Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses.

OBJECTIVE: Bladder cancer(BCa) was a disease that seriously affects patients' quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. METHODS: We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. RESULTS: The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. CONCLUSION: P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.

Structural and functional characterization of a mycobacterial methylenetetrahydrofolate reductase utilizing NADH as the exclusive cofactor.

5,10-Methylenetetraydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. MSMEG_6649, a non-canonical MTHFR from Mycobacterium smegmatis, was previously reported as a monomeric protein lacking the flavin coenzyme. However, the structural basis for its unique flavin-independent catalytic mechanism remains poorly understood. Here, we determined the crystal structures of apo MTHFR MSMEG_6649 and its complex with NADH from M. smegmatis. Structural analysis revealed that the groove formed by the loops 4 and 5 of non-canonical MSMEG_6649 interacting with FAD was significantly larger than that of canonical MTHFR. Meanwhile, the NADH-binding site in MSMEG_6649 is highly similar to the FAD binding site in canonical MTHFR, suggesting that NADH plays the same role (immediate hydride donor for methylenetetraydrofolate) as FAD in the catalytic reaction. Using biochemical analysis, molecular modeling, and site-directed mutagenesis, the critical residues participating in the binding of NADH and the substrate 5,10-methylenetetrahydrofolate as well as the product 5-methyltetrahydrofolate were identified and validated. Taken together, this work not only provides a good starting point for understanding the potential catalytic mechanism for MSMEG_6649, but also identifies an exploitable target for the development of anti-mycobacterial drugs.

When Parents Are at Fault: Development and Validation of the Parental Guilt and Shame Proneness Scale.

Research has linked individuals' dispositional guilt and shame to their interpersonal processes. Although caregivers' guilt and shame proneness in the parenting context likely have important implications for their mental health and parenting, there is a lack of validated measures for such dispositions. In three studies with Chinese parents, we developed and validated the Parental Guilt and Shame Proneness scale (PGASP), which was based on the Guilt and Shame Proneness scale (GASP). The PGASP comprises two guilt subscales-negative behavior-evaluations (guilt-NBE) and repair action tendencies (guilt-repair)-and two shame subscales-negative self-evaluations (shame-NSE) and withdrawal action tendencies (shame-withdraw). Study 1 (N = 604) provided support for the four-factor structure of the PGASP, which was replicated in Study 2 (N = 451). The concurrent validity of the PGASP was examined in Study 2 and Study 3 (N = 455). The two guilt subscales were associated with better mental health and more positive parenting, whereas parents' shame-withdraw exhibited the opposite pattern; weak or no relations were found for shame-NSE. Findings highlight the need to differentiate between parents' shame-NSE and shame-withdraw. PGASP may be a useful tool for identifying parents at risk of engaging in negative parenting.

Bioactivity evaluation and active compounds identification of Symphoricarpos orbiculatus as potential botanical herbicide.

BACKGROUND: Evaluation of herbicidal activity and identification of active compounds are important bases for the development of new botanical herbicides. RESULTS: This study confirmed that Symphoricarpos orbiculatus has high herbicidal activities against mono-dicotyledonous weeds, including Echinochloa crusgalli, Digitaria sanguinalis, Amaranthus retroflexus and Portulaca oleracea. By bioassay-guided isolation, 12 compounds were isolated and identified from S. orbiculatus for the first time, including iridoids: naucledal (K1), loganin (K2), loganigenin (K3), loganin acid (K4), glucologanin (K5) and vogeloside (K6), as well as flavonoids: quercetine (K7), luteolin (K8), nobiletin (K9), astragalin (K10), isorhamnetin 3-d-glucoside (K11) and rutin (K12). Biological assays showed that iridoids are the main active ingredients of S. orbiculatus. The compounds of K5 and K6 could inhibit both the root (IC50 = 37.54 and 38.91 µg mL-1, respectively) and shoot (IC50 = 42.78 and 45.72 µg mL-1, respectively) of Portulaca oleracea, which have a weeding toxicity similar to that of the commercialized plant-based herbicide pelargonic acid. In addition, the results of pot culture assay showed that S. orbiculatus ethanol extracts had high fresh weight control effect against Digitaria sanguinalis and P. oleracea at the concentration of 40 g L-1. After 7 days, both the soil treatment and the stem and leaf spray method resulted in severe leaf necrosis and significant leaf etiolation. CONCLUSION: Symphoricarpos orbiculatus and its herbicidal active compounds have the potential to develop into botanical herbicides, and are first reported in the present study. © 2024 Society of Chemical Industry.

High-level production of chitinase by multi-strategy combination optimization in Bacillus licheniformis.

In view of the extensive potential applications of chitinase (ChiA) in various fields such as agriculture, environmental protection, medicine, and biotechnology, the development of a high-yielding strain capable of producing chitinase with enhanced activity holds significant importance. The objective of this study was to utilize the extracellular chitinase from Bacillus thuringiensis as the target, and Bacillus licheniformis as the expression host to achieve heterologous expression of ChiA with enhanced activity. Initially, through structural analysis and molecular dynamics simulation, we identified key amino acids to improve the enzymatic performance of chitinase, and the specific activity of chitinase mutant D116N/E118N was 48% higher than that of the natural enzyme, with concomitant enhancements in thermostability and pH stability. Subsequently, the expression elements of ChiA(D116N/E118N) were screened and modified in Bacillus licheniformis, resulting in extracellular ChiA activity reached 89.31 U/mL. Further efforts involved the successful knockout of extracellular protease genes aprE, bprA and epr, along with the gene clusters involved in the synthesis of by-products such as bacitracin and lichenin from Bacillus licheniformis. This led to the development of a recombinant strain, DW2△abelA, which exhibited a remarkable improvement in chitinase activity, reaching 145.56 U/mL. To further improve chitinase activity, a chitinase expression frame was integrated into the genome of DW2△abelA, resulting in a significant increas to 180.26 U/mL. Optimization of fermentation conditions and medium components further boosted shake flask enzyme activity shake flask enzyme activity, achieving 200.28 U/mL, while scale-up fermentation experiments yielded an impressive enzyme activity of 338.79 U/mL. Through host genetic modification, expression optimization and fermentation optimization, a high-yielding ChiA strain was successfully constructed, which will provide a solid foundation for the extracellular production of ChiA.

Silicon photonic broadband polarization-insensitive switch based on polarization-mode diversity conversion.

We present a 2 × 2 polarization-insensitive switch on a 220-nm silicon-on-insulator platform, employing a balanced Mach-Zehnder interferometer (MZI) structure. This design incorporates polarization-insensitive adiabatic couplers, polarization rotators based on mode hybridization and evolution, and thermo-optic mode-insensitive phase shifters with wide waveguides. The switch exhibits broadband polarization-insensitive characteristics, with extinction ratios larger than 15 dB, insertion losses less than 2.3 dB, and polarization-dependent losses less than 1 dB for wavelengths ranging from 1500 nm to 1600 nm. The power consumption required for simultaneously switching the fundamental transverse electric (TE0) and transverse magnetic (TM0) polarized modes is 29.1 mW. These results highlight the potential of the switch as a building block for on-chip polarization-division-multiplexed optical interconnects.

A Graph Theory Study of Resting-State Functional MRI Connectivity in Children With Carbon Monoxide Poisoning.

BACKGROUND: The effect of carbon monoxide (CO) poisoning on the topology of brain functional networks is unclear, especially in children whose brains are still developing. PURPOSE: To investigate the topological alterations of the whole-brain functional connectome in children with CO poisoning and characterize its relationship with disease severity. STUDY TYPE: Cross-sectional and prospective study. SUBJECTS: A total of 26 patients with CO poisoning and 26 healthy controls. FIELD STRENGTH/SEQUENCE: A 3.0 T MRI system/echo planar imaging (EPI) and 3D brain volume imaging (BRAVO) sequences. ASSESSMENT: We used the network-based statistics (NBS) method to explore between-group differences in functional connectivity strength and a graph-theoretical-based analytic method to explore the topology of brain networks. STATISTICAL TESTS: Student's t-test, chi-square test, NBS, Pearson correlation coefficient, and false discovery rate correction. The statistical significance threshold was set at P < 0.05. RESULTS: The case group's brain functional network topology was impaired in comparison to the control group (reduced global efficiency and small-worldness, increased characteristic path length). According to node and edge analyses, the case group showed topologically damaged regions in the frontal lobe and basal ganglia, as well as neuronal circuits with weaker connections. Also, there was a significant correlation between the patients' coma time and the degree (r = -0.4564), efficiency (r = -0.4625), and characteristic path length (r = 0.4383) of the nodes in the left orbital inferior frontal gyrus. Carbon monoxide hemoglobin content (COHb) concentration and right rolandic operculum node characteristic path length (r = -0.3894) were significantly correlated. The node efficiency and node degree of the right middle frontal gyrus (r = 0.4447 and 0.4539) and right pallidum (r = 0.4136 and 0.4501) significantly correlated with the MMSE score. DATA CONCLUSION: The brain network topology of CO poisoned children is damaged, which is manifested by reduced network integration and may lead to a series of clinical symptoms in patients. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Safety of Direct Oral Anticoagulants for Gastrointestinal Hemorrhage in Patients With Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-world Studies.

GOALS AND BACKGROUND: Since the introduction of Direct Oral Anticoagulants (DOACs), "real-world" studies have investigated their safety profile on gastrointestinal hemorrhage (GIH) when used by patients with Non-Valvular Atrial Fibrillation. We performed a systematic review and meta-analysis to compile and summarize this data after Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. STUDY: Medline and Embase were systematically searched until April 2021. Observational studies that met predefined inclusion criteria were included and hazard ratios (HRs) with 95% CI were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, prior exposure to VKA (vitamin K antagonist), age, gender, geographic location of population samples, as well as Leave-One-Out and Low/Moderate Risk of Bias sensitivity analyses were performed. A random effects model was used. RESULTS: A total of 46 studies were included. Apixaban was associated with a reduced risk of GIH compared with Dabigatran (HR: 0.67, 95% CI, 0.56 to 0.81, I2 : 53.28%), Rivaroxaban (HR: 0.56, 95% CI, 0.44 to 0.70, I2 : 79.17%), and VKA (HR: 0.68, 95% CI, 0.60 to 0.78, I2 : 71.93%). Rivaroxaban was associated with increased GIH risk compared with Dabigatran (HR: 1.19, 95% CI, 1.02 to 1.40, I2 : 72.96%) and VKA (HR: 1.16, 95% CI, 1.05 to 1.27, I2 : 81.95%). Dabigatran was associated with similar GIH risk compared with VKA (HR: 1.11, 95% CI, 0.98 to 1.26, I2 : 87.28%). CONCLUSIONS: Our study shows that Apixaban was associated with a reduction in GIH risk compared with Dabigatran, Rivaroxaban and VKA, whereas Rivaroxaban was associated with an increase in GIH risk compared with both Dabigatran and VKA.

Development and validation of a clinical nomogram for differentiating hemorrhagic and ischemic stroke prehospital.

OBJECTIVES: The early detection and identification of stroke are essential to the prognosis of patients with suspected stroke symptoms out-of-hospital. We aimed to develop a risk prediction model based on the FAST score to identify the different types of strokes early for emergency medical services (EMS). METHODS: This retrospective observational study enrolled 394 stroke patients at a single center from January 2020 to December 2021. Demographic data, clinical characteristics, and stroke risk factors with patients were collected from the EMS record database. Univariate and multivariate logistic regression analysis was used to identify the independent risk predictors. The nomogram was developed based on the independent predictors, in which the discriminative value and calibration of the nomogram were verified by the receiver operator characteristic (ROC) curve and calibration plots. RESULTS: A total of 31.90% (88/276) of patients were diagnosed with hemorrhagic stroke in the training set, while 36.40% (43/118) in the validation set. The nomogram was developed based on the multivariate analysis, including age, systolic blood pressure, hypertension, vomiting, arm weakness, and slurred speech. The area under the curve (AUC) of the ROC with nomogram was 0.796 (95% CI: 0.740-0.852, P < 0.001) and 0.808 (95% CI:0.728-0.887, P < 0.001) in the training set and validation set, respectively. In addition, the AUC with the nomogram was superior to the FAST score in both two sets. The calibration curve showed a good agreement with the nomogram and the decision curves analysis also demonstrated that the nomogram had a wider range of threshold probabilities than the FAST score in the prediction risk of hemorrhagic stroke. CONCLUSIONS: This novel noninvasive clinical nomogram shows a good performance in differentiating hemorrhagic and ischemic stroke for EMS staff prehospital. Moreover, all of the variables of nomogram are acquired in clinical practice easily and inexpensively out-of-hospital.

Synergetic argentophilic and through space electronic interactions in a single-crystal-to-single-crystal photocycloaddition reaction: a mechanistic study.

Ag(I) is able to mediate single-crystal-to-single-crystal transformation through [2+2] photocycloaddition to prepare high-conductivity materials. However, the intrinsic mechanism of Ag(I) mediation, the detailed photophysical and photochemical processes as well as the origin of the enhanced conductivity of nanocrystals are still unclear. In this work, the comprehensive kinetic scheme and regulation mechanism are established by the accurate QM/MM calculations at the CASPT2//CASSCF/AMBER level of theory with consideration of the crystal environment. We find that the argentophilic interaction and through space electronic interaction are the key factors that promote Ag(I)-mediated [2+2] PCA reactions and may account for the enhancement of conductivity. These mechanistic insights into the Ag(I)-regulated photo-dimerization in the crystal surrounding are beneficial for the design of the structurally and electrically favorable skeletons of a metal-organic coordination polymer.

Mechanistic Understanding and Reactivity Analyses for the Photochemistry of Disubstituted Tetrazoles.

The photolysis of tetrazoles has undergone extensive research. However, there are still some problems to be solved in terms of mechanistic understanding and reactivity analyses, which leaves room for theoretical calculations. Herein, multiconfiguration perturbation theory at the CASPT2//CASSCF level was employed to account for electron correction effects involved in the photolysis of four disubstituted tetrazoles. Based on calculations of vertical excitation properties and evaluations of intersystem crossing (ISC) efficiencies in the Frank-Condon region, the combination of space and electronic effects is found in maximum-absorption excitation. Two types of ISC (1ππ* → 3nπ*, 1ππ* → 3ππ*) are determined in disubstituted tetrazoles, and the obtained rates follow the El-Sayed rule. Through mapping three representative types of minimum energy profiles for the photolysis of 1,5-, and 2,5-disubstituted tetrazoles, a conclusion can be drawn that the photolysis of tetrazoles exhibits reactivity characteristic of bond-breaking selectivity. Kinetic evaluations show that the photogeneration of singlet imidoylnitrene operates predominately over that in the triplet state, which can be confirmed by a double-well model in the triplet potential energy surface of 1,5-disubstituted tetrazole. Similar mechanistic explorations and reactivity analyses were also applied to the photolysis of 2,5-disubstituted tetrazole to unveil fragmentation patterns of nitrile imine generation. All computational efforts allow us to better understand the photoreactions of disubstituted tetrazoles and to provide useful strategies for regulating their unique reactivity.

Silencing of NLRP3 Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin.

Background: Ovarian cancer is a fatal gynecological malignancy. The resistance to chemotherapy in ovarian cancer treatment has been a thorny issue. This study is aimed at probing the molecular mechanism of cisplatin (DDP) resistance in ovarian cancer. Methods: Bioinformatics analysis was conducted to examine the role of Nod-like receptor protein 3 (NLRP3) in ovarian cancer. The NLRP3 level in DDP-resistant ovarian cancer tumors and cell lines (SKOV3/DDP and A2780/DDP) was evaluated by applying immunohistochemical staining, western blot, and qRT-PCR. Cell transfection was conducted to regulate the NLRP3 level. Cell abilities to proliferate, migrate, invade, and apoptosis were measured employing colony formation, CCK-8, wound healing, transwell, and TUNEL assays, respectively. Cell cycle analysis was completed via flow cytometry. Corresponding protein expression was measured by western blot. Results: NLRP3 was overexpressed in ovarian cancer, correlated with poor survival, and upregulated in DDP-resistant ovarian cancer tumors and cells. NLRP3 silencing exerted antiproliferative, antimigrative, anti-invasive, and proapoptotic effects in A2780/DDP and SKOV3/DDP cells. Additionally, NLRP3 silencing inactivated NLRPL3 inflammasome and blocked epithelial-mesenchymal transition via enhancing E-cadherin and lowering vimentin, N-cadherin, and fibronectin. Conclusion: NLRP3 was overexpressed in DDP-resistant ovarian cancer. NLRP3 knockdown hindered the malignant process of DDP-resistant ovarian cancer cells, providing a potential target for DPP-based ovarian cancer chemotherapy.

Improved multivariate multiscale sample entropy and its application in multi-channel data.

Entropy, as a nonlinear feature in information science, has drawn much attention for time series analysis. Entropy features have been used to measure the complexity behavior of time series. However, traditional entropy methods mainly focus on one-dimensional time series originating from single-channel transducers and are incapable of handling the multidimensional time series from multi-channel transducers. Previously, the multivariate multiscale sample entropy (MMSE) algorithm was introduced for multi-channel data analysis. Although MMSE generalizes multiscale sample entropy and provides a new method for multidimensional data analysis, it lacks necessary theoretical support and has shortcomings, such as missing cross-channel correlation information and having biased estimation results. This paper proposes an improved multivariate multiscale sample entropy (IMMSE) algorithm to overcome these shortcomings. This paper highlights the existing shortcomings in MMSE under the generalized algorithm. The rationality of IMMSE is theoretically proven using probability theory. Simulations and real-world data analysis have shown that IMMSE is capable of effectively extracting cross-channel correlation information and demonstrating robustness in practical applications. Moreover, it provides theoretical support for generalizing single-channel entropy methods to multi-channel situations.

Effect of Natural Variation and Rootstock on Fruit Quality and Volatile Organic Compounds of 'Kiyomi tangor' (Citrus reticulata Blanco) Citrus.

In this study, we compared the fruit quality and color of 'Kiyomi' (WT) and its mutant (MT) grafted on Ziyang xiangcheng (Cj) (WT/Cj, MT/Cj), and the MT grafted on Trifoliate orange (Pt) (MT/Pt). The differences in sugar, organic acid, flavonoids, phenols, and volatile substances of the three materials were also analyzed by high performance liquid chromatography (HPLC) and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results showed significant differences in the appearance of WT/Cj, MT/Cj, and MT/Pt. MT/Pt, compared to WT/Cj, MT/Cj, had lower sugar, acid, phenol and flavonoid contents in the pulp. However, MT/Pt pulp was higher in vitamin C (VC), and the peel had significantly higher total phenol and flavonoid contents. In terms of pulp, WT/Cj had the greatest diversity of volatile organic compounds (VOCs). 4-methyl-1-pentanol was significantly higher in MT/Cj pulp, while MT/Pt pulp had a unique octanoic acid, methyl ester. VOCs were more diverse in the peels of the three materials. ß-Myrcene and valencen were significantly higher in MT/Cj peels. In contrast, 16 unique VOCs were detected in MT/Pt, and D-limonene content was significantly higher than in WT/Cj and MT/Cj. The results suggest Trifoliate orange is a suitable rootstock for MT.

All-silicon multi-band TM-pass polarizer on a 220 nm SOI enabled by multiplexing grating regimes.

We propose an all-silicon design of a multi-band transverse-magnetic-pass (TM-pass) polarizer. The device is based on one-dimensional gratings that work under different regimes that depend on the polarization. With a tapered structure, it is revealed that the operation bandwidth can be extended by multiplexing the diffraction in O-band and the reflection in S-, C-, and L-bands for the transverse-electric (TE) mode. By simulation, we achieve a 343 nm device bandwidth with insertion loss (IL) < 0.4 dB and polarization extinction ratio (PER) > 20 dB. The operation wavelength range covers commonly-used optical telecommunication bands including the O-, S-, C-, and L- bands. Experimental results also show IL < 1.6 dB and PER > 20 dB from 1265 nm to 1360 nm corresponding to the O-band, and from 1500 nm to 1617 nm that corresponds to the C-band. The device is a single-etched design on the standard 220 nm silicon-on-insulator (SOI) with silicon oxide cladding. Such a simple and compatible design paves the way for developing practical multi-band silicon photonic integrated circuits.

Time-variant entropy regulated multiple access for flexible coherent PON.

To further increase the data rate and rate flexibility of next-generation passive optical networks (PONs), we propose a scheme jointing probabilistic constellation shaping (PCS), constellation diagram identification, and coherent detection. The rate of the coherent PON is dynamically regulated with time-variant entropy, and monitored by the image classifier in real-time. The transmitted cascade frames allocated to different optical network units (ONUs) from the optical line terminal (OLT) can be synchronized, identified, and distinguished by the labeled entropy values. The proposed graphic monitoring scheme is experimentally demonstrated based on a dual-polarized coherent optical transmission system. A 0.5 interval value of entropy is precisely tuned to achieve a 96.13% constellation identification accuracy for entropy/rate by a fast normalized cross correlation coefficient (NCC)-based image classifier. A real-time data rate from 350 to 550 Gb/s with PCS-64-quadrature amplitude modulation (64-QAM) format for a single ONU is achieved which can maximally support five independent ONUs with single wavelength and two polarization states and the entropy varying from 3.5 to 5.5 with 0.5 intervals, respectively.

Diagnostic performance and prognostic impact of coronary angiography-based Index of Microcirculatory Resistance assessment: A systematic review and meta-analysis.

BACKGROUND: The Index of Microcirculatory Resistance (IMR), measured with a pressure-thermistor tipped coronary guidewire has been established as a gold standard for coronary microvascular assessment. Angiography-based IMR (angio-IMR) is a novel method to derive IMR without intracoronary instrumentation or the need for adenosine. METHODS: PubMed and Embase databases were systemically searched in November 2021 for studies that measured angio-IMR. The primary outcomes were pooled sensitivity and specificity as well as the area under the curve (AUC) of the summary receiver operating characteristic curve using IMR as a reference standard. RESULTS: A total of 129 records were initially identified and 8 studies were included in the final analysis. Overall, 1653 lesions were included in this study, of which 733 were in patients presenting with ST-segment elevation myocardial infarction. Angio-IMR yielded high diagnostic performance predicting wire-based IMR with pooled sensitivity = 0.81 (95% confidence interval: 0.76, 0.85), specificity = 0.80 (0.72, 0.86), and AUC = 0.86 (0.82, 0.88), which was similar irrespective of patient presentation. When the clinical outcome was compared between high versus low angio-IMR in patients presenting with myocardial infarction, high angio-IMR predicted an increased risk of major adverse cardiac events (MACE). CONCLUSION: Our study found that coronary angio-IMR has relatively high diagnostic performance as well as prognostic values predicting MACE, supporting its use in clinical practice.

Development and validation of MRI-based radiomics signatures models for prediction of disease-free survival and overall survival in patients with esophageal squamous cell carcinoma.

OBJECTIVES: To develop and validate an optimal model based on the 1-mm-isotropic-3D contrast-enhanced StarVIBE MRI sequence combined with clinical risk factors for predicting survival in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Patients with ESCC at our institution from 2015 to 2017 participated in this retrospective study based on prospectively acquired data, and were randomly assigned to training and validation groups at a ratio of 7:3. Random survival forest (RSF) and variable hunting methods were used to screen for radiomics features and LASSO-Cox regression analysis was used to build three models, including clinical only, radiomics only and combined clinical and radiomics models, which were evaluated by concordance index (CI) and calibration curve. Nomograms and decision curve analysis (DCA) were used to display intuitive prediction information. RESULTS: Seven radiomics features were selected from 434 patients, combined with clinical features that were statistically significant to construct the predictive models of disease-free survival (DFS) and overall survival (OS). The combined model showed the highest performance in both training and validation groups for predicting DFS ([CI], 0.714, 0.729) and OS ([CI], 0.730, 0.712). DCA showed that the net benefit of the combined model and of the clinical model is significantly greater than that of the radiomics model alone at different threshold probabilities. CONCLUSIONS: We demonstrated that a combined predictive model based on MR Rad-S and clinical risk factors had better predictive efficacy than the radiomics models alone for patients with ESCC. KEY POINTS: • Magnetic resonance-based radiomics features combined with clinical risk factors can predict survival in patients with ESCC. • The radiomics nomogram can be used clinically to predict patient recurrence, DFS, and OS. • Magnetic resonance imaging is highly reproducible in visualizing lesions and contouring the whole tumor.

Effectiveness and safety of intracranial events associated with the use of direct oral anticoagulants for atrial fibrillation: A systematic review and meta-analysis of 92 studies.

AIMS: Observational studies have investigated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) used in nonvalvular atrial fibrillation. We performed a systematic review and meta-analysis assessing the risk of ischaemic stroke, thromboembolism (TE) and intracranial haemorrhage (ICH) associated with the use of DOACs and VKAs. METHODS: Medline and Embase were systematically searched until April 2021. Observational studies were gathered and hazard ratios (HRs) with 95% confidence intervals (CI) were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, exposure to VKA, age and sex were performed. A random-effects model was used. RESULTS: We included 92 studies and performed 107 comparisons. Apixaban was associated with lower risk of stroke (HR: 0.82, 95% CI: 0.68-0.99) compared to dabigatran. Rivaroxaban was associated with lower risk of stroke (HR: 0.90, 95% CI: 0.83-0.98) compared to VKA. Dabigatran (HR: 0.85, 95% CI: 0.80-0.91), rivaroxaban (HR: 0.83, 95% CI: 0.77-0.89) and apixaban (HR: 0.75, 95% CI: 0.65-0.86) were associated with lower risk for TE/stroke compared to VKA. Apixaban (HR: 1.32, 95% CI: 1.03-1.68) and rivaroxaban (HR: 1.58, 95% CI: 1.31-1.89) were associated with higher risk of ICH compared to dabigatran. Dabigatran (HR: 0.48, 95% CI: 0.44-0.52), apixaban (HR: 0.60, 95% CI: 0.49-0.73) and rivaroxaban (HR: 0.73, 95% CI: 0.65-0.81) were associated with lower risk of ICH compared to VKA. CONCLUSION: Our study demonstrated significant differences in the risk of ischaemic stroke, TE/stroke and ICH associated with individual DOACs compared to both other DOACs and VKA.

Epidemiologic and clinical characteristics of infective endocarditis: a single-center retrospective study in the Bronx, New York.

OBJECTIVE: There is paucity of data on the epidemiological, microbiological, and clinical characteristics of patients admitted with infective endocarditis (IE) in the Bronx, New York. PATIENT AND METHODS: We conducted a retrospective study at Jacobi Medical Center, a tertiary care hospital in the Bronx. All adult patients who were hospitalized with a primary diagnosis of new-onset IE between January 1st, 2010 and September 30th, 2020 were included. The primary outcome was in-hospital mortality. A logistic regression model was used to identify baseline variables associated with in-hospital mortality. RESULTS: 182 patients were included in this analysis (female sex: 38.5%, median age: 54 years). 46 patients (25.3%) reported intravenous drug use. 153 patients (84.1%) had positive blood cultures. Staphylococcus aureus (S. aureus) was the most common isolated pathogen (45.1% of monomicrobial IE). Nearly half of the cases secondary to S. aureus were methicillin resistant Staphylococcus aureus (MRSA) (34/69). 164 patients (90.1%) were diagnosed with native valve IE. The mitral valve was involved in 32.4% of patients followed by the aortic valve (19.8%). The in-hospital mortality was 18.1%. The mortality was higher in the cohort 2010-2015 compared to the cohort 2016-2020 (22.1% vs 14.6%). Increasing age, MRSA IE, and active malignancy were the only variables found to have significant association with in-hospital death. CONCLUSION: S. aureus was the most common causative agent and MRSA accounted for about half of the S. aureus IE cases. The incidence of IE in patients with intravenous drug use increased over time, while the median age decreased. The in-hospital death rate was higher in 2010-2015 compared to 2016-2020.