Based on the prognosis model of immunogenes, the prognosis model was constructed to predict the invasion of immune genes and immune cells related to primary liver cancer and its experimental validation.

Background: Primary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients. Purpose: Revealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients. Methods: PLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments. Results: Through database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs (P < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses. Conclusion: Our study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.

Highly Sensitive Near-Field Electrochemical Sensor for In Vivo Monitoring of Respiratory Patterns.

Real-time tracking of respiratory patterns provides noninvasive and quick access for evaluating pathophysiological conditions yet remains challenging due to limited temporal resolution and poor sensitivity to dig out fingerprints of respiratory waveforms. Here, we report an electrochemical sensor for accurately tracing respiratory patterns of small animal models based on the electrochemical impedance mechanism for wireless coupling of a graphdiyne oxide (GYDO)-modified sensing coil chip and a reader coil chip via near-field magnetic induction. In the electrochemical impedance measurement mode, an alternating current is applied through the reader coil chip to perturb proton transport at the GYDO interface of the sensing coil chip. As demonstrated, a high-frequency perturbing condition significantly reduces the interfacial resistance for proton transport by 5 orders of magnitude under 95% relative humidity (RH) and improves the low-humidity responses with a limit of detection down to 0.2% RH, enabling in vivo accurate profiling of respiratory patterns on epileptic rats. The electrochemical impedance coupling system holds great potential for new wireless bioelectronics.

Indole alkaloids isolated from the Nicotiana tabacum-derived Aspergillus fumigatus 0338 as potential inhibitors for tobacco powdery mildew and their mode of actions.

To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.

The pathological mechanisms and potential therapeutic drugs for myocardial ischemia reperfusion injury.

BACKGROUND: Cardiovascular disease is the main cause of death and disability, with myocardial ischemia being the predominant type that poses a significant threat to humans. Reperfusion, an essential therapeutic approach, promptly reinstates blood circulation to the ischemic myocardium and stands as the most efficacious clinical method for myocardial preservation. Nevertheless, the restoration of blood flow associated with this process can potentially induce myocardial ischemia-reperfusion injury (MIRI), thereby diminishing the effectiveness of reperfusion and impacting patient prognosis. Therefore, it is of great significance to prevent and treat MIRI. PURPOSE: MIRI is an important factor affecting the prognosis of patients, and there is no specific in-clinic treatment plan. In this review, we have endeavored to summarize its pathological mechanisms and therapeutic drugs to provide more powerful evidence for clinical application. METHODS: A comprehensive literature review was conducted using PubMed, Web of Science, Embase, Medline and Google Scholar with a core focus on the pathological mechanisms and potential therapeutic drugs of MIRI. RESULTS: Accumulated evidence revealed that oxidative stress, calcium overload, mitochondrial dysfunction, energy metabolism disorder, ferroptosis, inflammatory reaction, endoplasmic reticulum stress, pyroptosis and autophagy regulation have been shown to participate in the process, and that the occurrence and development of MIRI are related to plenty of signaling pathways. Currently, a range of chemical drugs, natural products, and traditional Chinese medicine (TCM) preparations have demonstrated the ability to mitigate MIRI by targeting various mechanisms. CONCLUSIONS: At present, most of the research focuses on animal and cell experiments, and the regulatory mechanisms of each signaling pathway are still unclear. The translation of experimental findings into clinical practice remains incomplete, necessitating further exploration through large-scale, multi-center randomized controlled trials. Given the absence of a specific drug for MIRI, the identification of therapeutic agents to reduce myocardial ischemia is of utmost significance. For the future, it is imperative to enhance our understanding of the pathological mechanism underlying MIRI, continuously investigate and develop novel pharmaceutical agents, expedite the clinical translation of these drugs, and foster innovative approaches that integrate TCM with Western medicine. These efforts will facilitate the emergence of fresh perspectives for the clinical management of MIRI.

Developmentally sensitive multispectral cortical connectivity profiles serving visual selective attention.

Throughout childhood and adolescence, the brain undergoes significant structural and functional changes that contribute to the maturation of multiple cognitive domains, including selective attention. Selective attention is crucial for healthy executive functioning and while key brain regions serving selective attention have been identified, their age-related changes in neural oscillatory dynamics and connectivity remain largely unknown. We examined the developmental sensitivity of selective attention circuitry in 91 typically developing youth aged 6 - 13 years old. Participants completed a number-based Simon task while undergoing magnetoencephalography (MEG) and the resulting data were preprocessed and transformed into the time-frequency domain. Significant oscillatory brain responses were imaged using a beamforming approach, and task-related peak voxels in the occipital, parietal, and cerebellar cortices were used as seeds for subsequent whole-brain connectivity analyses in the alpha and gamma range. Our key findings revealed developmentally sensitive connectivity profiles in multiple regions crucial for selective attention, including the temporoparietal junction (alpha) and prefrontal cortex (gamma). Overall, these findings suggest that brain regions serving selective attention are highly sensitive to developmental changes during the pubertal transition period.

Mesenchymal stem cells for repairing glaucomatous optic nerve.

Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells (RGCs) and axons. Currently, there is no effective method to address the cause of RGCs degeneration. However, studies on neuroprotective strategies for optic neuropathy have increased in recent years. Cell replacement and neuroprotection are major strategies for treating glaucoma and optic neuropathy. Regenerative medicine research into the repair of optic nerve damage using stem cells has received considerable attention. Stem cells possess the potential for multidirectional differentiation abilities and are capable of producing RGC-friendly microenvironments through paracrine effects. This article reviews a thorough researches of recent advances and approaches in stem cell repair of optic nerve injury, raising the controversies and unresolved issues surrounding the future of stem cells.

Dynamic change of metabolic dysfunction-associated steatotic liver disease in patients with hepatitis C virus infection after achieving sustained virologic response with direct-acting antivirals.

BACKGROUND: Information on the dynamics of metabolic dysfunction-associated steatotic liver disease (MASLD) among hepatitis C virus patients achieving sustained virologic response (SVR12) with direct-acting antivirals (DAAs) is limited. METHODS: We enrolled 1512 eligible participants in this prospective study. MASLD was defined by a controlled attenuation parameter (CAP) of ≥248 dB/m utilizing vibration-controlled transient elastography in conjunction with presence of ≥1 cardiometabolic risk factor. The distribution of MASLD and the changes in CAP were evaluated before treatment and at SVR12. Forward stepwise logistic regression analyses were performed to determine factors significantly associated with the regression or emergence of MASLD. RESULTS: The prevalence of MASLD decreased from 45.0% before treatment to 36.1% at SVR12. Among 681 participants with MASLD before treatment, 144 (21%) exhibited MASLD regression at SVR12. Conversely, among 831 participants without MASLD before treatment, 9 (1.1%) developed MASLD at SVR12. Absence of type 2 diabetes (T2D) [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.13-2.65, p = 0.011], age > 50 years (OR: 1.73, 95% CI: 1.11-2.68, p = 0.015), and alanine transaminase (ALT) ≤ 2 times the upper limit of normal (ULN) (OR: 1.56; 95% CI: 1.03-2.37, p = 0.035) were associated with the regression of MASLD. Presence of T2D was associated with the emergence of MASLD (OR: 5.83, 95% CI: 1.51-22.56, p = 0.011). CONCLUSIONS: The prevalence of MASLD decreased after achieving SVR12 with DAAs. Patients with pre-existing T2D showed a diminished probability of MASLD regression and a heightened risk of MASLD emergence post-SVR12.

PCKRF: Point Cloud Completion and Keypoint Refinement With Fusion Data for 6D Pose Estimation.

Some robust point cloud registration approaches with controllable pose refinement magnitude, such as ICP and its variants, are commonly used to improve 6D pose estimation accuracy. However, the effectiveness of these methods gradually diminishes with the advancement of deep learning techniques and the enhancement of initial pose accuracy, primarily due to their lack of specific design for pose refinement. In this paper, we propose Point Cloud Completion and Keypoint Refinement with Fusion Data (PCKRF), a new pose refinement pipeline for 6D pose estimation. The pipeline consists of two steps. First, it completes the input point clouds via a novel pose-sensitive point completion network. The network uses both local and global features with pose information during point completion. Then, it registers the completed object point cloud with the corresponding target point cloud by our proposed Color supported Iterative KeyPoint (CIKP) method. The CIKP method introduces color information into registration and registers a point cloud around each keypoint to increase stability. The PCKRF pipeline can be integrated with existing popular 6D pose estimation methods, such as the full flow bidirectional fusion network, to further improve their pose estimation accuracy. Experiments demonstrate that our method exhibits superior stability compared to existing approaches when optimizing initial poses with relatively high precision. Notably, the results indicate that our method effectively complements most existing pose estimation techniques, leading to improved performance in most cases. Furthermore, our method achieves promising results even in challenging scenarios involving textureless and symmetrical objects. Our source code is available at https://github.com/zhanhz/KRF.

Catalytic Asymmetric Cyclizative Rearrangement of Anilines and Vicinal Diketones to Access 2,2-Disubstituted Indolin-3-ones.

The efficient synthesis of chiral 2,2-disubstituted indolin-3-ones is of great importance due to its significant synthetic and biological applications. However, catalytic enantioselective methods for de novo synthesis of such heterocycles remain scarce. Herein, a novel cyclizative rearrangement of readily available anilines and vicinal diketones for the one-step construction of enantioenriched 2,2-disubstituted indolin-3-ones is presented. The reaction proceeds through a self-sorted [3+2] heteroannulation/regioselective dehydration/1,2-ester shift process. Only chiral phosphoric acid is employed to promote the entire sequence and simplify the manipulation of this protocol. Various common aniline derivatives are successfully applied to asymmetric synthesis as 1,3-binuclephiles for the first time. Remarkably, the observed stereoselectivity is proposed to originate from an amine-directed regio- and enantioselective ortho-Csp2-H addition of the anilines to the ketones. A range of synthetic transformations of the resulting products are demonstrated as well.

[Predictive Value of Baseline Serum Marker Levels for the Effect of Interferon Therapy in Patients With Chronic Hepatitis B]. / æ ¢æ€§ä¹™åž‹è‚ç‚Žæ‚£è€ çš„è¡€æ¸ æ ‡å¿—ç‰©åŸºçº¿æ°´å¹³å¯¹å¹²æ‰°ç´ æ²»ç–—æ•ˆæžœçš„é¢„æµ‹ä»·å€¼.

Objective: To study the changes in the serum markers in chronic hepatitis B patients who have had previous treatment with long-acting interferon therapy of nucleoside and those who have not and to assess the value of the serum markers for clinical prognosis evaluation. Methods: The clinical data of 411 cases of chronic hepatitis B were collected. All cases were given the additional treatment of long-acting interferon between October 2019 to April 2022. The cases were divided into two groups, a previously treated group consisting of patients who had been treated with nucleoside and nucleotide analogues (NAs) for more than 6 months after they became infected with hepatitis B virus (HBV) for over 6 months and an initial treatment group, or treatment naïve group, consisting of patients who had HBV infection for over 6 months and received no treatment or patients who have stopped NAs therapy for more than 6 months. The serum marker levels of the previously treated group and the initial treatment group, i.e., the previously treatment-naïve patients, were compared, and the receiver operating characteristics (ROC) curve was used to evaluate the value of the baseline levels of hepatitis B surface antigen (HBsAg) and HBV pregenomic RNA (pgRNA) for predicting the rate of cured cases in the two groups. Results: There was no significant difference in the rate of cured cases between the previously treated group and the initial treatment group. The baseline HBV DNA, HBsAg, and hepatitis B e antigen (HBeAg) levels of the cured cases in both groups were significantly lower than those in the uncured cases (P<0.0001). After 48 weeks of treatment, the serum HBsAb levels (mIU/mL) of the cured cases in both the previously treated and initial treatment groups were significantly higher than those of the uncured cases in the two groups (previously treated group: 78.97±22.57 vs. 0.99±0.38, P<0.0001; initial treatment group: 235.50±175.00 vs. 1.32±0.88, P<0.0001). The serum HBsAb levels (mIU/mL) of the cured cases in the initial treatment groups were significantly higher than that of cured cases in the previously treated group (235.50±175.00 vs. 78.97±22.57, P<0.0001). Within 0 to 60 weeks of treatment, HBV pgRNA levels of cured cases in both groups were significantly lower than those of the the uncured cases in both groups (P<0.0001). Multivariate logistic regression and ROC curve analysis showed that baseline serum HBsAg was the influencing factor and predictor of interferon efficacy in both the previously treated cases and the initial treatment cases, with the area under the curve (AUC) being 0.80 (95% confidence interval [CI]: 0.7423-0.8615, P<0.0001) and 0.74 (95% CI: 0.6283-0.8604, P=0.0079), respectively, and the optimal cut-off values being 244.60 IU/mL and 934.40 IU/mL, respectively. However, the baseline serum HBV pgRNA level of under 1340.00 copies/mL in the initial treatment cases led to better sensitivity and better specificity in efficacy prediction, with the AUC of the baseline HBV pgRNA being 0.9649 (95% CI: 0.9042-1.0000, P<0.0001). Conclusion: Among the previously treated cases and the initial treatment cases, patients who achieve clinical cure have lower levels of HBV DNA, HBsAg, and HBeAg at baseline, lower level of HBV pgRNA over the course of their treatment, and higher level of HBsAb at week 48. Baseline HBsAg levels can be used to effectively predict the clinical cure outcomes in previously treated cases and initial treatment cases. Baseline HBV pgRNA levels also exhibit a high predictive value for treatment outcomes in initial treatment cases.

ß-Phase Yb5Sb3Hx: Magnetic and Thermoelectric Properties Traversing from an Electride to a Semiconductor.

An electride is a compound that contains a localized electron in an empty crystallographic site. This class of materials has a wide range of applications, including superconductivity, batteries, photonics, and catalysis. Both polymorphs of Yb5Sb3 (the orthorhombic Ca5Sb3F structure type (ß phase) and hexagonal Mn5Si3 structure type (α phase)) are known to be electrides with electrons localized in 0D tetrahedral cavities and 1D octahedral chains, respectively. In the case of the orthorhombic ß phase, an interstitial H can occupy the 0D tetrahedral cavity, accepting the anionic electron that would otherwise occupy the site, providing the formula of Yb5Sb3Hx. DFT computations show that the hexagonal structure is energetically favored without hydrogen and that the orthorhombic structure is more stable with hydrogen. Polycrystalline samples of orthorhombic ß phase Yb5Sb3Hx (x = 0.25, 0.50, 0.75, 1.0) were synthesized, and both PXRD lattice parameters and 1H MAS NMR were used to characterize H composition. Magnetic and electronic transport properties were measured to characterize the transition from the electride (semimetal) to the semiconductor. Magnetic susceptibility measurements indicate a magnetic moment that can be interpreted as resulting from either the localized antiferromagnetically coupled electride or the presence of a small amount of Yb3+. At lower H content (x = 0.25, 0.50), a low charge carrier mobility consistent with localized electride states is observed. In contrast, at higher H content (x = 0.75, 1.0), a high charge carrier mobility is consistent with free electrons in a semiconductor. All compositions show low thermal conductivity, suggesting a potentially promising thermoelectric material if charge carrier concentration can be fine-tuned. This work provides an understanding of the structure and electronic properties of the electride and semiconductor, Yb5Sb3Hx, and opens the door to the interstitial design of electrides to tune thermoelectric properties.

Somatomotor-visual resting state functional connectivity increases after 2 years in the UK Biobank longitudinal cohort.

Purpose: Functional magnetic resonance imaging (fMRI) and functional connectivity (FC) have been used to follow aging in both children and older adults. Robust changes have been observed in children, in which high connectivity among all brain regions changes to a more modular structure with maturation. We examine FC changes in older adults after 2 years of aging in the UK Biobank (UKB) longitudinal cohort. Approach: We process fMRI connectivity data using the Power264 atlas and then test whether the average internetwork FC changes in the 2722-subject longitudinal cohort are statistically significant using a Bonferroni-corrected t-test. We also compare the ability of Power264 and UKB-provided, independent component analysis (ICA)-based FC to determine which of a longitudinal scan pair is older. Finally, we investigate cross-sectional FC changes as well as differences due to differing scanner tasks in the UKB, Philadelphia Neurodevelopmental Cohort, and Alzheimer's Disease Neuroimaging Initiative datasets. Results: We find a 6.8% average increase in somatomotor network (SMT)-visual network (VIS) connectivity from younger to older scans (corrected p<10-15) that occurs in male, female, older subject (>65 years old), and younger subject (<55 years old) groups. Among all internetwork connections, the average SMT-VIS connectivity is the best predictor of relative scan age. Using the full FC and a training set of 2000 subjects, one is able to predict which scan is older 82.5% of the time using either the full Power264 FC or the UKB-provided ICA-based FC. Conclusions: We conclude that SMT-VIS connectivity increases with age in the UKB longitudinal cohort and that resting state FC increases with age in the UKB cross-sectional cohort.

Factors Related to Mpox-Vaccine Uptake among Men Who Have Sex with Men in Taiwan: Roles of Information Sources and Emotional Problems.

An mpox outbreak occurred suddenly and rapidly spread worldwide in 2022. Research has demonstrated a link between the sexual behavior of men who have sex with men (MSM) and the contraction of mpox. This study assessed the factors related to mpox-vaccine uptake among MSM in Taiwan, focusing on the roles of information sources and emotional problems. In total, 389 MSM participated in an online survey. Data on the participants' vaccination statuses; anxiety symptoms, which were assessed using the State-Trait Anxiety Inventory; depressive symptoms, which were assessed using the Center for Epidemiologic Studies Depression Scale; and risk perceptions of contracting mpox were collected. Factors related to mpox-vaccine uptake were examined using a multivariable logistic regression model. The results revealed that MSM who were older (p < 0.001), perceived a higher risk of contracting mpox (p = 0.040), and received mpox information from health-care providers (p < 0.001) were more likely to receive mpox vaccination, whereas MSM who reported a greater severity of depression (p = 0.017) were less likely to receive mpox vaccination. However, age did not moderate the associations of perceiving a higher risk of contracting mpox, receiving mpox information from health-care providers, and depression with having an mpox vaccination. Health-care providers should consider these factors when developing intervention programs for enhancing mpox-vaccine uptake among MSM.

A genome-wide association study of Chinese and English language phenotypes in Hong Kong Chinese children.

Dyslexia and developmental language disorders are important learning difficulties. However, their genetic basis remains poorly understood, and most genetic studies were performed on Europeans. There is a lack of genome-wide association studies (GWAS) on literacy phenotypes of Chinese as a native language and English as a second language (ESL) in a Chinese population. In this study, we conducted GWAS on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; total N = 1046). We performed association tests at the single-variant, gene, and pathway levels. In addition, we tested genetic overlap of these phenotypes with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis. Totally 5 independent loci (LD-clumped at r2 = 0.01; MAF > 0.05) reached genome-wide significance (p < 5e-08; filtered by imputation quality metric Rsq>0.3 and having at least 2 correlated SNPs (r2 > 0.5) with p < 1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with EA and other neuropsychiatric phenotypes, such as MANEA and PLXNC1. In PRS analysis, EA and CP showed the most consistent and significant polygenic overlap with a variety of language traits, especially English literacy skills. To summarize, this study revealed the genetic basis of Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings.

Effects of Drying Methods on the Physicochemical and Functional Properties of Cinnamomum camphora Seed Kernel Protein Isolate.

Cinnamomum camphora seed kernel protein isolate (CPI) has attracted increasing attention due to its sustainability and potential applications. This study aimed to investigate the effects of freeze-drying (FD), vacuum-drying (VD), and spray-drying (SD) on the physicochemical and functional properties of CPI. The morphology observation results showed that the SD-CPI, SD-CPI, and VD-CPI were spherical, lamellar, and massive, respectively. Compared to FD and SD, VD had more impact on the color, surface hydrophobicity, intermolecular disulfide bonds, intrinsic fluorescence, and thermal stability of CPI. Fourier transform infrared spectroscopy (FTIR) analyses showed that among three CPI samples, VD-CPI had the highest content of ß-sheet but the lowest contents of α-helix and ß-turn. At different pH values, the solubility, emulsification, and foaming properties of VD-CPI were inferior to those of FD-CPI and SD-CPI. These results provide useful information on the changes in the physicochemical and functional properties of CPI subjected to different drying methods, and offer theoretical guidance for the production and use of CPI in the food industry.

Automatic quantitative stroke severity assessment based on Chinese clinical named entity recognition with domain-adaptive pre-trained large language model.

BACKGROUND: Stroke is a prevalent disease with a significant global impact. Effective assessment of stroke severity is vital for an accurate diagnosis, appropriate treatment, and optimal clinical outcomes. The National Institutes of Health Stroke Scale (NIHSS) is a widely used scale for quantitatively assessing stroke severity. However, the current manual scoring of NIHSS is labor-intensive, time-consuming, and sometimes unreliable. Applying artificial intelligence (AI) techniques to automate the quantitative assessment of stroke on vast amounts of electronic health records (EHRs) has attracted much interest. OBJECTIVE: This study aims to develop an automatic, quantitative stroke severity assessment framework through automating the entire NIHSS scoring process on Chinese clinical EHRs. METHODS: Our approach consists of two major parts: Chinese clinical named entity recognition (CNER) with a domain-adaptive pre-trained large language model (LLM) and automated NIHSS scoring. To build a high-performing CNER model, we first construct a stroke-specific, densely annotated dataset "Chinese Stroke Clinical Records" (CSCR) from EHRs provided by our partner hospital, based on a stroke ontology that defines semantically related entities for stroke assessment. We then pre-train a Chinese clinical LLM coined "CliRoberta" through domain-adaptive transfer learning and construct a deep learning-based CNER model that can accurately extract entities directly from Chinese EHRs. Finally, an automated, end-to-end NIHSS scoring pipeline is proposed by mapping the extracted entities to relevant NIHSS items and values, to quantitatively assess the stroke severity. RESULTS: Results obtained on a benchmark dataset CCKS2019 and our newly created CSCR dataset demonstrate the superior performance of our domain-adaptive pre-trained LLM and the CNER model, compared with the existing benchmark LLMs and CNER models. The high F1 score of 0.990 ensures the reliability of our model in accurately extracting the entities for the subsequent automatic NIHSS scoring. Subsequently, our automated, end-to-end NIHSS scoring approach achieved excellent inter-rater agreement (0.823) and intraclass consistency (0.986) with the ground truth and significantly reduced the processing time from minutes to a few seconds. CONCLUSION: Our proposed automatic and quantitative framework for assessing stroke severity demonstrates exceptional performance and reliability through directly scoring the NIHSS from diagnostic notes in Chinese clinical EHRs. Moreover, this study also contributes a new clinical dataset, a pre-trained clinical LLM, and an effective deep learning-based CNER model. The deployment of these advanced algorithms can improve the accuracy and efficiency of clinical assessment, and help improve the quality, affordability and productivity of healthcare services.

Efficacy and safety of nalbuphine for epidural labor analgesia at high altitude: An observational study.

Xining is located at the eastern edge of the Qinghai-Tibet Plateau, with an average altitude of >7000 feet (>2000 m). Nalbuphine is a kappa-opioid receptor agonist that can provide analgesia with fewer side effects than other opioid analgesics. This study aimed to evaluate pain control, side effects, and neonatal outcomes from combining nalbuphine with sufentanil and ropivacaine in 600 women during epidural anesthesia while giving birth at a high altitude in Xining, China. A total of 600 parturients receiving epidural labor analgesia were randomly divided into 2 groups, each group 300 parturients. The nalbuphine group received nalbuphine, sufentanil, and ropivacain, the control group only received sufentanil and ropivacain. The analgesic effect was evaluated through the Visual Analogue Scale scores. Neonatal outcomes were mainly evaluated through the Apgar Scores. Compared to the control group, the nalbuphine group showed lower Visual Analogue Scale scores at all time points after analgesia (P < .05). In comparison with the control group, parturients in the nalbuphine group showed lower incidence rates of fever at delivery, 24-hour postpartum bleeding, and pruritus (P < .05). However, between the 2 groups, there were no statistically significant differences in the remaining maternal and infant outcomes and neonatal outcomes (P > .05). Moreover, no adverse effects on neonatal outcomes were observed. The findings from this study support findings from previous studies that nalbuphine provided safe epidural analgesia without significant side effects for the mother and infant, and showed both safety and efficacy when used during labor at high altitude.

Geographic differences in psychological symptoms, sleep quality, and quality of life in patients with inflammatory bowel disease: A multicenter study in China.

OBJECTIVE: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD). METHODS: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022. RESULTS: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05). CONCLUSION: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice.

Multiview hyperedge-aware hypergraph embedding learning for multisite, multiatlas fMRI based functional connectivity network analysis.

Recently, functional magnetic resonance imaging (fMRI) based functional connectivity network (FCN) analysis via graph convolutional networks (GCNs) has shown promise for automated diagnosis of brain diseases by regarding the FCNs as irregular graph-structured data. However, multiview information and site influences of the FCNs in a multisite, multiatlas fMRI scenario have been understudied. In this paper, we propose a Class-consistency and Site-independence Multiview Hyperedge-Aware HyperGraph Embedding Learning (CcSi-MHAHGEL) framework to integrate FCNs constructed on multiple brain atlases in a multisite fMRI study. Specifically, for each subject, we first model brain network as a hypergraph for every brain atlas to characterize high-order relations among multiple vertexes, and then introduce a multiview hyperedge-aware hypergraph convolutional network (HGCN) to extract a multiatlas-based FCN embedding where hyperedge weights are adaptively learned rather than employing the fixed weights precalculated in traditional HGCNs. In addition, we formulate two modules to jointly learn the multiatlas-based FCN embeddings by considering the between-subject associations across classes and sites, respectively, i.e., a class-consistency module to encourage both compactness within every class and separation between classes for promoting discrimination in the embedding space, and a site-independence module to minimize the site dependence of the embeddings for mitigating undesired site influences due to differences in scanning platforms and/or protocols at multiple sites. Finally, the multiatlas-based FCN embeddings are fed into a few fully connected layers followed by the soft-max classifier for diagnosis decision. Extensive experiments on the ABIDE demonstrate the effectiveness of our method for autism spectrum disorder (ASD) identification. Furthermore, our method is interpretable by revealing ASD-relevant brain regions that are biologically significant.

Strong cathode electroluminescence biosensor based on CeO2 functionalized PCN-222@Ag NPs for sensitive detection of p-Tau-181 protein.

Electrochemiluminescence (ECL) biosensors provide a convenient and high sensitivity method for early disease diagnosis. However, creating luminophore arrays relying on powerful ECL signals remains a daunting task. Porphyrin-centered metal organic frameworks (MOFs) exhibit remarkable potential in ECL sensing applications. In this paper, based on a simple one-pot synthesis method, PCN-222@Ag NPs doped with CeO2 was synthesized to enhance the ECL performance. Due to the strong catalytic ability of CeO2, the ECL signal strength of the new material PCN-222@CeO2@Ag NPs is much higher than that of the PCN-222@Ag NPs and PCN-222. The luminous properties of PCN-222@CeO2@Ag NPs become more intense and stable due to the excellent electronic conductivity of Ag NPs. Based on the fact that CuS@PDA composite can quench the ECL signal of PCN-222@CeO2@Ag NPs, we constructed a novel sandwich ECL immune sensor for the detection of phosphorylated Tau 181 (p-Tau-181) protein. The ECL sensor has a great linear relationship with p-Tau-181 protein concentration, ranging from 1 pg/mL to 100 ng/mL. The detection limit is as low as 0.147 pg/mL. This work provides new ideas for developing sensitive ECL sensors for the p-Tau-181 protein, the marker of Alzheimer's disease.