responses over long distances are largely unexplored. A recent study has reported that the propagation of ERK signaling waves via longitudinal body-wall muscles play an essential role in wound response and whole-body regeneration in planarians, underscoring the significance of feedback interactions between spatially distinct tissues during whole-body regeneration over long distances. These findings not only address the central questions of regenerative biology but also have potential implications for regenerative medicine.

Agreement between distal and forearm radial arterial pressures in patients undergoing prone spinal surgery: a prospective, self-controlled, observational study.

OBJECTIVE: To test agreement and interchangeability between distal (dRA) and forearm radial arterial (RA) pressures (AP) during general anesthesia (GA) for prone spinal surgery. METHODS: This prospective observational study involved 40 patients scheduled for GA spinal surgery. The right dRA and left forearm RA were cannulated in all patients to continuously measure invasive blood pressures (IBP). We compared the agreement and trending ability of systolic AP (SAP), diastolic AP (DAP), and mean AP (MAP) at each site 15 minutes after tracheal intubation, start of surgery, 30 and 60 minutes after the start of surgery, and after skin suturing. RESULTS: Paired BP values (n = 184) (37 cases) were analyzed. The bias (standard deviation), limits of agreement, and percentage error were: SAP: 0.19 (3.03), -5.75 to 6.12, and 5.04%; DAP: -0.06 (1.75), -3.50 to 3.38, and 5.10%; and MAP: 0.08 (1.52), -2.90 to 3.05, and 3.54%, respectively. The linear regression coefficients of determination were 0.981, 0.982, and 0.988 for SAPs, DAPs, and MAPs, respectively; four-quadrant plot concordance rates were 95.11%, 92.03%, and 92.66%, respectively. CONCLUSION: All arterial BPs showed good agreement and trending capabilities for both the dRA and RA. The dRA may be substituted for the RA in IBP monitoring.

Chemical screening links disulfiram with cardiac protection after ischemic injury.

Ischemia-reperfusion injury occurs after reperfusion treatment for patients suffering myocardial infarction, however the underlying mechanisms are incompletely understood and effective pharmacological interventions are limited. Here, we report the identification and characterization of the FDA-approved drug disulfiram (DSF) as a cardioprotective compound. By applying high-throughput chemical screening, we found that DSF decreased H2O2-induced cardiomyocyte death by inhibiting Gasdermin D, but not ALDH1, in cardiomyocytes. Oral gavage of DSF decreased myocardial infarct size and improved heart function after myocardial ischemia-reperfusion injury in rats. Therefore, this work reveals DSF as a potential therapeutic compound for the treatment of ischemic heart disease.

The Opto-inflammasome in zebrafish as a tool to study cell and tissue responses to speck formation and cell death.

The inflammasome is a conserved structure for the intracellular detection of danger or pathogen signals. As a large intracellular multiprotein signaling platform, it activates downstream effectors that initiate a rapid necrotic programmed cell death (PCD) termed pyroptosis and activation and secretion of pro-inflammatory cytokines to warn and activate surrounding cells. However, inflammasome activation is difficult to control experimentally on a single-cell level using canonical triggers. We constructed Opto-ASC, a light-responsive form of the inflammasome adaptor protein ASC (Apoptosis-Associated Speck-Like Protein Containing a CARD) which allows tight control of inflammasome formation in vivo. We introduced a cassette of this construct under the control of a heat shock element into zebrafish in which we can now induce ASC inflammasome (speck) formation in individual cells of the skin. We find that cell death resulting from ASC speck formation is morphologically distinct from apoptosis in periderm cells but not in basal cells. ASC-induced PCD can lead to apical or basal extrusion from the periderm. The apical extrusion in periderm cells depends on Caspb and triggers a strong Ca2+ signaling response in nearby cells.

Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.

Risk factors for acute postoperative hypertension in non-cardiac major surgery: a case control study.

PURPOSE: Acute postoperative hypertension (APH) is a common complication during the anesthesia recovery period that can lead to adverse outcomes, including cardiovascular and cerebrovascular accidents. Identification of risk factors for APH will allow for preoperative optimization and appropriate perioperative management. This study aimed to identify risk factors for APH. PATIENTS AND METHODS: In this retrospective single-center study, 1,178 cases were included. Data was entered by two investigators, and consistency analysis was performed by another. Patients were divided into APH and non-APH groups. A predictive model was built by multivariate stepwise logistic regression. The predictive ability of the logistic regression model was tested by drawing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Hosmer and Lemeshow goodness-of-fit (GOF) test was performed to reflect the goodness of fit of the model. Calibration curve was created to represent the relationship between predicted risk and observed frequency. Sensitivity analysis was performed to evaluate the robustness of the results. RESULTS: Multivariate logistic regression analysis showed that age over 65 years (OR = 3.07, 95% CI: 2.14 ~ 4.42, P < 0.001), female patients (OR = 1.37, 95% CI: 1.02 ~ 1.84, P = 0.034), presence of intraoperative hypertension (OR = 2.15, 95% CI: 1.57 ~ 2.95, P < 0.001), and use of propofol in PACU (OR = 2.14, 95% CI: 1.49 ~ 3.06, P < 0.001) were risk factors for APH. Intraoperative use of dexmedetomidine (OR = 0.66, 95% CI: 0.49 ~ 0.89, P = 0.007) was a protective factor. Higher baseline SBP (OR = 0.90, 95% CI: 0.89 ~ 0.92, P < 0.001) also showed some correlation with APH. CONCLUSIONS: The risk of acute postoperative hypertension increased with age over 65 years, female patients, intraoperative hypertension and restlessness during anesthesia recovery. Intraoperative use of dexmedetomidine was a protective factor for APH.

Endothelial Brg1 fine-tunes Notch signaling during zebrafish heart regeneration.

Myocardial Brg1 is essential for heart regeneration in zebrafish, but it remains unknown whether and how endothelial Brg1 plays a role in heart regeneration. Here, we found that both brg1 mRNA and protein were induced in cardiac endothelial cells after ventricular resection and endothelium-specific overexpression of dominant-negative Xenopus Brg1 (dn-xbrg1) inhibited myocardial proliferation and heart regeneration and increased cardiac fibrosis. RNA-seq and ChIP-seq analysis revealed that endothelium-specific overexpression of dn-xbrg1 changed the levels of H3K4me3 modifications in the promoter regions of the zebrafish genome and induced abnormal activation of Notch family genes upon injury. Mechanistically, Brg1 interacted with lysine demethylase 7aa (Kdm7aa) to fine-tune the level of H3K4me3 within the promoter regions of Notch family genes and thus regulated notch gene transcription. Together, this work demonstrates that the Brg1-Kdm7aa-Notch axis in cardiac endothelial cells, including the endocardium, regulates myocardial proliferation and regeneration via modulating the H3K4me3 of the notch promoters in zebrafish.

Working Mode Recognition of Non-Specific Radar Based on ResNet-SVM Learning Framework.

Mode recognition is a basic task to interpret the behavior of multi-functional radar. The existing methods need to train complex and huge neural networks to improve the recognition ability, and it is difficult to deal with the mismatch between the training set and the test set. In this paper, a learning framework based on residual neural network (ResNet) and support vector machine (SVM) is designed, to solve the problem of mode recognition for non-specific radar, called multi-source joint recognition framework (MSJR). The key idea of the framework is to embed the prior knowledge of radar mode into the machine learning model, and combine the manual intervention and automatic extraction of features. The model can purposefully learn the feature representation of the signal on the working mode, which weakens the impact brought by the mismatch between training and test data. In order to solve the problem of difficult recognition under signal defect conditions, a two-stage cascade training method is designed, to give full play to the data representation ability of ResNet and the high-dimensional feature classification ability of SVM. Experiments show that the average recognition rate of the proposed model, with embedded radar knowledge, is improved by 33.7% compared with the purely data-driven model. Compared with other similar state-of-the-art reported models, such as AlexNet, VGGNet, LeNet, ResNet, and ConvNet, the recognition rate is increased by 12%. Under the condition of 0-35% leaky pulses in the independent test set, MSJR still has a recognition rate of more than 90%, which also proves its effectiveness and robustness in the recognition of unknown signals with similar semantic characteristics.

Derivation of Human Salivary Epithelial Progenitors from Pluripotent Stem Cells via Activation of RA and Wnt Signaling.

Derivation of salivary gland epithelial progenitors (SGEPs) from human pluripotent stem cells (hPSCs) has great potential in developmental biology and regenerative medicine. At present, no efficient method is available to generate salivary gland cells from hPSCs. Here, we described for the first time a robust protocol for direct differentiation of hPSCs into SGEPs by mimicking retinoic acid and Wnt signaling. These hPSC-derived SGEPs expressed SOX9, KRT5, and KRT19, important progenitor markers of developing salivary glands. CD24 and α-SMA positive cells, capable of restoring the functions of injured salivary glands, were also present in SGEP cultures. Importantly, RNA-sequencing revealed that the SGEPs resembled the transcript profiles of human fetal submandibular glands. Therefore, we provided an efficient protocol to induce hPSCs differentiation into SGEPs. Our study provides a foundation for generating functional hPSCs derived salivary gland acinar cells and three-dimensional organoids, potentially serving as new models for basic study and future translational research.

A DUSP6 inhibitor suppresses inflammatory cardiac remodeling and improves heart function after myocardial infarction.

Acute myocardial infarction (MI) results in loss of cardiomyocytes and abnormal cardiac remodeling with severe inflammation and fibrosis. However, how cardiac repair can be achieved by timely resolution of inflammation and cardiac fibrosis remains incompletely understood. Our previous findings have shown that dual-specificity phosphatase 6 (DUSP6) is a regeneration repressor from zebrafish to rats. In this study, we found that intravenous administration of the DUSP6 inhibitor (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI) improved heart function and reduced cardiac fibrosis in MI rats. Mechanistic analysis revealed that BCI attenuated macrophage inflammation through NF-κB and p38 signaling, independent of DUSP6 inhibition, leading to the downregulation of various cytokines and chemokines. In addition, BCI suppressed differentiation-related signaling pathways and decreased bone-marrow cell differentiation into macrophages through inhibiting DUSP6. Furthermore, intramyocardial injection of poly (D, L-lactic-co-glycolic acid)-loaded BCI after MI had a notable effect on cardiac repair. In summary, BCI improves heart function and reduces abnormal cardiac remodeling by inhibiting macrophage formation and inflammation post-MI, thus providing a promising pro-drug candidate for the treatment of MI and related heart diseases. This article has an associated First Person interview with the first author of the paper.

Scratch-AID, a deep learning-based system for automatic detection of mouse scratching behavior with high accuracy.

Mice are the most commonly used model animals for itch research and for development of anti-itch drugs. Most laboratories manually quantify mouse scratching behavior to assess itch intensity. This process is labor-intensive and limits large-scale genetic or drug screenings. In this study, we developed a new system, Scratch-AID (Automatic Itch Detection), which could automatically identify and quantify mouse scratching behavior with high accuracy. Our system included a custom-designed videotaping box to ensure high-quality and replicable mouse behavior recording and a convolutional recurrent neural network trained with frame-labeled mouse scratching behavior videos, induced by nape injection of chloroquine. The best trained network achieved 97.6% recall and 96.9% precision on previously unseen test videos. Remarkably, Scratch-AID could reliably identify scratching behavior in other major mouse itch models, including the acute cheek model, the histaminergic model, and a chronic itch model. Moreover, our system detected significant differences in scratching behavior between control and mice treated with an anti-itch drug. Taken together, we have established a novel deep learning-based system that could replace manual quantification for mouse scratching behavior in different itch models and for drug screening.

Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction.

Dual-specificity phosphatase 6 (DUSP6) serves a specific and conserved function on the dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). We previously identified Dusp6 as a regenerative repressor during zebrafish heart regeneration, therefore we propose to investigate the role of this repressor in mammalian cardiac repair. Utilizing a rat strain harboring Dusp6 nonsense mutation, rat neutrophil-cardiomyocyte co-culture, bone marrow transplanted rats and neutrophil-specific Dusp6 knockout mice, we find that Dusp6 deficiency improves cardiac outcomes by predominantly attenuating neutrophil-mediated myocardial damage in acute inflammatory phase after myocardial infarction. Mechanistically, Dusp6 is transcriptionally activated by p38-C/EBPß signaling and acts as an effector for maintaining p-p38 activity by down-regulating pERK and p38-targeting phosphatases DUSP1/DUSP16. Our findings provide robust animal models and novel insights for neutrophil-mediated cardiac damage and demonstrate the potential of DUSP6 as a therapeutic target for post-MI cardiac remodeling and other relevant inflammatory diseases.

DPP9 deficiency: An inflammasomopathy that can be rescued by lowering NLRP1/IL-1 signaling.

Dipeptidyl peptidase 9 (DPP9) is a direct inhibitor of NLRP1, but how it affects inflammasome regulation in vivo is not yet established. Here, we report three families with immune-associated defects, poor growth, pancytopenia, and skin pigmentation abnormalities that segregate with biallelic DPP9 rare variants. Using patient-derived primary cells and biochemical assays, these variants were shown to behave as hypomorphic or knockout alleles that failed to repress NLRP1. The removal of a single copy of Nlrp1a/b/c, Asc, Gsdmd, or Il-1r, but not Il-18, was sufficient to rescue the lethality of Dpp9 mutant neonates in mice. Similarly, dpp9 deficiency was partially rescued by the inactivation of asc, an obligate downstream adapter of the NLRP1 inflammasome, in zebrafish. These experiments suggest that the deleterious consequences of DPP9 deficiency were mostly driven by the aberrant activation of the canonical NLRP1 inflammasome and IL-1ß signaling. Collectively, our results delineate a Mendelian disorder of DPP9 deficiency driven by increased NLRP1 activity as demonstrated in patient cells and in two animal models of the disease.

Pupil maximum constriction velocity predicts post-induction hypotension in patients with lower ASA status: a prospective observational study.

BACKGROUND: Individuals affected by autonomic dysfunction are at a higher risk of developing hypotension following anesthesia induction. Dynamic pupillometry has previously been employed as a means of assessing autonomic function. This prospective observational study was developed to determine whether pupillary light reflex (PLR) parameters can reliably predict post-induction hypotension (PIH). METHODS: This study enrolled patients with lower ASA status (I-II) undergoing elective surgery. PLR recordings for these patients prior to anesthesia induction were made with an infrared pupil camcorder, with a computer being used to assess Average Constriction Velocity (ACV), Maximum Constriction Velocity (MCV), and Constriction Ratio (CR). PIH was defined by a > 30% reduction in mean arterial pressure (MAP) or any MAP recording < 65 mmHg for at least 1 min from the time of induction until 10 minutes following intubation. Patients were stratified into PIH and non-PIH groups based on whether or not they developed hypotension. RESULTS: This study enrolled 61 total patients, of whom 31 (50.8%) exhibited one or more hypotensive episodes. Patients in the PIH group exhibited significantly smaller ACV (P = 0.003) and MCV values (P < 0.001), as well as a higher CR (P = 0.003). Following adjustment for certain factors (Model 2), MCV was identified as a protective factor for PIH (Odds Ratio: 0.369). Receiver operating characteristic (ROC) analyses revealed that relative to CR (AUC: 0.695, 95% CI: 0.563-0.806; P = 0.004), the reciprocal of MCV (1/MCV) offered greater value as a predictor of PIH (AUC: 0.803,95%CI: 0.681-0.894; P < 0.001). CONCLUSION: These results indicate that pupil maximum constriction velocity is a reliable predictor of post-induction hypotension in individuals of ASA I-II status undergoing elective surgery. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2200057164, registration date: 01/03/2022).