GlcNAc-1,6-anhydro-MurNAc Moiety Affords Unusual Glycosyl Acceptor that Terminates Peptidoglycan Elongation.

Peptidoglycan (PG), an essential exoskeletal polymer in bacteria, is a well-known antibiotic target. PG polymerization requires the action of bacterial transglycosylases (TGases), which couple the incoming glycosyl acceptor to the donor. Interfering with the TGase activity can interrupt the PG assembly. Existing TGase inhibitors like moenomycin and Lipid II analogues always occupy the TGase active sites; other strategies to interfere with proper PG elongation have not been widely exploited. Inspired by the natural 1,6-anhydro-MurNAc termini that mark the ends of PG strands in bacteria, we hypothesized that the incorporation of an anhydromuramyl-containing glycosyl acceptor by TGase into the growing PG may effectively inhibit PG elongation. To explore this possibility, we synthesized 4-O-(N-acetyl-ß-d-glucosaminyl)-1,6-anhydro-N-acetyl-ß-d-muramyl-l-Ala-γ-d-Glu-l-Lys-d-Ala-d-Ala, 1, within 15 steps, and demonstrated that this anhydromuropeptide and its analogue lacking the peptide, 1-deAA, were both utilized by bacterial TGase as noncanonical anhydro glycosyl acceptors in vitro. The incorporation of an anhydromuramyl moiety into PG strands by TGases afforded efficient termination of glycan chain extension. Moreover, the preliminary in vitro studies of 1-deAA against Staphylococcus aureus showed that 1-deAA served as a reasonable antimicrobial adjunct of vancomycin. These insights imply the potential application of such anhydromuropeptides as novel classes of PG-terminating inhibitors, pointing toward novel strategies in antibacterial agent development.

A Strain-Promoted Divergent Chemical Steroidation Unveils Potent Anti-Inflammatory Pseudo-Steroidal Glycosides.

The development of novel agents with immunoregulatory effects is a keen way to combat the growing threat of inflammatory storms to global health. To synthesize pseudo-steroidal glycosides tethered by ether bonds with promising immunomodulatory potential, we develop herein a highly effective deoxygenative functionalization of a novel steroidal donor (steroidation) facilitated by strain-release, leveraging cost-effective and readily available Sc(OTf)3 catalysis. This transformation produces a transient steroid-3-yl carbocation which readily reacts with O-, C-, N-, S-, and P-nucleophiles to generate structurally diverse steroid derivatives. DFT calculations were performed to shed light on the mechanistic details of the regioselectivity, underlying an acceptor-dependent steroidation mode. This approach can be readily extended to the etherification of sugar alcohols to enable the achievement of a diversity-oriented, pipeline-like synthesis of pseudo-steroidal glycosides in good to excellent yields with complete stereo- and regiospecific control for anti-inflammatory agent discovery. Immunological studies have demonstrated that a meticulously designed cholesteryl disaccharide can significantly suppress interleukin-6 secretion in macrophages, exhibiting up to 99% inhibition rates compared to the negative control. These findings affirm the potential of pseudo-steroidal glycosides as a prospective category of lead agents for the development of novel anti-inflammatory drugs.

Ion-Molecule Co-Confining Ammonium Vanadate Cathode for High-Performance Aqueous Zinc-Ion Batteries.

Vanadium-based cathode materials have attracted great attention in aqueous zinc-ion batteries (AZIBs). However, the inferior ion transport and cyclic stability due to the strong Coulomb interaction between Zn2+ and the lattice limit their further application. In this work, CO2 molecules are in situ embedded in the interlayer structure of NH4V4O10 by decomposing excess H2C2O4·2H2O in the main framework, obtaining an ion-molecule co-confining NH4V4O10 for AZIB cathode material. The introduced CO2 molecules expanded the interlayer spacing of NH4V4O10, broadened the diffusion channel of Zn2+, and stabilized the structure of NH4V4O10 as the interlayer pillars together with NH 4 + ${\mathrm{NH}}_4^ + $ , which effectively improved the Zn2+ diffusion kinetics and cycle stability of the electrode. In addition, the binding between NH 4 + ${\mathrm{NH}}_4^ + $ and the host framework is stabilized via hydrogen bonds with CO2 molecules. NVO-CO2-0.8 exhibited excellent specific capacity (451.1 mAh g-1 at 2 A g-1), cycle stability (214.0 mAh g-1 at 10 A g-1 after 1000 cycles) and rate performance. This work provides new ideas and approaches for optimizing vanadium-based materials with high-performance AZIBs.

Clinical outcomes of carbapenem-resistant gram-negative bacterial bloodstream infection in patients with end-stage renal disease in intensive care units: a multicenter retrospective observational study.

BACKGROUND: Carbapenem-resistant gram-negative bacteria (CRGNB) present a considerable global threat due to their challenging treatment and increased mortality rates, with bloodstream infection (BSI) having the highest mortality rate. Patients with end-stage renal disease (ESRD) undergoing renal replacement therapy (RRT) face an increased risk of BSI. Limited data are available regarding the prognosis and treatment outcomes of CRGNB-BSI in patients with ESRD in intensive care units (ICUs). METHODS: This multi-center retrospective observational study included a total of 149 ICU patients with ESRD and CRGNB-BSI in Taiwan from January 2015 to December 2019. Clinical and microbiological outcomes were assessed, and multivariable regression analysis was used to evaluate the independent risk factors for day-28 mortality and the impact of antimicrobial therapy regimen on treatment outcomes. RESULTS: Among the 149 patients, a total of 127 patients (85.2%) acquired BSI in the ICU, with catheter-related infections (47.7%) and pneumonia (32.2%) being the most common etiologies. Acinetobacter baumannii (49.0%) and Klebsiella pneumoniae (31.5%) were the most frequently isolated pathogens. The day-28 mortality rate from BSI onset was 52.3%, and in-hospital mortality was 73.2%, with survivors experiencing prolonged hospital stays. A higher Sequential Organ Failure Assessment (SOFA) score (adjusted hazards ratio [aHR], 1.25; 95% confidence interval [CI] 1.17-1.35) and shock status (aHR, 2.12; 95% CI 1.14-3.94) independently predicted day-28 mortality. Colistin-based therapy reduced day-28 mortality in patients with shock, a SOFA score of ≥ 13, and Acinetobacter baumannii-related BSI. CONCLUSIONS: CRGNB-BSI led to high mortality in critically ill patients with ESRD. Day-28 mortality was independently predicted by a higher SOFA score and shock status. In patients with higher disease severity and Acinetobacter baumannii-related BSI, colistin-based therapy improved treatment outcomes.

Population pharmacokinetics and pharmacodynamics of efmarodocokin alfa (IL-22Fc).

Efmarodocokin alfa (IL-22Fc) is a fusion protein of human IL-22 linked to the crystallizable fragment (Fc) of human IgG4. It has been tested in multiple indications including inflammatory bowel disease (IBD). The purposes of the present analyses were to describe the population pharmacokinetics (PK) of efmarodocokin alfa and perform pharmacodynamic (PD) analysis on the longitudinal changes of the PD biomarker REG3A after efmarodocokin alfa treatment as well as identify covariates that affect efmarodocokin alfa PK and REG3A PD. The data used for this analysis included 182 subjects treated with efmarodocokin alfa in two clinical studies. The population PK and PD analyses were conducted sequentially. Efmarodocokin alfa concentration-time data were analyzed using a nonlinear mixed-effects modeling approach, and an indirect response model was adopted to describe the REG3A PD data with efmarodocokin alfa serum concentration linked to the increase in REG3A. The analysis software used were NONMEM and R. A 3-compartment model with linear elimination best described the PK of efmarodocokin alfa. The estimated population-typical value for clearance (CL) was 1.12 L/day, and volume of central compartment was 6.15 L. Efmarodocokin alfa CL increased with higher baseline body weight, C-reactive protein, and CL was 27.6% higher in IBD patients compared to healthy subjects. The indirect response PD model adequately described the longitudinal changes of REG3A after efmarodocokin alfa treatment. A popPK and PD model for efmarodocokin alfa and REG3A was developed and covariates affecting the PK and PD were identified.

Utilization of 3D evaluation for assessing selective caries removal practice in pre-clinical dental students: a pilot study.

BACKGROUND: Practicing and assessment of selective caries removal techniques in dental students remain challenges in many dental schools. The aim of this study was to utilize a 3D assessment technique, within a designated acceptable range of deviation, to evaluate the tendency of dental students in performing selective caries removal (SCR). The correlation between 3D assessment results and the conventional rubric rated by an instructor was also determined. METHODS: Fifth-year dental students (n = 61) performed the SCR task on 3D-printed teeth containing simulated deep caries lesions in occlusal and proximal surfaces. One instructor assessed the results using a conventional analytic rubric. The excavated teeth were additionally evaluated using 3D analysis software with the designated acceptable range of deviations (± 0.5 mm) from the standard cavities. The average root mean square (RMS) value, representing the deviation between student-prepared cavities and the predefined standard cavities, was recorded. A tendency towards over-excavation was defined for RMS values > 0.5 mm, and towards under-excavation for RMS values < 0.5 mm. RESULTS: The mean (min-max) of RMS was 0.27 (0.18-0.40) for occlusal and 0.29 (0.20-0.57)for proximal cavities. A tendency of dental students toward over-excavation was observed in both occlusal (74%) and proximal cavities (87%). There was a moderate negative correlation between the RMS values and the traditional rubric scores for both occlusal (R2 = 0.148, P = 0.002) and proximal cavities (R2 = 0.107, P = 0.010). CONCLUSIONS: The 3D evaluation technique effectively revealed specific tendencies in dental students' caries removal skills. The integration of computerized assessments with traditional methods could potentially assist the instructors in delivering more objective and specific feedback to students. Further research is encouraged to investigate the impact of this assessment technique on improving student performance in selective caries removal skills.

Single-Nucleus Transcriptional Profiling of Chronic Kidney Disease after Cisplatin Nephrotoxicity.

Cisplatin induces both acute and chronic nephrotoxicity during chemotherapy in patients with cancer. Presented here is the first study of single-nucleus RNA sequencing (snRNA-seq) of cisplatin-induced nephrotoxicity. Repeated low-dose cisplatin treatment (RLDC) led to decreases in renal function and kidney weight in mice at 9 weeks. The kidneys of these mice showed tubular degeneration and dilation. snRNA-seq identified 16 cell types and 17 cell clusters in these kidneys. Cluster-by-cluster comparison demonstrated cell type-specific changes in gene expression and identified a unique proximal tubule (PT) injury/repair cluster that co-expressed the injury marker kidney injury molecule-1 (Kim1) and the proliferation marker Ki-67. Compared with control, post-RLDC kidneys had 424 differentially expressed genes in PT cells, including tubular transporters and cytochrome P450 enzymes involved in lipid metabolism. snRNA-seq also revealed transcriptional changes in potential PT injury markers (Krt222, Eda2r, Ltbp2, and Masp1) and repair marker (Bex4). RLDC induced inflammation and proinflammatory cytokines (RelB, TNF-α, Il7, Ccl2, and Cxcl2) and the expression of fibrosis markers (fibronectin, collagen I, connective tissue growth factor, vimentin, and α-smooth muscle actin). Together, these results provide new insights into RLDC-induced transcriptional changes at the single-cell level that may contribute to the development of chronic kidney problems in patients with cancer after cisplatin chemotherapy.

Archway Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration 2-Year Results.

PURPOSE: To report 2-year results from the Archway clinical trial of the Port Delivery System with ranibizumab (PDS) for treatment of neovascular age-related macular degeneration (nAMD). DESIGN: Phase 3, randomized, multicenter, open-label, active-comparator-controlled trial. PARTICIPANTS: Patients with previously treated nAMD diagnosed within 9 months of screening and responsive to anti-vascular endothelial growth factor therapy. METHODS: Patients were randomized 3:2 to PDS with ranibizumab 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W) or intravitreal ranibizumab 0.5 mg injections every 4 weeks (monthly ranibizumab). Patients were followed through 4 complete refill-exchange intervals (∼2 years). MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline averaged over weeks 44 and 48, weeks 60 and 64, and weeks 88 and 92 (noninferiority margin, -3.9 ETDRS letters). RESULTS: The PDS Q24W was noninferior to monthly ranibizumab, with differences in adjusted mean change in BCVA score from baseline averaged over weeks 44/48, 60/64 and 88/92 of -0.2 (95% confidence interval [CI], -1.8 to +1.3), +0.4 (95% CI, -1.4 to +2.1) and -0.6 ETDRS letters (95% CI, -2.5 to +1.3), respectively. Anatomic outcomes were generally comparable between arms through week 96. Through each of 4 PDS refill-exchange intervals, 98.4%, 94.6%, 94.8%, and 94.7% of PDS Q24W patients assessed did not receive supplemental ranibizumab treatment. The PDS ocular safety profile was generally unchanged from primary analysis. Prespecified ocular adverse events of special interest (AESI) were reported in 59 (23.8%) PDS and 17 (10.2%) monthly ranibizumab patients. The most common AESI reported in both arms was cataract (PDS Q24W, 22 [8.9%]; monthly ranibizumab, 10 [6.0%]). Events in the PDS Q24W arm included (patient incidence) 10 (4.0%) conjunctival erosions, 6 (2.4%) conjunctival retractions, 4 (1.6%) endophthalmitis cases, and 4 (1.6%) implant dislocations. Serum ranibizumab sampling showed that the PDS continuously released ranibizumab over the 24-week refill-exchange interval and ranibizumab serum concentrations were within the range experienced with monthly ranibizumab. CONCLUSIONS: The PDS Q24W showed noninferior efficacy to monthly ranibizumab through approximately 2 years, with approximately 95% of PDS Q24W patients not receiving supplemental ranibizumab treatment in each refill-exchange interval. The AESIs were generally manageable, with learnings continually implemented to minimize PDS-related AEs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

C-H Bond Activation Relay (CHAR) of Proline Ester Derivatives Promoted by In Situ Triarylamine Radical Cation: Selective Synthesis of 4-Bromopyrrole Derivatives.

Using the in situ generated triarylamine radical cation as an initiator, the sp3 C-H bond of proline esters was smoothly oxidized and brominated through C-H activation relay (CHAR), giving a series of 4-bromopyrroles in good yields with high regioselectivity. The mechanistic study revealed that the oxidation of the active C-H bond initiated the followed 1,5-HAT and bromination, which provides a new method to realize the functionalization of the remote C-H bond.

Halogen Bond (XB) Promoted α-Tribromomethylation of N-Aryltetrahydroisoquinolines and Further Cyclization to 5,6-Dihydroindolo[2,1-a]isoquinolines.

Using CBr4 as a halogen bond donor and the source of tribromomethyl group, a halogen bond promoted tribromomethylation of N-aryltetrahydroisoquinolines was achieved. This reaction was also extended to the construction of the dibenzopyrrocoline alkaloid skeleton through a one-pot process. The mechanistic study confirmed the existence of the halogen bond.

Abbreviated Versus Full-Protocol MRI for Breast Cancer Neoadjuvant Chemotherapy Response Assessment: Diagnostic Performance by General and Breast Radiologists.

BACKGROUND. Abbreviated protocols could allow wider adoption of MRI in patients undergoing breast cancer neoadjuvant chemotherapy (NAC). However, abbreviated MRI has been explored primarily in screening settings. OBJECTIVE. The purpose of this article was to compare diagnostic performance of abbreviated MRI and full-protocol MRI for evaluation of breast cancer NAC response, stratifying by radiologists' breast imaging expertise. METHODS. This retrospective study included 203 patients with breast cancer (mean age, 52.1 ± 11.2 [SD] years) from two hospitals who underwent MRI before NAC initiation and after NAC completion before surgical resection from March 2017 to April 2021. Abbreviated MRI was extracted from full-protocol MRI and included the axial T2-weighted sequence and precontrast and single early postcontrast T1-weighted sequences. Three general radiologists and three breast radiologists independently interpreted abbreviated and full-protocol MRI in separate sessions, identifying enhancing lesions to indicate residual tumor and measuring lesion size. The reference standard was presence and size of residual tumor on pathologic assessment of post-NAC surgical specimens. RESULTS. A total of 50 of 203 patients had pathologic complete response (pCR). Intraobserver and interobserver agreement for abbreviated and full-protocol MRI for general and breast radiologists ranged from substantial to nearly perfect (κ = 0.70-0.81). Abbreviated MRI compared with full-protocol MRI showed no significant difference for general radiologists in sensitivity (54.7% vs 57.3%, p > .99), specificity (92.8% vs 95.6%, p = .29), or accuracy (83.4% vs 86.2%, p = .30), nor for breast radiologists in sensitivity (60.0% vs 61.3%, p > .99), specificity (94.6% vs 97.4%, p = .22), or accuracy (86.0% vs 88.5%, p = .30). Sensitivity, specificity, and accuracy were not significantly different between protocols for any reader individually (p > .05). Mean difference in residual tumor size on MRI relative to pathology for abbreviated protocol ranged for general radiologists from -0.19 to 0.03 mm and for breast radiologists from -0.15 to -0.05 mm, and for full protocol ranged for general radiologists from 0.57 to 0.65 mm and for breast radiologists from 0.66 to 0.79 mm. CONCLUSION. Abbreviated compared with full-protocol MRI showed similar intraobserver and interobserver agreement and no significant difference in diagnostic performance. Full-protocol MRI but not abbreviated MRI slightly overestimated pathologic tumor sizes. CLINICAL IMPACT. Abbreviated protocols may facilitate use of MRI for post-NAC response assessment by general and breast radiologists.

Machine discovery of partial differential equations from spatiotemporal data: A sparse Bayesian learning framework.

This study presents a general framework, namely, Sparse Spatiotemporal System Discovery (S3d), for discovering dynamical models given by Partial Differential Equations (PDEs) from spatiotemporal data. S3d is built on the recent development of sparse Bayesian learning, which enforces sparsity in the estimated PDEs. This approach enables a balance between model complexity and fitting error with theoretical guarantees. The proposed framework integrates Bayesian inference and a sparse priori distribution with the sparse regression method. It also introduces a principled iterative re-weighted algorithm to select dominant features in PDEs and solve for the sparse coefficients. We have demonstrated the discovery of the complex Ginzburg-Landau equation from a traveling-wave convection experiment, as well as several other PDEs, including the important cases of Navier-Stokes and sine-Gordon equations, from simulated data.

Survival of Four Conical Implant Abutment Connections After Removal of the Abutment Screw and Simulated Cyclic Loading: An In Vitro Comparative Study.

This in vitro study evaluated the mechanical behavior of different conical connection implant systems after abutment screw withdrawal. Four conical connection systems were selected based on different conical half-angles: Ankylos (5.7°), Cowell (7.0°), Straumann (7.5°), and Astra (11.0°). In each system, 5 implants and abutments were used (n = 5). According to the recommended value, each abutment screw was torqued to settle the abutment and then withdrawn through a predesigned hole of the cemented crown. The retentiveness of the abutment was evaluated by the following mechanical testing. All specimens were subjected to cyclic loading of 20-200 N, 30°, and 4-mm off-axis to the implant axis, for 106 cycles. The pullout forces and axial displacements of the abutments were measured. The data of the Cowell system was obtained from our previous work. All groups other than Astra group, in which abutment loosened after abutment screw withdrawal, passed the cyclic loading test. Straumann group demonstrated a significantly lower pullout force (27.4 ± 21.1 N) than Ankylos (160.1 ± 41.4 N) and Cowell (183.7 ± 30.5 N) groups. All groups showed abutment rebound after screw withdrawal except Straumann group. In addition, Ankylos, Cowell, and Straumann groups demonstrated axial displacement after cyclic loading. In terms of the retentiveness of the abutment after abutment screw withdrawal examined in this study, Ankylos and Cowell groups had much higher retentiveness than Straumann group, while Astra group had none. Conical angle could be a key design parameter to make abutment screw withdrawal after conical abutment settlement feasible, but more studies must be conducted for clinical application.

Effects of core buildup composite resin translucency on intraoral scanner accuracy: an in vitro study.

AIM: The accuracy of 3D images produced by an intraoral scanner (IOS) is affected by the optical characteristics of restorative materials such as metal, ceramic, and composite resin. The present in vitro study aimed to investigate the impact of core buildup composite resin translucency on IOS accuracy. MATERIALS AND METHODS: A core buildup procedure was performed on a proprietary 3D-printed model using injectable composite resins in four groups with different levels of translucency (highest to lowest: AE, A3, AO3, and EX). Ten experimental scans per group were performed using a Medit i700 IOS on a phantom head-mounted model. Reference scans were obtained using an industrial scanner (Solutionix C500). Values of accuracy (trueness and precision) for the respective groups were evaluated using mean deviation values following 3D superimposition. RESULTS: Composite resin translucency caused the scale reduction of the optical impressions. Values of trueness showed the highest scale reduction in AE, significantly, followed by A3, AO3, and EX. Considering 50 µm as the cut-off value of deviations for clinical acceptability, the analysis showed most deviations in AE and A3. Similar results were found with precision, where AE showed the highest deviation value statistically, followed by A3, AO3, and EX. CONCLUSIONS: Composite resin translucency affects the accuracy of optical impressions, causing a fitting error of CAD/CAM prostheses. The more translucent the composite resin, the less accurate the optical impression. This suggests the need for proper compensation during prosthesis designing for an optimal clinical result. In addition, practitioners should indicate in the digital workflow the proper restorative materials regarding not only the mechanical properties and esthetics, but also the optical characteristics.

Tris(4-bromophenyl)aminium Hexachloroantimonate as a "Waste-Utilized"-Type Initiator-Promoted C-H Chlorination via C-H Activation Relay: Synthesis of Chlorinated Pyrroles.

Using tris(4-bromophenyl)aminium hexachloroantimonate as a "waste-utilized"-type initiator, the aerobic oxidation of the sp3 C-H bond of proline esters was realized via C-H activation relay, giving a series of halogenated pyrroles in high yields. The mechanistic study revealed that the counterion, SbCl6-, was involved in the radical chlorination process, which provides a new way to understand the role of the counterions.

Effect of Baihe Gujin decoction combined with Shengmai powder on the expression of IL-1ß and IL-1Ra in peripheral blood CD14+ monocytes from patients with pulmonary tuberculosis.

This experiment was conducted to investigate the effect of taking Baihe Gujin decoction combined with Shengmai powder on IL-1ß and IL-1Ra expression in peripheral blood CD14+ monocytes from patients with pulmonary tuberculosis. For this purpose, one hundred adult patients with primary pulmonary tuberculosis were selected for the study. The age of the enrolled cases ranged from 18 to 60 years old, with a controlled male to the female sex ratio of about 1:1. The Chinese medical evidence was considered to be a qi-yin deficiency type of pulmonary consumption. The patients were randomly divided into experimental and control groups, 50 cases each. In addition, 50 cases of healthy people were selected as a healthy control group, totaling 150 cases. In the experimental group, patients were given Baihe gujin decoction and Shengmai powder based on conventional western medicine, 1 dose for 1 day, 150mL/time for 2 times. The control group was treated with conventional Western medicine. 2 mL of fasting elbow venous blood from the subjects was taken in the morning. Peripheral blood mononuclear cells were isolated by density centrifugation. Monocytes were obtained after incubation with 5 µL of CD14+ immune magnetic beads at 4°C. The relative expression of IL1ß and IL1R genes were measured using real-time quantitative PCR (RT-PCR), respectively. Results showed that the relative expression of IL1ß and IL1R genes was significantly lower in the experimental group after 3 months compared with the control group, and the statistical difference was highly significant (p<0.01). It was concluded that the administration of Baihe gujin decoction and Shengmai powder was closely related to the relative expression of IL1ß and IL1R genes in patients' serum, indicating that Baihe gujin decoction and Shengmai powder have an important role in improving the clinical symptoms of pulmonary tuberculosis.

A Statistical Prediction Model for Survival After Kidney Transplantation from Deceased Donors.

BACKGROUND In an environment of limited kidney donation resources, patient recovery and survival after kidney transplantation (KT) are highly important. We used pre-operative data of kidney recipients to build a statistical model for predicting survivability after kidney transplantation. MATERIAL AND METHODS A dataset was constructed from a pool of patients who received a first KT in our hospital. For allogeneic transplantation, all donated kidneys were collected from deceased donors. Logistic regression analysis was used to change continuous variables into dichotomous ones through the creation of appropriate cut-off values. A regression model based on the least absolute shrinkage and selection operator (LASSO) algorithm was used for dimensionality reduction, feature selection, and survivability prediction. We used receiver operating characteristic (ROC) analysis, calibration, and decision curve analysis (DCA) to evaluate the performance and clinical impact of the proposed model. Finally, a 10-fold cross-validation scheme was implemented to verify the model robustness. RESULTS We identified 22 potential variables from which 30 features were selected as survivability predictors. The model established based on the LASSO regression algorithm had shown discrimination with an area under curve (AUC) value of 0.690 (95% confidence interval: 0.557-0.823) and good calibration result. DCA demonstrated clinical applicability of the prognostic model when the intervention progressed to the possibility threshold of 2%. An average AUC value of 0.691 was obtained on the validation data. CONCLUSIONS Our results suggest that the proposed model can predict the mortality risk for patients after kidney transplants and could help kidney specialists choose kidney recipients with better prognosis.

Association of histological subtype with risk of recurrence in craniopharyngioma patients: a systematic review and meta-analysis.

It is controversial whether there is a different risk of recurrence between two histological subtypes in craniopharyngioma (CP) patients. Some reported that adamantinomatous craniopharyngioma (ACP) had a higher risk of recurrence than papillary craniopharyngioma (PCP), but others reported that there is no significant difference between them. So, we conducted this systematic review and meta-analysis to determine the association between the histological subtype of CP and the rate of recurrence. A comprehensive literature search was undertaken in PubMed, EMBASE, and Web of Science for all English articles published up to November 2020. Recurrence data stratified by ACP and PCP were extracted from studies meeting inclusion criteria. A pooled analysis of the association between the histological subtype of craniopharyngioma and rates of recurrence was performed. Thirteen articles containing 974 patients were included. When stratified by two pathological subtypes, the total recurrence rate of ACP was 26.0% and PCP was 14.1%, which showed ACP associated with a higher risk of tumor recurrence than PCP (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.36, 3.30, P = 0.00). This is the first meta-analysis focusing on histological subtypes of CP. PCP associates with a lower risk of recurrence than ACP, indicating that ACP could act as one of recurrence risk factors for CP patients. Nevertheless, large sample size and well-designed multicenter studies in which the other clinical variables are controlled to determine the histological subtype of CP as an independent recurrence risk factor are needed.

Pepsinogen C expression-related lncRNA/circRNA/mRNA profile and its co-mediated ceRNA network in gastric cancer.

The expression of pepsinogen C (PGC) is considered an ideal negative biomarker of gastric cancer, but its pathological mechanisms remain unclear. This study aims to analyze competing endogenous RNA (ceRNA) networks related to PGC expression at a post-transcriptional level and build an experimental basis for studying the role of PGC in the progression of gastric cancer. RNA sequencing technology was used to detect the differential expression (DE) profiles of PGC-related long non-coding (lnc)RNAs, circular (circ)RNAs, and mRNAs. Ggcorrplot R package and online database were used to construct DElncRNAs/DEcircRNAs co-mediated PGC expression-related ceRNA networks. In vivo and in vitro validations were performed using quantitative reverse transcription-PCR (qRT-PCR). RNA sequencing found 637 DEmRNAs, 698 DElncRNAs, and 38 DEcircRNAs. The PPI network of PGC expression-related mRNAs consisted of 503 nodes and 1179 edges. CFH, PPARG, and MUC6 directly interacted with PGC. Enrichment analysis suggested that DEmRNAs were mainly enriched in cancer-related pathways. Eleven DElncRNAs, 13 circRNAs, and 35 miRNA-mRNA pairs were used to construct ceRNA networks co-mediated by DElncRNAs and DEcircRNAs that were PGC expression-related. The network directly related to PGC was as follows: SNHG16/hsa_circ_0008197-hsa-mir-98-5p/hsa-let-7f-5p/hsa-let-7c-5p-PGC. qRT-PCR validation results showed that PGC, PPARG, SNHG16, and hsa_circ_0008197 were differentially expressed in gastric cancer cells and tissues: PGC positively correlated with PPARG (r = 0.276, P = 0.009), SNHG16 (r = 0.35, P = 0.002), and hsa_circ_0008197 (r = 0.346, P = 0.005). PGC-related DElncRNAs and DEcircRNAs co-mediated complicated ceRNA networks to regulate PGC expression, thus affecting the occurrence and development of gastric cancer at a post-transcriptional level. Of these, the network directly associated with PGC expression was a SNHG16/hsa_circ_0008197-mir-98-5p/hsa-let-7f-5p/hsa-let-7c-5p - PGC axis. This study may form a foundation for the subsequent exploration of the possible regulatory mechanisms of PGC in gastric cancer.

Development of a Portable Method for Serum Lithium Measurement Based on Low-Cost Miniaturized Ultrasonic Nebulization Coupled with Atmospheric-Pressure Air-Sustained Discharge.

An accurate, rapid but cheap, and portable method for monitoring of serum lithium (Li) is highly desirable for mental patients who take Li medicine for treatment. Conventional techniques are usually bulky, costly, and cannot provide on-site real-time measurements. Herein, a miniaturized, reliable, cost-effective, and portable optical emission method for rapid and sensitive determination of serum Li was developed based on a combination of miniaturized ultrasonic nebulization (MUN) and a low-power (≈22 W) atmospheric-pressure air-sustained discharge (APAD) excitation source. The proposed method eliminates the use of any compressed gas or pump and can achieve serum Li detection within 40 s with low sample consumption (less than 20 µL serum). Except for dilution with water, no extra treatment is needed for serum Li analysis by MUN-APAD-OES. In addition, it offers a significant advantage of good tolerance to the coexisting high concentration of Na, K, Ca, and Mg, which is in contrast with the obvious matrix effect encountered in conventional inductively coupled plasma optical emission spectrometry (ICP-OES). Different operating parameters affecting the performance of MUN-APAD-OES were evaluated. Under optimized conditions, the detection limit of Li (670.8 nm) was calculated to be 0.6 µg L-1 (6 µg L-1 in serum). Finally, the accuracy of the proposed method was validated by the analysis of two certified reference materials (Seronorm serum L-1 and L-2 RUO), six real human serum samples, and eight real animal serum samples. All of the results indicate that the low-cost and low-power MUN-APAD-OES provides a promising reliable method for on-site serum Li measurement and may also be extended to other elements.