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Background: Dendritic cell (DC) vaccine is an emerging immunotherapy that could potentially improve glioblastoma survival. The first phase III clinical trial of DC vaccine was recently published. This meta-analysis aims to update and reappraise existing evidence on the efficacy of DC vaccine in patients with glioblastoma., Methods: We searched PubMed, Embase, and Cochrane Library for clinical trials of DC vaccine for glioblastoma. The quality of the studies was assessed using the RoB 2.0 and ROBINS-I tools. The results of overall survival (OS) and progression-free survival (PFS) were pooled using hazard ratios (HRs) with corresponding 95% confidence intervals (CI). Summary effects were evaluated using random effects models. Trial sequential analysis (TSA) was performed., Results: Seven clinical trials involving 3,619 patients were included. DC vaccine plus standard care was associated with significantly improved OS (HR = 0.71; 95% CI, 0.57 - 0.88) and PFS (HR = 0.65; 95% CI, 0.43 - 0.98). In the subgroup of newly diagnosed glioblastoma, DC vaccine was associated with improved PFS (HR = 0.59; 95% CI, 0.39 - 0.90). TSA of OS showed that the cumulative z-score line for the DC vaccine crossed the benefit boundary and reached the required sample size. TSA of PFS and subgroup analysis of newly diagnosed glioblastoma showed that the required sample size was not reached., Conclusions: This updated meta-analysis, which included the first phase III trial of a DC vaccine for glioblastoma, demonstrated that the DC vaccine was associated with improved OS. Moreover, TSA showed that the required sample size was reached, indicating a true-positive result. Future studies are required for patient subgroups with newly diagnosed and recurrent glioblastoma., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Nonmuscle invasive bladder cancer (NMIBC) has a favorable prognosis but has high propensity for recurrence. Recent development in one of the urinary biomarker tests, Bladder EpiCheck™, offers a noninvasive and accurate method to detect NMIBC recurrence. In this study, we aimed to compare the diagnostic performance of Bladder EpiCheck™ with urine cytology to detect NMIBC recurrence., Methods: We performed a systematic review search through PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to July 2023. Diagnostic accuracy was defined by sensitivity, negative predictive value (NPV), specificity, and positive predictive value (PPV)., Results: A total of 6 studies involving 1588 patients were included. Bladder EpiCheck™ has a sensitivity and specificity of 0.81 (95% CI: 0.63-0.91; I 2 : 43%) and 0.87 (95% CI: 0.83-0.91; I 2 : 20%), respectively. On the other hand, urine cytology has a sensitivity and specificity of 0.63 (95% CI: 0.29-0.87; I 2 : 61%) and 0.97 (95% CI: 0.78-1.00; I 2 : 79%), respectively. EpiCheck™ has a higher NPV (0.94 (95% CI: 0.87-0.97) vs. 0.84 (95% CI: 0.80-0.87) though a lower PPV (0.62 (95% CI: 0.45-0.76) vs. 0.87 (95% CI: 0.56-0.97) than urine cytology. In our subgroup analysis, the sensitivity of Bladder EpiCheck™ for detecting high-grade tumors improved to 0.90 (95% CI: 0.83-0.94) while that for urine cytology improved to 0.72 (95% CI: 0.50-0.87)., Conclusion: Bladder EpiCheck™ has a high sensitivity and NPV for detecting recurrence among patients with NMIBC., Competing Interests: Declaration of competing interest No financial or personal conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

There are limited data on the optimal choice of anticoagulation in multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs). We conducted a propensity score-matched cohort study using the TriNetX database to compare the efficacy and safety of factor Xa inhibitors and warfarin in this patient population. Compared to warfarin, factor Xa inhibitors had a similar risk of deep vein thrombosis (hazard ratio [HR]: 1.11 [95% CI: 0.50-2.46]) or pulmonary embolism (HR: 1.08 [95% CI: 0.59-2.00]). There were no differences in the risk of gastrointestinal or intracranial bleeding. Factor Xa inhibitor-treated patients had lower all-cause mortality (HR: 0.56 [95% CI: 0.36-0.86]) compared with warfarin. These data suggest that factor Xa inhibitors had similar safety and efficacy compared with warfarin for MM patients on IMiDs., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

The molecular pathogenesis of extranodal NK/T-cell lymphoma (NKTCL) remains obscured despite the next-generation sequencing (NGS) studies explored on ever larger cohorts in the last decade. We addressed the highly variable mutation frequencies reported among previous studies with comprehensive amplicon coverage and enhanced sequencing depth to achieve higher genomic resolution for novel genetic discovery and comparative mutational profiling of the oncogenesis of NKTCL. Targeted exome sequencing was conducted to interrogate 415 cancer-related genes in a cohort of 36 patients with NKTCL, and a total of 548 single nucleotide variants (SNVs) and 600 Copy number variances (CNVs) were identified. Recurrent amplification of the MCL1 (67%) and PIM1 (56%) genes was detected in a dominant majority of patients in our cohort. Functional mapping of genetic aberrations revealed that an enrichment of mutations in the JAK-STAT signaling pathway, including the cytokine receptor LIFR (copy number loss) upstream of JAK3, STAT3 (activating SNVs), and downstream effectors of MYC, PIM1 and MCL1 (copy number gains). RNA in situ hybridization showed the significant consistence of MCL1 RNA level and copy number of MCL1 gene. We further correlated molecular and clinical parameters with overall survival (OS) of these patients. When correlations were analyzed by univariate followed by multivariate modelling, only copy number loss of LIFR gene and stage (III-IV) were independent prognostic factors of reduced OS. Our findings identified that novel loss of LIFR gene significantly correlated with the adverse clinical outcome of NKTCL patients and provided therapeutic opportunities for this disease through manipulating LIFR., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Current guidelines recommend limiting the rate of correction in patients with severe hyponatremia to avoid severe neurologic complications such as osmotic demyelination syndrome (ODS). However, published data have been conflicting. We aimed to evaluate the association between rapid sodium correction and ODS in patients with severe hyponatremia., Materials and Methods: We searched PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to November 2023. The primary outcome was ODS and the secondary outcomes were in-hospital mortality and length of hospital stay., Results: We identified 7 cohort studies involving 6,032 adult patients with severe hyponatremia. Twenty-nine patients developed ODS, resulting in an incidence rate of 0.48%. Seventeen patients (61%) had a rapid correction of serum sodium in the first or any 24-hour period of admission. Compared with a limited rate of sodium correction, a rapid rate of sodium correction was associated with an increased risk of ODS (RR, 3.91 [95% CI, 1.17 to 13.04]; I 2 = 44.47%; p = 0.03). However, a rapid rate of sodium correction reduced the risk of in-hospital mortality by approximately 50% (RR, 0.51 [95% CI, 0.39 to 0.66]; I 2 = 0.11%; p < 0.001) and the length of stay by 1.3 days (Mean difference, -1.32 [95% CI, -2.54 to -0.10]; I 2 = 71.47%; p = 0.03)., Conclusions: Rapid correction of serum sodium may increase the risk of ODS among patients hospitalized with severe hyponatremia. However, ODS may occur in patients regardless of the rate of serum sodium correction., Competing Interests: Conflict of interest None to declare., (© 2024 Xin Ya See et al., published by Sciendo.)

This study aimed to evaluate the impact of different pre-transplant local treatments on the survival of liver transplantation (LTx) recipients with BCLC Stage A Hepatocellular Carcinoma (HCC). We analyzed data from the Taiwan Cancer Registry and National Health Insurance Research Databases spanning 2012 to 2018. Employing propensity score matching, patients were categorized into three groups: those receiving local treatments (180 patients), hepatectomy (179 patients), and combined treatments (180 patients). The primary outcomes were overall mortality and HCC-specific death, assessed using time-varying Cox regression models and Kaplan-Meier survival analysis. During a median follow-up period of 3.92 years, all-cause mortality rates were observed as 74.44% for local treatments, 42.46% for hepatectomy, and 65.00% for combined treatments. HCC-specific mortality rates followed a similar pattern at 65.00%, 39.11%, and 59.44%, respectively. Adjusted hazard ratios demonstrated significantly elevated mortality risks associated with local and combined treatments compared to hepatectomy. Notably, the 2-year overall and HCC-specific survival rates were highest in the hepatectomy group, surpassing those observed in both the combined treatment and local treatment groups. The findings of our study highlight that for patients with BCLC Stage A HCC, undergoing hepatectomy prior to LTx is associated with superior survival outcomes compared to solely local treatments. This underscores the importance of considering hepatectomy as a vital component of the treatment strategy in this patient population., Competing Interests: None., (AJCR Copyright © 2024.)

Background: Despite the advances of therapies, multiple myeloma (MM) remains an incurable hematological cancer that most patients experience relapse. Tumor angiogenesis is strongly correlated with cancer relapse. Human leukocyte antigen G (HLA-G) has been known as a molecule to suppress angiogenesis. We aimed to investigate whether soluble HLA-G (sHLA-G) was involved in the relapse of MM., Methods: We first investigated the dynamics of serum sHLA-G, vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) in 57 successfully treated MM patients undergoing remission and relapse. The interactions among these angiogenesis-related targets (sHLA-G, VEGF and IL-6) were examined in vitro. Their expression at different oxygen concentrations was investigated using a xenograft animal model by intra-bone marrow and skin grafts with myeloma cells., Results: We found that HLA-G protein degradation augmented angiogenesis. Soluble HLA-G directly inhibited vasculature formation in vitro. Mechanistically, HLA-G expression was regulated by hypoxia-inducible factor-1α (HIF-1α) in MM cells under hypoxia. We thus developed two mouse models of myeloma xenografts in intra-bone marrow (BM) and underneath the skin, and found a strong correlation between HLA-G and HIF-1α expressions in hypoxic BM, but not in oxygenated tissues. Yet when stimulated with IL-6, both HLA-G and HIF-1α could be targeted to ubiquitin-mediated degradation via PARKIN., Conclusion: These results highlight the importance of sHLA-G in angiogenesis at different phases of multiple myeloma. The experimental evidence that sHLA-G as an angiogenesis suppressor in MM may be useful for future development of novel therapies to prevent relapse., (© 2024. The Author(s).)

The binary heterostructured semiconducting visible light photocatalyst of the iron-doped graphitic carbon nitride/bismuth molybdate (Fe-g-C 3 N 4 /Bi 2 MoO 6 ) composite was prepared by coupling with Fe-doped g-C 3 N 4 and Bi 2 MoO 6 particles. In the present study, a comparison of structural characteristics, optical properties, and photocatalytic degradation efficiency and activity between Fe-doped g-C 3 N 4 particles, Bi 2 MoO 6 particles, and Fe-g-C 3 N 4 /Bi 2 MoO 6 composite was investigated. The results of X-ray diffraction (XRD) examination indicate that the hydrothermal Bi 2 MoO 6 particles have a single orthorhombic phase and Fourier transform infrared (FTIR) spectroscopy analysis confirms the formation of Fe-doped g-C 3 N 4 . The optical bandgaps of the Fe-doped g-C 3 N 4 and Bi 2 MoO 6 particles are 2.74 and 2.73 eV, respectively, as estimated from the Taut plots obtained from UV-Vis diffuse reflectance spectroscopy (DRS) spectra. This characteristic indicates that the two semiconductor materials are suitable for absorbing visible light. The transmission electron microscopy (TEM) micrograph reveals the formation of the heterojunction Fe-g-C 3 N 4 /Bi 2 MoO 6 composite. The results of photocatalytic degradation revealed that the developed Fe-g-C 3 N 4 /Bi 2 MoO 6 composite photocatalyst exhibited significantly better photodegradation performance than the other two single semiconductor photocatalysts. This property can be attributed to the heterostructured nanostructure, which could effectively prevent the recombination of photogenerated carriers (electron-hole pairs) and enhance photocatalytic activity. Furthermore, cycling test showed that the Fe-g-C 3 N 4 /Bi 2 MoO 6 heterostructured photocatalyst exhibited good reproducibility and stability for organic dye photodegradation.

Patients with COVID-19 develop an increased risk of thromboembolism. Thromboprophylaxis is recommended for hospitalized COVID-19 patients, but the role of thromboprophylaxis in outpatients with COVID-19 is less well defined. We conducted a systematic review and meta-analysis to evaluate the safety and efficacy of thromboprophylaxis among outpatients with COVID-19. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to August 2023. The outcomes of interest were venous thromboembolic events including deep venous thrombosis and pulmonary embolism, all-cause mortality, cardiovascular events, hospitalization, major bleeding events, and non-major bleeding events. We included 6 trials comprising 3352 patients. Patients who received thromboprophylaxis had an approximately 70% reduction in venous thromboembolism (RR, 0.28 [95% CI, 0.08 to 0.93]) compared to patients who did not receive thromboprophylaxis. The risk of mortality (RR, 0.79 [95% CI, 0.35 to 1.77]), cardiovascular events (RR, 0.91 [95% CI, 0.30 to 2.73]), and hospitalization (RR, 1.09 [95% CI, 0.81 to 1.47]) were similar between the two groups. Patients who received thromboprophylaxis had a higher risk of non-major bleeding (RR, 3.48 [95% CI, 1.72 to 7.05) compared to patients who did not receive thromboprophylaxis. Thromboprophylaxis reduced the risk of venous thromboembolism but not mortality, cardiovascular events, or hospitalization among outpatients with COVID-19., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The rhizobacterial strain BJ3 showed 16S rDNA sequence similarity to species within the Burkholderia genus. Its complete genome sequence revealed a 97% match with Burkholderia contaminans and uncovered gene clusters essential for plant-growth-promoting traits (PGPTs). These clusters include genes responsible for producing indole acetic acid (IAA), osmolytes, non-ribosomal peptides (NRPS), volatile organic compounds (VOCs), siderophores, lipopolysaccharides, hydrolytic enzymes, and spermidine. Additionally, the genome contains genes for nitrogen fixation and phosphate solubilization, as well as a gene encoding 1-aminocyclopropane-1-carboxylate (ACC) deaminase. The treatment with BJ3 enhanced root architecture, boosted vegetative growth, and accelerated early flowering in Arabidopsis . Treated seedlings also showed increased lignin production and antioxidant capabilities, as well as notably increased tolerance to water deficit and high salinity. An RNA-seq transcriptome analysis indicated that BJ3 treatment significantly activated genes related to immunity induction, hormone signaling, and vegetative growth. It specifically activated genes involved in the production of auxin, ethylene, and salicylic acid (SA), as well as genes involved in the synthesis of defense compounds like glucosinolates, camalexin, and terpenoids. The expression of AP2/ERF transcription factors was markedly increased. These findings highlight BJ3's potential to produce various bioactive metabolites and its ability to activate auxin, ethylene, and SA signaling in Arabidopsis , positioning it as a new Burkholderia strain that could significantly improve plant growth, stress resilience, and immune function.

Celosia spp. is a widely cultivated ornamental plant in gardens or parks in Taiwan. In September 2021, withering leaves and grayish-brown lesions were observed on the lower stem of plumed cockscombs ( C. argentea var. plumosa ) in Taichung City, with an incidence of about 22% in 136 plants after continuous precipitation, impacting the aesthetic value of the landscape. Symptomatic plants were collected, surface disinfected with 70% EtOH for ~20 sec., blotted dried, and excised diseased tissues (~ 3×3 mm 2 ) were placed on 2% water agar. Four representative isolates were obtained after purification and the colonies were white with aerial and non-septated hyphae on V8 agar for 7 days. Sporangia were ovoid, ellipsoid or obpyriform, papillate, (26.3-55.9) 38.0 × 29.0 (20.1-40.6) µm (n = 200) (Ahonsi et al. 2007). Chlamydospores were spherical, terminal or intercalary, 26.0 (15.1-40.4) µm (n = 200). All isolates belong to A2 mating type with amphigynous antheridia and plerotic oospores, 21.0 (17.7-25.7) µm (n = 200), resembling the descriptions of Phytophthora (Erwin & Ribeiro 1996). For molecular identification, sequences of the ITS, β-tubulin (β-tub), and EF-1α regions of all isolates were amplified using ITS1/ITS4, TUBUF2/TUBUR1, and ELONGF1/ELONGR1 primers, respectively (White et al. 1990; Kroon et al. 2004). BLAST analyses of isolates cap1-2 (ITS: OQ581785; β-tub: OQ590022; EF-1α: OQ590026), cap1-3 (ITS: OQ581786; β-tub: OQ590023; EF-1α: OQ590027), cap2-1 (ITS: OQ581787; β-tub: OQ590024; EF-1α: OQ590028), and cap2-2 (ITS: OQ581788; β-tub: OQ590025; EF-1α: OQ590029) showed 100% of ITS identity, 99.5 to 99.9% of β-tub identity, and 99.4 to 99.6% of EF-1α identity with Phytophthora nicotianae (ITS: MG865551; β-tub: MH493987; EF-1α: MH359043). Phylogenetic trees were constructed using concatenated ITS, β-tub, and EF-1α sequences based on maximum likelihood with a GTR+G model in MEGA X and Bayesian inference method in Geneious Prime 2022.2. All isolates were clustered in P. nicotianae with similar topology, thereby were identified as P. nicotianae . To confirm pathogenicity, 7 to 10-day-old seedlings and 6-week-old plumed cockscomb plants were inoculated in separate trials and each experiment was conducted twice. For each seedling, the lower stem was inoculated with 50 μl of zoospore suspension (10 4 zoospores/ml), 3 plants per isolate, and then incubated at 30±2℃ with 12 h light. For adult plants, each was inoculated with mycelial plugs from one V8 plate of 10-day-old P. nicotianae , 5 plants per isolate, and incubated at 25±2℃ in a greenhouse. Control plants were inoculated with sterile water and V8 agar plugs, respectively. Stem and root rot were observed on seedlings 4 days after inoculation while wilting and lower stem browning were observed on adult plants 2 months after inoculation. All control plants remained healthy at the end of repeated trials and identical pathogens were re-isolated only from symptomatic plants, thus fulfilling Koch's rules. P. nicotianae has been reported causing root rot and stem necrosis not only on cockscomb ( C . plumosa Hort. ex Burvenich) in Argentina (Frezzi 1950), but also infecting several ornamental plants recently in Taiwan (Ann et al. 2018). To our knowledge, this is the first report of stem blight caused by P. nicotianae on plumed cockscombs in Taiwan. This finding suggests limited options for landscaping and the host preference of the isolates obtained in this study should warrant further studies.

This study investigated the disinfection efficiency of a photoreactor equipped with a helical water flow channel and ultraviolet-C (UV-C) light emitting diodes (LEDs). Theoretical simulations and biodosimetry tests were conducted to investigate the effects of coil diameter and flow rate on the reactor's performance in inactivating Escherichia coli . The interplay between hydrodynamics and UV radiation was analyzed to determine the UV fluence absorbed by the microbes. The simulations revealed that, primarily due to the specific radiation pattern of the UV LEDs, the coil diameter strongly influenced the distribution of irradiance in the water and the UV fluence received by microbes. The experimental results indicated that the photoreactor achieved the highest inactivation value of 2.8 log when the coil diameter was 48 mm for a flow rate of 40 mL/min; this log value was superior to those for coil diameters of 16, 32, 64, and 80 mm by approximately 1.9, 0.4, 0.5, and 0.7 log units, respectively. This optimal coil diameter leading to the maximal UV irradiance and the highest degree of irradiance uniformity along the flow channel. This study offers design guidelines for constructing a high-efficiency water disinfection reactor with a helical flow channel configuration.

This research successfully synthesized SnO 2 @ZnIn 2 S 4 composites for photocatalytic tap water splitting using a rapid two-step microwave-assisted synthesis method. This study investigated the impact of incorporating a fixed quantity of SnO 2 nanoparticles and combining them with various materials to form composites, aiming to enhance photocatalytic hydrogen production. Additionally, different weights of SnO 2 nanoparticles were added to the ZnIn 2 S 4 reaction precursor to prepare SnO 2 @ZnIn 2 S 4 composites for photocatalytic hydrogen production. Notably, the photocatalytic efficiency of SnO 2 @ZnIn 2 S 4 composites is substantially higher than that of pure SnO 2 nanoparticles and ZnIn 2 S 4 nanosheets: 17.9-fold and 6.3-fold, respectively. The enhancement is credited to the successful use of visible light and the facilitation of electron transfer across the heterojunction, leading to the efficient dissociation of electron-hole pairs. Additionally, evaluations of recyclability demonstrated the remarkable longevity of SnO 2 @ZnIn 2 S 4 composites, maintaining high levels of photocatalytic hydrogen production over eight cycles without significant efficiency loss, indicating their impressive durability. This investigation presents a promising strategy for crafting and producing environmentally sustainable SnO 2 @ZnIn 2 S 4 composites with prospective implementations in photocatalytic hydrogen generation.

Background and Aim: Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium-glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer., Methods: We performed a retrospective cohort study comprising adult patients with T2DM and colorectal adenocarcinoma. SGLT2i recipients were matched to non-SGLT2i recipients in a 1:1 ratio based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with SGLT2i., Results: We identified 1347 patients with T2DM and colorectal adenocarcinoma, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of 5-year OS (86.2% [95% CI: 72.0-93.5] vs 62.3% [95% CI: 50.9-71.8], P = 0.013) and 5-year PFS (76.6% [95% CI: 60.7-86.7] vs 57.0% [95% CI: 46.2-66.4], P = 0.021). In Cox proportional hazard analyses, SGLT2i were associated with a 50-70% reduction in all-cause mortality and disease progression. SGLT2i were not associated with an increased risk of serious adverse events., Conclusion: SGLT2i were associated with a higher rate of survival in T2DM patients with colorectal cancer., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Fuzzy neural networks (FNNs) have been very successful at handling uncertainty in data using fuzzy mappings and if-then rules. However, they suffer from generalization and dimensionality issues. Although deep neural networks (DNNs) represent a step toward processing high-dimensional data, their capacity to address data uncertainty is limited. Furthermore, deep learning algorithms designed to improve robustness are either time consuming or yield unsatisfactory performance. In this article, we propose a robust fuzzy neural network (RFNN) to overcome these problems. The network contains an adaptive inference engine that is capable of handling samples with high-level uncertainty and high dimensions. Unlike traditional FNNs that use a fuzzy AND operation to calculate the firing strength for each rule, our inference engine is able to learn the firing strength adaptively. It also further processes the uncertainty in membership function values. Taking advantage of the learning ability of neural networks, the acquired fuzzy sets can be learned from training inputs automatically to cover the input space well. Furthermore, the consequent layer uses neural network structures to enhance the reasoning ability of the fuzzy rules when dealing with complex inputs. Experiments on a range of datasets show that RFNN delivers state-of-the-art accuracy even at very high levels of uncertainty. Our code is available online. https://github.com/leijiezhang/RFNN.

Hypertriglyceridemia and decreased high-density lipoprotein cholesterol (HDL-C) persist despite statin therapy, contributing to residual atherosclerotic cardiovascular disease (ASCVD) risk. Asian subjects are metabolically more susceptible to hypertriglyceridemia than other ethnicities. Fenofibrate regulates hypertriglyceridemia, raises HDL-C levels, and is a recommended treatment for dyslipidemia. However, data on fenofibrate use across different Asian regions are limited. This narrative review summarizes the efficacy and safety data of fenofibrate in Asian subjects with dyslipidemia and related comorbidities (diabetes, metabolic syndrome, diabetic retinopathy, and diabetic nephropathy). Long-term fenofibrate use resulted in fewer cardiovascular (CV) events and reduced the composite of heart failure hospitalizations or CV mortality in type 2 diabetes mellitus. Fenofibrate plays a significant role in improving irisin resistance and microalbuminuria, inhibiting inflammatory responses, and reducing retinopathy incidence. Fenofibrate plus statin combination significantly reduced composite CV events risk in patients with metabolic syndrome and demonstrated decreased triglyceride and increased HDL-C levels with an acceptable safety profile in those with high CV or ASCVD risk. Nevertheless, care is necessary with fenofibrate use due to possible hepatic and renal toxicities in vulnerable individuals. Long-term trials and real-world studies are needed to confirm the clinical benefits of fenofibrate in the heterogeneous Asian population with dyslipidemia.

Atomically thin oxide semiconductors are emerging as potential materials for their potentiality in monolithic 3D integration and sensor applications. In this study, a charge transfer method employing viologen, an organic compound with exceptional reduction potential among n-type organics, is presented to modulate the carrier concentration in atomically thin In 2 O 3 without the need of annealing. This study highlights the critical role of channel thickness on doping efficiency, revealing that viologen charge transfer doping is increasingly pronounced in thinner channels owing to their increased surface-to-volume ratio. Upon viologen doping, an electron sheet density of 6.8 × 10 12 cm -2 is achieved in 2 nm In 2 O 3 back gate device while preserving carrier mobility. Moreover, by the modification of the functional groups, viologens can be conveniently removed with acetone and an ultrasonic cleaner, making the viologen treatment a reversible process. Based on this doping scheme, we demonstrate an n-type metal oxide semiconductor inverter with viologen-doped In 2 O 3 , exhibiting a voltage gain of 26 at V D = 5 V. This complementary pairing of viologen and In 2 O 3 offers ease of control over the carrier concentration, making it suitable for the next-generation electronic applications.

Objectives: Randomised controlled trials (RCTs) have demonstrated conflicting results regarding the effects of corticosteroids on the treatment of severe community-acquired pneumonia (CAP). We aimed to investigate the efficacy and safety of different corticosteroids on patients who were hospitalised for severe CAP., Methods: We performed a systematic search through PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to May 2023. The primary outcome was all-cause mortality. Data analysis was performed using a random-effects model., Results: A total of 10 RCTs comprising 1962 patients were included. Corticosteroids were associated with a lower rate of all-cause mortality (risk ratio (RR), 0.70 (95% CI 0.54 to 0.90); I 2 =0.00%). When stratified into different corticosteroid types, hydrocortisone was associated with an approximately 50% lower mortality risk (RR, 0.48 (95% CI 0.32 to 0.72); I 2 =0.00%). However, dexamethasone, methylprednisolone or prednisolone were not associated with an improvement in mortality. Furthermore, hydrocortisone was associated with a reduction in the rate of mechanical ventilation, acute respiratory distress syndrome, shock and duration of intensive care unit stay. These trends were not observed for dexamethasone, methylprednisolone or prednisolone. Corticosteroids were not associated with an increased risk of adverse events including gastrointestinal bleeding, secondary infection or hyperglycaemia., Conclusions: The use of hydrocortisone, but not other types of corticosteroids, was associated with a reduction in mortality and improvement in pneumonia outcomes among patients hospitalised with severe CAP.PROSPERO registration numberCRD42023431360., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The fragile nature of quantum circuits is a major bottleneck to scalable quantum applications. Operating at cryogenic temperatures, quantum circuits are highly vulnerable to amplifier backaction and external noise. Non-reciprocal microwave devices such as circulators and isolators are used for this purpose. These devices have a considerable footprint in cryostats, limiting the scalability of quantum circuits. As a proof-of-concept, here we report a compact microwave diode architecture, which exploits the non-linearity of a superconducting flux qubit. At the qubit degeneracy point we experimentally demonstrate a significant difference between the power levels transmitted in opposite directions. The observations align with the proposed theoretical model. At - 99 dBm input power, and near the qubit-resonator avoided crossing region, we report the transmission rectification ratio exceeding 90% for a 50 MHz wide frequency range from 6.81 GHz to 6.86 GHz, and over 60% for the 250 MHz range from 6.67 GHz to 6.91 GHz. The presented architecture is compact, and easily scalable towards multiple readout channels, potentially opening up diverse opportunities in quantum information, microwave read-out and optomechanics., (© 2024. The Author(s).)

Introduction: Breast cancer is the most common cancer in women with a 5-year survival over 90%. However, anthracycline-based chemotherapy causes significant cardiotoxicity often requiring discontinuation of chemotherapeutic regimen among breast cancer survivors. We conducted a systematic review and meta-analysis to evaluate the efficacy of exercise training in mitigating anthracycline-related cardiotoxicity among women with breast cancer., Methods: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases. The outcomes of interest were left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), early to atrial filling velocity (E/A) ratio, maximal oxygen consumption (VO2 max), and cardiac output (CO). We used the Cochrane risk-of-bias tool for randomized trials (RoB 2) to assess the risk of bias in individual studies., Results: We identified a total of 596 articles with 5 trials included in the final analysis. Exercise training was associated with an increase in VO2 max compared with no exercise training (mean difference, 3.95 [95% CI, 0.63-7.26]; I2 = 99.68%). Other cardiovascular outcomes such as LVEF (mean difference, 1.76 [95% CI, -1.95 to 5.46]; I2 = 99.44%), GLS (mean difference, 0.30 [95% CI, -0.49 to 1.10]; I2 = 96.63%), E/A ratio (mean difference, 0.05 [95% CI, -0.05 to 0.15]; I2 = 94.16%), and CO (mean difference, 0.38 [95% CI, -0.91 to 1.66]; I2 = 99.73%) are similar between patients who underwent exercise training and those who did not., Conclusions: Exercise was associated with an improvement in maximal oxygen uptake among women with breast cancer receiving anthracycline-based chemotherapy., (© 2023 S. Karger AG, Basel.)

Drowsy driving is one of the primary causes of driving fatalities. Electroencephalography (EEG), a method for detecting drowsiness directly from brain activity, has been widely used for detecting driver drowsiness in real-time. Recent studies have revealed the great potential of using brain connectivity graphs constructed based on EEG data for drowsy state predictions. However, traditional brain connectivity networks are irrelevant to the downstream prediction tasks. This article proposes a connectivity-aware graph neural network (CAGNN) using a self-attention mechanism that can generate task-relevant connectivity networks via end-to-end training. Our method achieved an accuracy of 72.6% and outperformed other convolutional neural networks (CNNs) and graph generation methods based on a drowsy driving dataset. In addition, we introduced a squeeze-and-excitation (SE) block to capture important features and demonstrated that the SE attention score can reveal the most important feature band. We compared our generated connectivity graphs in the drowsy and alert states and found drowsiness connectivity patterns, including significantly reduced occipital connectivity and interregional connectivity. Additionally, we performed a post hoc interpretability analysis and found that our method could identify drowsiness features such as alpha spindles. Our code is available online at https://github.com/ALEX95GOGO/CAGNN.

Background/purpose: The accumulation of advanced glycation end products (AGEs) lead to a series of immune responses such as: increased oxidative stress and inflammation which contribute to the development of diabetic complications and periodontal disease. Resveratrol is a natural compound that has anti-oxidant and anti-inflammatory effects. Studies have found that diabetes-induced periodontitis is mainly caused by oxidative stress, aging and increased inflammation. In view of resveratrol has been proposed to have the ability in anti-oxidant and anti-inflammation in a variety of tissues. However, the role of resveratrol in diabetic periodontitis remains to be investigated. In this study, we aimed to investigate the role of resveratrol in preventing and treating diabetic periodontitis., Materials and Methods: First, cell proliferation was measured in AGEs-treated human gingival fibroblast with or without resveratrol. We examined the reactive oxygen species (ROS) generation, senescence-associated beta-galactosidase (SA-β-gal) and senescence marker p16 in human gingival fibroblasts (HGFs) stimulated with AGEs with or without the treatment of resveratrol. To determine whether resveratrol has the potential to regulate inflammaging which is mediated via the NF-κB signaling pathway and, the expression of p65 and p-IκB were also investigated. Furthermore, the concentration of interleukin (IL)-6 and IL-8 were also measured in AGEs-stimulated HGFs treated with or without resveratrol., Results: ROS generation, cell senescence, and the secretion of IL-6 and IL-8 were significantly upregulated following the treatment of AGEs. However, the administration of resveratrol suppresses the generation of IL-6 and IL-8 and cell senescence via inhibiting NF-κB signaling pathway. Our results revealed that resveratrol inhibits inflammaging by downregulating NF-κB signaling pathway., Conclusion: According to our findings, AGEs increase senescence and the production of proinflammatory cytokines in the gingiva, while the administration of resveratrol impedes inflammaging via suppressing NF-κB signaling pathway., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

A multi-step procedure was effectively employed to synthesize innovative three-dimensional (3D) heterostructures encompassing sodium titanate (Na 2 Ti 3 O 7 ) nanowire cores, an intermediate resorcinol-formaldehyde (RF) layer, and outer silver (Ag) nanoparticle sheaths, referred to as Na 2 Ti 3 O 7 @RF@Ag heterostructures. Initially, a one-step hydrothermal technique facilitated the direct growth of single-crystal Na 2 Ti 3 O 7 nanowires onto a flexible Ti foil. Subsequently, a two-step wet chemical process facilitated the sequential deposition of an RF layer and Ag nanoparticles onto the Na 2 Ti 3 O 7 nanowires at a low reaction temperature. Optimal concentrations of silver nitrate and L-ascorbic acid can lead to the cultivation of Na 2 Ti 3 O 7 @RF@Ag heterostructures exhibiting heightened surface-enhanced Raman scattering (SERS), which is particularly beneficial for the detection of rhodamine B (RhB) molecules. This phenomenon can be ascribed to the distinctive geometry of the Na 2 Ti 3 O 7 @RF@Ag heterostructures, which offer an increased number of hot spots and surface-active sites, thereby showcasing notable SERS enhancement, commendable reproducibility, and enduring stability over the long term. Furthermore, the Na 2 Ti 3 O 7 @RF@Ag heterostructures demonstrate remarkable follow-up as first-order chemical kinetic and recyclable photocatalysts for the photodecomposition of an RhB solution under UV light irradiation. This result can be attributed to the enhanced inhibition of electron-hole pair recombination and increased surface-active sites.

Geometry optimization is a crucial step in computational chemistry, and the efficiency of optimization algorithms plays a pivotal role in reducing computational costs. In this study, we introduce a novel reinforcement-learning-based optimizer that surpasses traditional methods in terms of efficiency. What sets our model apart is its ability to incorporate chemical information into the optimization process. By exploring different state representations that integrate gradients, displacements, primitive type labels, and additional chemical information from the SchNet model, our reinforcement learning optimizer achieves exceptional results. It demonstrates an average reduction of about 50% or more in optimization steps compared to the conventional optimization algorithms that we examined when dealing with challenging initial geometries. Moreover, the reinforcement learning optimizer exhibits promising transferability across various levels of theory, emphasizing its versatility and potential for enhancing molecular geometry optimization. This research highlights the significance of leveraging reinforcement learning algorithms to harness chemical knowledge, paving the way for future advancements in computational chemistry.

Objective: Statins have been demonstrated to improve outcomes in patients receiving immune checkpoint blockade (ICB). This study aimed to investigate whether the timing of statin administration influences the outcomes of patients receiving ICB., Methods: We conducted a retrospective cohort study utilizing electronic health records from two tertiary referral centers in Taiwan. We compared the overall survival (OS) and progression-free survival (PFS) of patients who received statins before and after ICB initiation., Results: We included 734 patients who received ICB. Among them, 606 were non-statin users, 76 started statins after ICB initiation, and 52 started statins before ICB initiation. Post-ICB statin users demonstrated significantly prolonged OS (median 37.6 versus 10.3 versus 11.3 months, p  = 0.009) and PFS (median 10.5 versus 6.3 versus 5.6 months, p  = 0.024) compared to pre-ICB statin and non-statin users. Statin use after ICB initiation had a reduced risk of all-cause mortality (HR, 0.65 [95% CI: 0.45-0.94], p  = 0.022) and progressive disease (HR, 0.71 [95% CI: 0.53-0.95], p  = 0.021) by approximately 30-35%, compared to non-statin users. However, statin use prior to ICB initiation did not affect the risk of all-cause mortality or progressive disease. Similar results were observed after controlling for potential cofounders such as age, sex, cancer stage, and cancer type., Conclusions: These findings suggest that initiating statin therapy after the initiation of ICB, regardless of indication, is associated with improved patient prognosis.

There have been many clinical questions regarding whether the use of proton pump inhibitors (PPIs) could deteriorate the effects of cyclin-dependent kinase inhibitors (CDKIs) in HR+/HER2- advanced breast cancer patients. We performed a systematic review and meta-analysis of this clinical question, including studies enrolling HR+/HER2- metastatic breast cancer patients treated with CDKIs (Palbociclib or Ribociclib) and reporting at least one comparative survival outcome, either overall survival (OS) or progression-free survival (PFS), between concomitant PPI users and non-users. Eight studies met the eligibility criteria, with a total of 2584 patients included (PPI users: 830, PPI non-users: 1754), demonstrating that concomitant PPI use was associated with significantly higher risks of all-cause mortality (HR = 2.03; 95% CI, 1.49 to 2.77; I 2 = 0%) and disease progression (HR = 1.75; 95% CI, 1.26 to 2.43; I 2 = 59%) in breast cancer patients taking Palbociclib. In contrast, there were no significant survival impacts of PPIs on Ribociclib (HR = 1.46; 95% CI, 0.91 to 2.34; I 2 = 36%). Additionally, there was no significant difference in the risk associated with CDKI dose reduction due to drug toxicity (RR = 1.12; 95% CI, 0.97 to 1.29). Therefore, when HR+/HER2- advanced breast cancer patients require the use of PPIs, it may be reasonable to consider using Ribociclib.

Minimally invasive nonsurgical treatment (MINST) aims to remove an etiology with minimal damage to the healthy periodontium and provide the ideal healing environment. This case series introduces the novel protocol of laser-assisted MINST (LAMINST), combining minimally invasive surgery with a dental laser. A total of 25 patients (32 teeth) with advanced periodontal disease were enrolled and received periodontal treatment by following the LAMINST protocol. Probing depth (PD), recession, clinical attachment level (CAL), bleeding on probing (BOP), plaque presence, and site mobility were evaluated preoperatively and at 6 months. Based on the periodontal evaluations, all cases were diagnosed as stage III grade C periodontitis. Six months after LAMINST, the average PD reduction was 4.44 mm and CAL improved by 4.38 mm. Baseline mobility scores of 1 (6 teeth), 2 (9 teeth), and 3 (3 teeth) decreased to 1 (5 teeth) or 0 (13 teeth). The initial prognoses of 5 (hopeless; 15 teeth), 4 (questionable; 13 teeth), and 3 (poor; 4 teeth), improved to 4 (5 teeth), 3 (12 teeth), 2 (fair; 13 teeth), and 1 (good; 2 teeth). The number of BOP sites reduced from 179 to 12, and the number of plaque sites reduced from 173 to 9. All clinical parameters were improved after LAMINST. The application of LAMINST may overcome the traditional limitations of nonsurgical treatment, such as poor accessibility.

Molar-incisor pattern periodontitis (MIPP) is a severe form of periodontal disease characterized by rapid attachment loss and bone destruction affecting the molars and incisors. Formerly referred to as aggressive periodontitis, the terminology for this condition was revised after the 2017 workshop on the classification of periodontal and peri-implant diseases and conditions. Despite the modification in nomenclature, the treatment strategies for MIPP remain a critical area of investigation. The core principles of MIPP treatment involve controlling local and systemic risk factors, managing inflammation, and arresting disease progression. Traditional non-surgical periodontal therapy, including scaling and root planing, is commonly employed as an initial step together with the prescription of antibiotics. Surgical intervention may be necessary to address the severe attachment loss. Surgical techniques like resective and regenerative procedures can aid in achieving periodontal health and improving esthetic outcomes. This review article aims to provide an overview of the current understanding and advancements in the treatment modalities of MIPP. Through an extensive analysis of the existing literature, we discuss various modern therapeutic approaches that have been explored for managing this challenging periodontal condition.

Since the development of CBCT has been utilized in dentistry, the images of the CBCT can assist the surgeon to evaluate the anatomy carefully. Despite the value of radiology evaluation, implant procedures may require additional consideration rather than only evaluating the anatomical factors. The purpose of this study is to evaluate the predictability of using CBCT alone to plan for implant placement in edentulous patients digitally. CBCT images were analyzed by clinicians, measuring the maxillary and mandibular ridge heights and widths digitally of four predetermined implant sites in the maxillary and two selected implant sites in the mandibular arches of 91 patients planning for implant-supported overdenture. A total of 47 patients out of the 91 had completed implant placement on the edentulous ridge, contributing to 55 upper and/or lower arches (136 dental implants). Both predictabilities are low, implying that CBCT planning for implant placement on the edentulous ridge is not a good index and is insufficient to predict the surgical procedures as a solo method. The findings of this study indicate that digital planning by CBCT is insufficient to serve as an individual tool to predict implant procedures. Further information and evaluation must be considered for implant placement in the edentulous ridge.

Aim: To investigate the relationship between the prevalence of antinuclear antibody (ANA) -associated rheumatic diseases (AARD) and the presence of dense fine speckled (DFS) and homogeneous patterns in ANA tests., Methods: This retrospective study enrolled adult patients with either a DFS or homogeneous pattern in their ANA test. A mixed pattern was defined as the presence of more than one pattern reported in the test. The presence of anti-DFS70 antibodies and other common autoantibodies were detected using EUROLINE ANA Profile 23. A 1:2 propensity score matching was applied to control for demographic and other interfering factors., Results: A total of 59 patients with a DFS pattern were enrolled and compared with a matched homogeneous group. The DFS group had a significantly lower prevalence of AARD (3.4% vs. 16.9%, p = .008) and the subgroup with anti-DFS70 antibodies showed an even lower prevalence (2% vs. 20%, p = .002). Among the 33 patients with monospecific anti-DFS70 antibodies, five had a mixed pattern, and all patients with common autoantibodies had an isolated DFS pattern., Conclusions: The findings of this study suggest that patients with a DFS pattern in their ANA test may have a lower prevalence of AARD compared with those with a homogeneous pattern. However, an isolated DFS pattern in ANA testing does not necessarily indicate the presence of monospecific anti-DFS70 antibodies or AARD. Confirmatory testing for the monospecific anti-DFS70 antibody is mandatory to exclude AARD., (© 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Allergic asthma is an inflammatory lung disorder, and mast cells play crucial roles in the development of this allergic disease. Norisoboldine (NOR), the major isoquinoline alkaloid present in Radix Linderae, has received considerable attention because it has anti-inflammatory effects. Herein, the aim of this study was to explore the antiallergic effects of NOR on allergic asthma in mice and mast cell activation. In a murine model of ovalbumin (OVA)-induced allergic asthma, oral administration at 5 mg/kg body weight (BW) of NOR produced strong reductions in serum OVA-specific immunoglobulin E (IgE) levels, airway hyperresponsiveness, and bronchoalveolar lavage fluid (BALF) eosinophilia, while an increase in CD4 + Foxp3 + T cells of the spleen was detected. Histological studies demonstrated that NOR treatment significantly ameliorated the progression of airway inflammation including the recruitment of inflammatory cells and mucus production by decreasing levels of histamine, prostaglandin D 2 (PGD 2 ), interleukin (IL)-4, IL-5, IL-6, and IL-13 in BALF. Furthermore, our results revealed that NOR (3 ∼ 30 μM) dose-dependently reduced expression of the high-affinity receptor for IgE (FcεRI) and the production of PGD 2 and inflammatory cytokines (IL-4, IL-6, IL-13, and TNF-α), and also decreased degranulation of bone marrow-derived mast cells (BMMCs) activated by IgE/OVA. In addition, a similar suppressive effect on BMMC activation was observed by inhibition of the FcεRI-mediated c-Jun N-terminal kinase (JNK) signaling pathway using SP600125, a selective JNK inhibitor. Collectively, these results suggest that NOR may have therapeutic potential for allergic asthma at least in part through regulating the degranulation and the release of mediators by mast cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The recent development of closed-loop EEG phase-triggered transcranial magnetic stimulation (TMS) has advanced potential applications of adaptive neuromodulation based on the current brain state. Closed-loop TMS involves instantaneous acquisition of the EEG rhythm, timing prediction of the target phase, and triggering of TMS. However, the accuracy of EEG phase prediction algorithms is largely influenced by the system's transport delay, and their relationship is rarely considered in related work. This paper proposes a delay analysis that considers the delay of the closed-loop EEG phase-triggered TMS system as a primary factor in the validation of phase prediction algorithms. An in-silico validation using real EEG data was performed to compare the performance of commonly used algorithms. The experimental results indicate a significant influence of the total delay on the algorithm performance, and the performance ranking among algorithms varies at different levels of delay. We conclude that the delay analysis framework should be widely adopted in the design and validation of phase prediction algorithms for closed-loop EEG phase-triggered TMS systems.

In this study, a facile and rapid microwave-assisted synthesis method was used to synthesize In 2 S 3 nanosheets, ZnS nanosheets, and ZnIn 2 S 4 nanosheets with sulfur vacancies. The two-dimensional semiconductor photocatalysts of ZnIn 2 S 4 nanosheets were characterized by XRD, FESEM, BET, TEM, XPS, UV-vis diffuse reflectance, and PL spectroscopy. The ZnIn 2 S 4 with sulfur vacancies exhibited an evident energy bandgap value of 2.82 eV, as determined by UV-visible diffuse reflectance spectroscopy, and its energy band diagram was obtained through the combination of XPS and energy bandgap values. ZnIn 2 S 4 nanosheets exhibited about 33.3 and 16.6 times higher photocatalytic hydrogen production than In 2 S 3 nanosheets and ZnS nanosheets, respectively, under visible-light irradiation. Various factors, including materials, sacrificial reagents, and pH values, were used to evaluate the influence of ZnIn 2 S 4 nanosheets on photocatalytic hydrogen production. In addition, the ZnIn 2 S 4 nanosheets revealed the highest photocatalytic hydrogen production from seawater, which was about 209.4 and 106.7 times higher than that of In 2 S 3 nanosheets and ZnS nanosheets, respectively. The presence of sulfur vacancies in ZnIn 2 S 4 nanosheets offers promising opportunities for developing highly efficient and stable photocatalysts for photocatalytic hydrogen production from seawater under visible-light irradiation.

We have demonstrated a two-step wet chemical approach for synthesizing ternary Ag/Ag 2 S/CdS heterostructures for efficient photocatalytic hydrogen evolution. The CdS precursor concentrations and reaction temperatures are crucial in determining the efficiency of photocatalytic water splitting under visible light excitation. In addition, the effect of operational parameters (such as the pH value, sacrificial reagents, reusability, water bases, and light sources) on the photocatalytic hydrogen production of Ag/Ag 2 S/CdS heterostructures was investigated. As a result, Ag/Ag 2 S/CdS heterostructures exhibited a 3.1-fold enhancement in photocatalytic activities compared to bare CdS nanoparticles. Furthermore, the combination of Ag, Ag 2 S, and CdS can significantly enhance light absorption and facilitate the separation and transport of photogenerated carriers through the surface plasma resonance (SPR) effect. Furthermore, the Ag/Ag 2 S/CdS heterostructures in seawater exhibited a pH value approximately 2.09 times higher than in de-ionized water without an adjusted pH value under visible light excitation. The ternary Ag/Ag 2 S/CdS heterostructures provide new potential for designing efficient and stable photocatalysts for photocatalytic hydrogen evolution.

Background: Immune checkpoint inhibitors have transformed the treatment landscape of cancer treatment, but only a fraction of patients responds to treatment, leading to an increasing effort to repurpose clinically approved medications to augment ICI therapy. Metformin has been associated with improved survival outcomes in patients undergoing conventional chemotherapy. However, whether metformin provides survival benefits in patients receiving immune checkpoint inhibitors (ICIs) is unknown., Methods: We performed a retrospective cohort study at two tertiary referral centers in Taiwan. All adult diabetes mellitus patients who were treated with ICIs between January 2015 and December 2021 were included. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), respectively., Results: In total, 878 patients were enrolled in our study, of which 86 patients used metformin and 78 patients used non-metformin diabetes medications. Compared with non-users, metformin users had a longer median OS (15.4 [IQR 5.6-not reached] vs. 6.1 [IQR, 0.8-21.0] months, P = 0.003) and PFS (5.1 [IQR 2.0-14.3] vs. 1.9 [IQR 0.7-8.6] months, P = 0.041). In a univariate Cox proportional hazard analysis, the use of metformin was associated with a reduction in the risk of mortality (HR: 0.53 [95% confidence interval: 0.35-0.81], P = 0.004) and disease progression (HR: 0.69 [95% CI 0.49-0.99], P = 0.042). The use of metformin remained associated with a lower risk of mortality after adjusting for baseline variables such as age, cancer stage, and underlying comorbidities (OS, HR: 0.55 [95% CI 0.34-0.87], P = 0.011). Similarly, the use of metformin was associated with a lower risk of disease progression. Importantly, the use of metformin before ICI initiation was not associated with a reduction in mortality (HR: 0.61 [95% CI 0.27-1.42], P = 0.25) or disease progression (HR: 0.69 [95% CI 0.33-1.43], P = 0.32)., Conclusion: The use of metformin is associated with survival benefits in patients undergoing immunotherapy. Prospective clinical trials are warranted to define the role of metformin in augmenting immunotherapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Post-surgical pain following dental implant placement surgery is typically managed with non-opioid analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. However, the comparative analgesic efficacy of over-the-counter doses of non-steroidal anti-inflammatory drugs and acetaminophen in implant patients is unknown. Therefore, we compared the analgesic and anti-inflammatory effects of naproxen sodium and acetaminophen after surgical placement of one or two dental implants. Methods: Adult patients were treated with naproxen sodium (440 mg loading dose +220 mg q8h, n = 15) or acetaminophen (1,000 mg q6h-max daily dose 3,000 mg, n = 15) for 3 days after implant placement in a randomized, double-blind design. Pain was assessed on a 0-10 scale every 20 min for 6 h after study medication treatment. Tramadol (50 mg) was available as a rescue medication. Plasma and gingival crevicular fluid (GCF) were collected prior to the surgery and 0, 1, 2, 4, 6, 24, and 72 h after surgery for quantification of interleukin (IL)-6, IL-8, and IL-1β levels. Results: Pain scores were significantly lower in patients treated with naproxen sodium compared to those treated with acetaminophen. Inflammatory mediator levels in plasma and gingival crevicular fluid increased after surgery and returned to near baseline levels by 72 h. Plasma IL-6 levels were significantly lower 6 h after surgery in patients treated with naproxen sodium compared to acetaminophen. No differences in inflammatory mediator concentrations in gingival crevicular fluid were observed between the treatment groups. The number of implants placed and body mass index (BMI) influenced inflammatory mediator concentrations in plasma and gingival crevicular fluid, respectively. Discussion: Naproxen sodium was more effective than acetaminophen in reducing post-operative pain and systemic inflammation following surgical placement of one or two dental implants. Further studies are needed to determine whether these findings are applicable to more complex implant cases and how they affect clinical outcomes following implant placement. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04694300., Competing Interests: This study was supported by an investigator-initiated research grant from Bayer Healthcare, LLC to KT and EH. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Theken, Chen, Wall, Pham, Secreto, Yoo, Rascon, Chang, Korostoff, Mitchell and Hersh.)

Purpose: Artificial intelligence-based tools can be leveraged to improve detection and segmentation of brain metastases for stereotactic radiosurgery (SRS). VBrain by Vysioneer Inc. is a deep learning algorithm with recent FDA clearance to assist in brain tumor contouring. We aimed to assess the performance of this tool by various demographic and clinical characteristics among patients with brain metastases treated with SRS., Materials and Methods: We randomly selected 100 patients with brain metastases who underwent initial SRS on the CyberKnife from 2017 to 2020 at a single institution. Cases with resection cavities were excluded from the analysis. Computed tomography (CT) and axial T1-weighted post-contrast magnetic resonance (MR) image data were extracted for each patient and uploaded to VBrain. A brain metastasis was considered "detected" when the VBrain- "predicted" contours overlapped with the corresponding physician contours ("ground-truth" contours). We evaluated performance of VBrain against ground-truth contours using the following metrics: lesion-wise Dice similarity coefficient (DSC), lesion-wise average Hausdorff distance (AVD), false positive count (FP), and lesion-wise sensitivity (%). Kruskal-Wallis tests were performed to assess the relationships between patient characteristics including sex, race, primary histology, age, and size and number of brain metastases, and performance metrics such as DSC, AVD, FP, and sensitivity., Results: We analyzed 100 patients with 435 intact brain metastases treated with SRS. Our cohort consisted of patients with a median number of 2 brain metastases (range: 1 to 52), median age of 69 (range: 19 to 91), and 50% male and 50% female patients. The primary site breakdown was 56% lung, 10% melanoma, 9% breast, 8% gynecological, 5% renal, 4% gastrointestinal, 2% sarcoma, and 6% other, while the race breakdown was 60% White, 18% Asian, 3% Black/African American, 2% Native Hawaiian or other Pacific Islander, and 17% other/unknown/not reported. The median tumor size was 0.112 c.c. (range: 0.010-26.475 c.c.). We found mean lesion-wise DSC to be 0.723, mean lesion-wise AVD to be 7.34% of lesion size (0.704 mm), mean FP count to be 0.72 tumors per case, and lesion-wise sensitivity to be 89.30% for all lesions. Moreover, mean sensitivity was found to be 99.07%, 97.59%, and 96.23% for lesions with diameter equal to and greater than 10 mm, 7.5 mm, and 5 mm, respectively. No other significant differences in performance metrics were observed across demographic or clinical characteristic groups., Conclusion: In this study, a commercial deep learning algorithm showed promising results in segmenting brain metastases, with 96.23% sensitivity for metastases with diameters of 5 mm or higher. As the software is an assistive AI, future work of VBrain integration into the clinical workflow can provide further clinical and research insights., (© 2023. The Author(s).)

Background: Certain angiotensin receptor blockers (ARBs) have peroxisome proliferator-activated receptor-γ (PPAR-γ) activation property, which has been associated with improved programmed cell death ligand 1 blockade and cytotoxic T lymphocyte-mediated antitumor activity., Methods: We conducted a retrospective cohort study to investigate the impact of PPAR-γ-activating ARBs on patient survival in patients treated with immune checkpoint inhibitors (ICIs) across all types of cancers., Results: A total of 167 patients receiving both angiotensin receptor blockers (ARBs) and immune checkpoint inhibitors (ICIs) were included. Compared with non-PPAR-γ-ARB users (n = 102), PPAR-γ-ARB users (n = 65) had a longer median overall survival (not reached [IQR, 16.0-not reached] vs. 18.6 [IQR, 6.1-38.6] months) and progression-free survival (17.3 [IQR, 5.1-not reached] vs. 8.2 [IQR, 2.4-18.6] months). In Cox regression analysis, the use of PPAR-γ-activating ARBs had an approximately 50% reduction in all-cause mortality and disease progression. Patients who received PPAR-γ-activating ARBs also had higher clinical benefit rates than non-PPAR-γ-ARB users (82% vs. 61%, p = 0.005)., Conclusion: The use of ARBs with PPAR-γ-activating property is linked with better survival among patients receiving ICIs., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce heart failure (HF) in at-risk patients and may possess antitumour effects. We examined the effect of SGLT2i on HF and mortality among patients with cancer and diabetes., Methods: This was a retrospective propensity score-matched cohort study involving adult patients with type 2 diabetes mellitus diagnosed with cancer between January 2010 and December 2021. The primary outcomes were hospitalisation for incident HF and all-cause mortality. The secondary outcomes were serious adverse events associated with SGLT2i., Results: From a total of 8640 patients, 878 SGLT2i recipients were matched to non-recipients. During a median follow-up of 18.8 months, SGLT2i recipients had a threefold lower rate of hospitalisation for incident HF compared with non-SGLT2i recipients (2.92 vs 8.95 per 1000 patient-years, p=0.018). In Cox regression and competing regression models, SGLT2i were associated with a 72% reduction in the risk of hospitalisation for HF (HR 0.28 (95% CI: 0.11 to 0.77), p=0.013; subdistribution HR 0.32 (95% CI: 0.12 to 0.84), p=0.021). The use of SGLT2i was also associated with a higher overall survival (85.3% vs 63.0% at 2 years, p<0.001). The risk of serious adverse events such as hypoglycaemia and sepsis was similar between the two groups., Conclusions: The use of SGLT2i was associated with a lower rate of incident HF and prolonged overall survival in patients with cancer with diabetes mellitus., Competing Interests: Competing interests: TGN has been a consultant to and received fees from Parexel Imaging, Intrinsic Imaging, BMS, H3-Biomedicine, AbbVie, C4-Therapeutics, Roche, Sanofi and Genentech, outside of the current work. TGN has received grant funding from AstraZeneca and BMS. PA has served as a consultant for Merck, BMS, Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics, Celgene, Morphosys, Daiichi Sankyo, Miltenyi, Tessa, GenMab, C4, Enterome, Regeneron, Epizyme, Astra Zeneca, Genentech, Xencor, outside of the current work. PA has received research funding from Kite, Merck, BMS, Affimed, Adaptive, Tensha, Otsuka, Sigma Tau, Genentech/Roche, IGM, and speaking honoraria from Merck and BMS, all unrelated to the current work. LRP has stock in Johnson and Johnson, Exact Sciences, Adverum Biotechnology, Crisper Therapeutics, Editas Med., Integra Lifesciences, Medtronic, Seagen Inc., Shockwave Medical, outside of the current work. All other authors have no conflict of interest to disclose., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

New Guinea impatiens ( Impatiens hawkeri ) is a common ornamental crop usually planted in pots and planters, flower beds, home gardens, or parks in Taiwan. In June 2021, leaf spots on 87.1% (27/31) of potted I. hawkeri plants on National Chung Hsing University (NCHU) campus were observed. Initially, tiny chlorotic leaf spots were found, which aged into brown to grayish white necrotic spots with reddish-purple margins. The necrotic spots enlarged, coalesced, and formed concentric rings. To isolate the pathogen, diseased leaves were surface-disinfected with 70% ethanol for 15 seconds and blotted dry with a paper towel. Small pieces (~2×6 mm 2 ) of tissues were excised from the junction of the lesions and healthy areas, placed onto 2% water agar, and incubated at 25°C with 12-h photoperiod for three days. Individual hyphal tips growing out of diseased tissues were transferred onto potato dextrose agar (PDA). Three isolates, OM10, OM43, and OM45, were obtained and grown on half-strength PDA at 28°C in the dark for at least two weeks. Conidia of each isolate produced on the half-strength PDA were washed off in sterile water with 0.01% of Tween 20. Pathogenicity tests were performed by spraying leaves of 2- to 3-month-old potted healthy I. hawkeri plants with 5 ml of conidial suspension (1 × 10 5 conidia/ml) of the three isolates, respectively. Control plants were sprayed with sterile water. There were four plants per treatment and the experiments were conducted twice. Inoculated plants were covered with plastic bags for two days and incubated in a greenhouse with a temperature range of 19 to 31°C. Leaf spots similar to those observed in the field were observed at 7 to 14 days after inoculation in both trials. The same fungus was isolated from inoculated plants, whereas control plants showed no symptoms. Thereafter, the three isolates were subjected to morphological and molecular identification. Colonies were brown to gray in the center and white in the border with abundant aerial mycelia. Conidia were brown, obclavate to ovoid, produced in single or branched chains, one to seven transverse and zero to three longitudinal septa. Conidial size of the three isolates ranged between 11.2 to 43.1 × 6.0 to 12.7 μm (n = 50 for each isolate). Conidiophores of the three isolates were dark-brown, septate, branched or unbranched, and measured 27.0 to 147.65 × 2.71 to 4.54 μm (n = 50 for each isolate). Based on the morphological characteristics, the three isolates were identified as Alternaria spp. (Simmons 2007). For molecular identification, the internal transcribed spacer (ITS) region, RNA polymerase II second largest subunit (RPB2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and major allergen Alt-a-1 gene (Alt-a-1) were amplified using primer pairs ITS1/ITS4 (White et al. 1990), RPB2-5F2/RPB2-7cR (Sung et al. 2007), gpd1/gpd2 (Berbee et al. 1999), and Alt-for/Alt-rev (Hong et al. 2005), respectively. Sequence analyses of isolates OM10 (ITS: GenBank Accession no. OP358436; RPB2: OP377483; GAPDH: OP377468; Alt-a-1: OP377471), OM43 (ITS: OP358437; RPB2: OP377484; GAPDH: OP377469; Alt-a-1: OP377472), and OM45 (ITS: OP358438; RPB2: OP377485; GAPDH: OP377470; Alt-a-1: OP377473) showed 100%, 99.61 to 100%, 99.65%, and 100% identities with a reference strain CBS 107.38 of A. burnsii for ITS (KP124420), RPB2 (KP124889), GAPDH (JQ646305), and Alt-a-1 (KP123967), respectively. They also showed 100%, 99.61 to 100%, 99.65%, and 99.58% identities with an A. tomato strain CBS 103.30 for ITS (KP124445), RPB2 (KP124915), GAPDH (KP124294), and Alt-a-1 (KP123991), respectively. Based on the morphological and sequence characteristics, the pathogen causing New Guinea impatiens leaf spot was identified as a member of the Alternaria burnsii - A. tomato species complex. The diseased plants on NCHU campus were destroyed. There have been no reports of the disease in other landscape areas or nurseries. To our knowledge, this is the first report of A. burnsii - A. tomato species complex causing New Guinea impatiens leaf spot in Taiwan. Since the pathogens in the species complex have been documented causing diseases on several important economic crops and the New Guinea impatiens is widely planted in nurseries and landscapes, the host range and the significance of the pathogen in agro-ecosystem may warrant further investigations.

Identifying meaningful brain activities is critical in brain-computer interface (BCI) applications. Recently, an increasing number of neural network approaches have been proposed to recognize EEG signals. However, these approaches depend heavily on using complex network structures to improve the performance of EEG recognition and suffer from the deficit of training data. Inspired by the waveform characteristics and processing methods shared between EEG and speech signals, we propose Speech2EEG, a novel EEG recognition method that leverages pretrained speech features to improve the accuracy of EEG recognition. Specifically, a pretrained speech processing model is adapted to the EEG domain to extract multichannel temporal embeddings. Then, several aggregation methods, including the weighted average, channelwise aggregation, and channel-and-depthwise aggregation, are implemented to exploit and integrate the multichannel temporal embeddings. Finally, a classification network is used to predict EEG categories based on the integrated features. Our work is the first to explore the use of pretrained speech models for EEG signal analysis as well as the effective ways to integrate the multichannel temporal embeddings from the EEG signal. Extensive experimental results suggest that the proposed Speech2EEG method achieves state-of-the-art performance on two challenging motor imagery (MI) datasets, the BCI IV-2a and BCI IV-2b datasets, with accuracies of 89.5% and 84.07% , respectively. Visualization analysis of the multichannel temporal embeddings show that the Speech2EEG architecture can capture useful patterns related to MI categories, which can provide a novel solution for subsequent research under the constraints of a limited dataset scale.

(1) Although emerging evidence suggests that proton pump inhibitor (PPI)-induced dysbiosis negatively alters treatment response to immune checkpoint inhibitors (ICIs) in cancer patients, no study systematically investigates the association between PPIs, ICIs, and chemotherapy; (2) Cochrane Library, Embase, Medline, and PubMed were searched from inception to 20 May 2022, to identify relevant studies involving patients receiving ICIs or chemotherapy and reporting survival outcome between PPI users and non-users. Survival outcomes included overall survival (OS) and progression-free survival (PFS). Network meta-analyses were performed using random-effects models. p -scores, with a value between 0 and 1, were calculated to quantify the treatment ranking, with a higher score suggesting a higher probability of greater effectiveness. We also conducted pairwise meta-analyses of observational studies to complement our network meta-analysis; (3) We identified 62 studies involving 26,484 patients (PPI = 8834; non-PPI = 17,650), including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), melanoma, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and squamous cell carcinoma (SCC) of the neck and head. Eight post-hoc analyses from 18 randomized-controlled trials were included in our network, which demonstrated that, in advanced NSCLC and UC, patients under ICI treatment with concomitant PPI ( p -score: 0.2016) are associated with both poorer OS (HR, 1.49; 95% CI, 1.37 to 1.67) and poorer PFS (HR, 1.41; 95% CI, 1.25 to 1.61) than those without PPIs ( p -score: 1.000). Patients under ICI treatment with concomitant PPI also had poorer OS (HR, 1.18; 95% CI, 1.07 to 1.31) and poorer PFS (HR, 1.30; 95% CI, 1.14 to 1.48) in comparison with those receiving chemotherapy ( p -score: 0.6664), implying that PPIs may compromise ICI's effectiveness, making it less effective than chemotherapy. Our pairwise meta-analyses also supported this association. Conversely, PPI has little effect on patients with advanced melanoma, RCC, HCC, and SCC of the neck and head who were treated with ICIs; (4) "PPI-induced dysbiosis" serves as a significant modifier of treatment response in both advanced NSCLC and UC that are treated with ICIs, compromising the effectiveness of ICIs to be less than that of chemotherapy. Thus, clinicians should avoid unnecessary PPI prescription in these patients. "PPI-induced dysbiosis", on the other hand, does not alter the treatment response to ICIs in advanced melanoma, RCC, HCC, and SCC of the head and neck.

Vertically aligned ZnO: Ga nanotowers can be directly synthesized on a glass substrate with a ZnO seed film via the chemical bath method. A novel heterostructure of ZnO: Ga@ITO@Ag nanotowers was subsequently deposited in the ITO layer and Ag nanoparticles via the facile two-step ion-sputtering processes on the ZnO: Ga nanotowers. The appropriate ion-sputtering times of the ITO layer and Ag nanoparticles can benefit the fabrication of ZnO: Ga@ITO@Ag nanotowers with higher surface-enhanced Raman scattering (SERS) enhancement in detecting rhodamine 6G (R6G) molecules. Compared with ZnO: Ga@Ag nanotowers, ZnO: Ga@ITO@Ag nanotowers exhibited a high SERS enhancement factor of 2.25 × 10 8 and a lower detection limit (10 -14 M) for detecting R6G molecules. In addition, the ITO layer used as an intermediate layer between ZnO: Ga nanotowers and Ag nanoparticles can improve SERS enhancement, sensitivity, uniformity, reusability, detection limit, and stability for detecting amoxicillin molecules. This phenomenon shall be ascribed to the ITO layer exhibiting a synergistic Raman enhancement effect through interfacial charge transfer for enhancing SERS activity. As a result, ZnO: Ga@ITO@Ag nanotowers can construct a three-dimensional SERS substrate for potential applications in environmentally friendly and cost-effective chemical or drug detection.

ZnO nanowires and nanowalls can be fabricated on the glass substrate with a ZnO seed film and low-cost aluminum (Al) foil by the aqueous solution method (ASM), respectively. The different concentrations of ZnO precursors can use to control the densities of ZnO nanowalls. In addition, FESEM, FETEM, EDS, XRD, XPS, and CL were used to evaluate the characteristics of ZnO nanowalls. The ZnO nanowalls exhibited higher photocatalytic efficiency (99.4%) than that of ZnO nanowires (53.3%) for methylene blue (MB) degradation under UVC light irradiation at the ZnO precursors of 50 mM. This result is attributed to ZnO nanowalls with Al-doped, which can improve the separation of photogenerated electron-hole pairs for enhanced photocatalytic activity. In addition, ZnO nanowalls can also reveal higher photocatalytic activity for the degradation of tetracycline capsules (TC) rather than commercial ZnO nanopowder under UVC light irradiation. The superoxide and hydroxyl radicals play essential roles in the degradation of MB and TC solutions by the radical-trapping experiment. Furthermore, the ZnO nanowalls exhibit excellent recycling and reuse capacity for up to four cycles for the degradation of MB and TC. This study highlights the potential use of ZnO nanowalls directly grown on commercial and low-cost Al foil as noble metal-free photocatalysis.