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Abstract Fluorescence-guided surgery has emerged as an innovative technique with promising applications in the treatment of various tumors, including colon cancer. Tumor-initiating probe yellow (TiY) has been discovered for identifying tumorigenic cells by unbiased phenotypic screening with thousands of diversity-oriented fluorescence library (DOFL) compounds in a patient-derived lung cancer cell model. This study demonstrated the clinical feasibility of TiY for tumor-specific fluorescence imaging in the tissues of patients with colorectal cancer (CRC). To evaluate the efficacy of TiY in tumor imaging, surgical specimens were obtained, consisting of 36 tissues from 18 patients with CRC, for ex vivo molecular fluorescence imaging, histology, and immunohistochemistry. Orthotopic and chemically induced CRC mice models were administered TiY topically, and distinct tumor lesions were observed in 10 min by real-time fluorescence colonoscopy and ex vivo imaging. In a hepatic metastasis mouse model using splenic injection, TiY accumulation was detected in metastatic liver lesions through fluorescence imaging. Correlation analysis between TiY intensity and protein expression, assessed via immunohistochemistry and Western blotting, revealed a positive correlation between TiY and vimentin and Zeb1, which are known as epithelial–mesenchymal transition (EMT) markers of cancers. A comparative analysis of TiY with other FDA-approved fluorescence probes such as ICG revealed greater quantitative differences in TiY fluorescence intensity between tumor and normal tissues than those observed with ICG. Altogether, these results demonstrated that TiY has a strong potential for visualizing CRC by fluorescence imaging in various preclinical models, which can be further translated for clinical use such as fluorescence-guided surgery. Furthermore, our data indicate that TiY is preferentially uptaken by cells with EMT induction and progression, and overexpressing vimentin and Zeb1 in patients with CRC.

Abstract Background Air pollution may exacerbate diabetes-related indicators; however, the longitudinal associations between air pollutant concentrations and glycemic markers remain unclear. In this prospective cohort study, we examined the longitudinal associations between air pollution and glycemic indicators among older individuals with normoglycemia at baseline and determined whether these associations differed according to changes in physical activity levels. Methods Overall, 1,856 participants (mean age, 70.9 years) underwent baseline and 4-year follow-up surveys. We used linear mixed-effect models to examine the associations between previous 1-year exposures to air pollutants and glycemic indicators. We further investigated associations between previous 5-year exposures to air pollutants and glycemic indicators after the inverse probability of treatment weighting (IPTW). We explored effect modifications by the level of physical activity maintenance and changes in metabolic equivalent of task (METs) for physical activity. Results Levels of particulate matter with aerodynamic diameters ≤ 10 μm (PM10) and ≤ 2.5 μm, and nitrogen dioxide (NO2) were significantly associated with increased fasting blood glucose, Hemoglobin A1c, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) values. After IPTW, the associations remained significant for PM10 and NO2. The positive associations of NO2 with insulin and HOMA-IR remained significant in the maintained inactive group, but not in the maintained moderate-to-vigorous active group. The positive associations of PM10 or NO2 with insulin and HOMA-IR remained significant in the group with increased METs, but not in those with decreased METs. In the post-hoc analysis of non-linear relationships between an increase in METs and glycemic indicators, insulin and HOMA-IR remarkably increased in the higher PM10 and NO2 exposure group from the point of 12,000 and 13,500 METs-min/week increase, respectively. Conclusions We demonstrated longitudinal associations between air pollution exposures and increased insulin resistance in older individuals. Maintaining moderate-to-vigorous physical activity may mitigate the adverse effects of air pollution on insulin resistance. In older individuals dwelling in highly polluted areas, an increase of less than 12,000 METs-min/week may be beneficial for insulin resistance.

Purpose We aimed to investigate the relationship between the tri-ponderal mass index (TMI), a new indirect measure of fat mass, and insulin-like growth factor (IGF)-I/IGF binding protein (IGFBP)-3. Methods The study included 1,630 children and adolescents who visited Jeonbuk National University Children's Hospital. Each patient’s medical record was retrospectively reviewed for age, sex, height, weight, body mass index (BMI), TMI, and IGF-1 and IGFBP-3 levels. Study participants were divided by sex and then categorized by age, BMI, and TMI. Finally, the correlations of TMI with IGF-1 level, IGF-1 standard deviation score (SDS), IGFBP-3 level, IGFBP-3 SDS, and IGF-1/IGFBP-3 ratio were investigated. Results All participants were

Despite the potential role of health being recognised for more than a decade in fragile contexts, there are still gaps in understanding the possible paths towards peace. Particularly, current literature on health and development presents limitations, including insufficient evidence, a lack of thorough consideration for fragility and tensions between humanitarian and developmental approaches. Building upon prior discussions and limitations, this study aims to investigate the association between health indicators and the levels of economic and human development, employing panel data of 60 fragile states covering the years 1995–2021. Seven health outcome measures and three proxy measures for economic and human developments, including GDP per capita and Human Development Index with and without inequality adjustment, are employed in instrumental variable estimation. The analysis shows a positive association between the development measures and corresponding health indicators. These results suggest that promoting the health of the people, particularly among marginalised groups such as pregnant women and children, not only has the potential to protect them but also to facilitate economic and human developments of the fragile states. There is a need for approaching with people-centred and human capability perspectives to achieve the goal of ‘Health and Peace for All’.

Abstract Background Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform. Methods The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment. Discussion This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers. Trial registration NCT05525858.

Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrosing interstitial lung disease with a poor prognosis. While there is evidence suggesting that outdoor air pollution affects the clinical course of IPF, the impact of indoor air pollution on patients with IPF has not been extensively studied. Therefore, this prospective multicentre observational study aims to investigate the association between indoor air pollution and clinical outcomes in patients with IPF.Methods and analysis This study enrolled 140 patients with IPF from 12 medical institutes in the Seoul and Metropolitan areas of the Republic of Korea. Over the course of 1 year, participants visited the institutes every 3 months, during which their clinical data and blood samples were collected. Additionally, indoor exposure to particulate matter ≤2.5 µm (PM2.5) was measured using MicroPEM (RTI International, Research Triangle Park, North Carolina, USA) in each participant’s house for 5 days every 3 months. Lung function was assessed using both site spirometry at each institution and portable spirometry at each participant’s house every 3 months. The study will analyse the impact of indoor PM2.5 on clinical outcomes, including mortality, acute exacerbation, changes in lung function and health-related quality of life, in the participants. This study represents the first attempt to evaluate the influence of indoor air pollution on the prognosis of patients with IPF.Ethics and dissemination This study has received approval from the institutional review board of all participating institutions, including Asan Medical Center, Seoul, Republic of Korea (2021-0072).Trial registration number KCT0006217.

Abstract Unlike other thyroid hormone receptors (THRs), the beta 2 isoform (THRB2) has a restricted expression pattern and is uniquely and abundantly phosphorylated at a conserved serine residue S101 (S102 in humans). Using tagged and or phosphorylation-defective (S101A) THRB2 mutant mice, we show that THRB2 is present in a large subset of POMC neurons and mitigates ROS accumulation during ROS-triggering events, such as fasting/refeeding or high fat diet (HFD). Excessive ROS accumulation in mutant POMC neurons was accompanied by a skewed production of orexigenic/anorexigenic hormones, resulting in elevated food intake. The prolonged exposure to pathogenic hypothalamic ROS levels during HFD feeding lead to a significant loss of POMC neurons in mutant versus wild-type (WT) mice. In cultured cells, the presence of WT THRB2 isoform, but not other THRs, or THRB2S101A, reduced ROS accumulation upon exogenous induction of oxidative stress by tert-butyl hydroperoxide. The protective function of phospho-THRB2 (pTHRB2) did not require thyroid hormone (TH), suggesting a TH-independent role of the THRB2 isoform, and phospho-S101 in particular, in regulating oxidative stress. We propose that pTHRB2 has a fundamental role in neuronal protection against ROS cellular damage, and mitigates hypothalamic pathological changes found in diet-induced obesity.

Building damage due to various causes occurs frequently and has risk factors that can cause additional collapses. However, it is difficult to accurately identify objects in complex structural sites because of inaccessible situations and image noise. In conventional approaches, close-up images have been used to detect and segment damage images such as cracks. In this study, the method of using a deep learning model is proposed for the rapid determination and analysis of multiple damage types, such as cracks and concrete rubble, in disaster sites. Through the proposed method, it is possible to perform analysis by receiving image information from a robot explorer instead of a human, and it is possible to detect and segment damage information even when the damaged point is photographed at a distance. To accomplish this goal, damage information is detected and segmented using YOLOv7 and Deeplabv2. Damage information is quickly detected through YOLOv7, and semantic segmentation is performed using Deeplabv2 based on the bounding box information obtained through YOLOv7. By using images with various resolutions and senses of distance for training, damage information can be effectively detected not only at short distances but also at long distances. When comparing the results, depending on how YOLOv7 and Deeplabv2 were used, they returned better scores than the comparison model, with a Recall of 0.731, Precision of 0.843, F1 of 0.770, and mIoU of 0.638, and had the lowest standard deviation.

Asterarcys quadricellularis strain AQYS21, a green microalga isolated from the brackish waters near Manseong-ri Black Sand Beach in Korea, shows considerable potential as a source of bioactive compounds and biofuels. Therefore, this study analyzed the morphological, molecular, and biochemical characteristics of this strain; optimized its cultivation conditions; and evaluated its suitability for biodiesel production. Morphological analysis revealed characteristics typical of the Asterarcys genus: spherical to ellipsoidal cells with pyrenoid starch plates and mucilage-embedded coenobia. Additionally, features not previously reported in other A. quadricellularis strains were observed. These included young cells with meridional ribs and an asymmetric spindle-shaped form with one or two pointed ends. Molecular analysis using small-subunit rDNA and tufA sequences confirmed the identification of the strain AQYS21. This strain showed robust growth across a wide temperature range, with optimal conditions at 24 °C and 88 µmol m−2s−1 photon flux density. It was particularly rich in ω-3 α-linolenic acid and palmitic acid. Furthermore, its biodiesel properties indicated its suitability for biodiesel formulations. The biomass of this microalga may serve as a viable feedstock for biodiesel production and a valuable source of ω-3 fatty acids. These findings reveal new morphological characteristics of A. quadricellularis, enhancing our understanding of the species.

Abstract Background Ibrutinib, a first-in-class inhibitor of Bruton’s tyrosine kinase, is approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. Based on encouraging preclinical data, safety and efficacy of ibrutinib combined with companion drugs for advanced renal cell carcinoma (RCC), gastric/gastroesophageal junctional adenocarcinoma (GC), and colorectal adenocarcinoma (CRC) were evaluated. Methods Ibrutinib 560 mg or 840 mg once daily was administered with standard doses of everolimus for RCC, docetaxel for GC, and cetuximab for CRC. Endpoints included determination of the recommended phase 2 dose (RP2D) of ibrutinib in phase 1b and efficacy (overall response rate [ORR] for GC and CRC; progression-free survival [PFS] for CRC) in phase 2. Results A total of 39 (RCC), 46 (GC), and 50 (RCC) patients were enrolled and received the RP2D. Safety profiles were consistent with the individual agents used in the study. Confirmed ORRs were 3% (RCC), 21% (GC), and 19% (CRC). Median (90% CI) PFS was 5.6 (3.9–7.5) months in RCC, 4.0 (2.7–4.2) months in GC, and 5.4 (4.1–5.8) months in CRC. Conclusions Clinically meaningful increases in efficacy were not observed compared to historical controls; however, the data may warrant further evaluation of ibrutinib combinations in other solid tumours. Trial registration ClinicalTrials.gov, NCT02599324.

Abstract Background There have been many prediction studies for imported infectious diseases, employing air-travel volume or the importation risk (IR) index, which is the product of travel-volume and disease burden in the source countries, as major predictors. However, there is a lack of studies validating the predictability of the variables especially for infectious diseases that have rarely been reported. In this study, we analyzed the prediction performance of the IR index and air-travel volume to predict disease importation. Methods Rabies and African trypanosomiasis were used as target diseases. The list of rabies and African trypanosomiasis importation events, annual air-travel volume between two specific countries, and incidence of rabies and African trypanosomiasis in the source countries were obtained from various databases. Results Logistic regression analysis showed that IR index was significantly associated with rabies importation risk (p value

Abstract Background There is limited evidence on the individual and joint effect of socioeconomic status (SES) and unhealthy lifestyle on cancer. Therefore, this study aimed to examine the effects of these factors on cancer incidence and mortality. Methods In this population‐based cohort study, income was used as the proxy of SES. A combined unhealthy lifestyle score was obtained using data on smoking, alcohol consumption, physical activity, and body mass index. Hazard ratios were estimated using a Cox proportional hazards model. Results The study included data on 8,353,169 participants (median follow‐up period, 17 years). Although the association between low income and cancer incidence varied depending on cancer type, low income consistently increased the risk of cancer‐related death with a social gradient. Unhealthy behaviors increased the risk of cancer incidence and mortality, except for thyroid and breast cancer in women and prostate cancer in men. Compared with the wealthiest and healthiest individuals, the poorest and unhealthiest men and women showed 2.1‐fold (2.05–2.14) and 1.36‐fold (1.31–1.41) higher risk of cancer‐related death, respectively. The joint effect was most robust for lung, liver, head, and neck cancers in men and liver and cervical cancers in women; further, the effect was stronger with cancer‐specific mortality than with incidence. Conclusion In conclusion, income and combined healthy lifestyle behaviors have individual and joint effects on cancer incidence and mortality. The effect varies by cancer type and sex.

Abstract Background The temporal investigation of high‐risk areas of cancer incidence and mortality can provide practical implications in cancer control. We aimed to investigate the changes in spatial clusters of incidence and mortality from 1999 through 2013 by major cancer types in South Korea. Methods We applied flexible scan statistics to identify spatial clusters of cancer incidence and mortality by three 5‐year periods and seven major cancer types using the counts of new cases and deaths and population in 244 districts during 1999–2013. Then, we compared the changes across three periods in the locations of primary clusters of incidence and mortality by cancer types. To explore the determinants that possibly affect cancer cluster areas, we compared geographic characteristics between clustered and non‐clustered areas. Results While incidence clusters for lung, stomach, and liver cancer remained in the same areas over 15 years, mortality clusters were relocated to the areas similar to those of incidence clusters. In contrast, colorectal, breast, cervical, and prostate cancer displayed consistently different locations of clusters over time, indicating the disappearance of existing clusters and the appearance of new clusters. Cluster areas tended to show higher portions of older population, unemployment, smoking, and cancer screening compared to non‐cluster areas particularly for mortality. Conclusions Our findings of diverse patterns of changes in cancer incidence and mortality clusters over 15 years can indicate the degree of effectiveness in cancer prevention and treatment depending on the area and suggest the need for area‐specific applications of different cancer control programs.

Abstract Numerous biological systems contain vesicle‐like biomolecular compartments without membranes, which contribute to diverse functions including gene regulation, stress response, signaling, and skin barrier formation. Coacervation, as a form of liquid–liquid phase separation (LLPS), is recognized as a representative precursor to the formation and assembly of membrane‐less vesicle‐like structures, although their formation mechanism remains unclear. In this study, a coacervation‐driven membrane‐less vesicle‐like structure is constructed using two proteins, GG1234 (an anionic intrinsically disordered protein) and bhBMP‐2 (a bioengineered human bone morphogenetic protein 2). GG1234 formed both simple coacervates by itself and complex coacervates with the relatively cationic bhBMP‐2 under acidic conditions. Upon addition of dissolved bhBMP‐2 to the simple coacervates of GG1234, a phase transition from spherical simple coacervates to vesicular condensates occurred via the interactions between GG1234 and bhBMP‐2 on the surface of the highly viscoelastic GG1234 simple coacervates. Furthermore, the shell structure in the outer region of the GG1234/bhBMP‐2 vesicular condensates exhibited gel‐like properties, leading to the formation of multiphasic vesicle‐like compartments. A potential mechanism is proposed for the formation of the membrane‐less GG1234/bhBMP‐2 vesicle‐like compartments. This study provides a dynamic process underlying the formation of biomolecular multiphasic condensates, thereby enhancing the understanding of these biomolecular structures.

Objectives The effect of air pollution on the prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) remains poorly understood. We aimed to evaluate the effect of long-term exposure to particulate matter with an aerodynamic diameter of ≤10 µm (PM10) and nitrogen dioxide (NO2) on mortality in patients with RA-ILD.Methods We included 309 patients (mean age, 61.7 years; male, 44.3%) with RA-ILD. Individual-level long-term exposures to PM10 and NO2 at their residential addresses were estimated using a national-scale exposure prediction model. The effect of the two air pollutants on mortality was estimated using a Cox-proportional hazards model adjusted for individual-level and area-level characteristics.Results The median follow-up period was 4.8 years, and 40.8% of patients died or underwent lung transplantation. The annual average concentrations of PM10 and NO2 were 56.3 μg/m3 and 22.4 ppb, respectively. When air pollutant levels were stratified by quartiles, no association was observed between air pollutant concentration and mortality in patients with RA-ILD. However, when stratified by two groups (high exposure (top 25th percentile) vs low exposure (bottom 75th percentile)), we observed a significant association between high PM10 exposure and mortality (HR 1.68; 95% CI 1.11 to 2.52; p=0.013) but no association between NO2 exposure and mortality. In the subgroup analyses, the effect of high PM10 exposure on mortality was significant in patients aged

Introduction Previous research on post-diagnosis smoking among cancer survivors mainly relied on smoking status, which may not fully reflect the impact of changes in smoking levels. This study aimed to evaluate mortality risk according to smoking trajectories among Korean male cancer survivors, using a trajectory approach to comprehensively capture smoking patterns. Methods The study included 110555 men diagnosed with cancer between 2002 and 2018 from the Korean National Health Information Database. Group-based trajectory modelling was used to identify post-diagnosis smoking trajectories among pre-diagnosis current smokers (n=45331). Cox hazards models were fitted to evaluate mortality risk according to smoking trajectories for pooled cancers, pooled smoking-related cancers, smoking-unrelated cancers, and gastric, colorectal, liver, and lung cancers. Results Smoking trajectories included light-smoking quitters, heavy-smoking quitters, consistent moderate smokers, and decreasing heavy smokers. Smoking significantly increased all-cause and cancer mortality risks in cancer patients for pooled cancers, pooled smoking-related cancers, and pooled smoking-unrelated cancers. Compared to non-smokers, all-cause mortality risk for pooled cancers significantly increased according to smoking trajectories: (AHR=1.33; 95% CI: 1.27–1.40), (AHR=1.39; 95% CI: 1.34–1.44), (AHR=1.44; 95% CI: 1.34–1.54), and (AHR=1.47; 95% CI: 1.36–1.60), respectively. Smoking increased all-cause and cancer mortality risks in gastric and colorectal cancer patients and cancer-specific mortality in lung cancer patients. The significant associations of smoking trajectories with all-cause and cancer mortality risks were primarily observed in 5-year survivors but not in short-term survivors. Among heavy smokers, smoking cessation significantly reduced all-cause mortality risk in the long-term. Conclusions The post-diagnosis smoking trajectory independently predicts cancer prognosis among male cancer patients. Proactive cessation support should be strengthened, particularly for those who smoke heavily.

Abstract Carcinoembryonic antigen (CEA) is the most widely used tumor marker in metastatic colorectal cancer (mCRC). However, its potential as a predictive marker of progression in mCRC during systemic chemotherapy, particularly in patients receiving monoclonal antibodies as a combination therapy, has remained of interest. Herein, we investigated whether CEA changes could predict disease progression and clinical outcomes in patients with mCRC cotreated with systemic chemotherapy and/or biologic agents. A total of 1261 patients with mCRC undergoing a first-line systemic treatment were included in this retrospective study. We analyzed the optimal cut-off value for CEA changes to predict progression at the first response evaluation by the treatment arm (chemotherapy alone, chemotherapy plus anti-vascular endothelial growth factor (VEGF) monoclonal antibody [mAb], and chemotherapy plus anti-epidermal growth factor receptor [EGFR] mAb). These cut-off values were then used to predict overall survival (OS) and progression-free survival (PFS). When stratified by their treatment arm, 891 (70.6%), 266 (21.0%), and 104 (8.2%) of the study patients were included in the chemotherapy alone-, anti-VEGF mAb, and anti-EGFR mAb groups, respectively. The optimal CEA cut-off values were 16.5% and 38.9% increase in the whole cohort and anti-EGFR mAb group, respectively, and these values showed high sensitivity and specificity for predicting disease progression. The patients in the entire population and anti-EGFR mAb group with CEA changes below these cut-off values showed significantly better OS and PFS outcomes compared those whose changes were above cut-off values. Among the patients with mCRC treated with anti-VEGF mAb, no associations were found between OS or PFS outcomes and CEA changes. CEA is potentially a good surrogate marker for predicting disease progression and survival outcomes in patients with mCRC receiving first-line systemic chemotherapy alone or chemotherapy with anti-EGFR mAb, whereas it is less effective in those treated with anti-VEGF mAb.

Abstract Background The aim of the study is to evaluate the risk factors of anastomotic leakage (AL) and develop a nomogram to predict the risk of AL in surgical management of primary ovarian cancer. Methods We retrospectively reviewed 770 patients with primary ovarian cancer who underwent surgical resection of the rectosigmoid colon as part of cytoreductive surgery between January 2000 to December 2020. AL was defined based on radiologic studies or sigmoidoscopy with relevant clinical findings. Logistic regression analyses were performed to identify the risk factor of AL, and a nomogram was developed based on the multivariable analysis. The bootstrapped-concordance index was used for internal validation of the nomogram, and calibration plots were constructed. Results The incidence of AL after resection of the rectosigmoid colon was 4.2% (32/770). Diabetes (OR 3.79; 95% CI, 1.31–12.69; p = 0.031), co-operation with distal pancreatectomy (OR, 4.8150; 95% CI, 1.35–17.10; p = 0.015), macroscopic residual tumor (OR, 7.43; 95% CI, 3.24–17.07; p = 0

Abstract Enterococcus faecalis, a Gram-positive opportunistic pathogen having lipoteichoic acid (LTA) as a major virulence factor, is closely associated with refractory apical periodontitis. Short-chain fatty acids (SCFAs) are found in the apical lesion and may affect inflammatory responses induced by E. faecalis. In the current study, we investigated inflammasome activation by E. faecalis LTA (Ef.LTA) and SCFAs in THP-1 cells. Among SCFAs, butyrate in combination with Ef.LTA markedly enhanced caspase-1 activation and IL-1β secretion whereas these were not induced by Ef.LTA or butyrate alone. Notably, LTAs from Streptococcus gordonii, Staphylococcus aureus, and Bacillus subtilis also showed these effects. Activation of TLR2/GPCR, K+ efflux, and NF-κB were necessary for the IL-1β secretion induced by Ef.LTA/butyrate. The inflammasome complex comprising NLRP3, ASC, and caspase-1 was activated by Ef.LTA/butyrate. In addition, caspase-4 inhibitor diminished IL-1β cleavage and release, indicating that non-canonical activation of the inflammasome is also involved. Ef.LTA/butyrate induced Gasdermin D cleavage, but not the release of the pyroptosis marker, lactate dehydrogenase. This indicated that Ef.LTA/butyrate induces IL-1β production without cell death. Trichostatin A, a histone deacetylase (HDAC) inhibitor, enhanced Ef.LTA/butyrate-induced IL-1β production, indicating that HDAC is engaged in the inflammasome activation. Furthermore, Ef.LTA and butyrate synergistically induced the pulp necrosis that accompanies IL-1β expression in the rat apical periodontitis model. Taken all these results together, Ef.LTA in the presence of butyrate is suggested to facilitate both canonical- and non-canonical inflammasome activation in macrophages via HDAC inhibition. This potentially contributes to dental inflammatory diseases such as apical periodontitis, particularly associated with Gram-positive bacterial infection.

Abstract Introduction Colorectal cancer with peritoneal metastasis (PM) has been considered a non‐curative disease. PM is associated with reduced overall survival (OS) and worse prognosis compared with metastasis at other sites. We aimed to investigate the treatment outcome and recurrence after curative resection of colorectal PM during a long‐term follow‐up. Methods Patients who were diagnosed with colorectal PM and underwent surgery between December 2001 and December 2019 were included (n = 309). Curative resection was defined as PM resection without residual disease after surgery (complete macroscopic resection). Results Of 309 patients, 208 (67.8%) had PM as an initially metastatic disease. Curative (R0/1) resection was achieved in 155 (50.2%) patients, while non‐curative operation (R2 resection or palliative operation including colostomy) was performed in 154 (49.8%) patients. Compared with patients who underwent non‐curative operation, those with curative resection more often had a single PM on preoperative imaging (34.2% vs. 20.8%, p = 0.011) and postoperative results (59.4% vs. 22.7%, p

Abstract Background The COVID-19 pandemic has disrupted malaria control activities globally. Notably, high levels of excess malaria morbidity and mortality in low- and middle-income countries (LMICs) were reported. Although it is crucial to systematically understand the main causes of the disruption to malaria control and synthesize strategies to prepare for future pandemics, such studies are scarce. Therefore, this study aims to better identify barriers against and strategies for malaria control. Methods Following the PRISMA guidelines and through searches of electronic databases and Google Scholar, a systematic literature review was conducted to identify studies pertaining to malaria control published between January 2020 and December 2021. Only studies that discussed reported barriers and/or strategies related to malaria were included for the review. The Mixed Methods Quality Appraisal Tool (MMAT) and the Authority, Accuracy, Coverage, Objectivity, Date and Significance (AACODS) checklist were used for quality appraisal. Key information such as literature type, study design, setting and population, interventions, outcomes, barriers, and strategies were extracted. With an existing framework of four dimensions (accessibility, affordability, availability, and acceptability) further subdivided by the supply and demand sides, this study synthesized information on barriers and strategies related to malaria control and further categorized the strategies based on the time frame. Results From the 30 selected studies, 27 barriers and 39 strategies were identified. The lockdown measures, which mainly threatened geographic accessibility and availability of malaria control services, were identified to be the main barrier hindering effective mobilization of community health workers and resources. Among the identified strategies, clear risk communication strategies would alleviate psychosocial barriers, which challenged acceptability. Some strategies that cross-cut points across all four dimensions would, require systems-level integration to enhance availability and affordability of malaria control. The strategies were distinguished between short-term, for instant response, and mid to long-term for future readiness. Conclusions The pandemic resulted in complex barriers to malaria control, particularly imposing a double burden on LMICs. Identifying strategies to overcome said barriers provides useful insights in the decision-making processes for the current and future pandemic. Cross-cutting strategies that integrate all dimensions need to be considered. Health system strengthening and resilience strategy appropriate for country-specific context is fundamental.

With the development of electric vehicles, indoor driving robots, wearable devices, etc., research on technology for recognizing one's current location continues to progress. Self-localization is an essential need for autonomous driving and mainly requires global positioning system (GPS), thereby using technologies such as LiDAR, Wi-Fi, and visible light communication (VLC). However, GPS is greatly affected by its surrounding environment, and it can make errors, especially in spaces where signals are blocked, such as tunnels and buildings. In this paper, we propose a system for estimating one's location using LED lights and frequency components with different color temperatures in an indoor space such as a tunnel. We installed three types of LED lights with different color temperatures in a tunnel-like experimental environment and collected data using RGB sensors. We also estimated the user's current location according to the color temperature and frequency component analysis from the data. In most cases, it was measured within a margin of error of 0–2 cm. It is expected that this will be used for generating data on the location of indoor service robots and autonomous vehicles in spaces where it is difficult to use GPS.

Developing new plant varieties plays a crucial role in competitiveness in the agricultural and food industries and enhancing food security. Daehong (DH) is a new variety of Crataegus pinnatifida Bunge (CP); however, its physiological functions and potential as a nutraceutical ingredient remain unknown. Here, the efficacy of DH on inflammatory bowel disease (IBD) was investigated using dextran sulfate sodium (DSS)-induced colitis mice, and its relative pharmacological effects were analyzed against CP. DH improved colitis-induced weight loss, colon shortening, and inflammatory responses and reduced intestinal permeability. The reactive oxygen species (ROS)-mediated necroptotic signal that triggers enterocyte cell death in DSS-induced colitis was effectively controlled by DH, attributed to epicatechin. DSS-induced gut dysbiosis was recovered into a healthy gut microbiome environment by DH, increasing beneficial bacteria, like Akkermansia muciniphila, and changing harmful bacteria, including Bacteroides vulgatus and Peptostreptococcaceae. DH shows potential as a dietary or pharmaceutical ingredient to promote gut health and to prevent and treat IBD.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL), which is the most common type of ALL, has an excellent prognosis with long-term event-free survival of 90%. The malignancy has several genetic abnormalities that may influence patient prognosis. Rearrangements of the three immunoglobulin genes IGK(2p12), IGH(14q32), and IGL(22q11) are often seen, especially in non-Hodgkin lymphoma (NHL), but recombination of these genes are uncommon. The translocation, t(14;22)(q32;q11) has been reported in only 9 B-cell leukemia/lymphoma cases, but there has been no report about the clinical feature and prognosis of BCP-ALL with t(14;22)(q32;q11). In this paper, we describe the first pediatric case of BCP-ALL with t(14;22)(q32;q11) who presented with a very high white blood cell (WBC) count. He achieved cytogenetic complete remission after induction chemotherapy, and negative minimal residual disease (MRD) at the end of consolidation.

Abstract Background The aim of this study was to evaluate the influence of increased irradiation distance on the flexural strength (FS), dentin micro-shear bond strength (μSBS), and the degree of conversion (DC) of bulk-fill flowable, conventional flowable, and packable resin composites. Methods The resin composites tested were Surefil® SDR™ (SDR), Filtek Z350 XT Flowable Restorative A2 shade (Z3F), and Filtek Z350 XT Universal Restorative A2 shade (Z3P). Specimens were cured at four irradiation distances (0, 2, 4, and 8 mm) with an Elipar DeepCure-S LED curing light for 20 s. FS tests were performed (n = 15) using bar-shaped specimens (8 mm × 2 mm × 2 mm) of the resin composites. μSBS tests were performed on the occlusal surfaces of extracted third molars from humans that were ground to expose dentin (n = 15). DC was measured by using Raman spectroscopy on the top and bottom surfaces of disk specimens (2-mm thick) (n = 3). To further investigate whether extended irradiation times could compensate for reduced irradiance, additional Z3P specimens were prepared, which were light-cured at 8-mm distances for 40 and 60 s and subjected to FS tests, μSBS tests, and Raman spectroscopy. Both two-way and one-way ANOVA were used for statistical analyses. Results Both FS and DC of Z3P specimens cured at an 8-mm distance were significantly lower than those cured at shorter distances (p

The wheels of railway vehicles are of paramount importance in relation to railroad operations and safety. Currently, the management of railway vehicle wheels is restricted to post-event inspections of the wheels whenever physical phenomena, such as abnormal vibrations and noise, occur during the operation of railway vehicles. To address this issue, this paper proposes a method for predicting abnormalities in railway wheels in advance and enhancing the learning and prediction performance of machine learning algorithms. Data were collected during the operation of Line 4 of the Busan Metro in South Korea by directly attaching sensors to the railway vehicles. Through the analysis of key factors in the collected data, factors that can be used for tire condition classification were derived. Additionally, through data distribution analysis and correlation analysis, factors for classifying tire conditions were identified. As a result, it was determined that the z-axis of acceleration has a significant impact, and machine learning techniques such as SVM (Linear Kernel, RBF Kernel) and Random Forest were utilized based on acceleration data to classify tire conditions into in-service and defective states. The SVM (Linear Kernel) yielded the highest recognition rate at 98.70%.

Background: The interest in ultraviolet (UV) radiation from the sun and artificial sources has been recently increasing due to its toxic effects, including sunburn, erythema, photodamage, and photocarcinogenesis. In this study, we aimed to develop a valuable nanomaterial that can block total UV rays using an undervalued, yet profitable marine organism. We successfully developed carbon nanodots (CNDs) and a CNDs-polyvinyl alcohol (PVA) composite film that effectively protect against UV-A, UV-B, and UV-C radiation based on a common brown algae, sea cauliflower (Leathesia difformis), through simple hydrothermal synthesis in aqueous solution. Results: CNDs-PVA film protected rhodamine B from photobleaching and polydiacetylene vesicles with 10,12-tricosadiynoic acid from polymerization. As-fabricated CNDs in aqueous solution blocked >99% of UV-A light, which causes photoaging and skin cancer. The CNDs-PVA film showed excellent transparency, with >84% transmittance of visible light, and effectively blocked >60% of UV-A/B and >30% of UV-C rays under direct and strong irradiation. Conclusions: This preliminary work indicates that CNDs based on underutilized marine brown algae have strong potential for application in technologies for wide UV protection.How to cite: Kim KW, Kwon YM, Kim SY, et al. One-pot synthesis of UV-protective carbon nanodots from sea cauliflower (Leathesia difformis). Electron J Biotechnol 2022;56. https://doi.org/10.1016/j.ejbt.2021.12.004

Abstract Bacterial vaginosis (BV) is the most common vaginal infection in reproductive women, which is characterized by depleted level of lactic acid bacteria and overgrowth of anaerobes such as Gardnerella vaginalis spp. Lactic acid bacteria have been known to be beneficial for amelioration of BV, since they produce antimicrobial substances against G. vaginalis spp. The objectives of this study were to characterize different fractions of cell-free supernatant of Lactobacillus paracasei CH88 (LCFS) and investigate antibacterial activity of the LCFS fractions against G. vaginalis in-vitro and in-vivo. Antibacterial activity of the LCFS was stable during thermal treatment up to 120 °C for 30 min and maintained at pH ranging from 3.0 to 13.0 except pH 5.0. Fraction below 3 kDa of the LCFS partially lost its antibacterial activity after treatment with proteolytic enzymes. Precipitated protein fraction below 3 kDa of the LCFS (

Abstract Background This study was conducted to compare the reported adverse event (AE) profiles and unexpected use of medical services during chemotherapy between before and after the healthcare reimbursement of AE evaluation in patients with cancer. Patients and Methods Using the electronic medical record database system, extracted patients with breast, lung, gastric, and colorectal cancers receiving neoadjuvant or adjuvant chemotherapy between September 2013 and December 2016 at four centers in Korea were matched using the 1:1 greedy method: pre‐reimbursement group (n = 1084) and post‐reimbursement group (n = 1084). Unexpected outpatient department (OPD), emergency room (ER) visit, hospitalization rates, and chemotherapy completion rates were compared between the groups. Results The baseline characteristics were well‐balanced between the groups. By chemotherapy cycle, hospitalization (1.8% vs. 2.3%; p = 0.039), and ER visit rates (3.3% vs. 3.9%; p = 0.064) were lower in the post‐reimbursement group than that in the pre‐reimbursement group. In particular, since cycle 2, ER visit and hospitalization rates were significantly lower in the post‐reimbursement group than those in the pre‐reimbursement group (2.6% vs. 3.3%; p = 0.020 and 1.4% vs. 2.0%; p = 0.007, respectively), although no significant differences were observed during cycle 1. The OPD visit rates were similar between both groups, regardless of cycles. The post‐reimbursement group had a higher proportion of patients who completed chemotherapy as planned than the pre‐reimbursement group (93.5% vs. 90.1%; p = 0.006). Post‐reimbursement group had more AEs reported, including alopecia, fatigue, diarrhea, anorexia, and peripheral neuropathy, during cycle 1 than the pre‐reimbursement group, which significantly decreased after cycle 2. Conclusion The introduction of healthcare reimbursement for AE evaluation may help physicians capture and appropriately manage AEs, consequently, decreasing hospital utilization and increasing chemotherapy completion rates.

Abstract We aimed to investigate the dynamic changes of gene expression profiles and immune microenvironment linked to resistance to cetuximab-based treatments in patients with metastatic colorectal cancer (mCRC). A total of 106 patients with RAS-wild type mCRC who were treated with cetuximab-based treatments were included as the study population. RNA-sequencing and multiplexed immunohistochemistry were performed using paired or unpaired pre-treatment and post-treatment tumor tissues. Differentially expressed gene analysis of paired pre-treatment and post-treatment tumor tissues that develop acquired resistance (AR) identified the AR signature. Gene ontology analysis of the AR signature indicated enrichment of immune-related pathway genes. Among the immune subsets whose abundance was estimated by CIBERSORT, M2 macrophages showed the most prominent positive correlation with the expression of the AR signature. Among the post-treatment samples, progressive disease (PD) tumors showed a significantly higher abundance of M2 macrophages compared to non-PD tumors. These findings were validated by multiplexed immunohistochemistry analysis: the density of CD68+CD206+ M2 macrophages significantly increased at the time of PD following cetuximab-based treatment, whereas it did not consistently change in the tumor pairs of non-PD. In conclusion, a dynamic increase of M2 macrophages is associated with disease progression during cetuximab-based treatment of mCRCs. Targeting M2 macrophages is a promising immunotherapeutic strategy in this clinical context.

BackgroundLittle is known about applying machine learning (ML) techniques to identify the important variables contributing to the occurrence of gastrointestinal (GI) cancer in epidemiological studies. We aimed to compare different ML models to a Cox proportional hazards (CPH) model regarding their ability to predict the risk of GI cancer based on metabolic syndrome (MetS) and its components.MethodsA total of 41,837 participants were included in a prospective cohort study. Incident cancer cases were identified by following up with participants until December 2019. We used CPH, random survival forest (RSF), survival trees (ST), gradient boosting (GB), survival support vector machine (SSVM), and extra survival trees (EST) models to explore the impact of MetS on GI cancer prediction. We used the C-index and integrated Brier score (IBS) to compare the models.ResultsIn all, 540 incident GI cancer cases were identified. The GB and SSVM models exhibited comparable performance to the CPH model concerning the C-index (0.725). We also recorded a similar IBS for all models (0.017). Fasting glucose and waist circumference were considered important predictors.ConclusionsOur study found comparably good performance concerning the C-index for the ML models and CPH model. This finding suggests that ML models may be considered another method for survival analysis when the CPH model’s conditions are not satisfied.

Indocyanine green (ICG) has been used in clinical practice for more than 40 years and its safety and preferential accumulation in tumors has been reported for various tumor types, including colon cancer. However, reports on clinical assessments of ICG-based molecular endoscopy imaging for precancerous lesions are scarce. We determined visualization ability of ICG fluorescence endoscopy in colitis-associated colon cancer using 30 lesions from an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and 16 colon cancer patient tissue-samples. With a total of 60 images (optical, fluorescence) obtained during endoscopy observation of mouse colon cancer, we used deep learning network to predict four classes (Normal, Dysplasia, Adenoma, and Carcinoma) of colorectal cancer development. ICG could detect 100% of carcinoma, 90% of adenoma, and 57% of dysplasia, with little background signal at 30 min after injection via real-time fluorescence endoscopy. Correlation analysis with immunohistochemistry revealed a positive correlation of ICG with inducible nitric oxide synthase (iNOS; r > 0.5). Increased expression of iNOS resulted in increased levels of cellular nitric oxide in cancer cells compared to that in normal cells, which was related to the inhibition of drug efflux via the ABCB1 transporter down-regulation resulting in delayed retention of intracellular ICG. With artificial intelligence training, the accuracy of image classification into four classes using data sets, such as fluorescence, optical, and fluorescence/optical images was assessed. Fluorescence images obtained the highest accuracy (AUC of 0.8125) than optical and fluorescence/optical images (AUC of 0.75 and 0.6667, respectively). These findings highlight the clinical feasibility of ICG as a detector of precancerous lesions in real-time fluorescence endoscopy with artificial intelligence training and suggest that the mechanism of ICG retention in cancer cells is related to intracellular nitric oxide concentration.

Little is known about the effect of air pollution on Alzheimer’s disease (AD)-specific brain structural pathologies. There is also a lack of evidence on whether this effect leads to poorer cognitive function. We investigated whether, and the extent to which, AD-like cortical atrophy mediated the association between air pollution exposures and cognitive function in dementia-free adults. We used cross-sectional data from 640 participants who underwent brain magnetic resonance imaging and the Montreal Cognitive Assessment (MoCA). Mean cortical thickness (as the measure of global cortical atrophy) and machine learning-based AD-like cortical atrophy score were estimated from brain images. Concentrations of particulate matter with diameters ≤ 10 μm (PM10) and ≤ 2.5 μm (PM2.5) and nitrogen dioxide (NO2) were estimated based on each participant’s residential address. Following the product method, a mediation effect was tested by conducting a series of three regression analyses (exposure to outcome; exposure to mediator; and exposure and mediator to outcome). A 10 μg/m3 increase in PM10 (β = -1.13; 95 % CI, −1.73 to −0.53) and a 10 ppb increase in NO2 (β = -1.09; 95 % CI, −1.40 to −0.78) were significantly associated with a lower MoCA score. PM10 (β = 0.27; 95 % CI, 0.06 to 0.48) and NO2 (β = 0.35; 95 % CI, 0.25 to 0.45) were significantly associated with an increased AD-like cortical atrophy score. Effects of PM10 and NO2 on MoCA scores were significantly mediated by mean cortical thickness (proportions mediated: 25 %–28 %) and AD-like cortical atrophy scores (13 %–16 %). The findings suggest that air pollution exposures may induce AD-like cortical atrophy, and that this effect may lead to poorer cognitive function in dementia-free adults.

Abstract Background The addition of bioactive glass (BG), a highly bioactive material with remineralization potential, might improve the drawback of weakening property of mineral trioxide aggregates (MTA) when it encounters with body fluid. This study aims to evaluate the effect of BG addition on physical properties of MTA. Methods ProRoot (MTA), and MTA with various concentrations of BG (1, 2, 5 and 10% BG/MTA) were prepared. Simulated body fluid (SBF) was used to investigate the effect of the storage solution on dentin remineralization. Prepared specimens were examined as following; the push-out bond strength to dentin, compressive strength, setting time solubility and X-ray diffraction (XRD) analysis. Results The 2% BG/MTA showed higher push-out bond strengths than control group after 7 days of SBF storage. The 2% BG/MTA exhibited the highest compressive strength. Setting times were reduced in the 1 and 2% BG/MTA groups, and solubility of all experimental groups were clinically acceptable. In all groups, precipitates were observed in dentinal tubules via SEM. XRD showed the increased hydroxyapatite peaks in the 2, 5 and 10% BG/MTA groups. Conclusion It was verified that the BG-added MTA increased dentin push-out bond strength and compressive strength under SBF storage. The addition of BG did not negatively affect the MTA maturation reaction; it increased the amount of hydroxyapatite during SBF maturation.

This report describes a case of Scheimpflug topography oriented adequate repositioning of a misaligned thick free flap after laser in situ keratomileusis (LASIK). A 24-year-old patient consulted for irregular astigmatism and disoriented free right eye flap. The patient previously underwent binocular LASIK at a private clinic. During the right eye surgery, the flap was repositioned after laser ablation due to the free flap. The free flap was not repositioned to its original configuration due to insufficient preoperative corneal marking. On examination, the uncorrected visual acuity was 0.4, and refractive power was +2.00 Dsph with −4.25 Dcyl axis 66 in the right eye. Scheimpflug topography revealed irregular right eye astigmatism. The sagittal curvature of topography showed a 40° counterclockwise misalignment of the steep axis of the cornea. The free flap was repositioned by 40° clockwise rotation. After this, the refractive corneal power improved to −1.00 Dsph with −1.00 Dcyl Axis 19 in the right eye. The uncorrected and best-corrected visual acuity improved to 20/30 and 20/25 (x − 0.25Dsph −1.25 Dcyl A20), respectively. This is the first report on free flap repositioning using Scheimpflug topography. As proper flap positioning was compromised because of the free LASIK flap with no preoperative corneal marking, the flap was effectively repositioned using Scheimpflug topography.

Numerous molecular and physiological processes in the skeletal muscle undergo circadian time-dependent oscillations in accordance with daily activity/rest cycles. The circadian regulatory mechanisms underlying these cyclic processes, especially at the post-transcriptional level, are not well defined. Previously, we reported that the circadian E3 ligase FBXL21 mediates rhythmic degradation of the sarcomere protein TCAP in conjunction with GSK-3β, and Psttm mice harboring an Fbxl21 hypomorph allele show reduced muscle fiber diameter and impaired muscle function. To further elucidate the regulatory function of FBXL21 in skeletal muscle, we investigated another sarcomere protein, Myozenin1 (MYOZ1), that we identified as an FBXL21-binding protein from yeast 2-hybrid screening. We show that FBXL21 binding to MYOZ1 led to ubiquitination-mediated proteasomal degradation. GSK-3β co-expression and inhibition were found to accelerate and decelerate FBXL21-mediated MYOZ1 degradation, respectively. Previously, MYOZ1 has been shown to inhibit calcineurin/NFAT signaling important for muscle differentiation. In accordance, Fbxl21 KO and MyoZ1 KO in C2C12 cells impaired and enhanced myogenic differentiation respectively compared with control C2C12 cells, concomitant with distinct effects on NFAT nuclear localization and NFAT target gene expression. Importantly, in Psttm mice, both the levels and diurnal rhythm of NFAT2 nuclear localization were significantly diminished relative to wild-type mice, and circadian expression of NFAT target genes associated with muscle differentiation was also markedly dampened. Furthermore, Psttm mice exhibited significant disruption of sarcomere structure with a considerable excess of MYOZ1 accumulation in the Z-line. Taken together, our study illustrates a pivotal role of FBXL21 in sarcomere structure and muscle differentiation by regulating MYOZ1 degradation and NFAT2 signaling.

A better understanding of the effects of preoperative chemoradiotherapy (CRT) on tumor immune microenvironment (TIME) is essential to improve the treatment outcomes of patients with locally advanced rectal cancer (LARC). In this context, we performed a multiplex immunofluorescence staining to evaluate the TIME in 158 patients with LARC who underwent preoperative CRT followed by surgery and adjuvant chemotherapy in the ADORE trial. We found that higher levels of T-cell subsets (CD3+, CD4+, and CD8+) and dendritic cells in the tumor compartment of pretreatment biopsy samples were associated with good response to preoperative CRT. After CRT, there was a significant increase in the densities of CD3+ T cells, CD8+ T cells, and dendritic cells, while that of CD4+FoxP3+ regulatory T cells decreased, indicating that CRT changed the TIME into a more immune-active status. However, CRT also conferred an immunosuppressive effect by polarizing the tumor-associated macrophages from pro-inflammatory M1 macrophage to immune-suppressive M2 macrophages and decreasing the density of B cells. High delta values of CD3+ T cells and PD-L1+ lymphocytes after CRT were associated with good disease-free survival (DFS), while that of CD4+FoxP3+ regulatory T cells was associated with poor DFS. These findings provide a framework for future studies incorporating strategies to modulate the TIME in patients with LARC.

Background: The effect of ambient PM2.5 on the incidence of tuberculosis (TB) has been investigated in epidemiological studies. However, they did not separately study new and relapsed TB infection and focused on relatively short-term effects of PM2.5. In this regard, we examined the associations of long-term PM2.5 exposures with both new and relapsed TB incidences in South Korea, where the disease burden of TB is greatest among high-income countries. Methods: An area-level ecological study of 250 districts was conducted from 2015 to 2019. Age- and sex-standardized TB incidence ratios for each district and year were used as outcome variables, and their associations with PM2.5 concentrations for one to five-year average were examined. Negative binomial regression models incorporating spatiotemporal autocorrelation were employed using integrated nested Laplace approximations. Stratified analyses were conducted by type of TB (total, new, and relapsed cases). Results: Districts with higher PM2.5 concentrations tended to have significantly higher TB recurrence rate. The relative risks per 10 µg/m3 PM2.5 increase were 1.218 (95% credible interval 1.051–1.411), 1.260 (1.039–1.527) and 1.473 (1.015–2.137) using the two, three and five-year average PM2.5 exposures, respectively. Conclusions: The results imply that interventions for reducing air pollution might help prevent TB recurrence.

Abstract Background Much of the current evidence of associations between long-term PM2.5 and health outcomes relies on national or regional analyses using exposures derived directly from regulatory monitoring data. These findings could be affected by limited spatial coverage of monitoring data, particularly for time periods before spatially extensive monitoring began in the late 1990s. For instance, Pope et al. (2009) showed that between 1980 and 2000 a 10 μg/m3 reduction in PM2.5 was associated with an average 0.61 year (standard error (SE) = 0.20) longer life expectancy. That analysis used 1979–1983 averages of PM2.5 across 51 U.S. Metropolitan Statistical Areas (MSAs) computed from about 130 monitoring sites. Our reanalysis re-examines this association using modeled PM2.5 in order to assess population- or spatially-representative exposure. We hypothesized that modeled PM2.5 with finer spatial resolution provides more accurate health effect estimates compared to limited monitoring data. Methods We used the same data for life expectancy and confounders, as well as the same analysis models, and investigated the same 211 continental U.S. counties, as Pope et al. (2009). For modeled PM2.5, we relied on a previously-developed point prediction model based on regulatory monitoring data for 1999–2015 and back-extrapolation to 1979. Using this model, we predicted annual average concentrations at centroids of all 72,271 census tracts and 12,501 25-km national grid cells covering the contiguous U.S., to represent population and space, respectively. We averaged these predictions to the county for the two time periods (1979–1983 and 1999–2000), whereas the original analysis used MSA averages given limited monitoring data. Finally, we estimated regression coefficients for PM2.5 reduction on life expectancy improvement over the two periods, adjusting for area-level confounders. Results A 10 μg/m3 decrease in modeled PM2.5 based on census tract and national grid predictions was associated with 0.69 (standard error (SE) = 0.31) and 0.81 (0.29) -year increases in life expectancy. These estimates are higher than the estimate of Pope et al. (2009); they also have larger SEs likely because of smaller variability in exposure predictions, a standard property of regression. Two sets of effect estimates, however, had overlapping confidence intervals. Conclusions Our approach for estimating population- and spatially-representative PM2.5 concentrations based on census tract and national grid predictions, respectively, provided generally consistent findings to the original findings using limited monitoring data. This finding lends additional support to the evidence that reduced fine particulate matter contributes to extended life expectancy.

Abstract For the sensitive diagnosis of colorectal cancer lesions, advanced molecular imaging techniques using cancer-specific targets have emerged. However, issues regarding the clearance of unbound probes and immunogenicity remain unresolved. To overcome these limitations, we developed a small-sized scFv antibody fragment conjugated with FITC for the real-time detection of colorectal cancer by in vivo molecular endoscopy imaging. A small-sized scFv fragment can target colon cancer secreted protein-2 (CCSP-2), highly expressed in colorectal adenocarcinoma tissues; moreover, its full-length IgG probe has been used for molecular imaging previously. To assess the efficacy of anti-CCSP-2 scFv-FITC, surgical specimens were obtained from 21 patients with colorectal cancer for ex vivo molecular fluorescence analysis, histology, and immunohistochemistry. Orthotopic mice were administered with anti-CCSP-2 scFv-FITC topically and intravenously, and distinct tumor lesions were observed by real-time fluorescence colonoscopy. The fluorescence imaging of human colon cancer specimens allowed the differentiation of malignant tissues from non-malignant tissues (p

BackgroundDespite the increasing attention to electronic health management information systems (HMISs) in global health, most African countries still depend on inefficient paper-based systems. Good Neighbors International and Evaluate 4 Health have recently supported the Ghana Health Service on the rollout of a mobile health–based HMIS called the e-Tracker system in 2 regions in Ghana. The e-Tracker is an Android-based tracker capture app that electronically manages maternal and child health (MCH) data. The Ghana Health Service has implemented this new system in Community Health Planning and Services in the 2 regions (Volta and Eastern). ObjectiveThis study aims to evaluate changes in health workers’ capacity and behavior after using the e-Tracker to deliver MCH services. Specifically, the study assesses the changes in knowledge, attitude, and practice (KAP) of the health workers toward the e-Tracker system by comparing the pre- and postsurvey results. MethodsThe KAP of frontline health workers was measured through self-administered surveys before and after using the e-Tracker system to assess their capacity and behavioral change toward the system. A total of 1124 health workers from the Volta and Eastern regions responded to the pre-post surveys. This study conducted the McNemar chi-square test and Wilcoxon signed-rank test for a pre-post comparison analysis. In addition, random-effects ordered logistic regression analysis and random-effects panel analysis were conducted to identify factors associated with KAP level. ResultsThe pre-post comparison analysis showed significant improvement in health workers’ capacity, with higher knowledge and practice levels after using the e-Tracker system. As for knowledge, there was a 9.9%-point increase (from 559/1109, 50.41% to 669/1109, 60.32%) in the proportion of the respondents who were able to generate basic statistics on the number of children born in a random month within 30 minutes. In the practice section, the percentage of respondents who had scheduled clientencounters increased from 91.41% (968/1059) to 97.83% (1036/1059). By contrast, responses to the attitude (acceptability) became less favorable after experiencing the actual system. For instance, 48.53% (544/1121) initially expressed their preferences for an electronic system; however, the proportion decreased to 33.45% (375/1121) after the intervention. Random-effects ordered logistic regression showed that days of overwork were significantly associated with health workers’ attitudes toward the e-Tracker system. ConclusionsThis study provides empirical evidence that the e-Tracker system is conducive to enhancing capacity in MCH data management for providing necessary MCH services. However, the change in attitude implies that the users appear to feel less comfortable using the new system. As Ghana plans to scale up the electronic HMIS system using the e-Tracker to the national level, strategies to enhance health workers’ attitudes are necessary to sustain this new system.

Summary: Plasmid DNA (pDNA) transfection is advantageous for gene therapies requiring larger genetic elements, including “all-in-one” CRISPR/Cas9 plasmids, but is limited by toxicity as well as poor intracellular release and transfection efficiency in immune cell populations. Here, we developed a synthetic non-viral gene delivery platform composed of poly(ethylene glycol)-b-poly(propylene sulfide) copolymers linked to a cationic dendritic peptide (DP) via a reduceable bond, PEG-b-PPS-ss-DP (PPDP). A library of self-assembling PPDP polymers was synthesized and screened to identify optimal constructs capable of transfecting macrophages with small (pCMV-DsRed, 4.6 kb) and large (pL-CRISPR.EFS.tRFP, 11.7 kb) plasmids. The optimized PPDP construct transfected macrophages, fibroblasts, dendritic cells, and T cells more efficiently and with less toxicity than a commercial Lipo2K reagent, regardless of pDNA size and under standard culture conditions in the presence of serum. The PPDP technology described herein is a stimuli-responsive polymeric nanovector that can be leveraged to meet diverse challenges in gene delivery.