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Purpose Nurses play a crucial role in cases of victims of child abuse; however, but there is a need for a comprehensive understanding of their specific roles, responsibilities, and best practices is needed. Methods This integrative review aims to synthesize existing evidence on the role of nurses in cases of victims of child abuse. A literature search was conducted using PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and Scopus databases. A literature search was conducted using PubMed, CINAHL, PsycINFO, and Scopus databases. This review included 12 qualitative and quantitative studies. Results This review identified the following four themes: nurses’ responsibility, intention to report child abuse, perceptions of child abuse, and risk assessment of child abuse. The findings revealed that nurses play a multifaceted role in child abuse situations. Evidence-based practices and guidelines were identified to optimize recovery outcomes among children who have experienced abuse. Conclusion This integrative review contributes to the body of knowledge on nurses’ role in cases of victims of child abuse by providing valuable insights for nursing practice, education, and policy. These findings can help guide nurses in developing evidence-based interventions and collaborative approaches to support the recovery of victims of child abuse.

Abstract Background The intestinal epithelium performs essential physiological functions, such as nutrient absorption, and acts as a barrier to prevent the entry of harmful substances. Mycotoxins are prevalent contaminants found in animal feed that exert harmful effects on the health of livestock. Zearalenone (ZEA) is produced by the Fusarium genus and induces gastrointestinal dysfunction and disrupts the health and immune system of animals. Here, we evaluated the molecular mechanisms that regulate the effects of ZEA on the porcine intestinal epithelium. Results Treatment of IPEC-J2 cells with ZEA decreased the expression of E-cadherin and increased the expression of Snai1 and Vimentin, which induced Snail1-mediated epithelial-to-mesenchymal transition (EMT). In addition, ZEA induces Snail-mediated EMT through the activation of TGF-β signaling. The treatment of IPEC-J2 cells with atractylenolide III, which were exposed to ZEA, alleviated EMT. Conclusions Our findings provide insights into the molecular mechanisms of ZEA toxicity in porcine intestinal epithelial cells and ways to mitigate it.

Ovarian hilus cells (OHCs), a counterpart of testicular Leydig cells, are usually found in the ovarian poles and produce androstenedione. Their origin remains a matter of debate, although OHCs are assumed to come from the adrenogenital primordium. OHCs are rarely observed around the poles of the ovary, including the mesoovarium, stroma of the salpinx (perisalpinx), and the wall of paratubal cysts. Their clinical and pathological characteristics are not well-known because of their rarity. Herein, we present a case of ectopic OHCs in a 48-year-old woman. The patient underwent total hysterectomy and bilateral salpingectomy for vaginal bleeding due to multiple leiomyomas. We incidentally found OHCs in the stroma of the infundibulum of the salpinx, just beneath the tubal epithelium. Their size was less than 1 mm, and they were composed of large cells with central round nuclei and abundant clear or granular cytoplasm. OHCs share morphological and immunohistochemical profiles with ectopic adrenal glands, and the differential diagnosis is sometimes difficult. They do not exhibit microscopic encapsulation or the normal adrenal cortex zonation pattern. The patient was discharged and did not show any abnormal findings during 19 months of follow-up. Analyzing the characteristics of testicular Leydig cells will help understand how OHCs develop and why heterotopic OHCs occur in and around the salpinges.

CO2 is the main solvent used in enhanced oil recovery (EOR). However, its low density and viscosity compared to oil cause a decrease in sweep efficiency. Recently, dimethyl ether (DME), which is more efficient than CO2, has been introduced into the process. DME improves oil recovery by reducing minimum miscible pressure (MMP), interfacial tension (IFT), and oil viscosity. Since DME is an expensive solvent, price reduction and appropriate injection scenarios are needed for economic feasibility. In this study, a compositional model was developed to inject DME with impure CO2 streams, where the CO2 was derived from one of these three purification methods: dehydration, double flash, and distillation. It was assumed that such a mixed solvent was injected into a heterogeneous reservoir where gravity override was maximized. As a result, lower oil recovery is achieved for the higher impurity content of the CO2 stream, lower DME content, and more heterogeneous reservoir. When a high-purity CO2 stream is used, the change in oil recovery according to DME content and heterogeneity of the reservoir is increased. When the lowest-purity CO2 stream is used, the net present value (NPV) is the highest. For a homogeneous reservoir, the NPV is highest for all impure CO2 streams. This optimization indicates a greater impact on revenue from reduced CO2 purchase cost than on profit loss due to reduced oil recovery by impurities. Additional benefits can be expected when considering solvent reuse and carbon capture and storage (CCS) credits.

When predicting the health impacts of PM2.5 from future air quality changes, it is crucial to consider both air quality improvements and population aging. This study divided future emission scenarios into a base and control scenario to project air quality from 2015 to 2030 and assess health outcomes. The GUIDE model, an Integrated Assessment Model (IAM), was used to estimate future emissions, while the CMAQ (Chemical Transport Model) and BenMAP (Health Impact Model) evaluated health impacts resulting from changes in air quality in Korea. The study focused on the impact of population aging on future health outcomes. Both scenarios showed improved PM2.5 concentrations, with the control scenario showing more substantial improvements due to stronger policy measures. When applying current age patterns, health impacts decreased as PM2.5 concentrations decreased. However, when considering future population aging, health impacts increased despite improved air quality. The results excluding aging show that the number of premature deaths due to cardiovascular disease and all other causes caused by PM2.5 is 18,413 in the base year, while in the future control scenario, the number decreases to 11,729. In contrast, when aging is taken into account, the number of premature deaths increases to 23,037. This finding suggests that, although PM2.5 concentrations are expected to decline, the increasing proportion of elderly individuals will exacerbate health risks. Therefore, accounting for aging population trends is essential when studying the health impacts of future air quality changes.

Study Region: Hapcheon and Seomjingang Basins, South KoreaStudy Focus: This study investigated the impacts of climate change on water supply reliability and flood risk in two East Asian basins in South Korea. By employing three coupled hydrological and reservoir operation models, the analysis considered projections under SSP2-4.5 and SSP5-8.5, projected using 12 global climate models.New Hydrological Insights: Our results indicated that under SSP2-4.5, water supply reliability did not considerably decrease compared to the historical period (1995–2014), whereas it was reduced under SSP5-8.5 in one basin, Hapcheon. Meanwhile, a substantial increase in flood risk was modeled in both basins under both scenarios. The impact of climate change was amplified through a cascade from rainfall to runoff and then to flood volume, resulting in heightened flooding risk. In the far future (2081-2100) under SSP5-8.5, the dam-released flood volume was projected to increase rapidly by 73.2% and 74.1% in the Hapcheon and Seomjingang Basins, respectively, indicating considerable changes in flood risk due to climate change. Compared with SSP2-4.5, SSP5-8.5 exhibited more variability among climate models, especially in the far future period (2081–2100), leading to more uncertain projections in drought and flood risk assessments.

Abstract Objective Despite the widespread recognition of the importance of artificial intelligence (AI) in healthcare, its implementation is often limited. This article aims to address this implementation gap by presenting insights from an in-depth case study of an organisation that approached AI implementation with a holistic approach. Materials and methods We conducted a longitudinal, qualitative case study of the implementation of AI in radiology at a large academic medical centre in the Netherlands for three years. Collected data consists of 43 days of work observations, 30 meeting observations, 18 interviews and 41 relevant documents. Abductive reasoning was used for systematic data analysis, which revealed three change initiative themes responding to specific AI implementation challenges. Results This study identifies challenges of implementing AI in radiology at different levels and proposes a holistic approach to tackle those challenges. At the technology level, there is the issue of multiple narrow AI applications with no standard use interface; at the workflow level, AI results allow limited interaction with radiologists; at the people and organisational level, there are divergent expectations and limited experience with AI. The case of Southern illustrates that organisations can reap more benefits from AI implementation by investing in long-term initiatives that holistically align both social and technological aspects of clinical practice. Conclusion This study highlights the importance of a holistic approach to AI implementation that addresses challenges spanning technology, workflow, and organisational levels. Aligning change initiatives between these different levels has proven to be important to facilitate wide-scale implementation of AI in clinical practice. Critical relevance statement Adoption of artificial intelligence is crucial for future-ready radiological care. This case study highlights the importance of a holistic approach that addresses technological, workflow, and organisational aspects, offering practical insights and solutions to facilitate successful AI adoption in clinical practice. Key points 1. Practical and actionable insights into successful AI implementation in radiology are lacking. 2. Aligning technology, workflow, organisational aspects is crucial for a successful AI implementation 3. Holistic approach aids organisations to create sustainable value through AI implementation. Graphical Abstract

Bladder cancer is a common type of cancer around the world, and the majority of patients are diagnosed with non-muscle-invasive bladder cancer (NMIBC). Although low-risk NMIBC has a good prognosis, the disease recurrence rate and development of treatment-refractory disease remain high in intermediate- to high-risk NMIBC patients. To address these challenges for the treatment of NMIBC, a novel combination therapy composed of an oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), and relaxin (RLX; HY-oAd) and a clinical-stage glycogen synthase kinase (GSK)-3β inhibitor (9-ING-41; elraglusib) was investigated in the present report. Our findings demonstrate that HY-oAd and 9-ING-41 combination therapy (HY-oAd+9-ING-41) exerted superior inhibition of tumor growth compared with respective monotherapy in a syngeneic NMIBC tumor model. HY-oAd+9-ING-41 induced high-level tumor extracellular matrix (ECM) degradation and a more potent antitumor immune response than the respective monotherapy. In detail, HY-oAd+9-ING-41 induced superior accumulation of intratumoral T cells, prevention of immune cell exhaustion, and induction of tumor-specific adaptive immune response compared to either monotherapy. Collectively, these results demonstrate that the combination of HY-oAd and 9-ING-41 may be a promising approach to elicit a potent antitumor immune response against bladder cancer.

Molding processes with molds containing topographical structures have been used for fabrication of hydrogel and cryogel particles. However, they can involve difficulties in separation of fabricated particles with complex shape from the molds or repeated fabrication of the particles although the overall processes do not require much skill and equipment. In this study, molds with etched superhydrophobic patterns have been developed by etching polytetrafluoroethylene (PTFE) blocks in user-defined designs with a femtosecond (FS) laser-based etching system. Lyophilized cryogel particles with various designs and sizes were fabricated by molding precursors with these PTFE molds. Additionally, the clean and easy separation of particles from the molds allowed repeated fabrication of the particles. For an application, relatively ‘big’ gelatin-norbornene (GelNB) cryogel particles prepared via molding with polydimethylsiloxane (PDMS) molds, swelling in phosphate buffered saline (PBS) and slicing height in half and ‘small’ GelNB cryogel particles fabricated with the PTFE molds were fabricated. Then, they were used to study scaffold size effect on calvarial bone regeneration. The molds generated with the FS laser-based etching system can be useful for various applications that require the mass production of cryogel particles in various geometries.

Abstract Introduction Deep inspiratory breath‐hold (DIBH) has become standard in radiotherapy for left‐sided breast cancer to reduce the heart dose. This study evaluated breath‐hold stability and reproducibility using Elekta's Active Breathing Coordinator™ (ABC) and its effectiveness and feasibility in left‐sided breast cancer patients undergoing radiotherapy. Methods Eligible patients were planned with free breathing (FB) and DIBH protocols. DIBH treatment was considered if the mean heart dose (MHD) was ≥2 Gy on the FB plan. Those who proceeded with DIBH treatment were enrolled for the pilot study. Electronic portal images of DIBH treatment beams were taken using the movie‐exposure mode for breath‐hold stability and reproducibility analysis. DIBH effectiveness in heart dose reduction and impact on simulation and treatment durations were compared with FB protocol. Results Out of 56 eligible patients, 15 proceeded with DIBH treatment. The mean difference of patient setup within a single breath‐hold was 0.4 mm; between different breath‐holds of the same beam 1.1 mm and between different days 2.6 mm. DIBH reduced the MHD by 47% and the mean left anterior descending artery (LAD) dose by 35%. DIBH took longer time than FB in simulation and treatment. At least 14% of the eligible patients did not tolerate DIBH during simulation. Conclusions ABC leads to stable and reproducible breath‐holds and results in significant heart dose reductions. It may not be tolerated by all patients and has resource implications.

It has been reported that the essential oil extracted from Abies koreana has skin-improving activity, such as anti-wrinkle and whitening effect. However, the key ingredients that facilitate such biological activity has not been fully elucidated. In the present study, to identify the key skin-improving component(s) of the A. koreana essential oil, 10 sequentially fractioned essential oil from A. koreana pine by hydrodistillation were examined for their effect on tyrosinase activity. Out of 10 fractions, only 1 fraction significantly suppressed tyrosinase activity, and subsequent GC/MS analysis indicated that borneol and its acetate ester, bornyl acetate, were unique to the effective fraction, suggesting they are responsible for the skin-improving activity of the essential oil from A. koreana. The biological activity of borneol was evaluated, and borneol significantly inhibited ultraviolet irradiation-induced tyrosinase and matrix metalloproteinase 1 activity while maintain collagen type I synthesis. The results of this study suggest that borneol is a key component of A. koreana essential oil that has potential for mediating whitening and anti-wrinkle effects.

The simultaneous, composite, or sequential occurrence of follicular lymphoma (FL) and classical Hodgkin lymphoma (HL), both of which originate from germinal center B-cell, is rare. Questions have been raised with regard to the type of tests that pathologists should perform when observing the presence of a “large-cell lymphoma” following an FL and what are the most critical pathological points for diagnosis. Here, we present a case of a classical HL following an FL after administering rituximab-bendamustine (R-Benda) chemotherapy. Furthermore, we also summarized the literature and compared this case with other HLs that followed FLs. A 55-year-old woman was diagnosed with a grade 3A FL of the breast and axillary lymph node masses. She completed six R-Benda chemotherapy cycles for stage IV FL. Twenty-three months after the diagnosis, follow-up image studies showed an increase in the size and number of the lesions. Biopsies of the neck lymph node and liver were performed, and the diagnosis was classical HL. Sequential or composite FL and HL may sometimes develop from the same clone because they share the same genetic alterations, such as B-cell lymphoma (Bcl)-2 or Bcl-6 translocation. When a large-cell lymphoma is found after the treatment of FL, classical HL should be considered a pathological differential diagnosis, and histological, immunohistochemical, or molecular investigations must be considered during the diagnostic process.

Background: FOLFIRINOX, used in metastatic pancreatic cancer (MPC), is highly efficacious but also toxic. Various dose modifications for FOLFIRINOX have been introduced to reduce toxicity. However, these studies lack a unified pattern for ‘planned’ dose modification, and the ‘actually administered’ dose varied more. Objective: To map a 10-year trend for ‘planned’ and ‘actual’ doses of FOLFIRINOX and investigate the clinical outcomes according to dose modification. Data sources and methods: A comprehensive systematic literature search was conducted from January 2011 to September 2021. All studies for FOLFIRINOX as first-line treatment in MPC were considered. Selected studies were firstly classified according to prospective versus retrospective research, secondly standard versus modified FOLFIRINOX, and thirdly ‘planned’ versus ‘actual’ dose. For evidence-mapping for the trend of dose modification, we developed a web-based interactive bubble-plot program ( www.RDI-map.com ). Objective response rate (ORR) and hematologic toxicity were set as endpoints for the comparison of clinical outcomes according to dose modification. Results: A total of 37 studies were identified for evidence-mapping (11 prospective and 26 retrospective studies). There were 12 different types of ‘planned’ dose modification in FOLFIRINOX ranging 75–100% oxaliplatin, 75–100% irinotecan, 0–100% 5-fluorouracil (5-FU) bolus, and 75–133% 5-FU continuous injection. The ‘actual’ dose further decreased to 54–96%, 61–88%, 0–92%, and 63–98%, respectively. For the standard versus modified FOLFIRINOX, the ORR was 28.2% (95% CI: 22.5–33.9%) and 33.8% (95% CI: 30.3–37.3%), respectively ( p = 0.100), and the incidence of febrile neutropenia was 11.6% (95% CI: 0–16.0%) and 5.5% (95% CI: 0–8.9%), respectively ( p = 0.030). Conclusions: RDI-map.com enables multifactorial evidence-mapping for practical FOLFIRINOX dose reduction. The pattern of dose modification was not consistent across studies, and there was a significant gap between the ‘planned’ and ‘actual’ doses. Modified FOLFIRINOX showed similar efficacy to the standard regimen with reduced incidence of febrile neutropenia.

Natural killer (NK) cell enteropathy is not well understood. Although NK-cell enteropathy is typically benign, aggressive NK-cell lymphoma is an important differential diagnosis. This paper reports a rare case of NK-cell enteropathy of the stomach presenting with dyspepsia and weight loss. In this case, upper endoscopy revealed an ulcer-like lesion (approximately 7 mm) surrounded by erythema, edema, and mucosal hemorrhage. The biopsy revealed atypical lymphocyte cells expressing CD56 without an Epstein-Barr virus infection, which is consistent with NK-cell enteropathy. Follow-up endoscopy 2 months later revealed lesion regression with mild erythema. The patient was observed closely for 6 months, with no evidence of lymphoma.

PubMed is the most extensively used database and search engine in the biomedical and healthcare fields. However, users could experience several difficulties in acquiring their target papers facing massive numbers of search results, especially in their unfamiliar fields. Therefore, we developed a novel user interface for PubMed and conducted three steps of study: step A, a preliminary user survey with 76 medical experts regarding the current usability for the biomedical literature search task at PubMed; step B is implementing EEEvis, a novel interactive visual analytic system for the search task; step C, a randomized user study comparing PubMed and EEEvis. First, we conducted a Google survey of 76 medical experts regarding the unmet needs of PubMed and the user requirements for a novel search interface. According to the data of preliminary Google survey, we implemented a novel interactive visual analytic system for biomedical literature search. This EEEvis provides enhanced literature data analysis functions including (1) an overview of the bibliographic features including publication date, citation count, and impact factors, (2) an overview of the co-authorship network, and (3) interactive sorting, filtering, and highlighting. In the randomized user study of 24 medical experts, the search speed of EEEvis was not inferior to PubMed in the time to reach the first article (median difference 3 sec, 95% CI -2.1 to 8.5, P = 0.535) nor in the search completion time (median difference 8 sec, 95% CI -4.7 to 19.1, P = 0.771). However, 22 participants (91.7%) responded that they are willing to use EEEvis as their first choice for a biomedical literature search task, and 21 participants (87.5%) answered the bibliographic sorting and filtering functionalities of EEEvis as a major advantage. EEEvis could be a supplementary interface for PubMed that can enhance the user experience in the search for biomedical literature.

IntroductionFOLFIRINOX (the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is the preferred systemic regimen for locally advanced pancreatic cancer (LAPC). Furthermore, stereotactic body radiation therapy (SBRT) is a promising treatment option for achieving local control in these patients. However, clinical outcomes in patients with LAPC treated using FOLFIRINOX followed by SBRT have not been clarified. Therefore, we aimed to evaluate clinical outcomes of induction FOLFIRINOX treatment followed by SBRT in patients with LAPC.MethodsTo this end, we retrospectively reviewed the medical records of patients with LAPC treated with induction FOLFIRINOX followed by SBRT in a single tertiary hospital. We evaluated overall survival (OS), progression-free survival (PFS), resection rate, SBRT-related adverse events, and prognostic factors affecting survival.ResultsFifty patients were treated with induction FOLFIRINOX for a median of 8 cycles (range: 3–28), which was followed by SBRT. The median OS and PFS were 26.4 (95% confidence interval [CI]: 22.4–30.3) and 16.7 months (95% CI: 13.0–20.3), respectively. Nine patients underwent conversion surgery (eight achieved R0) and showed better OS than those who did not (not reached vs. 24.1 months, p = 0.022). During a follow-up period of 23.6 months, three cases of grade 3 gastrointestinal bleeding at the pseudoaneurysm site were noted, which were managed successfully. Analysis of the factors affecting clinical outcomes revealed that a high radiation dose (≥ 35 Gy) resulted in a higher rate of conversion surgery (25% [8/32] vs. 5.6% [1/18], respectively) and was an independent favorable prognostic factor for OS in the adjusted analysis (hazard ratio: 2.024, 95% CI: 1.042–3.930, p = 0.037).ConclusionOur findings suggest that induction FOLFIRINOX followed by SBRT in patients with LAPC results in better survival with manageable toxicities. A high total SBRT dose was associated with a high rate of conversion surgery and could afford better survival.

This study aimed to compare clinical characteristics and outcomes in patients with native joint septic arthritis (NJSA) due to methicillin-resistant Staphylococcus aureus (MRSA) in comparison to methicillin-sensitive S. aureus (MSSA) and identify treatment failure risk factors. We conducted a multi-center retrospective study on adult NJSA patients at three teaching hospitals in South Korea from 2005 to 2017. Among 101 patients diagnosed with S. aureus NJSA, 39 (38.6%) had MRSA strains. Compared to MSSA, patients with MRSA had a higher prevalence of nosocomial infections (17.9% vs. 1.6%; p = 0.005) and received inappropriate antibiotics within 48 h more frequently (74.4% vs. 0%; p < 0.001). In total, twenty patients (19.8%) experienced treatment failure, which encompassed five patients (5.0%) who passed away, nine (8.9%) requiring repeated surgical drainage after 30 days of antibiotic therapy, and seven (6.9%) with relapse. The MRSA group showed a higher rate of overall treatment failure (33.3% vs. 11.3%; p = 0.007) with a notably increased frequency of requiring repeated surgical interventions after 30 days of antibiotic therapy (17.9% vs. 3.2%, p = 0.026), in contrast to the MSSA group. Independent risk factors for treatment failure included Charlson comorbidity score, elevated CRP levels, and methicillin resistance. Methicillin resistance is an independent risk factor for treatment failure, emphasizing the need for vigilant monitoring and targeted interventions in MRSA-related NJSA cases.

Extra-ovarian sex cord-stromal tumors are often clinically and radiologically considered as ovarian malignancies. Pathologically, this poses a diagnostic challenge. Here, we present a case of extra-ovarian cellular fibroma in an eighty-four-year-old woman. The pedunculated solid mass was located in the posterior cul-de-sac, and intraoperative frozen section diagnosis was leiomyoma or fibroma. Both ovaries and salpinges were normal. A laparoscopy-assisted mass excision and bilateral salpingo-oophorectomy were performed. Microscopically, cellularity showed increased alternative pattern, mild cytological atypia, and the mitotic count was 2/10 high-power fields. Tumor cells were immunoreactive to antibodies produced against Wilms tumor-1 and progesterone receptors. The cells were weakly positive for inhibin-alpha and smooth muscle actin. The pathological diagnosis was an extra-ovarian cellular fibroma. We summarized the cases of extra-ovarian pure stromal tumors reported to date and compared them with our case. Immunohistochemical studies are essential because the pathological differential diagnosis of extra-ovarian fibromas includes extra-gastrointestinal stromal tumors and leiomyomas. Cellular fibromas should be carefully diagnosed due to their tendency to recur.

Clinical trials are complicated, time-consuming and costly. From the initial screening, informed consent and recruitment of the participants’ to study completion, the sponsor must undertake a wide array of complex and closely monitored operations, complying with international standards for human subject research and local requirements. Conducting these studies in an underdeveloped country, with limited resources, infrastructure, and experience with regulated clinical trials adds to this complexity. The initial site selection, set up and preparatory activities for the clinical trial are crucial to minimizing the risks to both participants and to successful completion during the subsequent study execution. In this paper, we describe the experience and lessons learned of building clinical trial site capacity in terms of infrastructure and human resource development for a Phase III vaccine clinical trial. We believe that sharing the experience of setting up a clinical trial in a resource-limited country will enable other entities contemplating clinical research in these countries, to prepare and plan ahead, to minimize the impact of barriers, and to contribute to bringing more studies to the countries where people live with the burden of vaccine-preventable, poverty-associated diseases.

Angelica keiskei Koidzumi (A. keiskei) is used as a traditional medicine, anti-aging agent, and health food, as well as to restore vitality. Xanthoangelol (xanol), a prenylated chalcone, is the predominant constituent of A. keiskei. Oral squamous cell carcinoma (OSCC), the most common malignancy, has a high proliferation rate and frequent metastasis. However, it is unknown whether xanol has anti-OSCC effects on apoptosis, autophagy, and necroptosis. In the present study, we purified xanol from A. keiskei and demonstrated that it suppressed cell proliferation and induced cytotoxicity in human OSCC. Xanol triggered apoptotic cell death by regulating apoptotic machinery molecules but inhibited necroptotic cell death by dephosphorylating the necroptotic machinery molecules RIP1, RIP3, and MLKL in human OSCC. We also found that xanol inhibited the PI3K/AKT/mTOR/p70S6K pathway and induced autophagosome formation by enhancing beclin-1 and LC3 expression levels and reducing p62 expression levels. Furthermore, we showed that xanol prevented the metastatic phenotypes of human OSCC by inhibiting migration and invasion via the reduction of MMP13 and VEGF. Finally, we demonstrated that xanol exerted anticancer effects on tumorigenicity associated with its transformed properties. Taken together, these findings demonstrate the anticancer effects and biological mechanism of action of xanol as an effective phytomedicine for human OSCC.

Abstract Background Bladder cancer (BC) is one of the most common malignancies of the urinary tract. The role of transient receptor potential melastatin 7 (TRPM7) in BC remains unclear. The aim of this study was to investigate the function and signal transduction pathway of TRPM7 in BC. Methods T24 and UMUC3 cells were used to evaluate the molecular mechanism of TRPM7 by immunoblot analysis. Small interfering RNA was used to knockdown TRPM7, and the effect of silencing TRPM7 was studied by wound healing, migration, and invasion assays in T24 and UMUC3 cells. Xenograft model study was obtained to analyze the effect of TRPM7 inhibition in vivo. Results Silencing of TRPM7 decreased the migration and invasion ability of T24 and UMUC3 cells. The phosphorylation of Src, Akt, and JNK (c-Jun N-terminal kinase) was also suppressed by TRPM7 silencing. Src, Akt, and JNK inhibitors effectively inhibited the migration and invasion of T24 and UMUC3 cells. In addition, the TRPM7 inhibitor, carvacrol, limited the tumor size in a xenograft model. Conclusion Our data reveal that TRPM7 regulates the migration and invasion of T24 and UMUC3 cells via the Src, Akt, and JNK signaling pathway. Therefore, TRPM7 suppression could be a potential treatment for BC patients.

ObjectiveTo evaluate the effect of intensive care unit (ICU) visit on the incidence of delirium, delirium subtype, and anxiety level in ICU patients.MethodsTrained psychiatrists and nurses evaluated ICU patients for delirium, delirium subtypes, and anxiety. Propensity score matching (PSM) was used to retrospectively analyze the data. Then, we compared the differences in the incidence of delirium, delirium subtypes, and anxiety level before and after the ICU visit ban. Logistic regression was conducted to identify the risk factors for delirium subtypes and high anxiety levels.ResultsAfter PSM, there was no statistically significant difference in the incidence of delirium between the non-visiting and restrictive visiting groups (non-visiting 27.4% versus restrictive visiting 30.9%, p = 0.162). The proportion of hyperactive and mixed subtypes was higher in the non-visiting than in the restrictive visiting group (non-visiting 35.3 and 30.1% versus restrictive visiting 27.7 and 20.1%, p = 0.002). The anxiety level was higher in the non-visiting than in the restrictive visiting group (state-trait anxiety inventory score: non-visiting 53.46 ± 4.58 versus restrictive visiting 52.22 ± 6.50, p = 0.009). Patients who stayed in the ICU during the visit ban were more likely to have hyperactive (p = 0.005) and mixed subtype (p = 0.001) than those who did not. Moreover, patients who stayed in the ICU during the visit ban were more likely to experience high anxiety levels than those who did not (p < 0.001).ConclusionProhibition of ICU visits during COVID-19 pandemic did not affect the incidence of delirium during COVID-19 but could change the delirium subtype and raise anxiety level. Moreover, visiting prohibition was a risk factor for non-hypoactive delirium subtype and high anxiety levels. Therefore, ICU visits are important in dealing with delirium subtypes and anxiety in ICU patients.

The prediction of tidal waves is essential for improving not only our understanding of the hydrological cycle at the boundary between the land and ocean but also energy production in coastal areas. As tidal waves are affected by various factors, such as astronomical, meteorological, and hydrological effects, the prediction of tidal waves in estuaries remains uncertain. In this study, we present a novel method that can be used to improve short-term tidal wave prediction using a fixed-lag smoother based on sequential data assimilation (DA). The proposed method was implemented for tidal wave predictions of the estuary of the Nakdong River. As a result, the prediction accuracy was improved by 63.9% through DA and calibration using regression. Although the accuracy of the DA diminished with the increasing forecast lead times, the 1 h lead forecast based on DA still showed a 44.4% improvement compared to the open loop without DA. Moreover, the optimal conditions for the fixed-lag smoother were analyzed in terms of the order of the smoothing function and the length of the assimilation window and forecast leads time. It was suggested that the optimal DA configuration could be obtained with the 8th-order polynomial as the smoothing function using past and future DA assimilation windows assimilated 6 h or longer.

Gentianae Scabrae Radix is used in traditional medicine and is known to possess bioactive compounds, including secoiridoid glycosides, flavonoids, lignans, and triterpenes. Trifloroside (TriFs) is a secoiridoid glycoside known for its antioxidant activity; however, its other effects have not been studied. In the present study, we investigated the biological effects of TriFs isolated from the roots of Gentianae Scabrae Radix using pre-osteoblast MC3T3E-1 cells. No cellular toxicity was observed with 1 μM TriFs, whereas 5–100 μM TriFs showed a gradual increase in cell viability. Alkaline phosphatase staining and microscopic observations revealed that 1–10 μM TriFs stimulated osteogenic activity during early osteoblast differentiation. Trifloroside also increased mineral apposition during osteoblast maturation. Biochemical analyses revealed that TriFs promoted nuclear RUNX2 expression and localization by stimulating the major osteogenic BMP2-Smad1/5/8-RUNX2 pathway. Trifloroside also increased p-GSK3β, β-catenin, p-JNK, and p-p38, but not Wnt3a, p-AKT, and p-ERK. Moreover, TriFs increased the MMP13 levels and promoted cell migration and adhesion. In contrast, TriFs-induced osteoblast differentiation and maturation had negligible effects on autophagy and necrosis. Our findings suggest that TriFs induces osteogenic effects through differentiation, adhesion, migration, and mineral apposition. Therefore, TriFs is suggested as a potential drug target in osteoblast-mediated bone diseases.

The transformation between hexavalent chromium (Cr6+) and trivalent chromium (Cr3+) has a significant impact on ecosystems, as Cr6+ has higher levels of toxicity than Cr3+. In this regard, a variety of Cr6+ reduction processes occurring in natural environments have been studied extensively. In this work, we investigate the reductive transformation of Cr6+ by ferrous ions (Fe2+) in ice at −20 °C, and compare the same process in water at 25 °C. The Fe2+-mediated reduction of Cr6+ occurred much faster in ice than it did in water. The accelerated reduction of Cr6+ in ice is primarily ascribed to the accumulation of Cr6+, Fe2+, and protons in the grain boundaries formed during freezing, which constitutes favorable conditions for redox reactions between Cr6+ and Fe2+. This freeze concentration phenomenon was verified using UV–visible spectroscopy with o-cresolsulfonephthalein (as a pH indicator) and confocal Raman spectroscopy. The reductive transformation of Cr6+ (20 µM) by Fe2+ in ice proceeded rapidly under various Fe2+ concentrations (20–140 µM), pH values (2.0–5.0), and freezing temperatures (–10 to −30 °C) with a constant molar ratio of oxidized Fe2+ to reduced Cr6+ (3:1). This result implies that the proposed mechanism (i.e., the redox reaction between Cr6+ and Fe2+ in ice) can significantly contribute to the natural conversion of Cr6+ in cold regions. The Fe2+-mediated Cr6+ reduction kinetics in frozen Cr6+-contaminated wastewater was similar to that in frozen Cr6+ solution. This indicates that the variety of substrates typically present in electroplating wastewater have a negligible effect on the redox reaction between Cr6+ and Fe2+ in ice; it also proposes that the Fe2+/freezing process can be used for the treatment of Cr6+-contaminated wastewater.

Background: While the incidence of patients with atopic dermatitis (AD) with atopic march (AM) showing respiratory allergy is steadily rising, the pathomechanism is still unknown. There are currently no biomarkers to predict progression of AM. Methods: To explore the mechanism of AM, patients with AD and AM and healthy controls were recruited and RNA microarray, flow cytometry, quantitative real-time polymerase chain reaction, and immunofluorescence staining were performed. We also co-cultured dendritic cells and CD4+ T cells with various Dermatophagoides farinae allergen fractions. Cytokine levels were evaluated using enzyme-linked immunosorbent assay. Findings: Both fatty-acid-binding protein 5 (FABP5) and Th17-related genes were more highly expressed in AM. FABP5 knockdown significantly decreased Th17-inducing cytokines in keratinocytes and IL-17A in T cells from AM patients. Further confirmation was obtained using an AM mice model compared to mice without AM. Der f 1, a major D. farinae allergen, increased FABP5 and IL-17A expression in T cells from AM patients. Higher serum FABP5 levels from AM patients were positively correlated with serum IL-17A levels. Interpretation: FABP5 expression, possibly enhanced by higher epicutaneous and respiratory sensitization to Der f 1, may directly promote Th17 responses in AD patients with AM. Thus, AM progression can be explained by Th17 reaction induced by FABP5. FABP5 was identified as a potential biomarker in AM. Funding: This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT; No. NRF-2017R1A2B4009568), grants of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, and the Republic of Korea (HI13C0010, HI14C1324, HI14C1799).

Background: Testicular torsion is a urologic emergency that can lead to testicular atrophy and infertility owing to ischemia-reperfusion injury (IRI). The aim of this study was to evaluate the long-term protective effect of tadalafil, a phosphodiesterase-5 inhibitor used to treat erectile dysfunction, on spermatogenesis in a rat testicular model of IRI. Methods: Forty-eight adolescent Sprague–Dawley rats were divided into six groups of 8 each (A–F). Sham operation was performed on group A. Group B underwent surgical 720∘ torsion of the left testis without any medication. Groups C, D, E and F underwent surgical torsion and administration of tadalafil at varying doses (0.3 and 1.0 mg/kg) and durations (single or daily administration for four weeks). After three hours of torsion, detorsion was performed on all groups except group A. Four weeks after the operation, both testes were evaluated for spermatogenesis using the Johnsen scoring system. To evaluate the protective effect of tadalafil against oxidative stress induced by IRI, the malondialdehyde and superoxide dismutase levels of both testes were analyzed four hours after detorsion using the same experimental protocol as for groups A, B, and C. Results: Experimental groups treated with high-dose tadalafil showed higher Johnsen scores for spermatogenesis than the low-dose groups. Groups that received daily tadalafil administration for four weeks showed higher Johnsen scores than those receiving single doses. Furthermore, histopathologic findings and molecular markers related to oxidative stress were markedly improved following tadalafil administration. Conclusions: Tadalafil alleviated the oxidative stress and long-term deterioration of spermatogenesis in a rat testicular model of IRI by restoring the antioxidant status.

Mirror image artifact in ultrasound is not an unusual phenomenon. However, it is rarely seen in thyroid ultrasound because of the natural convexity of the tracheal surface. We report a mirror artifact during thyroid ultrasound in a patient with an excessively collapsible trachea. Minor pressure with the transducer made the trachea surface flat or concave, and then a cyst in the thyroid was mirrored across the trachea, which mimicked an intratracheal cyst. This case illustrates how an unusual collapsible trachea can generate an image that simulates an intratracheal lesion during thyroid ultrasound. Keywords: Ultrasonography, Thyroid gland, Thyroid nodule, Artifacts

Incremental learning is a methodology that continuously uses the sequential input data to extend the existing network’s knowledge. The layer sharing algorithm is one of the representative methods which leverages general knowledge by sharing some initial layers of the existing network. To determine the performance of the incremental network, it is critical to estimate how much the initial convolutional layers in the existing network can be shared as the fixed feature extractors. However, the existing algorithm selects the sharing configuration through improper optimization strategy but a brute force manner such as searching for all possible sharing layers case. This is a non-convex and non-differential problem. Accordingly, this can not be solved using powerful optimization techniques such as the gradient descent algorithm or other convex optimization problem, and it leads to high computational complexity. To solve this problem, we firstly define this as a discrete combinatorial optimization problem, and propose a novel efficient incremental learning algorithm-based Bayesian optimization, which guarantees the global convergence in a non-convex and non-differential optimization. Additionally, our proposed algorithm can adaptively find the optimal number of sharing layers via adjusting the threshold accuracy parameter in the proposed loss function. With the proposed method, the global optimal sharing layer can be found in only six or eight iterations without searching for all possible layer cases. Hence, the proposed method can find the global optimal sharing layers by utilizing Bayesian optimization, which achieves both high combined accuracy and low computational complexity.

Fibroadenoma is a common, benign tumor of the breast, which is rarely associated with an increased risk of carcinoma. We report a case of ductal carcinoma in situ within a fibroadenoma in a 38-year-old woman. The lesion was a 1 cm, circumscribed, ovoid mass with internal calcifications evident on mammography and ultrasound, which is commonly found in fibroadenoma, but the calcifications were fine and linear, which is uncommon. This type of calcification is classified as suspicious by the American College of Radiology Breast Imaging-Reporting And Data System, and it is often correlated with comedo necrosis of ductal carcinoma, and, so, requires immediate pathologic confirmation. In our case, careful analysis of the unusual calcifications led to appropriate intervention and diagnosis. Radiologists should be aware that fibroadenomas can be malignant, and they should look for suspicious microcalcifications within a fibroadenoma.

Atypical adenomatous hyperplasia is a premalignant lesion reflecting a focal proliferation of atypical cells. These lesions are usually observed as incidental findings in lungs that have been resected due to other conditions, such as lung cancer. We report the youngest case of atypical adenomatous hyperplasia on record in a 12-year-old girl. In this patient, the lesion was found in association with pneumothorax.

Castleman's disease (CD) is an uncommon benign lymphoproliferative disorder which most commonly involves the mediastinum but rarely affects the pleura. We report a case of unicentric CD that presents as a pleural mass in a 45-year-old man, which was subsequently resected followed by an unexpected diagnosis on histologic examination. Although rare, CD should be included in the differential diagnosis of well-enhancing pleural mass.

Fungal communities in the rhizoplane (RP) and rhizosphere (RS) of geographically isolated C. takesimana habitats in different environments such as oceanic (Seodo, the Dokdo Islands), coastline (Sadong, Ulleungdo Island), and inland (Taeha, Ulleungdo Island) regions were analyzed by MiSeq sequencing. In total, 1279 operational taxonomic units (OTUs) were obtained and they were further classified into 185 genera belonging to five phyla. The total number of fungal taxa in the RP samples was lower than those in the RS samples in all the sampled locations, providing an indication of the existence of a certain level of the selective pressures from the host plant. The richness of the RP in the Dokdo Islands was higher than that of Ulleungdo Island, but the richness of the RS in the Dokdo Islands was lower than that of Ulleungdo Island. These results suggest evidence for strong effects of a harsh geo-climate on the RP and RS fungal diversities in the Dokdo Islands. Additionally, a total of 82 fungal genera were identified in all three RP samples and 63 genera (77%) were uniquely found in each of the geographical regions and 43 genera (52.4%) showed high dependency on the C. takesimana vegetation. It was found that the genus Mortierella was the most dominant taxon in all the samples. The geo-ecological isolation of the Korean bellflower may have caused unique formation of the RP and RS fungal communities in the natural habitats.

Noroviruses are the leading cause of acute gastroenteritis and food poisoning worldwide. In this study, we investigated the anti-noroviral activity of Lindera obtusiloba leaf extract (LOLE) using murine norovirus (MNV-1), a surrogate of human norovirus. Preincubation of MNV-1 with LOLE at 4, 8, or 12 mg/mL for 1 h at 25 °C significantly reduced viral infectivity, by 51.8%, 64.1%, and 71.2%, respectively. Among LOLE single compounds, β-pinene (49.7%), α-phellandrene (26.2%), and (+)-limonene (17.0%) demonstrated significant inhibitory effects on viral infectivity after pretreatment with MNV-1, suggesting that the anti-noroviral effects of LOLE may be due to the synergetic activity of several compounds, with β-pinene as a key molecule. The inhibitory effect of LOLE was tested on the edible surfaces of lettuce, cabbage, and oysters, as well as on stainless steel. After one hour of incubation at 25°C, LOLE (12 mg/mL) pretreatment significantly reduced MNV-1 plaque formation on lettuce (76.4%), cabbage (60.0%), oyster (38.2%), and stainless-steel (62.8%). These results suggest that LOLE effectively inhibits norovirus on food and metal surfaces. In summary, LOLE, including β-pinene, may inactivate norovirus and could be used as a natural agent promoting food safety and hygiene.

To explore the most desirable pathway for a successful local energy transition, a fuzzy-set qualitative comparative analysis was conducted on 16 regional cases in South Korea. We developed four propositions based on previous studies and theories as a causal set. Based on the South Korean context, we selected the solar photovoltaic (PV) generation and solar PV expansion rate as barometers for measuring the success of a local energy transition. Our analysis highlights the importance of the International Council for Local Environmental Initiatives (ICLEI) membership (network), local legislation, and the environmental surveillance of locally-based non-governmental organizations (NGOs). The implications of this study will provide insights for developing or newly industrialized countries where an energy transition is underway.

Effects of chromium and manganese as alloying elements on corrosion resistance of carbon steel were examined using evaluation of corrosion resistance in 60°C NaCl solution with a weight loss test, polarization test, analysis of rust with X-ray diffractometer, Raman spectroscopy, transmission electron microscopy, energy dispersive spectroscopy, and electron energy loss spectroscopy. The weight loss behavior conformed to a typical parabolic law, and the oxidation state of iron in rust was higher along the fast pathway but was disproportionate to the distance from the alloy/AR interface. It suggests that the corrosion process of the alloys was controlled by transport of oxygen to the rust layer. The improvements in corrosion resistance of 18Mn and 18Mn5Cr resulted from both the refinement of grain in adherent rust (AR) and the increase of the amounts of goethite in nonadherent rust (NAR) by chromium and manganese. Especially, the effectiveness of chromium on corrosion resistance was also related to the refinements of grain in AR and the amounts of goethite in NAR. The Tafel extrapolation method was inadequate to measure the instantaneous corrosion rate of steels with various alloying elements and immersion periods because of the difference in electrochemical reduction rates of rust, depending on its constituent.

Purpose: This study aimed to evaluate the macroscopic and microscopic peritoneal findings after intraperitoneal injection of alcohol in rats. Methods: From January to February 2012, 20 male rats were used in this study: 15 rats received intraperitoneal injection of 0.1 mL 99.9% alcohol (group 1: experiment group) and 5 rats received intraperitoneal injection of 0.1 mL normal saline (group 2: control group). Animals from each group were sacrificed the day after alcohol injection and each week thereafter. Macroscopic and microscopic examinations of the peritonea and abdominal cavity were performed in each rat. Results: There was no significant peritoneal abnormality on macroscopic view, except for a whitish-colored parietal peritoneum around the injection site in 3 animals from group 1. In all but 1 of the animals in group 1, mild to moderate peritoneal inflammation or fibrosis was observed 1 and 2 weeks after alcohol injection. However, the peritoneal abnormality of alcohol injection had dissipated by week 3. Peritoneal abnormalities were not observed in group 2. Conclusion: An intraperitoneal injection of alcohol in rats caused peritoneal inflammation or fibrosis during the first 2 weeks. However, these peritoneal abnormalities were short-lived and had completely disappeared after 3 weeks.

Children with complex chronic conditions (CCC) are presumed to be vulnerable to adverse drug reactions (ADRs). The clinical profiles of ADRs in CCC are not well known. Herein, we aim to describe the ADR profiles in CCC with regard to typical presentations and vulnerable groups. We accessed the ADR yearly reports at a tertiary children's hospital whose practice is mainly dedicated to CCC and descriptively analyzed their clinical profiles according to the presence of a complex chronic condition, ADR severity, and age groups. A total of 1841 cases were analyzed, among which 1258 (68.3%) were mild, 493 (26.8%) moderate, and 90 (4.9%) cases were severe. A total of 1581 (85.9%) cases of complex chronic condition were reported. The proportion of CCC in each severity group increased as the ADR becomes more severe. In CCC, ADRs were most frequently reported by nurses in the adolescent group and in cases where the symptoms involved the gastrointestinal system. The class of antineoplastic and immunomodulating drugs was the most commonly suspected of causing an ADR, followed by one of the antibiotics. When we focus on the trend across the age groups, the ratio of severe-to-total ADRs decreased with older age. Among severe cases, the ratio of off-label prescription-related cases was the highest in the infant/toddler group and decreased as the groups aged. In conclusion, ADRs of CCCs admitted to a tertiary children's hospital have a unique profile. These groups are vulnerable to ADRs and thus they should be monitored closely, especially when they are infants or toddlers, so that severe ADRs can be identified and treated immediately.

Airway inflammatory diseases, such as asthma, are a global public health concern owing to their chronic inflammatory effects on the respiratory mucosa. Molecular hydrogen (H2) has recently been recognized for its antioxidant and anti-inflammatory properties. In this study, we examined the therapeutic potential of H2 in airway inflammation using an ovalbumin (OVA)-induced BALB/c mouse model of allergic asthma. Female BALB/c mice were sensitized and challenged with OVA to induce airway inflammation, and 30 mice were randomly divided into five groups: NT (non-treatment), HTC (3% H2 treatment only), NC (negative control, OVA only), PC (positive control, OVA + intranasal 1 mg/mL salbutamol 50 μL), and HT (H2 treatment, OVA + inhaled 3% H2). Various inflammatory and oxidative stress (OS)-induced markers such as white blood cells (WBCs) and their differential counts, lung histology, cytokine levels such as interleukin (IL)-4, (IL)-5, (IL)-13, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), (IL)-10, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT), and total immunoglobulin E (IgE) levels were investigated. Our results showed that inhaled H2 significantly reduced inflammatory cell infiltration, OS markers, and pro-inflammatory cytokine expression while upregulating antioxidant enzyme activity. Furthermore, H2 also significantly decreased serum IgE levels, a marker of allergic inflammation. Collectively, our findings suggest that H2 inhalation is a promising treatment option for airway inflammation, offering a novel approach with potential clinical applications. [ABSTRACT FROM AUTHOR]