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ObjectiveThe goal of this study was to develop a nomogram that integrates clinical data to predict the likelihood of severe postoperative peritumoral brain edema (PTBE) following the surgical removal of intracranial meningioma.MethodWe included 152 patients diagnosed with meningioma who were admitted to the Department of Neurosurgery at the Affiliated People’s Hospital of Jiangsu University between January 2016 and March 2023. Clinical characteristics were collected from the hospital’s medical record system. Factors associated with severe postoperative PTBE were identified through univariate and LASSO regression analyses of clinical, pathological, and radiological features. A multivariate logistic regression analysis was then performed incorporating all features. Based on these analyses, we developed five predictive models using R software: conventional logistic regression, XGBoost, random forest, support vector machine (SVM), and k-nearest neighbors (KNN). Model performance was evaluated by calculating the area under the receiver operating characteristic curve (AUC) and conducting decision curve analysis (DCA). The most optimal model was used to create a nomogram for visualization. The nomogram was validated using both a validation set and clinical impact curve analysis. Calibration curves assessed the accuracy of the clinical-radiomics nomogram in predicting outcomes, with Brier scores used as an indicator of concordance. DCA was employed to determine the clinical utility of the models by estimating net benefits at various threshold probabilities for both training and testing groups.ResultsThe study involved 151 patients, with a prevalence of severe postoperative PTBE at 35.1%. Univariate logistic regression identified four potential risk factors, and LASSO regression identified four significant risk factors associated with severe postoperative PTBE. Multivariate logistic regression revealed three independent predictors: preoperative edema index, tumor enhancement intensity on MRI, and the number of large blood vessels supplying the tumor. Among all models, the conventional logistic model showed the best performance, with AUCs of 0.897 (95% CI: 0.829–0.965) and DCA scores of 0.719 (95% CI: 0.563–0.876) for each cohort, respectively. We developed a nomogram based on this model to predict severe postoperative PTBE in both training and testing cohorts. Calibration curves and Hosmer-Lemeshow tests indicated excellent agreement between predicted probabilities and observed outcomes. The Brier scores were 10.7% (95% CI: 6.7–14.7) for the training group and 25% (95% CI: 15.2–34.8) for the testing group. DCA confirmed that the nomogram provided superior net benefit across various risk thresholds for predicting severe postoperative PTBE, with a threshold probability range from 0 to 81%.ConclusionUtilizing conventional logistic regression within machine learning frameworks, we developed a robust prediction model. The clinical-radiological nomogram, based on conventional logistic regression, integrated clinical characteristics to enhance the prediction accuracy for severe PTBE in patients following intracranial meningioma resection. This nomogram showed promise in aiding clinicians to create personalized and optimal treatment plans by providing precise forecasts of severe PTBE.

Bacteriophages have been used across various fields, and the utilization of CRISPR/Cas-based genome editing technology can accelerate the research and applications of bacteriophages. However, some bacteriophages can escape from the cleavage of Cas protein, such as Cas9, and decrease the efficiency of genome editing. This study focuses on the bacteriophage T7, which is widely utilized but whose mechanism of evading the cleavage of CRISPR/Cas9 has not been elucidated. First, we test the escape rates of T7 phage at different cleavage sites, ranging from 10-2 to 10-5. The sequencing results show that DNA point mutations and microhomology-mediated end joining (MMEJ) at the target sites are the main causes. Next, we indicate the existence of the hotspot DNA region of MMEJ and successfully reduce MMEJ events by designing targeted sites that bypass the hotspot DNA region. Moreover, we also knock out the ATP-dependent DNA ligase 1.3 gene, which may be involved in the MMEJ event, and the frequency of MMEJ at 4.3 is reduced from 83% to 18%. Finally, the genome editing efficiency in T7 Δ1.3 increases from 20% to 100%. This study reveals the mechanism of T7 phage evasion from the cleavage of CRISPR/Cas9 and demonstrates that the special design of editing sites or the deletion of key gene 1.3 can reduce MMEJ events and enhance gene editing efficiency. These findings will contribute to advancing CRISPR/Cas-based tools for efficient genome editing in phages and provide a theoretical foundation for the broader application of phages.

C26H36N4O20Zn2, triclinic, P1‾$P\overline{1}$ (no. 2), a = 6.9872(4) Å, b = 8.9052(5) Å, c = 8.9052(5) Å, α = 94.441(4)°, β = 93.552(4)°$93.552(4){}^{\circ}$, γ = 90.045(5)°$90.045(5){}^{\circ}$, V = 1651.61(16) Å3, Z = 2, Rgt${R}_{gt}$(F) = 0.0748, wRref$w{R}_{ref}$(F2) = 0.2021, T = 293 K.

This paper analyzed the intervention effect of Huolong cupping therapy combined with complex decongestion therapy and nursing measures in a patient with stage Ⅲ lymphedema of lower limbs complicated with stage Ⅱ lymphedema of external genitalia after endometrial carcinoma operation. Based on the nursing evaluation, integrative nursing interventions including Huolong cupping therapy by syndrome differentiation, manual lymph drainage, pressure therapy by using low-elastic multi-layer pressure bandage, emotional care, skin care and exercises were carried out to reduce skin fibrosis, promote lymphatic reflux and prevent the infection (本文总结1例龙罐联合综合消肿治疗双下肢Ⅲ期合并外阴部Ⅱ期淋巴水肿1例的护理经验。完善护理评估, 在手法淋巴引流、多层低弹力绷带压力包扎、皮肤护理、运动锻炼等基础上, 基于中医辨证, 采用火龙罐、情志护理等中医护理干预, 促进淋巴液回流, 减轻水肿, 预防感染。)

C15H10K2O6, orthorhombic, Pna21 (no. 33), a = 11.4410(13) Å, b = 3.9881(5) Å, c = 32.465(4) Å, V = 1481.3(3) Å3, Z = 4, R gt(F) = 0.0356, wR ref(F 2) = 0.0918, T = 296.15 K.

C3H10CdNO9P3, monoclinic, P21/c (no. 14), a = 9.1770(5) Å, b = 8.3742(4) Å, c = 15.4660(6) Å, β = 119.657(2)°, V = 1032.86(9) Å3, Z = 4, Rgt(F) = 0.0202, wRref(F2) = 0.0515, T = 296 K.

C28H32MnN8O2Cl2, triclinic, P1‾$P\overline{1}$ (no. 2), a = 8.987(4) Å, b = 9.061(3) Å, c = 10.706(2) Å, α = 88.65(2)°, β = 66.12(2)°, γ = 89.89(2)°, V = 796.9(5) Å3, Z = 1, Rgt(F) = 0.1033, wRref(F2) = 0.2218, T = 293(2) K.

C27H28N4O16Zn2, monoclinic, C2/c (no. 15), a = 13.0720(3) Å, b = 15.7589(5) Å, c = 15.7589(5) Å, β = 95.373(3)°, V = 3062.48(18) Å3, Z = 4, Rgt(F) = 0.0499, wRref(F2) = 0.1059, T = 294 K.

The intracloud (IC) flashes can be classified into normal and inverted-polarity types according to their initial leader propagation directions. Due to the rare occurrence of inverted-polarity IC flashes with downward preliminary breakdown (PB) processes, the corresponding PB characteristics are much less understood than those in normal IC flashes.Based on the lightning data observed by a low-frequency lightning mapping system FALMA (fast antenna lightning mapping array) deployed in Ningxia, the characteristics of the PB process in 312 inverted-polarity IC flashes are statistically analyzed. The parameters of PB waveforms show that the arithmetical mean (AM) of the PB duration is 9.8 ms. The pulse shape is characterized by rise time, half-peak width, fall time, and pulse width, respectively, with AM values of 7.3 μs, 4.5 μs, 5.6 μs, and 24.7 μs. The pulse rate and pulse interval are 5.7 ms-1 and 169.2 μs.The statistical results for PB channels show that the inverted-polarity IC flashes are usually initiated at the AM altitude about 6.9 km, obviously higher than the initiation altitude of normal-polarity IC flashes. The difference indicates that there could be an inverted dipolar charge structure in the thunderclouds of Ningxia. The superposition of PB locations on the radar reflectivity suggests that these inverted IC flashes tend to be initiated in the region with radar echoes weaker than normal IC flashes (19.3 versus 27.8 dBZ). The vertical length and speed of PB channels are 2.0 km and 2.8×105 m·s-1.Furthermore, PB parameters show significant correlations with the initiation altitude. Specifically, both vertical speed and pulse rate decrease with the initiation altitude, and the correlation coefficients are -0.44 and -0.53, respectively. However, both PB durations and vertical distances show positive correlations with the initiation altitude, with the coefficients of 0.64 and 0.46, respectively.In general, the PB characteristics of inverted IC flashes present both similarities and differences to the PB processes in other flash types. It is believed more lightning observations in the northwest inland of China can facilitate the interpretation of these similarities and differences.

As a simple, rapid and effective research method, test-negative design (TND) has been widely used to support the evaluation of post-marketing effectiveness of vaccines and efficacies of interventions in healthcare institutions, showing a magnificent prospect of application. With the emergence of new derivative types such as real-time TND and cluster-randomized TND, TND has also been gradually applied to the exploration of disease risk factors and effectiveness evaluation of interventions. However, there are still few related research reports in China. We introduced the basic principles, methods and essentials of implementation, newly derivative types such as real-time TND and cluster-randomized TND, advantages and limitations of TND, as well as its applications in assessing post-marketing effectiveness for vaccines and efficacies of interventions, providing a theoretical and practical basis for researchers in China to carry out relevant research.

Background: Vitamin D deficiency is common in pregnant women. There is scarce information in the Asia-Pacific region on the understanding of vitamin D screening and supplementation in pregnancy among health care professionals. Methods: We performed a cross-sectional study among health care professionals who are part of the Integrated Platform for Research in Advancing Metabolic Health outcomes of Women and Children (IPRMAHO) international study group on their understanding and perception of Vitamin D screening and supplementation in pregnancy. The cross-sectional survey comprised 4 main sections: demographics, existing policies, nutrient supplementation in pregnancy and various practices on screening, treatment and perceptions, with a total of 22 questions. A total of 15 responses were obtained from attendees from distinct health facilities across eleven participating Asia-Pacific countries. Results: Majority of the surveyed hospitals (11/15, 78.6 %) did not have a national policy or regional guideline regarding Vitamin D screening and supplementation in pregnancy. More than half of respondents were (9/14, 64.3 %) were unsure of the percentage of women seen with Vitamin D deficiencies each year and were unsure of Vitamin D dosage prescribed to pregnant women with (8/15, 53.3 %) or without (6/14, 42.9 %) Vitamin D deficiency. Vitamin D was rarely prescribed in pregnancy when compared to other nutrient supplements such as folic acid and iron. Majority of respondents (9/11, 72.7 %) indicated that their hospital did not screen for Vitamin D deficiencies in pregnancy, even amongst high risk pregnant women. Nevertheless, majority of respondents indicated a need (12/15, 80.0 %) for a guideline or consensus regarding Vitamin D screening and supplementation in pregnancy. Conclusion: While majority of the surveyed hospitals did not have a national policy or regional guideline regarding Vitamin D screening and supplementation in pregnancy, majority of respondents indicated a need for the policy or guideline. There were varying clinical knowledge gaps and different perceptions on Vitamin D screening and supplementation in pregnancy among healthcare professionals.

ObjectiveTo assess the effects of countermeasures against coronavirus disease 2019 （COVID-19） in Shanghai from March to May 2022 in comparison with epidemiological trend of COVID-19 in New York City.MethodsDaily confirmed cases， asymptomatic SARS-CoV-2 carriers， and daily deaths were obtained in the Shanghai Municipal Health Commission and the Center for Disease Control and Prevention （CDC） of the United States. Descriptive study was conducted by using these data.ResultsFrom March 1 to May 17， the number of daily asymptomatic SARS-CoV-2 infections in Shanghai was up to 58 times as large as that of daily confirmed cases； however， the number of daily confirmed cases in Shanghai was generally less than that in New York in the same time period. At the peak of the COVID-19 epidemic， the growth of daily attack rate in Shanghai was significantly lower than that in New York （P

Objective To explore the application effect of simulated teaching based on standardized case database combined with guided feedback method in the practice teaching of nursing undergraduates. Methods Cluster sampling method was adopted to select 216 nursing undergraduates of 2016 in school as the research object. A standardized case database was established, and s simulated teaching combined with guided feedback method was adopted in the practice teaching of nursing undergraduates. The critical thinking and independent learning ability of nursing undergraduates before and after practical teaching were compared. Results After the implementation of scene simulation teaching based on standardized case database combined with guided feedback teaching mode, scores of assessments on critical thinking and independent learning ability of nursing undergraduates were improved, compared with those before intervention, the difference was statistically significant (P＜0. 05). Conclusion Scene simulation teaching based on standardized case database combined with guided feedback teaching mode can improve the critical thinking and independent learning ability of nursing undergraduates, which is worthy of promotion and application. (目的 探讨基于标准化案例库的情景教学结合引导性反馈在护理本科生实践教学中的应用效果。方法 采用整群抽样法, 选取本校2016级护理本科生216人作为研究对象。建立标准化案例库, 并在护理本科生实践教学中运用情景教学结合引导性反馈。评价护理本科生的评判性思维和自主学习能力。结果 实施基于标准化案例库的情景教学结合引导性反馈教学模式后, 护理本科生的批判性思维及自主学习能力各维度得分均有所提高, 与干预前相比, 差异有统计学意义(P＜0. 05)。结论 基于标准化案例库的情景教学结合引导性反馈教学模式, 能够提高护理本科生的批判性思维和自主学习能力。)

Combining a T cell-targeting mRNA vaccine encoding the conserved SARS-CoV-2 RNA-dependent RNA polymerase, RdRp, with a Spike-encoding mRNA vaccine may offer an additional pathway toward COVID-19 protection. Here, we show that a nucleoside-modified RdRp mRNA vaccine raises robust and durable CD8+ T cell responses in mice. Immunization drives a CD8+ T cell response enriched toward a specific RdRp epitope. Unexpectedly, coadministration of mRNA vaccines encoding RdRp or the Spike Receptor Binding Domain (RBD) dampens RBD-specific immune responses. Contralateral administration reduces the suppression of RBD-specific T cell responses while type I interferon signaling blockade restores RBD-specific antibodies. A staggered immunization strategy maintains both RBD vaccine-mediated antibody and T cell responses as well as protection against lethal SARS-CoV-2 challenge in human ACE2 transgenic mice. In HLA-A2.1 transgenic mice, the RdRp vaccine elicits CD8+ T cell responses against HLA-A*02:01-restricted epitopes recognized by human donor T cells. These results highlight RdRp as a candidate antigen for COVID-19 vaccines. The findings also offer insights into crafting effective multivalent mRNA vaccines to broaden CD8+ T cell responses against SARS-CoV-2 and potentially other viruses with pandemic potential.

BACKGROUND: An association between driving pressure (∆P) and the outcomes of invasive mechanical ventilation (IMV) may exist. However, the effect of a sustained limitation of ∆P on mortality in patients with acute respiratory distress syndrome (ARDS), including patients with COVID-19 (COVID-19-related acute respiratory distress syndrome (C-ARDS)) undergoing IMV, has not been rigorously evaluated. The use of emulations of a target trial in intensive care unit research remains in its infancy. To inform future, large ARDS target trials, we explored using a target trial emulation approach to analyse data from a cohort of IMV adults with C-ARDS to determine whether maintaining daily ∆p24 hours of IMV were considered to be assigned to limited ∆P or LTVV. Lung mechanics were measured twice daily after ventilator setting adjustments were made. To evaluate the effect of each lung-protective ventilation (LPV) strategy on the 28-day mortality, we fit a stabilised inverse probability weighted marginal structural model that adjusted for baseline and time-varying confounders known to affect protection strategy use/adherence or survival. RESULTS: Among the 92 patients included, 27 (29.3%) followed limited ∆P ventilation, 23 (25.0%) the LTVV strategy and 42 (45.7%) received no LPV strategy. The adjusted estimated 28-day survival was 47.0% (95% CI 23%, 76%) in the limited ∆P group, 70.3% in the LTVV group (95% CI 37.6%, 100%) and 37.6% (95% CI 20.8%, 58.0%) in the no LPV strategy group. INTERPRETATION: Limiting ∆P may not provide additional survival benefits for patients with C-ARDS over LTVV. Our results help inform the development of future target trial emulations focused on evaluating LPV strategies, including reduced ∆P, in adults with ARDS.

While studying transgene expression after systemic administration of lentiviral vectors, we found that splenic B cells are robustly transduced, regardless of the types of pseudotyped envelope proteins. However, the administration of two different pseudotypes resulted in transduction of two distinct B cell populations, suggesting that each pseudotype uses unique and specific receptors for its attachment and entry into splenic B cells. Single-cell RNA sequencing analysis of the transduced cells demonstrated that different pseudotypes transduce distinct B cell subpopulations characterized by specific B cell receptor (BCR) genotypes. Functional analysis of the BCRs of the transduced cells demonstrated that BCRs specific to the pseudotyping envelope proteins mediate viral entry, enabling the vectors to selectively transduce the B cell populations that are capable of producing antibodies specific to their envelope proteins. Lentiviral vector entry via the BCR activated the transduced B cells and induced proliferation and differentiation into mature effectors, such as memory B and plasma cells. BCR-mediated viral entry into clonally specific B cell subpopulations raises new concepts for understanding the biodistribution of transgene expression after systemic administration of lentiviral vectors and offers new opportunities for BCR-targeted gene delivery by pseudotyped lentiviral vectors.