SPIN: sex-specific and pathway-based interpretable neural network for sexual dimorphism analysis.

Sexual dimorphism in prevalence, severity and genetic susceptibility exists for most common diseases. However, most genetic and clinical outcome studies are designed in sex-combined framework considering sex as a covariate. Few sex-specific studies have analyzed males and females separately, which failed to identify gene-by-sex interaction. Here, we propose a novel unified biologically interpretable deep learning-based framework (named SPIN) for sexual dimorphism analysis. We demonstrate that SPIN significantly improved the C-index up to 23.6% in TCGA cancer datasets, and it was further validated using asthma datasets. In addition, SPIN identifies sex-specific and -shared risk loci that are often missed in previous sex-combined/-separate analysis. We also show that SPIN is interpretable for explaining how biological pathways contribute to sexual dimorphism and improve risk prediction in an individual level, which can result in the development of precision medicine tailored to a specific individual's characteristics.

Comparison of Hemodynamic Parameters Based on the Administration of Remimazolam or Sevoflurane in Patients under General Anesthesia in the Beach Chair Position: A Single-Blinded Randomized Controlled Trial.

Background: We aimed to evaluate whether the administration of remimazolam as a maintenance agent for general anesthesia affects the occurrence of hypotension compared with sevoflurane when switching to the beach chair position (BCP). Methods: We conducted a prospective randomized controlled trial from June 2023 to October 2023 in adult patients undergoing orthopedic surgery under general anesthesia in the BCP. A total of 78 participants were randomly allocated to the remimazolam (R) or sevoflurane (S) groups. The primary outcome was the incidence of hypotension that occurred immediately after switching to a BCP. The secondary outcomes included differences between the study groups in perioperative blood pressure (BP), heart rate (HR), endotracheal tube extubation time, postoperative complications, and hospital length of stay (LOS). Results: The incidence of hypotension immediately after switching to a BCP was significantly higher in the S group. The risk factors associated with hypotension included sevoflurane administration and a high baseline systolic BP. In the receiver operating characteristic curve analysis for the occurrence of hypotension after the transition to a BCP, the cutoff value for systolic BP was 142 mmHg. The perioperative BP and HR were higher in the R group at several timepoints. Postoperative endotracheal tube extubation time was shorter in the R group. There were no significant differences in the postoperative complications or hospital LOS between the two groups. Conclusions: Remimazolam should be considered as an anesthetic agent to prevent hypotension when switching to BCP, and hypotension may occur frequently in patients with high baseline BP.

New approach to measuring income inequality.

We show that the conventional income inequality indexes assess income inequality incorrectly because of three problems. The unequally distributed (UD) income-based approach solves the problems, decomposes income inequality into two kinds of departure from equality, and provides two indexes. The comprehensive assessment of income inequality requires the integration of two kinds of departure. This paper proposes the relative UD (RUD) income-based approach. The RUD income-based approach combines the cumulative distribution function and quantile function of the RUD income and produces a new index integrating two kinds of departure. We investigate the properties of the new index and demonstrate its applicability through example income distributions.

Coordinated recruitment of conserved defense-signaling pathways in PVYO-Infected Nicotiana benthamiana.

Potato virus Y (PVY) is an aphid-transmitted potyvirus that affects economically important solanaceous species. In this study, the phenomena and mechanisms following infection with PVY were investigated in tobacco (Nicotiana benthamiana). In tobacco plants, infection with a mild strain of PVY (PVYO) induced stunted growth in the first two leaves at the shoot apex starting 7 days post-infection (dpi), and mosaic symptoms began to appear on newly developing young leaves at 14 dpi. Using enzyme-linked immunosorbent assay and ultrastructure analysis, we confirmed that viral particles accumulated only in the upper developing leaves of infected plants. We analyzed reactive oxygen species (ROS) generation in leaves from the bottom to the top of the plants to investigate whether delayed symptom development in leaves was associated with a defense response to the virus. In addition, the ultrastructural analysis confirmed the increase of ATG4 and ATG8, which are autophagy markers by endoplasmic reticulum (ER) stress, and the expression of genes involved in viral RNA suppression. Overall, our results suggested that viral RNA silencing and induced autophagy may play a role in the inhibition of viral symptom development in host plants in response to PVYO infection.

Needlestick Injuries With Insulin Injections: Risk Factors, Concerns, and Implications of the Use of Safety Pen Needles in the Asia-Pacific Region.

Globally, health care workers (HCWs) are at a high risk of occupational exposure to needlestick injuries (NSIs). Needlestick injuries not only are associated with an increased risk of infections caused by bloodborne pathogens but are also a primary source of emotional distress and job burnout for HCWs and patients. Insulin injection-related NSIs are common among HCWs working in hospitals in the Asia-Pacific (APAC) region and impose a significant burden. Insulin pen needles have a high risk of transmitting infections (at both the patient-end and cartridge end of the sharp) after use. Recapping a needle after administering an insulin injection poses a major risk to HCWs. Currently, several safety-engineered needle devices (SENDs) are available with active or passive safety mechanisms. Passive insulin safety pen needles with dual-ended protection and automatic recapping capabilities have resulted in a significant drop in accidental punctures to HCWs while administering insulin to patients with diabetes. In this article, we have reviewed the burden and common causes of NSIs with insulin injections among HCWs in the APAC region. We have discussed current approaches to address the issues associated with NSIs and the benefits of introducing SENDs in health care settings, including long-term care facilities, nursing homes, and home care settings where patients may require assisted insulin injections. This review also summarizes key strategies/recommendations to prevent NSIs in HCWs and patients with diabetes in the APAC region.

Fabrication of Robust and Stable N-Doped ZnO/Single-Walled Carbon Nanotubes: Characterization, Photocatalytic Application, Kinetics, Degradation Products, and Toxicity Analysis.

The production of effective visible-light (VL) photocatalysts for the elimination of noxious organic pollutants from wastewater has attracted considerable interest owing to increasing awareness worldwide. Despite the large number of photocatalysts reported, the selectivity and activity of photocatalysts still need to be developed. The goal of this research is to eliminate toxic methylene blue (MB) dye from wastewater through a cost-effective photocatalytic process using VL illumination. A novel N-doped ZnO/carbon nanotube (NZO/CNT) nanocomposite was successfully synthesized via a facile cocrystallization method. The structural, morphological, and optical properties of the synthesized nanocomposite were systematically investigated. The as-prepared NZO/CNT composite exhibited remarkable photocatalytic performance (96.58%) within 25 min of VL irradiation. The activity was 92, 52, and 27% greater than that of photolysis, ZnO, and NZO, respectively, under identical conditions. The enhanced photocatalytic efficiency of NZO/CNT was attributed to the N atom and CNT involvement: N contributes to narrowing the band gap of ZnO, and CNT captures the electrons and maintains the electron flow in the system. The reaction kinetics of MB degradation, catalyst reusability, and stability were also investigated. In addition, the photodegradation products and their toxicity effects in our environment were analyzed using the liquid chromatography-mass spectrometry and ecological structure activity relationships programs, respectively. The findings of the current study demonstrate that the NZO/CNT nanocomposite can be utilized to remove contaminants in an environmentally acceptable manner, thereby providing a new window for practical applications.

Hi-LASSO: High-performance python and apache spark packages for feature selection with high-dimensional data.

High-dimensional LASSO (Hi-LASSO) is a powerful feature selection tool for high-dimensional data. Our previous study showed that Hi-LASSO outperformed the other state-of-the-art LASSO methods. However, the substantial cost of bootstrapping and the lack of experiments for a parametric statistical test for feature selection have impeded to apply Hi-LASSO for practical applications. In this paper, the Python package and its Spark library are efficiently designed in a parallel manner for practice with real-world problems, as well as providing the capability of the parametric statistical tests for feature selection on high-dimensional data. We demonstrate Hi-LASSO's outperformance with various intensive experiments in a practical manner. Hi-LASSO will be efficiently and easily performed by using the packages for feature selection. Hi-LASSO packages are publicly available at https://github.com/datax-lab/Hi-LASSO under the MIT license. The packages can be easily installed by Python PIP, and additional documentation is available at https://pypi.org/project/hi-lasso and https://pypi.org/project/Hi-LASSO-spark.

New evidence on technological acceptance model in preschool education: Linking project-based learning (PBL), mental health, and semi-immersive virtual reality with learning performance.

Despite significant research on student learning performance, the literature on preschool education is limited. The learning performance of different institutes in China has not been satisfactory, and students are not given enough technological resources to help them improve their learning performance. Although Chinese preschool students are active learners, their learning performance is inadequate. As a result, this research aimed to discover how project-based learning, semi-immersive virtual reality, and mental health influence learning performance. For data collection, 800 questionnaires were distributed to high schools, and 290 valid questionnaires were considered for the data analysis using Smart PLS-SEM. According to the study's findings, project-based learning is critical for improving learning performance. This study's findings are significant because they show that mental health and semi-immersive virtual reality significantly mediate the relationship between project-based learning and learning performance. The study's findings are critical for educational institutions interested in improving student performance through project-based learning opportunities. Furthermore, because it employs an innovative technology acceptance model, this study has significant practical implications for project-based learning and student learning performance.

A randomized controlled trial of the effect of ramosetron on postoperative restoration of bowel motility after gynecologic laparoscopic surgery.

OBJECTIVE: To investigate the effect of ramosetron after gynecological laparoscopic surgery on the recovery of bowel function. METHODS: A prospective randomized controlled trial conducted at Kyung Hee University hospital, South Korea, from August 2016 to September 2017. Patients were randomized to receive either 10 mg dexamethasone before induction of anesthesia (control group C), followed by intravenous administration of patient-controlled analgesia (IV-PCA) or 2 ml normal saline before induction of anesthesia and 0.6 mg ramosetron (study group R) administered with IV-PCA. RESULTS: A total of 88 patients were enrolled. Times to first flatus (group C 23.98 ± 6.31 vs. group R 27.14 ± 9.56 h; P = 0.148) and first defecation (group C 36.16 ± 16.04 vs. group R 43.41 ± 20.01 h; P = 0.138) showed no statistically significant differences. No significant differences were observed in the frequency of postoperative nausea and vomiting (PONV) and demand for additional analgesics. Multiple linear regression for analysis of factors affecting time to first flatus revealed no significant results. CONCLUSION: Ramosetron did not delay bowel movement recovery after gynecologic laparoscopic surgery and was as effective as dexamethasone in regulating PONV. Ramosetron can be used with IV-PCA without concerns about delay in recovery of bowel function. CLINICALTRIALS: gov registration number: NCT02849483.

Respiration monitoring in PACU using ventilation and gas exchange parameters.

The importance of perioperative respiration monitoring is highlighted by high incidences of postoperative respiratory complications unrelated to the original disease. The objectives of this pilot study were to (1) simultaneously acquire respiration rate (RR), tidal volume (TV), minute ventilation (MV), SpO2 and PETCO2 from patients in post-anesthesia care unit (PACU) and (2) identify a practical continuous respiration monitoring method by analyzing the acquired data in terms of their ability and reliability in assessing a patient's respiratory status. Thirteen non-intubated patients completed this observational study. A portable electrical impedance tomography (EIT) device was used to acquire RREIT, TV and MV, while PETCO2, RRCap and SpO2 were measured by a Capnostream35. Hypoventilation and respiratory events, e.g., apnea and hypopnea, could be detected reliably using RREIT, TV and MV. PETCO2 and SpO2 provided the gas exchange information, but were unable to detect hypoventilation in a timely fashion. Although SpO2 was stable, the sidestream capnography using the oronasal cannula was often unstable and produced fluctuating PETCO2 values. The coefficient of determination (R2) value between RREIT and RRCap was 0.65 with a percentage error of 52.5%. Based on our results, we identified RR, TV, MV and SpO2 as a set of respiratory parameters for robust continuous respiration monitoring of non-intubated patients. Such a respiration monitor with both ventilation and gas exchange parameters would be reliable and could be useful not only for respiration monitoring, but in making PACU discharge decisions and adjusting opioid dosage on general hospital floor. Future studies are needed to evaluate the potential clinical utility of such an integrated respiration monitor.

Pathway-based deep clustering for molecular subtyping of cancer.

Cancer is a genetic disease comprising multiple subtypes that have distinct molecular characteristics and clinical features. Cancer subtyping helps in improving personalized treatment and making decision, as different cancer subtypes respond differently to the treatment. The increasing availability of cancer related genomic data provides the opportunity to identify molecular subtypes. Several unsupervised machine learning techniques have been applied on molecular data of the tumor samples to identify cancer subtypes that are genetically and clinically distinct. However, most clustering methods often fail to efficiently cluster patients due to the challenges imposed by high-throughput genomic data and its non-linearity. In this paper, we propose a pathway-based deep clustering method (PACL) for molecular subtyping of cancer, which incorporates gene expression and biological pathway database to group patients into cancer subtypes. The main contribution of our model is to discover high-level representations of biological data by learning complex hierarchical and nonlinear effects of pathways. We compared the performance of our model with a number of benchmark clustering methods that recently have been proposed in cancer subtypes. We assessed the hypothesis that clusters (subtypes) may be associated to different survivals by logrank tests. PACL showed the lowest p-value of the logrank test against the benchmark methods. It demonstrates the patient groups clustered by PACL may correspond to subtypes which are significantly associated with distinct survival distributions. Moreover, PACL provides a solution to comprehensively identify subtypes and interpret the model in the biological pathway level. The open-source software of PACL in PyTorch is publicly available at https://github.com/tmallava/PACL.

The quality characteristics, antioxidant activity, and sensory evaluation of reduced-fat yogurt and nonfat yogurt supplemented with basil seed gum as a fat substitute.

This study investigated the use of basil seed gum (BSG) as a fat substitute on the physicochemical properties and antioxidant activities of yogurt. A 0.5 and 1% BSG solution was supplemented to reduced-fat and nonfat yogurts, and their physicochemical properties, quality properties, antioxidant activity, and sensory evaluation were compared with each control group. We prepared 3 yogurts as controls and 4 yogurt samples containing BSG as follows: FFY (yogurt made from full-fat milk: a control group), LFY (yogurt made from reduced-fat milk: a control group), SY (yogurt made from nonfat milk: a control group), LFY 0.5% (0.5% BSG added to reduced-fat yogurt), LFY 1.0% (1.0% BSG added to reduced-fat yogurt), SY 0.5% (0.5% BSG added to nonfat yogurt), and SY 1.0% (1.0% BSG added to nonfat yogurt). The pH of LFY 0.5% and LFY 1.0% was decreased compared with LFY control, whereas pH of SY 0.5% and SY 1.0% had no significant difference. The titratable acidity showed no significant increase. The viscosity was the highest in FFY among the control groups and increased with the concentration of BSG in the SY group. The L-value (brightness) and b-value (yellowness) were the highest in FFY at 85.05 among the control groups. The L-value and b-value of LFY 0.5% and SY 0.5% showed higher values than LFY 1% and SY 1%. The a-value (redness) was the highest in SY 0.5% at -2.36, and ΔE (total color difference) was the highest in SY 1% at 7.33. The moisture content of SY was the highest among the control groups and addition of 1% BSG to SY was highest among the BSG-added group. Total contents of phenol and flavonoid slightly increased as the concentration of BSG increased (increase in the contents of phenol and flavonoid). The results of ferric reducing antioxidant power were similar to the findings of phenol and flavonoid content (an increase as the concentration of BSG increased). The overall acceptability of sensory characteristics was improved in all groups of samples when BSG 1% concentration increased. Application of BSG for the production of nonfat yogurt can enhance physicochemical properties, antioxidant activity, and sensory characteristics of reduced-fat and nonfat yogurt. Addition of BSG to reduced-fat and nonfat yogurt can improve their physical and antioxidant properties to the level of FFY.

Interpretable deep neural network for cancer survival analysis by integrating genomic and clinical data.

BACKGROUND: Understanding the complex biological mechanisms of cancer patient survival using genomic and clinical data is vital, not only to develop new treatments for patients, but also to improve survival prediction. However, highly nonlinear and high-dimension, low-sample size (HDLSS) data cause computational challenges to applying conventional survival analysis. RESULTS: We propose a novel biologically interpretable pathway-based sparse deep neural network, named Cox-PASNet, which integrates high-dimensional gene expression data and clinical data on a simple neural network architecture for survival analysis. Cox-PASNet is biologically interpretable where nodes in the neural network correspond to biological genes and pathways, while capturing the nonlinear and hierarchical effects of biological pathways associated with cancer patient survival. We also propose a heuristic optimization solution to train Cox-PASNet with HDLSS data. Cox-PASNet was intensively evaluated by comparing the predictive performance of current state-of-the-art methods on glioblastoma multiforme (GBM) and ovarian serous cystadenocarcinoma (OV) cancer. In the experiments, Cox-PASNet showed out-performance, compared to the benchmarking methods. Moreover, the neural network architecture of Cox-PASNet was biologically interpreted, and several significant prognostic factors of genes and biological pathways were identified. CONCLUSIONS: Cox-PASNet models biological mechanisms in the neural network by incorporating biological pathway databases and sparse coding. The neural network of Cox-PASNet can identify nonlinear and hierarchical associations of genomic and clinical data to cancer patient survival. The open-source code of Cox-PASNet in PyTorch implemented for training, evaluation, and model interpretation is available at: https://github.com/DataX-JieHao/Cox-PASNet.

An Unusual Delayed Onset of Systemic Toxicity After Fluoroscopy-Guided Cervical Epidural Steroid Injection With Levobupivacaine: A Case Report.

BACKGROUND: Cervical epidural steroid injection (CESI) with local anesthetics is commonly used to treat neck pain and radicular pain of the upper extremity. Local anesthetic systemic toxicity (LAST) occurs shortly after injection as a complication; however, delayed onset is a very rare event, especially in central nervous system (CNS) block. CASE REPORT: We present a case in which delayed onset of LAST occurred in a patient who received CESI for cervical and arm radiating pain due to a cervical disc protrusion. We performed the interlaminar approach for CESI using fluoroscopic guidance. After confirming the location of the epidural space using the loss of resistance technique and spreading of contrast agent (Telebrix® 30), a mixture of 0.25% levobupivacaine 12.5 mg (5 mL in volume), hyaluronidase 1,500 IU (1 mL), dexamethasone 5 mg (1 mL), and normal saline 3 mL was administrated. After 50 minutes of injection, the patient showed CNS toxicity (unconsciousness, seizure) with normal blood pressure and tachycardia; therefore, she was immediately sedated with intravenous midazolam (3 mg), and 15 L/min of oxygen was administered. The patient fully recovered after 30 minutes of sedation without any sequelae. CONCLUSION: Delayed onset of LAST is a rare complication of a common procedure in CESI, so it is important to be aware of this complication and the presentation of toxicity.

Transthoracic radiofrequency ablation for hepatic tumor located beneath the diaphragm under one-lung ventilation: A case report.

RATIONALE: Radiofrequency ablation (RFA) has become the reliable, effective, and less invasive treatment for small primary or metastatic hepatic tumors. Hepatic tumors that located immediately beneath the diaphragm are difficult to treat with percutaneous RFA due to poor visualization by percutaneous ultrasonography and the close location of the heart or lung. A transthoracic approach has been proposed to be an alternative for hepatic tumors located beneath the diaphragm that are difficult to access by conventional percutaneous or laparoscopic approaches. There has been no report regarding the anesthetic management of the transthoracic RFA for hepatic tumor. PATIENT CONCERNS: A 69-year-old female had undergone segmentectomy due to hepatocellular carcinoma 4 years ago. DIAGNOSES: Newly developed hepatic tumor located in the liver dome and beneath the diaphragm was diagnosed by follow-up imaging study. INTERVENTIONS: Because the tumor could not be identified by transabdominal ultrasonography (US), transthoracic approach for RFA under one-lung ventilation was planned. General anesthesia was induced with propofol and remifentanil via target-controlled infusion system and rocuronium was administered. Orotracheal intubation with double-lumen endotracheal tube was performed and position of the tube in the trachea was confirmed by bronchoscope. The RFA electrode was introduced percutaneously into the right pleural cavity, guided by visualization through the thoracoscope and inserted into the tumor after visualizing the tumor by US. Radiofrequency waves can be successfully administered through the needle. OUTCOMES: We performed successfully RFA of the hepatic tumor through one-lung ventilation and transthoracic approach. At 5 days postoperatively, she was discharged in a stable condition without any complication. LESSONS: Transthoracic RFA can be successfully performed under one-lung ventilation, optimal analgesia, and vigilant monitoring.

PASNet: pathway-associated sparse deep neural network for prognosis prediction from high-throughput data.

BACKGROUND: Predicting prognosis in patients from large-scale genomic data is a fundamentally challenging problem in genomic medicine. However, the prognosis still remains poor in many diseases. The poor prognosis may be caused by high complexity of biological systems, where multiple biological components and their hierarchical relationships are involved. Moreover, it is challenging to develop robust computational solutions with high-dimension, low-sample size data. RESULTS: In this study, we propose a Pathway-Associated Sparse Deep Neural Network (PASNet) that not only predicts patients' prognoses but also describes complex biological processes regarding biological pathways for prognosis. PASNet models a multilayered, hierarchical biological system of genes and pathways to predict clinical outcomes by leveraging deep learning. The sparse solution of PASNet provides the capability of model interpretability that most conventional fully-connected neural networks lack. We applied PASNet for long-term survival prediction in Glioblastoma multiforme (GBM), which is a primary brain cancer that shows poor prognostic performance. The predictive performance of PASNet was evaluated with multiple cross-validation experiments. PASNet showed a higher Area Under the Curve (AUC) and F1-score than previous long-term survival prediction classifiers, and the significance of PASNet's performance was assessed by Wilcoxon signed-rank test. Furthermore, the biological pathways, found in PASNet, were referred to as significant pathways in GBM in previous biology and medicine research. CONCLUSIONS: PASNet can describe the different biological systems of clinical outcomes for prognostic prediction as well as predicting prognosis more accurately than the current state-of-the-art methods. PASNet is the first pathway-based deep neural network that represents hierarchical representations of genes and pathways and their nonlinear effects, to the best of our knowledge. Additionally, PASNet would be promising due to its flexible model representation and interpretability, embodying the strengths of deep learning. The open-source code of PASNet is available at https://github.com/DataX-JieHao/PASNet .

Effect of remifentanil during drug-induced sleep endoscopy in patients with obstructive sleep apnea.

PURPOSE: During drug-induced sleep endoscopy (DISE) in patients with obstructive sleep apnea, the increased depth of propofol anesthesia is related to the increased collapsibility of the upper airway with dose-dependent. We examined the effect of remifentanil on propofol concentration during DISE. METHODS: In a prospective randomized trial, 56 adult patients were divided into remifentanil-propofol (n = 28) and propofol alone (n = 28) groups. Anesthesia was administered using a target-controlled infusion system. In the remifentanil-propofol group, 0.5 ng/ml remifentanil was administered prior to propofol infusion and its concentration maintained; thereafter, in the propofol alone group, normal saline was injected instead of remifentanil. Propofol was infused at a concentration of 1.5 µg/ml after the target concentration of remifentanil was reached. In both groups, the concentration of propofol was increased by 0.5 µg/ml if the degree of sedation was not sufficient. The sedation level was targeted at observer's assessment of alertness/sedation (OAA/S) scale 3. RESULTS: The mean propofol concentration was 2.87 ± 0.60 µg/ml in the remifentanil-propofol group, which was lower than that in the propofol alone group (3.38 ± 0.72 µg/ml, P < 0.001). The time until sufficient sedation to perform DISE was shorter in the remifentanil-propofol group (P < 0.001). Apnea-hypopnea index and the lowest peripheral capillary oxygen saturation (SpO2) during polysomnography showed no statistical difference between groups (P > 0.05). The lowest SpO2 and VOTE classification during DISE were also not statistically different (P > 0.05). CONCLUSIONS: Use of remifentanil during DISE reduces the target concentration of propofol required for patient sedation to perform DISE without respiratory depression.