Cross-domain Denoising for Low-dose Multi-frame Spiral Computed Tomography.

Computed tomography (CT) has been used worldwide as a non-invasive test to assist in diagnosis. However, the ionizing nature of X-ray exposure raises concerns about potential health risks such as cancer. The desire for lower radiation doses has driven researchers to improve reconstruction quality. Although previous studies on low-dose computed tomography (LDCT) denoising have demonstrated the effectiveness of learning-based methods, most were developed on the simulated data. However, the real-world scenario differs significantly from the simulation domain, especially when using the multi-slice spiral scanner geometry. This paper proposes a two-stage method for the commercially available multi-slice spiral CT scanners that better exploits the complete reconstruction pipeline for LDCT denoising across different domains. Our approach makes good use of the high redundancy of multi-slice projections and the volumetric reconstructions while leveraging the over-smoothing issue in conventional cascaded frameworks caused by aggressive denoising. The dedicated design also provides a more explicit interpretation of the data flow. Extensive experiments on various datasets showed that the proposed method could remove up to 70% of noise without compromised spatial resolution, while subjective evaluations by two experienced radiologists further supported its superior performance against state-of-the-art methods in clinical practice. Code is available at https://github.com/YCL92/TMD-LDCT.

Difficult endotracheal intubation in a patient with progressed tracheobronchopathia osteoplastica: A case report.

Tracheobronchopathia osteoplastica is a rare condition involving large airways with multiple bone and cartilage nodules in the tracheobronchial submucosa. This can cause tracheal stenosis, leading to difficulty in endotracheal intubation. A 79-year-old female patient, who had a history of successful endotracheal intubation for general anesthesia 8 years prior, was scheduled for abdominal surgery. Preoperative chest computed tomography and bronchoscopy revealed slight progression of tracheobronchopathia osteoplastica. Attempts to intubate with a smaller endotracheal tube failed; even the smaller endotracheal tube could barely pass. Mechanical ventilation was successfully administered and the surgery was completed without complications. The use of a smaller endotracheal tube may be beneficial for managing difficult airways in patients with tracheobronchopathia osteoplastica. Chest CT and bronchoscopic examination may be beneficial for evaluating the airway and determining the most appropriate airway management strategy. However, relying solely on these measures may lead to unexpected challenges because there is no established method to evaluate airway in patient with tracheobronchopathia osteoplastica. It is crucial for anesthesiologists to be aware of the potential existence of rare conditions such as tracheobronchopathia osteoplastica and be prepared to handle anticipated or unanticipated difficult airway management.

Hyaluronic acid stimulation of stem cells for cardiac repair: a cell-free strategy for myocardial infarct.

BACKGROUND: Myocardial infarction (MI), a representative form of ischemic heart disease, remains a huge burden worldwide. This study aimed to explore whether extracellular vesicles (EVs) secreted from hyaluronic acid (HA)-primed induced mesenchymal stem cells (HA-iMSC-EVs) could enhance the cardiac repair after MI. RESULTS: HA-iMSC-EVs showed typical characteristics for EVs such as morphology, size, and marker proteins expression. Compared with iMSC-EVs, HA-iMSC-EVs showed enhanced tube formation and survival against oxidative stress in endothelial cells, while reduced reactive oxygen species (ROS) generation in cardiomyocytes. In THP-1 macrophages, both types of EVs markedly reduced the expression of pro-inflammatory signaling players, whereas HA-iMSC-EVs were more potent in augmenting anti-inflammatory markers. A significant decrease of inflammasome proteins was observed in HA-iMSC-EV-treated THP-1. Further, phospho-SMAD2 as well as fibrosis markers in TGF-ß1-stimulated cardiomyocytes were reduced in HA-iMSC-EVs treatment. Proteomic data showed that HA-iMSC-EVs were enriched with multiple pathways including immunity, extracellular matrix organization, angiogenesis, and cell cycle. The localization of HA-iMSC-EVs in myocardium was confirmed after delivery by either intravenous or intramyocardial route, with the latter increased intensity. Echocardiography revealed that intramyocardial HA-iMSC-EVs injections improved cardiac function and reduced adverse cardiac remodeling and necrotic size in MI heart. Histologically, MI hearts receiving HA-iMSC-EVs had increased capillary density and viable myocardium, while showed reduced fibrosis. CONCLUSIONS: Our results suggest that HA-iMSC-EVs improve cardiac function by augmenting vessel growth, while reducing ROS generation, inflammation, and fibrosis in MI heart.

Enhancing the anticancer effect of androgen deprivation therapy by monocarboxylate transporter 1 inhibitor in prostate cancer cells.

BACKGROUND: Tumor initiation and progression necessitate a metabolic shift in cancer cells. Consequently, the progression of prostate cancer (PCa), a leading cause of cancer-related deaths in males globally, involves a shift from lipogenic to glycolytic metabolism. Androgen deprivation therapy (ADT) serves as the standard treatment for advanced-stage PCa. However, despite initial patient responses, castrate resistance emerges ultimately, necessitating novel therapeutic approaches. Therefore, in this study, we aimed to investigate the role of monocarboxylate transporters (MCTs) in PCa post-ADT and evaluate their potential as therapeutic targets. METHODS: PCa cells (LNCaP and C4-2 cell line), which has high prostate-specific membrane antigen (PSMA) and androgen receptor (AR) expression among PCa cell lines, was used in this study. We assessed the expression of MCT1 in PCa cells subjected to ADT using charcoal-stripped bovine serum (CSS)-containing medium or enzalutamide (ENZ). Furthermore, we evaluated the synergistic anticancer effects of combined treatment with ENZ and SR13800, an MCT1 inhibitor. RESULTS: Short-term ADT led to a significant upregulation in folate hydrolase 1 (FOLH1) and solute carrier family 16 member 1 (SLC16A1) gene levels, with elevated PSMA and MCT1 protein levels. Long-term ADT induced notable changes in cell morphology with further upregulation of FOLH1/PSMA and SLC16A1/MCT1 levels. Treatment with ENZ, a nonsteroidal anti-androgen, also increased PSMA and MCT1 expression. However, combined therapy with ENZ and SR13800 led to reduced PSMA level, decreased cell viability, and suppressed expression of cancer stem cell markers and migration indicators. Additionally, analysis of human PCa tissues revealed a positive correlation between PSMA and MCT1 expression in tumor regions. CONCLUSIONS: Our results demonstrate that ADT led to a significant upregulation in MCT1 levels. However, the combination of ENZ and SR13800 demonstrated a promising synergistic anticancer effect, highlighting a potential therapeutic significance for patients with PCa undergoing ADT.

Initial experience with the enhanced recovery after surgery (ERAS) protocols in gynecologic surgery at an urban academic tertiary medical center.

Background: The enhanced recovery after surgery (ERAS) protocols have been consistently associated with improved patient experience and surgical outcomes. Despite the release of ERAS Society guidelines specific to gynecologic oncology, the adoption of ERAS in gynecology on global level has been disappointingly low and some centers have shown minimal improvement in clinical outcomes after adopting ERAS. The aim of this study is to describe the development and early experience of ERAS protocols in gynecologic surgery at an urban academic tertiary medical center. Methods: This was an observational prospective cohort study. The target patient population included those with low comorbidities who were scheduled to undergo various types of gynecologic surgeries for both benign and malignant diseases between October 2020 and February 2021. Two attending surgeons implemented the protocols for their patients (ERAS cohort) while three attending surgeons maintained the conventional perioperative care for their patients (non-ERAS cohort). Baseline characteristics, surgical outcomes and patients' answers to a 12-question survey were compared. A case-matched comparative analysis was also performed between the ERAS cohort and the historical non-ERAS cohort (those who received the same types of surgical procedures from the two ERAS attending surgeons prior to the implementation of the protocols). Results: A total of 244 patients were evaluated (122 in the ERAS cohort vs. 122 in the non-ERAS cohort). The number of vials of opioid analgesia used during the first two postoperative days was significantly lower whereas the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen was more frequent in the ERAS cohort group. The patients in the ERAS group reported less postoperative pain, feelings of hunger and thirst, and greater amount of exercise postoperatively. These benefits of the ERAS cohort were more pronounced in the patients who underwent laparotomic surgeries than those who underwent laparoscopic surgeries. The case-matched comparative analysis also showed similar results. The length of hospital stay did not differ between those who underwent the ERAS protocols and those who did not. Conclusions: The results of the study demonstrated the safety, clinical feasibility and benefits of the ERAS protocols for patients undergoing gynecologic surgeries for both benign and malignant indications.

Pan PPAR agonist stimulation of induced MSCs produces extracellular vesicles with enhanced renoprotective effect for acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) has a complex pathophysiology and imposes serious health concerns worldwide. Extracellular vesicles (EVs) derived from induced mesenchymal stem cells (iMSCs) have been recognized as novel cell-free therapeutics for various inflammatory and degenerative disorders. In this study, we investigated whether iMSCs stimulated with a pan-peroxisome proliferator-activated receptor (PPAR) agonist could enhance the therapeutic efficacy of EVs against AKI. METHODS: Human iMSCs were primed with or without lanifibranor, a PPAR agonist for 24 h, and EVs were collected after an additional 24 h. The basic characteristics of EVs were evaluated using cryo-transmission electron microscopy imaging, immunoblot detection of EV markers, nanoparticle tracking analysis, and localization in AKI kidneys. In vitro, the potential of the EVs to promote the growth and survival of HK-2 cells undergoing cisplatin-induced apoptosis and anti-inflammatory effects in M1-polarized THP-1 was compared. Subsequently, AKI was induced in BALB/c mice using cisplatin. After 8 and 24 h of cisplatin treatment, iMSC-EVs or pan-PPAR-iMSC-EVs were injected intravascularly. At 96 h after cisplatin administration, the renoprotective effects of iMSC-EVs or pan-PPAR-iMSC-EVs in inhibiting inflammation and apoptosis were compared using serum biochemistry, histology, immunohistochemistry, and gene expression analysis by qPCR. RESULTS: Both EV types expressed EV markers and had typical EV morphology, and their localization in the renal tissue was confirmed. The proliferation and survival of HK-2 cells were higher in pan-PPAR-iMSC-EVs than those in iMSC-EVs. In M1-polarized THP-1 cells, the reduction in the mRNA expression of inflammatory cytokines was more significant in pan-PPAR-iMSC-EVs than that in iMSC-EVs. In the mouse model of cisplatin-induced AKI, pan-PPAR-iMSC-EVs markedly enhanced renoprotective effects compared to iMSC-EVs. Specifically, pan-PPAR-iMSC-EVs reduced tissue inflammation, immune cell infiltration, and apoptosis. Pan-PPAR-iMSC-EVs also increased renal capillary density. CONCLUSION: Priming iMSCs with a PPAR agonist significantly improved the therapeutic potential of EVs by reducing inflammation and apoptosis. The reported strategy may contribute to the development of a novel cell-free option for AKI treatment. TRIAL REGISTRATION: Not applicable.

Impact of glucose metabolism on PD-L1 expression in sorafenib-resistant hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality worldwide. Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that binds to programmed cell death-1 (PD-1), which is expressed in activated T cells and other immune cells and has been employed in cancer therapy, including HCC. Recently, PD-L1 overexpression has been documented in treatment-resistant cancer cells. Sorafenib is a multikinase inhibitor and the only FDA-approved treatment for advanced HCC. However, several patients exhibit resistance to sorafenib during treatment. This study aimed to assess the effect of glucose deprivation on PD-L1 expression in HCC cells. We used PD-L1-overexpressing HepG2 cells and IFN-γ-treated SK-Hep1 cells to explore the impact of glycolysis on PD-L1 expression. To validate the correlation between PD-L1 expression and glycolysis, we analyzed data from The Cancer Genome Atlas (TCGA) and used immunostaining for HCC tissue analysis. Furthermore, to modulate PD-L1 expression, we treated HepG2, SK-Hep1, and sorafenib-resistant SK-Hep1R cells with rapamycin. Here, we found that glucose deprivation reduced PD-L1 expression in HCC cells. Additionally, TCGA data and immunostaining analyses confirmed a positive correlation between the expression of hexokinase II (HK2), which plays a key role in glucose metabolism, and PD-L1. Notably, rapamycin treatment  decreased the expression of PD-L1 and HK2 in both high PD-L1-expressing HCC cells and sorafenib-resistant cells. Our results suggest that the modulation of PD-L1 expression by glucose deprivation may represent a strategy to overcome PD-L1 upregulation in patients with sorafenib-resistant HCC.

Comparative Effects of Bivalent, Quadrivalent, and Nonavalent Human Papillomavirus Vaccines in The Prevention of Genotype-Specific Infection: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Human papillomavirus (HPV) infection is a major global disease burden and the main cause of cervical cancer. Certain HPV genotypes, with are the most common etiologic pathogens and cause a significant disease burden, are being targeted for vaccine development. However, few studies have focused on the comparative effectiveness of the bivalent HPV (2v-HPV), quadrivalent HPV (4v-HPV), and nonavalent HPV (9v-HPV) vaccines against HPV strain-specific infection. This study investigated the comparative effects of these vaccines against genotype-specific infection. MATERIALS AND METHODS: We conducted a pairwise and network meta-analysis of published randomized clinical trials of HPV vaccines according to sex and HPV infection status for nine HPV genotypes (HPV 6/11/16/18/31/33/45/52/58). RESULTS: Overall, 10 randomized controlled trials (12 articles) were included in this study. In the network meta-analysis, no statistically significant differences were observed in the prevention of carcinogenic HPV strains (16/18/31/33/45/52/58) between the 2v-HPV and 4v-HPV vaccines in female HPV infection-naïve populations. However, the 9v-HPV vaccine showed a significantly superior effect compared with 2v-HPV and 4v-HPV vaccines in preventing HPV 31/33/45/52/58 infections. Although 2v-HPV and 4v-HPV vaccines provided some cross-protection against HPV 31/33/45/52/58 infections, the effect was significant only on HPV 31 infection. For HPV 16 and 18, neither statistically significant nor small differences were found in the prevention of HPV infection among the 2v-HPV, 4v-HPV, and 9v-HPV vaccines. CONCLUSION: Our study complements previous understanding of how the effect of HPV vaccines differs according to the HPV genotype. This is important because HPV genotype prevalence varies among countries. We advocate for continued efforts in vaccinating against HPV, while public health agencies should consider the difference in the vaccine effect and HPV genotype prevalence when implementing HPV vaccination in public vaccination programs.

Extracellular vesicles from induced pluripotent stem cell-derived mesenchymal stem cells enhance the recovery of acute kidney injury.

BACKGROUND AIMS: To investigate whether the extracellular vesicles (EVs) from mesenchymal stem cell-like cells derived from induced pluripotent stem cells (iMSC-EVs) can inhibit the progression of acute kidney injury (AKI). METHODS: The characteristics of iMSC-EVs were confirmed by immunoblotting, cryo-transmission electron microscopy, nanoparticle tracking analysis, and their localization in kidneys. Using human renal epithelial cells, the potential of iMSC-EVs to stimulate the growth and survival of HK-2 cells undergoing cisplatin-induced cell death was investigated. The anti-inflammatory effects of iMSC-EVs was examined in M1-polarized THP-1 macrophages. Subsequently, the therapeutic potential of iMSC-EVs was assessed in cisplatin-induced acute kidney injury in BALB/c mice. The anti-apoptotic and anti-inflammatory effect of iMSC-EVs was evaluated using serum biochemistry, histology, immunohistochemistry, and gene expression analysis. RESULTS: iMSC-EVs promoted the growth of renal epithelial cell (HK-2) and enhanced the survival of HK-2 undergoing cisplatin-induced cell death. In cisplatin-induced mice with AKI, iMSC-EVs alleviated AKI, as shown by reduced blood nitrogen urea/creatinine and increased body weight. Also, iMSC-EVs enhanced renal tissue integrity and the number of proliferating cell nuclear antigen-positive tubules. iMSC-EVs decreased the infiltration of immune cells, reduced the expression of inflammatory genes in M1-induced THP-1 cells and enhanced capillary density in the kidney of AKI mice. Real-time quantitative polymerase chain reaction analysis showed that the expression of inflammatory genes in the kidney of AKI mice was reduced compared with that received vehicle. Immunoblotting revealed that iMSC-EVs led to a decreased protein expression of key inflammatory genes. Also, iMSC-EVs reversed the activation of ERK1/2 signaling induced by AKI. Finally, iMSC-EVs inhibited the apoptosis of HK-2 cells induced by cisplatin as well as that of renal tissue of AKI mice. CONCLUSIONS: Our data suggest that iMSC-EVs have potential to become a novel, cell-free therapeutic for cisplatin-induced AKI.

3D MR fingerprinting-derived myelin water fraction characterizing brain development and leukodystrophy.

BACKGROUND: Magnetic resonance fingerprinting (MRF) enables fast myelin quantification via the myelin water fraction (MWF), offering a noninvasive method to assess brain development and disease. However, MRF-derived MWF lacks histological evaluation and remains unexamined in relation to leukodystrophy. This study aimed to access MRF-derived MWF through histology in mice and establish links between myelin, development, and leukodystrophy in mice and children, demonstrating its potential applicability in animal and human studies. METHODS: 3D MRF was performed on normal C57BL/6 mice with different ages, megalencephalic leukoencephalopathy with subcortical cyst 1 wild type (MLC1 WT, control) mice, and MLC 1 knock-out (MLC1 KO, leukodystrophy) mice using a 3 T MRI. MWF values were analyzed from 3D MRF data, and histological myelin quantification was carried out using immunohistochemistry to anti-proteolipid protein (PLP) in the corpus callosum and cortex. The associations between 'MWF and PLP' and 'MWF and age' were evaluated in C57BL/6 mice. MWF values were compared between MLC1 WT and MLC1 KO mice. MWF of normal developing children were retrospectively collected and the association between MWF and age was assessed. RESULTS: In 35 C57BL/6 mice (age range; 3 weeks-48 weeks), MWF showed positive relations with PLP immunoreactivity in the corpus callosum (ß = 0.0006, P = 0.04) and cortex (ß = 0.0005, P = 0.006). In 12-week-old C57BL/6 mice MWF showed positive relations with PLP immunoreactivity (ß = 0.0009, P = 0.003, R2 = 0.54). MWF in the corpus callosum (ß = 0.0022, P < 0.001) and cortex (ß = 0.0010, P < 0.001) showed positive relations with age. Seven MLC1 WT and 9 MLC1 KO mice showed different MWF values in the corpus callous (P < 0.001) and cortex (P < 0.001). A total of 81 children (median age, 126 months; range, 0-199 months) were evaluated and their MWF values according to age showed the best fit for the third-order regression model (adjusted R2 range, 0.44-0.94, P < 0.001). CONCLUSION: MWF demonstrated associations with histologic myelin quantity, age, and the presence of leukodystrophy, underscoring the potential of 3D MRF-derived MWF as a rapid and noninvasive quantitative indicator of brain myelin content in both mice and humans.

Effects of natural products on polycystic ovary syndrome: From traditional medicine to modern drug discovery.

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder with a worldwide prevalence of 6-10 % of women of reproductive age. PCOS is a risk factor for cardiometabolic disorders such as type 2 diabetes, myocardial infarction, and stroke in addition to exhibiting signs of hyperandrogenism and anovulation. However, there is no known cure for PCOS, and medications have only ever been used symptomatically, with a variety of adverse effects. Drugs made from natural plant products may help treat PCOS because several plant extracts have been widely recognized to lessen the symptoms of PCOS. In light of this, 72 current studies on natural products with the potential to control PCOS were examined. By controlling the PI3K/AKT signaling pathway and decreasing NF-κB and cytokines such as tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6), certain plant-derived chemicals might reduce inflammation. Other substances altered the HPO axis, which normalized hormones. Additionally, other plant components increased glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels to reduce radiation-induced oxidative stress. The other substances prevented autophagy by impairing beclin 1, autophagy-related 5 (ATG5), and microtubule-associated protein 1A/1B-light chain 3 - II (LC3- II). The main focus of this comprehensive review is the possibility of plant extracts as natural bio-resources of PCOS treatment by regulating inflammation, hormones, reactive oxygen species (ROS), or autophagy.

Dataset on the assessment of pervious concrete containing palm oil kernel shell and seashell in heavy metal removal from stormwater.

The dataset currently available comprises data on the removal rates of heavy metals (Ba, Se, Cr, Fe, Cd, As, and Co) through the incorporation of seashells and palm oil kernel shells into pervious concrete for stormwater treatment. Stormwater runoff was collected from commercial areas in Taman University, Skudai, Johor, Malaysia. The stormwater samples underwent filtration and were preserved in high-density polyethylene (HDPE) bottles at a temperature of 4 °C for use as incoming water. The outgoing water, referred to as effluent, was obtained from tests performed on pervious concrete samples after a curing period of 28 days. The pervious concrete mixes were created with a water-to-binder ratio (w/b ratio) of 32% and a sand ratio of 10%. Three different levels of palm oil kernel shell and seashell content were used as coarse aggregate replacements: 0%, 25%, and 50%. Two single-size group were considered for both palm oil kernel shell and seashell: (6.3-9.5 mm) and (4.75-6.3 mm). Heavy metal analyses were conducted on the influent and effluent using a PerkinElmer ELAN 6100 Series Inductively Coupled Plasma- Mass Spectrometer (ICP-MS). The available datasets consist of both raw and analyzed data.

Two Years of Experience and Methodology of Korean COVID-19 Living Clinical Practice Guideline Development.

BACKGROUND: In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. METHODS: The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. RESULTS: An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3-4 months. CONCLUSION: We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media. Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.

Subcutaneous Myoepithelioma in the Extremity: A Potential Pitfall in the Differential Diagnosis of Subcutaneous Tumors.

We present a rare case of myoepithelioma in the subcutaneous layer of the shoulder with ultrasonography (US) and magnetic resonance imaging (MRI). US showed a lobulated hyperechoic mass, leading to an impression of lipoma. MRI showed the mass with low signal intensity on T1-weighted images (T1WI), high signal intensity on fat-suppressed T2-weighted images (T2WI), intermediate signal intensity on T2WI, and intense enhancement with adjacent fascial thickening. Imaging findings of soft tissue myoepithelioma have not been established. We report its US and MRI features mimicking features from a lipomatous tumor to infiltrative malignancy. Although soft tissue myoepithelioma has nonspecific image findings to confirm its diagnosis, some findings may help to make the differential diagnosis. Preoperative pathologic confirmation is recommended in a soft tissue neoplasm.

Characterization of aerosols generated by high-power electronic nicotine delivery systems (ENDS): Influence of atomizer, temperature and PG:VG ratios.

The aerosol characteristics of electronic nicotine delivery systems (ENDS) are important parameters in predicting health outcomes since parameters such as aerosol particle size correlate strongly to aerosol delivery and deposition efficiency. However, many studies to date do not account for aerosol aging, which may affect the measurement of ultra-fine particles that typically coagulate or agglomerate during puff development. To reduce aerosol aging, we herein present a unique instrumentation method that combines a) positive pressure ENDS activation and sample collection, b) minimization of both sample tubing length and dilution factors, and c) a high-resolution, electrical low-pressure impactor. This novel approach was applied to systematically investigate the effects of coil design, coil temperature, and propylene glycol to vegetable glycerol ratios on aerosol characteristics including aerosol mass generation, aerosol count generation, and the mass and count size distributions for a high-powered ENDS. Aerosol count measurements revealed high concentrations of ultra-fine particles compared to fine and coarse particles at 200°C, while aerosol mass measurements showed an increase in the overall aerosol mass of fine and coarse particles with increases in temperature and decreases in propylene glycol content. These results provide a better understanding on how various ENDS design parameters affect aerosol characteristics and highlight the need for further research to identify the design parameters that most impact ultra-fine particle generation.

Effect of Echinochrome A on Submandibular Gland Dysfunction in Ovariectomized Rats.

Post-menopausal dry mouth or xerostomia is caused by reduced salivary secretion. This study aimed to investigate the efficacy of echinochrome A (Ech A) in alleviating submandibular gland dysfunctions in ovariectomized rats that mimic menopause. Female rats that were eight-weeks-old were randomly divided into SHAM-6, -12; OVX-6, -12; and ECH-6, -12 groups (consisting of 6- and 12-weeks post-sham-operated, ovariectomized, and Ech A-treated ovariectomized rats, respectively). The ECH groups had lower body weight than OVX but similar food intake and estradiol or estrogen receptor ß expression. However, the ECH groups had lower mRNA expression of sterol-regulatory element binding protein-1c (Srebp-1c), acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), cluster of differentiation 36 (Cd36), and lipid vacuole deposition than OVX mice. Moreover, reactive oxygen species (ROS), malondialdehyde (MDA), and iron accumulation were lower in the ECH than in the OVX groups. Fibrosis markers, transforming growth factor ß (Tgf-ßI and Tgf-ßII mRNA) increased in the OVX than SHAM groups but decreased in the ECH groups. Aquaporin (Aqp-1 and Aqp-5 mRNA) and mucin expressions were downregulated in the OVX groups but improved with Ech A. In addition, Ech A prevented post-menopausal salivary gland dysfunction by inhibiting lipogenesis and ferroptosis. These findings suggest Ech A as an effective remedy for treating menopausal dry mouth.

Extracellular vesicles from IFN-γ-primed mesenchymal stem cells repress atopic dermatitis in mice.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune dysregulation, pruritus, and abnormal epidermal barrier function. Compared with conventional mesenchymal stem cell (MSC), induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) is recognized as a unique source for producing extracellular vesicles (EVs) because it can be obtained in a scalable manner with an enhanced homogeneity. Stimulation of iMSCs with inflammatory cytokines can improve the immune-regulatory, anti-inflammatory, and tissue-repairing potential of iMSC-derived EVs. RESULTS: Proteome analysis showed that IFN-γ-iMSC-EVs are enriched with protein sets that are involved in regulating interferon responses and inflammatory pathways. In AD mice, expression of interleukin receptors for Th2 cytokines (IL-4Rα/13Rα1/31Rα) and activation of their corresponding intracellular signaling molecules was reduced. IFN-γ-iMSC-EVs decreased itching, which was supported by reduced inflammatory cell infiltration and mast cells in AD mouse skin; reduced IgE receptor expression and thymic stromal lymphopoietin and NF-kB activation; and recovered impaired skin barrier, as evidenced by upregulation of key genes of epidermal differentiation and lipid synthesis. CONCLUSIONS: IFN-γ-iMSC-EVs inhibit Th2-induced immune responses, suppress inflammation, and facilitate skin barrier restoration, contributing to AD improvement.

Aryloxypropanolamine targets amyloid aggregates and reverses Alzheimer-like phenotypes in Alzheimer mouse models.

BACKGROUND: Aggregated amyloid-ß (Aß) is considered a pathogenic initiator of Alzheimer's disease (AD), in strong association with tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and cognitive decline. As the removal of amyloid burden from AD patient brains by antibodies has shown therapeutic potential, the development of small molecule drugs inducing chemical dissociation and clearance of Aß is compelling as a therapeutic strategy. In this study, we synthesized and screened aryloxypropanolamine derivatives and identified 1-(3-(2,4-di-tert-pentylphenoxy)-2-hydroxypropyl)pyrrolidin-1-ium chloride, YIAD002, as a strong dissociator of Aß aggregates. METHODS: The dissociative activity of aryloxypropanolamine derivatives against Aß aggregates were evaluated through in vitro assays. Immunohistochemical staining, immunoblot assays, and the Morris water maze were used to assess the anti-Alzheimer potential in YIAD002-treated 5XFAD and transgenic APP/PS1 mice. Target-ligand interaction mechanism was characterized via a combination of peptide mapping, fluorescence dissociation assays, and constrained docking simulations. RESULTS: Among 11 aryloxypropanolamine derivatives, YIAD002 exerted strongest dissociative activity against ß-sheet-rich Aß aggregates. Upon oral administration, YIAD002 substantially reduced amyloid burden and accordingly, improved cognitive performance in the Morris water maze and attenuated major pathological hallmarks of AD including tauopathy, neuroinflammation, and synaptic protein loss. Mechanism studies suggest that YIAD002 interferes with intermolecular ß-sheet fibrillation by directly interacting with KLVFFA and IGLMVG domains of Aß. In addition, YIAD002 was found to possess dissociative activity against aggregates of pyroglutamate-modified Aß and tau. CONCLUSIONS: Collectively, our results evince the potential of chemical-driven dissociation of Aß aggregates by aryloxypropanolamines as a therapeutic modality of the amyloid clearance approach.

Identifying the Risk of Sepsis in Patients With Cancer Using Digital Health Care Records: Machine Learning-Based Approach.

BACKGROUND: Sepsis is diagnosed in millions of people every year, resulting in a high mortality rate. Although patients with sepsis present multimorbid conditions, including cancer, sepsis predictions have mainly focused on patients with severe injuries. OBJECTIVE: In this paper, we present a machine learning-based approach to identify the risk of sepsis in patients with cancer using electronic health records (EHRs). METHODS: We utilized deidentified anonymized EHRs of 8580 patients with cancer from the Samsung Medical Center in Korea in a longitudinal manner between 2014 and 2019. To build a prediction model based on physical status that would differ between sepsis and nonsepsis patients, we analyzed 2462 laboratory test results and 2266 medication prescriptions using graph network and statistical analyses. The medication relationships and lab test results from each analysis were used as additional learning features to train our predictive model. RESULTS: Patients with sepsis showed differential medication trajectories and physical status. For example, in the network-based analysis, narcotic analgesics were prescribed more often in the sepsis group, along with other drugs. Likewise, 35 types of lab tests, including albumin, globulin, and prothrombin time, showed significantly different distributions between sepsis and nonsepsis patients (P<.001). Our model outperformed the model trained using only common EHRs, showing an improved accuracy, area under the receiver operating characteristic (AUROC), and F1 score by 11.9%, 11.3%, and 13.6%, respectively. For the random forest-based model, the accuracy, AUROC, and F1 score were 0.692, 0.753, and 0.602, respectively. CONCLUSIONS: We showed that lab tests and medication relationships can be used as efficient features for predicting sepsis in patients with cancer. Consequently, identifying the risk of sepsis in patients with cancer using EHRs and machine learning is feasible.

Health-Related Quality of Life of Patients with Cervical Cancer According to the Duration of Treatment and Cancer Progression.

OBJECTIVE: The purpose of this study was to assess health-related quality of life (HRQoL) in Korean patients with cervical cancer according to the duration of treatment and cancer progression of cervical cancer. METHODS: This study included 452 outpatients with cervical intraepithelial neoplasia (CIN) or invasive cervical cancer from six tertiary hospitals in South Korea. The questionnaire included the EQ-5D-3L instrument, patients' age, cancer progression (CIN or invasive cervical cancer), treatment duration (<1 year, ≥1 year but <2 years, and ≥2 years), treatment method (surgery, chemotherapy, radiation therapy), and presence of recurrence. HRQoL indices were calculated for these independent factors, and the mean was compared using ANOVA. Multiple regression analysis was performed to analyze factors affecting HRQoL in patients with cervical cancer. RESULTS: The EQ-5D index was 0.93 for patients with CIN, 0.87 for patients with invasive cervical cancer, and 0.78 for patients with recurrent invasive cervical cancer. HRQoL was significantly lower as the CIN progresses to cervical cancer. HRQoL of patients with invasive cervical cancer was lowest within 1 year of treatment in all stages. In addition, the HRQoL of patients with CIN or invasive cervical cancer who received chemotherapy and radiotherapy was lower than that of patients who underwent surgery. Multiple regression analysis showed that the HRQoL decreased significantly as increasing age, the first year of treatment after diagnosis, cancer recurrence, or chemotherapy. CONCLUSION: The HRQoL of patients with cervical cancer is affected not only by the stage of cancer progression but also by the duration of treatment and the type of treatment. As a result, when trying to apply the quality of life of patients with cervical cancer to cost-utility analysis, it is necessary to consider the duration and the type of treatment they receive.