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To investigate the diagnostic performance of fully automated radiomics-based models for multiclass classification of a single enhancing brain tumor among glioblastoma, central nervous system lymphoma, and metastasis.The training and test sets were comprised of 538 cases (300 glioblastomas, 73 lymphomas, and 165 metastases) and 169 cases (101 glioblastomas, 29 lymphomas, and 39 metastases), respectively. After fully automated segmentation, radiomic features were extracted. Three conventional machine learning classifiers, including least absolute shrinkage and selection operator (LASSO), adaptive boosting (Adaboost), and support vector machine with the linear kernel (SVC), combined with one of four feature selection methods, including forward sequential feature selection, F score, mutual information, and LASSO, were trained. Additionally, one ensemble classifier based on the three classifiers was used. The diagnostic performance of the optimized models was tested in the test set using the accuracy, F1-macro score, and the area under the receiver operating characteristic curve (AUCROC).The best performance was achieved when the LASSO was used as a feature selection method. In the test set, the best performance was achieved by the ensemble classifier, showing an accuracy of 76.3% (95% CI, 70.0-82.7), a F1-macro score of 0.704, and an AUCROC of 0.878.Our fully automated radiomics-based models for multiclass classification might be useful for differential diagnosis of a single enhancing brain tumor with a good diagnostic performance and generalizability.

Alzheimer's disease (AD), as the most typical type of dementia, is a chronic neurodegenerative disorder characterized by progressive learning and memory impairment. It is known that the main causes of AD are the accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Naringin is a flavonoid from citrus fruits, especially in grapefruit, which has anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective activities. However, the effect of naringin in AD caused by Aβ has not been clearly studied, and there are few studies on the electrophysiological aspect. Thus, we investigated the ex vivo neuroprotective effect of naringin through the long-term potentiation (LTP) on organotypic hippocampal slice cultures. We evaluated the in vivo effects of naringin (100mg/kg/day) orally treated for 20 days on learning, memory, and cognition which was impaired by bilateral CA1 subregion injection of Aβ. Cognitive behaviors were measured 2 weeks after Aβ injection using behavioral tests and the hippocampal expression of apoptotic and neurotrophic regulators were measured by immunoblotting. In hippocampal tissue slices, naringin dose-dependently increased the field excitatory postsynaptic potential (fEPSP) after theta burst stimulation and attenuated Aβ-induced blockade of fEPSP in the hippocampal CA1 area. In Aβ injected rats, naringin improved object recognition memory in the novel object test, avoidance memory in the passive avoidance test and spatial recognition memory in the Morris water maze test. In the hippocampus, naringin attenuated the Aβ-induced cyclooxygenase-2, Bax activation and Bcl-2, CREB, BDNF and TrkB inhibition. These results suggest that naringin has therapeutic potential to reduce neuronal inflammation and apoptosis induced by Aβ related with the BDNF/TrkB/CREB signaling.

The CoV2-001 Phase 1 randomized trial evaluated the safety and immunogenicity of the GLS-5310 bi-cistronic DNA vaccine through 48 weeks of follow-up.Forty-five vaccine-naïve participants were recruited between 31 December 2020 and 30 March 2021. GLS-5310, encoding for the SARS-CoV-2 spike (S) and ORF3a proteins, was administered intradermally at 0.6 mg or 1.2 mg per dose, followed by application of the GeneDerm suction device as part of a two-dose regimen spaced either 8 or 12 weeks between vaccinations.GLS-5310 was well tolerated with no SAE's reported. Antibody and T cell responses were dose-independent. Anti-S antibodies were induced in 95.5% of participants with average GMT of ∼480 four-weeks post-vaccination, and declined minimally through 48 weeks. Neutralizing antibodies were induced in 55.5% of participants with post-vaccination GMT of 28.4. T cell responses were induced in 97.8% of participants, averaged 716 SFU/10GLS-5310 administered with the GeneDerm suction device was well tolerated and induced high levels of binding antibodies and T-cell responses. Antibody responses were similar to other DNA vaccines, whereas T cell responses were many-fold greater than DNA and non-DNA vaccines.

Thymic epithelial tumors (TETs) are rare but are the most common tumors of the anterior mediastinum. Platinum-based combination chemotherapy is the standard of care for such tumors and is associated with a 50% to 90% objective response rate (ORR) in metastatic disease. Nevertheless, there is no standard chemotherapeutic option after failure of platinum-based combination chemotherapy. Genetic alterations associated with the cell cycle, including pRB, p16This is a phase 2, multicenter, open-label, single-arm study of palbociclib monotherapy in patients with recurrent or metastatic advanced TETs who failed one or more cytotoxic chemotherapies. The patients received 125 mg of oral palbociclib daily for 21 days, followed by a 7-day break. The primary end point was progression-free survival (PFS). The secondary end points were ORR, duration of response, overall survival, and safety.Between August 2017 and October 2019, a total of 48 patients were enrolled. The median number of previous chemotherapies was one (range: one to four), and 21 (43.7%) of 48 patients received thymectomy. By the WHO classification, the patients were type A (n = 1), type B1 (n = 2), type B2 (n = 8), type B3 (n = 13), thymic carcinoma (n = 23), and unknown (n = 1). With a median follow-up of 14.5 months (range: 0.8-38.2), the median number of cycles of palbociclib monotherapy was 10 (range: 1-40). The ORR was 12.5% (four partial responses in thymoma and two partial responses in thymic carcinoma). The PFS at 6 months was 60.2%, and the median PFS was 11.0 months (95% confidence interval: 4.6-17.4). The median overall survival was 26.4 months (95% confidence interval: 17.4-35.4). The most common treatment-related adverse events of any grade were neutropenia (62.5%), anemia (37.5%), and thrombocytopenia (29.1%), and the most common grade 3/4 treatment-related hematologic adverse event was neutropenia (41.7%). Neutropenia above grade 3 was reversible, and there were no cases with neutropenic fever.Palbociclib monotherapy was well tolerated and had encouraging efficacy in patients with TETs who failed platinum-based combination chemotherapy.

To present the long-term clinical outcomes of laparoscopic gastric greater curvature plication (LGGCP) in terms of weight loss and revision surgery rate.This single-center study involved a retrospective analysis of patients that underwent revision surgery after LGGCP due to weight regain. Demographic and anthropometric data, comorbidities, operation time, hospital stays, mortalities, and immediate and long-term postoperative complications were analyzed. Postoperative Body Mass Index (BMI), %total weight loss (TWL), and complications were collected during follow-up.Of the 75 patients that underwent LGGCP at our hospital from March 2013 to February 2016, 13 (13/75, 17.3%) underwent revision surgery. All patients except one opted for sleeve gastrectomy. The mean interval between LGGCP and revision surgery was 71.0 ± 12.0 months (range, 54.8-93.6), and mean body weight, BMI, and TWL at revision were 89.2 ± 11.3 kg, 33.9 ± 4.2 kg/mAlthough LGGCP showed initial acceptable weight loss outcomes, long term (5 years) follow-up showed that LGGCP is associated with a high rate of revision surgery (17.3%) due to weight regain.

Despite the introduction of intraoral scanners (IOSs) with dual camera triangulation, only a few comparative clinical studies have evaluated their clinical performances in the digital workflow for cast-free restorations.The purpose of this clinical trial was to assess the clinical efficacy of 2 different technology-based IOSs by evaluating the marginal and internal gaps of cast-free monolithic zirconia crowns fabricated by using a fully digital workflow.A prospective randomized clinical trial was conducted in 35 participants requiring a single-unit restoration. One crown was fabricated from the scan data obtained with a confocal microscopy-based IOS (Group T), while the other was made with the scan data obtained from an IOS using dual camera triangulation (Group I). A replica technique was used to assess the marginal and internal gaps. The buccolingual and mesiodistal cross-sections were measured, and noninferiority trials were performed.A total of 39 teeth from 35 participants were restored with a single-unit crown. The marginal and axial wall gaps of the crowns in Group I was not inferior to that of the crowns in Group T (upper limit confidence interval [CI] 30). In contrast, the gap of the crowns at the line angle in Group T was inferior to that of the crowns in Group I (lower limit CI -30). From an occlusal space perspective, the gap of the crowns in Group I was inferior to that of the crowns in Group T (upper limit CI30). Twenty-five crowns were selected from Group I, and 14 crowns were selected from Group T for definitive placement.The marginal gap of the crown fabricated by using the scan data obtained from the dual camera triangulation-based IOS was noninferior to that obtained from the confocal microscopy-based IOS and was within the clinically applicable limit.

To evaluate the applicant experience with preference signaling during the 2022 Urology Residency Match.An anonymous electronic survey was emailed to all urology residency applicants who applied to Rutgers Robert Wood Johnson Medical School during the 2021-2022 application cycle. The survey collected information regarding applicant demographics, applicant characteristics, preference signal destinations, match outcomes, and attitude towards preference signaling.A total of 601 applicants applied to the 2022 Urology Residency Match, 283 of which applied to the urology residency program at Rutgers Robert Wood Johnson Medical School. Of the 283 applicants, 53 (19%) responded to our survey. Rate of interview for preference signaled programs was 54.23%, with a significantly lower rate of interview for comparative, non-signaled programs (40.54%; P = .001). Of respondents, 14.29%, 26.19%, and 35.71% matched to their home program, a program they signaled, or a program where they completed an away rotation, respectively. 96% of applicants favored continuation of the preference signaling program.Our study suggests preference signaling in the 2022 Urology Match may have been an effective method of expressing interest in a program. Respondents of our survey overwhelmingly favor continuation of the program in future urology matches. However, it may not address the underlying, growing problem of the increasing application burden on applicants and programs alike. We encourage more comprehensive studies to further clarify the effects of preference signaling on the Urology Match.

Although the production of several founder animals (F0) for gene editing in livestock has been reported in cattle, very few studies have assessed germline transmission to the next generation due to the long sexual maturation and gestation periods. The present study aimed to assess the germline transmission of MSTN mutations (-12bps deletion) in MSTN mutant F0 male and female cattle. For this purpose, oocytes and semen were collected after the sexual maturation of MSTN cattle, and embryos produced by in vitro fertilization were analyzed. In addition, the embryos were subjected to additional gene (PRNP) editing using electroporation. Embryos produced by in vitro fertilization with MSTN male and female cattle were transferred to a surrogate, and one calf was successfully born. MSTN heterozygous mutation was shown by sequencing of the F1 calf, which had no health issues. As a further experiment, using electroporation, additional gene-edited embryos fertilized with the MSTN male sperm showed a high mutation rate of PRNP (86.2 ± 3.4%). These data demonstrate that the cattle produced through gene editing matured without health issues and had transmitted MSTN mutation from the germ cells. Also, additional mutation of embryos fertilized with the MSTN male sperm could enable further mutagenesis using electroporation.

Mouse embryonic stem cells (mESCs) can be maintained in a pluripotent state under R2i culture conditions that inhibit the TGF-β and ERK signaling pathways. BMP4 is another member of the TGF-β family that plays a crucial role in maintaining the pluripotency state of mESCs. It has been reported that inhibition of BMP4 caused the death of R2i-grown cells. In this study, we used the loss-of-function approach to investigate the role of BMP4 signaling in mESC self-renewal. Inhibition of this pathway with Noggin and dorsomorphin, two bone morphogenetic protein (BMP) antagonists, elicited a quick death of the R2i-grown cells. We showed that the canonical pathway of BMP4 (BMP/SMAD) was dispensable for self-renewal and maintaining pluripotency of these cells. Transcriptome analysis of the BMPi-treated cells revealed that the p53 signaling and two adhesion (AD) and apoptotic mitochondrial change (MT) pathways could be involved in the cell death of the BMPi-treated cells. According to our results, inhibition of BMP4 signaling caused a decrease in cell adhesion and ECM detachment, which triggered anoikis in the R2i-grown cells. Altogether, these findings demonstrate that endogenous BMP signaling is required for the survival of mESCs under the R2i condition.

Antimicrobial resistance is one of the most urgent global health threats. The need for the qualitative evaluation of antibiotic use at the national level is increasing. To identify areas for improvement, we aimed to assess the prevalence and appropriateness of antibiotic prescriptions during hospitalization and ambulatory care in Korea.The prevalence and appropriateness of antibiotic prescriptions on 29 August 2018 were assessed for 20 hospitals in Korea. Infectious disease specialists determined appropriateness. Except for antiviral and anti-tuberculosis agents, all antibacterial or antifungal agent prescriptions during hospitalization or ambulatory care were evaluated.The prevalence of antibiotic prescription was 14.1% (8,400/59 216 patients) on the study date. Antibiotics were prescribed for 50.8% of inpatients (6557/12 902), with two or more antibiotics prescribed for 27.4% (1798/6557) of patients. A total of 10 948 prescriptions (7999 therapeutic, 2105 surgical prophylaxes, and 844 medical prophylaxes) were included in the final analysis, and 27.7% of these were inappropriate. Surgical prophylaxis was inadequately prescribed most frequently (54.4%), followed by medical prophylaxis (29.5%) and therapeutic antibiotics (20.5%). The most common indications for therapeutic antibiotics were respiratory (29.1%, n=2332), gastrointestinal (22.4%, n=1791), and urinary tract infections (13.1%, n=1050). The most frequently prescribed antibiotics were cephalosporins (52.0%, n=5490), followed by beta lactam/beta lactamase inhibitors (13.7%, n=1373), fluoroquinolones (9.1%, n=957), and metronidazole (6.6%, n=699).This was the first nationwide qualitative antibiotic prescription adequacy evaluation in Korea. A significant proportion of antibiotic prescriptions were inappropriate. Therefore, interventions for high-frequency infections and prescription antibiotics are needed.

The aim of this work was to evaluate Gd-FC705, a prostate-specific membrane antigen (PSMA)-targeted MRI contrast agent. The r

The ongoing SARS-CoV-2 evolution has resulted in many variants, contributing to the striking drop in vaccine efficacy and necessitated the development of next-generation vaccines to tackle antigenic diversity. Herein we developed a multivalent Semliki Forest virus replicon-based mRNA vaccine targeting the receptor binding domain (RBD), heptad repeat domain (HR), membrane protein (M) and epitopes of nsp13 of SARS-CoV-2. The bacteria-mediated gene delivery offers the rapid production of large quantities of vaccine at a highly economical scale and notably allows the needle-free mass vaccination. A favourable Th1 dominated potent antibody and cellular immune responses were detected in the immunized mice. Further, immunization induced strong cross-protective neutralizing antibodies (NAbs) against the B.1.617.2 delta variant (Clade G). We recorded a difference in induction of IgA response by the immunization route with the oral route eliciting a strong mucosal sIgA response, which possibly has contributed to the enhanced protection conferred by the oral immunization. Hamsters immunized orally were completely protected against the viral replication in the lungs and the nasal cavity. Importantly, the vaccine protected the hamsters against SARS-CoV-2-induced pneumonia. The study provides proof-of-principle findings for the development of a feasible and efficacious oral mRNA vaccine against SARS-CoV-2 and its variants., Graphical Abstract, Exploiting Semliki Forest virus replicon allows the development of bacteria-mediated oral mRNA vaccine. The vaccine induces potent Th1 polarized humoral and cellular immune responses. Oral administration elicits robust mucosal IgA response in lung and intestine. Oral replicon-based mRNA vaccine protects hamsters against parental and delta variant SARS-CoV-2 challenge.

Urinary retinol-binding protein 4 (RBP4) has been known as a biomarker of chronic kidney disease. In this study, we evaluated the association of urinary RBP4 with renal function and progression of renal function in kidney transplant recipients (KTRs).A total 50 KTRs were included in this study. Proteomic analysis with liquid chromatography-mass spectrometry and tandem mass spectrometry was performed to discover potential urinary biomarkers. Several urinary proteins including RBP4 were identified and then validated by enzyme-linked immunosorbent assay. Rapid renal function decline was defined as estimated glomerular filtration rate (eGFR) decline of3 mL/min/1.73 mUrinary RBP4/creatinine was inversely correlated with allograft function (r = -0.54, P.001 with eGFR, and r = 0.49, P.001 with serum creatinine, respectively). Urinary RBP4/creatinine was higher in rapid renal function decline group than in stable renal function group (184.9 ± 156.7 vs 83.1 ± 99.9, P = .017). Log-transformed urinary RBP4/creatinine was significantly associated with rapid renal function decline in univariate logistic regression analysis (Odds ratio [OR] 7.59, confidence interval [CI] 2.04-36.70, P = .005). In multivariate logistic regression adjusted with recipient age and sex, donor age, number of HLA mismatch, and acute rejection episode, urinary RBP4/creatinine remained a significant factor for rapid renal function decline (OR 9.43, CI 1.99-65.65, P = .010). Receiver operating characteristic analysis showed that the area under the curve of urinary RBP4/creatinine was 0.747 (CI 0.608-0.886, P.001) for rapid renal function decline.Urinary RBP4 levels are associated with renal function and might be used to predict rapid renal function decline in KTRs.

The purpose of this study was to evaluate the impact of the different region-of-interest (ROI) methods of 2-D shear wave elastography (2-D SWE) on hepatic fibrosis diagnosis. In this retrospective study, 83 patients who underwent 2-D SWE with three ROI methods (a circle ROI, a box ROI and multiple ROIs in an elastogram) and transient elastography (TE) were included. Liver stiffness (LS) was measured five times with each ROI method. These LS values were compared, and their correlation with those obtained from TE was evaluated. The LS values obtained using the three different ROI methods differed statistically (p0.001). However, the LS values obtained using each ROI method of 2-D SWE were highly correlated with those obtained using TE (r0.7, p0.001). All three ROI methods of 2-D SWE had high areas under the receiver operating characteristic curve in diagnosing significant fibrosis and cirrhosis (0.841, 0.820 and 0.840, respectively; 0.962, 0.946 and 0.945, respectively). There were no significant differences in area under the receiver operating characteristic curve among the ROI methods of 2-D SWE. Regardless of the ROI method, 2-D SWE had high performance in diagnosing hepatic fibrosis.

Graphical abstract, Introduction The emergence of SARS-CoV-2 variants has raised concerns on future vaccine efficacy as most vaccines target only the spike protein. Hence, vaccines targeting multiple SARS-CoV-2 proteins will offer broader protection and improve our preparedness to combat the pandemic. Objectives The study aimed to develop a novel vaccine strategy by combining a eukaryotic vector expressing multiple SARS-CoV-2 genes and Salmonella-mediated in vivo DNA delivery. Methods The eukaryotic vector was designed to function as a DNA-launched RNA replicon in a self-replicating and self-amplifying mRNA mechanism. By exploiting the self-cleaving peptide, P2A, we fused four SARS-CoV-2 targets, including receptor-binding domain (RBD), heptad repeat domain (HR), membrane protein (M) and epitopes of nsp13, in a single open reading frame. Western blot and immunofluorescence assays were used to determine protein expression. In mice, the vaccine's safety and immunogenicity were investigated. Results Western blot analysis revealed co-expression all four proteins from the vaccine construct, confirming the efficiency of Salmonella-mediated gene delivery and protein expression. The vaccine candidate was safe and elicited robust antigen-specific antibody titers in mice, and a recall response from splenocytes revealed induction of strong cell-mediated immunity. Flow cytometry demonstrated an increase in sub-populations of CD4+ and CD8+ T cells with the highest CD4+ and CD8+ T cells recorded for HR and RBD, respectively. Overall, humoral and cellular immune response data suggested the induction of both Th1 and Th2 immunity with polarization towards an antiviral Th1 response. We recorded a potent SARS-CoV-2 neutralizing antibody titers in the immunized mice sera. Conclusions The Salmonella bactofection ensured optimum in vivo gene delivery, and through a P2A-enabled efficient multicistronic expression, the vaccine candidate elicited potent anti-SARS-CoV-2 immune responses. These findings provide important insight into development of an effective multivalent vaccine to combat SARS-CoV-2 and its variants.

Diverse methods have been developed for the synthesis of active nanocatalysts involving various heterogeneous catalytic reactions. Thus far, numerous trial-and-error runs have been done to find the effective and practical ways. In the present work, the All-In-One (AIO) reactor system with a well-designed synthesis program, now in pilot stage, was first exploited as a reliable synthesis tool to find the optimum conditions for the production of Ni nanocatalysts. Using an activated charcoal support, active Ni nanoparticles of 7.8–11.8 nm (labeled A001–A007 in the program) were produced. These were achieved using a melt-impregnation process, which was controlled by variations in the applied gas (N2 and H2) and temperature (400 °C, 450 °C, and 500 °C) used as critical factors in the calcination step. Based on the optimization of the reaction sequence, each Ni nanocatalyst could be prepared within 5 h and 22 min. In particular, the optimum Ni nanocatalyst (A006) with the smallest particle size (7.8 nm), prepared under H2 flow at 400 °C, exhibits the highest catalytic activity (0.748 mmol4-NP·gcat-1·s-1) among the Ni catalysts for 4-nitrophenol (4-NP) reduction to 4-aminophenol (4-AP). This activity is much higher than that of conventional supported Ni nanocatalysts (0.551 mmol4-NP·gcat-1·s-1) produced using the wetness method.

The conversion efficiency of energy-harvesting devices can be increased by utilizing hot-carriers (HCs). However, due to ultrafast carrier-carrier scattering and the lack of carrier injection dynamics, HC-based devices have low efficiencies. In the present work, we report the effective utilization of HCs at the nanoscale and their transfer dynamics from a non-noble metal to a metal oxide interface by means of real-space photocurrent mapping by using local probe techniques and conducting femtosecond transient absorption (TA) measurements. The photocurrent maps obtained under white light unambiguously show that the HCs are injected into the metal oxide layer from the TiN layer, as also confirmed by conductive atomic force microscopy. In addition, the increased photocurrent in the bilayer structure indicates the injection of HCs from both layers due to the broadband absorption efficiency of TiN layer, passivation of the surface states by the top TiN layer, and smaller barrier height of the interfaces. Furthermore, electrostatic force microscopy and Kelvin probe force microscopy provide direct evidence of charge injection from TiN to the MoOx film at the nanoscale. The TA absorption spectra show a strong photo-bleaching signal over wide spectral range and ultrafast decaying behavior at the picosecond time scale, which indicate efficient electron transfer from TiN to MoOx. Thus, our simple and effective approach can facilitate HC collection under white light, thereby achieving high conversion efficiency for optoelectronic devices.

The subchronic toxicity of oral L-tryptophan produced by fermentation with metabolically engineered

This study sought to compare postoperative outcomes after scaphocapitate arthrodesis (SCA) for the treatment of late-stage Kienböck disease according to the amount of ulnar translation of the carpus and to identify surgical factors associated with carpal-ulnar translation.Thirty-nine patients diagnosed with Kienböck disease (Lichtman stages III-IV) and treated with SCA were retrospectively reviewed. They were divided into the translated group (n=28) and untranslated group (n=11) according to the presence of carpal-ulnar translation. The following surgical factors in the patients were assessed: excision of the lunate, postoperative carpal height ratio, and radioscaphoid angle (RSA). Pain Visual Analog scale (VAS) score, wrist range of motion, grip strength, modified Mayo wrist score (MMWS), the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, and progression of radioscaphoid osteoarthritis were also assessed.All patients showed functional improvement after a mean postoperative follow-up period of 40 months (VAS: 4.1 vs. 1.1, p0.001; grip strength, 42.3 vs. 51.2 lb., p = 0.002; MMWS, 52.6 vs. 69.5, p0.001; QuickDASH, 33.7 vs. 21.5, p0.001). No statistically significant differences were found between the two groups in terms of outcome measures. Among the assessed surgical factors, the mean postoperative RSA was significantly smaller in the translated group than in the untranslated group (34.8° vs. 46.8°, p = 0.008). The proportion of patients with postoperative RSA30° was significantly higher in the translated group than in the untranslated group (54.5% vs. 0%, p0.001).These results suggest that sufficient pain relief and functional improvement can be achieved after SCA for the treatment of late-stage Kienböck disease disregarding the occurrence of carpal-ulnar translation. In this study, overcorrection to RSA30° induced more frequent carpal-ulnar translation after SCA.