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Contamination of deoxynivalenol (DON) in grains is common worldwide and pigs are particularly susceptible to this mycotoxin. The distribution of DON in porcine tissues following intravenous administration was investigated in this study. Fifteen pigs were randomly divided into three groups. Animals in groups A and B were administrated with DON at the dose of 250 and 750 µg kg−1 body weight, respectively, while group C served as blank control. Plasma, bile and 27 tissues were collected at 30 min post-administration. DON concentrations in all samples were tested using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). To observe the distribution of DON in tissues, these samples were further subjected to the immunohistochemical analyses. Totally, the bile and 13 tissues were sampled for DON-based detection, including kidney, mesenteric lymph nodes, muscle, stomach, jejunum, colon, plasma, spleen, rectum, cecum, liver, ileum, and duodenum. No significant difference was observed for the concentrations of DON in duodenum, ileum and liver samples between groups A and B; while the DON concentrations in cecum and rectum of group B were significantly higher (P-value

Objectives This meta-analysis aimed to evaluate the association between the Geriatric Nutritional Risk Index (GNRI) and survival outcomes in patients with urological cancer.Design Systematic review and meta-analysis of observational studies.Data sources A comprehensive literature search was conducted in Medline, EMBASE, Google Scholar and the Cochrane Library from inception to 7 July 2024.Eligibility criteria Studies were included if they examined the correlation between the GNRI and long-term survival outcomes in adult patients (≥18 years old) with urological cancers.Data extraction and synthesis Two researchers independently extracted data and assessed study quality using the Newcastle-Ottawa Scale and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. Publication bias was evaluated using funnel plots and Egger’s test for outcomes with more than 10 studies. Pooled HRs and 95% CIs were calculated using a random-effects model. Subgroup analyses, meta-regression and sensitivity analyses were performed.Results 17 studies involving 8816 patients were included. Study quality assessment showed that 15 studies had a low risk of bias (scores 7–9) and two had a high risk (scores 5–6). Low GNRI was significantly associated with poor overall survival (OS) (HR: 2.6, 95% CI: 2.0 to 3.38, p

Abstract Background Remimazolam is a novel ultra-short-acting benzodiazepine that has been recently introduced as an alternative to propofol for general anesthesia. While both agents have been compared in terms of safety and efficacy, their relative effects on postoperative quality of recovery (QoR) remain unclear. Therefore, this meta-analysis aimed to compare the effects of remimazolam and propofol on subjective QoR in surgical patients who underwent general anesthesia. Methods Medline, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched from inception to May 28, 2024 to identify randomized controlled trials comparing remimazolam and propofol in terms of postoperative QoR. The Cochrane risk-of-bias tool (RoB 2) was used to assess study quality. QoR score on postoperative day (POD) 1 (primary outcome), QoR scores on PODs 2–3, QoR dimensions, time to loss of consciousness, other recovery characteristics, and rescue analgesia requirement were evaluated using random-effects meta-analyses. Results This meta-analysis included 13 studies published between 2022 and 2024 involving 1,418 patients. QoR was evaluated using either the QoR-15 (10 studies) or QoR-40 (3 studies) questionnaire. The pooled results indicated no significant difference in the QoR scores on POD 1 (standardized mean difference: 0.02, 95% confidence interval [CI]: − 0.20, 0.23, P = 0.88, I2 = 73%) and PODs 2–3 between remimazolam and propofol. Furthermore, no significant differences were observed in QoR dimensions, length of postanesthesia care unit (PACU) stay, and time to extubation as well as in the risks of agitation and postoperative nausea and vomiting. Patients administered remimazolam exhibited slower anesthetic induction (mean difference (MD): 32.27 s) but faster recovery of consciousness (MD: − 1.60 min) than those administered propofol. Moreover, remimazolam was associated with a lower risk of rescue analgesia requirement in the PACU (risk ratio: 0.62, 95% CI: 0.43, 0.89, P = 0.009, I 2 = 0%) but not in the ward. Conclusion Remimazolam is a potential alternative to propofol for general anesthesia as it offers similar QoR to the latter and has advantages in terms of consciousness recovery and immediate postoperative analgesia requirement.

Abstract Background Monitoring Intraabdominal Pressure (IAP) is essential in critical care, as elevated IAP can lead to severe complications, including Abdominal Compartment Syndrome (ACS). Advances in technology, such as digital capsules, have opened new avenues for measuring IAP non-invasively. This study assesses the feasibility and effectiveness of using a capsular device for IAP measurement in an animal model. Method In our controlled experiment, we anesthetized pigs and simulated elevated IAP conditions by infusing CO2 into the peritoneal cavity. We compared IAP measurements obtained from three different methods: an intravesical catheter (IAPivp), a capsular device (IAPdot), and a direct peritoneal catheter (IAPdir). The data from these methods were analyzed to evaluate agreement and accuracy. Results The capsular sensor (IAPdot) provided continuous and accurate detection of IAP over 144 h, with a total of 53,065,487 measurement triplets recorded. The correlation coefficient (R²) between IAPdot and IAPdir was excellent at 0.9241, demonstrating high agreement. Similarly, IAPivp and IAPdir showed strong correlation with an R² of 0.9168. Conclusion The use of capsular sensors for continuous and accurate assessment of IAP marks a significant advancement in the field of critical care monitoring. The high correlation between measurements from different locations and methods underscores the potential of capsular devices to transform clinical practices by providing reliable, non-invasive IAP monitoring.

Abstract This study demonstrates a novel use of the U-Net convolutional neural network (CNN) for modeling pixel-based electrostatic potential distributions in GaN metal–insulator-semiconductor high-electron mobility transistors (MIS-HEMTs) with various gate and source field plate designs and drain voltages. The pixel-based images of the potential distribution are successfully modeled from the developed U-Net CNN with an error of less than 1% error relative to a TCAD simulated reference of a 500-V electrostatic potential distribution in the AlGaN/GaN interface. Furthermore, the modeling time of potential distributions by U-Net takes about 80 ms. Therefore, the U-Net CNN is a promising approach to efficiently model the pixel-based distributions characteristics in GaN power devices.

Fibromyalgia is a chronic illness usually accompanied by long-lasting, general pain throughout the body, often accompanied by anxiety, depression, fatigue, and sleep disruption. Meanwhile, doctors and scientists have not entirely discovered detailed mechanisms; patients always have an exaggerated sensation to pervasive pain without satisfied medical service. Given the lack of knowledge on its underlying mechanism, current treatments aim to provide pain and/or symptom relief. The present study aimed to clarify the role of cannabinoid receptor 1 (CB1) signaling in a mouse fibromyalgia pain model. To develop the mouse fibromyalgia model, mice were subjected to intermittent cold stress (ICS). Our results indicated that mechanical (2.09 ± 0.09 g) and thermal hyperalgesia (4.77 ± 0.29 s), which were evaluated by von Frey and Hargraves’ tests, were induced by ICS, suggesting successful modeling. The hurting replies were then provoked by electroacupuncture (EA) but not for sham EA mice. Further, in a Western blot analysis, we found significantly decreased CB1 protein levels in the thalamus, somatosensory cortex, and anterior cingulate cortex. In addition, the levels of pain-related protein kinases and transcription factor were increased. Treatment with EA reliably increased CB1 expression in various brain regions sequentially alleviated by nociceptive mediators. Furthermore, the administration of a CB1 agonist significantly attenuated fibromyalgia pain, reversed EA analgesia by the CB1 antagonist, and further reversed the chemogenetic inhibition of SSC. Our innovative findings evidence the role of CB1 signaling in the interaction of EA and fibromyalgia, suggesting its potential for clinical trials and as a treatment target.

Purpose To develop a rib and clavicle fracture detection model for chest radiographs in trauma patients using a deep learning (DL) algorithm.Materials and methods We retrospectively collected 56 145 chest X-rays (CXRs) from trauma patients in a trauma center between August 2008 and December 2016. A rib/clavicle fracture detection DL algorithm was trained using this data set with 991 (1.8%) images labeled by experts with fracture site locations. The algorithm was tested on independently collected 300 CXRs in 2017. An external test set was also collected from hospitalized trauma patients in a regional hospital for evaluation. The receiver operating characteristic curve with area under the curve (AUC), accuracy, sensitivity, specificity, precision, and negative predictive value of the model on each test set was evaluated. The prediction probability on the images was visualized as heatmaps.Results The trained DL model achieved an AUC of 0.912 (95% CI 87.8 to 94.7) on the independent test set. The accuracy, sensitivity, and specificity on the given cut-off value are 83.7, 86.8, and 80.4, respectively. On the external test set, the model had a sensitivity of 88.0 and an accuracy of 72.5. While the model exhibited a slight decrease in accuracy on the external test set, it maintained its sensitivity in detecting fractures.Conclusion The algorithm detects rib and clavicle fractures concomitantly in the CXR of trauma patients with high accuracy in locating lesions through heatmap visualization.

ObjectiveThis meta-analysis aimed to compare videolaryngoscope (VL)-assisted transesophageal echocardiography (TEE) probe insertion with conventional methods in terms of efficacy and safety.MethodsSeveral major databases such as Medline and Embase were systematically searched to identified relevant studies from inception to June 2024. The primary outcome was complication rate, defined as the proportion of patients experiencing complications related to TEE probe insertion. Injuries at specific sites (e.g., posterior hypopharyngeal wall) from both groups were also analyzed. The secondary outcomes included the first-attempt success rate and total insertion time of VL and conventional methods.ResultsSeven trials involving 716 participants were identified. The use of VL was found to significantly reduce the complication rate (risk ratio[RR]:0.28, 95% confidence interval[CI]:0.17-0.46, P < 0.00001) and increased the first-attempt success rate [FASR] (RR:1.33, 95%CI: 1.10-1.60, P = 0.003) compared with conventional methods. These findings were confirmed by trial sequential analysis. No significant difference was found in the TEE insertion time among the two techniques (mean difference: -2.94s, 95%CI: -10.28-4.4, P = 0.43). VL significantly reduced the risk of trauma to the hypopharyngeal wall but showed no significant benefits in other areas (e.g., pyriform sinus). The certainty of evidence was moderate for the complication rate, very low for the FAS rate, and low for the TEE insertion time.ConclusionThe use of VL for TEE probe insertion is associated with a significantly lower complication rate and higher FAS rate than conventional methods. These findings suggest that VL enhances patient safety and improves the efficiency of TEE probe insertion.

In this work, the methodology using Graph Attention Network (GAT) for the reserve design in GaN power MIS-HEMTs based on hand-drawn characteristics is demonstrated for the first-time. The hand-drawn ID-VG characteristic is constructed by Ramer-Douglas-Peucker algorithm. Then, the extracted information is sent to the Graph Attention Network to receive the corresponding device design variables, including tAlGaN, recessed depth, Al%, Lg, Lgd, and Lgs. Less than 30 seconds is consumed to generate the design variables and less than 8% of the differences in the key extracted parameters, such as threshold voltage (Vth), On-state current (Ion), and subthreshold slope (SS), can be achieved by comparing hand-drawn ID-VG and simulated ID-VG characteristic based on the design variables from GAT model. Therefore, the developed GAT approach is promising for the reverse design of GaN power MIS-HEMTs, which can provide users with efficient and valuable design suggestions to optimize the devices toward the targeting performance.

The introduction of hydrophilic segments into the main-chain of polymer photocatalysts allows water to efficiently enter the interior through these hydrophilic segments, and results in effective water/polymer interfaces for hydrogen evolution.

Abstract Background Peripartum cardiomyopathy (PPCM) is defined as an idiopathic cardiomyopathy occurring in the last month of pregnancy or the first 6 months postpartum without an identifiable cause. PPCM is suspected to be triggered by the generation of a cardiotoxic fragment of prolactin and the secretion of a potent antiangiogenic protein from the placental, but no single factor has been identified or defined as the underlying cause of the disease. Influenza virus can cause PPCM through immune-mediated response induced by proinflammatory cytokines from host immunity and endothelial cell dysfunction. We report a case in a parturient woman undergoing a cesarean delivery, who had influenza A pneumonia and PPCM. Case presentation A parturient woman at 40 weeks and 1 day of gestation who had experienced gestational hypertension accompanied by pulmonary edema developed hypotension after undergoing an emergency cesarean delivery. An elevation of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was noted, and echocardiography revealed a left ventricular ejection fraction of 20%. She underwent a nasopharyngeal swab test, in which influenza A antigen was positive. She was diagnosed as having PPCM and received anti-viral treatment. After antiviral treatment, hemodynamic dysfunction stabilized. We present and discuss the details of this event. Conclusion PPCM is a heart disease that is often overlooked by medical personnel. Rapid swab tests, serum creatine kinase measurement, and echocardiography are imperative diagnostic approaches for the timely recognition of virus-associated cardiomyopathy in peripartum women with influenza-like disease and worsening dyspnea, especially during the epidemic season. Prompt antiviral treatment should be considered, particularly after PPCM is diagnosed.

Abstract Hypertension and pain are both prevalent conditions in the older adult population. We aimed to report the prevalence of pain discomforts and investigated the association between hypertension and pain discomforts among older adults in the United States. Data from the 2011 National Health and Aging Trends Study were analyzed. In-person interviews were conducted in 7601 adults ages ≥ 65 years. Prevalence of bothersome pain, activity-limiting pain, locations of pain and usage of pain medicine were evaluated. Demographics, comorbidities, and other covariates were compared between older adults with hypertension and those without. Multivariate regression was further performed to yield adjusted odd ratios. Among 6825 older adults, 4533 of them had a history of hypertension while 2272 of them had not. Prevalence of bothersome pain (57.12% versus 44.81%, p

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines based on variant strains have been in use as booster doses to update immunity against circulating variants. Here we present the results of a phase one prospective, randomized, and open-labeled trial to study the safety and immunogenicity of a booster dose consisting of a subunit vaccine based on the stabilized prefusion SARS-CoV-2 spike protein, MVC-COV1901, or its Beta version, MVC-COV1901-Beta. Participants aged ≥18 and

BackgroundTo evaluate the analgesic efficacy and risk of low-to-medium dose intrathecal morphine (ITM) (i.e., ≤0.5 mg) following cardiac surgery.MethodsMedline, Cochrane Library, Google scholar and EMBASE databases were searched from inception to February 2022. The primary outcome was pain intensity at postoperative 24 h, while the secondary outcomes included intravenous morphine consumption (IMC), extubation time, hospital/intensive care unit (ICU) length of stay (LOS), and ITM-associated side effects (e.g., respiratory depression). Subgroup analysis was performed on ITM dosage (low:

Plant growth promoting fungi are receiving increased attention as valuable beneficial microorganisms in crop cultivation due to their capacity to produce bioactive substances, promote plant growth and enhance immune defense functions. In this study, a novel Trichoderma isolate, designated as TM2-4, was screened from healthy tomato rhizosphere soil and identified as Trichoderma afroharzianum. Culture filtrate of the isolate TM2-4 displayed obvious bioactive substance production and an evident effect in promoting tomato seed germination, with hypocotyl length, radical length and vigor index increased by 28.7, 19.4 and 62.1%, respectively, after a 100-fold dilution treatment. To assess the promotion effect and related mechanism of isolate TM2-4, the plant biological indexes and gene expression profiles of tomato plants treated with or without T. afroharzianum TM2-4 microbial agent were investigated by greenhouse pot experiment and RNA sequencing. The results demonstrated that T. afroharzianum TM2-4 significantly promoted tomato plant growth in terms of plant height, dry weight, number of leaves per plant and root activity, through efficient colonization in the rhizosphere and root system of the plants. Transcriptome analyses identified a total of 984 differentially expressed genes in T. afroharzianum microbial agent inoculated tomato roots, which were mainly engaged in the biological process of phytohormone homeostasis, antioxidant activity, as well as metabolic pathways including phenylpropanoid biosynthesis and glutathione metabolism. These findings provide useful information for understanding the mechanism of isolate TM2-4 for tomato plant growth promotion, which would facilitate further development of T. afroharzianum TM2-4 microbial agent for use in vegetable crop production.

Abstract The COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 µg or 5 µg of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 μg or 5 μg of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.

Background/purpose: The palate has become a popular site for the placement of temporary anchorage devices (TADs) owing to its bone quantity and quality. This study aimed to investigate total and cortical bone thicknesses in the whole palate as well as palatal width using a standard grid system and cone-bean computed tomography (CBCT) images. Materials and methods: The CBCT images of 43 samples were selected. The total bone and cortical bone thicknesses of the palate were surveyed on 64 points per patient. The palatal width was measured. The difference between the age and sex groups was analyzed. Results: The total palatal bone thickness in the adult group ranged from 9.85 ± 2.04 to 1.87 ± 0.79 mm. In the adolescent group, we found one-third of the incisor roots in the area 3 mm distal to the incisive foramen and 8 mm lateral to the mid-palatal suture. The cortical bone thickness in adults was significantly thicker in the posterior paramedian area than that in adolescents. Conclusion: The thickest vertical bone is located in the zone 3 mm distal to the incisive foramen and 4–8 mm lateral to the midpalate. The zone 6 mm posterior to the incisive foramen and 2–8 mm lateral to the midpalate exhibited optimal thickness and was away from the incisor roots. This region could be a safe zone for adolescent patients to place TADs. When TADs are to be inserted at the posterior palate, the 2-mm paramedian area should be the first region of choice.

Radiation-induced stenosis of the carotid artery is a significant risk factor for large-vessel ischemic stroke, which usually leads to significant impairment of neurological function. We performed intra-arterial thrombectomy on a 63-year-old male patient who had laryngeal cancer and postradiation carotid stenosis. He presented with acute-onset dysarthria and left hemiplegia. Brain computed tomography perfusion scan showed right middle cerebral artery ischemic change. Angiography confirmed total occlusion of the right internal carotid artery. Intra-arterial mechanical thrombectomy with carotid stenting was performed immediately, and recanalization was achieved. The patient fully recovered and was discharged after a 1-week hospitalization. Our experience suggests that early intervention for radiation-related carotid stenosis might be essential and beneficial for the outcome of large-vessel ischemic stroke.

(1) Background: Design thinking is a problem-solving approach that has been applied in various sectors, including healthcare and medical education. While deep learning (DL) algorithms can assist in clinical practice, integrating them into clinical scenarios can be challenging. This study aimed to use design thinking steps to develop a DL algorithm that accelerates deployment in clinical practice and improves its performance to meet clinical requirements. (2) Methods: We applied the design thinking process to interview clinical doctors and gain insights to develop and modify the DL algorithm to meet clinical scenarios. We also compared the DL performance of the algorithm before and after the integration of design thinking. (3) Results: After empathizing with clinical doctors and defining their needs, we identified the unmet need of five trauma surgeons as “how to reduce the misdiagnosis of femoral fracture by pelvic plain film (PXR) at initial emergency visiting”. We collected 4235 PXRs from our hospital, of which 2146 had a hip fracture (51%) from 2008 to 2016. We developed hip fracture DL detection models based on the Xception convolutional neural network by using these images. By incorporating design thinking, we improved the diagnostic accuracy from 0.91 (0.84–0.96) to 0.95 (0.93–0.97), the sensitivity from 0.97 (0.89–1.00) to 0.97 (0.94–0.99), and the specificity from 0.84 (0.71–0.93) to 0.93(0.990–0.97). (4) Conclusions: In summary, this study demonstrates that design thinking can ensure that DL solutions developed for trauma care are user-centered and meet the needs of patients and healthcare providers.

(1) Background: Hip degenerative disorder is a common geriatric disease is the main causes to lead to total hip replacement (THR). The surgical timing of THR is crucial for post-operative recovery. Deep learning (DL) algorithms can be used to detect anomalies in medical images and predict the need for THR. The real world data (RWD) were used to validate the artificial intelligence and DL algorithm in medicine but there was no previous study to prove its function in THR prediction. (2) Methods: We designed a sequential two-stage hip replacement prediction deep learning algorithm to identify the possibility of THR in three months of hip joints by plain pelvic radiography (PXR). We also collected RWD to validate the performance of this algorithm. (3) Results: The RWD totally included 3766 PXRs from 2018 to 2019. The overall accuracy of the algorithm was 0.9633; sensitivity was 0.9450; specificity was 1.000 and the precision was 1.000. The negative predictive value was 0.9009, the false negative rate was 0.0550, and the F1 score was 0.9717. The area under curve was 0.972 with 95% confidence interval from 0.953 to 0.987. (4) Conclusions: In summary, this DL algorithm can provide an accurate and reliable method for detecting hip degeneration and predicting the need for further THR. RWD offered an alternative support of the algorithm and validated its function to save time and cost.

In this work, we demonstrated the thermal analysis of different flip-chip bonding designs for high power GaN HEMT developed for power electronics applications, such as power converters or photonic driver applications, with large gate periphery and chip size, as well as an Au metal heat-spreading layer deposited on top of a planarized dielectric/passivation layer above the active region. The Au bump patterns can be designed with high flexibility to provide more efficient heat dissipation from the large GaN HEMT chips to an AlN package substrate heat sink with no constraint in the alignment between the HEMT cells and the thermal conduction bumps. Steady-state thermal simulations were conducted to study the channel temperatures of GaN HEMTs with various Au bump patterns at different levels of current and voltage loadings, and the results were compared with the conventional face-up GaN die bonding on an AlN package substrate. The simulations were started from a single finger isolated HEMT cell and then extended to multiple fingers HEMT cells (total gate width > 40 mm) to investigate the “thermal cross-talk” effect from neighboring devices. Thermal analysis of the GaN HEMT under pulse operation was also performed to better reflect the actual conditions in power conversion or pulsed laser driver applications. Our analysis provides a combinational assessment of power GaN HEMT dies under a working condition (e.g., 1MHz, 25% duty cycle) with different flip chip packaging schemes. The analysis indicated that the channel temperature rise (∆T) of a HEMT cell in operation can be reduced by 44~46% by changing from face-up die bonding to a flip-chip bonding scheme with an optimized bump pattern design.

Background: Patients with type 2 diabetes (T2DM) often experience depression during treatment, negatively influencing their treatment compliance and clinical outcomes. Recently, the pay-for-performance (P4P) program for chronic diseases, with high-cost and high-risk feature, such as T2DM, has been implemented and has been operational for several years. Nevertheless, its effect on the risk of developing depression among T2DM cases is unknown. This study aims to explore the association of P4P use with the subsequent risk of developing depression among these patients.Methods: This cohort study used a nationwide health insurance database to identify patients 20–70 years of age newly diagnosed with T2DM who enrolled in the P4P program between 2001 and 2010. From this group, we enrolled 17,022 P4P users and then 17,022 non-P4P users who were randomly selected using propensity-score–matching. Enrolled patients were followed until the end of 2012 to record the occurrence of depression. The Cox proportional hazards regression was utilized to obtain the adjusted hazard ratio (aHR) for P4P use.Results: During the study period, a total of 588 P4P users and 1,075 non-P4P users developed depression at incidence rates of 5.89 and 8.41 per 1,000 person-years, respectively. P4P users had a lower depression risk than did non-P4P users (aHR, 0.73; 95% Confidence Interval, 0.65–0.80). This positive effect was particularly prominent in those receiving high-intensity use of the P4P program.Conclusion: Integrating P4P into routine care for patients with T2DM may have beneficial effects on curtailing the subsequent risk of depression.

Abstract Background Circular RNAs are a class of regulatory RNA transcripts, which are ubiquitously expressed in eukaryotes. In the current study, we evaluate the function of a novel circRNA derived from the β-catenin gene locus, circβ-catenin. Results Circβ-catenin is predominantly localized in the cytoplasm and displays resistance to RNase-R treatment. We find that circβ-catenin is highly expressed in liver cancer tissues when compared to adjacent normal tissues. Silencing of circβ-catenin significantly suppresses malignant phenotypes in vitro and in vivo, and knockdown of this circRNA reduces the protein level of β-catenin without affecting its mRNA level. We show that circβ-catenin affects a wide spectrum of Wnt pathway-related genes, and furthermore, circβ-catenin produces a novel 370-amino acid β-catenin isoform that uses the start codon as the linear β-catenin mRNA transcript and translation is terminated at a new stop codon created by circularization. We find that this novel isoform can stabilize full-length β-catenin by antagonizing GSK3β-induced β-catenin phosphorylation and degradation, leading to activation of the Wnt pathway. Conclusions Our findings illustrate a non-canonical function of circRNA in modulating liver cancer cell growth through the Wnt pathway, which can provide novel mechanistic insights into the underlying mechanisms of hepatocellular carcinoma.

MEMS based 3D double stacked tower pixel biosensor 10 × 10 array with integration of readout circuit for detection of saliva pH ion is demonstrated. The pixel biosensor comprised a driving electrode, sensing electrode and double stack tower pixel structure. The sensitivity of double stacked tower biosensor can be auxiliary enhanced by proposed lower-jitter low dropout regulator circuit and dual offset cancellation comparator. The double stacked tower sensor is fabricated by MEMS backend-of-line CMOS process, it is compatible with CMOS frontend readout circuits and integrated as a system-on-chip (SoC). The double stacked tower pixel by MEMS process is to obtain a larger volume ratio of charge groups in a pixel of biosensor to enhance the sensitivity and linearity for ion detection. With the double stacked tower structure in biosensor, the sensitivity is improved by 31% than that of single tower structure proved by simulation. A wide-range linearity from pH 2.0 to pH 8.3, high sensitivity of −21 ADC counts/pH (or 212 mV/pH), response time of 5 s, repetition of 98.9%, and drift over time of 0.5 mV are achieved. Furthermore, the proposed biosensor was performed to confirm the artificial saliva from healthy gingiva, chronic gingivitis and chronic periodontitis, the measured ADC counts from proposed biosensor SoC was in consistent of that measured cyclic voltametric (CV) method very well. The proposed 3D double stack tower biosensor and readout circuit can be further integrated with internet-of-thing (IoT) device and NFC for data transmission for continuous pH sensing to facilitate the chronic gingiva disease health care at home.

Background: This was a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVCCOV1901, a SARS-CoV-2 S-2P protein vaccine adjuvanted with aluminum hydroxide and CpG 1018. Methods: Between September 28 and November 13 2020, 77 participants were screened. Of these, 45 healthy adults from 20 to 49 years of age were to be administered two doses of MVCCOV1901 in doses of 5 μg, 15 μg, or 25 μg of spike protein at 28 days apart. There were 15 participants in each dose group; all were followed for 28 days after the second dose at the time of the interim analysis. Adverse events and laboratory data were recorded for the safety evaluation. Blood samples were collected for humoral, and cellular immune response at various time points. Trial Registration: ClinicalTrials.gov NCT 04487210. Findings: Solicited adverse events were mostly mild and similar. No subject experienced fever. After the second dose, the geometric mean titers (GMTs) for SARS-CoV-2 spike-specific immunoglobulin G were 7178.2, 7746.1, 11,220.6 in the 5 μg, 15 μg, and 25 μg dose groups, respectively. The neutralizing activity were detected in both methods. (Day 43 GMTs, 538.5, 993.1, and 1905.8 for pseudovirus; and 33.3, 76.3, and 167.4 for wild-type virus). The cellular immune response induced by MVCCOV1901 demonstrated substantially higher numbers of IFN-γ- producing cells, suggesting a Th1-skewed immune response. Interpretation: The MVCCOV1901 vaccine was well tolerated and elicited robust immune responses and is suitable for further development. Funding: Medigen Vaccine Biologics Corporation

A wireless sensor network (WSN) is made up of multiple sensors deployed in a specific sensing area to identify the occurrence of events and quickly transmit useful information back to the base station (BS). In WSNs, schemes to reduce energy consumption are an important topic of research. A well-designed data transmission scheme can effectively extend the lifetime of a network. In this paper, we propose an energy aware grid-based clustering power efficient data aggregation protocol (GB-PEDAP) for WSNs. The proposed scheme has a two-layer architecture: the inner layer and the outer layer. The inner layer uses direct transmission to collect the data of the cluster (cell), and the outer layer uses a tree structure transmission to collect the data of the cluster head (cell head). In our simulations, the number of rounds executed by GB-PEDAP was approximately 1.2 rounds of TBEEP, 1.3 rounds of GSTEB, and 1.5 rounds of PEDAP. With the initial energy, 0.25 J, the execution rounds of the first node death for GB-PEDAP, TBEEP, GSTEB, and PEDAP were 751, 572, 486, and 339, respectively. The proposed GB-PEDAP can evenly disperse the energy consumption of sensors to avoid the rapid death of sensors, extending the lifetime of a WSN.

Although several studies have investigated the back-muscle flexion-relaxation phenomenon (FRP), the effect of individual flexibility on the FRP has been discussed infrequently, with very limited data on the influence of flexibility training on the FRP. This study thus examined the effect of flexibility training on the change of back-muscle FRP pattern in relatively inflexible young men. We collected and analyzed the valid data from 20 male participants (10 each with high and low flexibility included in the control and trained groups, respectively) when flexing their trunks at seven trunk flexion positions (0°-90°, in increments of 15°); their erector spinae and hamstring activation, pelvic tilt, and lumbosacral angle were then recorded. After 7 weeks of flexibility training for the low-flexibility group, no difference in flexibility was discovered between this group and the control (originally high-flexibility) group. The trunk flexion experiment was then repeated. The results showed that before the training stage, the low-flexibility group had lower erector spinae and higher hamstring activation, a larger pelvic tilt, and a smaller lumbosacral angle. By contrast, after training, the erector spinae and hamstring activation, pelvic tilt, and lumbosacral angle were significantly changed, and no intergroup differences were observed in FRP patterns. The study results suggest that flexibility training changes lumbopelvic movement and thereby reduces the degree of the back-muscle FRP when trunk flexion is performed.

Abstract Background The prevalence rate of reflux esophagitis (RE) in Asia, including Taiwan, has increased dramatically in recent years. However, few studies have discussed on its relationship with metabolic syndrome (MetS). This study aimed to evaluate the correlation between RE and MetS and its components. Methods We conducted a cross-sectional study during 2013 to 2014 in Taiwan. A total of 4895 subjects who completed upper gastrointestinal endoscopy at the Health Examination Center of Changhua Christian Hospital were enrolled. RE was defined according to the upper gastrointestinal endoscopic findings and MetS was defined according to the Taiwanese criteria. Univariate and multivariate logistic regression analyses were applied to calculate odds ratios and 95% confidence intervals for each variable to assess the associated features for RE. We analyzed the relationship between the number of MetS components and the severity of RE using the chi-square test for trend. Results The prevalence rates of MetS and RE were respectively 28.5 and 59.6%. According to univariate logistic regression analysis, MetS was significantly associated with RE and remained a positive association in multivariate logistic regression analysis (adjusted ORß = 1.251; 95% CI = 1.071–1.462; p = 0.005). Furthermore, among the five MetS components, elevated blood pressure (adjusted ORγ = 1.163; 95% CI = 1.023–1.323; p = 0.021), abdominal obesity (adjusted ORγ = 1.173; 95% CI = 1.020–1.349; p = 0.026) and hyperglycemia (adjusted ORγ = 1.306; 95% CI = 1.142–1.495; p

Abstract Background Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in de novo GTP biosynthesis, plays an important role in cell metabolism and proliferation. It has been demonstrated that IMPDH can aggregate into a macrostructure, termed the cytoophidium, in mammalian cells under a variety of conditions. However, the regulation and function of the cytoophidium are still elusive. Results In this study, we report that spontaneous filamentation of IMPDH is correlated with rapid cell proliferation. Intracellular IMP accumulation promoted cytoophidium assembly, whereas elevated GTP level triggered disassociation of aggregates. By using IMPDH2 CBS domain mutant cell models, which are unable to form the cytoophidium, we have determined that the cytoophidium is of the utmost importance for maintaining the GTP pool and normal cell proliferation in the condition that higher IMPDH activity is required. Conclusions Together, our results suggest a novel mechanism whereby cytoophidium assembly upregulates IMPDH activity and mediates guanine nucleotide homeostasis.

The rapid increase of malware attacks has become one of the main threats to computer security. Finding the best way to detect malware has become a critical task in cybersecurity. Previous work shows that machine learning approaches could be a solution to address this problem. Many proposed methods convert malware executables into grayscale images and apply convolutional neural networks (CNNs) for malware classification. However, converting malware executables into images could twist the one-dimensional structure of binary codes. To address this problem, we explore the bit and byte-level sequences from malware executables and propose efficient one-dimensional (1D) CNNs for the malware classification. Our experiments evaluate our proposed 1D CNN models with two benchmark datasets. Our proposed 1D CNN models achieve better performance from the experimental results than the existing 2D CNNs malware classification models by providing smaller resizing bit/byte-level sequences with less computational cost.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by impaired insulin sensitivity (Si) and insulin secretion. Previous studies may have underestimated differences in the incidence of risk factors in insulin-sensitive diabetes mellitus (IS-DM) and insultin-resistant diabetes mellitus (IR-DM) patients and have not been conducted in the Chinese population. OBJECTIVES: We explored differences in metabolic risk factors between Chinese patients with newly diagnosed, insulin-resistant (IR) and insulin-sensitive (IS) T2DM. DESIGN: Cross-sectional study. SETTING: Cardinal Tien Hospital, Taiwan in 2011. METHODS: All participants received a frequently sampled intravenous glucose tolerance test. The acute insulin response after a glucose load (AIRg), Si, disposition index (DI), and glucose effectiveness (GE) were determined. Using the median Si value from 90 people without diabetes as a cutoff (1.19 ×10-4 mU/L/min), patients were divided into two groups, IS-DM and IR-DM. Multivariate regression analysis was used to examine the independent influence of MetS components on Si and AIRg. MAIN OUTCOME MEASURE(S): Insulin sensitivity. RESULTS: We enrolled 122 participants. In addition to higher probabilities of having MetS, IR-DM patients had a significantly higher body mass index (BMI), AIRg, and GE but a lower DI than IS-DM patients. Si correlated with BMI and triglycerides, and AIRg correlated with BMI and high-density lipoprotein cholesterol. BMI was the only component related to Si in the multivariate analysis. Furthermore, the AIRg was associated with BMI and fasting plasma glucose. Because BMI was the most critical factor, a cutoff value (25.0 kg/m2) was obtained from the receiver operating characteristic curve for predicting IR-DM. It showed a sensitivity and specificity of 60.8% and 60.9%, respectively. CONCLUSIONS: IR-DM patients had more MetS components than IS-DM patients. In Chinese patients obesity is the most critical factor for discriminating IR-DM from IS-DM. Patients with a BMI higher than 25 kg/m2 were prone to develop IR-DM. LIMITATIONS: The size of our study cohort was relatively small, which may weaken the statistical power of the study.

This study aims to develop a dynamic pad monitoring system (DPMS) for measuring the surface topography of polishing pad. Chemical mechanical planarization/polishing (CMP) is a vital process in semiconductor manufacturing. The process is applied to assure the substrate wafer or thin film on wafer that has reached the required planarization after deposition for lithographic processing of the desired structures of devices. Surface properties of polishing pad have a huge influence on the material removal rate (MRR) and quality of wafer surface by CMP process. A DPMS has been developed to analyze the performance level of polishing pad for CMP. A chromatic confocal sensor is attached on a designed fixture arm to acquire pad topography data. By swing-arm motion with continuous data acquisition, the surface topography information of pad can be gathered dynamically. Measuring data are analyzed with a designed FFT filter to remove mechanical vibration and disturbance. Then the pad surface profile and groove depth can be calculated, which the pad’s index PU (pad uniformity) and PELI (pad effective lifetime index) are developed to evaluate the pad’s performance level. Finally, 50 rounds of CMP experiments have been executed to investigate the correlations of MRR and surface roughness of as-CMP wafer with pad performance. Results of this study can be used to monitor the pad dressing process and CMP parameter evaluation for production of IC devices.

Use of a lead–tin mixed perovskite is generally considered an effective method to broaden the absorption wavelength of perovskite thin films. However, the preparation of lead–tin mixed perovskites is a major challenge due to the multivalent state of tin and stability in the atmosphere. This study attempted to replace the organic cation and metal elements of perovskites with a relatively thermal stable formamidinium (FA+) and a more environmentally friendly tin element. MA0.5FA0.5Pb0.8Sn0.2I3 lead–tin mixed perovskite thin films were prepared with the one-step spin-coating method. By adjusting the dimethylformamide (DMF):dimethyl sulfoxide (DMSO) concentration ratio of the lead–tin mixed perovskite precursor solution, the surface morphologies, crystallinity, and light-absorbing properties of the films were changed during synthesis to optimize the lead–tin mixed perovskite films as a light-absorbing layer of the inverted perovskite solar cells. The quality of the prepared lead–tin mixed perovskite film was the highest when the ratio of DMF:DMSO = 1:4. The power-conversion efficiency of the perovskite solar cell prepared with the film was 8.05%.

Summary: CTP synthase (CTPS) forms compartmentalized filaments in response to substrate availability and environmental nutrient status. However, the physiological role of filaments and mechanisms for filament assembly are not well understood. Here, we provide evidence that CTPS forms filaments in response to histidine influx during glutamine starvation. Tetramer conformation-based filament formation restricts CTPS enzymatic activity during nutrient deprivation. CTPS protein levels remain stable in the presence of histidine during nutrient deprivation, followed by rapid cell growth after stress relief. We demonstrate that filament formation is controlled by methylation and that histidine promotes re-methylation of homocysteine by donating one-carbon intermediates to the cytosolic folate cycle. Furthermore, we find that starvation stress and glutamine deficiency activate the GCN2/ATF4/MTHFD2 axis, which coordinates CTPS filament formation. CTPS filament formation induced by histidine-mediated methylation may be a strategy used by cancer cells to maintain homeostasis and ensure a growth advantage in adverse environments. : Metabolic enzymes form membraneless compartments to adapt to environmental changes. Lin et al. demonstrate that histidine catabolism coupled with the folate cycle contributes to methionine synthesis, which promotes protein methylation. This post-translational modification in turn induces CTPS filament formation to preserve CTPS but reduces its enzymatic activity under starvation. Keywords: histidine, CTP synthase, CTPS filament, ATF4, MTHFD2, folate cycle, one carbon, methylation, nutrient deprivation, cancer

Nonverbal communication plays a key role in conveying emotions during clinical interactions, but assessing it can be challenging. This study aims to develop a model for nonverbal communication using facial expression recognition and deep learning. A hybrid approach combining convolutional neural network (CNN)-based face detection and Extra Trees classifier was used to leverage CNN’s feature extraction and Extra Trees’ classification abilities. The study involved 88 nursing students participating in communication exercises with standardized patients, with their facial expressions scored by senior nurses and instructors, resulting in 3,318 labeled scores. The model, built using Extra Trees Regressor, found that students displayed adequate receptiveness, politeness, friendliness, and nonverbal empathy, with scores primarily between 60 and 70. By integrating clinical simulations with artificial intelligence, subjective bias was minimized, improving the stability of nonverbal behavior simulations. This model will be integrated into a nonverbal behavior learning platform to help nursing students develop communication skills and reduce anxiety during practice. The platform offers objective feedback, potentially enhancing healthcare education and telemedicine by providing advanced tools for evaluating nonverbal communication.

A simple procedure for SnCl2/TiCl3-mediated deoximation of ketoximes in an aqueous solvent is reported. Under the conditions developed in this effort, various ketones and aldehydes are produced in good to excellent yields.

Noise parameters of silicon germanium (SiGe) heterojunction bipolar transistors (HBTs) for different sizes are investigated in the breakdown region for the first time. When the emitter length of SiGe HBTs shortens, minimum noise figure at breakdown decreases. In addition, narrower emitter width also decreases noise figure of SiGe HBTs in the avalanche region. Reduction of noise performance for smaller emitter length and width of SiGe HBTs at breakdown resulted from the lower noise spectral density resulting from the breakdown mechanism. Good agreement between experimental and simulated noise performance at breakdown is achieved for different sized SiGe HBTs. The presented analysis can benefit the RF circuits operating in the breakdown region.

Aims. There are two phases of insulin secretion, the first (FPIS) and second phase (SPIS). In this study, we built equations to predict FPIS with metabolic syndrome (MetS) components and fasting plasma insulin (FPI). Methods. Totally, 186 participants were enrolled. 75% of participants were randomly selected as the study group to build equations. The remaining 25% of participants were selected as the external validation group. All participants received a frequently sampled intravenous glucose tolerance test, and acute insulin response after the glucose load (AIRg) was obtained. The AIRg was considered as FPIS. Results. When MetS components were only used, the following equation was built: log (FPIS) = 1.477 − 0.119 × fasting plasma glucose (FPG) + 0.079 × body mass index (BMI) − 0.523 × high-density lipoprotein cholesterol (HDL-C). After FPI was added, the second equation was formulated: log (FPIS) = 1.532 − 0.127 × FPG + 0.059 × BMI - 0.511 × HDL-C + 0.375 × log (FPI), which provided a better accuracy than the first one. Conclusions. Using MetS components, the FPIS could be estimated accurately. After adding FPI into the equation, the predictive power increased further. We hope that these equations could be widely used in daily practice.

BackgroundAlthough much attention has been focused on the association between chronic hyperglycemia and cerebrovascular diseases in type 2 diabetes mellitus (DM) patients, there is no data regarding the risk of ischemic stroke after a hyperosmolar hyperglycemic state (HHS) attack. The objective of this study was to investigate the risk of ischemic stroke in type 2 DM patients after an HHS attack.MethodsFrom 2004 to 2008, this retrospective observational study was conducted on a large cohort of Taiwanese using Taiwan's National Health Insurance Research Database (NHIRD). We identified 19,031 type 2 DM patients who were discharged with a diagnosis of HHS and 521,229 type 2 DM patients without an HHS diagnosis. Using the propensity score generated from logistic regression models, conditional on baseline covariates, we matched 19,031 type 2 DM patients with an HHS diagnosis with the same number from the comparison cohort. The one-year cumulative rate for ischemic stroke was estimated using the Kaplan-Meier method. After adjusting covariates, Cox proportional hazard regression was used to compute the adjusted one-year rate of ischemic stroke.ResultsOf the patients sampled, 1,810 (9.5%) of the type 2 DM patients with HHS and 996 (5.2%) of the comparison cohort developed ischemic stroke during the one-year follow-up period. After adjusting for covariates, the adjusted HR for developing ischemic stroke during the one-year follow-up period was 1.8 (95% C.I., 1.67 to 1.95, PConclusionAlthough DM is a well-recognized risk factor for atherosclerosis, type 2 DM patients that have suffered a HHS attacks are at an increased risk of developing ischemic stroke compared with those without HHS.

BACKGROUND: This population-based study investigated the relationship between individual and neighborhood socioeconomic status (SES) and mortality rates for major cancers in Taiwan. METHODS: A population-based follow-up study was conducted with 20,488 cancer patients diagnosed in 2002. Each patient was traced to death or for 5 years. The individual income-related insurance payment amount was used as a proxy measure of individual SES for patients. Neighborhood SES was defined by income, and neighborhoods were grouped as living in advantaged or disadvantaged areas. The Cox proportional hazards model was used to compare the death-free survival rates between the different SES groups after adjusting for possible confounding and risk factors. RESULTS: After adjusting for patient characteristics (age, gender, Charlson Comorbidity Index Score, urbanization, and area of residence), tumor extent, treatment modalities (operation and adjuvant therapy), and hospital characteristics (ownership and teaching level), colorectal cancer, and head and neck cancer patients under 65 years old with low individual SES in disadvantaged neighborhoods conferred a 1.5 to 2-fold higher risk of mortality, compared with patients with high individual SES in advantaged neighborhoods. A cross-level interaction effect was found in lung cancer and breast cancer. Lung cancer and breast cancer patients less than 65 years old with low SES in advantaged neighborhoods carried the highest risk of mortality. Prostate cancer patients aged 65 and above with low SES in disadvantaged neighborhoods incurred the highest risk of mortality. There was no association between SES and mortality for cervical cancer and pancreatic cancer. CONCLUSIONS: Our findings indicate that cancer patients with low individual SES have the highest risk of mortality even under a universal health-care system. Public health strategies and welfare policies must continue to focus on this vulnerable group.