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Eun Hye Lee,1,* Hyun Tae Kim,2,* So Young Chun,3 Jae-Wook Chung,2 Seock Hwan Choi,2 Jun Nyung Lee,2 Bum Soo Kim,2 Eun Sang Yoo,2 Tae Gyun Kwon,2 Tae-Hwan Kim,2 Yun-Sok Ha2 1Joint Institution of Regenerative Medicine, Kyungpook National University, Daegu, Korea; 2Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea; 3BioMedical Research Institute, Kyungpook National University Hospital, Daegu, Korea*These authors contributed equally to this workCorrespondence: Tae-Hwan Kim; Yun-Sok Ha, Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea, Email doctork@knu.ac.kr; Koreayunsokha@gmail.comAbstract: Bladder cancer, one of the most frequently diagnosed cancers worldwide, is associated with high morbidity and mortality and a poor prognosis. The bladder cancer types include 1) non-muscle invasive bladder cancer (NMIBC) and 2) muscle invasive bladder cancer (MIBC). Metastases and chemoresistance in MIBC patients are the leading causes of the high death rate. c-Jun N-terminal kinase (JNK) is an important factor for the undifferentiated state of cancer cells. JNK belongs to the mitogen-activated protein kinases (MAPKs) family; it is activated by various extracellular stimuli, such as stress, radiation, and growth factors and mediates diverse cellular functions, such as apoptosis, autophagy, proliferation, invasion, and migration by mediating AKT (Ak strain transforming), ATG (Autophagy related), mTOR (Mammalian target of rapamycin), and caspases 3, 8, and 9. This review describes the JNK-related functions, mechanisms, and signaling in bladder cancer.Keywords: bladder cancer, JNK, proliferation, apoptosis, metastasis, chemoresistance, autophagy

It has become evident that apoptosis, an active form of cell 'suicide', plays an important role in the normal function of all tissues. A balance of cell proliferation and apoptosis is maintained in a healthy individual and any imbalance of the two processes could lead to pathological changes. In both sexes, massive apoptosis accounts for the demise of a majority of gonadal cells (ovarian granulosa cells and male germ cells) during reproductive life. Recent studies have indicated the important role of gonadotrophins as survival factors in both the ovary and the testis. Furthermore, intra-gonadal survival. factors in the ovary (oestrogens, insulin-like growth factor I, epidermal growth factor, basic fibroblast growth factor, interleukin-1 beta, nitric oxide, etc.) and testis (androgens) have been shown to act in concert with the gonadotrophins. In contrast, several apoptotic factors (androgens, gonadotrophin-releasing hormone-like peptide and interleukin-6) may be important in inducing the demise of ovarian follicles. Understanding of the hormonal and cellular mechanisms responsible for gonadal cell apoptosis will provide new approaches for the treatment of gonadal degenerative conditions such as premature ovarian failure and cryptorchidism, as well as for the design of new contraceptive approaches. [ABSTRACT FROM AUTHOR]

Background: Uncontrollable and widespread bleeding caused by surgery or sudden accidents can lead to death if not treated with appropriate hemostasis. To prevent excessive life-threatening bleeding, various hemostatic agents based on polymeric biomaterials with various additives for accelerated blood coagulation have been adopted in clinical fields. In particular, platelet-rich plasma (PRP), which contains many blood coagulation factors that can accelerate blood clot formation, is considered as one of the most effective hemostatic additives., Methods: We investigated a PRP-embedded porous film using discarded (expired) PRP and a film with a leaf-stacked structure (FLSS), as a hemostatic agent to induce rapid hemostasis. The film, which contained an LSS on one side (PCL-FLSS), was fabricated by a simple heating-cooling technique using tetraglycol and polycaprolactone (PCL) film. Activated PRP was obtained by the thawing of frozen PRP at the end of its expiration date (the platelet cell membrane is disrupted during the freezing and thawing of PRP, thus releasing various coagulation factors) and embedded in the PCL-FLSS (PRP-FLSS)., Results: From in vitro and in vivo experiments using a rat hepatic bleeding model, it was recognized that PRP-FLSS is not only biocompatible but also significantly accelerates blood clotting and thus prevents rapid bleeding, probably due to a synergistic effect of the sufficient supply of various blood coagulants from activated PRP embedded in the LSS layer and the large surface area of the LSS itself., Conclusion: The study suggests that PRP-FLSS, a combination of a porous polymer matrix with a unique morphology and discarded biofunctional resources, can be an advanced hemostatic agent as well as an upcycling platform to avoid the waste of biofunctional resources., (© 2024. Korean Tissue Engineering and Regenerative Medicine Society.)

Inspired by the functions of biological neural networks, volatile memristors are essential for implementing neuromorphic computing. These devices enable large-scale and energy-efficient data processing by emulating neural functionalities through dynamic resistance changes. The threshold switching characteristics of volatile memristors, which are driven by various mechanisms in materials ranging from oxides to chalcogenides, make them versatile and suitable for neuromorphic computing systems. Understanding these mechanisms and selecting appropriate devices for specific applications are crucial for optimizing the performance. However, the existing literature lacks a comprehensive review of switching mechanisms, their compatibility with different applications, and a deeper exploration of the spatiotemporal processing capabilities and inherent stochasticity of volatile memristors. This review begins with a detailed analysis of the operational principles and material characteristics of volatile memristors. Their diverse applications are then explored, emphasizing their role in crossbar arrays, artificial receptors, and neurons. Furthermore, the potential of volatile memristors in artificial inference systems and reservoir computing is discussed, due to their spatiotemporal processing capabilities. Hardware security applications and probabilistic computing are also examined, where the inherent stochasticity of the devices can improve the system robustness and adaptability. To conclude, the suitability of different switching mechanisms for various applications is evaluated, and future perspectives for the development and implementation of volatile memristors are presented. This review aims to fill the gaps in existing research and highlight the potential of volatile memristors to drive innovation in neuromorphic computing, paving the way for more efficient and powerful computational paradigms.

Magnetic resonance imaging (MRI) can extract the tissue conductivity values from in vivo data using the so-called phase-based magnetic resonance electrical properties tomography (MR-EPT). However, this procedure suffers from noise amplification caused by the use of the Laplacian operator. To counter this issue, we propose a novel preprocessing denoiser for magnetic resonance transceive phase images, operating in an unsupervised manner. Inspired by the deep image prior approach, we apply the random initialization of a convolutional neural network, which enforces an implicit regularization. Additionally, we introduce Stein's unbiased risk estimator, which is the unbiased estimator of the mean square error for optimizing the network without the need for label images. This modification not only tackles the overfitting problem inherent in the deep image prior approach but also operates within a purely unsupervised framework. In addition, instead of using phase images, we use real and imaginary images, which aligns with the theoretical model of the risk estimator. Our generative model needs neither the preparation of training datasets nor prior training procedure, and it maintains adaptability across various resolutions and signal-to-noise ratio levels. In testing. our method significantly diminished residual error remaining in phase maps, quantitatively as well as qualitatively, for both phantom and simulated brain data. Furthermore, it outperformed other denoising methods in reducing noise amplification and boundary error. When applied to healthy volunteer and patient data, the proposed method revealed reduced error in the reconstructed conductivity maps, with conductivity values aligning well with established literature values. To the best of our knowledge, this is the first blind approach using a purely unsupervised denoising framework that can implement a 2D phase-based MR-EPT reconstruction algorithm. The source code is available at https://github.com/Yonsei-MILab/Implicit-Regularization-forMREPT-with-SURE.

To identify the best combination of potential predictors of septic shock in patients with obstructive acute pyelonephritis associated with ureteral stones (OAPN-US) according to Sepsis-3 criteria. Patients who underwent percutaneous nephrostomy (PCN) with OAPN-US were retrospectively evaluated. Recursive feature elimination (RFE) was applied to patients with and without septic shock to identify factors associated with the prediction of progression to septic shock. We compared combinations of the selected features based on area under the receiver operating curve (AUROC) to determine which combination was most effective. This study included 81 patients who were treated with PCN due to OAPN-US. A comparison was made between 37 patients with septic shock (SS) and 44 patients without septic shock (NSS). SS group had a higher age, poorer Eastern Cooperative Oncology Group status, and significantly higher levels of positivity in urine cultures and blood cultures. There were also differences in laboratory tests between the 2 groups. Procalcitonin (PCT), international normalized ratio (INR), and absolute lymphocyte count (ALC) were selected based on RFE. We compared the predictive power for SS when each marker was used alone, when 2 markers were combined, and when all 3 markers were combined. Among these combinations, using all 3 variables together yielded the highest AUROC of 0.942. Of the 3 variables, PCT had the highest Gini importance score, indicating that it was the most influential factor. Clinical characteristics were different between the SS and the NSS groups. In patients with OAPN-US, the combination of PCT, ALC, and INR was an excellent predictor of septic shock., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Advancements in Li-ion battery (LIB) technology hinge on an understanding of Li-ion solvation and charge transport dynamics. Ultrafast two-dimensional infrared (2D-IR) spectroscopy has been used to investigate these dynamics in electrolytes by probing chemical exchange processes through time-dependent cross-peak analysis. However, accurate interpretation is complicated by factors such as vibrational energy transfer and molecular photothermal effect (MPTE), affecting cross-peak evolution. Pinpointing the precise origin of these cross-peaks has posed a significant challenge in time-resolved IR spectroscopic studies of LIB electrolytes. Here, we trace the origin of 2D-IR cross-peaks of LIB electrolytes utilizing acetonitrile as a solvent. Time-dependent analysis of LiSCN and CH 3 SCN mixtures in CD 3 CN revealed distinctive MPTE features. Furthermore, direct observation of intermolecular MPTE through two-color IR pump-probe spectroscopy lends support to the findings. Our results emphasize the non-negligible artifacts induced by MPTE and the necessity of considering these effects to accurately observe the ultrafast dynamics within LIB electrolytes.

Purpose: This study describes the emergence of Candida auris in Hong Kong, focusing on the incidence and trends of different Candida species over time. Additionally, the study analyzes the relationship between C. auris and antifungal prescription, as well as the impact of outbreaks caused by C. auris ., Patients and Methods: Data were collected from 43 public hospitals across seven healthcare networks (A to G) in Hong Kong, including Candida species culture and antifungal prescription information. Among 150,267 patients with 206,405 hospitalization episodes, 371,653 specimens tested positive for Candida species. Trends in Candida species and antifungal prescription were analyzed before (period 1: 2015 1Q to 2019 1Q) and after (period 2: 2019 2Q to 2023 2Q) the emergence of C. auris in Hong Kong., Results: Candida albicans was the most prevalent species, accounting for 57.1% (212,163/371,653) of isolations, followed by Candida glabrata (13.1%, 48,666), Candida tropicalis (9.2%, 34,261), and Candida parapsilosis (5.3%, 19,688). C. auris represented 2.0% of all Candida species isolations. Comparing period 2 to period 1, the trend of C. albicans remained stable, while C. glabrata, C. tropicalis, and C. parapsilosis demonstrated a slower increasing trend in period 2 than in period 1. Other species, including C. auris , exhibited a 1.1% faster increase in trend during period 2 compared to period 1. Network A, with the highest antifungal prescription, did not experience any outbreaks, while networks F and G had 40 hospital outbreaks due to C. auris in period 2. Throughout the study period, healthcare networks B to G had significantly lower antifungal prescription compared to network A, ranging from 54% to 78% less than that of network A., Conclusion: There is no evidence showing correlation between the emergence of C. auris and antifungal prescription in Hong Kong. Proactive infection control measures should be implemented to prevent nosocomial transmission and outbreak of C. auris ., Competing Interests: Dr Celine Chui reports grants from Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, MSD, Amgen; personal fees from Primevigilance, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2024 Wong et al.)

A Gram-staining-positive, motile, aerobic and rod-shaped bacterium, designated strain MA9 T was isolated from wetland soil of ecology park, in Seoul, Republic of Korea. This bacterium was characterized to determine its taxonomic position by using the polyphasic approach. Strain MA9 T grew at 10-37 °C and at pH 6.0-9.5 on TSB. Menaquinone MK-7 was the predominant respiratory quinone and iso-C 15 : 0 , iso-C 16 : 0 and C 16 : 1  ω7 c alcohol were the major fatty acids. The main polar lipids were phosphatidylethanolamine (PE), phosphatidylserine (PS), diphosphatidylglycerol (DPG) and phosphatidylglycerol (PG). The peptidoglycan type of the cell wall was A4α l-Lys-d-Glu. Based on 16S rRNA gene sequencing, strain MA9 T clustered with species of the genus Solibacillus and appeared closely related to S. silvestris DSM 12223 T (97.8 % sequence similarity), S. cecembensis DSM 21993 T (97.6 %), S. isronensis DSM 21046 T (97.6 %) and S. kalamii DSM 101595 T (96.6 %). The G+C content of the genomic DNA was 37.0 mol%. Digital DNA-DNA hybridization between strain MA9 T and type strains of S. silvestris , S. isronensis , S. cecembensis and S. kalamii resulted in values below 70 %. Strain MA9 T could be differentiated genotypically and phenotypically from the recognized species of the genus Solibacillus . The isolate therefore represents a novel species, for which the name Solibacillus palustris sp. nov. is proposed, with the type strain MA9 T (=KACC 22212 T = LMG 32188 T ).

Cytochrome b5 reductase 3 (CYB5R3) is involved in various cellular metabolic processes, including fatty acid synthesis and drug metabolism. However, the role of CYB5R3 in cancer development remains poorly understood. Here, we show that CYB5R3 expression is downregulated in human lung cancer cell lines and tissues. Adenoviral overexpression of CYB5R3 suppresses lung cancer cell growth in vitro and in vivo. However, CYB5R3 deficiency promotes tumorigenesis and metastasis in mouse models. Transcriptome analysis revealed that apoptosis- and endoplasmic reticulum (ER) stress-related genes are upregulated in CYB5R3-overexpressing lung cancer cells. Metabolomic analysis revealed that CYB5R3 overexpression increased the production of nicotinamide adenine dinucleotide (NAD + ) and oxidized glutathione (GSSG). Ectopic CYB5R3 is mainly localized in the ER, where CYB5R3-dependent ER stress signaling is induced via activation of protein kinase RNA-like ER kinase (PERK) and inositol-requiring enzyme 1 alpha (IRE1α). Moreover, NAD + activates poly (ADP-ribose) polymerase16 (PARP16), an ER-resident protein, to promote ADP-ribosylation of PERK and IRE1α and induce ER stress. In addition, CYB5R3 induces the generation of reactive oxygen species and caspase-9-dependent intrinsic cell death. Our findings highlight the importance of CYB5R3 as a tumor suppressor for the development of CYB5R3-based therapeutics for lung cancer., (© 2024. The Author(s).)

Sepsis is a life-threatening disease, contributing to significant morbidity and mortality. This study aimed to investigate the association between low muscle mass and the prognosis of patients with biliary sepsis, focusing on outcomes such as length of hospital stay (LOS), intensive care unit (ICU) admission, and in-hospital mortality. This retrospective, single-center, observational study included adult patients with biliary sepsis who visited the emergency department between January 2016 and December 2021. Low muscle mass was assessed using the psoas muscle index (PMI). Using computed tomography imaging, the area of both sides of the psoas muscle at the L3 level was measured, and the PMI, corrected by the patient's height was calculated. The primary outcome was in-hospital mortality, and the secondary outcomes were intensive care unit (ICU) admission, LOS, and 14-day mortality. A total of 745 patients were included in this study. Low muscle mass was defined as a PMI < 421 mm 2 /m 2 for males and < 268 mm 2 /m 2 for females with the lower quartile of PMI according to sex. The cohort was classified into sarcopenic (n = 189) and non-sarcopenic (n = 556) groups. There was a significant association between low muscle mass and in-hospital mortality (odds ratio, 3.81; 95% confidence interval, 1.08-13.47; p < 0.001), while there was no significant association between low muscle mass and ICU admission. In addition, the median LOS in the sarcopenic group (10 [7-14] days) was significantly longer than the median (8 [6-11] days) in the non-sarcopenic group. Low muscle mass was significantly associated with clinical outcomes, particularly in-hospital mortality and LOS, in patients with biliary sepsis., (© 2024. The Author(s).)

The long-term outcome of first-line moderate-intensity statin with ezetimibe combination therapy for secondary prevention after percutaneous coronary intervention in patients with acute coronary syndrome (ACS) compared to high-intensity statin monotherapy remains elusive. The objective of this study was to compare the effectiveness of moderate-intensity statin and ezetimibe combination therapy with high-intensity statin monotherapy. We conducted a nationwide, population-based, retrospective, cohort study of patients with ACS from 2013 to 2019. The patients using combination therapy were matched (1:1) to those using monotherapy. The primary outcome was a composite of myocardial infarction, stroke and all-cause mortality. We estimated the hazard ratios (HR) and 95% confidence intervals (CIs) using the Cox proportional hazards regression. After propensity score matching, 10,723 pairs were selected. Men accounted for 70% of the patients and 37% aged > 70 years. The primary endpoint occurred in 1297 patients (12.1%) in the combination group and in 1426 patients (13.3%) in the monotherapy group, and decreased risk (HR 0.85, 95% CI 0.78-0.92, P < 0.001) in the combination group. Among the patients with ACS, moderate-intensity statin with ezetimibe combination therapy was associated with decreased risk of adverse cardiovascular outcomes compared with high-intensity statin monotherapy in a nationwide population-based study representing routine clinical practice., (© 2024. The Author(s).)

Due to the short storage period, large quantities of platelet concentrate (PC) are expiring. The expired PC cannot be injected into a blood vessel, but the activity of bioactive molecules, especially growth factors, is still preserved. In this paper, we organized a process to obtain a growth factor-rich bioproduct for use as a supplement in human cell culture by optimizing freezing, thawing, and sterilization conditions. Each unit of PC displayed visual differences, diverse biochemical values, and growth factor concentrations. To minimize lot-to-lot variation, we pooled a minimum of 10 PC units. The concentrations of growth factors were maximized through five freeze-thaw cycles for 12 h at -80 °C for freezing and for 5 min at 36 °C for thawing. We used a cell strainer with 40 µm pores, followed by a 0.45 μm filter and a 0.22 μm filter sequentially to sterilize the bioproduct with minimizing loss. The obtained growth factors remained stable for 4-6 h at room temperature (23 °C), 24 h at 4 °C, and 12 months at -80 °C. Cellular responses to the growth factor-rich bioproduct were tested with primary human renal proximal tubule epithelial cells. The cells exhibited a significantly increased growth rate, compared to the fetal bovine serum (FBS)-treated control group. The cells maintained their characteristic cuboidal shape, and stem cells and renal progenitor cells also preserved their genetic characteristics during culture. Therefore, the growth factor-rich bioproduct isolated from expired PC through our process can be used as a medium supplement to replace FBS in human cell culture for clinical application.

In the biological nervous system, the integration and cooperation of parallel system of receptors, neurons, and synapses allow efficient detection and processing of intricate and disordered external information. Such systems acquire and process environmental data in real-time, efficiently handling complex tasks with minimal energy consumption. Memristors can mimic typical biological receptors, neurons, and synapses by implementing key features of neuronal signal-processing functions such as selective adaption in receptors, leaky integrate-and-fire in neurons, and synaptic plasticity in synapses. External stimuli are sensitively detected and filtered by "artificial receptors," encoded into spike signals via "artificial neurons," and integrated and stored through "artificial synapses." The high operational speed, low power consumption, and superior scalability of memristive devices make their integration with high-performance sensors a promising approach for creating integrated artificial sensory systems. These integrated systems can extract useful data from a large volume of raw data, facilitating real-time detection and processing of environmental information. This review explores the recent advances in memristor-based artificial sensory systems. The authors begin with the requirements of artificial sensory elements and then present an in-depth review of such elements demonstrated by memristive devices. Finally, the major challenges and opportunities in the development of memristor-based artificial sensory systems are discussed., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.)

Modern deep neural networks cannot be often trained on a single GPU due to large model size and large data size. Model parallelism splits a model for multiple GPUs, but making it scalable and seamless is challenging due to different information sharing among GPUs with communication overhead. Specifically, we identify two key issues to make the parallelism being inefficient and inaccurate; an efficient pipelining technique is crucial to maximize GPU utilization and normalizations in deep neural networks may affect the performance due to different statistics sharing of mini-batch. In this work, we address these issues by investigating efficient pipelining for model parallelism and effective normalizations in model / data parallelisms when training a model with large mini-batch in multiple GPUs so that the model performance in accuracy can not be compromised. Firstly, we propose a novel method to search for an optimal micro-batch size considering the number of GPUs and memory size for model parallelism. For efficient pipelining, mini-batch is usually divided into smaller batches (called micro-batch). To maximize the utilization of GPU computing resources, training should be performed with the optimal micro-batch size. Our proposed micro-batch size search algorithm achieved increased image throughput by up to 12% and improved trainable mini-batch size by 25% as compared to the conventional model parallelism method. Secondly, we investigate normalizations in distributed deep learning training for different parallelisms. Our experiments using different normalization methods suggested that the performance with batch normalization can be improved by sharing the batch information among GPUs when performing data parallelism. It was also confirmed that group normalization helped minimizing accuracy degradation when performing model parallelism with pipelining and yielded consistent accuracies for diverse mini-batch sizes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim of the Study: As sepsis is a life-threatening disease, it is important to predict the prognosis in the early stages to establish treatment plans. This study aimed to investigate the association between sarcopenia, determined by the psoas muscle area, and the prognosis of sepsis due to acute cholecystitis., Methods: This retrospective single-center observational study included adult patients with sepsis due to acute cholecystitis who visited the emergency department between January 2016 and December 2021. The area of both sides of the psoas muscle at the L3 level was measured, and the psoas muscle index (PMI) corrected by the patient's height was calculated. Sarcopenia was determined based on PMI. The primary outcome was in-hospital mortality, and secondary outcomes were intensive care unit (ICU) admission, length of hospital stay (LOS), and 14-day mortality., Results: A total of 374 patients were included in this study. In this cohort, the lower quartile of PMI according to gender was set as the cut-off value to define sarcopenia. Sarcopenia was defined as PMI < 423 mm 2 /m 2 for males and < 269 mm 2 /m 2 for females. There were 94 patients in the sarcopenic group and 280 in the non-sarcopenic group. There was a significant association between sarcopenia and ICU admission (odds ratio [OR], 1.98; 95% confidence interval [CI], 1.05-3.76), and there was also a significant association between sarcopenia and in-hospital mortality (OR, 6.40; 95%CI, 1.13-36.09). Additionally, the median LOS in the sarcopenic group (11.5 (Cruz-Jentoft et al., 2010; Kawaguchi et al., 2019; Kim et al., 2017; Ritz et al., 2021; Cox et al., 2021; Lee et al., 2018; Okada et al., 2021; Prashanthi et al., n.d.; Amini et al., 2015; Fearon et al., 2011) days) was significantly longer than the median (8 (Rosenberg, 1989, 1997; Cruz-Jentoft et al., 2010; Kawaguchi et al., 2019; Kim et al., 2017; Ritz et al., 2021) days) in the non-sarcopenic group., Conclusions: In patients with sepsis due to acute cholecystitis, sarcopenia was significantly associated with ICU admission, LOS, and in-hospital mortality., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The purpose of this study was to automatically classify the three-dimensional (3D) positional relationship between an impacted mandibular third molar (M3) and the inferior alveolar canal (MC) using a distance-aware network in cone-beam CT (CBCT) images. We developed a network consisting of cascaded stages of segmentation and classification for the buccal-lingual relationship between the M3 and the MC. The M3 and the MC were simultaneously segmented using Dense121 U-Net in the segmentation stage, and their buccal-lingual relationship was automatically classified using a 3D distance-aware network with the multichannel inputs of the original CBCT image and the signed distance map (SDM) generated from the segmentation in the classification stage. The Dense121 U-Net achieved the highest average precision of 0.87, 0.96, and 0.94 in the segmentation of the M3, the MC, and both together, respectively. The 3D distance-aware classification network of the Dense121 U-Net with the input of both the CBCT image and the SDM showed the highest performance of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve, each of which had a value of 1.00. The SDM generated from the segmentation mask significantly contributed to increasing the accuracy of the classification network. The proposed distance-aware network demonstrated high accuracy in the automatic classification of the 3D positional relationship between the M3 and the MC by learning anatomical and geometrical information from the CBCT images., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Microsatellite instability (MSI) refers to alterations in the length of simple repetitive genomic sequences. MSI status serves as a prognostic and predictive factor in colorectal cancer. The MSI-high status is a good prognostic factor in stage II/III cancer, and predicts a lack of benefit to adjuvant fluorouracil chemotherapy in stage II cancer but a good response to immunotherapy in stage IV cancer. Therefore, determining MSI status in patients with colorectal cancer is important for identifying the appropriate treatment protocol. In the Pathology Artificial Intelligence Platform (PAIP) 2020 challenge, artificial intelligence researchers were invited to predict MSI status based on colorectal cancer slide images. Participants were required to perform two tasks. The primary task was to classify a given slide image as belonging to either the MSI-high or the microsatellite-stable group. The second task was tumor area segmentation to avoid ties with the main task. A total of 210 of the 495 participants enrolled in the challenge downloaded the images, and 23 teams submitted their final results. Seven teams from the top 10 participants agreed to disclose their algorithms, most of which were convolutional neural network-based deep learning models, such as EfficientNet and UNet. The top-ranked system achieved the highest F1 score (0.9231). This paper summarizes the various methods used in the PAIP 2020 challenge. This paper supports the effectiveness of digital pathology for identifying the relationship between colorectal cancer and the MSI characteristics., 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. Published by Elsevier B.V.)

Accurate scatter estimation is important in quantitative SPECT for improving image contrast and accuracy. With a large number of photon histories, Monte-Carlo (MC) simulation can yield accurate scatter estimation, but is computationally expensive. Recent deep learning-based approaches can yield accurate scatter estimates quickly, yet full MC simulation is still required to generate scatter estimates as ground truth labels for all training data. Here we propose a physics-guided weakly supervised training framework for fast and accurate scatter estimation in quantitative SPECT by using a 100× shorter MC simulation as weak labels and enhancing them with deep neural networks. Our weakly supervised approach also allows quick fine-tuning of the trained network to any new test data for further improved performance with an additional short MC simulation (weak label) for patient-specific scatter modelling. Our method was trained with 18 XCAT phantoms with diverse anatomies / activities and then was evaluated on 6 XCAT phantoms, 4 realistic virtual patient phantoms, 1 torso phantom and 3 clinical scans from 2 patients for 177Lu SPECT with single / dual photopeaks (113, 208 keV). Our proposed weakly supervised method yielded comparable performance to the supervised counterpart in phantom experiments, but with significantly reduced computation in labeling. Our proposed method with patient-specific fine-tuning achieved more accurate scatter estimates than the supervised method in clinical scans. Our method with physics-guided weak supervision enables accurate deep scatter estimation in quantitative SPECT, while requiring much lower computation in labeling, enabling patient-specific fine-tuning capability in testing.

Technologies based on the fusion of gas sensors and neuromorphic computing to mimic the olfactory system have immense potential. However, the implementation of neuromorphic olfactory systems remains in a state of infancy because conventional gas sensors lack the necessary functions. Therefore, this study proposes a hysteretic "chemi-memristive gas sensor" based on oxygen vacancy chemi-memristive dynamics that differ from that of conventional gas sensors. After the memristive switching operation, the redox reaction with the external gas molecules is enhanced, resulting in the generation and elimination of oxygen vacancies that induce rapid current changes. In addition, the pre-generated oxygen vacancies enhance the post-sensing properties. Therefore, fast responses, short recovery times, and hysteretic gas response are achieved by the proposed sensor at room temperature. Based on the advantageous functionality of the sensor, device-level olfactory systems that can monitor the history of input gas stimuli are experimentally demonstrated as a potential application. Moreover, analog conductance modulation induced by oxidizing and reducing gases enables the conversion of external gas stimuli into synaptic weights and hence the realization of typical synaptic functionalities without an additional device or circuit. The proposed chemi-memristive device represents an advance in the bioinspired technology adopted in creating artificial intelligence systems., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Ulcerative colitis is an inflammatory bowel disease characterized by inflammation in the mucosal and submucosal layers of the colon. Obesity is closely related to the occurrence and progression of colitis. The most plausible mechanism linking obesity and colitis is an excessive adipogenesis-related inflammatory response, which causes mucosal dysfunction. Obesity and colitis are linked by several etiologic mechanisms, including excessive adipogenesis, lipotoxicity, pro-inflammatory adipokines/cytokines, macrophage polarization, oxidative stress, endoplasmic reticulum (ER) stress, and gut microbiota. These low-grade enteric inflammations cause mucosal layer damage, especially goblet cell dysfunction through mucin 2 (MUC2) misfolding, ultimately leading to colitis. Inhibiting the inflammatory response can be the most effective approach for treating obesity-related colitis. We focused on the anti-inflammatory effects of polyphenols in Protaectia brevitas larvae. The P. brevitas was prepared as a low molecular protein hydrolysate (PHPB) to increase the concentration of anti-inflammatory molecules. In the current study, we investigated the anti-inflammatory effect of PHPB in an obesity-induced colitis mouse model. Compared with the high-fat diet (HFD) group, the group treated with PHPB exhibited reduced body/organ/fat weight, appetite/food intake inhibition, hypolipidemic effect on ectopic fat, and anti-adipogenic mechanism through the AMPK signaling pathway. Furthermore, we observed attenuated expression of PPARγ and C/EBPα, inhibition of pro-inflammatory molecules, stimulation of anti-inflammatory molecules, probiotic-like effect against obesogenic gut microbiota, inhibition of macrophage polarization into M1, suppression of oxidative/ER stress, and reduction of Muc2 protein misfolding in colon. These diverse anti-inflammatory responses caused histological and functional recovery of goblet cells, eventually improving colitis. Therefore, our findings suggest that the protein hydrolysate of Protaetia brevitarsis can improve obesity-related colitis through its anti-inflammatory activities.

This study compares the efficacy of the early low-intensity shock wave therapy (LI-SWT) plus daily tadalafil with daily tadalafil only therapy as penile rehabilitation for postprostatectomy erectile dysfunction in patients with prostate cancer who underwent bilateral interfascial nerve-sparing radical prostatectomy (robotic or open). From April 2019 to March 2021, 165 patients were enrolled, and 80 of them successfully completed this prospective study. Daily tadalafil were administered to all the patients. LI-SWT consisted of a total of six sessions. Each session was performed on days 4, 5, 6, and 7, and on the second and fourth weeks after surgery. Each LI-SWT session consisted of 300 shocks at an energy density of 0.09 mJ/mm 2 and a frequency of 120 shocks per minute that were delivered at each of the five treatment points for 15 min. Thirty-nine patients were treated with tadalafil-only (group A) while 41 were treated with tadalafil and LI-SWT simultaneously (group B). At postoperative 6 months, the proportion of patients with erection hardness scores (EHS) ≥ 3 (4/39 vs. 12/41) was significantly higher in group B (p = 0.034), and LI-SWT was the only independent factor for predicting EHS ≥ 3 (OR, 3.621; 95% CI, 1.054-12.437; p = 0.041). There were no serious side effects related to early LI-SWT. Early LI-SWT plus daily tadalafil therapy as penile rehabilitation for postprostatectomy erectile dysfunction is thought to be more efficacious than tadalafil only. Further large-scaled randomized controlled trials will be needed to validate these findings., (© 2022. The Author(s).)

We obtained 24 air samples in 8 general wards temporarily converted into negative-pressure wards admitting coronavirus disease 2019 (COVID-19) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant BA.2.2 in Hong Kong. SARS-CoV-2 RNA was detected in 19 (79.2%) of 24 samples despite enhanced indoor air dilution. It is difficult to prevent airborne transmission of SARS-CoV-2 in hospitals.

Introduction: Traditionally, a pigtail catheter (PCN) is placed for preoperative renal access before performing percutaneous nephrolithotomy (PCNL). However, PCN can hamper the passage of the guidewire to the ureter, due to which, access tract can be lost. Therefore, Kumpe Access Catheter (KMP) has been proposed for preoperative renal access before PCNL. In this study, we analyzed the efficacy and safety of KMP for surgical outcomes in modified supine PCNL compared to those in PCN., Materials and Methods: From July 2017 to December 2020, 232 patients underwent modified supine PCNL at a single tertiary center, of which 151 patients were enrolled in this study after excluding patients who underwent bilateral surgery, multiple punctures, or combined operations. Enrolled patients were divided into two groups according to the type of pre-PCNL nephrostomy catheter used: PCN versus KMP. A pre-PCNL nephrostomy catheter was selected based on the radiologist's preference. A single surgeon performed all PCNL procedures. Patient characteristics and surgical outcomes, including stone-free rate, operation time, radiation exposure time (RET), and complications, were compared between the two groups., Results: Of the 151 patients, 53 underwent PCN placement, and 98 underwent KMP placement for pre-PCNL nephrostomy. Patient baseline characteristics were comparable between the two groups, except for the renal stone type and multiplicity. The operation time, stone-free rate, and complication rate were not significantly different between the two groups; however, RET was significantly shorter in the KMP group., Conclusion: The surgical outcomes of KMP placement were comparable to those of PCN and showed shorter RET during modified supine PCNL. Based on our results, we recommend KMP placement for pre-PCNL nephrostomy, particularly for reducing RET during supine PCNL., (© 2023. The Author(s).)

Background: The coronavirus disease 2019 (COVID-19) has influenced antimicrobial consumption and incidence of multidrug-resistant organisms (MDROs). We aimed to study the epidemiology of MDROs before and during the COVID-19 pandemic in Hong Kong., Methods: With the maintenance of infection control measures, we described the trend of MDRO infections, including methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter species (CRA), and extended-spectrum-beta-lactamase-(ESBL)-producing Enterobacterales, in a healthcare region with 3100-bed before (1 January 2016 to 31 December 2019, period 1) and during COVID-19 (1 January 2020 to 30 September 2022, period 2), together with the antimicrobial consumption using piecewise Poisson regression. The epidemiological characteristics of newly diagnosed COVID-19 patients with or without MDRO infections were analyzed., Results: Between period 1 and 2, we observed a significant increase in the trend of CRA infections ( P <0.001), while there was no significant increase in the trend of MRSA ( P =0.742) and ESBL-producing Enterobacterales ( P =0.061) infections. Meanwhile, a significant increase in the trend of carbapenems ( P <0.001), extended-spectrum beta-lactam-beta-lactamase inhibitor combinations (BLBI) ( P =0.045), and fluoroquinolones ( P =0.009) consumption was observed. The observed opportunity (23,540 ± 3703 vs 26,145 ± 2838, p =0.359) and compliance (81.6% ± 0.5% vs 80.1% ± 0.8%, P =0.209) of hand hygiene per year was maintained. In a multivariable model, older age, male sex, referral from residential care home for the elderly, presence of indwelling device, presence of endotracheal tube, and use of carbapenems, use of BLBI, use of proton pump inhibitors and history of hospitalization in the past 3 months were associated with higher risks of infections by MDROs among COVID-19 patients., Conclusion: Infection control measures may control the surge of MDROs despite an increasing trend of antimicrobial consumption., (© 2023 The Authors.)

Background: Air dispersal of respiratory viruses other than SARS-CoV-2 has not been systematically reported. The incidence and factors associated with air dispersal of respiratory viruses are largely unknown., Methods: We performed air sampling by collecting 72,000 L of air over 6 hours for pediatric and adolescent patients infected with parainfluenza virus 3 (PIF3), respiratory syncytial virus (RSV), rhinovirus, and adenovirus. The patients were singly or 2-patient cohort isolated in airborne infection isolation rooms (AIIRs) from December 3, 2021, to January 26, 2022. The viral load in nasopharyngeal aspirates (NPA) and air samples were measured. Factors associated with air dispersal were investigated and analyzed., Results: Of 20 singly isolated patients with median age of 30 months (range, 3 months-15 years), 7 (35%) had air dispersal of the viruses compatible with their NPA results. These included 4 (40%) of 10 PIF3-infected patients, 2 (66%) of 3 RSV-infected patients, and 1 (50%) of 2 adenovirus-infected patients. The mean viral load in their room air sample was 1.58×10 3 copies/mL. Compared with 13 patients (65%) without air dispersal, these 7 patients had a significantly higher mean viral load in their NPA specimens (6.15×10 7 copies/mL vs 1.61×10 5 copies/mL; P < .001). Another 14 patients were placed in cohorts as 7 pairs infected with the same virus (PIF3, 2 pairs; RSV, 3 pairs; rhinovirus, 1 pair; and adenovirus, 1 pair) in double-bed AIIRs, all of which had air dispersal. The mean room air viral load in 2-patient cohorts was significantly higher than in rooms of singly isolated patients (1.02×10 4 copies/mL vs 1.58×10 3 copies/mL; P = .020)., Conclusion: Air dispersal of common respiratory viruses may have infection prevention and public health implications.

Background: Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients' quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model., Methods: From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 μg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation., Results: The mean pain scores in the SVF 20 μl group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group. In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group., Conclusion: This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity., (© 2023. The Author(s).)

Liquid-liquid phase separation (LLPS) plays a significant role in various biological processes, including the formation of membraneless organelles and pathological protein aggregation. Although many studies have found various factors that modulate the LLPS process or the liquid-to-solid phase transition (LSPT) using microscopy or fluorescence-based methods, the molecular mechanistic details underlying LLPS and protein aggregation within liquid droplets remain uncharacterized. Therefore, structural information on proteins inside liquid droplets is required to understand the mechanistic link to amyloid formation. In the present study, we monitored droplet formation related to protein fibrillation using micro-Raman spectroscopy in combination with differential interference contrast (DIC) microscopy to study the conformational change in proteins and the hydrogen-bonding (H-bonding) structure of water during LLPS. Interestingly, we found that the O-D stretching band for water (HOD in H 2 O) inside the droplets exhibited a distinct Raman spectrum from that of the bulk water, suggesting that the time-dependent change in the hydration environment in the protein droplets during the process of LLPS can be studied. These results demonstrate that the superior spatial resolution of micro-Raman spectroscopy offers significant advantages in investigating the molecular mechanisms of LLPS and following LSPT processes.

This study aimed to examine the association between familial aggregation of chronic kidney disease (CKD) and risk of CKD development and its progression. This nationwide family study comprised 881,453 cases with newly diagnosed CKD between 2004 and 2017 and 881,453 controls without CKD matched by age and sex, using data from the Korean National Health Insurance Service with linkage to the family tree database. The risks of CKD development and disease progression, defined as an incident end-stage renal disease (ESRD), were evaluated. The presence of any affected family member with CKD was associated with a significantly higher risk of CKD with adjusted ORs (95% CI) of 1.42 (1.38-1.45), 1.50 (1.46-1.55), 1.70 (1.64-1.77), and 1.30 (1.27-1.33) for individuals with affected parents, offspring, siblings, and spouses, respectively. In Cox models conducted on patients with predialysis CKD, risk of incident ESRD was significantly higher in those with affected family members with ESRD. The corresponding HRs (95% CI) were 1.10 (1.05-1.15), 1.38 (1.32-1.46), 1.57 (1.49-1.65), and 1.14 (1.08-1.19) for individuals listed above, respectively. Familial aggregation of CKD was strongly associated with a higher risk of CKD development and disease progression to ESRD., (© 2023. The Author(s).)

Background: To evaluate the cost-effectiveness of the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) following interval cytoreductive surgery (ICS) for stage III-IV ovarian cancer from a randomized controlled phase III trial., Methods: A comparative cost-effective analysis was performed using a Markov health-state transition model derived from the current trial cohort (ClinicalTrials.gov Identifier: NCT01091636). The incremental cost-effectiveness ratio (ICER) was evaluated by dividing the incremental costs by incremental quality-adjusted life-years (QALYs) with a time horizon of 10 years. Costs were calculated from the perspective of Korean healthcare, and health utility values were extracted from published sources., Results: Based on data from the trial, the mean QALY in the ICS group was 7.16 compared to 10.8 in ICS followed by the HIPEC group. With an incremental QALY of 3.64, the ICS followed by HIPEC, was estimated to obtain an ICER of KRW 954,598 (USD 708.3) per QALY., Conclusion: The findings of the study suggest that ICS followed by HIPEC, is cost-effective with a significant gain in QALYs. These results may support the current reimbursement of HIPEC from Korean insurance services and the management of long-term conditions., Competing Interests: Declaration of Competing Interest Dr. Lim reported having a consulting or advisory role for AstraZeneca, Boryung, CKD Pharm, Genexine, Hospicare, GI Innovation, and Takeda and receiving research funding from AbbVie, Amgen, Astellas, AstraZeneca, BeiGene, Cellid, CKD Pharm, Clovis, Eisai, Genexine, GSK, Incyte, Merck, MSD, OncoQuest, Pfizer, and Roche outside the submitted work. Dr. Park reported having a consulting or advisory role for Boryung and Takeda and receiving research funding from AbbVie, Amgen, Astellas, AstraZeneca, BeiGene, Cellid, CKD Pharm, Clovis, Eisai, Genexine, GSK, Incyte, Merck, MSD, OncoQuest, Pfizer, and Roche outside the submitted work. No other disclosures were reported. Other authors declare they have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier Inc.)

Background: No nosocomial infection was recorded in our healthcare workers (HCWs) during the early phase of the coronavirus disease 2019 (COVID-19) pandemic. With the emergence of the Omicron variant of increased transmissibility, infection in HCWs occurred as expected. We aimed to study the epidemiology of infection in HCWs and to describe the infection control measures during the outbreak of the Omicron variant., Methods: With daily rapid antigen testing and molecular confirmation test for COVID-19, infected HCWs were interviewed by infection control nurses (ICNs) to investigate the potential source of infection. The epidemiology of COVID-19 in Hong Kong served as reference., Results: During the fifth wave of COVID-19 (31 December 2021 to 31 May 2022), 1,200,068 cases were reported (incidence 95 times higher than in preceding waves in Hong Kong; 162,103 vs 1,707 per million population respectively, P <0.001). The proportion of infected HCWs was significantly higher than that of the general population (24.9%, 1,607/6,452 vs 16.2%, 1,200,068/7,403,100 respectively; P <0.01). The proportion of infected non-clinical staff was significantly higher than that of clinical staff (31.8%, 536/1,687 vs 22.5%, 1,071/4,765 respectively; P <0.001). Of 82.8% (1,330/1,607) infected HCWs interviewed by ICNs, 99.5% (1,324/1,330) had been fully vaccinated; 49.5% (659/1,330) had no identifiable source; 40.7% (541/1,330) were probably infected from household members; 9.8% (130/1,330) had possible exposure to confirmed patients or HCWs, but no lapse in infection control measures or inappropriate use of personal protective equipment was recalled., Conclusion: Omicron variant is highly transmissible such that breakthrough infection occurred despite high level of vaccination., (© 2022 The Authors.)

Active cation-based diffusive memristors featuring essentially volatile threshold switching have been proposed for novel applications, such as a selector in a one-selector-and-one-resistor structure and signal generators in neuromorphic computing. However, the high variability of the switching behavior, which results from the high electroforming voltage, external environmental conditions, and transition to the non-volatile switching mode in a high-current range, is considered a major impediment to such applications. Herein, for the first time, we developed a highly reliable threshold switching device immune to atmospheric changes based on an ultraviolet-ozone (UVO)-treated diffusive memristor consisting of Ag and SiO 2 nanorods (NRs). UVO treatment forms a stable water reservoir on the surface of SiO 2 NRs, facilitating the redox reaction and ion migration of Ag. Consequently, diffusive memristors possess reliable switching characteristics, including electroforming-free, repeatable, and consistent switching with resistance to changes in ambient conditions and compliance levels during operation. We demonstrated that our approach is suitable for various metal oxides and can be used in numerous applications.

Bacteremia caused by extended-spectrum β-lactamases-producing Enterobacterales has increased rapidly and is mainly attributed to CTX-M enzymes. This study aimed to evaluate the NG-Test ® CTX-M MULTI lateral flow assay (CTX-M LFA) for rapid detection of CTX-M producers in blood cultures (BCs) positive for Gram-negative bacilli in spiked and clinical BCs. Retrospective testing was performed on BC bottles spiked with a collection of well-characterized Enterobacterales isolates producing CTX-M ( n = 15) and CTX-M-like ( n = 27) β-lactamases. Prospective testing of clinical, non-duplicate BCs ( n = 350) was performed in two hospital microbiology laboratories from April 2021 to March 2022 following detection of Gram-negative bacilli by microscopic examination. Results were compared against molecular testing as the reference. In the spiked BCs, the CTX-M LFA correctly detected all CTX-M producers including 5 isolates with hybrid CTX-M variants. However, false-positive results were observed for several CTX-M-like β-lactamases, including OXY-1-3, OXY-2-8, OXY-5-3, FONA-8, -9, -10, 11, 13 and SFO-1. In clinical BCs, the CTX-M LFA showed 100% (95% CI, 96.0-100%) sensitivity and 99.6% (97.9-100%) specificity. In conclusion, this study showed that rapid detection of CTX-M producers in BC broths can be reliably achieved using the CTX-M LFA, thus providing an opportunity for early optimization of antibiotics.

Elastin is very rarely repaired extracellular matrix (ECM) in physiological condition. The commercial human elastin for exogenous medical treatment is very expensive, and has a potential for disease transmission. Animal-origin elastin is relatively low price, but has concerns for xenogeneic immune responses. Considering cost and safety, we focused on the perirenal adipose tissue, donated from healthy young people via donor nephrectomy. Until now, all of the perirenal adipose tissues are discarded as a medical waste after kidney transplantation. In the present study, we applied perirenal adipose tissues as the source of human elastin, and optimized the extraction process to get high purified and quantified elastin. Through pre-processing step, the delipidated and decellularized ECM was prepared. Next, with four different elastin extraction process (acidic solvents, neutral salt, organic solvents or hot alkali method), elastin was extracted, and the concentration of amino acid between each product was compared, and bright-field/electron microscopy, Fourier transform infrared (FT-IR) spectroscopy and cytotoxicity analysis were also performed. As controls, bovine neck ligament-derived and human skin-derived elastin were used. Among the elastin extraction methods, the hot alkali insoluble product showed (1) relatively high positive area of Verhoeff's and low Masson's trichrome stain, (2) 64.24% purity, 159.29 mg/g quantity, and ∼6.37% yield in amino acid analysis, (3) β-sheet second structure, and (4) thin fiber composed mesh-like sheet structure in SEM image. These values were higher than those of the commercial human skin elastin. When comparing hydrolyzed forms, α-elastin from hot alkali insoluble product showed enhanced cell proliferation and maintained cell properties compared to the κ-elastin. Therefore, we confirmed that the perirenal adipose tissue is an ideal source of human elastin with safety assurance, and the hot alkali process combined with pre-process seems to be the optimal method for elastin extraction with high purity and quantity.

Chronic Kidney Disease (CKD) is increasingly recognized as a global public health issue. Diabetic nephropathy (DN), also known as diabetic kidney disease, is a leading cause of CKD. Regenerative medicine strategy employing nephron progenitor cells (NPCs) is worthy of consideration as an alternative to shortage of donor organs for kidney transplantation. In previous study, we successfully generated induced NPCs (iNPCs) from human urine-derived cells that resembled human embryonic stem cell-derived NPCs. Here, we aimed to investigate the therapeutic potential of iNPCs in DN animal model. The results revealed the therapeutic effect of iNPCs as follows: (1) diminished glomerular hypertrophy, (2) reduced tubulointerstitial fibrosis, (3) low blood urea nitrogen, serum creatinine and albuminuria value, (4) decreased inflammation/fibrosis, (5) enhanced renal regeneration and (6) confirmed safety. This study demonstrates that human iNPCs have a therapeutic potential as a cell source for transplantation in patients with kidney diseases., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

No definitive criteria regarding the performance of preoperative chest computed tomography (CT) in patients with cT1a renal cell carcinoma (RCC) exists. We aimed to establish an objective standard for the optimal timing of preoperative chest CT in patients with RCC. Data from 890 patients who underwent surgical treatment for RCC between January 2011 and December 2020 were retrospectively collected. The primary endpoint was detection of lung metastasis on chest CT before nephrectomy. A multivariable logistic regression model predicting positive chest CT scans was used. Predictors included preoperative cTN stage, presence of systemic symptoms, Charlson comorbidity index (CCI), platelet count/hemoglobin ratio, albumin/globulin ratio (AGR), and De Ritis ratio. The overall rate of positive chest CT scans before nephrectomy was 3.03% (27/890). Only one patient had lung metastasis before surgery for cT1a. cT stage (≥cT1b), CCI ≥4, and low AGR were associated with a higher risk of positive chest CT scans. The best cutoff value for AGR was 1.39. After 890-sample bootstrap validation, the concordance index was 0.80. The net benefit of the proposed strategy was superior to that of the select-all and select-none strategies according to decision curve analysis. Therefore, when chest CT scans were performed with a risk of a positive result ≥10%, 532 (59.8%) negative chest CT scans could be prevented. Only 24 (2.7%) potentially positive chest CT scans were misdiagnosed. Therefore, we recommend chest CT in patients with ≥cT1b disease, CCI ≥4, and low AGR.

Bladder cancer is a common global cancer with a high percentage of metastases and high mortality rate. Thus, it is necessary to identify new biomarkers that can be helpful in diagnosis. Pyruvate dehydrogenase kinase 4 (PDK4) belongs to the PDK family and plays an important role in glucose utilization in living organisms. In the present study, we evaluated the role of PDK4 in bladder cancer and its related protein changes. First, we observed elevated PDK4 expression in high-grade bladder cancers. To screen for changes in PDK4-related proteins in bladder cancer, we performed a comparative proteomic analysis using PDK4 knockdown cells. In bladder cancer cell lines, PDK4 silencing resulted in a lower rate of cell migration and invasion. In addition, a PDK4 knockdown xenograft model showed reduced bladder cancer growth in nude mice. Based on our results, PDK4 plays a critical role in the metastasis and growth of bladder cancer cells through changes in ERK, SRC, and JNK.

The switching characteristics and performance of oxide-based memristors are predominately determined by oxygen- or oxygen-vacancy-mediated redox reactions and the consequent formation of conducting filaments (CFs). Devices using oxide thin films as the switching layer usually require an electroforming process for subsequent switching operations, which induces large device-to-device variations. In addition, the hard-to-control redox reaction during repeated switching causes random fluctuations or degradation of each resistance state, hindering reliable switching operations. In this study, an HfO 2 nanorod (NR)-based memristor is proposed for simultaneously achieving highly uniform, electroforming-free, fast, and reliable analogue switching properties. The well-controlled redox reaction due to the easy gas exchange with the environment at the surface of the NRs enhances the generation of oxygen or oxygen vacancies during the switching operation, resulting in electroforming-free and reliable switching behavior. In addition, the one-dimensional surface growth of CFs facilitates highly linear conductance modulation with smaller conductance changes compared with the two-dimensional volume growth in thin-film-based memristors, resulting in a high accuracy of >92% in the Modified National Institute of Standards and Technology pattern-recognition test and desirable spike-timing-dependent plasticity.

The epidemiology of patients with gastrointestinal colonization of carbapenem-resistant Acinetobacter baumannii (CRAB) has not been systematically analyzed. We aimed to analyze the incidence, risk factors, and clinical outcomes of patients with newly identified gastrointestinal colonization of CRAB in a healthcare region in Hong Kong, where a multi-pronged screening strategy for gastrointestinal colonization of CRAB, together with other multidrug-resistant organisms (MDROs), was conducted by collecting fecal specimens (rectal swab or stool) upon admission and during hospitalization. From 1 October 2015 to 31 December 2019, a total of 161,339 fecal specimens from 63,588 patients, 61,856 (97.3%) of whom were hospitalized patients, and 54,525 (88.1%) were screened upon admission, with 1309 positive for CRAB (2.4% prevalence). Among patients positive for CRAB in fecal specimens, 698 (53.3%) had newly detected gastrointestinal colonization of CRAB, giving an incidence of 10.03 per 10,000 patient admissions and constituting 2646 CRAB colonization days in the general wards. Excluding the 164 patients with co-colonization of other MDROs, 534 patients had gastrointestinal colonization with only CRAB, and 12.5% (67/534) developed symptomatic CRAB infections at a median of 61 days (range: 2 to 671 days), during prospective follow-up for 2 years. Compared with age- and sex-matched controls, patients being referred from residential care homes for the elderly, the presence of indwelling devices, use of beta-lactam/beta-lactamase inhibitors, carbapenems, and proton pump inhibitors in the preceding 6 months, and history of hospitalization in the past 6 months were significantly associated with gastrointestinal colonization with CRAB, as shown by multivariable analysis. Log-rank test showed that cases had significantly shorter survival duration than controls (p < 0.001). The adjusted hazard ratio of gastrointestinal colonization of CRAB was 1.8 (95% CI: 1.5−2.2; p < 0.001), as shown by Cox regression analysis. Whole-genome sequencing of eight patients with CRAB isolates in their blood cultures and rectal swabs during the same episode of hospitalization revealed ST-195 as the predominant type, as shown by multilocus sequencing type. Gastrointestinal colonization of CRAB poses a considerable challenge for infection prevention and control.

Background: A chronic disease management program was implemented in April 2012 to lower out-of-pocket costs for repeat visits to the same clinic. The aim of this study was to investigate the association between participating in this program and the onset of complications among patients with hypertension using whole-nation claims data., Methods: We used National Health Insurance Service data (2011-2018) and patients with newly detected hypertension from 2012 to 2014 were selected. Chronic disease management program reduces the out-of-pocket expenses of consultation fee from 30% to 20% when patients enroll in this program by agreeing to visit the same clinic for the treatment of hypertension or diabetes. As the dependent variable, acute myocardial infarction (MI), stroke, chronic kidney disease (CKD), and heart failure (HF) were selected. For analysis, cox proportional hazards model was used., Results: Total participants were 827,577, among which 102,831(12.6%) subjects participated in the chronic disease management. Participants of the chronic disease management program were more likely to show lower hazard ratios (HRs) than those of non-participants in terms of all complications (MI: HR, 0.75; 95% confidence interval [CI], 0.68-0.82; stroke: HR, 0.75; 95% CI, 0.72-0.78; CKD: HR, 0.90; 95% CI, 0.85-0.96; HF: HR, 0.56; 95% CI, 0.52-0.61)., Conclusion: The results showed that participants of the chronic disease management program were less likely to have hypertension complications compared to non-participants. Enhancing the participation rate may be related to better outcomes and reducing medical expenses among patients with chronic diseases., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Antimicrobial stewardship and infection control measures are equally important in the control of antimicrobial-resistant organisms. We conducted a retrospective analysis of the incidence rate of hospital-onset carbapenem-resistant Acinetobacter baumannii (CRAB) infection (per 1000 patient days) in the Queen Mary Hospital, a 1700-bed, university-affiliated teaching hospital, from period 1 (1 January 2007 to 31 December 2013) to period 2 (1 January 2014 to 31 December 2019), where enhanced infection control measures, including directly observed hand hygiene before meal and medication rounds to conscious patients, and the priority use of single room isolation, were implemented during period 2. This study aimed to investigate the association between enhanced infection control measures and changes in the trend in the incidence rate of hospital-onset CRAB infection. Antimicrobial consumption (defined daily dose per 1000 patient days) was monitored. Interrupted time series, in particular segmented Poisson regression, was used. The hospital-onset CRAB infection increased by 21.3% per year [relative risk (RR): 1.213, 95% confidence interval (CI): 1.162−1.266, p < 0.001], whereas the consumption of the extended spectrum betalactam-betalactamase inhibitor (BLBI) combination and cephalosporins increased by 11.2% per year (RR: 1.112, 95% CI: 1.102−1.122, p < 0.001) and 4.2% per year (RR: 1.042, 95% CI: 1.028−1.056, p < 0.001), respectively, in period 1. With enhanced infection control measures, the hospital-onset CRAB infection decreased by 9.8% per year (RR: 0.902, 95% CI: 0.854−0.953, p < 0.001), whereas the consumption of the extended spectrum BLBI combination and cephalosporins increased by 3.8% per year (RR: 1.038, 95% CI: 1.033−1.044, p < 0.001) and 7.6% per year (RR: 1.076, 95% CI: 1.056−1.097, p < 0.001), respectively, in period 2. The consumption of carbapenems increased by 8.4% per year (RR: 1.84, 95% CI: 1.073−1.094, p < 0.001) in both period 1 and period 2. The control of healthcare-associated CRAB could be achieved by infection control measures with an emphasis on directly observed hand hygiene, despite an increasing trend of antimicrobial consumption.