Transjugular intrahepatic portosystemic shunt for esophagogastric variceal bleeding in patients with hepatocellular carcinoma and portal vein tumor thrombus.

BACKGROUND: Whether hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) and acute esophagogastric variceal bleeding (EGVB) can improve the success rate of endoscopic hemostasis and overall survival (OS) from transjugular intrahepatic portosystemic shunt (TIPS) remains controversial. AIM: To compare the clinical outcomes between TIPS and standard treatment for such HCC patients. METHODS: This monocenter, retrospective cohort study included patients diagnosed as HCC with PVTT and upper gastrointestinal bleeding. Patients were grouped by the treatment (TIPS or standard conservative treatment). The success rate of endoscopic hemostasis, OS, rebleeding rates, and main causes of death were analyzed. RESULTS: Between July 2015 and September 2021, a total of 77 patients (29 with TIPS and 48 with standard treatment) were included. The success rate of endoscopic hemostasis was 96.6% in the TIPS group and 95.8% in the standard treatment group. All the 29 patients in TIPS group successful underwent TIPS procedure and had a better OS compared with standard treatment within the first 160 days after treatment (68 days vs 43 days, P = 0.022), but shorter OS after 160 days (298 days vs 472 days, P = 0.022). Cheng's Classification of PVTT, total bilirubin and Child-Pugh class were independently negative associated with OS (all P < 0.05). The main causes of death were liver failure or hepatic encephalopathy (75.9%) in the TIPS group and rebleeding (68.8%) in the standard treatment. CONCLUSION: TIPS could reduce the risk of early death due to rebleeding and prolong short-term survival in HCC patients with PVTT and acute EGVB, which deserves further investigation.

Novel WFS1 variants are associated with different diabetes phenotypes.

Background: The WFS1 gene encodes the protein wolframin, which is crucial for maintaining endoplasmic reticulum homeostasis. Variants in this gene are predominantly associated with Wolfram syndrome and have been implicated in other disorders such as diabetes mellitus and psychiatric diseases, which increases the rate of clinical misdiagnosis. Methods: Patients were diagnosed with early-onset unclassified diabetes according to their clinical and laboratory data. We performed whole-exome sequencing (WES) in 165 patients, interpreting variants according to the American College of Medical Genetics/Association for Molecular Pathology (ACMG/AMP) 2015 guidelines. Variant verification was done by Sanger sequencing. In vitro experiments were conducted to evaluate the effects of WFS1 compound heterozygous variants. Results: We identified WFS1 compound heterozygous variants (p.A214fs*74/p.F329I and p.I427S/p.I304T) in two patients with Wolfram Syndrome-Like disorders (WSLD). Both WFS1 compound heterozygous variants were associated with increased ER stress, reduced cell viability, and decreased SERCA2b mRNA levels. Additionally, pathogenic or likely pathogenic WFS1 heterozygous variants were identified in the other three patients. Conclusion: Our results underscore the importance of early genetic testing for diagnosing young-onset diabetes and highlight the clinical relevance of WFS1 variants in increasing ER stress and reducing cell viability. Incorporating these genetic insights into clinical practice can reduce misdiagnoses and improve treatment strategies for related disorders.

Joint multi-feature extraction and transfer learning in motor imagery brain computer interface.

Motor imagery brain computer interface (BCI) systems are considered one of the most crucial paradigms and have received extensive attention from researchers worldwide. However, the non-stationary from subject-to-subject transfer is a substantial challenge for robust BCI operations. To address this issue, this paper proposes a novel approach that integrates joint multi-feature extraction, specifically combining common spatial patterns (CSP) and wavelet packet transforms (WPT), along with transfer learning (TL) in motor imagery BCI systems. This approach leverages the time-frequency characteristics of WPT and the spatial characteristics of CSP while utilizing transfer learning to facilitate EEG identification for target subjects based on knowledge acquired from non-target subjects. Using dataset IVa from BCI Competition III, our proposed approach achieves an impressive average classification accuracy of 93.4%, outperforming five kinds of state-of-the-art approaches. Furthermore, it offers the advantage of enabling the design of various auxiliary problems to learn different aspects of the target problem from unlabeled data through transfer learning, thereby facilitating the implementation of innovative ideas within our proposed approach. Simultaneously, it demonstrates that integrating CSP and WPT while transferring knowledge from other subjects is highly effective in enhancing the average classification accuracy of EEG signals and it provides a novel solution to address subject-to-subject transfer challenges in motor imagery BCI systems.

Pressure-induced generation of heterogeneous electrocatalytic metal hydride surfaces for sustainable hydrogen transfer.

Metal hydrides are crucial intermediates in numerous catalytic reactions. Intensive efforts have been dedicated to constructing molecular metal hydrides, where toxic precursors and delicate mediators are usually involved. Herein, we demonstrate a facile pressure-induced methodology to generate a cost-effective heterogeneous electrocatalytic metal hydride surface for sustainable hydrogen transfer. Taking carbon dioxide (CO2) electroreduction as a model system and zinc (Zn), a well-known carbon monoxide (CO)-selective catalyst, as a model catalyst, we showcase a homogeneous-type hydrogen atom transfer process induced by heterogeneous hydride surfaces, enabling direct hydrogenation pathways traditionally considered "prohibited". Specifically, the maximal Faradaic efficiency for formate is enhanced by ~fivefold to 83% under ambient conditions. Experimental and theoretical analyses reveal that unlike the distal hydrogenation route for CO2 to CO over pristine Zn, the Zn hydride surface enables direct hydrogenation at the carbon site of CO2 to form formate. This work provides a promising material platform for sustainable synthesis.

[Comparison on effects of Lycii Fructus from different origins on NaIO_3-induced retinal degenerative diseases in mice by multivariate statistical analysis].

The multivariate statistical analysis was performed to compare the therapeutic effects of Lycii Fructus from different origins on the retinal degenerative diseases(RDD) in mice. The mouse model of RDD was established by intraperitoneal injection of NaIO_3, and the visual function and retinal apoptosis were assessed by dark-light transition and TUNEL assay. Retinal thickness was measured by fundus optical coherence tomography(OCT), and the levels of antioxidant, inflammatory, and angiogenic markers in the serum and eyeball were determined. The therapeutic effects were compared by hierarchical cluster analysis, principal component analysis, and partial least squares-discriminant analysis. The results showed that the extracts of Lycii Fructus from different origins reversed NaIO_3-induced visual damage and retinal apoptosis, reduced oxidative stress, and restored the expression of inflammatory mediators and angiogenic markers in mice. The multivariate statistical analysis based on 17 pharmacodynamic indices suggested that the extract of Lycii Fructus from Ningxia demonstrated better therapeutic effects on RDD than the samples from the other four origins. The results of this study provide a scientific basis for the selection of the advantageous production region of Lycii Fructus for the prevention and treatment of RDD.

Altered functional connectivity of resting-state networks and the correlation with clinical characteristics in intermittent exotropia adult patients: a resting-state magnetic resonance imaging study.

BACKGROUND: The pathogenesis of intermittent exotropia (IXT) remains unclear. The study aims to investigate alterations of resting-state networks (RSNs) in IXT adult patients using resting-state functional magnetic resonance imaging (rs-fMRI) data to explore the potential neural mechanisms. METHODS: Twenty-six IXT adult patients and 22 age-, sex-, handedness-, and education-matched healthy controls (HCs) underwent fMRI scanning and ophthalmological examinations. Brain areas with significant functional connectivity (FC) differences between the IXT and HC groups were selected as regions of interest (ROI) and mean z-scores were calculated to control for individual differences. RESULTS: Compared with HCs, IXT patients exhibited altered FC in various brain regions within RSNs involved in binocular fusion, stereopsis, ocular movement, emotional processes and social cognition, including the default mode network (DMN), the dorsal attention network (DAN), the visual network (VN), the sensorimotor network (SMN), the executive control network (ECN), the frontoparietal network (FPN) and the auditory network (AN). The degree of exodeviation was positively correlated with FC value of left middle occipital gyrus (MOG) within the VN. Correspondingly, we found a negative correlation between the degree of exodeviation and the FC value of left angular gyrus (AG) within FPN (P < 0.05). The FNC analysis between different RSNs also provides evidence on visual-motor cortical plasticity. CONCLUSIONS: IXT patients showed widespread changes of brain activity within RSNs related to binocular fusion, stereopsis, oculomotor control, emotional processes, and social cognition. These findings extend our current understanding of the neuropathological mechanisms of IXT. TRIAL REGISTRATION: Beginning date of the trial: 2021-09-01. Date of registration:2021-07-18. Trial registration number: ChiCTR 2,100,048,852. Trial registration site: http://www.chictr.org.cn/index.aspx .

Imatinib­induced gynecomastia: A case report.

Chronic myeloid leukemia is a myeloproliferative neoplasm characterized by the unregulated and abnormal proliferation of both mature and immature granulocytes, which results in the proliferation of peripheral blood leukocytes. Imatinib, a tyrosine kinase inhibitor, is the first-line treatment for patients diagnosed with chronic myeloid leukemia. However, despite its favorable safety profile, imatinib use is associated with a number of side effects. Gynecomastia is a rare adverse effect of imatinib treatment and may be associated with an imbalance in sex hormones. The present study reports the case of a patient with chronic myeloid leukemia diagnosed with gynecomastia after imatinib treatment. The aim of the present report was to highlight to clinicians this adverse reaction to imatinib treatment and investigate a treatment strategy with fewer side effects.

Antifungal Activity of Phloroglucinol Derivatives against Botrytis cinerea and Monilinia fructicola.

Naturally derived compounds show promise as treatments for microbial infections. Polyphenols, abundantly found in various plants, fruits, and vegetables, are noted for their physiological benefits including antimicrobial effects. This study introduced a new set of acylated phloroglucinol derivatives, synthesized and tested for their antifungal activity in vitro against seven different pathogenic fungi. The standout compound, 3-methyl-1-(2,4,6-trihydroxyphenyl) butan-1-one (2b), exhibited remarkable fungicidal strength, with EC50 values of 1.39 µg/mL against Botrytis cinerea and 1.18 µg/mL against Monilinia fructicola, outperforming previously screened phenolic compounds. When tested in vivo, 2b demonstrated effective antifungal properties, with cure rates of 76.26% for brown rot and 83.35% for gray mold at a concentration of 200 µg/mL, rivaling the commercial fungicide Pyrimethanil in its efficacy against B. cinerea. Preliminary research suggests that 2b's antifungal mechanism may involve the disruption of spore germination, damage to the fungal cell membrane, and leakage of cellular contents. These results indicate that compound 2b has excellent fungicidal properties against B. cinerea and holds potential as a treatment for gray mold.

Self-Supervised Contrastive Learning on Attribute and Topology Graphs for Predicting Relationships Among lncRNAs, miRNAs and Diseases.

Exploring potential association between long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and diseases is an essential part of prevention, diagnosis and treatment of diseases. Since determining these relationships experimentally is resource-intensive and time-consuming, therefore computational methods have emerged as an attractive way to address this issue. However, existing computational approaches for inferring lncRNA-disease associations (LDA), miRNA-disease associations (MDA) and lncRNA-miRNA interactions (LMI) tend to focus on single task, neglecting the benefits of leveraging multiple biomolecular interactions and domain-specific knowledge for multi-task prediction. Furthermore, labeled data for LDA, MDA and LMI is scarce and costly in real-word applications, making it challenging for models to learn comprehensive node embedding patterns. Building on our previous work, this paper proposes a multi-task prediction model (called SSCLMD) that employs self-supervised contrastive learning on attribute and topology graphs to identify potential LDAs, MDAs and LMIs. Specifically, firstly, domain knowledge of lncRNAs, miRNAs and diseases as well as their interactions are exploited to construct attribute graph and topology graph, respectively. Then, the nodes are encoded in the attribute and topology spaces to extract the specific and common feature. Meanwhile, the attention mechanism is performed to adaptively fuse the embedding from different views. SSCLMD incorporates a contrastive self-supervised learning task as a regularize to guide the learning of node embeddings in both attribute and topology space without relying on labels. Severing as a regularize in multi-task learning paradigm, it to improves the model's generalization capabilities. Extensive experiments on 2 manually curated datasets demonstrate that SSCLMD significantly outperforms other baseline methods in LDA, MDA and LMI prediction tasks. Additionally, case studies on both new and old datasets further supported the ability of SSCLMD to uncover novel disease-related lncRNAs and miRNAs. The source codes and supplementary file of this work are publicly available on \url{https://github.com/sheng-n/SSCLMD}.

Evaluating a Natural Language Processing-Driven, AI-Assisted International Classification of Diseases, 10th Revision, Clinical Modification, Coding System for Diagnosis Related Groups in a Real Hospital Environment: Algorithm Development and Validation Study.

BACKGROUND: International Classification of Diseases codes are widely used to describe diagnosis information, but manual coding relies heavily on human interpretation, which can be expensive, time consuming, and prone to errors. With the transition from the International Classification of Diseases, Ninth Revision, to the International Classification of Diseases, Tenth Revision (ICD-10), the coding process has become more complex, highlighting the need for automated approaches to enhance coding efficiency and accuracy. Inaccurate coding can result in substantial financial losses for hospitals, and a precise assessment of outcomes generated by a natural language processing (NLP)-driven autocoding system thus assumes a critical role in safeguarding the accuracy of the Taiwan diagnosis related groups (Tw-DRGs). OBJECTIVE: This study aims to evaluate the feasibility of applying an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), autocoding system that can automatically determine diagnoses and codes based on free-text discharge summaries to facilitate the assessment of Tw-DRGs, specifically principal diagnosis and major diagnostic categories (MDCs). METHODS: By using the patient discharge summaries from Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUCHH) from April 2019 to December 2020 as a reference data set we developed artificial intelligence (AI)-assisted ICD-10-CM coding systems based on deep learning models. We constructed a web-based user interface for the AI-assisted coding system and deployed the system to the workflow of the certified coding specialists (CCSs) of KMUCHH. The data used for the assessment of Tw-DRGs were manually curated by a CCS with the principal diagnosis and MDC was determined from discharge summaries collected at KMUCHH from February 2023 to April 2023. RESULTS: Both the reference data set and real hospital data were used to assess performance in determining ICD-10-CM coding, principal diagnosis, and MDC for Tw-DRGs. Among all methods, the GPT-2 (OpenAI)-based model achieved the highest F1-score, 0.667 (F1-score 0.851 for the top 50 codes), on the KMUCHH test set and a slightly lower F1-score, 0.621, in real hospital data. Cohen κ evaluation for the agreement of MDC between the models and the CCS revealed that the overall average κ value for GPT-2 (κ=0.714) was approximately 12.2 percentage points higher than that of the hierarchy attention network (κ=0.592). GPT-2 demonstrated superior agreement with the CCS across 6 categories of MDC, with an average κ value of approximately 0.869 (SD 0.033), underscoring the effectiveness of the developed AI-assisted coding system in supporting the work of CCSs. CONCLUSIONS: An NLP-driven AI-assisted coding system can assist CCSs in ICD-10-CM coding by offering coding references via a user interface, demonstrating the potential to reduce the manual workload and expedite Tw-DRG assessment. Consistency in performance affirmed the effectiveness of the system in supporting CCSs in ICD-10-CM coding and the judgment of Tw-DRGs.

Theoretical insights into layered IrO2 for the oxygen evolution reaction.

Here we present the density functional theory-based exploration of layered IrO2 polymorphs for the oxygen evolution reaction, as well as a data-driven geometric descriptor for catalytic activity. The layer edges are identified as promising active site motifs with not only low theoretical overpotential but also intriguing structural flexibility and to break the universal energetic scaling through torsional distortion.

Serotypes and Genotypes of Streptococcus pneumoniae in an Unvaccinated Population in Suzhou, China.

Background: Streptococcus pneumoniae is a significant etiological agent of infection and commonly inhabits the human nasopharynx, alongside other potentially pathogenic bacteria. In this study, S. pneumoniae strains were obtained from a community population and subjected to investigation of their phenotypes, genotypes, and vaccine coverage. Methods: S. pneumoniae was isolated from nasopharyngeal swab samples of a healthy population in the Guangfu Community. Capsular serotypes and genotypes were identified using Quellung reaction and multilocus sequence typing (MLST), respectively. The antimicrobial susceptibility was tested using minimum inhibitory concentrations. Results: In total, 500 unvaccinated people were sampled. Ninety-four S. pneumoniae strains were identified. Common serotypes were 19F, 6A, and 9V. The strain coverages of PCV13 and PPV23 were 61.7% and 58.5%, respectively. About 27.6% isolates were non-susceptible to penicillin, and over 80% were resistant to erythromycin and doxycycline. Among 27 novel sequence types (STs) identified in all strains, the most common STs were ST236 (6/94, 6.4%) and ST12669 (6/94, 6.4%). Nearly half of the strains were grouped into four clone complexes (CC12665, CC271, CC6011, and CC180), of which CC271 showed the highest resistance to PEN. Conclusion: In our study, various drug-resistant clone complexes of Streptococcus pneumoniae were found in the healthy population, the elderly, and children. Consequently, pneumococcal vaccines should be included in the national immunization schedule to prevent disease spread.

Organic matter excreted by the protozoan Tetrahymena thermophila and its effects on the bioaccumulation of nanoparticles.

Although organic matter (exudate) excreted by aquatic organisms is an important component of dissolved organic matter (DOM) in the natural environment, its potential effects on the bioaccumulation of nanoparticles (NPs) remain unclear. In the present study, we examined the effects of the exudates from the protozoan Tetrahymena thermophila on the bioaccumulation (including uptake and cell surface adsorption) of iron oxide (Fe2O3, polyacrylate coated) and silica (SiO2) NPs in T. thermophila. The exudates were mostly (93.6 %, in carbon) composed of < 1-kDa molecules (e.g., lipids). When the exudates were mixed with the NPs, significant adsorption occurred on SiO2 NPs but not on Fe2O3 NPs. Independent of their adsorption by the NPs, the exudates significantly inhibited the bioaccumulation of both SiO2 NPs and Fe2O3 NPs by T. thermophila. This inhibitory effect was shown to be mainly due to their inhibition of NP adsorption on the cell surface. By contrast, the exudates had negligible effects on the uptake of either NP type, most likely due to their low molecular weight. Since DOM in the aquatic environment is dominated by molecules < 1 kDa, the potential effects of low-molecular-weight DOM, such as exudates from aquatic organisms, on the bioaccumulation of NPs merits greater attention. ENVIRONMENTAL IMPLICATION: Nanoparticles (NPs) are hazardous materials widespread in the natural environment. Previous studies showed that dissolved organic matter (DOM) in aquatic environments determine the environmental behavior and ecological effects of NPs. Although organic matter (exudate) excreted by aquatic organisms is an important component of DOM, its potential effects on the bioaccumulation of NPs remain unclear. In the present study, we found that the exudates inhibited the cell-surface adsorption of NPs but had no effects on NP uptake, as different from the well-known effects of DOM on NP bioaccumulation. This finding merits attention during evaluations of the environmental risks of NPs.

Fluorescence collection efficiency of atoms in dipole traps.

The fluorescence collection from single atoms and emitters has been extensively utilized in quantum information and quantum optics research. Here, we investigated the collection efficiency of an objective lens by drawing an analogy between the free-space beam (FSB) and a waveguide mode. We explored how efficiency is influenced by their thermal motion within a dipole trap. Furthermore, we introduce an effective energy fraction ratio to quantify potential imperfections in the focusing of the objective lens. Our results provide valuable insights for optimizing the fluorescence collection in single-atom experiments and highlight the importance of considering realistic experimental conditions when estimating achievable efficiencies.

Association of Accommodation and Convergence with Axial Length Elongation in Children with Basic Intermittent Exotropia: A 12-Month Observational Study.

INTRODUCTION: The aim of the study was to investigate the association of parameters related to accommodation and convergence and axial elongation in basic intermittent exotropia (IXT) patients and the potential clinical predictors of axial length (AL) growth. METHODS: A total of 140 basic IXT patients were recruited in this study. The medians of AL growth in different age brackets were chosen to divide the subjects into group A (slower axial elongation group, n = 69) and group B (faster axial elongation group, n = 71). Parameters of dominant and nondominant eyes were compared and analyzed during the 12-month follow-up period. The parameters, including baseline refraction, angle of deviation, Newcastle control score (NCS), accommodative amplitude (AMP), accommodative facility (AMF), accommodative response, positive or negative relative accommodation (PRA/NRA), and near point of convergence (NPC), were analyzed via univariate and multivariate regression. RESULTS: Subjects in the faster axial elongation group tended to have more myopic spherical equivalents (t = 3.956, p < 0.001), greater AMPs of dominant eyes (t = -2.238, p = 0.027), and fewer near points of convergence (t = 2.347, p = 0.020) than in the slower axial elongation group. For dominant eyes, logistic and linear regression analysis revealed that more negative spherical equivalents (OR = 0.603, p < 0.001; ß = -0.045, p < 0.001), greater AMPs (OR = 1.201, p = 0.027; ß = 0.023, p = 0.010), and less near points of convergence (OR = 0.883, p = 0.021; ß = -0.012, p = 0.019) were correlated with the faster axial elongation. For nondominant eyes, a more myopic spherical equivalent (OR = 0.682; p = 0.001; ß = -0.029, p = 0.005) was the only parameter correlated with faster axial elongation through regression analysis. CONCLUSION: In children with basic IXT, faster axial elongation in the dominant eyes was associated with more myopic spherical equivalents, greater AMPs, and lower NPCs. These accommodative parameters can serve as potential clinical indicators for monitoring myopia progression in addition to AL.

Prenylated Flavonoids Isolated from the Root of Sophora flavescens as Potent Antifungal Agents against Botrytis cinerea.

Sophora flavescens, a traditional Chinese herb, produces a wide range of secondary metabolites with a broad spectrum of biological activities. In this study, we isolated six isopentenyl flavonoids (1-6) from the roots of S. flavescens and evaluated their activities against phytopathogenic fungi. In vitro activities showed that kurarinone and sophoraflavanone G displayed broad spectrum and superior activities, among which sophoraflavanone G displayed excellent activity against tested fungi, with EC50 values ranging from 4.76 to 13.94 µg/mL. Notably, kurarinone was easily purified and showed potential activity against Rhizoctonia solani, Botrytis cinerea, and Fusarium graminearum with EC50 values of 16.12, 16.55, and 16.99 µg/mL, respectively. Consequently, we initially investigated the mechanism of kurarinone against B. cinerea. It was found that kurarinone disrupted cell wall components, impaired cell membrane integrity, increased cell membrane permeability, and affected cellular energy metabolism, thereby exerting its effect against B. cinerea. Therefore, kurarinone is expected to be a potential candidate for the development of plant fungicides.

The adhesin RadD enhances Fusobacterium nucleatum tumour colonization and colorectal carcinogenesis.

Fusobacterium nucleatum can bind to host cells and potentiate intestinal tumorigenesis. Here we used a genome-wide screen to identify an adhesin, RadD, which facilitates the attachment of F. nucleatum to colorectal cancer (CRC) cells in vitro. RadD directly binds to CD147, a receptor overexpressed on CRC cell surfaces, which initiated a PI3K-AKT-NF-κB-MMP9 cascade, subsequently enhancing tumorigenesis in mice. Clinical specimen analysis showed that elevated radD gene levels in CRC tissues correlated positively with activated oncogenic signalling and poor patient outcomes. Finally, blockade of the interaction between RadD and CD147 in mice effectively impaired F. nucleatum attachment and attenuated F. nucleatum-induced oncogenic response. Together, our study provides insights into an oncogenic mechanism driven by F. nucleatum RadD and suggests that the RadD-CD147 interaction could be a potential therapeutic target for CRC.

Visible Light-Promoted Aromatization-Driven Deconstructive Fluorination of Spiro Carbocycles.

A visible light-promoted aromatization-driven deconstructive fluorination of spiro carbocycles is presented. A series of spiro dihydroquinazolinones reacted efficiently with NFSI under visible light irradiation to afford the 2-(4-fluoroalkyl)quinazolin-4(3H)-ones in good yields with excellent functional group tolerance. A radical pathway involving C-C bond cleavage and F atom transfer is proposed for the reaction. In addition, the ring-opening chlorination of spiro dihydroquinazolinones with NCS was also applicable.