BrBCAT1 mutation resulted in deficiency of epicuticular wax crystal in Chinese cabbage.

KEY MESSAGE: BrBCAT1 encoding a branched-chain amino acid aminotransferase was responsible for the glossy trait, which was verified by allelic mutants in Chinese cabbage. The glossy characteristic, thanks to the epicuticular wax crystal deficiency, is an excellent commodity character for leafy vegetables. Herein, two allelic glossy green mutants, wdm11 and wdm12, were isolated from an ethyl methane sulfonate (EMS)-mutagenized population of Chinese cabbage, and the mutant phenotype was recessive inherited. Cryo-SEM detected that epicuticular wax crystal in the mutant leaves was virtually absent. MutMap and Kompetitive allele-specific PCR analyses demonstrated that BraA06g006950.3C (BrBCAT1), homologous to AtBCAT1, encoding a branched-chain amino acid aminotransferase was the candidate gene. A SNP (G to A) on the fourth exon of BrBCAT1 in wdm11 caused the 233rd amino acid to change from glycine (G) to aspartic acid (D). A SNP (G to A) on the second exon of BrBCAT1 in wdm12 led to the 112th amino acid change from glycine (G) to arginine (R). Both of the allelic mutants had genetic structural variation in the candidate gene, which indicated that the mutant phenotype was triggered by the BrBCAT1 mutation. The expression levels of BrBCAT1 and genes related to fatty acid chain extension were decreased significantly in the mutant compared to the wild-type, which might result in epicuticular wax crystal deficiency in the mutants. Our findings proved that the mutation of BrBCAT1 induced the glossy phenotype and provided a valuable gene resource for commodity character improvement in Chinese cabbage.

Life cycle assessment of carbonaceous pellets used in blast furnaces in the context of "double carbon".

As the sole carbonaceous renewable energy source, biomass is distinguished by its abundant yield, widespread distribution, and carbon neutrality. It is integral to the achievement of zero and negative carbon production via conventional carbonaceous pellet technology. This study introduces a cradle-to-gate life cycle assessment methodology for biomass preparation in carbonaceous pellets. We prepare high-quality biochar through a process combining hydrothermal carbonization and pyrolytic carbonization. Biomass high molecular weight extracts are obtained via organic pyrolytic extraction, while biomass high-temperature binders result from the modification and treatment of biochar. Biomass carbonaceous pellets are then formed using hot press technology. The ReCiPe model facilitates a comprehensive life cycle assessment of biomass carbonaceous pellets used in blast furnace production. The study leverages two comprehensive evaluation indicators - renewability, and environmental performance - to enhance the environmental performance of the process system and to maximize energy-saving and emission reduction potential.

The effects of ambient temperature on road traffic injuries in Jinan city: a time-stratified case-crossover study based on distributed lag nonlinear model.

Objectives: The impact of climate change, especially extreme temperatures, on health outcomes has become a global public health concern. Most previous studies focused on the impact of disease incidence or mortality, whereas much less has been done on road traffic injuries (RTIs). This study aimed to explore the effects of ambient temperature, particularly extreme temperature, on road traffic deaths in Jinan city. Methods: Daily data on road traffic deaths and meteorological factors were collected among all residents in Jinan city during 2011-2020. We used a time-stratified case-crossover design with distributed lag nonlinear model to evaluate the association between daily mean temperature, especially extreme temperature and road traffic deaths, and its variation in different subgroups of transportation mode, adjusting for meteorological confounders. Results: A total of 9,794 road traffic deaths were collected in our study. The results showed that extreme temperatures were associated with increased risks of deaths from road traffic injuries and four main subtypes of transportation mode, including walking, Bicycle, Motorcycle and Motor vehicle (except motorcycles), with obviously lag effects. Meanwhile, the negative effects of extreme high temperatures were significantly higher than those of extreme low temperatures. Under low-temperature exposure, the highest cumulative lag effect of 1.355 (95% CI, 1.054, 1.742) for pedal cyclists when cumulated over lag 0 to 6 day, and those for pedestrians, motorcycles and motor vehicle occupants all persisted until 14 days, with ORs of 1.227 (95% CI, 1.102, 1.367), 1.453 (95% CI, 1.214, 1.740) and 1.202 (95% CI, 1.005, 1.438), respectively. Under high-temperature exposure, the highest cumulative lag effect of 3.106 (95% CI, 1.646, 5.861) for motorcycle occupants when cumulated over lag 0 to 12 day, and those for pedestrian, pedal cyclists, and motor vehicle accidents all peaked when persisted until 14 days, with OR values of 1.638 (95% CI, 1.281, 2.094), 2.603 (95% CI, 1.695, 3.997) and 1.603 (95% CI, 1.066, 2.411), respectively. Conclusion: This study provides evidence that ambient temperature is significantly associated with the risk of road traffic injuries accompanied by obvious lag effect, and the associations differ by the mode of transportation. Our findings help to promote a more comprehensive understanding of the relationship between temperature and road traffic injuries, which can be used to establish appropriate public health policies and targeted interventions.

Identifying the risk factors of ICU-acquired fungal infections: clinical evidence from using machine learning.

Background: Fungal infections are associated with high morbidity and mortality in the intensive care unit (ICU), but their diagnosis is difficult. In this study, machine learning was applied to design and define the predictive model of ICU-acquired fungi (ICU-AF) in the early stage of fungal infections using Random Forest. Objectives: This study aimed to provide evidence for the early warning and management of fungal infections. Methods: We analyzed the data of patients with culture-positive fungi during their admission to seven ICUs of the First Affiliated Hospital of Chongqing Medical University from January 1, 2015, to December 31, 2019. Patients whose first culture was positive for fungi longer than 48 h after ICU admission were included in the ICU-AF cohort. A predictive model of ICU-AF was obtained using the Least Absolute Shrinkage and Selection Operator and machine learning, and the relationship between the features within the model and the disease severity and mortality of patients was analyzed. Finally, the relationships between the ICU-AF model, antifungal therapy and empirical antifungal therapy were analyzed. Results: A total of 1,434 cases were included finally. We used lasso dimensionality reduction for all features and selected six features with importance ≥0.05 in the optimal model, namely, times of arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation. The area under the curve of the model for predicting ICU-AF was 0.981 in the test set, with a sensitivity of 0.960 and specificity of 0.990. The times of arterial catheter (p = 0.011, OR = 1.057, 95% CI = 1.053-1.104) and invasive mechanical ventilation (p = 0.007, OR = 1.056, 95%CI = 1.015-1.098) were independent risk factors for antifungal therapy in ICU-AF. The times of arterial catheter (p = 0.004, OR = 1.098, 95%CI = 0.855-0.970) were an independent risk factor for empirical antifungal therapy. Conclusion: The most important risk factors for ICU-AF are the six time-related features of clinical parameters (arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation), which provide early warning for the occurrence of fungal infection. Furthermore, this model can help ICU physicians to assess whether empiric antifungal therapy should be administered to ICU patients who are susceptible to fungal infections.

Anisotropic optical property of ferroelectric Bi2O2X(X = S,Se,Te) monolayer and strain engineering.

Based on the first-principles calculations, ferroelectricBi2O2X(X=S,Se,Te)monolayers with unequivalent in-plane lattice constants are confirmed to be the ground state, which is consistent with the experiment result (Ghoshet al2019Nano Lett.195703-09), and the anisotropic optical property is firstly investigated. We find that the polarizations ofBi2O2Xmonolayers points along the direction ofa-axis, andBi2O2Temonolayer process the largest polarization. Furthermore, both the biaxial and uniaxial strains are favor for the enhancement of polarization ofBi2O2Xmonolayers. It should be mentioned that the type of band gap will convert from indirect to direct forBi2O2Temonolayer when thea-axial tensile strain is larger than 2%. At last, the optical absorption coefficient forBi2O2Xmonolayers are calculated, and we obtain thatBi2O2Temonolayer has the strongest optical absorption within the range of visible light, the anisotropy and possible strain engineering to improve the optical absorption are discussed in detail. Our findings are significant in fields of optoelectronics and photovoltaics.

Discovery of an immunosuppressive functional metabolite from the insect-derived endophytic Aspergillus taichungensis SMU01.

Three p-terphenyl metabolites (1-3), three indole-diterpenoids (4-6), an herbicide sesquiterpene (7), a flavonoid (8), and five other small molecules containing nitrogen (9-13) were isolated from the medicinal insect (Periplaneta americana)-derived endophytic Aspergillus taichungensis SMU01. Their chemical structures were elucidated on the basis of spectroscopic data and quantum chemical computational methods. Biological activity of these isolates in the differentiation of mouse CD4+ T cell subsets was evaluated. Importantly, metabolites 2 targeting JAK-STAT signaling pathway could hold potential benefits in maintaining peripheral immune homeostasis and alleviating the progression of autoimmune diseases.

Hemodynamic effects of withholding vs. continuing angiotensin II receptor blockers on the day of prone positioning spinal surgery in elderly patients.

Introduction: The hemodynamic effects of withholding vs. continuing angiotensin II receptor blockers (ARBs) before surgery in elderly patients undergoing spinal surgery in a prone position during anesthesia induction to skin incision are still unknown. Methods: In this prospective study, 80 patients undergoing spinal surgery in a prone position with general anesthesia, aged 60-79 years, American Society of Anesthesiologists (ASA) II or III, were enrolled. Patients who had ARBs only in their preoperative medication list were randomly divided into two groups at a 1:1 ratio: In Group A, ARBs were continued on the morning of surgery, while in Group B, they were withhold. Norepinephrine was infused to maintain the blood pressure at the baseline level of ±20% during anesthesia induction in all patients. The primary outcome was the consumption of norepinephrine in each group from anesthesia induction to skin incision. The secondary outcomes include changes in invasive arterial blood pressure and heart rate, the fluid infusion volumes, the amounts of anesthetic drugs, and the total time from induction to skin incision. Results: There were no significant differences in the demographics, the fluid infusion volumes, the amounts of anesthetic drugs, the total time from induction to skin incision, and hemodynamics at different time points (p > 0.05), while significant differences were found in norepinephrine consumption between the two groups (p < 0.001). Compared with Group B, the consumption of norepinephrine increased significantly in Group A (93.3 ± 29.8 vs. 124.1 ± 38.7 µg, p = 0.000). In addition, the same trend was illustrated in the pumping rate of norepinephrine between Group B (0.04 ± 0.01 µg·kg-1·min-1) and Group A (0.06 ± 0.02 µg·kg-1·min-1) (p = 0.004). Conclusion: Our study conducted in elderly patients with hypotension undergoing prone spinal surgery demonstrated a greater pumping rate of norepinephrine during anesthesia induction in patients with ARBs continuing before surgery than those withholding, indicating that it was more difficult to maintain hemodynamic stability.Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=141081, ChiCTR2100053583.

Immunization with a low dose of zymosan A confers resistance to depression-like behavior and neuroinflammatory responses in chronically stressed mice.

Stimulation of the innate immune system prior to stress exposure is a possible strategy to prevent depression under stressful conditions. Based on the innate immune system stimulating activities of zymosan A, we hypothesize that zymosan A may prevent the development of chronic stress-induced depression-like behavior. Our results showed that a single injection of zymosan A 1 day before stress exposure at a dose of 2 or 4 mg/kg, but not at a dose of 1 mg/kg, prevented the development of depression-like behaviors in mice treated with chronic social defeat stress (CSDS). The prophylactic effect of a single zymosan A injection (2 mg/kg) on CSDS-induced depression-like behaviors disappeared when the time interval between zymosan A and stress exposure was extended from 1 day or 5 days to 10 days, which was rescued by a second zymosan A injection 10 days after the first zymosan A injection and 4 days (4×, once daily) of zymosan A injections 10 days before stress exposure. Further analysis showed that a single zymosan A injection (2 mg/kg) 1 day before stress exposure could prevent the CSDS-induced increase in pro-inflammatory cytokines in the hippocampus and prefrontal cortex. Inhibition of the innate immune system by pretreatment with minocycline (40 mg/kg) abolished the preventive effect of zymosan A on CSDS-induced depression-like behaviors and CSDS-induced increase in pro-inflammatory cytokines in the brain. These results suggest that activation of the innate immune system triggered by zymosan A prevents the depression-like behaviors and neuroinflammatory responses in the brain induced by chronic stress.

DDX21 mediates co-transcriptional RNA m6A modification to promote transcription termination and genome stability.

N6-methyladenosine (m6A) is a crucial RNA modification that regulates diverse biological processes in human cells, but its co-transcriptional deposition and functions remain poorly understood. Here, we identified the RNA helicase DDX21 with a previously unrecognized role in directing m6A modification on nascent RNA for co-transcriptional regulation. DDX21 interacts with METTL3 for co-recruitment to chromatin through its recognition of R-loops, which can be formed co-transcriptionally as nascent transcripts hybridize onto the template DNA strand. Moreover, DDX21's helicase activity is needed for METTL3-mediated m6A deposition onto nascent RNA following recruitment. At transcription termination regions, this nexus of actions promotes XRN2-mediated termination of RNAPII transcription. Disruption of any of these steps, including the loss of DDX21, METTL3, or their enzymatic activities, leads to defective termination that can induce DNA damage. Therefore, we propose that the R-loop-DDX21-METTL3 nexus forges the missing link for co-transcriptional modification of m6A, coordinating transcription termination and genome stability.

Impact of the method of calculating 30-day readmission rate after hospitalization for heart failure. Data from the VancOuver CoastAL Acute Heart Failure (VOCAL-AHF) registry.

BACKGROUND: Thirty-day readmission rate after heart failure (HF) hospitalization is widely used to evaluate healthcare quality. Methodology may substantially influence estimated rates. We assessed the impact of different definitions on HF and all-cause readmission rates. METHODS: Readmission rates were examined in 1,835 patients discharged following HF hospitalization using 64 unique definitions derived from five methodological factors: (1) ICD-10 codes (broad vs narrow), (2) index admission selection (single admission only first-in-year vs. random sample; or multiple admissions in year with vs. without 30-day blanking period), (3) variable denominator (number alive at discharge vs. number alive at 30-days), (4) follow-up period start (discharge date vs day following discharge), and (5) annual reference-period (calendar vs fiscal). The impact of different factors was assessed using linear-regression. RESULTS: The calculated 30-day readmission rate for HF varied more than 2-fold depending solely on the methodological approach (6.5% to 15.0%). All-cause admission rates exhibited similar variation (18.8% to 29.9%). The highest rates included all consecutive index admissions (HF 11.1-15.0%, all-cause 24.0-29.9%), and lowest only one index admission per patient per year (HF 6.5-11.3%, all-cause 18.8-22.7%). When including multiple index admissions and compared to blanking the 30-days post-discharge, not blanking was associated with 2.3% higher readmission rates. Selecting a single admission per year with a first-in-year approach lowered readmission rates by 1.5%, while random-sampling admissions lowered estimates further by 5.2% (p<0.001). CONCLUSION: Calculated 30-day readmission rates varied more than 2-fold by altering methods. Transparent and consistent methods are needed to ensure reproducible and comparable reporting.

Analysis of the efficacy of separation surgery for severe neurological compression in multiple myeloma: a retrospective analysis of 35 cases.

PURPOSE: To investigate the effectiveness and safety of separation surgery for Epidural Spinal Cord Compression (ESCC) graded ≥ 2 in patients with Multiple Myeloma (MM), analyze factors influencing surgical outcomes, and develop a preliminary treatment decision framework for these patients. METHODS: A retrospective analysis was conducted on clinical data from 35 MM patients who underwent separation surgery for ESCC graded ≥ 2 between 2013 and 2018. Patient data, including baseline information, surgical details, complications, and pre-operative as well as one-month post-operative efficacy evaluation indicators were recorded. Statistical analysis was performed on pre-operative and post-operative efficacy indicators to determine if there were significant improvements (p < 0.05). Ordered logistic regression was utilized to assess factors associated with an unfavorable post-operative quality of life outcome. RESULTS: Compared to pre-operative values, at one-month post-surgery, patients showed significant improvements in Frankel Score Classification (4 vs 5, p < 0.05), Karnofsky Performance Score (30 vs 70, p < 0.05), and Visual Analogue Scale (8 vs 3, p < 0.05). Complications occurred in 7 cases (20%). The number of segments with ESCC (OR = 0.171, p < 0.05) and pre-operative chemotherapy (OR = 5.202, p = 0.05) were identified as independent factors influencing patient outcomes. Patients with more than two vertebral segments with ESCC exhibited significantly worse post-operative conditions. CONCLUSIONS: Separation surgery effectively alleviates pain, improves neurological function, and enhances the quality of life in patients with ESCC graded ≥ 2 due to MM.

Targeting aging and age-related diseases with vaccines.

Aging is a major risk factor for numerous chronic diseases. Vaccination offers a promising strategy to combat these age-related diseases by targeting specific antigens and inducing immune responses. Here, we provide a comprehensive overview of recent advances in vaccine-based interventions targeting these diseases, including Alzheimer's disease, type II diabetes, hypertension, abdominal aortic aneurysm, atherosclerosis, osteoarthritis, fibrosis and cancer, summarizing current approaches for identifying disease-associated antigens and inducing immune responses against these targets. Further, we reflect on the recent development of vaccines targeting senescent cells, as a strategy for more broadly targeting underlying causes of aging and associated pathologies. In addition to highlighting recent progress in these areas, we discuss important next steps to advance the therapeutic potential of these vaccines, including improving and robustly demonstrating efficacy in human clinical trials, as well as rigorously evaluating the safety and long-term effects of these vaccine strategies.

Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1.

This study is to probe into the meaning of serum miR-532-5p in nontraumatic osteonecrosis of the femoral head (ONFH), and a molecular mechanism of miR-532-5p in the development of nontraumatic ONFH. This study enrolled 96 patients diagnosed with nontraumatic ONFH and 96 patients with femoral neck fracture. The levels of miR-532-5p, ABL1, MMP-3, MMP-13, and cleaved-caspase3 were determined. Radiographic progression was assessed by ARCO staging system. Visual analog scale (VAS) and Harris hip score (HHS) were employed for evaluation of the symptomatic severity of nontraumatic ONFH. Cell viability and apoptosis in chondrocytes isolated from clinical samples were investigated with CCK-8 and flow cytometry. The levels of lactic dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), mitochondrial membrane potential (ΔΨm), and reactive oxygen species (ROS) were determined. miR-532-5p was downregulated in tissues and serum of patients with nontraumatic ONFH, negatively related with ARCO staging and VAS, and positively correlated with HHS. Cell apoptosis, LDH, MDA, and ROS strengthened, while cell viability, ΔΨm, and SOD reduced in chondrocytes of nontraumatic ONFH patients. ABL1 was upregulated in cartilage tissues from nontraumatic ONFH patients. miR-532-5p targeted ABL1, and overexpressed miR-532-5p alleviated nontraumatic ONFH-induced oxidative stress damage of chondrocytes by restraining ABL1. miR-532-5p ameliorated oxidative stress injury in nontraumatic ONFH by inhibiting ABL1.

The effects of different durations of exposure to hypomagnetic field on the number of active mitochondria and ROS levels in the mouse hippocampus.

Reactive oxygen species (ROS) are one of the potential molecules in response to a hypomagnetic field (HMF), and exposure to an HMF for eight weeks led to an increase in ROS levels in the whole hippocampus area in mice. ROS are mainly derived from the byproducts of mitochondrial metabolism. However, previous in vivo studies mostly focus on the influence of one time point of HMF exposure on the mouse hippocampus and lack comparative studies on the effects of different durations of HMF exposure on the mouse hippocampus. Here, we investigated the effects of different durations of HMF on the number of active mitochondria and ROS levels in mouse hippocampus. Compared with the geomagnetic field (GMF) group, we found that the number of active mitochondria in the hippocampus was significantly reduced during the sixth week of HMF exposure, whereas the number of active mitochondria was significantly reduced and the ROS levels was significantly increased during the eighth week of HMF exposure. The number of active mitochondria gradually decreased and ROS levels gradually increased in both GMF and HMF groups with prolonged exposure time. In addition, the expression level of the PGC-1α gene in the hippocampus, the main regulator of mitochondrial biogenesis, decreased significantly in the eighth week of HMF exposure. These results reveal that the changes in active mitochondria number and ROS levels were dependent on the durations of HMF exposure, and prolonged exposure to HMF exacerbates these changes.

Research on the slip deformation characteristics and improvement measures of concrete-faced rockfill dams on dam foundations with large dip angles.

The pumped storage power station (PSPS) is an important measure to achieve the strategic goal of "dual carbon". As one of the preferred types for the upper reservoir dams of PSPSs, the concrete-faced rockfill dam (CFRD) often has a dam foundation on a steep transverse slop and is prone to produce slip deformation along the slope, resulting in poor anti-sliding stability of the dam slope. It is dangerous for the operation safety of PSPSs. Therefore, the slip deformation of CFRDs on dam foundations with large dip angles is investigated. The mechanism for the initiation of slip deformation is revealed. The design measures of physical mechanic and geometric structure are proposed to reduce slip deformation. The results show that the larger sliding forces and smaller anti-sliding forces are the fundamental reasons that CFRDs on dam foundations with large dip angles are prone to produce slip deformation. The larger the dip angle of the dam foundation, the larger the slip deformation of the dam body and face slab, and the smaller the safety factor of the dam slope. When the dip angle of the dam foundation is greater than 15°, the safety factor of the dam slope is less than the minimum value of 1.5 required by codes. The addition of pressure slopes can effectively reduce the slip deformation of the dam body or face slab and significantly improve the anti-sliding stability of the dam slope. When the height or width of the pressure slope platform is greater and the cohesion or internal friction angle of the pressure slope is larger, the slip deformations of the dam body and face slab are smaller, and the safety factor of the dam slope is greater. It is recommended that the height and width of the pressure slope platform be 1/2 times the maximum height of the main dam, and the density (cohesion and internal friction angle) of the pressure slope be equivalent to that of the main dam's rockfill material. The research results can provide theoretical and technical support for the design and construction of CFRDs for the upper reservoir of PSPSs.

[Facial nerve protection in surgery for rare tumors of the internal auditory canal].

Objective:To explore strategies for preserving facial nerve function during surgeries for rare tumors of the internal auditory canal. Methods:A total of 235 cases of internal auditory canal tumors treated between 2010 and 2023 were included, encompassing vestibular schwannomas, cavernous hemangiomas, meningiomas, and other rare tumors. Various data, including clinical presentations, imaging classifications, and treatment processes, were meticulously analyzed to delineate the characteristics of rare tumors and assess pre-and postoperative facial nerve function. Results:Among all internal auditory canal tumors, vestibular schwannomas accounted for 91.9%. In rare tumors, facial nerve schwannomas constituted 5.3%, cavernous hemangiomas 26.3%, meningiomas 15.8%, and arterial aneurysms 10.5%. Significantly, patients with cavernous hemangiomas displayed pronounced invasion of the facial nerve by the tumor, in contrast to other tumor types where clear boundaries with the facial nerve were maintained. During surgery, individualized approaches and strategies for facial nerve protection were implemented for different tumor types, involving intraoperative dissection, tumor excision, and facial nerve reconstruction. Conclusion:Preservation of the facial nerve is crucial in the surgical management of rare tumors of the internal auditory canal. Accurate preoperative diagnosis, appropriate timing of surgery, selective surgical approaches, and meticulous intraoperative techniques can maximize the protection of facial nerve function. Personalized treatment plans and strategies for facial nerve functional reconstruction are anticipated to enhance surgical success rates, reduce the risk of postoperative facial nerve dysfunction, and ultimately improve the quality of life for patients.

Comprehensive analysis of bulk and single-cell transcriptomic data reveals a novel signature associated with endoplasmic reticulum stress, lipid metabolism, and liver metastasis in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high probability of recurrence and distant metastasis. Liver metastasis is the predominant metastatic mode developed in most pancreatic cancer cases, which seriously affects the overall survival rate of patients. Abnormally activated endoplasmic reticulum stress and lipid metabolism reprogramming are closely related to tumor growth and metastasis. This study aims to construct a prognostic model based on endoplasmic reticulum stress and lipid metabolism for pancreatic cancer, and further explore its correlation with tumor immunity and the possibility of immunotherapy. METHODS: Transcriptomic and clinical data are acquired from TCGA, ICGC, and GEO databases. Potential prognostic genes were screened by consistent clustering and WGCNA methods, and the whole cohort was randomly divided into training and testing groups. The prognostic model was constructed by machine learning method in the training cohort and verified in the test, TCGA and ICGC cohorts. The clinical application of this model and its relationship with tumor immunity were analyzed, and the relationship between endoplasmic reticulum stress and intercellular communication was further explored. RESULTS: A total of 92 characteristic genes related to endoplasmic reticulum stress, lipid metabolism and liver metastasis were identified in pancreatic cancer. We established and validated a prognostic model for pancreatic cancer with 7 signatures, including ADH1C, APOE, RAP1GAP, NPC1L1, P4HB, SOD2, and TNFSF10. This model is considered to be an independent prognosticator and is a more accurate predictor of overall survival than age, gender, and stage. TIDE score was increased in high-risk group, while the infiltration levels of CD8+ T cells and M1 macrophages were decreased. The number and intensity of intercellular communication were increased in the high ER stress group. CONCLUSIONS: We constructed and validated a novel prognostic model for pancreatic cancer, which can also be used as an instrumental variable to predict the prognosis and immune microenvironment. In addition, this study revealed the effect of ER stress on cell-cell communication in the tumor microenvironment.

US-based Sequential Algorithm Integrating an AI Model for Advanced Liver Fibrosis Screening.

Background Noninvasive tests can be used to screen patients with chronic liver disease for advanced liver fibrosis; however, the use of single tests may not be adequate. Purpose To construct sequential clinical algorithms that include a US deep learning (DL) model and compare their ability to predict advanced liver fibrosis with that of other noninvasive tests. Materials and Methods This retrospective study included adult patients with a history of chronic liver disease or unexplained abnormal liver function test results who underwent B-mode US of the liver between January 2014 and September 2022 at three health care facilities. A US-based DL network (FIB-Net) was trained on US images to predict whether the shear-wave elastography (SWE) value was 8.7 kPa or higher, indicative of advanced fibrosis. In the internal and external test sets, a two-step algorithm (Two-step#1) using the Fibrosis-4 Index (FIB-4) followed by FIB-Net and a three-step algorithm (Three-step#1) using FIB-4 followed by FIB-Net and SWE were used to simulate screening scenarios where liver stiffness measurements were not or were available, respectively. Measures of diagnostic accuracy were calculated using liver biopsy as the reference standard and compared between FIB-4, SWE, FIB-Net, and European Association for the Study of the Liver guidelines (ie, FIB-4 followed by SWE), along with sequential algorithms. Results The training, validation, and test data sets included 3067 (median age, 42 years [IQR, 33-53 years]; 2083 male), 1599 (median age, 41 years [IQR, 33-51 years]; 1124 male), and 1228 (median age, 44 years [IQR, 33-55 years]; 741 male) patients, respectively. FIB-Net obtained a noninferior specificity with a margin of 5% (P < .001) compared with SWE (80% vs 82%). The Two-step#1 algorithm showed higher specificity and positive predictive value (PPV) than FIB-4 (specificity, 79% vs 57%; PPV, 44% vs 32%) while reducing unnecessary referrals by 42%. The Three-step#1 algorithm had higher specificity and PPV compared with European Association for the Study of the Liver guidelines (specificity, 94% vs 88%; PPV, 73% vs 64%) while reducing unnecessary referrals by 35%. Conclusion A sequential algorithm combining FIB-4 and a US DL model showed higher diagnostic accuracy and improved referral management for all-cause advanced liver fibrosis compared with FIB-4 or the DL model alone. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ghosh in this issue.

Causes and global, regional, and national burdens of traumatic brain injury from 1990 to 2019.

PURPOSE: Traumatic brain injury (TBI), currently a major global public health problem, imposes a significant economic burden on society and families. We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence, prevalence, and years lived with disability (YLDs). The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention, treatment, and incidence-reducing measures for TBI. METHODS: A secondary analysis was performed on the incidence, prevalence, and YLDs of TBI by sex, age group, and region (n = 21,204 countries and territories) between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported. RESULTS: In 2019, there were 27.16 million (95% uncertainty intervals (UI): 23.36 - 31.42) new cases of TBI worldwide, with age-standardized incidence and prevalence rates of 346 per 100,000 population (95% UI: 298-401) and 599 per 100,000 population (95% UI: 573-627), respectively. From 1990 to 2019, there were no significant trends in global age-standardized incidence (estimated annual percentage changes: -0.11%, 95% UI: -0.18% - -0.04%) or prevalence (estimated annual percentage changes: 0.01%, 95% UI: -0.04% - 0.06%). TBI caused 7.08 million (95% UI: 5.00 - 9.59) YLDs in 2019, with age-standardized rates of 86.5 per 100,000 population (95% UI: 61.1 - 117.2). In 2019, the countries with higher incidence rates were mainly distributed in Central Europe, Eastern Europe, and Australia. The 2019 global age-standardized incidence rate was higher in males than in females. The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population, accounting for 52.8% of all TBI, with falls and road traffic injuries being the main causes in most regions. CONCLUSIONS: The incidence of moderate and severe TBI was slightly higher in 2019, and TBI still accounts for a significant portion of the global injury burden. The likelihood of moderate to severe TBI and the trend of major injury under each injury cause from 1990 to 2019 and the characteristics of injury mechanisms in each age group are presented, providing a basis for further research on injury causes in each age group and the future establishment of corresponding policies and protective measures.