Eggplant NAC domain transcription factor SmNST1 as an activator promotes secondary cell wall thickening.

NAC-domain transcription factors (TFs) are plant-specific transcriptional regulators playing crucial roles in plant secondary cell wall (SCW) biosynthesis. SCW is important for plant growth and development, maintaining plant morphology, providing rigid support, ensuring material transportation and participating in plant stress responses as a protective barrier. However, the molecular mechanisms underlying SCW in eggplant have not been thoroughly explored. In this study, the NAC domain TFs SmNST1 and SmNST2 were cloned from the eggplant line 'Sanyue qie'. SmNST1 and SmNST2 expression levels were the highest in the roots and stems. Subcellular localization analysis showed that they were localized in the cell membrane and nucleus. Their overexpression in transgenic tobacco showed that SmNST1 promotes SCW thickening. The expression of a set of SCW biosynthetic genes for cellulose, xylan and lignin, which regulate SCW formation, was increased in transgenic tobacco. Bimolecular fluorescence and luciferase complementation assays showed that SmNST1 interacted with SmNST2 in vivo. Yeast one-hybrid, electrophoretic mobility shift assay (EMSA) and Dual-luciferase reporter assays showed that SmMYB26 directly bound to the SmNST1 promoter and acted as an activator. SmNST1 and SmNST2 interact with the SmMYB108 promoter and repress SmMYB108 expression. Altogether, we showed that SmNST1 positively regulates SCW formation, improving our understanding of SCW biosynthesis transcriptional regulation.

Refractory lupus hepatitis successfully treated with telitacicept who failed to belimumab: A case report and literature review.

Background: Systemic lupus erythematosus (SLE)-associated hepatitis ("lupus hepatitis") was one of the most frequent causes of liver function abnormalities in patients with SLE. Lupus hepatitis (LH) is commonly treated with conventional treatment, including non-steroidal anti-inflammatory drugs, corticosteroids, and immunomodulators. However, in refractory cases, other treatment options may be required.Methodology: We report the case of a patient with lupus hepatitis refractory to both conventional therapy and belimumab who was successfully treated with telitacicept, a new dual B lymphocyte stimulator (BLyS)/APRIL (a proliferation-inducing ligand) inhibitor.Literature review was performed on PubMed search forum.Result: The specific search term was "telitacicept", 23 papers were searched, among them 10 case reports/series articles reporting telitacicept treatment were elected.Apart from our literature reporting the effectiveness of telitacicept in treating LH, there is no report on it in treating LH.Conclusion: This case suggests that telitacicept should be an effective and safe treatment for LH refractory, even to those who failed to belimumab based on the standard treatment, and can reduce the dosage of glucocorticoids.However, further investigations, particularly prospective randomized controlled trials, are warranted to verify our findings and ensure patient safety.

Dengue encephalopathy in an adult due to dengue virus type 1 infection.

BACKGROUND: Dengue is an important public health problem, which caused by the dengue virus (DENV), a single-stranded RNA virus consisted of four serotypes. Central nervus system (CNS) impairment in dengue usually results from DENV-2 or DENV-3 infection, which lead to life-threatening outcomes. Furthermore, neurological complications due to DENV-1 was rare especially in adult patients. CASE PRESENTATION: A 44-year-old man without comorbidities had lethargy after hyperpyrexia and a positive DENV NS1 antigen was detected for confirming the diagnosis of dengue on day 8 of onset. Then logagnosia, decreased muscle strength, delirium and irritability were occurred even radiographic examination were normal. He was treated with low-dose hormone, sedatives and gamma goblin with a short duration of 6 days. The cerebrospinal fluid (CSF) tests were persistent normal. However, presence of DENV-1 RNA was confirmed both in CSF and serum. Furthermore, the complete sequence of the DENV isolated from the patient's serum was performed (GenBank No.: MW261838). The cytokines as IL-6, IL-10 and sVCAM-1 were increased in critical phase of disease. Finally, the patient was discharged on day 24 of onset without any neurological sequelae. CONCLUSION: Encephalopathy caused by a direct CNS invasion due to DENV-1 during viremia was described in an adult patient. Treatment with low-dose hormone and gamma goblin was helpful for admission.

Development of a TLR-Based Model That Can Predict Prognosis, Tumor Microenvironment, and Drug Response for Esophageal Squamous Cell Carcinoma.

The toll-like receptor (TLR) family is an important class of proteins involved in the immune response. However, little is known about the association between TLRs and Esophageal squamous cell cancer (ESCC). We explored differentially expressed genes (DEGs) between ESCC and esophagus tissues in TCGA and GTEx database. By taking the intersection with TLR gene set and using univariate Cox analysis and multivariate Cox regression analysis to discriminate the hub genes, we created a TLR-prognostic model. Our model separated patients with ESCC into high- and low-risk score (RS) groups. Prognostic analysis was performed with Kaplan-Meier curves. The two groups were also compared regarding tumor immune microenvironment and drug sensitivity. Six hub genes (including CD36, LGR4, MAP2K3, NINJ1, PIK3R1, and TRAF3) were screened to construct a TLR-prognostic model. High-RS group had a worse survival (p < 0.01), lower immune checkpoint expression (p < 0.05), immune cell abundance (p < 0.05) and decreased sensitivity to Epirubicin (p < 0.001), 5-fluorouracil (p < 0.0001), Sorafenib (p < 0.01) and Oxaliplatin (p < 0.05). We constructed a TLR-based model, which could be used to assess the prognosis of patients with ESCC, provide new insights into drug treatment for ESCC patients and investigate the TME and drug response.

Safety and efficacy of telitacicept in refractory systemic lupus erythematosus patients who failed treatment with belimumab : A case series.

OBJECTIVE: This study aimed to determine the effect and safety of telitacicept, an antagonist of BLyS/APRIL-mediated B cell activation, in patients with systemic lupus erythematosus (SLE) who failed treatment with belimumab and in whom telitacicept was administered combined with conventional therapy. A review of published reports on telitacicept for SLE was also performed. METHODS: A retrospective review was performed of the records of patients seen in the Department of Rheumatology at the Wuhan Hospital of Chinese and Western Medicine, Wuhan, China, with refractory SLE who had failed treatment with belimumab. The terms "systemic lupus erythematosus" and "telitacicept" were used to identify patients reported in the English medical literature. RESULTS: Identified were 14 refractory SLE patients, 3 males (21%) and 11 females (79%). The median age was 32.9 years. The median disease duration was 8.9 years. Patients in this cohort received telitacicept for an average of 34.1 weeks (17-62 weeks) and the total SLE responder index 4 (SRI-4) response rate was 78.9% (n = 11). The mean SLE Disease Activity Index (SLEDAI) score declined from 8.6 at baseline (95% confidence interval [CI] 7.87-9.28) to 4.29 at the endpoint (95% CI 3.4-5.16). All cases (100%) had hypocomplementemia at baseline, and 7 cases (50%) reported normal C3 and C4 levels at the follow-up endpoint. At the observation endpoint, the 24­h urinary protein value of the 13 cases with proteinuria (baseline 24­h urinary protein > 0.5 g/d) displayed a reduction, and 3 values turned negative. Although some patients had low serum total immunoglobulin (Ig) levels, subnormal IgG levels, and absolute counts of peripheral blood lymphocytes after treatment, no serious infection was reported. One case was refractory lupus hepatitis confirmed by liver pathology, and upon change to change to telitacicept treatment, liver function returned to normal. CONCLUSION: This is the first case series in SLE patients who accepted telitacicept treatment after failed treatment with belimumab. Our case series and review of the literature show that telitacicept combined with the original standard treatment may significantly improve disease activity while reducing prednisone use. No major safety issues were seen in this group of patients. Telitacicept may be a promising drug for the treatment of refractory lupus hepatitis.

Association between dietary intake of α-tocopherol and cadmium related osteoporosis in population ≥ 50 years.

INTRODUCTION: To analyze the association between α-tocopherol intake and cadmium (Cd) exposure and osteoporosis in population ≥ 50 years. MATERIALS AND METHODS: Sociodemographic data, physical examination, and laboratory indicators including serum Cd level and dietary α-tocopherol intake of 8459 participants were extracted from the National Health and Nutrition Examination Survey (NHANES) database in this cross-sectional study. The associations between α-tocopherol intake, serum Cd levels and osteoporosis were evaluated using univariate and multivariate logistic regression analyses, with the estimated value (ß), odds ratios (ORs) and 95% confidence intervals (CIs). We further explored the impact of α-tocopherol intake on Cd exposure and the bone mineral density (BMD) in total femur and femur neck. RESULTS: A total of 543 old adults suffered from osteoporosis. The serum Cd level (0.52 µg/L vs. 0.37 µg/L) and α-tocopherol intake (5.28 mg vs. 6.50 mg) were statistical different in osteoporosis group and non-osteoporosis group, respectively. High level of Cd exposure was related to the increased risk of osteoporosis [OR = 1.60, 95% CI (1.15-2.21)]. In the total femur, α-tocopherol intake may improve the loss of BMD that associated with Cd exposure [ß = - 0.047, P = 0.037]. Moreover, high α-tocopherol intake combined with low Cd exposure [OR = 0.54, 95% CI (0.36-0.81)] was linked to the decreased risk of osteoporosis comparing with low α-tocopherol intake combined with high Cd exposure. CONCLUSION: High α-tocopherol intake may improve the Cd-related osteoporosis and loss of BMD that could provide some dietary reference for prevention of osteoporosis in population ≥ 50 years old.

Validation of pre-operative risk scores of contrast-induced acute kidney injury in a Chinese cohort.

BACKGROUND: Pre-operative risk scores are more valuable than post-procedure risk scores because of lacking effective treatment for contrast-induced acute kidney injury (CI-AKI). A number of pre-operative risk scores have been developed, but due to lack of effective external validation, most of them are also difficult to apply accurately in clinical practice. It is necessary to review and validate the published pre-operative risk scores for CI-AKI. MATERIALS AND METHODS: We systematically searched PubMed and EMBASE databases for studies of CI-AKI pre-operative risk scores and assessed their calibration and discriminatory in a cohort of 2669 patients undergoing coronary angiography or percutaneous coronary intervention (PCI) from September 2007 to July 2017. The definitions of CI-AKI may affect the validation results, so three definition were included in this study, CI-AKI broad1 was defined as an increase in serum creatinine (Scr) of 44.2 µmol/L or 25%; CI-AKI broad2, an increase in Scr of 44.2 µmol/L or 50%; and CI-AKI-narrow, an increase in Scr of 44.2 µmol/L. The calibration of the model was assessed with the Hosmer-Lemeshow test and the discriminatory capacity was identified by C-statistic. RESULTS: Of the 8 pre-operative risk scores for CI-AKI identified, 7 were single-center study and only 1 was based on multi-center study. In addition, 7 of the scores were just validated internally and only Chen score was externally validated. In the validation cohort of 2669 patients, the incidence of CI-AKI ranged from 3.0%(Liu) to 16.4%(Chen) for these scores. Furthermore, the incidence of CI-AKI was 6.59% (178) for CI-AKI broad1, 1.44% (39) for CI-AKI broad2, and 0.67% (18) for CI-AKI-narrow. For CI-AKI broads, C-statistics varied from 0.44 to 0.57. For CI-AKI-narrow, the Maioli score had the best discrimination and calibration, what's more, the C-statistics of Maioli, Chen, Liu and Ghani was ≥0.7. CONCLUSION: Most pre-operative risk scores were established based on single-center studies and most of them lacked external validation. For CI-AKI broads, the prediction accuracy of all risk scores was low. The Maioli score had the best discrimination and calibration, when using the CI-AKI-narrow definition.

High-throughput, non-invasive prenatal testing for fetal rhesus D status in RhD-negative women: a systematic review and meta-analysis.

BACKGROUND: High-throughput non-invasive prenatal testing (NIPT) for fetal Rhesus D (RhD) status could avoid unnecessary treatment with anti-D immunoglobulin for RhD-negative women found to be carrying an RhD-negative fetus. We aimed to assess the diagnostic accuracy of high-throughput NIPT for fetal RhD status in RhD-negative women not known to be sensitized to the RhD antigen, by performing a systematic review and meta-analysis. METHODS: Prospective cohort studies of high-throughput NIPT used to determine fetal RhD status were included. The eligible population were pregnant women who were RhD negative and not known to be sensitized to RhD antigen. The index test was high-throughput, NIPT cell-free fetal DNA tests of maternal plasma used to determine fetal RhD status. The reference standard considered was serologic cord blood testing at birth. Databases including MEDLINE, EMBASE, and Science Citation Index were searched up to February 2016. Two reviewers independently screened titles and abstracts and assessed full texts identified as potentially relevant. Risk of bias was assessed using QUADAS-2. The bivariate and hierarchical summary receiver-operating characteristic (HSROC) models were fitted to calculate summary estimates of sensitivity, specificity, false positive and false negative rates, and the associated 95% confidence intervals (CIs). RESULTS: A total of 3921 references records were identified through electronic searches. Eight studies were included in the systematic review. Six studies were judged to be at low risk of bias. The HSROC models demonstrated high diagnostic performance of high-throughput NIPT testing for women tested at or after 11 weeks gestation. In the primary analysis for diagnostic accuracy, women with an inconclusive test result were treated as having tested positive. The false negative rate (incorrectly classed as RhD negative) was 0.34% (95% CI 0.15 to 0.76) and the false positive rate (incorrectly classed as RhD positive) was 3.86% (95% CI 2.54 to 5.82). There was limited evidence for non-white women and multiple pregnancies. CONCLUSIONS: High-throughput NIPT is sufficiently accurate to detect fetal RhD status in RhD-negative women and would considerably reduce unnecessary treatment with routine anti-D immunoglobulin. The applicability of these findings to non-white women and women with multiple pregnancies is uncertain.

Analysis on the treatment and prevention of epidemic conjunctivitis in 108 cases.

To explore the treatment method and preventive measures on epidemic keratoconjunctivitis. 108 patients with epidemic keratoconjunctivitis who received treatment in our hospital from January, 2015 to September, 2015.were selected. These patients were treated with interferon eye drops, Ganciclovir ophthalmic gel, and alternating eye treatment of tobramycin-dexamethasone eye drops and diclofenac sodium eye drops. Meanwhile, health education was also performed among patients, so as to promote the recovery of the disease as soon as possible and to prevent the spread of the disease Among the 108 patients, there were 101 patients recovered. 7 patients had cornea remained sub epithelial round hoary haze, including 2 patients with evident cornea remained sub epithelial round hoary haze due to the occurrence of glucocorticoid-induced intraocular pressure and the tobramycin and dexamethasone eye drops were suspend. The clinical cure rate was 91.79%. There was no pathophoresis to health patients among the 108 patients. Active treatment of epidemic keratoconjunctivitis, combined with health education and publicity could increase the clinical cure rate and control the transmit of the disease spread.

Capturing judgement strategies in risk assessments with improved quality of clinical information: How nurses' strategies differ from the ecological model.

BACKGROUND: Nurses' risk assessments of patients at risk of deterioration are sometimes suboptimal. Advances in clinical simulation mean higher quality information can be used as an alternative to traditional paper-based approaches as a means of improving judgement. This paper tests the hypothesis that nurses' judgement strategies and policies change as the quality of information used by nurses in simulation changes. METHODS: Sixty-three student nurses and 34 experienced viewed 25 paper-case based and 25 clinically simulated scenarios, derived from real cases, and judged whether the (simulated) patient was at 'risk' of acute deterioration. Criteria of judgement "correctness" came from the same real cases. Information relative weights were calculated to examine judgement policies of individual nurses. Group comparisons of nurses and students under both paper and clinical simulation conditions were undertaken using non parametric statistical tests. Judgment policies were also compared to the ecological statistical model. Cumulative relative weights were calculated to assess how much information nurses used when making judgements. Receiver operating characteristic (ROC) curves were generated to examine predictive accuracy amongst the nurses. RESULTS: There were significant variations between nurses' judgement policies and those optimal policies determined by the ecological model. Nurses significantly underused the cues of consciousness level, respiration rate, and systolic blood pressure than the ecological model requires. However, in clinical simulations, they tended to make appropriate use of heart rate, with non-significant difference in the relative weights of heart rate between clinical simulations and the ecological model. Experienced nurses paid substantially more attention to respiration rate in the simulated setting compared to paper cases, while students maintained a similar attentive level to this cue. This led to a non-significant difference in relative weights of respiration rate between experienced nurses and students. CONCLUSIONS: Improving the quality of information by clinical simulations significantly impacted on nurses' judgement policies of risk assessments. Nurses' judgement strategies also varied with the increased years of experience. Such variations in processing clinical information may contribute to nurses' suboptimal judgements in clinical practice. Constructing predictive models of common judgement situations, and increasing nurses' awareness of information weightings in such models may help improve judgements made by nurses.

Do nurses reason 'adaptively' in time limited situations: the findings of a descriptive regression analysis.

BACKGROUND: Time pressure is common in acute healthcare and significantly influences clinical judgement and decision making. Despite nurses' judgements being studied since the 1960s, the empirical picture of how time pressure impacts on nurses' judgement strategies and outcomes remain undeveloped. This paper aims to assess alterations in nurses' judgement strategies and outcomes under time pressure in a simulated acute care setting. METHODS: In a simulated acute care environment, ninety-seven nurses were exposed to 25 clinical scenarios under time pressured and no time pressured conditions. Scenarios were randomly sampled from a large dataset of patient cases. A reference standard (judgement correctness) was generated from the same patient case records. In 12 of the scenarios only 20 seconds per judgement was allowed, in the other 13 scenarios no time pressure existed. Percentage of correct judgments in both conditions was calculated. Logistic regression modelling (of 2,425 observations) described the relationship between information cues used and judgments made. The degree of attention paid to particular cues was captured by calculating cue relative weights. The clustering effect of nurses was countered by estimating robust standard errors. The Chow test was used to test the null hypothesis that differences in regression coefficients in time pressure and no time pressure models were zero. RESULTS: Compared to no time pressure, no significant difference was observed in the proportion of correct judgments when nurses were put under time pressure. However, time pressure significantly impacted on the judgment strategies employed. Whilst nurses predominantly used respiration rate to make judgements, they used fewer cues to reach their clinical judgements under time pressure. The relative weighting afforded to heart rate was much smaller in the time pressure regression model, indicating that nurses paid significantly less attention to it when making judgements under time pressure. CONCLUSIONS: Time pressure had a significant effect on nurses' judgement strategies but not outcomes. Nurses tended to use less information to reach judgements under time pressure, but not at the expense of judgment accuracy. Findings imply that nurses are capable of using adaptive judgement strategies to cope with moderate time pressures when making clinical judgements in acute care.

Identifying and enhancing risk thresholds in the detection of elder financial abuse: a signal detection analysis of professionals' decision making.

BACKGROUND: Financial abuse of elders is an under acknowledged problem and professionals' judgements contribute to both the prevalence of abuse and the ability to prevent and intervene. In the absence of a definitive "gold standard" for the judgement, it is desirable to try and bring novice professionals' judgemental risk thresholds to the level of competent professionals as quickly and effectively as possible. This study aimed to test if a training intervention was able to bring novices' risk thresholds for financial abuse in line with expert opinion. METHODS: A signal detection analysis, within a randomised controlled trial of an educational intervention, was undertaken to examine the effect on the ability of novices to efficiently detect financial abuse. Novices (n = 154) and experts (n = 33) judged "certainty of risk" across 43 scenarios; whether a scenario constituted a case of financial abuse or not was a function of expert opinion. Novices (n = 154) were randomised to receive either an on-line educational intervention to improve financial abuse detection (n = 78) or a control group (no on-line educational intervention, n = 76). Both groups examined 28 scenarios of abuse (11 "signal" scenarios of risk and 17 "noise" scenarios of no risk). After the intervention group had received the on-line training, both groups then examined 15 further scenarios (5 "signal" and 10 "noise" scenarios). RESULTS: Experts were more certain than the novices, pre (Mean 70.61 vs. 58.04) and post intervention (Mean 70.84 vs. 63.04); and more consistent. The intervention group (mean 64.64) were more certain of abuse post-intervention than the control group (mean 61.41, p = 0.02). Signal detection analysis of sensitivity (A´) and bias (C) revealed that this was due to the intervention shifting the novices' tendency towards saying "at risk" (C post intervention -.34) and away from their pre intervention levels of bias (C-.12). Receiver operating curves revealed more efficient judgments in the intervention group. CONCLUSION: An educational intervention can improve judgements of financial abuse amongst novice professionals.

Laser-machined microcavities for simultaneous measurement of high-temperature and high-pressure.

Laser-machined microcavities for simultaneous measurement of high-temperature and high-pressure are demonstrated. These two cascaded microcavities are an air cavity and a composite cavity including a section of fiber and an air cavity. They are both placed into a pressure chamber inside a furnace to perform simultaneous pressure and high-temperature tests. The thermal and pressure coefficients of the short air cavity are ~0.0779 nm/°C and ~1.14 nm/MPa, respectively. The thermal and pressure coefficients of the composite cavity are ~32.3 nm/°C and ~24.4 nm/MPa, respectively. The sensor could be used to separate temperature and pressure due to their different thermal and pressure coefficients. The excellent feature of such a sensor head is that it can withstand high temperatures of up to 400 °C and achieve precise measurement of high-pressure under high temperature conditions.

Liquid-Metal Molecular Scissors.

Molecules are the smallest units of matter that can exist independently, relatively stable, maintaining their physical and chemical activities. The key factors that dominate the structures and properties of molecules include atomic species, alignment commands, and chemical bonds. Herein, we reported a generalized effect in which liquid metals can directly cut off oxygen-containing groups in molecular matter at room temperature, allowing the remaining groups to recombine to form functional materials. Thus, we propose basic liquid-metal scissors for molecular directional clipping and functional transformations. As a proof of concept, we demonstrate the capabilities of liquid-metal scissors and reveal that the gallium on the surface of liquid metals directly extracts oxygen atoms from H2O or CH3OH molecules to form oxides. After clipping, the remaining hydrogen atoms from the H2O molecules recombine to form H2, while the remaining fragments of CH3OH produce H2, carbon materials, and carboxylates. This finding refreshes our basic understanding of chemistry and should lead to the development of straightforward molecular weaving techniques, which can help to overcome the limitations of molecular substances with single purposes. It also opens a universal route for realizing future innovations in molecular chemical engineering, life sciences, energy and environment research, and biomedicine.

Clinical characteristics, viral dynamics, and antibody response of monkeypox virus infections among men with and without HIV infection in Guangzhou, China.

Background: Monkeypox virus (MPXV) is spreading globally and nearly half of the infected people were human immunodeficiency virus (HIV) positive. Therefore, an in-depth understanding of the effects of HIV infection on the outcomes of MPXV infection is urgently needed. This study aimed to explore the clinical features, viral dynamics, and antibody response to MPXV infections in men who had sex with men (MSM) with and without HIV co-infection. Design or methods: MPXV-infected patients diagnosed by PCR were recruited in this study and were divided into MPXV and MPXV + HIV groups based on whether they were co-infected with HIV. Clinical data and samples were collected during of the hospital stay and follow up interviews. The symptoms and signs, laboratory examinations, viral shedding in various body fluids or swabs, antibody dynamics were tracked and compared between the two groups. Results: A total of 41 MPXV patients were recruited through June 2023 to September 2023 in Guangzhou. The MPXV group and MPXV + HIV group comprised 20 and 21 MSM, respectively. Patients in the two groups exhibited similar clinical characteristics except for pruritus and eschar, both were significantly fewer in MPXV + HIV group than in MPXV only group. Among the 355 clinical samples collected, MPXV DNA was detected in 100% of scabs, 97.4% of skin swabs, and 92.3% of exudate swabs from lesions, while the positive rate was 87.5% from oropharyngeal swabs, 59% from saliva, 51.3% from anal swabs, 50% from feces, 30.6% from urine samples, 37.5% of semen, and 28.2% from sera. Dynamics analysis revealed that viral DNA was undetectable in most patients 20 days after symptom onset. IgM and IgG antibodies to MPXV were detected in all patients with 3-5 days earlier in the MPXV group than in the MPXV + HIV group. Conclusion: This cohort analysis based on a large outbreak among MSM in Guangzhou indicated no obvious differences in clinical symptoms, viral DNA data, but antibody responses were 3-5 days later in mpox patients with HIV infection.

Identification of neutralizing antibodies against monkeypox virus using high-throughput sequencing of A35+H3L+B cells from patients with convalescent monkeypox.

The global monkeypox virus (MPXV) outbreak in 2022 emphasizes the urgent need for effective and accessible new-generation vaccines and neutralizing antibodies. Herein, we identified MPXV-neutralizing antibodies using high-throughput single-cell RNA and V(D)J sequencing of antigen-sorted B cells from patients with convalescent monkeypox. IgG1-expressing B cells were obtained from 34 paired heavy- and light-chain B cell receptor sequences. Subsequently, three potent neutralizing antibodies, MV127, MV128, and MV129, were identified and reacted with the MPXV A35 protein. Among these, MV129, which has a half-maximal inhibitory concentration of 2.68µg/mL against authentic MPXV, was considered to be the putative candidates for MPXV neutralization in response to monkeypox disease.

A CIC-related-epigenetic factors-based model associated with prediction, the tumor microenvironment and drug sensitivity in osteosarcoma.

Osteosarcoma is generally considered a cold tumor and is characterized by epigenetic alterations. Although tumor cells are surrounded by many immune cells such as macrophages, T cells may be suppressed, be inactivated, or not be presented due to various mechanisms, which usually results in poor prognosis and insensitivity to immunotherapy. Immunotherapy is considered a promising anti-cancer therapy in osteosarcoma but requires more research, but osteosarcoma does not currently respond well to this therapy. The cancer immunity cycle (CIC) is essential for anti-tumor immunity, and is epigenetically regulated. Therefore, it is possible to modulate the immune microenvironment of osteosarcoma by targeting epigenetic factors. In this study, we explored the correlation between epigenetic modulation and CIC in osteosarcoma through bioinformatic methods. Based on the RNA data from TARGET and GSE21257 cohorts, we identified epigenetic related subtypes by NMF clustering and constructed a clinical prognostic model by the LASSO algorithm. ESTIMATE, Cibersort, and xCell algorithms were applied to analyze the tumor microenvironment. Based on eight epigenetic biomarkers (SFMBT2, SP140, CBX5, HMGN2, SMARCA4, PSIP1, ACTR6, and CHD2), two subtypes were identified, and they are mainly distinguished by immune response and cell cycle regulation. After excluding ACTR6 by LASSO regression, the prognostic model was established and it exhibited good predictive efficacy. The risk score showed a strong correlation with the tumor microenvironment, drug sensitivity and many immune checkpoints. In summary, our study sheds a new light on the CIC-related epigenetic modulation mechanism of osteosarcoma and helps search for potential drugs for osteosarcoma treatment.

Applying improved ddPCR to reliable quantification of MPXV in clinical settings.

Monkeypox virus (MPXV) poses a global health threat. Droplet digital PCR (ddPCR) holds potential as an accurate diagnostic tool for clinical microbiology. However, there is limited literature on the applicability of ddPCR in clinical settings. In this study, the clinical features of patients with MPXV during the initial outbreak in China in June 2023 were reviewed, and an optimized ddPCR method with dilution and/or inhibitor removal was developed to enhance MPXV detection efficiency. Eighty-two MPXV samples were tested from nine different clinical specimen types, including feces, urine, pharyngeal swabs, anal swabs, saliva, herpes fluid, crust, and semen, and the viral load of each specimen was quantified. A comparative analysis was performed with qPCR to assess sensitivity and specificity and to investigate the characteristics of MPXV infection by analyzing viral loads in different clinical specimens. Consequently, common pharyngeal and gastrointestinal symptoms were observed in patients with MPXV. The optimized ddPCR method demonstrated relatively high sensitivity for MPXV quantification in the clinical materials, with a limit of detection of 0.1 copies/µL. This was particularly evident in low-concentration samples like whole blood, semen, and urine. The optimized ddPCR demonstrated greater detection accuracy compared with normal ddPCR and qPCR, with an area under the curve (AUC) of 0.939. Except for crust samples, viral loads in the specimens gradually decreased as the disease progressed. Virus levels in feces and anal swabs kept a high detection rate at each stage of post-symptom onset, and feces and anal swabs samples may be suitable for clinical diagnosis and continuous monitoring of MPXV. IMPORTANCE: The ddPCR technique proved to be a sensitive and valuable tool for accurately quantifying MPXV viral loads in various clinical specimen types. The findings provided valuable insights into the necessary pre-treatment protocols for MPXV diagnosis in ddPCR detection and the potentially suitable sample types for collection. Therefore, such results can aid in comprehending the potential characteristics of MPXV infection and the usage of ddPCR in clinical settings.

Severe Organ Impairment Was Common in Elderly Individuals with Dengue in Guangdong, China.

Guangdong, China, has experienced several dengue epidemics involving thousands of confirmed cases in recent decades, and elderly individuals suffered severe dengue (SD) most seriously. However, the clinical characteristics and risk factors for SD among elderly patients in Guangdong have not been investigated. Patients older than 65 years were recruited and divided into a dengue fever (DF) group and an SD group according to the 2009 Dengue Guidelines of the WHO. We analyzed the clinical manifestations of the elderly patients with dengue and then assessed the risk factors for SD. Of a total of 1,027 patients, 868 patients were diagnosed as having DF and 159 as having SD. Of the 159 elderly patients with SD, 129 (81%) had comorbidities, with hypertension being the most common. Severe organ impairment (SOI) (115, 54%) was the most common presentation in SD patients, followed by severe plasma leakage (52, 24.4%) and severe hemorrhage (46, 21.6%). The most common symptom of SOI was kidney injury, followed by heart injury and central nervous system injury. Furthermore, multivariate regression revealed that the presence of chronic obstructive pulmonary disease (COPD), a lower red blood cell (RBC) count (≤3.5 × 1012/L; odds ratio [OR], 0.35; 95% CI, 0.17-0.55; P <0.001), lower serum albumin (ALB) (≤35 U/L; OR, 0.18; 95% CI, 0.09-0.32; P <0.001), and hyperpyrexia (body temperature ≥39°C; OR, 1.8; 95% CI, 1.2-2.6, P <0.001) were risk factors for SD. Severe organ impairment was the predominant manifestation in elderly individuals with SD characterized by kidney injury. The potential risk factors of SD such as presence of COPD and hyperpyrexia and lower RBC and ALB levels might help clinicians identify patients with SD early.

Machine-learning-based models assist the prediction of pulmonary embolism in autoimmune diseases: A retrospective, multicenter study.

BACKGROUND: Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD. METHODS: In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort. RESULTS: In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone. CONCLUSION: ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. TRIAL REGISTRATION: Chictr.org.cn: ChiCTR2200059599.