Prediction of sepsis mortality in ICU patients using machine learning methods.

PROBLEM: Sepsis, a life-threatening condition, accounts for the deaths of millions of people worldwide. Accurate prediction of sepsis outcomes is crucial for effective treatment and management. Previous studies have utilized machine learning for prognosis, but have limitations in feature sets and model interpretability. AIM: This study aims to develop a machine learning model that enhances prediction accuracy for sepsis outcomes using a reduced set of features, thereby addressing the limitations of previous studies and enhancing model interpretability. METHODS: This study analyzes intensive care patient outcomes using the MIMIC-IV database, focusing on adult sepsis cases. Employing the latest data extraction tools, such as Google BigQuery, and following stringent selection criteria, we selected 38 features in this study. This selection is also informed by a comprehensive literature review and clinical expertise. Data preprocessing included handling missing values, regrouping categorical variables, and using the Synthetic Minority Over-sampling Technique (SMOTE) to balance the data. We evaluated several machine learning models: Decision Trees, Gradient Boosting, XGBoost, LightGBM, Multilayer Perceptrons (MLP), Support Vector Machines (SVM), and Random Forest. The Sequential Halving and Classification (SHAC) algorithm was used for hyperparameter tuning, and both train-test split and cross-validation methodologies were employed for performance and computational efficiency. RESULTS: The Random Forest model was the most effective, achieving an area under the receiver operating characteristic curve (AUROC) of 0.94 with a confidence interval of ±0.01. This significantly outperformed other models and set a new benchmark in the literature. The model also provided detailed insights into the importance of various clinical features, with the Sequential Organ Failure Assessment (SOFA) score and average urine output being highly predictive. SHAP (Shapley Additive Explanations) analysis further enhanced the model's interpretability, offering a clearer understanding of feature impacts. CONCLUSION: This study demonstrates significant improvements in predicting sepsis outcomes using a Random Forest model, supported by advanced machine learning techniques and thorough data preprocessing. Our approach provided detailed insights into the key clinical features impacting sepsis mortality, making the model both highly accurate and interpretable. By enhancing the model's practical utility in clinical settings, we offer a valuable tool for healthcare professionals to make data-driven decisions, ultimately aiming to minimize sepsis-induced fatalities.

Psychological distress, sexual satisfaction and quality of life of gynaecological cancer patients and their spouses during cancer survivorship: A comparison of husbands and wives.

AIMS AND OBJECTIVES: To investigate the psychological distress, sexual satisfaction, and quality of life of gynaecological cancer survivors and their spouses during cancer survivorship. BACKGROUND: The survival rate of patients with cancer is increasing owing to advances in medical treatment technology. Spouses are the closest companions of gynaecological cancer survivors. Patients with gynaecological cancer and their spouses face different situations and challenges after experiencing cancer invasion. DESIGN: Questionnaire-based cross-sectional study. METHODS: Convenience sampling was employed, and 180 participants, including patients with gynaecological cancer and their spouses, were enrolled. A structured questionnaire was used to investigate the psychological distress, sexual satisfaction, and quality of life of gynaecological cancer survivors and their spouses during acute, extended, and permanent survivorship. The STROBE checklist guided the study preparation. RESULTS: For gynaecological cancer survivors and their spouses, (1) severe psychological distress was present during acute survivorship, with anxiety extending until permanent survivorship; (2) no significant differences were observed in pre- and post-treatment sexual satisfaction, although pre-treatment sexual satisfaction was higher than post-treatment sexual satisfaction in all three cancer survivorship stages and (3) quality of life decreased during acute survivorship and gradually improved with time. CONCLUSIONS: Psychological distress, sexual satisfaction and quality of life of gynaecological cancer survivors and their spouses worsened during acute survivorship and improved over time until permanent survivorship. RELEVANCE TO CLINICAL PRACTICE: Gynaecological cancer survivors and their spouses experience anxiety and depression from diagnosis confirmation until permanent survivorship (>5 years survival). Therefore, clinical nurses' sensitivity to emotional distress in cancer survivors and their spouses can be improved and a consistent and routine evaluation method has been established for the early detection of such emotional distress. The results of this study can provide a reference for clinical healthcare professionals and contribute to a better quality of care.

Access Site Complication Rates Following Peripheral Artery Revascularization in patients With End-Stage Renal Disease: A Comparison of Vascular Closure Devices and Manual Compression.

OBJECTIVES: Manual compression (MC) or vascular closure devices (VCDs) are used to achieve hemostasis after percutaneous transluminal angioplasty (PTA). However, limited data on the comparative safety and effectiveness of VCDs vs MC in patients with end-stage renal disease (ESRD) undergoing PTA are available. Accordingly, this study compared the safety and effectiveness of VCD and MC in patients with ESRD undergoing PTA. METHODS: This single-center retrospective cohort study included the data of patients with ESRD undergoing peripheral intervention at Chang Gung Memorial Hospital, Taiwan, from January 1, 2019, to June 30, 2022. The patients were divided into VCD and MC groups. The primary endpoint was a composite of puncture site complications, including acute limb ischemia, marked hematoma, pseudoaneurysm, and puncture site bleeding requiring blood transfusion. RESULTS: We included 264 patients with ESRD undergoing PTA, of whom 60 received a VCD and 204 received MC. The incidence of puncture site complications was 3.3% in the VCD group and 4.4% in the MC group (hazard ratio: .75; 95% confidence interval: .16-3.56 L P = 1.000), indicating no significant between-group difference. CONCLUSION: VCDs and MC had comparable safety and effectiveness for hemostasis in patients with ESRD undergoing peripheral intervention.

Factors influencing health-related quality of life in women with endometriosis: A cross-sectional study.

This study aimed to assess the health-related quality of life and identify its associated factors in women with endometriosis. A cross-sectional correlation study design and convenience sampling were conducted in the gynecological outpatient clinic of a teaching hospital in northern Taiwan. A total of 216 women with endometriosis were recruited. The data were collected using structured questionnaires and analyzed using descriptive and inferential statistics. Participants reported a moderate level of health-related quality of life. The most significant impact of endometriosis on health-related quality of life was emotional well-being, followed by feeling of control or powerless, pain, social support, and self-image. Educational attainment, menstrual cycle, period length, perceived menstrual flow, symptom distress, and self-management strategies explained 66% of the variance in health-related quality of life. Factors influencing health-related quality of life in women with endometriosis play a key role in promoting women's well-being. Interventions based on these related factors should be developed and taken into practice to effectively manage the disease-related symptoms for women with endometriosis and thereby improve their overall health-related quality of life.

Factors related to sleep quality in hospitalized antepartum women: A cross-sectional study.

This study investigated the sleep quality and its psychological correlates among hospitalized antepartum women. A cross-sectional correlation study design and convenience sampling were conducted in the gynecological ward of a medical center in northern Taiwan. A total of 101 hospitalized antepartum women were recruited. A self-administered structured questionnaire including demographic profiles, State-Trait Anxiety Inventory (STAI), Antepartum Hospital Stressors Inventory (AHSI), and Pittsburgh Sleep Quality Index (PSQI) was used for the study. Bivariate and multiple linear regressions were used to analyze the data. A majority of the participants had poor sleep quality (82.8%), based on the global PSQI score. Sleep quality correlated with age, marital and employment status, parity, method of conception, multiple gestation, history of pregnant complications, anxiety symptom and hospital stressors which explained 21% of the variance in sleep quality. This study found a high prevalence of poor sleep quality in hospitalized antepartum women. Anxiety symptom was a significant predictor of sleep quality. Healthcare providers should be encouraged to assess sleep and emotional status in antepartum women during hospitalization and provide them appropriate interventions to improve sleep and reduce anxiety symptoms and hospital stressors.

Cette étude a examiné la qualité du sommeil et ses corrélats psychologiques chez les femmes hospitalisées en période antepartum. Une conception d'étude de corrélation transversale et un échantillonnage de commodité ont été menés dans le service de gynécologie d'un centre médical du nord de Taiwan. Au total, 101 femmes hospitalisées en période antepartum ont été recrutées. Un questionnaire structuré auto-administré comprenant des profils démographiques, l'inventaire des traits d'état d'anxiété (STAI), l'inventaire des facteurs de stress de l'hôpital avant l'accouchement (AHSI) et l'indice de qualité du sommeil de Pittsburgh (PSQI) a été utilisé pour l'étude. Des régressions linéaires bivariées et multiples ont été utilisées pour analyser les données. Une majorité des participants avaient un sommeil de mauvaise qualité (82,8 %), sur la base du score PSQI global. La qualité du sommeil était corrélée à l'âge, à la situation matrimoniale et professionnelle, à la parité, à la méthode de conception, aux grossesses multiples, aux antécédents de complications liées à la grossesse, aux symptômes d'anxiété et aux facteurs de stress hospitaliers, ce qui expliquait 21 % de la variance de la qualité du sommeil. Cette étude a révélé une prévalence élevée de mauvaise qualité du sommeil chez les femmes hospitalisées en période antepartum. Les symptômes d'anxiété étaient un prédicteur significatif de la qualité du sommeil. Les prestataires de soins de santé devraient être encouragés à évaluer le sommeil et l'état émotionnel des femmes antepartum pendant leur hospitalisation et à leur proposer des interventions appropriées pour améliorer le sommeil et réduire les symptômes d'anxiété et les facteurs de stress hospitaliers.

Rapid and highly potent humoral responses to mpox nanovaccine candidates adjuvanted by thermostable scaffolds.

Monkeypox (mpox) is a zoonotic disease caused by monkeypox virus (MPXV) of the orthopoxvirus genus. The emergence and global spread of mpox in 2022 was declared as a public health emergency by World Health Organization. This mpox pandemic alarmed us that mpox still threaten global public health. Live vaccines could be used for immunization for this disease with side effects. New alternative vaccines are urgently needed for this re-emerging disease. Specific antibody responses play key roles for protection against MPXV, therefore, vaccines that induce high humoral immunity will be ideal candidates. In the present study, we developed thermostable nanovaccine candidates for mpox by conjugating MPXV antigens with thermostable nanoscafolds. Three MPXV protective antigens, L1, A29, and A33, and the thermostable Aquafex aeolicus lumazine synthase (AaLS), were expressed in E. coli and purified by Ni-NTA methods. The nanovaccines were generated by conjugation of the antigens with AaLS. Thermal stability test results showed that the nanovaccines remained unchanged after one week storage under 37℃ and only partial degradation under 60℃, indicating high thermostability. Very interesting, one dose immunization with the nanovaccine could induce high potent antibody responses, and two dose induced 2-month high titers of antibodes. In vitro virus neutralization test showed that nanovaccine candidates induced significantly higher levels of neutralization antibodies than monomers. These results indicated that the AaLS conjugation nanovaccines of MPXV antigens are highly thermostable in terms of storage and antigenic, being good alternative vaccine candidates for this re-emerging disease.

Potent immune responses against thermostable Foot-and-Mouth disease virus VP1 nanovaccine adjuvanted with polymeric thermostable scaffold.

Foot-and-mouth disease (FMD) is an acute zoonosis causes significant economic losses. Vaccines able to stimulate efficient protective immune responses are urgently needed. In this study, Escherichia coli-derived recombinant VP1 of serotype A and O FMD virus (FMDV) was conjugated to thermostable scaffold lumazine synthase (LS) or Quasibacillus thermotolerans encapsulin (QtEnc) using a robust plug-and-display SpyTag/SpyCatcher system to generate multimeric nanovaccines. These nanovaccines induced highly potent antibody responses in vaccinated mice. On day 14 after the first immunisation, antibody titres were approximately 100 times higher than those of monomer antigens. Both vaccines induced high and long-term IgG antibody production. Moreover, the QtEnc-VP1 nanovaccine induced higher antibody titres than the LS-VP1 nanovaccine. The nanovaccines also induced Th1-biased immune responses and higher levels of neutralising antibodies. These data indicated that FMDV nanovaccines generated by conjugating VP1 with a thermostable scaffold are highly immunogenic and ideal candidates for FMDV control in low-resource areas.

Metagenomic next-generation sequencing of cell-free DNA for the identification of viruses causing central nervous system infections.

IMPORTANCE: This study provides significant new data on the application of metagenomic next-generation sequencing (mNGS) to clinical diagnostics of central nervous system (CNS) viral infections, which can have high mortality rates and severe sequelae. Conventional diagnostic procedures for identifying viruses can be inefficient and rely on preconceived assumptions about the pathogen, making mNGS an appealing alternative. However, the effectiveness of mNGS is affected by the presence of human DNA contamination, which can be minimized by using cell-free DNA (cfDNA) instead of whole-cell DNA (wcDNA). This multi-center retrospective study of patients with suspected viral CNS infection found that mNGS using cfDNA had a significantly lower proportion of human DNA and higher sensitivity for detecting viruses than mNGS using wcDNA. Herpesviruses, particularly VZV, were found to be the most common DNA viruses in these patients. Overall, mNGS using cfDNA is a promising complementary diagnostic method for detecting CNS viral infections.

Associated factors of sexual dysfunction among postpartum women in Taiwan- a cross-sectional study.

Sexual function among postpartum women is often overlooked by health-care professionals. This study aimed to investigate associated factors of sexual dysfunction among postpartum women. This study used a cross-sectional study design. A total of 135 postpartum women from a teaching hospital in northern Taiwan who met the inclusion criteria were recruited. SPSS version 22.0 was used to analyze data including descriptive and bivariate analysis. A multiple linear regression was using to identify the predictors of sexual dysfunction among Taiwanese postpartum women. Results indicated that the categories of sexual dysfunction that most commonly experienced in postpartum women were lack of sexual desire, delay or absence of orgasm, pain during intercourse, and inability to become physically aroused. Parity, types of delivery, perineal laceration, breastfeeding, postpartum fatigue, and postpartum depression were significantly associated with sexual dysfunction (p< .05). Sexual counseling and mental support should be necessary for women at risk of postpartum sexual problems such as nulliparous with perineal laceration, breastfeeding mothers, experiencing postpartum fatigue and depressive symptoms to improve their sexual health and quality of life.

La fonction sexuelle des femmes en post-partum est souvent négligée par les professionnels de la santé. Cette étude visait à étudier les facteurs associés au dysfonctionnement sexuel chez les femmes en post-partum. Cette étude a utilisé un plan d'étude transversal. Au total, 135 femmes en post-partum provenant d'un hôpital universitaire du nord de Taiwan et répondant aux critères d'inclusion ont été recrutées. SPSS version 22.0 a été utilisé pour analyser les données, y compris une analyse descriptive et bivariée. Une régression linéaire multiple était utilisée pour identifier les prédicteurs de dysfonctionnement sexuel chez les femmes taïwanaises en post-partum. Les résultats ont indiqué que les catégories de dysfonctionnement sexuel les plus fréquemment rencontrées chez les femmes en post-partum étaient le manque de désir sexuel, le retard ou l'absence d'orgasme, la douleur pendant les rapports sexuels et l'incapacité d'être physiquement excitée. La parité, les types d'accouchement, les lacérations périnéales, l'allaitement, la fatigue post-partum et la dépression post-partum étaient significativement associés à la dysfonction sexuelle (p < 0,05). Des conseils sexuels et un soutien mental devraient être nécessaires pour les femmes présentant un risque de problèmes sexuels post-partum, telles que les nullipares présentant une lacération périnéale, les mères allaitantes, les femmes souffrant de fatigue post-partum et de symptômes dépressifs, afin d'améliorer leur santé sexuelle et leur qualité de vie.

Comparative Effectiveness of Olive Oil and Breast Milk on Nipple Soreness in Breastfeeding Mothers.

Background: Breastfeeding has health benefits for both mothers and children. Nipple problems may result in the child being weaned prematurely before the recommended 6 months minimum period of exclusive breastfeeding. Purposes of the Study: The study aimed to compare the effectiveness of topically applying olive oil and breast milk in treating nipple pain and soreness in breastfeeding mothers during the early postpartum period. Methods: A quasi-randomized controlled trial was conducted in a maternity ward of a medical center in northern Taiwan. Eighty breastfeeding mothers were recruited, and randomly assigned to the olive oil or breast milk group. Visual analogue pain scale (intensity of nipple pain) and nipple soreness scores were collected at 24, 48, and 72 hours after delivery. Differences in postintervention outcomes between groups were examined using the Generalized Estimating Equation model. Results: The results indicated that both olive oil and breast milk groups reported a significant increase in the intensity of nipple pain and nipple soreness at 24, 48, and 72 hours after delivery. However, differences in the outcome measurements between olive oil and breast milk groups were statistically insignificant at p-value >0.05. Conclusion: This study found that olive oil had similar effects on nipple pain and soreness to breast milk. In addition, most breastfeeding mothers provided positive feedback on using olive oil. Olive oil can be a safe, accessible, and alternative choice for breastfeeding mothers in treating nipple pain and soreness, especially early in the breastfeeding period. The Clinical Trail Registration Number: NCT03568370.

Comparison of long-term outcomes of complete vs. incomplete revascularization in elderly patients (≥75 years) with acute coronary syndrome and multi-vessel disease undergoing percutaneous coronary intervention.

Background: The optimal revascularization strategy for elderly patients with acute coronary syndrome (ACS) remains uncertain. We evaluated the impact of complete revascularization (CR) vs. incomplete revascularization (IR) in elderly ACS patients with multivessel disease (MVD) undergoing percutaneous coronary intervention (PCI). Methods: Using registry data from 2011 to 2019, we conducted a propensity-score matched cohort study. Elderly patients (≥75 years) with ACS and MVD who underwent PCI were divided into CR and IR groups based on angiography during index hospitalization. Major adverse cardiovascular events (MACEs), including all-cause mortality, recurrent non-fatal myocardial infarction, and any revascularization, were assessed at 3-year follow-up. Results: Among 1,018 enrolled patients, 496 (48.7%) underwent CR and 522 (51.3%) received IR. After 1:1 propensity-score matching, we analyzed 395 pairs. At 3-year follow-up, CR was significantly associated with lower MACE risk compared to IR (16.7% vs. 25.6%, HR = 0.65, 95% CI: 0.47-0.88, p = 0.006), driven by reduced all-cause mortality. This benefit was consistent across all pre-specified subgroups, particularly in ST segment elevation (STE)-ACS patients. In non-STE (NSTE)-ACS subgroup analysis, CR was also associated with a lower risk of cardiac mortality compared to IR (HR = 0.30, 95% CI: 0.12-0.75, p = 0.01). Conclusion: In elderly ACS patients with MVD undergoing PCI, CR demonstrates superior long-term outcomes compared to IR, irrespective of STE- or NSTE-ACS presentation.

T Cell Activating Thermostable Self-Assembly Nanoscaffold Tailored for Cellular Immunity Antigen Delivery.

Antigen delivery based on non-virus-like particle self-associating protein nanoscffolds, such as Aquifex aeolicus lumazine synthase (AaLS), is limited due to the immunotoxicity and/or premature clearance of antigen-scaffold complex resulted from triggering unregulated innate immune responses. Here, using rational immunoinformatics prediction and computational modeling, we screen the T epitope peptides from thermophilic nanoproteins with the same spatial structure as hyperthermophilic icosahedral AaLS, and reassemble them into a novel thermostable self-assembling nanoscaffold RPT that can specifically activate T cell-mediated immunity. Tumor model antigen ovalbumin T epitopes and the severe acute respiratory syndrome coronavirus 2 receptor-binding domain are loaded onto the scaffold surface through the SpyCather/SpyTag system to construct nanovaccines. Compared to AaLS, RPT -constructed nanovaccines elicit more potent cytotoxic T cell and CD4+ T helper 1 (Th1)-biased immune responses, and generate less anti-scaffold antibody. Moreover, RPT significantly upregulate the expression of transcription factors and cytokines related to the differentiation of type-1 conventional dendritic cells, promoting the cross-presentation of antigens to CD8+ T cells and Th1 polarization of CD4+ T cells. RPT confers antigens with increased stability against heating, freeze-thawing, and lyophilization with almost no antigenicity loss. This novel nanoscaffold offers a simple, safe, and robust strategy for boosting T-cell immunity-dependent vaccine development.

Ultrasensitive optical modulation in hybrid metal-perovskite and metal-graphene metasurface THz devices.

Implementation of efficient terahertz (THz) wave control is essential for THz technology development for applications including sixth-generation communications and THz sensing. Therefore, realization of tunable THz devices with large-scale intensity modulation capabilities is highly desirable. By integrating perovskite and graphene with a metallic asymmetric metasurface, two ultrasensitive devices for dynamic THz wave manipulation through low-power optical excitation are demonstrated experimentally here. The perovskite-based hybrid metadevice offers ultrasensitive modulation with a maximum modulation depth for the transmission amplitude reaching 190.2% at the low optical pump power of 5.90 mW/cm2. Additionally, a maximum modulation depth of 227.11% is achieved in the graphene-based hybrid metadevice at a power density of 18.87 mW/cm2. This work paves the way toward design and development of ultrasensitive devices for optical modulation of THz waves.

Isoorientin ameliorates H2O2-induced apoptosis and oxidative stress in chondrocytes by regulating MAPK and PI3K/Akt pathways.

Osteoarthritis (OA) is a chronic and complicated degenerative disease for which there is currently no effective treatment. Isoorientin (ISO) is a natural plant extract that has antioxidant activity and could be used to treat OA. However, due to a lack of research, it has not been widely used. In this study, we investigated the protective effects and molecular mechanisms of ISO on H2O2-induced chondrocytes, a widely used cell model for OA. Based on RNA-seq and bioinformatics, we discovered that ISO significantly increased the activity of chondrocytes induced by H2O2, which was associated with apoptosis and oxidative stress. Furthermore, the combination of ISO and H2O2 significantly reduced apoptosis and restored mitochondrial membrane potential (MMP), which may be achieved by inhibiting apoptosis and mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, ISO increased superoxide dismutase (SOD), heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO-1) and reduced malondialdehyde (MDA) levels. Finally, ISO inhibited H2O2-induced intracellular reactive oxygen species (ROS) in chondrocytes by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathways. This study establishes a theoretical framework for ISO's ability to inhibit OA in vitro models.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Metformin attenuates sevoflurane-induced neurogenesis damage and cognitive impairment: involvement of the Nrf2/G6PD pathway.

Anesthetics such as sevoflurane are commonly administered to infants and children. However, the possible neurotoxicity caused by prolonged or repetitive exposure to it should be a concern. The neuroprotective effects of metformin are observed in many models of neurological disorders. In this study, we investigated whether metformin could reduce the developmental neurotoxicity induced by sevoflurane exposure in neonatal rats and the potential mechanism. Postnatal day 7 (PND 7) Sprague-Dawley rats and neural stem cells (NSCs) were treated with normal saline or metformin before sevoflurane exposure. The Morris water maze (MWM) was used to observe spatial memory and learning at PND 35-42. Immunofluorescence staining was used to detect neurogenesis in the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus at PND 14. MTT assays, immunofluorescence staining, and TUNEL staining were used to assess the viability, proliferation, differentiation, and apoptosis of NSCs. Western blotting and ELISA were used to assess the protein expression of cleaved caspase-3, nuclear factor erythroid 2-related factor 2 (Nrf2), and glucose-6-phosphate dehydrogenase (G6PD) pathway-related molecules. Exposure to sevoflurane resulted in late cognitive defects, impaired neurogenesis in both the SVZ and SGZ, reduced NSC viability and proliferation, increased NSC apoptosis, and decreased protein expression of G6PD in vitro. Metformin pretreatment attenuated sevoflurane-induced cognitive functional decline and neurogenesis inhibition. Metformin pretreatment also increased the protein expression of Nrf2 and G6PD. However, treatment with the Nrf2 inhibitor, ML385 or the G6PD inhibitor, dehydroepiandrosterone (DHEA) reversed the protective effect of metformin on sevoflurane-induced NSC damage in vitro. Our findings suggested that metformin could reduce sevoflurane-induced neurogenesis damage and neurocognitive defects in the developing rat brain by influencing the Nrf2/G6PD signaling pathways.

Selected ssDNA aptamers-graphene oxide-based fluorescent biosensor to detect sulfameter in milk.

The abuse of sulfameter (SME) in animal husbandry can cause drug resistance and toxic or allergic reactions in humans. Therefore, it is very important to establish a simple, inexpensive, and efficient method for detecting SME in food. In this work, we propose a single fluorescent aptamer/graphene oxide (GO)-based biosensor to detect SME residues in milk. Aptamers that specifically bind to SME were screened using capture-SELEX and a ssDNA library immobilized on magnetic beads. The 68 active candidate aptamers were chemically synthesized for specificity and affinity characterization. Among the aptamers, the aptamer sulf-1 revealed the highest affinity (Kd = 77 ± 15 nM) to SME and was selected to construct a GO-based fluorescent biosensor for real milk sample detection. Under optimal conditions, the single fluorescent aptasensor had a wide linear range (R2 was 0.997) from 7 to 336 ng/ml and a low detection limit of 3.35 ng/ml that was calculated with a 3SD/slope. The single fluorescent method was also validated using SME-fortified milk samples, showing average recoveries ranging from 99.01% to 104.60% with a relative standard deviation of less than 3.88%. These results demonstrate that this novel aptamer sensor provides an opportunity for sensitive, convenient, and accurate detection of SME residues in milk.

A Multivalent and Thermostable Nanobody Neutralizing SARS-CoV-2 Omicron (B.1.1.529).

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants have risen to dominance, which contains far more mutations in the spike protein in comparison to previously reported variants, compromising the efficacy of most existing vaccines or therapeutic monoclonal antibodies. Nanobody screened from high-throughput naïve libraries is a potential candidate for developing preventive and therapeutic antibodies. Methods: Four nanobodies specific to the SARS-CoV-2 wild-type receptor-binding domain (RBD) were screened from a naïve phage display library. Their affinity and neutralizing activity were evaluated by surface plasmon resonance assays, surrogate virus neutralization tests, and pseudovirus neutralization assays. Preliminary identification of the binding epitopes of nanobodies by peptide-based ELISA and competition assay. Then four multivalent nanobodies were engineered by attaching the monovalent nanobodies to an antibody-binding nanoplatform constructed based on the lumazine synthase protein cage nanoparticles isolated from the Aquifex aeolicus (AaLS). Finally, the differences in potency between the monovalent and multivalent nanobodies were compared using the same methods. Results: Three of the four specific nanobodies could maintain substantial inhibitory activity against the Omicron (B.1.1.529), of them, B-B2 had the best neutralizing activity against the Omicron (B.1.1.529) pseudovirus (IC50 = 1.658 µg/mL). The antiviral ability of multivalent nanobody LS-B-B2 was improved in the Omicron (B.1.1.529) pseudovirus assays (IC50 = 0.653 µg/mL). The results of peptide-based ELISA indicated that LS-B-B2 might react with the linear epitopes in the SARS-CoV-2 RBD conserved regions, which would clarify the mechanisms for the maintenance of potent neutralization of Omicron (B.1.1.529) preliminary. Conclusion: Our study indicated that the AaLS could be used as an antibody-binding nanoplatform to present nanobodies on its surface and improve the potency of nanobodies. The multivalent nanobody LS-B-B2 may serve as a potential agent for the neutralization of SARS-CoV-2 variants.

Driving effect of multiplex factors on human brucellosis in high incidence region, implication for brucellosis based on one health concept.

Brucellosis is a typical zoonosis driven by various risk factors, including environmental ones. The present study aimed to explore the driving effect of environmental factors on human brucellosis in a high incidence rate area, which provides understanding and implications in mitigating disease transmission risk in a multi-system between the human-animal-environment interface for preventing and controlling brucellosis based on the One Health concept. Based on the monthly time series data of human brucellosis and environmental variables, a Seasonal Autoregressive Integrated Moving Average Model with explanatory variables (SARIMAX) was applied to assess the association between environmental indicators and human brucellosis incidence (IHB). The results indicated distinct seasonal fluctuation during the study duration, tending to climb from April to August. Atmospheric pressure, precipitation, relative humidity, mean temperature, sunshine duration, and normalized difference vegetation index significantly drive IHB. Moreover, the well-fitting and predicting capability were performed and assessed in the optimal model was the SARIMAX (0,1,1) (0,1,1)12 model with the normalized difference vegetation index (ß = 0.349, P = 0.036) and mean temperature (ß = 0.133, P = 0.046) lagged in 6 months, and the precipitation lagged in 1 month (ß = -0.090, P = 0.004). Our study suggests the association between environmental risk factors and human brucellosis infection, which can be contributed to mitigating the transmission risk in the environmental drivers in a multi-system interface through comprehensive prevention and intervention strategies based on the One Health concept.

Comparisons in the changes of clinical characteristics and cerebrospinal fluid cytokine profiles between varicella-zoster virus meningitis/encephalitis and other central nervous system infections. / 水痘-å¸¦çŠ¶ç–±ç–¹ç— æ¯’è„‘è†œç‚Ž/è„‘ç‚Žä¸Žå ¶ä»–ä¸­æž¢ç¥žç»ç³»ç»Ÿæ„ŸæŸ“çš„ä¸´åºŠç‰¹å¾å’Œè„‘è„Šæ¶²ç»†èƒžå› å­æ¯”è¾ƒï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Varicella-zoster virus (VZV) is one of the most common etiologies of viral meningitis/encephalitis. The early clinical manifestations and cerebrospinal fluid (CSF) changes of VZV meningitis/encephalitis lack specificity, and it is easy to be misdiagnosed as other viral encephalitides or tuberculous meningitis. This study aims to investigate whether the clinical characteristics, CSF analysis findings, and CSF cytokine levels could distinguish VZV meningitis/encephalitis from central nervous system (CNS) herpes simplex virus (HSV) and Mycobacterium tuberculosis (MTB) infections. METHODS: The medical records from 157 CNS infections, including 49 HSV (45 HSV-1, 4 HSV-2), 55 VZV, and 53 MTB infections between January 2018 and June 2021 in the Cytology Laboratory, Department of Neurology, Third Xiangya Hospital of Central South University were retrospectively reviewed. The data of 3 groups included demographic characteristics, laboratory results, radiographic findings, and outcomes. The levels of 12 cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, IFN-γ, IFN-α, and TNF-α) in the CSF of 68 patients (13 HSV, 22 VZV, and 33 MTB infection cases) were quantified. Clinical and laboratory data were compared among the 3 groups. RESULTS: The most common clinical manifestations in the 3 groups were fever, headache, vomiting, and neck stiffness. The clinical manifestations of HSV and VZV CNS disease were similar, although fever and altered consciousness were less common in the VZV group than those in the HSV and MTB groups (63.6% vs 87.8% vs 96.2%, P<0.001, and 14.5% vs 26.5% vs 47.2%, P=0.004, respectively). Seven patients (7/55, 12.7%) presented cutaneous zoster in the VZV group. CSF leukocyte count was significantly higher in the VZV group (230×106 cells/mL) and MTB groups (276×106 cells/mL) than that in the HSV group (87×106 cells/mL, P=0.002). CSF protein level was significantly higher in the VZV than that in the HSV group (1 034 mg/L vs 694 mg/L, P=0.011) but lower than that in the MTB group (1 744 mg/L, P<0.001). IL-6 (VZV vs HSV vs MTB: 2 855.93 pg/mL vs 2 128.26 pg/mL vs 354.77 pg/mL, P=0.029) and IL-8 (VZV vs HSV vs MTB: 4 001.46 pg/mL vs 1 578.11 pg/mL vs 1 023.25 pg/mL, P=0.046) levels were significantly different among the 3 groups and were elevated in the VZV group.Post hoc analysis revealed that IL-6 and IL-8 were significantly higher in the VZV group than those in the MTB group (P=0.002 and P=0.035, respectively), but not in the HSV group (P>0.05). CONCLUSIONS: VZV meningitis/encephalitis presents with CSF hypercellularity and proteinemia, challenging the classical view of CSF profiles in viral encephalitis. CSF IL-6 and IL-8 levels are elevated in patients with VZV meningitis/encephalitis, indicating a more intense inflammatory response in these patients.