Risk factors for distant metastasis and prognosis of the penile cancer with distant metastasis.

Background: Penile cancer (PC) is a rare malignant tumor, whose distant metastasis (DM) is associated with the poorest outcomes. The risk factors associated with DM and prognosis of the PC with DM remain elusive. This study was aimed at investigating risk factors associated with DM and constructing prediction models of PC with DM. Methods: This study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database over a period of 2000-2020, including clinical characteristics such as age, marital status, tumor size, Tumor Node Metastasis (TNM) staging, and treatment information. Utilizing univariate and multivariate logistic regression, alongside cox regression analysis, we identified independent risk factors for DM and prognosis in the total cases and the cases with DM. Nomograms were developed for predicting DM and prognosis in PC patients. Results: Enrolling 1,488 cases, our study identified tumor size and N stage as independent predictors of DM. The predictive nomogram for DM achieved an area under the curve (AUC) of 0.904. Notably, the 1-, 3-, and 5-year cumulative survival rates for PC with DM were 35%, 17%, and 13%, respectively, with larger tumor size associated with prognosis of PC cases with DM. This study verified a correlation between advanced age and TNM stage, as well as chemotherapy with the poor PC prognosis. The nomogram yielded 0.72, 0.69 and 0.69, in predicting 1-, 3-, and 5-year overall survivals (OS), while 0.73, 0.70 and 0.69 in predicting 1-, 3-, 5-year cancer specific survivals (CSS), respectively. Conclusions: This study investigated risk factors of PC with DM. Also, nomograms for predicting DM, OS and CSS of PC patients were developed.

Design and synthesis of an environment-sensitive 3-methyleneisoindolin-1-one fluorophore for labeling DNA-interacting proteins.

We designed 6-dimethylamino 3-methyleneisoindolin-1-one as an environment-sensitive fluorophore, examining its applications for protein labeling. Synthesized 3-methyleneisoindolin-1-one exhibits solvatochromic fluorescence (λemmax; 472 nm in 2-PrOH, 512 nm in H2O). A positive linear dependence between λemmax and solvent dielectric constant (DC), as well as between Stokes shift and DC, and a negative correlation between fluorescence quantum yield and DC are observed in protic solvents. These properties are similar to those of the oxygen isosteric fluorophore, 4-dimethylaminophthalimide, a slovatochromic fluorophore utilized for labeling oligodeoxynucleotides (ODNs) and peptides. Notably, fluorescence intensity of 3-methyleneisoindolin-1-one is higher than the phthalimide in protic solvents used in this study. The 3-methyleneisoindolin-1-one demonstrated the higher stability in pH 8 solution than in pH 6 solution in contrast to the stability profile of the phthalimide, which was stable at pH 6 but was hydrolyzed at pH 8. We also synthesized an o-keto benzaldehyde derivative that converts a primary amine to 6-dimethylamino 3-methyleneisoindolin-1-one under biocompatible conditions and introduced it into ODNs for turn-on fluorescent protein labeling. The synthesized ODN with a protein-binding sequence of Escherichia coli DnaA was employed to modify the DNA-binding domain of DnaA, and the fluorescent properties of the modified protein were investigated.

ST6GALNAC1-mediated sialylation in uterine endometrial epithelium facilitates the epithelium-embryo attachment.

INTRODUCTION: Embryo implantation requires synergistic interaction between the embryo and the receptive endometrium. Glycoproteins and glycan-binding proteins are involved in endometrium-embryo attachment. Sialyl Tn (sTn), a truncated O-glycan, is catalyzed by ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) and can be detected by specific Sialic-acid-binding immunoglobulin-like lectins (Siglecs). Whether the sTn-Siglecs axis supports embryo implantation remains unknown. OBJECTIVES: This paper aims to study the role of ST6GALNAC1/sTn-Siglecs axis in embryo implantation. METHODS: ST6GALNAC1 and sTn in human endometrium were analyzed by immunohistochemistry. An in vitro implantation model was conducted to evaluate the effects of ST6GALNAC1/sTn on the receptivity of human endometrial AN3CA cells to JAR spheroids. Immunoprecipitation combined with mass spectrometry analysis was carried out to identify the key proteins modified by sTn in endometrial cells. Siglec-6 in human embryos was analyzed by published single-cell RNA sequencing (scRNA-seq) datasets. Protein interaction assay was applied to verify the bond between the Siglec-6 with sTn-modified CD44. St6galnac1 siRNAs and anti-sTn antibodies were injected into the uterine horn of the mouse at the pre-implantation stage to evaluate the role of endometrial St6galnac1/sTn in embryo implantation. Siglec-G in murine embryos was analyzed by immunofluorescence staining. The function of Siglec-G is evidenced by uterine horn injection and protein interaction assay. RESULTS: Both human and murine endometrium at the receptive stage exhibit higher ST6GALNAC1 and sTn levels compared to the non-receptive stage. Overexpression of ST6GALNAC1 significantly enhanced the receptivity of AN3CA cells to JAR spheroids. Inhibition of endometrial ST6GALNAC1/sTn substantially impaired embryo implantation in vivo. CD44 was identified as a carrier for sTn in the endometrial cells of both species. Siglec-6 and Siglec-G, expressed in the embryonic trophectoderm, were found to promote embryo attachment, which may be achieved through binding with sTn-modified CD44. CONCLUSION: ST6GALNAC1-regulated sTn in the endometrium aids in embryo attachment through interaction with trophoblastic Siglecs.

Dual Dynamic Cross-Linked Epoxy Vitrimers Used for Strong, Detachable, and Reworkable Adhesives.

Novel reprocessable thermosetting adhesives (RTAs), which combine high adhesive strength, reusability, disassembly, and recyclability features, have attracted increasing attention. However, developing RTAs with a rapidly adhesive rate while ensuring high adhesive strength and self-healing ability is still a significant challenge. Here, we prepared a novel vitrimer called DAx-DTSAy, which can be used as an RTA. First, by adjusting the ratio of rigid and flexible segments, maximum tensile strength reached 35.92 MPa. Second, the combined effect of dynamic hydroxyl ester bonds and dynamic disulfide bonds resulted in a rapid stress relaxation behavior, with a complete relaxation time 13.6 times shorter than a vitrimer only cross-linked with hydroxy ester bonds. This feature endowed its good self-healing and reprocessing capabilities. After self-healing at 180 °C, the maximum healing rate of mechanical properties was 91.8%. After three reprocesses, the maximum recovery rate of tensile strength was 120.2%. Furthermore, the combination of rigid and flexible segments and the synergistic effect of dual dynamic covalent bonds made DAx-DTSAy capable of use as a high-performance RTA. The lap shear strength of a DAx-DTSAy film on stainless steel reached 18.18 MPa after 15 min, with a recovery rate of 91.9% after 5 rebonding cycles. Additionally, DAx-DTSAy can be disassembled in chemical agents and exhibited better insulation properties compared to traditional epoxy resins. DAx-DTSAy can be employed as a novel high-performance adhesive in applications such as electronic devices and transportation, contributing to the development of thermosetting adhesives toward recyclability and sustainability.

Scurvy and vitamin C deficiency in an Australian tertiary children's hospital.

AIM: We aimed to investigate the frequency of vitamin C deficiency scurvy in the Australian paediatric context, describe cohorts at risk, and identify factors associated with development of symptoms in children with vitamin C deficiency. We also aimed to propose a management guideline for children with features of scurvy. METHOD: A retrospective study was done at a tertiary paediatric hospital in Australia over a three-year period, from August 2019 to July 2022. Children from birth to 18 years old, whose vitamin C levels were low (<23 µmol/L), were included. Data extracted from hospital medical records included demographics, weight, co-morbidities, eating disorder diagnoses, clinical features, investigations and treatment. Descriptive statistics and risk statistics were performed. RESULTS: In a cohort of 887 patients who had their vitamin C levels checked, we identified 272 (31%) who had a vitamin C level <23 µmol/L. Of these, 13 (5%) were symptomatic of vitamin C deficiency and 19 (7%) may have been symptomatic. In patients with vitamin C deficiency, 248 (91%) had comorbidities, neurodevelopmental disorders being most common, and 176 (65%) had restricted eating. When the asymptomatic and symptomatic groups were compared, in the symptomatic group, there was a significantly lower vitamin C level and disordered eating related to autism spectrum disorders was more common. CONCLUSION: In order to avoid delayed diagnoses and unnecessary investigations, clinicians should be familiar with symptoms of scurvy and perform a dietary assessment, vitamin C assay, and commence empiric vitamin C supplementation where appropriate.

Green credit policy and residents' health: quasi-natural experimental evidence from China.

Background: Residents' health plays an important role in economic prosperity and national development. Methods: The research analyzes data from 262 prefecture-level cities in China spanning the period from 2010 to 2021. Utilizing the implementation of green credit policy in China as a quasi-natural experiment, the paper employs the time-varying Differences-in- Differences (DID) model to evaluate the influence of green credit policy on residents' health. Results: The paper results show that: (1) the green credit policy significantly improves residents' health, and this conclusion still holds after a series of robustness tests. (2) Mechanism analysis reveals that the green credit policy affects residents' health through the improvements of the environment and the elevation of public services standards in demonstration cities. (3) Heterogeneity analysis shows that the impact of green credit policy on residents' health is more significant in the western cities and resource-based cities than in the central-eastern cities and non-resource-based cities. This paper explains the specific path and realization of green credit policy to enhance residents' health, which provides a reference for further designing and improving effective green credit policy. Discussion: The deficiencies within the green credit policy has resulted in limited improvements. It is recommended that China should broaden the ambit of the green credit policy and refine the criteria for its execution.

Extracellular NCOA4 is a mediator of septic death by activating the AGER-NFKB pathway.

Sepsis, a life-threatening condition resulting from a dysregulated response to pathogen infection, poses a significant challenge in clinical management. Here, we report a novel role for the autophagy receptor NCOA4 in the pathogenesis of sepsis. Activated macrophages and monocytes secrete NCOA4, which acts as a mediator of septic death in mice. Mechanistically, lipopolysaccharide, a major component of the outer membrane of Gram-negative bacteria, induces NCOA4 secretion through autophagy-dependent lysosomal exocytosis mediated by ATG5 and MCOLN1. Moreover, bacterial infection with E. coli or S. enterica leads to passive release of NCOA4 during GSDMD-mediated pyroptosis. Upon release, extracellular NCOA4 triggers the activation of the proinflammatory transcription factor NFKB/NF-κB by promoting the degradation of NFKBIA/IκB molecules. This process is dependent on the pattern recognition receptor AGER, rather than TLR4. In vivo studies employing endotoxemia and polymicrobial sepsis mouse models reveal that a monoclonal neutralizing antibody targeting NCOA4 or AGER delays animal death, protects against organ damage, and attenuates systemic inflammation. Furthermore, elevated plasma NCOA4 levels in septic patients, particularly in non-survivors, correlate positively with the sequential organ failure assessment score and concentrations of lactate and proinflammatory mediators, such as TNF, IL1B, IL6, and HMGB1. These findings demonstrate a previously unrecognized role of extracellular NCOA4 in inflammation, suggesting it as a potential therapeutic target for severe infectious diseases. Abbreviation: BMDMs: bone marrow-derived macrophages; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; ELISA: enzyme-linked immunosorbent assay; LPS: lipopolysaccharide; NO: nitric oxide; SOFA: sequential organ failure assessment.

Deep profiling of plasmalogens by coupling the Paternò-Büchi derivatization with tandem mass spectrometry.

Plasmalogens are a special class of glycerophospholipids characterized by a vinyl ether bond (-C = C-O-) at the sn-1 position of the glycerol backbone. Altered plasmalogen profiles have been observed in neurodegenerative diseases and cancers. Profiling of plasmalogens requires specifying the vinyl ether bond and differentiating them from various types of isobars and isomers. Herein, by coupling C = C derivatization via offline Paternò-Büchi reaction with liquid chromatography-tandem mass spectrometry, we have developed a sensitive workflow for analysis of plasmalogens from biological samples. Using bovine heart lipid extract as a model system, we profiled more than 100 distinct structures of plasmenylethanolamines (PE-Ps) and plasmenylcholines (PC-Ps) at the C = C location level, far exceeding previous reports. Analysis of human glioma and normal brain tissue samples revealed elevated n-10 C = C isomers of PE-Ps in the glioma tissue samples. These findings suggest that the developed workflow holds potential in aiding the study of altered metabolism of plasmalogens in clinical samples.

Access to New Clinic Appointments for Patients With Cancer.

Importance: Racial and ethnic disparities have been observed in the outpatient visit rates for specialist care, including cancer care; however, little is known about patients' experience at the critical step of attempting to access new clinic appointments for cancer care. Objective: To determine simulated English-speaking, Spanish-speaking, and Mandarin-speaking patient callers' ability to access new clinic appointments for 3 cancer types (colon, lung, and thyroid cancer) that disproportionately impact Hispanic and Asian populations. Design, Setting, and Participants: This cross-sectional audit study was conducted between November 2021 and March 2023 using 479 clinic telephone numbers that were provided by the hospital general information personnel at 143 hospitals located across 12 US states. Using standardized scripts, trained research personnel assigned to the roles of English-speaking, Spanish-speaking, and Mandarin-speaking patients called the telephone number for a clinic that treats colon, lung, or thyroid cancer to inquire about a new clinic appointment. Data analysis was conducted from June to September 2023. Main Outcomes and Measures: The primary outcome was whether the simulated patient caller was able to access cancer care (binary variable, yes or no), which was defined to include being provided with a clinic appointment date or scheduling information. Multivariable logistic regression analysis was performed to determine factors independently associated with simulated patient callers being able to access cancer care. Results: Of 985 total calls (399 English calls; 302 Spanish calls; 284 Mandarin calls), simulated patient callers accessed cancer care in 409 calls (41.5%). Differences were observed based on language type, with simulated English-speaking patient callers significantly more likely to access cancer care compared with simulated Spanish-speaking and Mandarin-speaking patient callers (English, 245 calls [61.4%]; Spanish, 110 calls [36.4%]; Mandarin, 54 calls [19.0%]; P < .001). A substantial number of calls ended due to linguistic barriers (291 of 586 Spanish or Mandarin calls [49.7%]) and workflow barriers (239 of 985 calls [24.3%]). Compared with English-speaking simulated patient callers, the odds of accessing cancer care were lower for Spanish-speaking simulated patient callers (adjusted odds ratio [aOR], 0.34; 95% CI, 0.25-0.46) and Mandarin-speaking simulated patient callers (aOR, 0.13; 95% CI, 0.09-0.19). Compared with contacting clinics affiliated with teaching hospitals, callers had lower odds of accessing cancer care when contacting clinics that were affiliated with nonteaching hospitals (aOR, 0.53; 95% CI, 0.40-0.70). Conclusions and Relevance: In this cross-sectional audit study, simulated patient callers encountered substantial barriers when attempting to access clinic appointments for cancer care. These findings suggest that interventions focused on mitigating these barriers are necessary to increase access to cancer care for all patients.

Interplay of graphene-DNA interactions: Unveiling sensing potential of graphene materials.

Graphene-based materials and DNA probes/nanostructures have emerged as building blocks for constructing powerful biosensors. Graphene-based materials possess exceptional properties, including two-dimensional atomically flat basal planes for biomolecule binding. DNA probes serve as excellent selective probes, exhibiting specific recognition capabilities toward diverse target analytes. Meanwhile, DNA nanostructures function as placement scaffolds, enabling the precise organization of molecular species at nanoscale and the positioning of complex biomolecular assays. The interplay of DNA probes/nanostructures and graphene-based materials has fostered the creation of intricate hybrid materials with user-defined architectures. This advancement has resulted in significant progress in developing novel biosensors for detecting DNA, RNA, small molecules, and proteins, as well as for DNA sequencing. Consequently, a profound understanding of the interactions between DNA and graphene-based materials is key to developing these biological devices. In this review, we systematically discussed the current comprehension of the interaction between DNA probes and graphene-based materials, and elucidated the latest advancements in DNA probe-graphene-based biosensors. Additionally, we concisely summarized recent research endeavors involving the deposition of DNA nanostructures on graphene-based materials and explored imminent biosensing applications by seamlessly integrating DNA nanostructures with graphene-based materials. Finally, we delineated the primary challenges and provided prospective insights into this rapidly developing field. We envision that this review will aid researchers in understanding the interactions between DNA and graphene-based materials, gaining deeper insight into the biosensing mechanisms of DNA-graphene-based biosensors, and designing novel biosensors for desired applications.

Fluorescent Chiral Quantum Dots to Unveil Origin-Dependent Exosome Uptake and Cargo Release.

Exosomes are promising nanocarriers for drug delivery. Yet, it is challenging to apply exosomes in clinical use due to the limited understanding of their physiological functions. While cellular uptake of exosomes is generally known through endocytosis and/or membrane fusion, the mechanisms of origin-dependent cellular uptake and subsequent cargo release of exosomes into recipient cells are still unclear. Herein, we investigated the intricate mechanisms of exosome entry into recipient cells and intracellular cargo release. In this study, we utilized chiral graphene quantum dots (GQDs) as representatives of exosomal cargo, taking advantage of the superior permeability of chiral GQDs into lipid membranes as well as their excellent optical properties for tracking analysis. We observed that the preferential cellular uptake of exosomes derived from the same cell-of-origin (intraspecies exosomes) is higher than that of exosomes derived from different cell-of-origin (cross-species exosomes). This uptake enhancement was attributed to receptor-ligand interaction-mediated endocytosis, as we identified the expression of specific ligands on exosomes that favorably interact with their parental cells and confirmed the higher lysosomal entrapment of intraspecies exosomes (intraspecies endocytic uptake). On the other hand, we found that the uptake of cross-species exosomes primarily occurred through membrane fusion, followed by direct cargo release into the cytosol (cross-species direct fusion uptake). We revealed the underlying mechanisms involved in the cellular uptake and subsequent cargo release of exosomes depending on their cell-of-origin and recipient cell types. Overall, this study envisions valuable insights into further advancements in effective drug delivery using exosomes, as well as a comprehensive understanding of cellular communication, including disease pathogenesis.

Research Progress of Pericytes in Pulmonary Fibrosis.

Pericytes, a specific type of mesenchymal cell that surround the basement membrane of pulmonary venules and capillaries. They are crucial pathological features observed in individuals with the severe lung disease of pulmonary fibrosis (PF). The presence of pericytes leads to inflammation and fibrosis in the lung interstitium and alveolar space due to the release of various cytokines and chemokines. Pericytes also stimulate the proliferation and activation of fibroblasts, thereby promoting the progression of PF. Previous studies examining the mechanism of action of pericytes have primarily focused on cell signal transduction pathways, cell growth and death processes, and the synthesis and breakdown of extracellular matrix (ECM). Notably, the transforming growth factor-ß (TGF-ß) and Wnt signaling pathways have been associated with the action of pericytes in driving the progression of PF. It is therefore clear that pericytes play an essential role in the development of PF, while also offering possible avenues for targeted therapeutic intervention against this condition. The current article provides a comprehensive review on how pericytes contribute to inflammatory responses, as well as their importance for understanding the mechanism of PF. In addition, this review discusses the potential use of pericyte-targeted approaches for the treatment of patients affected by this debilitating lung disease.

Stimulative piezoelectric nanofibrous scaffolds for enhanced small extracellular vesicle production in 3D cultures.

Small extracellular vesicles (sEVs) have great promise as effective carriers for drug delivery. However, the challenges associated with the efficient production of sEVs hinder their clinical applications. Herein, we report a stimulative 3D culture platform for enhanced sEV production. The proposed platform consists of a piezoelectric nanofibrous scaffold (PES) coupled with acoustic stimulation to enhance sEV production of cells in a 3D biomimetic microenvironment. Combining cell stimulation with a 3D culture platform in this stimulative PES enables a 49 fold increase in the production rate per cell with minimal deviations in particle size and protein composition compared with standard 2D cultures. We find that the enhanced sEV production is attributable to the activation and upregulation of crucial sEV production steps through the synergistic effect of stimulation and the 3D microenvironment. Moreover, changes in cell morphology lead to cytoskeleton redistribution through cell matrix interactions in the 3D cultures. This in turn facilitates intracellular EV trafficking, which impacts the production rate. Overall, our work provides a promising 3D cell culture platform based on piezoelectric biomaterials for enhanced sEV production. This platform is expected to accelerate the potential use of sEVs for drug delivery and broad biomedical applications.

Regulation of quorum sensing activities by the stringent response gene rsh in sphingomonads is species-specific and culture condition dependent.

Stringent response and quorum sensing (QS) are two essential mechanisms that control bacterial global metabolism for better survival. Sphingomonads are a clade of bacteria that survive successfully in diverse ecosystems. In silico survey indicated that 36 out of 79 investigated sphingomonads strains contained more than one luxI homolog, the gene responsible for the biosynthesis of QS signal acyl homoserine lactones (AHLs). Investigation of the regulatory effects of the stringent response gene rsh on QS related bioactivities were carried out using rsh mutants of Sphingobium japonicum UT26 and Sphingobium sp. SYK-6, both had three luxI homologs. Results indicated that deletion of rsh upregulated the overall production of AHLs and extracellular polymeric substances (EPS) in both UT26 and SYK-6 in rich medium, but affected expressions of these luxI/luxR homologs in different ways. In the poor medium (1% LB), rsh mutant of SYK-6 significantly lost AHLs production in broth cultivation but not in biofilm cultivation. The regulatory effects of rsh on QS activities were growth phase dependent in UT26 and culture condition dependent in SYK-6. Our results demonstrated the negative regulatory effect of rsh on QS activities in sphingomonads, which were very different from the positive effect found in sphingomonads containing only one luxI/R circuit. This study extends the current knowledge on the intricate networks between stringent response and QS system in sphingomonads, which would help to understand their survival advantage.

Diagnosis of benign and malignant peripheral lung lesions based on a feature model constructed by the random forest algorithm for grayscale and contrast-enhanced ultrasound.

Rationale and objectives: To construct a predictive model for benign and malignant peripheral pulmonary lesions (PPLs) using a random forest algorithm based on grayscale ultrasound and ultrasound contrast, and to evaluate its diagnostic value. Materials and methods: We selected 254 patients with PPLs detected using chest lung computed tomography between October 2021 and July 2023, including 161 malignant and 93 benign lesions. Relevant variables for judging benign and malignant PPLs were screened using logistic regression analysis. A model was constructed using the random forest algorithm, and the test set was verified. Correlations between these relevant variables and the diagnosis of benign and malignant PPLs were evaluated. Results: Age, lesion shape, size, angle between the lesion border and chest wall, boundary clarity, edge regularity, air bronchogram, vascular signs, enhancement patterns, enhancement intensity, homogeneity of enhancement, number of non-enhancing regions, non-enhancing region type, arrival time (AT) of the lesion, lesion-lung AT difference, AT difference ratio, and time to peak were the relevant variables for judging benign and malignant PPLs. Consequently, a model and receiver operating characteristic curve were constructed with an AUC of 0.92 and an accuracy of 88.2%. The test set results showed that the model had good predictive ability. The index with the highest correlation for judging benign and malignant PPLs was the AT difference ratio. Other important factors were lesion size, patient age, and lesion morphology. Conclusion: The random forest algorithm model constructed based on clinical data and ultrasound imaging features has clinical application value for predicting benign and malignant PPLs.

More attention should be paid to Omicron-associated sepsis: a multicenter retrospective study in south China.

Background: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible but causes less severe disease compared to other variants. However, its association with sepsis incidence and outcomes is unclear. This study aimed to investigate the incidence of Omicron-associated sepsis, as per the Sepsis 3.0 definition, in hospitalized patients, and to explore its relationship with clinical characteristics and prognosis. Methods: This multicenter retrospective study included adults hospitalized with confirmed SARS-CoV-2 infection across six tertiary hospitals in Guangzhou, China from November 2022 to January 2023. The Sequential Organ Failure Assessment (SOFA) score and its components were calculated at hospital admission to identify sepsis. Outcomes assessed were need for intensive care unit (ICU) transfer and mortality. Receiver operating characteristic curves evaluated the predictive value of sepsis versus other biomarkers for outcomes. Results: A total of 299 patients (mean age: 70.1±14.4 years, 42.14% female) with SOFA score were enrolled. Among them, 152 were categorized as non-serious cases while the others were assigned as the serious group. The proportion of male patients, unvaccinated patients, patients with comorbidity such as diabetes, chronic cardiovascular disease, and chronic lung disease was significantly higher in the serious than non-serious group. The median SOFA score of all enrolled patients was 1 (interquartile range, 0-18). In our study, 147 patients (64.19%) were identified as having sepsis upon hospital admission, with the majority of these septic patients (113, representing 76.87%) being in the serious group, the respiratory, coagulation, cardiovascular, central nervous, and renal organ SOFA scores were all significantly higher in the serious compared to the non-serious group. Among septic patients, 20 out of 49 (40.81%) had septic shock as indicated by lactate measurement within 24 hours of admission, and the majority of septic patients were in the serious group (17/20, 76.87%). Sepsis was present in 118 out of 269 (43.9%) patients in the general ward, and among those with sepsis, 34 out of 118 (28.8%) later required ICU care during hospitalization. By contrast, none of the patients without sepsis required ICU care. Moreover, the mortality rate was significantly higher in patients with than without sepsis. Conclusions: A considerable proportion of patients infected with Omicron present with sepsis upon hospital admission, which is associated with a poorer prognosis. Therefore, early recognition of viral sepsis by evaluation of the SOFA score in hospitalized coronavirus disease 2019 patients is crucial.

The role of shear rates on amyloid formation from biofilm peptide phenol-soluble modulins.

Biofilms, microbial communities enclosed in the self-produced extracellular matrix, have a significant impact on human health, environment, and industry. The pathogen Staphylococcus aureus (S. aureus) is recognized as one of the most frequent causes of biofilm-related infections. Phenol-soluble modulins (PSMs) serve as a crucial component, fortifying S. aureus biofilm matrix through self-assembly into amyloid fibrils, which enhances S. aureus colonization and resistance to antibiotics. However, the role of shear rate, one of the critical physiological factors within blood vessels, on the formation of PSM amyloids remains poorly understood. In this work, using a combination of thioflavin T fluorescence kinetic studies, circular dichroism spectrometry, and electron microscopy, we demonstrated that shear rates ranging from 150 to 300 s-1 accelerate fibrillation of PSMα1, α3, and α4 into amyloids, resulting in elongated amyloid structures. Furthermore, PSMα1, α3, and α4 predominantly self-assembled into amyloid fibers with a cross-α structure under shear conditions, deviating from the typical ß-sheet configuration of PSM amyloids. These findings imply the role of shear rates within the bloodstream on enhancing PSM self-assembly that is associated with S. aureus biofilm formation.

The potential of 18F-FDG PET/CT metabolic parameter-based nomogram in predicting the microvascular invasion of hepatocellular carcinoma before liver transplantation.

PURPOSE: Microvascular invasion (MVI) is a critical factor in predicting the recurrence and prognosis of hepatocellular carcinoma (HCC) after liver transplantation (LT). However, there is a lack of reliable preoperative predictors for MVI. The purpose of this study is to evaluate the potential of an 18F-FDG PET/CT-based nomogram in predicting MVI before LT for HCC. METHODS: 83 HCC patients who obtained 18F-FDG PET/CT before LT were included in this retrospective research. To determine the parameters connected to MVI and to create a nomogram for MVI prediction, respectively, Logistic and Cox regression models were applied. Analyses of the calibration curve and receiver operating characteristic (ROC) curves were used to assess the model's capability to differentiate between clinical factors and metabolic data from PET/CT images. RESULTS: Among the 83 patients analyzed, 41% were diagnosed with histologic MVI. Multivariate logistic regression analysis revealed that Child-Pugh stage, alpha-fetoprotein, number of tumors, CT Dmax, and Tumor-to-normal liver uptake ratio (TLR) were significant predictors of MVI. A nomogram was constructed using these predictors, which demonstrated strong calibration with a close agreement between predicted and actual MVI probabilities. The nomogram also showed excellent differentiation with an AUC of 0.965 (95% CI 0.925-1.000). CONCLUSION: The nomogram based on 18F-FDG PET/CT metabolic characteristics is a reliable preoperative imaging biomarker for predicting MVI in HCC patients before undergoing LT. It has demonstrated excellent efficacy and high clinical applicability.

Ultrasound-based radiomics nomogram for predicting axillary lymph node metastasis in early-stage breast cancer.

PURPOSE: We aimed at assessing the predictive ability of ultrasound-based radiomics combined with clinical characteristics for axillary lymph node (ALN) status in early-stage breast cancer patients and to compare performance in different peritumoral regions. MATERIALS AND METHODS: A total of 755 patients (527 in the primary cohort and 228 in the external validation cohort) were enrolled in this study. Ultrasound images for all patients were acquired and radiomics analysis performed for intratumoral and different peritumoral regions. The MRMR and LASSO regression analyses were performed on extracted features from the primary cohort to construct a radiomics signature formula combined with clinical characteristics. Pearson's coefficient and the variance inflation factor (VIF) were performed to check the correlation and the multicollinearity among the final predictors. The best performing model was selected to develop a nomogram, which was established by performing binary logistic regression and acquiring cut-off values based on the corresponding nomogram scores of the masses. RESULTS: Among all the radiomics models, the "Mass + Margin3mm" model exhibited the best performance. The areas under the curves (AUC) of the nomogram in the primary and external validation cohorts were 0.906 (95% confidence intervals [CI] 0.882-0.930) and 0.922 (95% CI 0.894-0.960), respectively. They both showed good calibrations. The nomogram exhibited a good ability to discriminate between positive and negative lymph nodes (AUC: 0.853 (95% CI 0.816-0.889) in primary cohort, 0.870 (95% CI 0.818-0.922) in validation cohort), and between low-volume and high-volume lymph nodes (AUC: 0.832 (95% CI 0.781-0.884) in primary cohort, 0.911 (95% CI 0.858-0.964) in validation cohort). CONCLUSIONS: The established nomogram is a prospective clinical prediction tool for non-invasive assessment of ALN status. It has the ability to enhance the accuracy of early-stage breast cancer treatment.

A Model Combining Conventional Ultrasound Characteristics, Strain Elastography and Clinicopathological Features to Predict Ki-67 Expression in Small Breast Cancer.

To establish a predictive model incorporating conventional ultrasound, strain elastography and clinicopathological features for Ki-67 expression in small breast cancer (SBC) which defined as maximum diameter less than2 cm. In this retrospective study, 165 SBC patients from our hospital were allocated to a high Ki-67 group (n = 104) and a low Ki-67 group (n = 61). Multivariate regression analysis was performed to identify independent indicators for developing predictive models. The area under the receiver operating characteristic (AUC) curve was also determined to establish the diagnostic performance of different predictive models. The corresponding sensitivities and specificities of different models at the cutoff value were compared. Conventional ultrasound parameters (spiculated margin, absence of posterior shadowing and Adler grade 2-3), strain elastic scores and clinicopathological information (HER2 positive) were significantly correlated with high expression of Ki-67 in SBC (all p < .05). Model 2, which incorporated conventional ultrasound features and strain elastic scores, yielded good diagnostic performance (AUC = 0.774) with better sensitivity than model 1, which only incorporated ultrasound characteristics (78.85%vs. 55.77%, p = .000), with specificities of 77.05% and 62.30% (p = .035), respectively. Model 3, which incorporated conventional ultrasound, strain elastography and clinicopathological features, yielded better performance (AUC = 0.853) than model 1 (AUC = 0.694) and model 2 (AUC = 0.774), and the specificity was higher than model 1 (86.89% vs. 77.05%, p = .001). The predictive model combining conventional ultrasound, strain elastic scores and clinicopathological features could improve the predictive performance of Ki-67 expression in SBC.