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Objectives This study aimed to evaluate the importance and performance of sodium reduction practices among childcare center cooks in the Yongin area before and after a 3-month salinometer support program. Methods In total, 313 cooks employed in childcare centers in Yongin were surveyed before and after participating in a salinometer support program. The survey included questions on general information, sodium-related dietary habits, and perceived importance and performance levels of sodium reduction approaches in the purchasing, cooking, and serving areas. The centers were divided into childcare centers registered as group-feeding facilities (FS group, n = 68) and those not registered as such (non-FS group, n = 245). The differences between the two groups were analyzed. Results The overall importance levels increased significantly after the program in both the FS-group (P < 0.001) and non-FS group (P = 0.005). The overall performance levels also increased significantly in both groups (P < 0.001 for all). Consequently, the significant difference between the importance and performance levels disappeared in both groups after the program. However, unlike the FS group, which showed no significant differences between the importance and performance levels after the program in all three areas, the non-FS group still demonstrated lower performance levels than importance levels in the purchasing (P = 0.011) and serving (P = 0.034) areas after the program. Conclusions The use of salinometers significantly enhanced the performance and importance of low-sodium management practices among cooks in childcare centers, especially in the FS group. The continuous monitoring of salinity measurements and tailored education specialized for the FS and non-FS groups are recommended.

Abstract Synthetic aperture radar (SAR) utilizes an aircraft-carried antenna to emit electromagnetic pulses and detect the returning echoes. As the aircraft travels across a designated area, it synthesizes a large virtual aperture to improve image resolution. Inspired by SAR, we introduce synthetic aperture ptycho-endoscopy (SAPE) for micro-endoscopic imaging beyond the diffraction limit. SAPE operates by hand-holding a lensless fiber bundle tip to record coherent diffraction patterns from specimens. The fiber cores at the distal tip modulate the diffracted wavefield within a confined area, emulating the role of the ‘airborne antenna’ in SAR. The handheld operation introduces positional shifts to the tip, analogous to the aircraft’s movement. These shifts facilitate the acquisition of a ptychogram and synthesize a large virtual aperture extending beyond the bundle’s physical limit. We mitigate the influences of hand motion and fiber bending through a low-rank spatiotemporal decomposition of the bundle’s modulation profile. Our tests demonstrate the ability to resolve a 548-nm linewidth on a resolution target. The achieved space-bandwidth product is ~1.1 million effective pixels, representing a 36-fold increase compared to that of the original fiber bundle. Furthermore, SAPE’s refocusing capability enables imaging over an extended depth of field exceeding 2 cm. The aperture synthesizing process in SAPE surpasses the diffraction limit set by the probe’s maximum collection angle, opening new opportunities for both fiber-based and distal-chip endoscopy in applications such as medical diagnostics and industrial inspection.

Abstract Background The association between antihypertensive medication and schizophrenia has received increasing attention; however, evidence of the impact of antihypertensive medication on subsequent schizophrenia based on large-scale observational studies is limited. We aimed to compare the schizophrenia risk in large claims-based US and Korea cohort of patients with hypertension using angiotensin-converting enzyme (ACE) inhibitors versus those using angiotensin receptor blockers (ARBs) or thiazide diuretics. Methods Adults aged 18 years who were newly diagnosed with hypertension and received ACE inhibitors, ARBs, or thiazide diuretics as first-line antihypertensive medications were included. The study population was sub-grouped based on age (> 45 years). The comparison groups were matched using a large-scale propensity score (PS)-matching algorithm. The primary endpoint was incidence of schizophrenia. Results 5,907,522; 2,923,423; and 1,971,549 patients used ACE inhibitors, ARBs, and thiazide diuretics, respectively. After PS matching, the risk of schizophrenia was not significantly different among the groups (ACE inhibitor vs. ARB: summary hazard ratio [HR] 1.15 [95% confidence interval, CI, 0.99–1.33]; ACE inhibitor vs. thiazide diuretics: summary HR 0.91 [95% CI, 0.78–1.07]). In the older subgroup, there was no significant difference between ACE inhibitors and thiazide diuretics (summary HR, 0.91 [95% CI, 0.71–1.16]). The risk for schizophrenia was significantly higher in the ACE inhibitor group than in the ARB group (summary HR, 1.23 [95% CI, 1.05–1.43]). Conclusions The risk of schizophrenia was not significantly different between the ACE inhibitor vs. ARB and ACE inhibitor vs. thiazide diuretic groups. Further investigations are needed to determine the risk of schizophrenia associated with antihypertensive drugs, especially in people aged > 45 years.

Background: Regular physical activities reduce the growth of breast cancer, but research on the effects of steady exercise on metastasis and its mechanisms is limited. In this study, the effects of steady exercise on breast cancer metastasis and its possible mechanism were demonstrated. Methods: Experimental metastasis was induced after 8 weeks of steady exercise using a mouse model. Furthermore, one of the myokines, irisin, was studied to elucidate the effects of metastasis-regulating protein expression, and colony and sphere formation, which are cancer stem cell properties. Results: Low- and moderate-intensity exercise significantly reduced the number and volume of metastasized tumors. Among myokines, only irisin was significantly increased by steady exercise but decreased by a high-fat diet. In vitro studies, irisin significantly decreased the number of colonies and sphere formation. Irisin also inhibited cell migration and invasion and suppressed the malignancy of breast cancer cells by reducing the expression of vimentin, MMP-2, MMP-9, and HIF-1 and by increasing the expression of TIMP-1 and TIMP-2. Conclusion: Steady exercise modulates myokine secretions and among them, irisin suppresses breast cancer metastasis by decreasing self-renewal properties and invasion regulating protein expressions. Thus, regular exercise may be beneficial in the prevention of breast tumor metastasis.

Abstract High-rate production of multicarbon chemicals via the electrochemical CO2 reduction can be achieved by efficient CO2 mass transport. A key challenge for C−C coupling in high-current-density CO2 reduction is how to promote *CO formation and dimerization. Here, we report molecularly enhanced CO2-to-*CO conversion and *CO dimerization for high-rate ethylene production. Nanoconfinement of ascorbic acid by graphene quantum dots enables immobilization and redox reversibility of ascorbic acid in heterogeneous electrocatalysts. Cu nanowire with ascorbic acid nanoconfined by graphene quantum dots (cAA-CuNW) demonstrates high-rate ethylene production with a Faradaic efficiency of 60.7% and a partial current density of 539 mA/cm2, a 2.9-fold improvement over that of pristine CuNW. Furthermore, under low CO2 ratio of 33%, cAA-CuNW still exhibits efficient ethylene production with a Faradaic efficiency of 41.8%. We find that cAA-CuNW increases *CO coverage and optimizes the *CO binding mode ensemble between atop and bridge for efficient C−C coupling. A mechanistic study reveals that ascorbic acid can facilitate *CO formation and dimerization by favorable electron and proton transfer with strong hydrogen bonding.

Fonts are a critical element that determines the perception of any medium. To ensure consistent and culturally appropriate font selection across diverse language groups, a multilingual font matching system is currently in development. This research focuses on leveraging the latest advancements in machine learning and computer vision to deeply understand font characteristics and enhance the accuracy of multilingual font matching. Utilizing the ‘stroke elements’ of fonts is crucial for this matching, building upon the successful development of a method to calculate similarity between Korean fonts in previous studies. We have applied this approach to the English alphabet, defining distinctive ‘stroke elements’ and developing a deep learning model for their automatic extraction. Additionally, we evaluate the performance of this stroke element extraction model and discuss strategies to further improve extraction accuracy. This groundwork establishes the basis for multilingual font matching and enables the recommendation of similar fonts using the ‘stroke elements’ of the English alphabet.

Objectives The objective of this study is to evaluate the feasibility of sustainable operation in a conventional full-scale slow sand filter process. Methods A slow sand filtration process was operated in small scale water treatment plants for valley water. The water quality such as particle matter, dissolved organic matter, the number of bacteria, and disinfection by-product (DBP) were monitored at four designated points once a week and was compared during summer (July-August) and winter season (December-January). Results and Discussion Although the number of particle matter in summer was higher than in winter by 39% (2.91×104 /mL), particle matter in slow sand filter process was removed by 99% regardless of season (temperature). The removal efficiency of dissolved organic carbon (DOC) and UV254 was higher in summer than in winter by 15% and 21%, respectively. In addition, concerning the organic fraction, higher molecular weight led to higher removal efficiency in the following sequence: BP (biopolymer, MW: 20,000 g/mol) > HS(humic substances, MW : 1,000~20,000 g/mol) > BB(building blocks, MW : 300~500 g/mol) > LMWs(low molecular weights, MW : 350 g/mol. The concentration of trihalomethanes (THMs) and haloacetic acids (HAAs), indicator of DBP, were detected at 12.2 and 9.4 μg/L in summer and 8.1 and 6.3 μg/L in winter, respectively, which would be considered very low concentration related to the drinking water regulation of 100 μg/L. Finally, the active bacteria was removed up to 93 and 92% in summer and winter, respectively. Conclusion The feasibility of a slow filtration process was evaluated to compare particle and dissolved matter in summer and winter operation. Despite a 39% increase in particle matter in summer, the removal efficiency was maintained at 98% in summer and winter. Due to the increased activation of biofilm in summer, the removal of DOC and UV254 was higher in summer than winter by 15 and 21%, respectively. The significant low concentration of THMs and HAAs, regardless of season, would be negligible. In addition, achieving over 92% removal of activated bacteria secured the biological safety. These stable operations ensure that slow filtration process is effective in controlling of water quality.

Abstract Transparent and FAIR disclosure of meta-information about healthcare data and infrastructure is essential but has not been well publicized. In this paper, we provide a transparent disclosure of the process of standardizing a common data model and developing a national data infrastructure using national claims data. We established an Observational Medical Outcome Partnership (OMOP) common data model database for national claims data of the Health Insurance Review and Assessment Service of South Korea. To introduce a data openness policy, we built a distributed data analysis environment and released metadata based on the FAIR principle. A total of 10,098,730,241 claims and 56,579,726 patients’ data were converted as OMOP common data model. We also built an analytics environment for distributed research and made the metadata publicly available. Disclosure of this infrastructure to researchers will help to eliminate information inequality and contribute to the generation of high-quality medical evidence.

Abstract Both the uterus and breasts have sex hormone dependence, yet there are few studies on the association between breast disease and uterine fibroids (UFs). The purpose of this study was to investigate the incidence of benign breast disease (BBD), carcinoma in situ (CIS), and breast cancer (BC) in women treated for UFs compared to women who were not treated for UFs. This retrospective cohort study used national health insurance data from January 1st, 2011, to December 31st, 2020. We selected women between 20 and 50 years old who (1) were treated for UFs (UF group) or (2) visited medical institutions for personal health screening tests without UFs (control group). We analyzed independent variables such as age, socioeconomic status (SES), region, Charlson comorbidity index (CCI), delivery status, menopausal status, menopausal hormone therapy (MHT), endometriosis, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia based on the first date of uterine myomectomy in the UF group and the first visiting date for health screening in the non-UF group. There were 190,583 and 439,940 participants in the UF and control groups, respectively. Compared with those of the control group, the RRs of BBD, CIS, and BC were increased in the UF group. The hazard ratios (HRs) of BBD, CIS, and BC in the UF group were 1.335 (95% confidence interval (CI) 1.299–1.372), 1.796 (95% CI 1.542–2.092), and 1.3 (95% CI 1.198–1.41), respectively. When we analyzed the risk of BC according to age at inclusion, UFs group had the increased risk of BCs in all age groups in comparison with control group. Women with low SES (HR 0.514, 95% CI 0.36–0.734) and living in rural areas (HR 0.889, 95% CI 0.822–0.962) had a lower risk of BC. Our study showed that women with UFs had a higher risk of BBD, CIS, and BC than those without UFs. This result suggests that women with UFs should be more conscious of BC than those without UFs. Therefore, doctors should consider recommending regular breast self-exams, mammography, or ultrasound for the early detection of BC in women with UFs.

Abstract Background Several population-based studies and observational studies have shown that oophorectomy is associated with an increased risk of colorectal cancer (CRC), and hormone replacement therapy has been associated with a reduction in the risk of colorectal cancer. This study was carried out to investigate whether hysterectomy, which may affect the levels of female hormones, is associated with a risk of cancer of the specific gastrointestinal tract. Methods This population-based retrospective cohort study was conducted using insurance data provided by the Health Insurance Review and Assessment Service (HIRA) from January 1, 2007, to December 31, 2020. The hysterectomy group included 40- to 59-year-old women who underwent hysterectomy with uterine leiomyoma or uterine endometriosis from January 1, 2011, to December 31, 2014. The control group included women aged 40 to 59 years who visited medical institutions for medical examination from January 1, 2011 to December 31, 2014. Results The hysterectomy and non-hysterectomhy groups comprised 66,204 and 89,768 subjects, respectively. The median ages in the non-hysterectomy group and hysterectomy group were 48 (range: 43–53) and 46 (range: 44–49) years, respectively. In the unadjusted results of the analysis, all colorectal cancer (CRC) increased in the hysterectomy alone group (HR 1.222, 95% confidence interval (CI) 1.016–1.47, p = 0.033), sigmoid colon cancer increased in the hysterectomy alone group (HR 1.71, 95% CI 1.073–2.724, p = 0.024), and rectal cancer increased in the hysterectomy with adnexal surgery group (HR 1.924, 95% CI 1.073–2.724, p = 0.002). The adjusted results showed that all CRC increased in the hysterectomy alone group (HR 1.406, 95% CI 1.057–1.871, p = 0.019), colon cancer increased in the hysterectomy alone group (HR 1.523, 95% CI 1.068–2.17, p = 0.02), and rectal cancer increased in the hysterectomy with adnexal surgery group (HR 1.933, 95% CI 1.131–3.302, p = 0.016). The all-cause mortality of GI cancer increased in the hysterectomy alone group (HR 3.495, 95% CI 1.347–9.07, p = 0.001). Conclusions This study showed that the risk of all CRC increased in women who underwent hysterectomy compared with women who did not. In particular, the risk of rectal cancer was significantly higher in the women who underwent hysterectomy with adnexal surgery than in the controls. There was no association between hysterectomy and other GI cancers.

ABSTRACTThe objective of this experiment was to select D. hansenii isolates that are stable in dry fermented sausage (DFS) production and can positively affect the quality. D. hansenii isolates were examined for production of biogenic amines, β-glucuronidase, β-glucosidase, proteolytic, and lipolytic enzymatic activities. The acid and salt tolerance of D. hansenii isolates were also examined. DFS inoculated with selected D. hansenii isolates were analyzed for microorganisms, weight loss, Aw, and pH. DFS was also subjected to analyses of color, texture profile, reducing sugar, volatile basic nitrogen (VBN), lipid oxidation, and free fatty acid. Twenty-two D. hansenii isolates were isolated. None of these D. hansenii isolates produced biogenic amines, and all strains were negative for β-glucuronidase and β-glucosidase activities. After examining these strains for proteolysis, lipolysis, and salt and acid tolerance, D. hansenii isolates SMFM2021-C14, SMFM2021-S8, and SMFM2021-SL3 were selected to be used in DFS. During the processing of DFS, the groups treated with D. hansenii isolate SMFM2021-S8 or SMFM2021-SL3 showed lower (p

Computer vehicle simulators are used to model real-world situations to overcome time and cost limitations. The vehicle simulators provide virtual scenarios for real-world driving. Although the existing simulators precisely observe movement on the basis of good-quality graphics, they focus on a few driving vehicles instead of accident simulation. In addition, it is difficult to represent vehicle collisions. We propose a vehicle crash simulator with simulation and animation components. The proposed simulator synthesizes and simulates models of vehicles and environments. The simulator animates corresponding to the simulation through the execution results. The simulation results validate that the proposed simulator provides collision and non-collision results according to the speed of two vehicles at an intersection.

We developed machine learning algorithms for distinguishing scintillation signals from a plastic-liquid coupled detector known as a phoswich. The challenge lies in discriminating signals from organic scintillators with similar shapes and short decay times. Using a single-readout phoswich detector, we successfully identified γ radiation signals from two scintillating components. Our Boosted Decision Tree algorithm demonstrated a maximum discrimination power of 3.02 ± 0.85 standard deviation in the 950 keV region, providing an efficient solution for self-shielding and enhancing radiation detection capabilities.

ABSTRACT The casein kinase 2 (CK2) complex has garnered extensive attention over the past decades as a potential therapeutic target for diverse human diseases, including cancer, diabetes, and obesity, due to its pivotal roles in eukaryotic growth, differentiation, and metabolic homeostasis. While CK2 is also considered a promising antifungal target, its role in fungal pathogens remains unexplored. In this study, we investigated the functions and regulatory mechanisms of the CK2 complex in Cryptococcus neoformans, a major cause of fungal meningitis. The cryptococcal CK2 complex consists of a single catalytic subunit, Cka1, and two regulatory subunits, Ckb1 and Ckb2. Our findings show that Cka1 plays a primary role as a protein kinase, while Ckb1 and Ckb2 have major and minor regulatory functions, respectively, in growth, cell cycle control, morphogenesis, stress response, antifungal drug resistance, and virulence factor production. Interestingly, triple mutants lacking all three subunits (cka1Δ ckb1Δ ckb2Δ) exhibited more severe phenotypic defects than the cka1Δ mutant alone, suggesting that Ckb1/2 may have Cka1-independent functions. In a murine model of systemic cryptococcosis, cka1Δ and cka1Δ ckb1Δ ckb2Δ mutants showed severely reduced virulence. Transcriptomic, proteomic, and phosphoproteomic analyses further revealed that the CK2 complex controls a wide array of effector proteins involved in transcriptional regulation, cell cycle control, nutrient metabolisms, and stress responses. Most notably, CK2 disruption led to dysregulation of key signaling cascades central to C. neoformans pathogenicity, including the Hog1, Mpk1 MAPKs, cAMP/PKA, and calcium/calcineurin signaling pathways. In summary, our study provides novel insights into the multifaceted roles of the fungal CK2 complex and presents a compelling case for targeting it in the development of new antifungal drugs.IMPORTANCEThe casein kinase 2 (CK2) complex, crucial for eukaryotic growth, differentiation, and metabolic regulation, presents a promising therapeutic target for various human diseases, including cancer, diabetes, and obesity. Its potential as an antifungal target is further highlighted in this study, which explores CK2’s functions in C. neoformans, a key fungal meningitis pathogen. The CK2 complex in C. neoformans, comprising the Cka1 catalytic subunit and Ckb1/2 regulatory subunits, is integral to processes like growth, cell cycle, morphogenesis, stress response, drug resistance, and virulence. Our findings of CK2’s role in regulating critical signaling pathways, including Hog1, Mpk1 MAPKs, cAMP/PKA, and calcium/calcineurin, underscore its importance in C. neoformans pathogenicity. This study provides valuable insights into the fungal CK2 complex, reinforcing its potential as a target for novel antifungal drug development and pointing out a promising direction for creating new antifungal agents.

Abstract Accumulating evidence indicates that mitochondria play crucial roles in immunity. However, the role of the mitochondrial Krebs cycle in immunity remains largely unknown, in particular at the organism level. Here we show that mitochondrial aconitase, ACO-2, a Krebs cycle enzyme that catalyzes the conversion of citrate to isocitrate, inhibits immunity against pathogenic bacteria in C. elegans. We find that the genetic inhibition of aco-2 decreases the level of oxaloacetate. This increases the mitochondrial unfolded protein response, subsequently upregulating the transcription factor ATFS-1, which contributes to enhanced immunity against pathogenic bacteria. We show that the genetic inhibition of mammalian ACO2 increases immunity against pathogenic bacteria by modulating the mitochondrial unfolded protein response and oxaloacetate levels in cultured cells. Because mitochondrial aconitase is highly conserved across phyla, a therapeutic strategy targeting ACO2 may eventually help properly control immunity in humans.

Collision tumors of the ovaries are rare, with only a few reports in the literature. Adult granulosa cell tumors are a relatively common primary tumor component of previously reported collision tumors. The combination of serous and mucinous tumors with adult granulosa cell tumors has been reported in several cases. On the other hand, mesonephric-like adenocarcinomas are rare neoplasms that commonly arise in the uterine corpus and ovaries. In this report, we present the case of a collision tumor composed of an adult granulosa cell tumor and mesonephric-like adenocarcinoma of the ovary in a 63-year-old woman. The initial magnetic resonance imaging findings showed a cystic mass with an internal hemorrhage, which suggested an adult granulosa cell tumor, and a solid mass with different enhancements. Microscopically, the tumor had two distinct components: An adult granulosa cell tumor and a mesonephric-like adenocarcinoma. Recognizing collision tumors consisting of slow-growing and aggressive tumors may prove beneficial in future diagnostic and treatment strategies.

Introduction: In 2019, mild vestibular function deficiency in elder populations was defined as presbyvestibulopathy (PVP) by the Classification Committee of the Bárány Society. The diagnostic criteria include tests for low-, mid-, and high-frequency vestibular function, represented by caloric testing, rotary chair testing, and head impulse testing, respectively. However, there is still a lack of large-scale reports supporting the relationship between vestibular function tests (VFTs) and aging. In this study, we evaluated whether each test is correlated with aging in the elderly population aged over 50. Methods: This study retrospectively enrolled 1043 subjects from a single university hospital database after excluding those with unilateral and bilateral vestibulopathy, central dizziness, and acute dizziness. Enrolled subjects had caloric canal paresis 0.6, vHIT interaural difference 50 years old. Results: Significant negative correlations with age were identified in the vHIT (p < 0.001) and rotary chair test (RCT) 1.0 Hz gain (p = 0.030). However, the caloric test (p = 0.739 and 0.745 on the left and right sides, respectively) and RCT 0.12 Hz gain (p = 0.298) did not show a significant correlation with age. A total of 4.83% of subjects aged 70 years or older showed sub-normal vHIT gain that met the criteria of PVP, whereas only 0.50% of subjects aged 60 to 69 did. The prevalence of sub-normal caloric test results, however, was not significantly different between the two age groups (21.55% in the 60–69 age group and 26.59% in the >70 age group). Conclusions: The high-frequency range vestibular function seems vulnerable to aging, and this is more discernible at age >70 years. The weak correlation between age and low-frequency vestibular function tests, such as the caloric test and low-frequency rotary chair testing, suggests the need to revisit the diagnostic criteria for PVP.

EGFRvIII is expressed only in tumor cells and strongly in glioblastoma and is considered a promising target in cancer diagnosis and therapy. Aptamers are synthetic single-stranded oligonucleotides that bind to biochemical target molecules with high binding affinity and specificity. This study examined the potential of the 68Ga-NOTA-EGFRvIII aptamer as a nuclear imaging probe for visualizing EGFRvIII-expressing glioblastoma by positron emission tomography (PET). EGFRvIII aptamer was selected using the SELEX technology, and flow cytometry and fluorescence microscopy verified the high binding affinity to EGFRvIII positive U87MG vIII 4.12 glioma cells but not to EGFRvIII negative U87MG cells. The EGFRvIII aptamer was conjugated with a chelator (1,4,7-triazanonane-1,4,7-triyl)triacetic acid (NOTA) for 68Ga-labeling. The 68Ga-NOTA-EGFRvIII aptamer was prepared using the preconcentration-based labeling method with a high radiolabeling yield at room temperature. Ex vivo biodistribution analyses confirmed the significantly higher tumor uptake of the 68Ga-NOTA-EGFRvIII aptamer in EGFRvIII-expressing xenograft tumors than that in EGFRvIII negative tumors, confirming the specific tumor uptake of the 68Ga-NOTA-EGFRvIII aptamer in vivo. PET imaging studies revealed a high retention rate of the 68Ga-NOTA-EGFRvIII aptamer in U87MG vIII 4.12 tumors but only low uptake levels in U87-MG tumors, suggesting that the 68Ga-NOTA-EGFRvIII aptamer may be used as a PET imaging agent for EGFRvIII-expressing glioblastoma.

Background Epinephrine is administered to increase coronary perfusion pressure during advanced life support and promote short‐term survival. Recent cardiopulmonary resuscitation (CPR) guidelines recommend an epinephrine dosing interval of 3 to 5 minutes during resuscitation; however, scientific evidence supporting this recommendation is lacking. Therefore, we aimed to investigate the hemodynamic effects of repeated epinephrine doses during CPR by monitoring augmented blood pressure after its administration in a swine model of cardiac arrest. Methods and Results A secondary analysis of data from a published study was performed using a swine cardiac arrest model. The epinephrine dose was fixed at 1 mg, and the first dose of epinephrine was administered after no‐flow and low‐flow times of 2 minutes and 8 minutes, respectively, and subsequently administered every 4 minutes. Four cycles of dosing intervals were defined because a previous study was terminated 26 minutes after the induction of ventricular fibrillation. Augmented blood pressures and corresponding timelines were determined. Augmented blood pressure trends following cycles and the epinephrine effect duration were also monitored. Among the 140 CPR cycles, the augmented blood pressure after epinephrine administration was the highest during the first cycle of CPR and decreased gradually with further cycle repetitions. The epinephrine effect duration did not differ between repeated cycles. The maximum blood pressure was achieved 78 to 97 seconds after epinephrine administration. Conclusions Hemodynamic augmentation with repeated epinephrine administration during CPR decreased with cycle progression. Further studies are required to develop an epinephrine administration strategy to maintain its hemodynamic effects during prolonged resuscitation.

Abstract Current clinical tools for breast cancer (BC) diagnosis are insufficient but liquid biopsy of different bodily fluids has recently emerged as a minimally invasive strategy that provides a real-time snapshot of tumour biomarkers for early diagnosis, active surveillance of progression, and post-treatment recurrence. Extracellular vesicles (EVs) are nano-sized membranous structures 50–1000 nm in diameter that are released by cells into biological fluids. EVs contain proteins, nucleic acids, and lipids which play pivotal roles in tumourigenesis and metastasis through cell-to-cell communication. Proteins and miRNAs from small EVs (sEV), which range in size from 50–150 nm, are being investigated as a potential source for novel BC biomarkers using mass spectrometry-based proteomics and next-generation sequencing. This review covers recent developments in sEV isolation and single sEV analysis technologies and summarises the sEV protein and miRNA biomarkers identified for BC diagnosis, prognosis, and chemoresistance. The limitations of current sEV biomarker research are discussed along with future perspective applications.

Abstract Techniques for detecting chemicals dispersed at low concentrations in air continue to evolve. These techniques can be applied not only to manage the quality of agricultural products using a post-ripening process but also to establish a safety prevention system by detecting harmful gases and diagnosing diseases. Recently, techniques for rapid response to various chemicals and detection in complex and noisy environments have been developed using M13 bacteriophage-based sensors. In this review, M13 bacteriophage-based multi-array colourimetric sensors for the development of an electronic nose is discussed. The self-templating process was adapted to fabricate a colour band structure consisting of an M13 bacteriophage. To detect diverse target chemicals, the colour band was utilised with wild and genetically engineered M13 bacteriophages to enhance their sensing abilities. Multi-array colourimetric sensors were optimised for application in complex and noisy environments based on simulation and deep learning analysis. The development of a multi-array colourimetric sensor platform based on the M13 bacteriophage is likely to result in significant advances in the detection of various harmful gases and the diagnosis of various diseases based on exhaled gas in the future.

PURPOSE Recreation specialization theory, which is characterized by a unique development process and progress, has been found to have varied pathways that develop in different patterns based on each dimension of recreation specialization. This study aimed to investigate how each sub-dimension of specialization changes as the degrees of experiential participation (frequency, period, and intensity of participation) and goods investment (expenditure) of the scuba divers increase. METHODS In the summer of 2021 (May-August), a purposive sampling method was used to collect samples from young scuba divers, and 278 copies of valid data were used for the final analysis. Frequency analysis, descriptive statistical analysis, confirmatory factor analysis, reliability analysis, correlation analysis, curve estimation analysis, and hierarchical regression analysis were performed using SPSS 24.0 and AMOS 24.0 ver. RESULTS The findings were as follows. First, the quadratic nonlinear model was identified as the optimal model for the relationships between the scuba divers’ participation intensity and cognitive, behavioral, and affective recreation specializations based on experience. Second, the cubic nonlinear model was identified as the optimal model for the relationships between the participation period, frequency of participation, and cognitive, behavioral, and affective recreation specializations of scuba divers. Third, the cubic nonlinear model was identified as the optimal model for the relationships between the expenditure cost of scuba divers and the cognitive, behavioral, and affective recreation specializations in the center of the goods. As the period, frequency, and expenditure of scuba diving participants increased, the relevant cognitive, behavioral, and affective specializations did not progress in a linear manner; instead, they went through an intermediate maintenance stage and developed to a higher level. CONCLUSIONS Progressive and meaningful consumption of experiences and goods further promotes recreation specialization. Any future follow-up study should identify a trade-off point in the development of the recreation specialization in a step by step manner.

Objectives This study evaluated the effect of dosing yellow clay powder as a sedimentation aid when Microcystis sp. bloomed. Methods Pre-oxidation (chlorination and ozonation) treatment and coagulation/precipitation experiments of Microcystis sp. - laden source water were performed with a jar-tester. Treatment efficiency was evaluated by analyzing the turbidity and particulate matter of the supernatant after sedimentation according to the presence or not of pre-oxidation, the concentrations of yellow clay powder, and polyamine dosing. Results and Discussion As a result of evaluating the turbidity and particulate matter of the supernatant after coagulation/sedimentation according to the dosing concentrations of yellow clay powder, the turbidity of the supernatant decreased as the dosing concentrations of yellow clay powder increased regardless of the presence or not of pre-oxidation. In particular, when pre-oxidation was not performed, both turbidity and particulate matter of the supernatant after sedimentation were significantly reduced. In addition, without pre-oxidation, when yellow clay powder (50 mg/L) and polyamine (1.0 mg/L) were dosed together, turbidity was reduced by 25% and the amount of particulate matter by 41% compared to utilizing pre-oxidation. Regarding the concentrating efficiency of sedimentation sludge, when yellow clay powder was added, concentrating efficiency increased by more than 31~38% regardless of pre-oxidation treatment compared to when yellow clay powder was not added. However, with pre-oxidation, the concentrating efficiency decreased by about 27~34% under the same yellow clay powder and polyamine dosing conditions compared to without pre-oxidation. Conclusion When yellow clay powder was added to Microcystis sp. - laden source water, turbidity and particulate matter were effectively reduced after coagulation/sedimentation regardless of the presence or not of pre-oxidation. In particular, when pre-oxidation was not performed, the turbidity and particulate matter after coagulation/sedimentation were significantly reduced as compared with utilizing pre-oxidation, and using yellow clay powder together with a polyamine reduced turbidity and particulate matter the most. In addition, the sludge concentration of Microcystis sp. - containing sludge with low concentrating efficiency was increased by dosing yellow clay powder.

V-ATPase, which comprises 13-14 subunits, is essential for pH homeostasis in all eukaryotes, but its proper function requires a regulator to assemble its subunits. While RAVE (regulator of H+-ATPase of vacuolar and endosomal membranes) and Raboconnectin-3 complexes assemble V-ATPase subunits in Saccharomyces cerevisiae and humans, respectively, the function of the RAVE complex in fungal pathogens remains largely unknown. In this study, we identified two RAVE complex components, Rav1 and Wdr1, in the fungal meningitis pathogen Cryptococcus neoformans, and analyzed their roles. Rav1 and Wdr1 are orthologous to yeast RAVE and human Rabconnectin-3 counterparts, respectively, forming the hybrid RAVE (hRAVE) complex. Deletion of RAV1 caused severe defects in growth, cell cycle control, morphogenesis, sexual development, stress responses, and virulence factor production, while the deletion of WDR1 resulted in similar but modest changes, suggesting that Rav1 and Wdr1 play central and accessary roles, respectively. Proteomics analysis confirmed that Wdr1 was one of the Rav1-interacting proteins. Although the hRAVE complex generally has V-ATPase-dependent functions, it also has some V-ATPase-independent roles, suggesting a unique role beyond conventional intracellular pH regulation in C. neoformans. The hRAVE complex played a critical role in the pathogenicity of C. neoformans, and RAV1 deletion attenuated virulence and impaired blood-brain barrier crossing ability. This study provides comprehensive insights into the pathobiological roles of the fungal RAVE complex and suggests a novel therapeutic strategy for controlling cryptococcosis.

Cases of foreign body ingestion are frequently seen in gastroenterology. However, it is not common for the foreign body to be located in the submucosa, which obscures it from view, even during endoscopy. A 74-year-old woman visited the emergency room 10 days after swallowing an implant screw during an implant procedure at a dental clinic. Abdominal CT revealed a 14-mm-long radio-opaque screw in the posterior wall of the proximal body of the stomach. On endoscopy, the screw was not observed in the stomach; however, fluoroscopic examination revealed that it was located under the mucosa of the posterior wall of the proximal body of the stomach. The screw was grasped using alligator forceps and retrieved. There was no evidence of perforation on chest radiography. Herein, we present a case wherein a foreign body embedded under the mucosa was removed.

ABSTRACT Blocking of nutrient uptake and amino acid biosynthesis are considered potential targets for next-generation antifungal drugs against pathogenic fungi, including Cryptococcus neoformans. In this regard, the sulfate assimilation pathway is particularly attractive, as it is only present in eukaryotes such as plants and fungi, yet not in mammals. Here, we demonstrated that the adenylyl sulfate kinase (Met14) in the sulfate assimilation pathway is not essential yet is required for the viability of C. neoformans due to its involvement in biosynthesis of two sulfur-containing amino acids, cysteine and methionine. Met14-dependent cysteine and methionine biosynthesis was found to significantly contribute to a diverse range of pathobiological processes in C. neoformans. Met14-dependent cysteine rather than methionine biosynthesis was also found to play pivotal roles in cell growth and tolerance to environmental stresses and antifungal drugs. In contrast, the Met14-dependent methionine biosynthesis was found to be more important than cysteine biosynthesis for the production of major cryptococcal virulence factors of melanin pigments and polysaccharide capsules. Finally, we also found that despite its attenuated virulence in an insect model, Galleria mellonella, the met14Δ mutant yielded no difference in virulence in a murine model of systemic cryptococcosis. Hence, clinical inhibition of Met14-dependent amino acid biosynthetic pathways may not be advantageous for the treatment of systemic cryptococcosis. IMPORTANCE Current antifungal drugs have several limitations, such as drug resistance, severe side effects, and a narrow spectrum. Therefore, novel antifungal targets are urgently needed. To this end, fungal sulfur amino acid biosynthetic pathways are considered potential targets for development of new antifungal agents. Here, we demonstrated that Met14 in the sulfate assimilation pathway promotes growth, stress response, and virulence factor production in C. neoformans via synthesis of sulfur-containing amino acids methionine and cysteine. Met14-dependent cysteine rather than methionine synthesis was found to be critical for growth and stress responses, whereas Met14-dependent methionine synthesis was more important for the production of antiphagocytic capsules and antioxidant melanin in C. neoformans. Surprisingly, deletion of the MET14 gene was found to attenuate cryptococcal virulence in an insect model, yet not in a murine model. Collectively, our results showed that Met14-dependent cysteine and methionine biosynthesis play roles that are distinct from each other in C. neoformans. Moreover, Met14 is unlikely to be a suitable anticryptococcal drug target.

Abstract Background Falls impose significant health and economic burdens among older populations, making their prevention a priority. Health economic models can inform whether the falls prevention intervention represents a cost-effective use of resources and/or meet additional objectives such as reducing social inequities of health. This study aims to conduct a systematic review (SR) of community-based falls prevention economic models to: (i) systematically identify such models; (ii) synthesise and critically appraise modelling methods/results; and (iii) formulate methodological and commissioning recommendations. Methods The SR followed PRISMA 2021 guideline, covering the period 2003–2020, 12 academic databases and grey literature. A study was included if it: targeted community-dwelling persons aged 60 and over and/or aged 50–59 at high falls risk; evaluated intervention(s) designed to reduce falls or fall-related injuries; against any comparator(s); reported outcomes of economic evaluation; used decision modelling; and had English full text. Extracted data fields were grouped by: (A) model and evaluation overview; (B) falls epidemiology features; (C) falls prevention intervention features; and (D) evaluation methods and outcomes. A checklist for falls prevention economic evaluations was used to assess reporting/methodological quality. Extracted fields were narratively synthesised and critically appraised to inform methodological and commissioning recommendations. The SR protocol is registered in the Prospective Register of Systematic Reviews (CRD42021232147). Results Forty-six models were identified. The most prevalent issue according to the checklist was non-incorporation of all-cause care costs. Based on general population, lifetime models conducting cost-utility analyses, seven interventions produced favourable ICERs relative to no intervention under the cost-effectiveness threshold of US$41,900 (£30,000) per QALY gained; of these, results for (1) combined multifactorial and environmental intervention, (2) physical activity promotion for women, and (3) targeted vitamin D supplementation were from validated models. Decision-makers should explore the transferability and reaches of interventions in their local settings. There was some evidence that exercise and home modification exacerbate existing social inequities of health. Sixteen methodological recommendations were formulated. Conclusion There is significant methodological heterogeneity across falls prevention models. This SR’s appraisals of modelling methods should facilitate the conceptualisation of future falls prevention models. Its synthesis of evaluation outcomes, though limited to published evidence, could inform commissioning.

Abstract Background Falls impose significant health and economic burdens on older people. The volume of falls prevention economic evaluations has increased, the findings from which have been synthesised by systematic reviews (SRs). Such SRs can inform commissioning and design of future evaluations; however, their findings can be misleading and incomplete, dependent on their pre-specified criteria. This study aims to conduct a systematic overview (SO) to: (1) systematically identify SRs of community-based falls prevention economic evaluations; (2) describe the methodology and findings of SRs; (3) critically appraise the methodology of SRs; and (4) suggest commissioning recommendations based on SO findings. Methods The SO followed the PRISMA guideline and the Cochrane guideline on SO, covering 12 databases and grey literature for the period 2003–2020. Eligible studies were SRs with 50% or more included studies that were economic evaluations of community-based falls prevention (against any comparator) for older persons (aged 60 +) or high-risk individuals aged 50–59. Identified SRs’ aims, search strategies and results, extracted data fields, quality assessment methods/results, and commissioning and research recommendations were synthesised. The comprehensiveness of previous SRs’ data synthesis was judged against criteria drawn from literature on falls prevention/public health economic evaluation. Outcomes of general population, lifetime decision models were re-analysed to inform commissioning recommendations. The SO protocol is registered in the Prospective Register of Systematic Reviews (CRD42021234379). Results Seven SRs were identified, which extracted 8 to 33 data fields from 44 economic evaluations. Four economic evaluation methodological/reporting quality checklists were used; three SRs narratively synthesised methodological features to varying extent and focus. SRs generally did not appraise decision modelling features, including methods for characterising dynamic complexity of falls risk and intervention need. Their commissioning recommendations were based mainly on cost-per-unit ratios (e.g., incremental cost-effectiveness ratios) and neglected aggregate impact. There is model-based evidence of multifactorial and environmental interventions, home assessment and modification and Tai Chi being cost-effective but also the risk that they exacerbate social inequities of health. Conclusions Current SRs of falls prevention economic evaluations do not holistically inform commissioning and evaluation. Accounting for broader decisional factors and methodological nuances of economic evaluations, particularly decision models, is needed.

Acute liver failure due to malignant melanoma is uncommon. We presents a case of acute liver failure secondary to hepatic infiltration of a malignant melanoma. An 86-year-old man was admitted with elevated liver enzymes and an increased lactate dehydrogenase level. His condition progressed to acute liver failure, but the etiology of liver failure was unclear. Esophagogastroduodenoscopy was performed to evaluate dyspepsia, which showed signs indicative of malignant melanoma. Based on the endoscopy findings and elevated liver enzyme levels, liver biopsy was performed to confirm the presence of malignant melanoma. Hepatic infiltration of malignant melanoma was observed histologically. However, massive and diffuse liver metastasis is very rare and difficult to identify on imaging studies. If the etiology of liver failure is unclear, diffuse metastatic melanoma infiltration should be considered as differential diagnosis. Early liver biopsy can help to clarify the diagnosis.

Abstract The present study examined the impact of a leadership development program, Leading for Change (LfC) that focused on building the capacity of early educators to lead change as frontline leaders and change agents. Bringing together a relational-entrepreneurial leadership theory lens, the LfC was designed to foster early educators’ leadership mindset, knowledge, and skills that could potentially bring a long-lasting impact on many aspects of the early care and education (ECE) field. With a sample of 31 racially and linguistically diverse early educators, the present study compared participants’ entrepreneurial mindset, leadership competencies, and capacity to act as change agents and leaders before and after the LfC program. Results showed that participants’ perceptions of themselves as leaders were increased after completing the LfC. They also demonstrated more confidence in their own ability to drive positive change where they work and more broadly in the ECE field. Findings from this study suggest that the relational-entrepreneurial leadership approach taps into early educators’ insights, passions, and knowledge and equips them to participate in leadership for quality improvement and positive change.

We report on the construction of a lensless camera with a phase-modulating mask layer integrated directly on an image sensor using the UV-imprint lithography method. By replicating the master phase mask’s surface structure directly on the image sensor, our method further simplifies the fabrication of lensless cameras and delivers a rigid and durable device with a small form factor. Our prototype device has an open-faced design without any apertures and generates high-quality photographic reconstructions with high light collection efficiency. We analyze the performance of our prototype device and demonstrate various imaging applications, including the digital refocusing capabilities.

Lensless cameras have recently emerged as a compact imaging system based on computational imaging with various multiplexing capabilities. Here, we propose a compact, low-cost, lensless camera that enables snapshot full-Stokes polarization imaging. While polarization imaging provides additional contrast based on the birefringence and surface properties of the object, most polarization cameras require bulky hardware or are limited to measuring only the linear polarization information. Our device, composed of a phase mask, a polarization-encoded aperture, and a regular image sensor, performs compressed imaging to recover linear as well as circular polarization information of the scene from single image capture. We demonstrate the full-Stokes imaging capabilities of our device and describe the image reconstruction and calibration processes.

Purpose Adjuvant chemotherapy (AC) is recommended for patients with stage II colorectal cancer with adverse features. However, the effect of adjuvant treatment in elderly patients with high-risk stage II colorectal cancer remains controversial. This study aimed to investigate the oncologic outcomes in elderly high-risk stage II colorectal cancer patients who underwent curative resection with or without AC. Methods Patients aged over 70 years having stage II colorectal adenocarcinoma with at least 1 adverse feature who underwent radical surgery between 2008 and 2017 at a single center were included. We compared recurrence-free survival (RFS) and overall survival (OS) between patients who received more than 80% of the planned AC cycle (the AC+ group) and those who did not receive it (the AC− group). Results The AC+ and AC– group contained 46 patients and 50 patients, respectively. The log-rank test revealed no significant intergroup differences in RFS (P=0.083) and OS (P=0.122). In the subgroup of 27 patients with more than 2 adverse features, the AC+ group (n=16) showed better RFS (P=0.006) and OS (P=0.025) than the AC− group. In this subgroup, AC was the only significant factor affecting RFS in the multivariate analysis (P=0.023). AC was significantly associated with OS (P=0.033) in the univariate analysis, but not in the multivariate analysis (P=0.332). Conclusion Among elderly patients with stage II high-risk colorectal cancer, the AC+ group did not show better RFS or OS than the AC− group. However, selected patients with more than 2 adverse features might benefit from AC.

Abstract Background High prevalence of falls among older persons makes falls prevention a public health priority. Yet community-based falls prevention face complexity in implementation and any commissioning strategy should be subject to economic evaluation to ensure cost-effective use of healthcare resources. The study aims to capture the views of older people on implementing the National Institute for Health and Care Excellence (NICE) guideline on community-based falls prevention and explore how the qualitative data can be used to inform commissioning strategies and conceptual modelling of falls prevention economic evaluation in the local area of Sheffield. Methods Focus group and interview participants (n = 27) were recruited from Sheffield, England, and comprised falls prevention service users and eligible non-users of varying falls risks. Topics concerned key components of the NICE-recommended falls prevention pathway, including falls risk screening, multifactorial risk assessment and treatment uptake and adherence. Views on other topics concerning falls prevention were also invited. Framework analysis was applied for data analysis, involving data familiarisation, identifying themes, indexing, charting and mapping and interpretation. The qualitative data were mapped to three frameworks: (1) facilitators and barriers to implementing the NICE-recommended pathway and contextual factors; (2) intervention-related causal mechanisms for formulating commissioning strategies spanning context, priority setting, need, supply and demand; and (3) methodological and evaluative challenges for public health economic modelling. Results Two cross-component factors were identified: health motives of older persons; and professional competence. Participants highlighted the need for intersectoral approaches and prioritising the vulnerable groups. The local commissioning strategy should consider the socioeconomic, linguistic, geographical, legal and cultural contexts, priority setting challenges, supply-side mechanisms spanning provider, organisation, funding and policy (including intersectoral) and health and non-health demand motives. Methodological and evaluative challenges identified included: incorporating non-health outcomes and societal intervention costs; considering dynamic complexity; considering social determinants of health; and conducting equity analyses. Conclusions Holistic qualitative research can inform how commissioned falls prevention pathways can be feasible and effective. Qualitative data can inform commissioning strategies and conceptual modelling for economic evaluations of falls prevention and other geriatric interventions. This would improve the structural validity of quantitative models used to inform geriatric public health policies.

Abstract Metformin is a major treatment for type 2 diabetes. This study was conducted to investigate the impact of gut microbiome dysbiosis on the pharmacokinetics and antihyperglycemic effects of metformin. Healthy adult males aged 19–45 years with no defecation abnormalities were recruited for this 4‐period clinical study: baseline; post‐metformin (i.e., multiple oral doses of 1000 mg metformin on days 1–4); post‐vancomycin (i.e., multiple oral doses of 500 mg vancomycin on days 11–17 inducing gut microbiome changes); and post‐metformin + vancomycin (i.e., multiple oral doses of 1000 mg metformin on days 16–19). In each period, serum glucose and insulin concentrations following an oral glucose tolerance test, fecal samples for gut microbiome composition, and safety data were obtained. Following metformin dosing, plasma and urine samples for pharmacokinetics were collected. Nine subjects completed the study. The pharmacokinetics of metformin remained unchanged, and the antihyperglycemic effect was significantly decreased after vancomycin administration (p value = 0.039), demonstrating the weak relationship between the pharmacokinetics and pharmacodynamics of metformin. Relative abundances of some genus were changed after vancomycin administration, and tended to correlate with the antihyperglycemic effects of metformin (p value = 0.062 for Erysipelatoclostridium; p value = 0.039 for Enterobacter; and p value = 0.086 for Faecalibacterium). Adverse events occurred in all subjects and were resolved without sequelae. In conclusion, a decrease in the antihyperglycemic effect of metformin was observed after concomitant administration with vancomycin, without changes in metformin pharmacokinetics. The antihyperglycemic effect was tended to correlate with the relative abundance of several genus, suggesting that the effect of metformin is partly attributable to the gut microbiome (ClinicalTrials.gov, NCT03809260).

Mutations in daf-2/insulin/IGF-1 receptor impair the growth and reproduction of C. elegans but conversely enhance immunity and lifespan. Here, the authors show that a missense mutation in the gene retains the effects on lifespan and immunity and improves motility.

Abstract To investigate pharmacokinetic and pharmacodynamic differences of zolpidem between males and females and their causes, including CYP3A4 activity. A single oral dose of zolpidem (10 mg) was administered to 15 male and 15 female healthy subjects. Blood samples were collected up to 12 h post-dose to determine plasma zolpidem concentrations. Pharmacokinetic parameters were obtained using non-compartmental analysis. Digit symbol substitution test, choice reaction time, and visual analog scale of sleepiness were used to evaluate pharmacodynamics. We measured CYP3A4 activity using 4β-hydroxycholesterol, an endogenous metabolite. Mean maximum plasma concentration and area under the plasma concentration–time curve were higher for females than for males (9.9% and 32.5%, respectively); other pharmacokinetic parameters showed no significant differences. Pharmacodynamic scores for females showed delayed recovery compared with that for males. CYP3A4 activity was higher in females than in males (p = 0.030). There was no serious adverse event, and adverse event incidence was not different between the sexes. Zolpidem exposure was about 30% higher in females than in males. Delayed pharmacodynamic score recovery in females could be related to higher zolpidem concentrations. Although apparent clearance was lower in females, systemic clearance might not be the cause of the different exposures to zolpidem.

Uninterrupted monitoring of pressure and temperature at skin interfaces can help to minimize the potential for pressure injuries in hospitalized or bedridden patients. Here, the authors introduce a soft, skin-mountable sensor that can continuously provide readings via antennas mounted under bedding, and demonstrate the functionality and robustness of the devices on patients.

Purpose It is known that as the T stage of a carcinoma progresses, the prognosis becomes poorer. However, there are few studies about factors that affect the prognosis of T4 advanced colon cancer. This study aimed to identify the prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in T4 colon cancer. Methods Patients diagnosed with stage T4 on histopathology after undergoing curative surgery for colon cancer between March 2009 and March 2018 were retrospectively analyzed for factors related to postoperative survival. Primary outcomes were DFS and OS. Results Eighty-two patients were included in the study. DFS and OS of the pathologic (p) T4b group were not inferior to that of the pT4a group. Multivariate analysis showed that differentiation (hazard ratio [HR], 4.994; P = 0.005), and laparoscopic surgery (HR, 0.323; P = 0.008) were significant prognostic factors for DFS, while differentiation (HR, 7.904; P ≤ 0.001) and chemotherapy (HR, 0.344; P = 0.038) were significant prognostic factors for OS. Conclusion Tumor differentiation, laparoscopic surgery, and adjuvant chemotherapy were found to be significant prognostic factors in patients with T4 colon cancer. Adjuvant chemotherapy and curative resections by laparoscopy might improve the prognosis in these patients.

UNESCO Global Geoparks were established in 2015. With respect to sustainable development, there are numerous sites globally that have potential for immediate substantial economic development because of the diverse range of geological phenomena they offer including, among many others, structures, minerals and fossils. UNESCO Global Geoparks play an important role in achieving the Sustainable Development Goals. This study explored how UNESCO Global Geoparks have been contributing to the local economic development by promoting sustainable geotourism. Literature review was carried out to understand UNESCO Global Geoparks’ strategies on sustainable geotourism, and local community’s participation and involvement in economic activities in UNESCO Global Geoparks worldwide. A case study with three UNESCO Global Geoparks in Asia showed that the designation of UNESCO Global Geoparks vitalized economic activities by local communities and brought more visitors to the regions. Moreover, UNESCO Global Geoparks can be a brand with the image of treasured Earth heritage sites, and local communities can utilize the image as a marketing strategy as well as create their own brands along with geoparks.

A Pleural effusion cytology is vital for treating metastatic breast cancer; however, concerns have arisen regarding the low accuracy and inter-observer variability in cytologic diagnosis. Although artificial intelligence-based image analysis has shown promise in cytopathology research, its application in diagnosing breast cancer in pleural fluid remains unexplored. To overcome these limitations, we evaluate the diagnostic accuracy of an artificial intelligence-based model using a large collection of cytopathological slides, to detect the malignant pleural effusion cytology associated with breast cancer. This study includes a total of 569 cytological slides of malignant pleural effusion of metastatic breast cancer from various institutions. We extracted 34,221 augmented image patches from whole-slide images and trained and validated a deep convolutional neural network model (DCNN) (Inception-ResNet-V2) with the images. Using this model, we classified 845 randomly selected patches, which were reviewed by three pathologists to compare their accuracy. The DCNN model outperforms the pathologists by demonstrating higher accuracy, sensitivity, and specificity compared to the pathologists (81.1% vs. 68.7%, 95.0% vs. 72.5%, and 98.6% vs. 88.9%, respectively). The pathologists reviewed the discordant cases of DCNN. After re-examination, the average accuracy, sensitivity, and specificity of the pathologists improved to 87.9, 80.2, and 95.7%, respectively. This study shows that DCNN can accurately diagnose malignant pleural effusion cytology in breast cancer and has the potential to support pathologists.

Abstract Propyl-paraben exposure is associated with aeroallergen sensitization, but its association with atopic dermatitis (AD) is inconclusive. No studies have been conducted on the metabolomic pathways underlying these associations. We investigated the associations between propyl-paraben exposure and aeroallergen sensitization, AD, and Eczema Area and Severity Index (EASI) score and identified the underlying pathways using untargeted metabolomics analysis. We enrolled 455 children in a general population study. Skin prick tests were performed with the assessment of EASI score. Urinary propyl-, butyl-, ethyl-, and methyl-paraben levels were measured. Untargeted metabolomics analysis was performed on the first and fifth urine propyl-paraben quintile groups. The highest urine propyl-paraben quintile group was associated with aeroallergen sensitization, but not with AD. Glycine, threonine, serine, ornithine, isoleucine, arabinofuranose, d-lyxofuranose, citrate, and picolinic acid levels were higher, whereas palmitic acid and 2-palmitoylglycerol levels were lower in the highest quintile propyl-paraben group, than in the lowest quintile group. The propyl-paraben-induced metabolic perturbations were associated with serine and glycine metabolisms, branched-chain amino acid metabolism, and ammonia recycling. Propyl-paraben exposure was associated with aeroallergen sensitization and EASI score, partially via metabolomic changes related with oxidative stress, mTOR, peroxisome proliferator-activated receptors pathway, aryl hydrocarbon receptor signaling pathways, and tricarboxylic acid cycle.

Abstract Background Although recipients and donors in living kidney transplantation experience psychological distress—including depression and anxiety—during the pre-operative period, very few studies have evaluated the related psychological reactions. This study aimed to determine the characteristics and correlations of the mood states and personality of recipients and donors (genetically related and unrelated) of living kidney transplantations. Methods A total of 66 pairs of living donors and recipients were enrolled from April 2008 to June 2019 in this study, of whom 53 eligible pairs of living donors and recipients were included in the retrospective analysis of their psychological assessments in the pre-transplantation states. While participants’ personality patterns were assessed using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), mood states were evaluated via both the State-Trait Anxiety Inventory (STAI) and The Center for Epidemiologic Studies Depression Scale (CES-D). Statistical analysis was performed using paired t-tests and Spearman’s correlation analyses. Results The recipient group showed significantly higher scores for Hypochondriasis (t = − 4.49, p = .0001), Depression (t = − 3.36, p = .0015), and Hysteria (t = − 3.30, p = .0018) of MMPI-2 and CES-D (t = − 3.93, p = .0003) than the donor group. The biologically unrelated recipient group reported higher scores of Hypochondriasis (t = − 3.37, p = .003) and Depression (t = − 2.86, p = 0.0098) than the unrelated donor group. Higher scores for Hypochondriasis (t = − 3.00, p = 0.0054) and CES-D (t = − 3.53, p = .0014) were found in the related recipient group. A positive association was found for Hypomania (r = .40, p = .003) of MMPI-2, STAI-S (r = .36, p = .009), and CES-D (r = .36, p = .008) between the recipient and donor groups. Conclusions Recipients suffered from a higher level of depression and somatic concerns than donors before living kidney transplantation. Psychological problems like depression and anxiety can occur in both living kidney transplantation donors and recipients. This study suggests that clinicians must pay attention to mood states not only in recipients but also in donors because of emotional contagion.

Purpose To identify factors significantly associated with the mortality of patients with left colonic perforation, and to compare the outcome of Hartmann’s procedure (HP) and primary repair (PR) or primary anastomosis (PA) in patients with left colonic perforation without factors associated with mortality. Methods This retrospective study included patients who underwent surgery for left colonic perforation from January 2009 to February 2018. Preoperative factors related to postoperative mortality, including vital signs, laboratory findings, and intraoperative findings, were analyzed by type of operation. The chi-square, Fisher exact, and Mann-Whitney U-tests were used to analyze the data. Results Ninety-one patients were included (36 men, 55 women), and 15 (16.5%) died postoperatively. Prognostic factors were age, leukopenia, thrombocytopenia, bleeding tendency, acute kidney injury, hemodynamic instability, and the existence of feculent ascites. Leukopenia and longer operative time were independent risk factors for mortality. Seventy-nine patients did not have leukopenia and 30 of these patients who underwent PR without diversion were excluded from the subanalysis. HP was performed in 30 patients, and PR with diversion and PA with or without diversion were performed in 19. Compared to the other operative methods, HP had no advantage in reducing hospital mortality (P=0.458) and morbidity. Conclusion Leukopenia could be an objective prognostic factor for left colonic perforation. Although HP is the gold standard for septic left colonic perforation, it did not improve the hospital mortality of the patients without leukopenia. For such patients, PR or PA may be suggested as an alternative option for left colonic perforation.

There have been many attempts in pharmaceutical industries and academia to improve the pharmacokinetic characteristics of anti-tumor small-molecule drugs by conjugating them with large molecules, such as monoclonal antibodies, called ADCs. In this context, albumin, one of the most abundant proteins in the blood, has also been proposed as a large molecule to be conjugated with anti-cancer small-molecule drugs. The half-life of albumin is 3 weeks in humans, and its distribution to tumors is higher than in normal tissues. However, few studies have been conducted for the in vivo prepared albumin-drug conjugates, possibly due to the lack of robust bioanalytical methods, which are critical for evaluating the ADME/PK properties of in vivo prepared albumin-drug conjugates. In this study, we developed a bioanalytical method of the albumin-conjugated MAC glucuronide phenol linked SN-38 ((2S,3S,4S,5R,6S)-6-(4-(((((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano [3′,4′:6,7] indolizino [1,2-b] quinolin-9-yl)oxy)methyl)(2 (methylsulfonyl)ethyl)carbamoyl)oxy)methyl)-2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-methylpropanamido)acetamido)phenoxy)-3,4,5-trihydroxytetra-hydro-2H-pyran-2-carboxylic acid) as a proof-of-concept. This method is based on immunoprecipitation using magnetic beads and the quantification of albumin-conjugated drug concentration using LC-qTOF/MS in mouse plasma. Finally, the developed method was applied to the in vivo intravenous (IV) mouse pharmacokinetic study of MAC glucuronide phenol-linked SN-38.

Background Trimethylamine N‐oxide (TMAO) is a gut microbiota‐dependent metabolite of dietary choline, L‐carnitine, and phosphatidylcholine‐rich foods. On the basis of experimental studies and patients with prevalent disease, elevated plasma TMAO may increase risk of atherosclerotic cardiovascular disease (ASCVD). TMAO is also renally cleared and may interact with and causally contribute to renal dysfunction. Yet, how serial TMAO levels relate to incident and recurrent ASCVD in community‐based populations and the potential mediating or modifying role of renal function are not established. Methods and Results We investigated associations of serial measures of plasma TMAO, assessed at baseline and 7 years, with incident and recurrent ASCVD in a community‐based cohort of 4131 (incident) and 1449 (recurrent) older US adults. TMAO was measured using stable isotope dilution liquid chromatography–tandem mass spectrometry (laboratory coefficient of variation,

Bifidobacterium animalislactis

Mesh erosion or migration is a rare and late complication after hernia repair. Its incidence is increasing as the utilization of prosthetic mesh gains popularity for abdominal hernia repair. However, mesh migration is exceedingly rare and its clinical presentation is atypical and diverse. Therefore, the management of mesh migration should be individualized to each patient. This research reports the case of a 94-year-old man with transmural migration of Prolene mesh (Ethicon) from the abdominal wall to the rectum 14 years after incisional hernia repair. He presented with only chronic abdominal pain and constipation. Migration of the mesh and a fistula between the right abdominal wall and transverse colon was observed on computed tomography. The mesh was evacuated manually from the anus without any sequelae. These findings made this case atypical, since complete transluminal migration of mesh is exceedingly rare and mesh erosion or migration requires surgical treatment in many cases.

Although several scoring systems have been used to differentiate simple acute appendicitis from perforated appendicitis, no particular system has been widely accepted. Therefore, this study aimed to investigate preoperative factors associated with complicated appendicitis and to develop a scoring system that distinguishes complicated appendicitis in children aged

Objective Tourniquet use in total knee replacement (TKR) is believed to improve the bone-cement interface by reducing bleeding, potentially prolonging implant survival. This study aimed to compare the risk of revision for primary cemented TKR performed with or without a tourniquet.Design We analysed data from the National Joint Registry (NJR) for all primary cemented TKRs performed in England and Wales between April 2003 and December 2003. Kaplan-Meier plots and Cox regression were used to assess the influence of tourniquet use, age at time of surgery, sex and American Society of Anaesthesiologists (ASA) classification on risk of revision for all-causes.Results Data were available for 16 974 cases of primary cemented TKR, of which 16 132 had surgery with a tourniquet and 842 had surgery without a tourniquet. At 10 years, 3.8% had undergone revision (95% CI 2.6% to 5.5%) in the no-tourniquet group and 3.1% in the tourniquet group (95% CI 2.8% to 3.4%). After adjusting for age at primary surgery, gender and primary ASA score, the HR for all-cause revision for cemented TKR without a tourniquet was 0.82 (95% CI 0.57 to 1.18).Conclusions We did not find evidence that using a tourniquet for primary cemented TKR offers a clinically important or statistically significant reduction in the risk of all-cause revision up to 13 years after surgery. Surgeons should consider this evidence when deciding whether to use a tourniquet for cemented TKR.