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Jeong-Hui Park,1,&ast; Min Jee Lee,2,&ast; Meng-Han Tsai,3,4 Huan-Ju Shih,5 Jongwha Chang6 1Department of Health Behavior, School of Public Health, Texas A&M University, College Station, TX, USA; 2Population Science and Policy, School of Medicine, Southern Illinois University, Springfield, IL, USA; 3Georgia Prevention Institute, Augusta University, Augusta, GA, USA; 4Cancer Prevention, Control, & Population Health Program, Georgia Cancer Center, Augusta University, Augusta, GA, USA; 5Department of Health Administration and Policy, School of Public Health, George Mason University, Fairfax, VA, USA; 6Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University, College Station, TX, USA&ast;These authors contributed equally to this workCorrespondence: Jongwha Chang, Email jc2345@tamu.eduObjective: The primary objective of this study is to conduct a comparative analysis of telemedicine utilization patterns among adult populations residing in both rural and urban areas and evaluate the probability of telemedicine adoption among adults dwelling in both rural and urban areas amid the backdrop of the COVID-19 pandemic.Methods: Our study has attained sample populations (n = 279,260, National Weighted Estimates = 2,391,188,373) through the secondary analysis of the National Health Interview Survey (NHIS) for the year 2021. We examined the relationship between the rural, regional, and racial variables using chi-square tests and binary logistic regression associated with telemedicine use in our multivariable analysis.Results: Telemedicine use by population decreased with decreasing urbanization level, from 40.2% among adults living in large central metropolitan to 29.7% among adults living in rural area (p< 0.0001). Regarding household income, adults with 400% or more of the federal poverty level (FPL) were significantly more likely to use telemedicine than adults with less than 100% of the FPL. Females were more likely than males to utilize telemedicine. In terms of region, adults living in the West were 1.25 times more likely to use telemedicine than adults living in the Northeast, and minority race/ethnicity groups (eg, Non-Hispanic Black, Hispanic, and other) are less likely to use the telemedicine rather than Non-Hispanic White.Conclusion: Health equity is attained when all demographic groups enjoy uniform access to healthcare services, but disparities emerge when there are discernible variations in access to treatment. Considering this study’s findings, it becomes evident that the distinctions in poverty rates, median income levels, and healthcare utilization patterns across racial and regional lines may serve as indicators of potential health equity concerns.Keywords: telemedicine, COVID-19, NHIS sample, healthcare utilization

Huan-Ju Shih,1 Hong Xue,1 Hua Min,1 Janusz Wojtusiak,1 Jongwha Chang2 1Department of Health and Human Services, George Mason University, Fairfax City, VA, USA; 2Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University, College Station, TX, USACorrespondence: Jongwha Chang, Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University, College Station, TX, 77843, USA, Tel +1-979-436-0664, Email jc2345@tamu.eduObjective: The study utilized a cross-sectional dataset to identify demographic and health factors associated with patient utilization of mHealth applications for engaging with healthcare providers. The focus was on adults with chronic health conditions as the primary app user group. The goal was to reveal specific barriers and facilitators to app adoption among smartphone users, with the aim of highlighting opportunities for upgrades that promote patient empowerment as a prerequisite for shared decision-making (SDM).Methods: Data from the Health Information National Trends Survey (HINTS 5, Cycle 4, 2020) with 3865 respondents (≥ 18 years old) stratified analyses and weighted logistic regression were used.Results: The study found that individuals having a wellness app on a smartphone increased the likelihood (OR 2.68, CI: 2.02– 3.56, p-value < 0.0001) of discussing health conditions with providers. Furthermore, individuals with multiple chronic health conditions were more likely (OR 1.93, CI 1.26– 2.95, p-value < 0.01) to use apps to use mobile health applications to engage with healthcare providers. Other significant variables affecting app usage such as race, marital status, and educational level.Conclusion: Due to difficulties obtaining in-person healthcare, the COVID-19 epidemic forced a swift deployment of mHealth technologies. Even in the absence of a crisis, mobile health applications continue to be crucial for improving patient-provider engagement and developing novel approaches to healthcare delivery. During the pandemic, people with numerous chronic diseases used apps to stay in touch with doctors and maintain their reliance on these platforms. Nonetheless, different smartphone users continue to use mHealth application in different ways. The findings revealing barriers in mHealth app adoption among certain patient subgroups suggest opportunities for developers, in collaboration with users and providers, to enhance inclusion and acceptability when upgrading mHealth application platforms.Keywords: mobile health, digital equity, post-SARS Cov2 care management, healthcare policy, chronic care

We report the case of a 79-year-old woman with primary lymphoma of mucosa-associated lymphoid tissue (MALT) in the urinary bladder. The patient, with urinary frequency, urgency and suprapubic pain had several emergency room visits due to recurrent urinary tract infection. Both sonogram and cystoscopy identified bladder tumors near the bladder neck. An abdominal contrast-enhanced computed tomography scan revealed a polypoid lesion on the anterior bladder wall without enlarged lymph nodes. Transurethral resection of the bladder tumor was conducted. The pathology report confirmed extranodal marginal zone MALT lymphoma. The clinical stage was IEA. Follow-up imaging reported residual bladder tumors, prompting adjuvant radiotherapy. The patient was treated successfully and was disease-free at the 9-month follow-up visit. Primary lymphoma is an uncommon pathological subtype. Its clinical and radiological differentiation from urothelial carcinoma (UC) can be challenging, but treatment strategies differ significantly. A definitive diagnosis relies on histopathology and immunohistochemistry. Typically, bladder lymphoma has a favorable prognosis, but further research is required to identify the optimal treatment., (© 2024. The Author(s).)

Background and Objectives : This paper evaluates the efficacy and safety of ureteral access sheath (UAS) utilization in retrograde intrarenal surgery (RIRS). Materials and Methods : We searched PubMed, Embase, and the Cochrane Library up to 30 August 2023. The inclusion criteria comprised English-language original studies on RIRS with or without UAS in humans. The primary outcome was SFR, while the secondary outcomes included intraoperative and postoperative complications, the lengths of the operation and the hospitalization period, and the duration of the fluoroscopy. Subgroup analyses and a sensitivity analysis were performed. Publication bias was assessed using funnel plots and Egger's regression tests. Dichotomous variables were analyzed using odds ratios (ORs) with 95% confidence intervals (CIs), while mean differences (MDs) were employed for continuous variables. Results : We included 22 studies in our analysis. These spanned 2001 to 2023, involving 12,993 patients and 13,293 procedures. No significant difference in SFR was observed between the UAS and non-UAS groups (OR = 0.90, 95% CI 0.63-1.30, p = 0.59). Intraoperative (OR = 1.13, 95% CI 0.75-1.69, p = 0.5) and postoperative complications (OR = 1.29, 95% CI 0.89-1.87, p = 0.18) did not significantly differ between the groups. UAS usage increased operation times (MD = 8.30, 95% CI 2.51-14.10, p = 0.005) and fluoroscopy times (MD = 5.73, 95% CI 4.55-6.90, p < 0.001). No publication bias was detected for any outcome. Conclusions : In RIRS, UAS usage did not significantly affect SFR, complications, or hospitalization time. However, it increased operation time and fluoroscopy time. Routine UAS usage is not supported, and decisions should be patient-specific. Further studies with larger sample sizes and standardized assessments are needed to refine UAS utilization in RIRS.

The field of public health informatics has undergone significant evolution in recent years, and advancements in technology and its applications are imperative to address emerging public health challenges. Interdisciplinary approaches and training can assist with these challenges. In 2023, the inaugural Public Health Informatics and Technology (PHIAT) Conference was established as a hybrid 3-day conference at the University of California, San Diego, and online. The conference's goal was to establish a forum for academics and public health organizations to discuss and tackle new opportunities and challenges in public health informatics and technology. This paper provides an overview of the quest for interest, speakers and topics, evaluations from the attendees, and lessons learned to be implemented in future conferences., (©April Moreno Arellano, Huan-ju Shih, Karmen S Williams. Originally published in the Online Journal of Public Health Informatics (https://ojphi.jmir.org/), 11.06.2024.)

This study compared the therapeutic effects of engineered exosomes derived from RAW264.7 cells overexpressing hsa-let-7i-5p (engineered exosomes) to exosomes from human placenta-derived mesenchymal stem cells (hpMSC exosomes) against sepsis-induced acute lung injury. Adult male C57BL/6 mice were divided into lipopolysaccharide (LPS), LPS plus engineered exosome (LEExo), or LPS plus hpMSC exosome (LMExo) groups, alongside control groups. The results showed that lung injury scores (based on pathohistological characteristics) and the levels of lung function alterations, tissue edema, and leukocyte infiltration in LEExo and LMExo groups were comparable and significantly lower than in the LPS group (all p < 0.05). Furthermore, the levels of inflammation (nuclear factor-κB activation, cytokine upregulation), macrophage activation (hypoxia-inducible factor-1α activation, M1 phase polarization), oxidation, and apoptosis were diminished in LEExo and LMExo groups compared to the LPS group (all p < 0.05). Inhibition of hsa-let-7i-5p attenuated the therapeutic effects of both engineered and hpMSC exosomes. These findings underscore the potent therapeutic capacity of engineered exosomes enriched with hsa-let-7i-5p and their potential as an alternative to hpMSC exosomes for sepsis treatment. Continued research into the mechanisms of action and optimization of engineered exosomes could pave the way for their future clinical application.

Background: Topography and tomography are valuable techniques for measuring the corneal shape, but they cannot directly assess its internal mechanical stresses. And nonuniform corneal stress plays a crucial biomechanical role in the progression of diseases and postoperative changes. Given the cornea's inherent transparency, analyzing corneal stresses using the photoelasticity method is highly advantageous. However, quantification of photoelasticity faces challenges in obtaining the stress-optic coefficient due to wrinkles caused by the non-spherical geometry during tensional experiments., Objective: In this study, we propose an innovative experimental setup aimed at generating a gradient field of simple shear stress and achieving surface flatness during corneal stretching experiments, enabling the acquisition of the stress-optic coefficient through comparison with numerical results., Methods: Our designed setup applies fluid pressure and force couples on the cornea. The internal fluid pressure maintains the corneal shape, preventing wrinkles, while the force couples create a stress field leading to isochromatic fringes., Results: We successfully measured the stress-optic coefficients of the porcine anisotropic cornea in ex-vivo as 1.87 × 10 -9 (horizontal) and 1.97 × 10 -9 (vertical) (m 2 /N). Each isochromatic fringe order represents a shear stress range of 6.05 × 10 4  Pa under a low tension., Conclusions: This study establishes a significant connection between corneal photoelastic patterns and the quantification of corneal stress by enabling direct measurement through advanced photoelastic visualization technology for clinical applications., 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 © 2024 Elsevier Ltd. All rights reserved.)

Objective: In a previous study, we proved that an experienced urologist is more likely to adapt to the Hugo RAS system. Based on this, we further examine various parameters in this study. Parameters included in this study consisted of console time, functional outcomes, and oncological outcomes., Materials and Methods: A total of 60 patients who underwent robot-assisted radical prostatectomy (RARP) performed by a single surgeon using the da Vinci (DV) system (n = 30) or the Hugo RAS system (n = 30) between March 2023 and August 2023 were included in the analysis. The intraoperative operative time was categorized into vesicourethral anastomosis time and overall console time. Functional and oncological outcomes were documented at the 1st and 3rd postoperative months. Parametric and non-parametric methods were adopted after checking skewness and kurtosis, and an α value of 5% was used to determine the significance., Results: The vesicourethral anastomosis time was significantly lengthened (Hedge's g: 0.87; 95% confidence interval (CI): 0.34-1.39; J factor = 0.987). However, the overall console time was not affected. The functional (postoperative 3rd month: p = 0.130) and oncological outcomes (postoperative 3rd month: p = 0.103) were not significantly different. We also found that the adverse effect on surgical specimens and positive surgical margins was not affected ( p = 0.552)., Conclusion: During the process of adaptation, although intricate motions (such as the vesicourethral anastomosis time) would be lengthened, the overall console time would not change remarkably. In this process, the functional and oncological outcomes would not be compromised. This encourages urologists to adopt the Hugo RAS system in RARP if they have previous experiences of using the DV system, since their trifecta advantage would not be compromised.

Background: A non-contact tonometer is used to measure intraocular pressure, and studies have primarily relied on apex displacements to assess corneal properties. However, previous studies have overlooked the asymmetric characteristics of lateral corneal perturbations, leading to a gap in understanding of the lateral mechanical properties and its application., Method: To investigate these lateral perturbations, we designed an experiment to sequentially record the corneal profiles when two consecutive air-puffs were applied at the center of the same cornea within a short period. Moreover, we used modal decomposition to decompose anterior surface profiles into symmetric and antisymmetric modes to comprehensively analyze the asymmetric characteristics. To extract mechanical properties, we utilized high-pass frequency analysis (>250 Hz) to filter out noise and errors., Results: Symmetric modes between the two consecutive air-puffs exhibited major similarities during vibration; however, antisymmetric modes exhibited minor differences in lateral perturbations of asymmetric vibration. The antisymmetric modes might be related to air-puff misalignment and mechanical properties. Through applying frequency analysis, the mechanical properties could be proven at high frequencies and misalignment shown at low frequencies. Furthermore, we compared the corneal vibration profiles of 259 healthy participants and 50 patients with keratoconus. Their properties showed that the antisymmetric modes of the keratoconus group exhibited a completely opposite direction of deformation compared to that in the healthy group., Conclusions: Our proposed algorithm not only extracts antisymmetric characteristics but also offers valuable insights into decompose misalignment and mechanical properties of healthy and keratoconus corneas, presenting a new perspective for corneal biomechanics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Benign prostatic enlargement (BPE) and lower urinary tract symptoms present challenges in aging men, often addressed through transurethral resection of the prostate (TURP). Despite technological advancements, bladder neck contracture (BNC) remains a concern. This study explores predictors, including comorbidities, influencing BNC after TURP., Methods: A retrospective cohort study at Changhua Christian Hospital analyzed 2041 BPE patients undergoing bipolar TURP. Preoperative urinary catheterization and resection speed were categorized. Patient data included demographics, comorbidities, operative details, and outcomes. Statistical analyses utilized χ2, Kruskal-Wallis tests, and Cox regression models., Results: Within 3 years, 306 (15%) patients developed BNC. Univariate Cox regression identified chronic heart failure (p = 0.033), chronic obstructive pulmonary disease (COPD; p = 0.002), preoperative urinary catheterization (p &lt; 0.001), and low resection speed (p = 0.045) as significant BNC risk factors. Notably, COPD (p = 0.011) and preoperative urinary catheterization (p &lt; 0.001) emerged as independent risk factors for BNC development in multivariate Cox regression analysis., Conclusions: Preoperative urinary catheterization and COPD were significant predictors of BNC post-TURP, while resection speed showed no significant influence. These findings offer clinicians insights for risk assessment, enhancing patient outcomes, and optimizing resources post-TURP., (© 2024 S. Karger AG, Basel.)

The effective prognostic factors for primary mediastinal large B-cell lymphoma (PMLBCL) vary among published studies. The aim of the present study was to explore the factors influencing the overall survival (OS) and progression-free survival (PFS) of patients with PMLBCL at a single institute in Taiwan. This retrospective study was conducted to analyze the prognostic impact of age, sex, disease stage, International Prognostic Index (IPI) score, treatment modality and initial response. A total of 72 patients with a median age of 28 years were included in the study. The mean OS and PFS were 171.40 and 159.77 months, respectively. Female sex, age ≤60 years, receiving radiotherapy (RT) and achieving a complete response were found to be associated with a significantly improved OS and PFS. In addition, high-intensity chemotherapy and an IPI score ≤1 were associated with longer OS, and early-stage disease was associated with a PFS superior to that of advanced-stage disease. The predictive value of IPI is limited in PMLBCL. Therefore, it is necessary to develop a novel prognostic system. The present study revealed the impact of sex on prognosis and, therefore, this factor should be considered in future prognostic evaluations. Since a complete post-treatment response was found to be important, high-intensity chemotherapy is recommended. However, low-intensity treatment followed by RT consolidation appears to be a feasible approach in elderly patients., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023, Spandidos Publications.)

Prognosis of diffuse large B cell lymphoma (DLBCL) can be predicted by various factors. The most widely used tool for prediction is the international prognostic index (IPI). β2-microglobulin is a tumor marker commonly used in hematological malignancies. β2-microglobulin is well correlated with outcome of DLBCL. It has been used as an adjunctive tool in some scoring systems for prognostication of DLBCL. In this study, we collected data of patients with diagnosis of DLBCL between 2015 and 2019 in our institute. For each patient, IPI was calculated according to published literature. At diagnosis, serum levels of β2-microglobulin were measured in the clinical laboratory and the results were retrieved from medical records. A total of 516 patients (269 male and 247 female) were enrolled for retrospective analysis. The median age was 64 (range 22-96). The median follow-up period was 32.2 months. The median level of β2-microglobulin was 2319 μg/L (normal range < 2366 μg/L in the clinical laboratory). Level of β2-microglobulin was significantly different between survivors and patients who succumbed to the disease. β2-microglobulin level was correlated with tumor stage, extranodal involvement, B symptoms and IPI, suggesting that it may be a good surrogate marker for disease severity and outcome prediction. We selected the intermediate-risk patients for further analysis. Patients with intermediate-risk IPI and high β2-microglobulin levels have overall survival comparable to patients with high-risk IPI, suggesting an important role of β2-microglobulin in subdivision of DLBCL patients. In conclusion, β2-microglobulin levels correlated with outcome of DLBCL. It may be used independently as a prognostic factor. Subdivision of patients with intermediate-risk IPI may identify a group of high-risk patients, which can be helpful in refining plans of treatment and follow-up., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Pancreatic cancer can induce a hypercoagulable state which may lead to clinically apparent thrombosis. However, the effect of anticoagulants remains ambiguous. This study aimed to investigate the potential effect of long-term systemic anticoagulant usage on hospitalization outcomes of patients with pancreatic cancer. Methods: This retrospective study extracted all data from the U.S. Nationwide Inpatient Sample (NIS) database from 2005 to 2018. We included hospitalized adults ≥18 years old with a pancreatic cancer diagnosis identified by International Classification of Diseases ninth revision (ICD-9) and tenth revision (ICD-10) codes. We utilized diagnostic codes ICD9 V58.61 and ICD10 Z79.01, i.e., 'long-term use of anticoagulant', to identify individuals who were on a long-term systemic anticoagulant. The study cohort were then further grouped as being with or without long-term systemic use of an anticoagulant. Propensity score matching was performed to balance the characteristics of the two groups. The risks of life-threatening events, e.g., acute myocardial infarction (AMI), acute heart failure (AHF), sepsis, shock, and acute kidney injury (AKI), in-hospital death, and prolonged length of stay (LOS) in the hospital were compared between the groups by univariable and multivariable logistic regression analyses. Results: The study population consisted of 242,903 hospitalized patients with pancreas cancer, 6.5% ( n = 15,719) of whom were on long-term systemic anticoagulants. A multivariable regression analysis showed that long-term systemic anticoagulant use was independently associated with lower odds of sepsis (aOR: 0.81, 95% CI: 0.76-0.85), shock (aOR: 0.59, 95% CI: 0.51-0.68), AKI (aOR: 0.86, 95% CI: 0.81-0.91), in-hospital mortality (aOR: 0.65, 95% CI: 0.60-0.70), and prolonged LOS (aOR: 0.84, 95% CI: 0.80-0.89). Conclusions: Long-term systemic anticoagulant use is associated with better clinical outcomes in terms of decreased risks of some life-threatening events, in-hospital death, and prolonged LOS among hospitalized patients with pancreatic cancer in the U.S.

Background: Since the mass vaccination for COVID-19, several case reports indicated the risk of autoimmune disease flare-ups after the vaccination. Among them, COVID-19 vaccine-induced glomerular diseases have drawn attention worldwide. The cases demonstrating the association between the mRNA vaccine and IgA nephropathy (IgAN) exacerbation had been noticed. Mostly mentioned, the flare-ups usually occurred after the second dose., Methods: We present a Taiwanese female with IgAN who developed gross hematuria within only six hours after the first dose of the Moderna vaccine., Results: Six hours after the first dose of Moderna vaccine on 8 June 2021, the patient developed gross hematuria and significantly decreased urine output. All symptoms resolved spontaneously on the fifth day after the vaccination without any intervention. On the fourth day after the vaccination, the patient were able to back to her original condition., Conclusion: This was an intriguing case of IgAN flare-up following the first dose of mRNA-based COVID-19 vaccination., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Both high-fat diet (HFD) alone and high-fructose plus HFD (HFr/HFD) cause diet-induced non-alcoholic fatty liver disease in murine models. However, the mechanisms underlying their impacts on inducing different levels of liver injury are yet to be elucidated. This study employed a proteomic approach to elucidate further on this issue. Adult male C57BL/6J mice were allocated to the HFD or the HFr/HFD group. After feeding for 12 weeks, all mice were euthanized and samples were collected. The proteomic profiles in liver tissues were analyzed using liquid chromatography-tandem mass spectrometry followed by canonical pathway analysis. We demonstrated that the mitochondrial oxidative phosphorylation (OXPHOS) pathway was the most significantly downregulated canonical pathway in the HFr/HFD group when compared with the HFD group. Within the OXPHOS pathway, the HFr/HFD group demonstrated significant downregulation of complexes I and III and significant upregulation of complex IV when compared with the HFD group. Moreover, the HFr/HFD group had lower protein levels of NADH: ubiquinone oxidoreductase subunits S3, S6, A5, and A12 in complex I ( p < 0.001, =0.03, <0.001, and <0.001, respectively), lower protein level of cytochrome C in complex III ( p < 0.001), and higher protein level of cytochrome C oxidase subunit 2 in complex IV ( p = 0.002), when compared with the HFD group. To summarize, we have demonstrated that the hepatic mitochondrial OXPHOS pathway is significantly downregulated in long-term HFr/HFD feeding when compared with long-term HFD feeding. These data support the concept that the hepatic mitochondrial OXPHOS pathway should be involved in mediating the effects of HFr/HFD on inducing more severe liver injury than HFD alone.

Background: Airway microbiota may play an important role in regulating the immune response related to allergic respiratory diseases. A molecular-based approach was used to analyze the association between nasopharyngeal microbiota, serum immunoglobin (Ig)E levels, and childhood respiratory allergies., Methods: Nasopharyngeal swabs were collected from children aged 36 months with three phenotypes, including allergic respiratory diseases plus atopy, atopy alone, and healthy controls for microbiome analysis using Illumina-based 16S rRNA gene sequencing., Results: In total, 87 children were enrolled, including 36 with allergic respiratory diseases plus atopy, 21 with atopy alone, and 30 healthy controls. Proteobacteria (45.7%), Firmicutes (29.3%), and Actinobacteria (15.3%) were the most prevalent phyla in the study population. Compared with healthy controls, a lower Chao1 index was found in children with allergies (P < 0.035), indicating that bacterial richness was inversely associated with airway allergies. Additionally, in comparison with healthy controls, the genera Acinetobacter, Moraxella, Asaia, and Rhodococcus were more abundant and positively correlated with total serum IgE levels in children with allergies (P < 0.01), whereas the genera Enterococcus and Rickettsia were inversely correlated with total IgE levels, and also appeared to be negatively associated with airway allergies (P < 0.01)., Conclusions: The composition of the nasopharyngeal microbiota alteration may have an influence on childhood respiratory allergies. The inverse association between bacterial richness and allergies postulated that children living in a microbially hygienic environment may increase their risk of developing respiratory allergies., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier B.V.)

Background/aim: Prostate cancer (PC) is one of the major diseases that affects male health and ranks as the second most frequent cancer in men worldwide. Although most newly-diagnosed PCs are well-differentiated tumors with a high cure probability, there are some patients with aggressive malignancies that show potential for recurrence and metastasis. Cytotoxic T lymphocytes are a specific immune effector cell population that mediates immune responses against cancer., Materials and Methods: In the present study, the cytotoxicity of peripheral blood mononuclear cells (PBMCs)-derived γδ T cells and cytokine-induced killer (CIK) cells in combination with chemoradiotherapy against PC cells was evaluated using Alamar blue cell viability and cell membrane permeability assays., Results: Advanced PC-3 cells, which were more resistant to docetaxel (Doc), also showed higher viability following pretreatment with radiation. The cell proliferation inhibition was significantly increased upon additional γδ T or CIK treatment. Furthermore, the proportion of apoptotic cells was significantly (p<0.05) increased in the Doc-γδ T cell co-treatment group as compared with the Doc or γδ T cell treated alone group., Conclusion: γδ T cell therapy may provide additional benefit compared to traditional chemoradiotherapy for PC treatment., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction and Hypothesis: The association of vitamin D deficiency with female urinary incontinence is unclear., Methods: A systematic review of English and non-English articles was conducted. All observational studies in databases including PubMed, EMBASE, the Cochrane Library Trials Register, and Google Scholar were searched until 5 October 2020. Additional studies were identified by contacting clinical experts and searching the bibliographies and abstracts of the compiled articles. Search terms included urinary incontinence and vitamin D. Article data, including study quality indicators, were independently extracted by two authors using predefined data fields., Results: Two cohort studies, four case-control studies and five cross-sectional studies were included in the qualitative synthesis. Two cohort studies and one cross-sectional study, with a total of 2501 females, were included in the meta-analysis. Heterogeneity among the three studies was not observed (I2 = 0.0%, P = 0.69). All pooled analyses were based on fixed-effects models. No difference in vitamin D level was observed between the urinary incontinence group and the control group (mean difference 0.07 ng/ml; 95% confidence interval [CI] -0.57-0.72, P = 0.81, I2 = 0%)., Conclusions: Our meta-analysis revealed that adult females with urinary incontinence did not have lower serum vitamin D levels than control females., (© 2021. The International Urogynecological Association.)

Endoplasmic reticulum (ER) stress mediates the effects of obesity on aggravating sepsis-induced lung injury. We investigated whether exosomes from human placenta choriodecidual membrane-derived mesenchymal stem cells (pcMSCs) can mitigate pulmonary ER stress, lung injury, and the mechanisms of inflammation, oxidation, and apoptosis in lipopolysaccharide-treated obese mice. Diet-induced obese (DIO) mice (adult male C57BL/6J mice fed with a 12-week high-fat diet) received lipopolysaccharide (10 mg/kg, i.p.; DIOLPS group) or lipopolysaccharide plus exosomes (1 × 108 particles/mouse, i.p.; DIOLPSExo group). Our data demonstrated lower levels of ER stress (upregulation of glucose-regulated protein 78, phosphorylated eukaryotic initiation factor 2α, and C/EBP homologous protein; p = 0.038, <0.001, and <0.001, respectively), inflammation (activation of nuclear factor-kB, hypoxia-inducible factor-1α, macrophages, and NLR family pyrin domain containing 3; upregulation of tumor necrosis factor-α, interleukin-1β, and interleukin-6; p = 0.03, <0.001, <0.001, <0.001, <0.001, <0.001, and <0.001, respectively), lipid peroxidation (p < 0.001), and apoptosis (DNA fragmentation, p = 0.003) in lung tissues, as well as lower lung injury level (decreases in tidal volume, peak inspiratory flow, and end expiratory volume; increases in resistance, injury score, and tissue water content; p < 0.001, <0.001, <0.001, <0.001, <0.001, and =0.002, respectively) in the DIOLPSExo group than in the DIOLPS group. In conclusion, exosomes from human pcMSCs mitigate pulmonary ER stress, inflammation, oxidation, apoptosis, and lung injury in lipopolysaccharide-treated obese mice.

Moiré lattice in artificially stacked monolayers of two-dimensional (2D) materials effectively modulates the electronic structures of materials, which is widely highlighted. Formation of the electronic Moiré superlattice promises the prospect of uniformity among different moiré cells across the lattice, enabling a new platform for novel properties, such as unconventional superconductivity, and scalable quantum emitters. Recently, epitaxial growth of the monolayer transition metal dichalcogenide (TMD) is achieved on the sapphire substrate by chemical vapor deposition (CVD) to realize scalable growth of highly-oriented monolayers. However, fabrication of the scalable Moiré lattice remains challenging due to the lack of essential manipulation of the well-aligned monolayers for clean interface quality and precise twisting angle control. Here, scalable and highly-oriented monolayers of TMD are realized on the sapphire substrates by using the customized CVD process. Controlled growth of the epitaxial monolayers is achieved by promoting the rotation of the nuclei-like domains in the initial growth stage, enabling aligned domains for further grain growth in the steady-state stage. A full coverage and distribution of the highly-oriented domains are verified by second-harmonic generation (SHG) microscopy. By developing the method for clean monolayer manipulation, hetero-stacked bilayer (epi-WS 2 /epi-MoS 2 ) is fabricated with the specific angular alignment of the two major oriented monolayers at the edge direction of 0°/ ± 60°. On account of the optimization for scalable Moiré lattice with a high-quality interface, the observation of interlayer exciton at low temperature illustrates the feasibility of scalable Moiré superlattice based on the oriented monolayers., (© 2022. The Author(s).)

Endotoxemia induces lung injury. We assessed the therapeutic efficacy between triple cytokine (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], and IL-6) inhibition (mediated by KCF18 peptide) and single cytokine (TNF-α) inhibition (mediated by SEM18 peptide) on alleviating lung injury in the early phase of endotoxemia. Mice receiving endotoxin (Endo group), endotoxin plus KCF18 (EKCF group), or endotoxin plus SEM18 (ESEM) were monitored and euthanized at 24 h after endotoxin. Our data demonstrated altered lung function (decreases in tidal volume, minute ventilation, and dynamic compliance; and by contrast, increases in airway resistance and end expiration work) and histology (increases in injury scores, leukocyte infiltration, vascular permeability, and tissue water content) in the Endo group with significant protection observed in the EKCF and ESEM groups (all p < 0.05). Levels of inflammation (macrophage activation and cytokine upregulations), oxidation (lipid peroxidation), necroptosis, pyroptosis, and apoptosis in EKCF and ESEM groups were comparable and all were significantly lower than in the Endo group (all p < 0.05). These data demonstrate that single cytokine TNF-α inhibition can achieve therapeutic effects similar to triple cytokines TNF-α, IL-1β, and IL-6 inhibition on alleviating endotoxin-induced lung injury, indicating that TNF-α is the major cytokine in mediating lung injury in the early phase of endotoxemia.

Energy harvesters are devices that accumulate ambient vibrational energy from the environment, and for the time being, variable capacitance is the most widely used mechanism. Various designs were proposed to increase the power of such devices, and in particular, the interdigitated electrode (IDE) pattern is the mainstream. Nevertheless, most IDE designs focus merely on the parallel-type vibrations of electrodes. In this study, the performance of a novel harvester, which combined circular membrane and interdigitated ring electrodes (IRE), was investigated. This design allows the device to collect energy from the rotational structure motions of electrodes through the vibrating membrane. Besides, the circular structure provides a dense capacitive arrangement that is higher than that of the arrangement obtained using regular rectangular chips. The IRE diagram is composed of many capacitive rings, each of which harvests vibrated energy simultaneously. Three gaps (1, 10, and 100 μm) of the ring are investigated for the first four vibrational modes of the membrane to understand the effect of energy output. It is found that the energy outputs are approximately the same for the three gaps; however, rings with a wider gap are easier to manufacture in MEMS.

Introduction : Schwannoma of the male genital system is very uncommon and is mostly treated by surgery. However, prostatic schwannoma presenting with elevated prostate-specific antigen (PSA) level and treated conservatively are extremely rare. Case presentation : Herein, we present a rare case of a prostatic schwannoma in a 65-year-old man who initially presented with an elevated PSA level. Digital rectal examination revealed an enlarged prostate with a palpable hard nodule on the left side. Transrectal ultrasonography revealed an enlarged prostate with a well-defined homogeneously hypoechoic nodule in the left peripheral lobe. Biopsy was done, and histopathology revealed a prostatic schwannoma. Conservative treatment with regular image follow-up was done per the patient's preference. Mild PSA progression but no worsening of symptoms was found in 6 years of follow-up. Conclusions : PSA elevation could be a rare presentation of prostatic schwannoma. Treatment options other than surgery, such as conservative treatment with close observation, could be feasible for these rare tumors and long-term survivorship can be achieved., (Copyright ©2021, Yale Journal of Biology and Medicine.)

Obesity complicates sepsis and increases the mortality of sepsis. We examined the effects of exosomes (from human placenta choriodecidual membrane-derived mesenchymal stem cells, pcMSCs) on preventing sepsis in obesity and the mitigating role of hsa-let-7i-5p microRNA. Obese mice (adult male C57BL/6J mice fed a high-fat diet for 12 weeks) received normal saline (HFD), endotoxin (10 mg/kg, intraperitoneal (ip); HFDLPS), endotoxin with exosomes (1 × 10 8 particles/mouse, ip; HLE), or endotoxin with let-7i-5p microRNA inhibitor-pretreated exosomes (1 × 10 8 particles/mouse, ip; HLEi). Our data demonstrated that the 48-h survival rate in the HLE (100%) group was significantly higher than in the HFDLPS (50%) and HLEi (58.3%) groups (both p < 0.05). In the surviving mice, by contrast, levels of liver injury (injury score, plasma aspartate transaminase and alanine transaminase concentrations, tissue water content, and leukocyte infiltration in liver tissues; all p < 0.05), inflammation (nuclear factor-κB activation, hypoxia-inducible factor-1α activation, macrophage activation, and concentrations of tumor necrosis factor-α, interleukin-6, and leptin in liver tissues; all p < 0.05), and oxidation (malondialdehyde in liver tissues, with p < 0.001) in the HLE group were significantly lower than in the HFDLPS group. Levels of mitochondrial injury/dysfunction and apoptosis in liver tissues in the HLE group were also significantly lower than in the HFDLPS group (all p < 0.05). Inhibition of let-7i-5p microRNA offset the effects of the exosomes, with most of the aforementioned measurements in the HLEi group being significantly higher than in the HLE group (all p < 0.05). In conclusion, exosomes mitigated endotoxin-induced mortality and liver injury in obese mice, and these effects were mediated by let-7i-5p microRNA.

Abstract: A high-cholesterol diet increases the risk of bladder cancer. The purpose of this nationwide longitudinal population-based retrospective cohort study is to investigate whether hyperlipidemia is a risk factor for bladder cancer.Data from Taiwan National Health Insurance Database were analyzed. The primary study end point was the occurrence of newly diagnosed bladder cancer. The relative risk of bladder cancer in a hyperlipidemia cohort was compared with that in an age- and gender-matched non-hyperlipidemia cohort by using the Cox proportional hazards regression model. Cox regression analyses were further adjusted by the propensity score.Our data revealed that the hyperlipidemia cohort (n = 33,555) had a significantly higher subsequent risk of bladder cancer than did the non-hyperlipidemia cohort (n = 33,555) (adjusted hazard ratio [HR] = 1.37, P = .005) after propensity score adjustment. Subgroup analyses revealed that men in the hyperlipidemia cohort had a significantly higher subsequent risk of bladder cancer than did those in the non-hyperlipidemia cohort (adjusted HR = 1.36, P = .040). However, the risk of bladder cancer was not significantly different between women in the hyperlipidemia cohort and those in the non-hyperlipidemia cohort. Subgroup analyses further revealed that the risk of bladder cancer was significantly higher in men aged 20 to 39 years in the hyperlipidemia cohort than in those in the non-hyperlipidemia cohort (adjusted HR = 5.45, P = .029).In conclusion, hyperlipidemia is a risk factor for bladder cancer in young adult men., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

That intensity-modulated radiotherapy (IMRT) plus antiandrogen therapy (IMRT-ADT) and radical prostatectomy (RP) are the definitive optimal treatments for relatively young patients (aged ≤ 65 years) with high- or very high-risk localized prostate cancer (HR/VHR-LPC), but remains controversial. We conducted a national population-based cohort study by using propensity score matching (PSM) to evaluate the clinical outcomes of RP and IMRT-ADT in relatively young patients with HR/VHR-LPC. Methods : We used the Taiwan Cancer Registry database to evaluate clinical outcomes in relatively young (aged ≤ 65 years) patients with HR/VHR-LPC, as defined by the National Comprehensive Cancer Network risk strata. The patients had received RP or IMRT-ADT (high-dose, ≥72 Gy plus long-term, 1.5-3 years, ADT). Head-to-head PSM was used to balance potential confounders. A Cox proportional hazards regression model was used to analyze oncologic outcomes. Results : High-dose IMRT-ADT had a higher risk of biochemical failure (adjusted hazard ratio [aHR] = 2.03, 95% confidence interval [CI] 1.56-2.65, p < 0.0001) compared with RP; IMRT-ADT did not have an increased risk of all-cause death (aHR = 1.2, 95% CI 0.65-2.24, p = 0.564), locoregional recurrence (aHR = 0.88, 95% CI 0.67-1.06, p = 0.3524), or distant metastasis (aHR = 1.03, 95% CI 0.56-1.9, p = 0.9176) compared with RP. Conclusion : In relatively young patients with HR/VHR-LPC, RP and IMRT-ADT yielded similar oncologic outcomes and RP reduced the risk of biochemical failure compared with IMRT-ADT.

Ovarian cancer is the most lethal gynecological cancer, and it is frequently diagnosed at advanced stages, with recurrences after treatments. Treatment failure and resistance are due to hypoxia-inducible factors (HIFs) activated by cancer cells adapt to hypoxia. IGFBP3, which was previously identified as a growth/invasion/metastasis suppressor of ovarian cancer, plays a key role in inhibiting tumor angiogenesis. Although IGFBP3 can effectively downregulate tumor proliferation and vasculogenesis, its effects are only transient. Tumors enter a hypoxic state when they grow large and without blood vessels; then, the tumor cells activate HIFs to regulate cell metabolism, proliferation, and induce vasculogenesis to adapt to hypoxic stress. After IGFBP3 was transiently expressed in highly invasive ovarian cancer cell line and heterotransplant on mice, the xenograft tumors demonstrated a transient growth arrest with de-vascularization, causing tumor cell hypoxia. Tumor re-proliferation was associated with early HIF-1α and later HIF-2α activations. Both HIF-1α and HIF-2α were related to IGFBP3 expressions. In the down-expression of IGFBP3 in xenograft tumors and transfectants, HIF-2α was the major activated protein. This study suggests that HIF-2α presentation is crucial in the switching of epithelial ovarian cancer from dormancy to proliferation states. In highly invasive cells, the cancer hallmarks associated with aggressiveness could be activated to escape from the growth restriction state., (© 2021. The Author(s).)

Background: Semen quality impairment is a serious consequence of testicular torsion-detorsion. Adequate germ-cell mitochondrial oxidative phosphorylation plays a crucial role in male fertility. Changes in cellular oxidative phosphorylation in testicular tissues after testicular torsion-detorsion remain unclear., Objectives: This study investigated whether testicular torsion-detorsion induces alternations of mitochondrial oxidative phosphorylation in testicular tissues., Materials and Methods: BALB/c male mice were divided into a Sham group and a testicular torsion-detorsion group. At the end of the procedure, the mice were euthanized, and their bilateral testicles were removed. Mitochondria morphology was evaluated through transmission electron microscopy. The cellular respiratory functions of germ cells were evaluated using a Seahorse analyzer assay. The proteome profiles in testicular tissues were analyzed using liquid chromatography-tandem mass spectrometry. The differences in the expression levels of each component in the oxidative phosphorylation were revealed using Ingenuity Pathways Analysis., Results: Inner mitochondrial membrane disruption was found in ipsilateral twisted testicular mitochondria in the torsion-detorsion group but not in contralateral untwisted testes. The cellular respiratory function in germ cells was significantly decreased after testicular torsion-detorsion in ipsilateral twisted testes but not in contralateral untwisted testes. Liquid chromatography-tandem mass spectrometry analysis of ipsilateral twisted testicular tissue revealed that mitochondrial proteins were differentially expressed after testicular torsion-detorsion. Testicular torsion-detorsion induced downregulation of oxidative phosphorylation and revealed alternations of specific proteins in the oxidative phosphorylation complexes., Discussion and Conclusion: Testicular torsion-detorsion produced mitochondria injury and dysregulation of mitochondrial oxidative phosphorylation in ipsilateral twisted testes. Different protein expressions were identified in the mitochondrial oxidative phosphorylation complexes with testicular torsion-detorsion; new therapeutic targets may be identified to restore the oxidative phosphorylation function of germ cells., (© 2021 American Society of Andrology and European Academy of Andrology.)

Background: Methicillin-resistant Staphylococcus aureus (MRSA) colonization in infants may pose a risk for subsequent infection in children. The study aimed to determine S. aureus colonization patterns in infancy, and strain relatedness between maternal and infant colonization. Methods: A prospective cohort study was conducted for nasopharyngeal S. aureus detection in neonates at delivery; in children at 1, 6, 12, 24, 36, and 60 months of age; and from mothers immediately after the delivery of their baby and when their child is 1 month old. A questionnaire for infants and mothers was administered at each planned visit. Results: In total, 521 and 135 infant-mother dyads underwent nasopharyngeal swab collection at 1 month and immediately after delivery, respectively. Among the 521 dyads at 1 month of age, concordant S. aureus colonization was found in 95 dyads, including MRSA in 48.4% (46/95). No concordant MRSA carriage was present among the 135 dyads at delivery. The genetic relatedness of concurrent MRSA-colonized dyads showed that more than two-thirds (32/46 [69.6%]) had identical genotypes, mainly ST 59/PVL-negative/SCC mec IV. Infants aged 1 month had the highest incidence of S. aureus , and the trend declined to a nadir at the age of 12 months. Carrier mothers who smoked cigarettes may increase the risk of infant Staphylococcus colonization (odds ratio, 2.12; 95% confidence interval, 1.23-3.66; p < 0.01). Conclusions: Maternal-infant horizontal transmission may be the primary source of MRSA acquisition in early infancy. The avoidance of passive smoking could be recommended for the prevention of S. aureus carriage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tsai, Chiu, Su, Liao, Shih, Hua, Yao, Lai, Yeh, Chen and Huang.)

Background/aim: Cancer stem cells (CSCs) have been suggested playing a crucial role in the tumorigenesis and tumor progression. Clinically, concurrent chemoradiotherapy (CCRT) after transurethral resection of the bladder is the widely accepted treatment option for high-grade bladder urothelial carcinoma (UC); however, a proportion of bladder UC patients still suffer from recurrence and metastasis. In the present study, we investigated the stemness properties of bladder UC cells with respect to various disease stages. The metastatic capability and epithelial-mesenchymal transition (EMT) of the parental cells and the CSC cells of bladder UC, after chemotherapy with cisplatin alone or CCRT were also studied, respectively., Materials and Methods: The aldehyde dehydrogenase (ALDH)-positive cells were analyzed by a flow cytometer. The inhibitory effects of radiation in combination with cisplatin on the cell viability, migration, invasion and EMT characteristics were also examined., Results: We found that the proportion of ALDH + -CSCs of bladder UC cells and the disease grading were independent. Furthermore, cisplatin alone significantly (p<0.05) enhanced the migration of both grade-III T24 cells and advanced-stage HT1197 cells, while CCRT treatment significantly (p<0.05) inhibited the T24 cell migration capability, compared to the cisplatin alone group. Interestingly, we found that the cell invasion capability was obviously increased upon the treatment with CCRT in both T24 and HT1197 CSCs. Furthermore, cisplatin played a promoting role in EMT whether in the presence or absence of irradiation., Conclusion: CSCs as well as EMT signaling might contribute to the resistance and metastasis of one-shot CCRT in malignant bladder cancer., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

To improve bovine corneal endothelial cell (BCEC) migration, enhance cell energy, and facilitate symmetric cell distribution in corneal surfaces, an electromagnet device was fabricated. Twenty nanometer superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with fourth-generation dendrimer macromolecules were synthesized, and their size and structure were evaluated using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR). The results confirmed the configuration of the dendrimer on the SPION surfaces. In vitro biocompatibility was assessed using the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide assay. No significant toxicity was noted on BCECs within 24 h of incubation. In the cell migration assay, cells treated with dendrimer-coated SPIONs exhibited a relatively high wound healing rate under sample addition (1 μg/mL) under a magnetic field. Real-time PCR on BCECs treated with dendrimer-coated SPIONs revealed upregulation of specific genes, including AT1P1 and NCAM1, for BCECs-dendrimer-coated SPIONs under a magnetic field. The three-dimensional dispersion of BCECs containing dendrimer-coated SPIONs under a magnetic field was evaluated using COMSOL Multiphysics software. The results revealed the BCECs-SPION vortex pattern layers in the corneal surface corresponded to the electromagnet's displacement from the ocular surface. Magnetic resonance imaging (MRI) indicated that dendrimer-coated SPIONs can be used as a T 2 contrast agent.

Rationale: Malakoplakia and xanthogranulomatous pyelonephritis are chronic inflammatory conditions of the kidney characterized by the infiltration of inflammatory cells., Patient Concerns: An 82-year-old female patient had a history of hypertension, type 2 diabetes mellitus, dyslipidemia, and end-stage renal disease under hemodialysis. She was admitted repeatedly 4 times within 4 months due to urosepsis., Diagnosis: The enlarged right kidney with a low-density lesion at the right middle calyx, and a well-enhanced ureter were noted on the computed tomography scan. Therefore, xanthogranulomatous inflammation was suspected. Semi-rigid ureteroscopy with biopsy was performed, and xanthogranulomatous inflammation of the ureter was confirmed on the pathology report., Interventions: After right open radical nephrectomy was performed, the final pathology report revealed malakoplakia with xanthogranulomatous pyelonephritis., Outcomes: After the surgery, she has no longer suffered from urosepsis for 8 months, and there were no adverse event or recurrence noted., Lessons: With this case report, we aim to emphasize that these 2 diseases are not mutually exclusive, but they may exist simultaneously in the same patient., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Breast and prostate cancer patients may experience physical and psychological distress, and a possible decrease in sleep quality. Subjective and objective methods measure different aspects of sleep quality. Our study attempted to determine differences between objective and subjective measurements of sleep quality using bivariate and Pearson's correlation data analysis. Forty breast ( n = 20) and prostate ( n = 20) cancer patients were recruited in this observational study. Participants were given an actigraphy device (ACT) and asked to continuously wear it for seven consecutive days, for objective data collection. Following this period, they filled out the Pittsburgh Sleep Quality Index Questionnaire (PSQI) to collect subjective data on sleep quality. The correlation results showed that, for breast cancer patients, PSQI sleep duration was moderately correlated with ACT total sleeping time (TST) (r = -0.534, p < 0.05), and PSQI daytime dysfunction was related to ACT efficiency (r = 0.521, p < 0.05). For prostate cancer patients, PSQI sleep disturbances were related to ACT TST (r = 0.626, p < 0.05). Both objective and subjective measurements are important in validating and determining details of sleep quality, with combined results being more insightful, and can also help in personalized care to further improve quality of life among cancer patients.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disorder with complex pathogenesis and lacks effective treatment. Chronic inflammation is the main pathogenesis of Hunner-type IC/BPS. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome-related transforming growth factor-β (TGF-β)/Smad signaling pathway plays a crucial role in inflammation-related tissue fibrosis. Lipopolysaccharide (LPS) and protamine sulfate (LPS/PS) were instilled into the mouse bladder twice a week for 5 consecutive weeks to establish a chronic inflammation-induced IC/BPS model (LPS/PS model). Following LPS/PS treatment, curcumin (oral, 100 mg/kg; a potent NLRP3 modulator) was administered for 2 weeks in the curcumin treatment group, and normal saline was used for the sham group. Bladder function was evaluated by performing the voiding spot assay and examining the status of urothelial denudation and fibrosis in bladder tissues. The expression of NLRP3 inflammasome, interleukin-1β, TGF-β, Smad, vimentin, and E-cadherin in bladder tissues was evaluated through immunohistochemistry staining. Results revealed that the repeated instillation of LPS/PS leads to voiding dysfunction, bladder urothelium denudation, and detrusor muscle fibrosis through the upregulation of the NLRP3 inflammasome/IL-1β-related TGF-β/Smad pathway and the increased epithelial-mesenchymal transition process in bladder tissues. The downregulation of the NLRP3 inflammasome/IL-1β-related TGF-β/Smad pathway in bladder tissues through curcumin effectively mitigated bladder injury in the LPS/PS model. In conclusion, the NLRP3 inflammasome/IL-1β-related TGF-β/Smad pathway plays a crucial role in bladder injury in the LPS/PS model, and modulation of this pathway, such as by using curcumin, can effectively mitigate the sequelae of chronic inflammation-induced IC/BPS., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Three major cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, mediate endotoxemia-induced liver injury. With the similar structures to the binding domains of the three cytokines to their cognate receptors, the novel peptide KCF18 can simultaneously inhibit TNF-α, IL-1β, and IL-6. We elucidated whether KCF18 can alleviate injury of liver in endotoxemic mice. Adult male mice (BALB/cJ) were intraperitoneally (i.p.) administered lipopolysaccharide (LPS, 15 mg/kg; LPS group) or LPS with KCF18 (LKCF group). Mice in the LKCF group received KCF18 (i.p.) at 2 h (0.6 mg/kg), 4 h (0.3 mg/kg), 6 h (0.3 mg/kg), and 8 h (0.3mg/kg) after LPS administration. Mice were sacrificed after receiving LPS for 24 h. Our results indicated that the binding levels of the three cytokines to their cognate receptors in liver tissues in the LKCF group were significantly lower than those in the LPS group (all p < 0.05). The liver injury level, as measured by performing functional and histological analyses and by determining the tissue water content and vascular permeability (all p < 0.05), was significantly lower in the LKCF group than in the LPS group. Similarly, the levels of inflammation (macrophage activation, cytokine upregulation, and leukocyte infiltration), oxidation, necroptosis, pyroptosis, and apoptosis (all p < 0.05) in liver tissues in the LKCF group were significantly lower than those in the LPS group. In conclusion, the KCF18 peptide-based simultaneous inhibition of TNF-α, IL-1β, and IL-6 can alleviate liver injury in mice with endotoxemia.

Deciphering gene regulatory networks (GRNs) is both a promise and challenge of systems biology. The promise lies in identifying key transcription factors (TFs) that enable an organism to react to changes in its environment. The challenge lies in validating GRNs that involve hundreds of TFs with hundreds of thousands of interactions with their genome-wide targets experimentally determined by high-throughput sequencing. To address this challenge, we developed ConnecTF, a species-independent, web-based platform that integrates genome-wide studies of TF-target binding, TF-target regulation, and other TF-centric omic datasets and uses these to build and refine validated or inferred GRNs. We demonstrate the functionality of ConnecTF by showing how integration within and across TF-target datasets uncovers biological insights. Case study 1 uses integration of TF-target gene regulation and binding datasets to uncover TF mode-of-action and identify potential TF partners for 14 TFs in abscisic acid signaling. Case study 2 demonstrates how genome-wide TF-target data and automated functions in ConnecTF are used in precision/recall analysis and pruning of an inferred GRN for nitrogen signaling. Case study 3 uses ConnecTF to chart a network path from NLP7, a master TF in nitrogen signaling, to direct secondary TF2s and to its indirect targets in a Network Walking approach. The public version of ConnecTF (https://ConnecTF.org) contains 3,738,278 TF-target interactions for 423 TFs in Arabidopsis, 839,210 TF-target interactions for 139 TFs in maize (Zea mays), and 293,094 TF-target interactions for 26 TFs in rice (Oryza sativa). The database and tools in ConnecTF will advance the exploration of GRNs in plant systems biology applications for model and crop species., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Objective: Prostate cancer (PCa) incidence has stabilized but not in patients at a young age. We assessed patient characteristics and disease progression in early-onset PCa., Methods: A retrospective cohort of 28,039 newly diagnosed PCa patients aged ≥35 years was constructed using the Taiwan Cancer Registry in 2008-2016. Patients were categorized by age at diagnosis (≤54, 55-59, 60-69, 70-74, and ≥75 years). The clinical stage at diagnosis, Gleason score, prostate-specific antigen level at diagnosis, Charlson's comorbidity index, and primary and secondary treatments for PCa were included in the analysis. All-cause mortality and prostate cancer-specific mortality (PCSM) were reported. Hazard ratios (HRs) and 95% confidence intervals (CIs) estimating the risks of death and of receiving secondary cancer treatment were generated by Cox hazard models., Results: In patients aged ≤54, 55-59, and 60-69 years, about 60% of them in each group were classified into the high-risk, very high-risk, or metastatic group. However, young patients ≤54 years had a higher risk of PCSM than patients aged 60-69 years (HR = 1.22; 95% CI = 1.10-1.49). This trend of an increased risk in PCSM remained for high-risk, very high-risk, or metastatic patients (HR = 1.24; 95% CI = 1.01-1.51), but not in low- or intermediate-risk patients. Besides, young patients diagnosed with high-risk diseases had the highest risk of receiving secondary cancer treatment within 180 days after completing primary treatment among all age groups (HR = 1.32; 95% CI = 1.07-1.63)., Conclusions: PCa arising in young patients ≤54 years of age, especially those with a high risk or metastatic form, might be more aggressive than that in other age groups., (© 2020 Wiley Periodicals LLC.)

Objective: To evaluate the therapeutic efficacy of a steroid switch from prednisone to dexamethasone in Asians with metastatic castration-resistant prostate cancer (mCRPC) that progressed after docetaxel chemotherapy., Methods: This study included postdocetaxel patients with mCRPC treated with abiraterone acetate combined with prednisone (AA + P) who had experienced prostate-specific antigen (PSA) progression. All patients underwent a steroid switch from prednisone (10 mg/day) to dexamethasone (1 mg/day). The PSA level and clinical symptoms were recorded. Moreover, follow-up was conducted until patients were either lost to follow-up or death., Results: This study included 11 patients from a single center in Taiwan. The median follow-up time starting from AA + P treatment was 19.47 months. Seven patients (63.64%) had >30% PSA decline, and 6 patients (54.55%) had >50% PSA decline. The median percentage of PSA decline was 83.6%. The median time until PSA progression after the steroid switch was 11.38 months. No adverse events greater than grade 3 were noted., Conclusions: Steroid switching is a feasible and effective therapy in docetaxel-treated Asian patients with mCRPC., (© 2020 S. Karger AG, Basel.)

Objectives: To compare the therapeutic effects of locoregional deep hyperthermia combined with intravesical chemotherapy with those of intravesical chemotherapy alone in patients with intermediate-/high-risk non-muscle invasive bladder cancer (NMIBC). To evaluate the impact of thermal dose in hyperthermia treatment., Methods: We analyzed data retrieved from the medical records of patients with intermediate-/high-risk NMIBC treated with intravesical mitomycin (IM group) or locoregional deep hyperthermia combined with intravesical mitomycin (CHT group) at a single tertiary care hospital between May 2016 and June 2019. The primary and secondary endpoints were the recurrence-free survival rate and progression-free survival rate, respectively. Thermal dose was evaluated and adverse events were also recorded., Results: In total, 43 patients (CHT: 18 patients, IM: 25 patients) were enrolled. The median follow-up durations were 14 and 23 months, respectively. The recurrence rate at 12 months was significantly lower in the CHT group than in the IM group (11.1% vs. 44%, p  = .048); this trend persisted at 24 months (CHT: 11.1%, IM: 48%; p  = .027). The recurrence-free survival was also significantly higher in the CHT group than in the IM group ( p  = .028). No tumor recurrence was noted in patients who received a thermal dose of ≥4 CEM43. All adverse events were well tolerated, and there was no treatment-related mortality., Conclusions: Intravesical chemotherapy combined with locoregional deep hyperthermia for intermediate-/high-risk papillary NMIBC can significantly decrease the recurrence rate relative to that observed after intravesical chemotherapy alone.

Objective: To evaluate the impacts of statin treatment on the risk of benign prostatic enlargement (BPE) progression in hyperlipidemia patients., Methods: Newly diagnosed hyperlipidemia patients ( n  = 7961), identified from Taiwan's National Health Insurance Research Database, were divided into four statin cohorts (statin use >365 days, n  = 1604; statin use 181-365 days, n  = 813; statin use 91-180 days, n  = 739; and statin use 31-90 days, n  = 713) and one control cohort (cohort that used no statins, n  = 4092). Study endpoint was occurrence of BPE progression (BPE diagnosis plus receiving BPE-related medications or surgery). Relative risks of BPE progression in the statin cohorts compared to the control cohort were analyzed., Results: Multivariable Cox proportional hazards regression analyses demonstrated that BPE progression risk in the cohort used statins for >365 days was significantly lower than the control cohort (adjusted hazard ratio: 0.70, 95% confidence interval: 0.58 ∼ 0.85, p  < .001). However, BPE progression risks of the other three statin cohorts did not significantly differ from the control cohort. Trend analysis revealed that the effects of statin treatment on decreasing BPE progression risk were significantly related to statin treatment duration ( p  = .001)., Conclusions: Hyperlipidemia patients with long-term statin treatment (more than 365 days) are associated with a reduced risk of BPE progression.

Cholangiocarcinoma (CCA) is a malignant tumor with aggressive biological behavior. Immune checkpoints such as cytotoxic T-lymphocyte antigen 4 (CTLA4) and antiprogrammed death 1 (PD-1) are critical immune-checkpoint molecules that repress T-cell activation. The DNA vaccine potential against CTLA4 and PD-1 in CCA is unknown. We used a thioacetamide (TAA)-induced intrahepatic cholangiocarcinoma (iCCA) rat model to investigate the DNA vaccine potential against CTLA4, PD-1, and PD-L1. We detected PD-L1 expression in CCA and CD8 + T-cell infiltration during CCA progression in rats. We validated antibody production, carcinogenesis, and CD8 + T-cell infiltration in rats receiving DNA vaccination against PD-1, PD-L1, or CTLA4. In our TAA-induced iCCA rat model, the expression of PD-L1 and the infiltration of CD8 + T cells increased as in rat CCA tumorigenesis. PD-1 antibodies in rats were not increased after receiving PD-1 DNA vaccination, and CCA tumor growth was not suppressed. However, in rats receiving PD-L1-CTLA4 DNA vaccination, CCA tumor growth was inhibited, and the antibodies of PD-L1 and CTLA4 were produced. Furthermore, the number of CD8 + T cells was enhanced after PD-L1-CTLA4 DNA vaccination. DNA vaccination targeting CTLA4-PD-L1 triggered the production of specific antibodies and suppressed tumor growth in TAA-induced iCCA rats.

A peptide named SEM18, possessing structural similarity to the binding site of tumor necrosis factor (TNF)-α to TNF receptor 1 (TNFR1), was designed. We investigated whether the SEM18 peptide can mitigate lipopolysaccharide (LPS)-induced liver injury in mice. Adult male Balb/cJ mice received LPS (15 mg/kg; LPS group) or LPS plus SEM18 (LSEM group). Control groups were run simultaneously. At 2 h after LPS, the first dose of SEM18 (0.3 mg/kg) was administered, followed by three supplemental doses of SEM18 (0.15 mg/kg, every 2 h). At 24 h after LPS, surviving mice were euthanized for analyses. Compared with the LPS group, binding of TNF-α to TNFR1 in liver tissues was significantly lower in the LSEM group ( p < 0.001). Plasma concentrations of aspartate transaminase and alanine transaminase, as well as Suzuki's scores (liver damage assessment), wet/dry weight ratios, levels of polymorphonuclear neutrophil infiltration, and levels of mitochondrial injury in liver tissues, of the LSEM group were significantly lower than in the LPS group (all p < 0.05). Levels of necroptosis, pyroptosis, apoptosis, and autophagy upregulation in liver tissues in the LSEM group were also significantly lower than in the LPS group (all p < 0.05). Notably, exogenous TNF-α counteracted these effects of SEM18. SEM18 peptide mitigates LPS-induced liver injury in mice.

Streptococcus pneumoniae is a common cause of infectious diseases such as pneumonia and sepsis. Its colonization is thought to be the first step in the development of invasive pneumococcal diseases. This study aimed to investigate pneumococcal colonization patterns in early childhood. A longitudinal birth cohort study was conducted for investigating nasopharyngeal colonized pneumococci at 1, 6, 12, 18, 24, and 36 months of age, particularly focusing on the serotype distribution and antimicrobial susceptibilities. Pneumococcal conjugate vaccine (PCV) effect on nasopharyngeal colonization was also assessed. During 2013-2017, 855 infants were enrolled and a total of 107 isolates were recovered from 95 infants during the first three years of life. In this period, the prevalence of pneumococcal colonization increased, with values ranging from 0.2% (2/834) at 1 month of age to 5.9% (19/323) at 36 months of age. The investigation of serotype revealed that 81.1% (73/90) belonged to the non-PCV13 serotypes-23A, 15A, 15C, and 15B. Moreover, PCV13 serotypes significantly decreased during 2014-2015, when routine PCV13 vaccination was initiated in Taiwan. PCV13 introduction may lead to the reduction in the rates of pneumococcal isolates resistant (R) to penicillin. Under conditional PCV13 vaccination, pneumococcal isolates primarily belonged to non-PCV13 serotypes. This non-PCV13 serotype replacement exhibited lower rates of penicillin R isolates, suggesting that PCV13 administration may reduce the antibiotic-nonsusceptible pneumococcal disease burden and antibiotic use., Competing Interests: The authors have declared that no competing interests exist.

Insulin-like growth factor binding protein-3 (IGFBP3) has been postulated to be a mediator of growth suppression signaling. It was shown to function as a suppressor of invasion in epithelial ovarian cancer (EOC). In this study, we identified an angiogenesis inhibitor, thrombospondin-1 (THBS1), which correlated with IGFBP3 expression in EOC cells. After restoring IGFBP3 expression in an EOC cell line using an inducible plasmid, the transfectants showed an increase in IGFBP3 associated with a parallel increase in THBS1. IGFBP3 decreased cell capillary tube formation in HUVECs, which was reversed after anti-THBS1 treatment. IGFBP3 also decreased blood vessel development in chick embryo chorioallantoic membrane (CAM) assay, which was reversed after THBS1 silencing using THBS1 siRNA. Heterotransplantation of IGFBP3 transfectants significantly decreased tumor growth and vascular formation. Luciferase promoter assay illustrated that THBS1 promoter was activated in the presence of both intracellular and extracellular IGFBP3. The signal was stronger in intracellular IGFBP3 expression than that in extracellular IGFBP3 neutralization. In conclusion, we have identified a novel association between IGFBP3 expression and THBS1 elevation, which consequently results in a decrease in angiogenesis. IGFBP3 could activate THBS1 through promoter regulation mainly via an intracellular signaling pathway. Such angiogenesis-regulating ability could be associated with tumor progression and may represent a major function of IGFBP3 as an onco-suppressor in the pathogenesis of ovarian cancer., Competing Interests: None., (AJCR Copyright © 2020.)

Few studies have assessed the benefits of androgen deprivation therapy (ADT) in men with metastatic prostate cancer (PC; mPC) at an old age or with major cardiovascular conditions. A retrospective cohort consisted of 3835 men with newly diagnosed mPC from the Taiwan Cancer Registry of 2008-2014. Among them, 2692 patients received only ADT in the first year after the cancer diagnosis, and 1143 patients were on watchful waiting. The inverse probability of treatment-weighted Cox model was used to estimate the effects of ADT on all-cause mortality and PC-specific mortality according to age, and the status of congestive heart failure (CHF), coronary arterial diseases (CADs), and stroke at the baseline. After a median follow-up of 2.65 years, 1650 men had died. ADT was associated with a 17-22% risk reduction in all-cause and PC-specific mortality in men without stroke, CAD, or CHF in the 65-79-year group. The survival benefit diminished in men with any of these preexisting conditions. In contrast, ADT was not found to be associated with any survival benefit in the ≥80-year group, even though they did not present with any major cardiovascular disease at the baseline. Patients who had CHF, CAD, or stroke at the baseline did not show a survival benefit following ADT in any of the age groups. Men who have preexisting major cardiovascular diseases or are ≥80 years do not demonstrate a survival benefit from ADT for mPC. The risk-benefit ratio should be considered when using ADT for mPC in older men especially those with major cardiovascular comorbidities.

The mechanistic basis for the biogenesis of peptide hormones and growth factors is poorly understood. Here, we show that the conserved endoplasmic reticulum membrane translocon-associated protein α (TRAPα), also known as signal sequence receptor 1, plays a critical role in the biosynthesis of insulin. Genetic analysis in the nematode Caenorhabditis elegans and biochemical studies in pancreatic β cells reveal that TRAPα deletion impairs preproinsulin translocation while unexpectedly disrupting distal steps in insulin biogenesis including proinsulin processing and secretion. The association of common intronic single-nucleotide variants in the human TRAPα gene with susceptibility to type 2 diabetes and pancreatic β cell dysfunction suggests that impairment of preproinsulin translocation and proinsulin trafficking may contribute to the pathogenesis of type 2 diabetes., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)