Comparison of metagenomic next-generation sequencing and blood culture for diagnosis of bloodstream infections.

Objectives: This study aimed to evaluate the clinical performance of plasma cell-free DNA (cfDNA) next-generation sequencing (NGS) for pathogen detection in patients with sepsis. Methods: A total of 43 pairs of blood and plasma samples form 33 blood culture-positive patients were used as testing samples in metagenomic NGS (mNGS) and NGS of 16S ribosomal RNA gene amplicons (16S rRNA NGS). The results of routine tests, including microbial culture, complete blood count, and biochemical tests, were collected from electronic medical records. Results: Using blood as an mNGS testing sample, the proportion of host DNA was 99.9%, with only three bacteria and no fungi detected. When using plasma in mNGS, the proportion of host DNA was approximately 97%, with 84 bacteria and two fungi detected. Notably, 16S rRNA NGS detected 15 and 16 bacteria in 43 pairs of blood and plasma samples, respectively. Blood culture detected 49 bacteria (23 gram-negative bacilli and 26 gram-positive cocci) and four fungi, with 14 bacteria considered contaminants by clinical microbiologists. For all blood cultures, plasma cfDNA mNGS detected 78.26% (19/23) gram-negative rods, 17% (2/12) gram-positive cocci, and no fungi. Compared to blood cultures, the sensitivity and specificity of plasma cfDNA mNGS for detecting bacteria and fungi were 62.07% and 57.14%, respectively. Conclusion: Compared to blood, plasma is more suitable for the detection of bloodstream infections using mNGS and is less affected by host DNA. The positive detection rate of plasma cfDNA mNGS for bloodstream infections caused by gram-negative bacteria was higher than that caused by gram-positive cocci.

Predictive response and outcome of peripheral CD4+ T cell subpopulations to combined immunotherapy and chemotherapy in advanced gastric cancer patients.

BACKGROUND: The identification of predictive biomarkers for patient stratification in immunotherapy is of utmost importance, given the limited benefit observed in certain populations. However, only limited information is so far available on the association between peripheral CD4+ T cell subpopulations and immunotherapy for advanced gastric cancer. Our current report aimed to investigate the predictive value of peripheral CD4+ T cell subpopulations in advanced gastric cancer patients treated with immunotherapy. METHODS: A retrospective cohort analysis of 169 advanced gastric cancer patients treated with sintilimab combined with capecitabine and oxaliplatin in The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University (Xinghua, China) between June 2019 and October 2022 was conducted. Clinical outcomes of peripheral CD4+ T cell subpopulations were analyzed by receiver operating characteristic (ROC) curve, chi-square test, Kaplan-Meier method and the univariate and multivariate Cox proportional hazards regression models. RESULTS: The optimal cutoff values for percentages of CD4+ T cells, naive CD4+ T cells (CD4+ Tn), memory CD4+ T cells (CD4+ Tm), central memory CD4+ T cells (CD4+ Tcm) and effector memory CD4+ T cells (CD4+ Tem) expressing PD-1 were 30.16 %, 17.79 %, 42.49 %, 31.54 % and 74.64 %, respectively. It was found that the percentages of CD4+ T, CD4+ Tn, CD4+ Tm, CD4+ Tcm and CD4+ Tem expressing PD-1 were significantly higher in responder (R) than non-responder (NonR) advanced gastric cancer patients associated with a longer progression free survival (PFS) and overall survival (OS). This correlation was also observed in the PD-L1 combined positive score (CPS) ≥ 5 populations. Univariate and multivariate Cox regression analyses indicated that lower CD4+ T, CD4+ Tn, CD4+ Tm, CD4+ Tcm and CD4+ Tem expressing PD-1 were independent risk factors of PFS and OS in advanced gastric cancer patients treated with combined immunotherapy and chemotherapy. CONCLUSION: The peripheral CD4+ T cell subpopulations demonstrated the high predictive value for therapeutic response and prolonged survival outcomes in advanced gastric cancer patients. CD4+ T cell subpopulations have the potential in predicting and screening benefit populations in advanced gastric cancer patients.

Grain boundary defects passivation by bridging diammonium toward stable and efficient perovskite solar cells.

The grain boundary defects of polycrystalline perovskite could induce severe carrier recombination loss to restrict the photovoltaic and stability advancement of perovskite-based solar cells (PSCs). Inserting fixed molar ratio organic cations spacers into halide perovskite slabs to reduce the dimension of the crystal structure is still limited in finding a compromise of efficiency and stability for the widened bandgap and increasing barriers for carrier transport. Here, we select a direct additive bridging engineering to introduce a rationally designed organic amine salt 1,4-Benzene diammonium iodide (BDAI2) with ammonium group on both terminals of the benzene ring to passivate the grain boundary and interface defects of perovskite. Bridging diammonium could ameliorate the interface contact and achieve electrostatic interactions with negatively charged traps (such as uncoordinated I-, PbI3-, and methylammonium vacancies) to inhibit cation migration, reduce halogen ion vacancy, and then suppress trap-induced recombination in perovskite. As a result, the bridging diammonium could improve the power conversion efficiency (PCE) from 19.86% to 21.91%. This study highlights the importance of rational bridging diammonium for perovskite surface modification and passivation to boost photovoltaic performance and stability.

Characterizing the penumbras of white matter hyperintensities in patients with cerebral small vessel disease.

PURPOSE: The white matter hyperintensity penumbra (WMH-P) is the subtly changed normal-appearing white matter (NAWM) that surrounds white matter hyperintensities (WMHs). The goal of this study was to define WMH-P in cerebral small vessel disease (CSVD) by arterial spin labeling (ASL) and diffusion tensor imaging (DTI)/diffusion kurtosis imaging (DKI). MATERIALS AND METHODS: We prospectively analyzed 42 patients with CSVD. To determine the range of cerebral blood flow (CBF) and DTI/DKI penumbras around white matter hyperintensities, we generated NAWM layer masks from periventricular WMHs (PVWMHs) and deep WMHs (DWMHs). Mean values of CBF, fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, mean kurtosis, axial kurtosis, and radial kurtosis within the WMHs and their corresponding NAWM layer masks were analyzed. Paired sample t tests were used for analysis, and differences were considered statistically significant if the associated p value was ≤ 0.05. RESULTS: For DWMHs, the CBF penumbras were 13 mm, and the DTI/DKI penumbras were 8 mm. For PVWMHs, the CBF penumbras were 14 mm, and the DTI/DKI penumbras were 14 mm. CONCLUSIONS: Our findings revealed that DTI/DKI and ASL can show structural and blood flow changes in brain tissue surrounding WMHs. In DWMHs, the blood flow penumbra was larger than the structural penumbra, while in PVWMHs, the blood flow penumbra was almost the same as the structural penumbra.

Molecular Synergistic Passivation for Efficient Perovskite Solar Cells and Self-Powered Photodetectors.

The interface between the perovskite and electron-transporting material is often treated for defect passivation to improve the photovoltaic performance of devices. A facile 4-Acetamidobenzoic acid (containing an acetamido, a carboxyl, and a benzene ring)-based molecular synergistic passivation (MSP) strategy is developed here to engineer the SnOx /perovskite interface, in which dense SnOx are prepared using an E-beam evaporation technology while the perovskite is deposited with vacuum flash evaporation deposition method. MSP engineering can synergistically passivate defects at the SnOx /perovskite interface by coordinating with Sn4+ and Pb2+ with functional group CO in the acetamido and carboxyl. The optimized solar cell devices can achieve the highest efficiency of 22.51% based on E-Beam deposited SnOx and 23.29% based on solution-processed SnO2 , respectively, accompanied by excellent stability exceeding 3000 h. Further, the self-powered photodetectors exhibit a remarkably low dark current of 5.22 × 10-9  A cm-2 , a response of 0.53 A W-1 at zero bias, a detection limit of 1.3 × 1013  Jones, and a linear dynamic range up to 80.4 dB. This work proposes a molecular synergistic passivation strategy to enhance the efficiency and responsivity of solar cells and self-powered photodetectors.

Managing Interfacial Defects and Carriers by Synergistic Modulation of Functional Groups and Spatial Conformation for High-Performance Perovskite Photovoltaics Based on Vacuum Flash Method.

Interfacial nonradiative recombination loss is a huge barrier to advance the photovoltaic performance. Here, one effective interfacial defect and carrier dynamics management strategy by synergistic modulation of functional groups and spatial conformation of ammonium salt molecules is proposed. The surface treatment with 3-ammonium propionic acid iodide (3-APAI) does not form 2D perovskite passivation layer while the propylammonium ions and 5-aminopentanoic acid hydroiodide post-treatment lead to the formation of 2D perovskite passivation layers. Due to appropriate alkyl chain length, theoretical and experimental results manifest that COOH and NH3 + groups in 3-APAI molecules can form coordination bonding with undercoordinated Pb2+ and ionic bonding and hydrogen bonding with octahedron PbI6 4- , respectively, which makes both groups be simultaneously firmly anchored on the surface of perovskite films. This will strengthen defect passivation effect and improve interfacial carrier transport and transfer. The synergistic effect of functional groups and spatial conformation confers 3-APAI better defect passivation effect than 2D perovskite layers. The 3-APAI-modified device based on vacuum flash technology achieves an alluring peak efficiency of 24.72% (certified 23.68%), which is among highly efficient devices fabricated without antisolvents. Furthermore, the encapsulated 3-APAI-modified device degrades by less than 4% after 1400 h of continuous one sun illumination.

Zwitterionic ionic liquid synergistically induces interfacial dipole formation and traps state passivation for high-performance perovskite solar cells.

Defects at the interface and grain boundaries of perovskite solar cells (PSCs) will result in severe non-radiative recombination and open-circuit voltage (Voc) loss. Herein, we reported a zwitterionic ionic liquid imidazolium tetrafluoroborate (IMBF4) to passivate the defects at tin dioxide (SnO2)/perovskite interface. The results showed that the electron-rich nitrogen atom contained IM+ could diffuse into the buried perovskite to exhibit a strong chemical passivation effect on the organic vacancy defect by interacting with uncoordinated Pb2+. The F- in BF4- has a strong coordination effect with Pb2+in perovskite and Sn2+ in SnO2 synchronously to fill the anion vacancy defect. Also, the BF4- anions could help to form an interface dipole layer to increase the charge transfer rate and reduce the work function. The IMBF4 modified device could achieve an efficiency enhancement from 20.18% to 23.05% by vacuum flash-assisted solution-processed, with the increased Voc from 1.09 V to 1.15 V. The unencapsulated IMBF4 modified device could maintain 93% of the initial efficiency after ageing for 2000 h under ambient conditions by the ISOS-D-1 stability-testing protocols. This work emphasizes the importance of multifunctional additives in passivating defects and improving interface contact for achieving efficient and stable perovskite solar cells.

The Predictive Value of Systemic Inflammatory Factors in Advanced, Metastatic Esophageal Squamous Cell Carcinoma Patients Treated with Camrelizumab.

Objective: Systemic inflammatory factors are independent risk factors in the formation and progression of various solid tumors. However, whether systemic inflammatory factors are associated with effect and prognosis of esophageal squamous cell carcinoma patients treated with immunotherapy remains unknown. The aim of this study is to assess the value of systemic inflammatory factors in the efficacy of camrelizumab for patients with advanced, metastatic esophageal squamous cell carcinoma. Methods: We conducted a retrospective analysis of 90 patients with advanced, metastatic esophageal squamous cell carcinoma who received treatment with camrelizumab in Xinghua People's Hospital between August 2019 and October 2021. The optimal cut-off values of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) for predicting efficacy and prognosis were identified based on the receiver operating characteristic (ROC) curve. Progression free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, and differences in PFS or OS between groups were compared by the Log rank test. Univariate and multivariate Cox proportional hazards regression models were performed to analyze prognostic values of each variable. Results: The optimal cutoff values of PLR, NLR and SII predicted survival outcomes were 157.7, 3.84 and 750.8, respectively. Higher PLR, NLR and SII were associated with shorter PFS (HR for PLR = 2.899, P = 0.001; HR for NLR = 3.629, P < 0.001; HR for SII = 10.251, P < 0.001) and OS (HR for PLR = 4.583, P < 0.001; HR for NLR = 3.921, P < 0.001; HR for SII = 38.606, P < 0.001). Multivariate Cox regression analysis revealed that high PLR, NLR and SII were independent risk factors of PFS and OS in the advanced, metastatic esophageal squamous cell carcinoma patients receiving camrelizumab. Conclusion: PLR, NLR and SII are potentially effective prognostic predictors in advanced, metastatic esophageal squamous cell carcinoma patients treated with camrelizumab.

Heterojunction In Situ Constructed by a Novel Amino Acid-Based Organic Spacer for Efficient and Stable Perovskite Solar Cells.

The optical properties and stability of metal halide perovskites can be improved by reducing their dimensionality. Because defects at the perovskite film grain body and boundaries cause significant energetic losses by nonradiative recombination, perovskite films with manageable crystal size and macroscopic grains are essential to improve the photovoltaic properties. Through theoretical calculation models and experiments, we show that the carboxyl group of 4-ammonium butyric acid-based cation (4-ABA+) can interact with the three-dimensional (3D) perovskite to produce in situ a secondary grain growth by post-treatment. It passivates the trap defects and broadens the light absorption. 4-ABA+ could induce a 2D capping layer on top of 3D mixed cation-based perovskite to construct a 2D/3D heterojunction. The 4-ABA+-modified perovskite film consists of large-sized grains with extremely low trap state densities and possesses a longer charge carrier lifetime and good stability, resulting in efficient perovskite solar cells with a champion efficiency of 23.16% and a VOC of 1.20 V. We show that the 4-ABA+-treated devices outperform the 3-ammonium propionic acid (3-APA+)- and 5-ammonium valeric acid (5-AVA+)-treated ones. Moreover, the devices exhibit high stability under high humidity and continuous light soaking conditions. This work gives a hint that our approach based on 4-ABA+ treatment is key to achieving better electrical properties, a controlled crystal growth, and highly stable perovskite solar cells.

Functionalizing phenethylammonium by methoxy to achieve low-dimensional interface defects passivation for efficient and stable perovskite solar cells.

Low dimensional interface passivation has been proved to be an efficient method to lessen the nonradiative recombination loss in perovskite solar cells. To overcome the limitation of Phenethylammonium (PEA+) for carrier transport and water molecule intrusion, we developed a modification strategy by functioning the typical PEA+with the 4-methoxy to optimize the interface defects and carrier transport performance, thus maximizing the synchronous improvement of device efficiency and stability. Our results indicate that the 2 mg ml-14-methoxy-phenethylammonium (MeO-PEA+) modified device could achieve a best power conversion efficiency of 19.64% with improved shelf-life stability in ambient conditions. The new passivation molecule of MeO-PEA+could possess the capability of defect passivation, carrier transfer, and moisture blocking, demonstrating that rationally designed organic components for interface passivation could help to achieve efficient and stable PSCs.

Visual signal generation for the detection of influenza viruses by duplex recombinase polymerase amplification with lateral flow dipsticks.

We present a detailed study on visual detection of influenza viruses by duplex recombinase polymerase amplification (RPA) with lateral flow dipsticks (LFDs). The LFD consisted of two test lines and a control line, on which anti-fluorescein isothiocyanate antibodies, anti-digoxigenin antibodies, and biotinylated bovine serum albumin were immobilized, respectively. The performance of the LFD was evaluated with dual-labeled DNA amplicons. The results indicate that the detection of DNA amplicons by LFDs is specific and sensitive, with detection limits of 5.80 fmol for fluorescein isothiocyanate-labeled amplicons and 8.39 fmol for digoxigenin-labeled amplicons. We next developed a duplex RPA-LFD assay for simultaneous detection of influenza A virus and influenza B virus, and then optimized the parameters, including the reaction temperature, reaction time, and concentrations of primers and probes. Assessment of the specificity and sensitivity indicated that this assay is sensitive and specific for simultaneous detection of influenza viruses, with detection limits of 50 copies per reaction for influenza B virus and 500 copies per reaction for influenza A virus, without cross-reactivity with other pathogens. Compared with real-time PCR as a reference method to detect influenza viruses in clinical samples, the clinical sensitivity of the duplex RPA-LFD assay was 78.57% for influenza A virus and 87.50% for influenza B virus, with 100% specificity. In conclusion, the duplex RPA-LFD assay is a rapid, cost-effective, and sensitive method for the identification of influenza viruses.

Identification of citrullinated peptides in the synovial fluid of patients with rheumatoid arthritis using LC-MALDI-TOF/TOF.

The objective of the study is to investigate potential citrullinated autoantigens as targets of anti-citrullinated protein antibodies (ACPAs) response in synovial fluids (SFs) of patients with rheumatoid arthritis (RA). SFs from six RA patients and six osteoarthritis (OA) patients as controls were collected. The citrullinated proteins in SFs were extracted by immunoprecipitation with rabbit anti-citrulline antibodies. Matrix-assisted laser desorption/ionization time of flight mass spectrometry/time of flight mass spectrometry (MALDI-TOF/TOF) mass spectrometry was subsequently performed to discover a characteristic neutral loss to finally determine citrullinated autoantigens. A total of 182 citrullinated peptides and 200 citrullinated sites were identified in RA SFs, while 3 citrullinated peptides and 4 citrullinated sites were identified in OA SFs. The 182 citrullinated peptides from RA SFs and the 3 citrullinated peptides from OA SFs were derived from 83 and 3 autoantigens, respectively. Eighty-three autoantigens except protein-arginine deiminase type-2 (PADI2) and protein-arginine deiminase type-2 (PADI4) were over-citrullinated compared with controls, and the citrullinated sites of PADI2 and PADI4 were different in two groups. Interestingly, citrullinated histone H3.3 (H3F3A) was found in OA controls, but not in RA groups. The differential citrullinated proteins identified in RA SFs suggested potential autoantigens were targeted for ACPAs response and might contribute to the induction and perpetuation of complement activation and joint inflammation in RA.

Proteomic analysis of synovial fibroblast-like synoviocytes from rheumatoid arthritis.

OBJECTIVES: The purpose of this study was to identity protein expression patterns of fibroblast-like synoviocytes (FLSs) derived from the synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis. METHODS: Two-dimensional gel electrophoresis (2-DE) in combination with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) was used to visualise and identify differential cellular protein expression profiles in FLSs between RA and control groups. Western-blot analysis was performed to further verify selected differentially-expressed proteins. RESULTS: A total of 1633 and 1603 protein spots were examined in synovial FLSs of RA patients and controls, respectively. Ninety-two spots in the RA group were statistically over- or under-expressed compared with controls. Among them, 33 proteins over-expressed by more than 3-fold were then identified by MALDI-TOF-MS analysis. These proteins included enzymatic and structural proteins (e.g. PKM1/M2, α-enolase, ERp60, lamin-A/C), signal transduction proteins (e.g. annexin 11, peroxiredoxin 1, TrpRS), heat-shock/chaperone proteins (e.g. TCP-1, GRP75, HspB5, Bip) and some unknown protein species. Three proteins, namely α-enolase, GRP75 and PKM2, were verified by Western blot and the results were found to be consistent with proteomic analysis. CONCLUSIONS: The differentially expressed proteins identified in RA synovial FLSs might be candidate RA-associated proteins and may prove to be promising diagnostic indicators or new therapeutic targets for RA.