An ultralong-life SnS-based anode through phosphate-induced structural regulation for high-performance sodium ion batteries.

As a star representative of transition metal sulfides, SnS is viewed as a promising anode-material candidate for sodium ion batteries due to its high theoretical capacity and unique layered structure. However, the extremely poor electrical conductivity and severe volume expansion strongly hinder its practical application while achieving a high reversible capacity with long-cyclic stability still remains a grand challenge. Herein, different from the conventional enhancement method of elemental doping, we report a rational strategy to introduce PO43- into the SnS layers using phytic acid as the special phosphorus source. Intriguingly, the presence of PO43- in the form of Sn-O-P covalent bonds can act as a conductive pillar to buffer the volume expansion of SnS while expanding its interlay spacing to allow more Na+ storage, supported by both experimental and theoretical evidences. Profiting from this effect combined with microstructural metrics by loading on high pyridine N-doped reduced graphene oxide, the as-prepared material presented an unprecedented ultra-long cyclic stability even after 10,000 cycles along with high reversible capacity and excellent full-cell performances. The findings herein open up new opportunities for elevating electrochemical performances of metal sulfides and provide inspirations for the fabrication of advanced electrode materials for broad energy use.

RpoS contributes in a host-dependent manner to Salmonella colonization of the leaf apoplast during plant disease.

Contaminated fresh produce has been routinely linked to outbreaks of Salmonellosis. Multiple studies have identified Salmonella enterica factors associated with successful colonization of diverse plant niches and tissues. It has also been well documented that S. enterica can benefit from the conditions generated during plant disease by host-compatible plant pathogens. In this study, we compared the capacity of two common S. enterica research strains, 14028s and LT2 (strain DM10000) to opportunistically colonize the leaf apoplast of two model plant hosts Arabidopsis thaliana and Nicotiana benthamiana during disease. While S. enterica 14028s benefited from co-colonization with plant-pathogenic Pseudomonas syringae in both plant hosts, S. enterica LT2 was unable to benefit from Pto co-colonization in N. benthamiana. Counterintuitively, LT2 grew more rapidly in ex planta N. benthamiana apoplastic wash fluid with a distinctly pronounced biphasic growth curve in comparison with 14028s. Using allelic exchange, we demonstrated that both the N. benthamiana infection-depedent colonization and apoplastic wash fluid growth phenotypes of LT2 were associated with mutations in the S. enterica rpoS stress-response sigma factor gene. Mutations of S. enterica rpoS have been previously shown to decrease tolerance to oxidative stress and alter metabolic regulation. We identified rpoS-dependent alterations in the utilization of L-malic acid, an abundant carbon source in N. benthamiana apoplastic wash fluid. We also present data consistent with higher relative basal reactive oxygen species (ROS) in N. benthamiana leaves than in A. thaliana leaves. The differences in basal ROS may explain the host-dependent disease co-colonization defect of the rpoS-mutated LT2 strain. Our results indicate that the conducive environment generated by pathogen modulation of the apoplast niche can vary from hosts to host even with a common disease-compatible pathogen.

A Wide Bandgap Halide Perovskite Based Self-Powered Blue Photodetector with 84.9% of External Quantum Efficiency.

A self-powered, color-filter-free blue photodetector (PD) based on halide perovskites is reported. A high external quantum efficiency (EQE) of 84.9%, which is the highest reported EQE in blue PDs, is achieved by engineering the A-site monovalent cations of wide-bandgap perovskites. The optimized composition of formamidinium (FA)/methylammonium (MA) increases the heat of formation, yielding a uniform and smooth film. The incorporation of Cs+ ions into the FA/MA composition suppresses the trap density and increases charge-carrier mobility, yielding the highest average EQE of 77.4%, responsivity of 0.280 A W-1 , and detectivity of 5.08 × 1012 Jones under blue light. Furthermore, Cs+ improves durability under repetitive operations and ambient atmosphere. The proposed device exhibits peak responsivity of 0.307 A W-1 , which is higher than that of the commercial InGaN-based blue PD (0.289 A W-1 ). This study will promote the development of next-generation image sensors with vertically stacked perovskite PDs.

Nonbiodegradable Spiegelmer-Driven Colorimetric Biosensor for Bisphenol A Detection.

Spiegelmers are enantiomers of natural D-oligonucleotides that bind to targets with distinct structures such as aptamers. The high susceptibility of natural D-form aptamers to nucleases greatly hinders their application in biological environments. Here, a nonbiodegradable spiegelmer-based platform for the sensitive detection of bisphenol A (BPA) was developed. Due to the symmetric molecule of BPA, the D-form aptamer can be directly converted into mirror forms via chemical synthesis. Aptamer-target interactions that involve chemically synthesized spiegelmers were characterized by biolayer interferometry, and their stabilities were tested in various biological fluids by exposure to nucleases. We demonstrate for the first time the use of a nuclease-resistant spiegelmer in a simple, label-free gold nanoparticle-based colorimetric assay to detect BPA in a highly sensitive and selective manner. The aptasensor exhibits an LOD of 0.057 ng/mL and dynamic range of 105 (100 pg/mL to 10 mg/mL). With sensing capacity and biological stability, the developed aptasensor shows great potential to utilize in in-field applications such as water quality monitoring.

Microfluidic Acoustophoresis for Flowthrough Separation of Gram-Negative Bacteria using Aptamer Affinity Beads.

This article describes the fabrication and operation of microfluidic acoustophoretic chips using a microfluidic acoustophoresis technique and aptamer-modified microbeads that can be used for the fast, efficient isolation of Gram-negative bacteria from a medium. This method enhances the separation efficiency using a mix of long, square microchannels. In this system, the sample and buffer are injected into the inlet port through a flow controller. For bead centering and sample separation, AC power is applied to the piezoelectric transducer via a function generator with a power amplifier to generate acoustic radiation force in the microchannel. There is a bifurcated channel at both the inlet and outlet, enabling simultaneous separation, purification, and concentration. The device has a recovery rate of >98% and purity of 97.8% up to a 10x dose concentration. This study has demonstrated a recovery rate and purity higher than the existing methods for separating bacteria, suggesting that the device can separate bacteria efficiently.

The Feasibility of Computer Simulations and 3-Dimensional-Printed Resection Guides for Skin Cancer Resection.

The surgical resection margin in skin cancer is traditionally determined by the lesion's surface boundary without 3-dimensional information. Computed tomography (CT) can offer additional information, such as tumor invasion and the exact cancer extent. This study aimed to demonstrate the clinical application of and to evaluate the safety and accuracy of resection guides for skin cancer treatment. This prospective randomized comparison of skin cancer resection with (guide group; n=34) or without (control group; n=28) resection guide use was conducted between February 2020 and November 2021. Patients with squamous cell carcinoma or basal cell carcinoma were included. In the guide group, based on CT images, the surgical margin was defined, and a 3-dimensional-printed resection guide was fabricated. The intraoperative frozen biopsy results and distance from tumor boundary to resection margin were measured. The margin involvement rates were 8.8% and 17.9% in the guide and control groups, respectively. The margin involvement rate was nonsignificantly higher in the control group as compared with the guide group (P=0.393). The margin distances of squamous cell carcinoma were 2.3±0.8 and 3.4±1.6 mm (P=0.01) and those of basal cell carcinoma were 2.8±1.0 and 4.7±3.2 mm in the guide and control groups, respectively (P=0.015). Margin distance was significantly lower in the guide group than the control group. The resection guide demonstrated similar safety to traditional surgical excision but enabled the minimal removal of normal tissue by precisely estimating the tumor border on CT scans.

A study of quantitative indicators for slice sorting in cine-mode 4DCT.

The uncertainties of four-dimensional computed tomography (4DCT), also called as residual motion artefacts (RMA), induced from irregular respiratory patterns can degrade the quality of overall radiotherapy. This study aims to quantify and reduce those uncertainties. A comparative study on quantitative indicators for RMA was performed, and based on this, we proposed a new 4DCT sorting method that is applicable without disrupting the current clinical workflow. In addition to the default phase sorting strategy, both additional amplitude information from external surrogates and the quantitative metric for RMA, investigated in this study, were introduced. The comparison of quantitative indicators and the performance of the proposed sorting method were evaluated via 10 cases of breath-hold (BH) CT and 30 cases of 4DCT. It was confirmed that N-RMSD (normalised root-mean-square-deviation) was best matched to the visual standards of our institute's regime, manual sorting method, and could accurately represent RMA. The performance of the proposed method to reduce 4DCT uncertainties was improved by about 18.8% in the averaged value of N-RMSD compared to the default phase sorting method. To the best of our knowledge, this is the first study that evaluates RMA indicators using both BHCT and 4DCT with visual-criteria-based manual sorting and proposes an improved 4DCT sorting strategy based on them.

Square microchannel enables to focus and orient ellipsoidal Euglena gracilis cells by two-dimensional acoustic standing wave.

Flow cytometry has become an indispensable tool for counting, analyzing, and sorting large cell populations in biological research and medical practice. Unfortunately, it has limitations in the analysis of non-spherically shaped cells due to the variation of their alignment with respect to the flow direction and, hence, the optical interrogation axis, resulting in unreliable cell analysis. Here, we present a simple on-chip acoustofluidic method to fix the orientation of ellipsoidal cells and focus them into a single, aligned stream. Specifically, by generating acoustic standing waves inside a 100 ⋅ 100 µm square-shaped microchannel, we successfully aligned and focused up to 97.7% of a population of Euglena gracilis (an ellipsoidal shaped microalgal species) cells in the center of the microchannel with high precision at a volume rate of 25 to 200 µL min-1. Uniform positioning of ellipsoidal cells is essential for making flow cytometry applicable to the investigation of a greater variety of cell populations and is expected to be beneficial for ecological studies and aquaculture.

IntraBrain Injector (IBI): A Stereotactic-Guided Device for Repeated Delivery of Therapeutic Agents Into the Brain Parenchyma.

BACKGROUND: To deliver therapeutics into the brain, it is imperative to overcome the issue of the blood-brain-barrier (BBB). One of the ways to circumvent the BBB is to administer therapeutics directly into the brain parenchyma. To enhance the treatment efficacy for chronic neurodegenerative disorders, repeated administration to the target location is required. However, this increases the number of operations that must be performed. In this study, we developed the IntraBrain Injector (IBI), a new implantable device to repeatedly deliver therapeutics into the brain parenchyma. METHODS: We designed and fabricated IBI with medical grade materials, and evaluated the efficacy and safety of IBI in 9 beagles. The trajectory of IBI to the hippocampus was simulated prior to surgery and the device was implanted using 3D-printed adaptor and surgical guides. Ferumoxytol-labeled mesenchymal stem cells (MSCs) were injected into the hippocampus via IBI, and magnetic resonance images were taken before and after the administration to analyze the accuracy of repeated injection. RESULTS: We compared the planned vs. insertion trajectory of IBI to the hippocampus. With a similarity of 0.990 ± 0.001 (mean ± standard deviation), precise targeting of IBI was confirmed by comparing planned vs. insertion trajectories of IBI. Multiple administrations of ferumoxytol-labeled MSCs into the hippocampus using IBI were both feasible and successful (success rate of 76.7%). Safety of initial IBI implantation, repeated administration of therapeutics, and long-term implantation have all been evaluated in this study. CONCLUSION: Precise and repeated delivery of therapeutics into the brain parenchyma can be done without performing additional surgeries via IBI implantation.

Preoperative prediction of the need for arterial and central venous catheterization using machine learning techniques.

Some surgical patients require an arterial or central venous catheterization intraoperatively. This decision relied solely on the experience of individual anesthesiologists; however, these decisions are not easy for clinicians who are in an emergency or inexperienced. Therefore, applying recent artificial intelligence techniques to automatically extractable data from electronic medical record (EMR) could create a very clinically useful model in this situation. This study aimed to develop a model that is easy to apply in real clinical settings by implementing a prediction model for the preoperative decision to insert an arterial and central venous catheter and that can be automatically linked to the EMR. We collected and retrospectively analyzed data from 66,522 patients, > 18 years of age, who underwent non-cardiac surgeries from March 2019 to April 2021 at the single tertiary medical center. Data included demographics, pre-operative laboratory tests, surgical information, and catheterization information. When compared with other machine learning methods, the DNN model showed the best predictive performance in terms of the area under receiver operating characteristic curve and area under the precision-recall curve. Operation code information accounted for the largest portion of the prediction. This can be applied to clinical fields using operation code and minimal preoperative clinical information.

Inertia-Acoustophoresis Hybrid Microfluidic Device for Rapid and Efficient Cell Separation.

In this paper, we proposed an integrated microfluidic device that could demonstrate the non-contact, label-free separation of particles and cells through the combination of inertial microfluidics and acoustophoresis. The proposed device integrated two microfluidic chips which were a PDMS channel chip on top of the silicon-based acoustofluidic chip. The PDMS chip worked by prefocusing the particles/cells through inducing the inertial force of the channel structure. The connected acoustofluidic chips separated particles based on their size through an acoustic radiation force. In the serpentine-shaped PDMS chip, particles formed two lines focusing in the channel, and a trifugal-shaped acoustofluidic chip displaced and separated particles, in which larger particles focused on the central channel and smaller ones moved to the side channels. The simultaneous fluidic works allowed high-efficiency particle separation. Using this novel acoustofluidic device with an inertial microchannel, the separation of particles and cells based on their size was presented and analyzed, and the efficiency of the device was shown. The device demonstrated excellent separation performance with a high recovery ratio (up to 96.3%), separation efficiency (up to 99%), and high volume rate (>100 µL/min). Our results showed that integrated devices could be a viable alternative to current cell separation based on their low cost, reduced sample consumption and high throughput capability.

Multi-center validation of machine learning model for preoperative prediction of postoperative mortality.

Accurate prediction of postoperative mortality is important for not only successful postoperative patient care but also for information-based shared decision-making with patients and efficient allocation of medical resources. This study aimed to create a machine-learning prediction model for 30-day mortality after a non-cardiac surgery that adapts to the manageable amount of clinical information as input features and is validated against multi-centered rather than single-centered data. Data were collected from 454,404 patients over 18 years of age who underwent non-cardiac surgeries from four independent institutions. We performed a retrospective analysis of the retrieved data. Only 12-18 clinical variables were used for model training. Logistic regression, random forest classifier, extreme gradient boosting (XGBoost), and deep neural network methods were applied to compare the prediction performances. To reduce overfitting and create a robust model, bootstrapping and grid search with tenfold cross-validation were performed. The XGBoost method in Seoul National University Hospital (SNUH) data delivers the best performance in terms of the area under receiver operating characteristic curve (AUROC) (0.9376) and the area under the precision-recall curve (0.1593). The predictive performance was the best when the SNUH model was validated with Ewha Womans University Medical Center data (AUROC, 0.941). Preoperative albumin, prothrombin time, and age were the most important features in the model for each hospital. It is possible to create a robust artificial intelligence prediction model applicable to multiple institutions through a light predictive model using only minimal preoperative information that can be automatically extracted from each hospital.

Application of the New Preoperative Frailty Risk Score in Elderly Patients Undergoing Emergency Surgery.

BACKGROUND: Predicting preoperative frailty risk in emergency surgery is difficult with limited information because preoperative evaluation is not commonly performed properly. A recent study attempted to predict preoperative frailty risk using only diagnostic and surgical codes that can be extracted from the electronic medical records system. OBJECTIVE: This study aimed to validate whether the prediction model of preoperative frailty risk presented in the previous study is well applied to other medical hospitals' data. METHODS: This is a retrospective cohort study including 1,557 patients (≥75 years old) who were admitted to a single institution for emergency operations between January 1, 2010, and December 31, 2019, for study analysis. The Charlson comorbidity index, Hospital Frailty Risk Score, and the recently developed Operation Frailty Risk Score (OFRS) were calculated using the patient's diagnostic and operation codes. The predictive performances of these calculated risk scores and the American Society of Anesthesiologists-Physical Status classification for postoperative 90-day mortality were compared by using the receiver operating characteristic curve analysis. FINDINGS: The predictive performance of the OFRS, Charlson comorbidity index, American Society of Anesthesiologists-Physical Status, and Hospital Frailty Risk Score for postoperative 90-day mortality was 0.81, 0.630, 0.699, and 0.549 on a c-statistics basis, respectively. CONCLUSIONS: The OFRS using diagnostic and operation codes may show the best predictive performance for 90-day mortality compared to other risk scores, and it can be the clinically applicable model to evaluate the preoperative frailty risk in elderly patients undergoing emergency surgery.

A New Prognostic index for Extranodal Natural killer/T cell Lymphoma: Incorporation of Serum ß-2 Microglobulin to PINK.

Purpose: Prognostic Index for Natural Killer Lymphoma (PINK) is the most widely accepted prognostic model for patients with Extranodal natural killer/T-cell lymphoma (ENKTL) treated with non-anthracycline based therapy. We aimed to evaluate the prognostic implications of serum ß-2 microglobulin (ß2M) in the context of PINK and proposed a new prognostic model. Materials and Methods: A total of 138 patients who were newly diagnosed with ENKTL and treated with non-anthracycline-based chemotherapy were identified. The cut-off value of high serum ß2M was calculated by maximal-chi square methods (4.1 mg/L). A new prognostic model incorporating serum ß2M into PINK was proposed and validated in an independent validation cohort (n=88). Results: The patients' median age was 53.5 years (range, 19-80). Patients with high serum ß2M levels had significantly worse overall survival (OS) and progression-free survival (PFS). In multivariate analysis, high serum ß2M was an independent adverse prognostic factor for OS. A new PINK-B model stratified patients into three groups with distinct OS and PFS in the training cohort (3-year OS, 84.1% [95% CI 75.1-94.2], 46.8% [36.1-60.8] and 17.6% [6.32-49.2] for the low-, intermediate, and high-risk groups, respectively; 3-year PFS, 70.6% [59.4-83.8], 35.9% [25.9-49.8], and 7.35% [1.16-46.7] for the low-, intermediate, and high-risk groups, respectively). The PINK-B model was further validated in an independent cohort. Conclusion: Serum ß2M is an independent prognostic factor for ENKTL patients. The new serum ß2M-based prognostic model may be useful for identifying ultra-high-risk patients, and it can easily be adopted into daily clinical practice.

Radiation-induced C-reactive protein triggers apoptosis of vascular smooth muscle cells through ROS interfering with the STAT3/Ref-1 complex.

Damage to normal tissue can occur over a long period after cancer radiotherapy. Free radical by radiation can initiate or accelerate chronic inflammation, which can lead to atherosclerosis. However, the underlying mechanisms remain unclear. Vascular smooth muscle cells (VSMCs) proliferate in response to JAK/STAT3 signalling. C-reactive protein (CRP) can induce VSMCs apoptosis via triggering NADPH oxidase (NOX). Apoptotic VSMCs promote instability and inflammation of atherosclerotic lesions. Herein, we identified a VSMCs that switched from proliferation to apoptosis through was enhanced by radiation-induced CRP. NOX inhibition using lentiviral sh-p22phox prevented apoptosis upon radiation-induced CRP. CRP overexpression reduced the amount of STAT3/Ref-1 complex, decreased JAK/STAT phosphorylation and formed a new complex of Ref-1/CRP in VSMC. Apoptosis of VSMCs was further increased by CRP co-overexpressed with Ref-1. Functional inhibition of NOX or p53 also prevented apoptotic activity of the CRP-Ref-1 complex. Immunofluorescence showed co-localization of CRP, Ref-1 and p53 with α-actin-positive VSMC in human atherosclerotic plaques. In conclusion, radiation-induced CRP increased the VSMCs apoptosis through Ref-1, which dissociated the STAT3/Ref-1 complex, interfered with JAK/STAT3 activity, and interacted with CRP-Ref-1, thus resulting in transcription-independent cell death via p53. Targeting CRP as a vascular side effect of radiotherapy could be exploited to improve curability.

Reduced acoustic resonator dimensions improve focusing efficiency of bacteria and submicron particles.

In this study, we demonstrate an acoustofluidic device that enables single-file focusing of submicron particles and bacteria using a two-dimensional (2D) acoustic standing wave. The device consists of a 100 µm × 100 µm square channel that supports 2D particle focusing in the channel center at an actuation frequency of 7.39 MHz. This higher actuation frequency compared with conventional bulk acoustic systems enables radiation-force-dominant motion of submicron particles and overcomes the classical size limitation (≈2 µm) of acoustic focusing. We present acoustic radiation force-based focusing of particles with diameters less than 0.5 µm at a flow rate of 12 µL min-1, and 1.33 µm particles at flow rates up to 80 µL min-1. The device focused 0.25 µm particles by the 2D acoustic radiation force while undergoing a channel cross-section centered, single-vortex acoustic streaming. A suspension of bacteria was also investigated to evaluate the biological relevance of the device, which demonstrated the alignment of bacteria in the channel at a flow rate of up to 20 µL min-1. The developed acoustofluidic device can align submicron particles within a narrow flow stream in a highly robust manner, validating its use as a flow-through focusing chamber to perform high-throughput and accurate flow cytometry of submicron objects.

BCL2 super-expressor diffuse large B-cell lymphoma: a distinct subgroup associated with poor prognosis.

Overexpression of the BCL2 protein has been reported as a poor prognostic factor for diffuse large B-cell lymphoma (DLBCL). However, there are currently no standardized criteria for evaluating BCL2 protein expression. We aimed to evaluate the prognostic value of BCL2 expression determined by immunohistochemistry (IHC), incorporating both the staining intensity and proportion, in patients with de novo DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment. We defined tumors with BCL2 expression in nearly all tumor cells with a uniformly strong intensity by IHC as BCL2 super-expressor. The BCL2 super-expressors (n = 35) showed significantly worse event-free survival (EFS; HR, 1.903; 95% CI, 1.159-3.126, P = 0.011) and overall survival (OS; HR, 2.467; 95% CI, 1.474-4.127, P = 0.001) compared with the non-BCL2 super-expressors (n = 234) independent of the international prognostic index (IPI), cell of origin (COO), and double expressor status in the training set (n = 269). The adverse prognostic impact of BCL2 super-expression was confirmed in the validation set (n = 195). When the survival outcomes were evaluated in the entire cohort (n = 464), BCL2 super-expressor group was significantly associated with inferior EFS and OS regardless of IPI, COO, MYC expression, and stages. BCL2 super-expressors had genetic aberrations enriched in the NOTCH and TP53 signaling pathways. This study suggests that the BCL2 super-expressor characterizes a distinct subset of DLBCL with a poor prognosis and warrants further investigation as a target population for BCL-2 inhibitors.

Prognostic significance of serum ß2-microglobulin levels in patients with peripheral T-cell lymphoma not otherwise specified.

We aimed to investigate the prognostic value of serum ß2-microglobulin in patients with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS). A cohort study of PTCL-NOS patients (n = 147) was conducted. An elevated serum ß2-microglobulin level was associated with the presence of previously identified predictors of a poor prognosis for PTCL-NOS. Patients with an elevated serum ß2-microglobulin level exhibited a significantly worse progression-free survival (PFS) and overall survival (OS). Multivariate analyses revealed that an elevated serum ß2-microglobulin level was independently associated with a shorter PFS and OS. A new prognostic index incorporating the serum ß2-microglobulin level allowed for the stratification of patients into three distinct risk subgroups. The index was validated to stratify patients with distinct survival outcomes in an independent cohort of PTCL-NOS (n = 89). In conclusion, serum ß2-microglobulin level is an independent prognostic factor in patients with PTCL-NOS. Our ß2-microglobulin-based prognostic index for PTCL-NOS deserves further investigation and validation.