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The conventional alginate technique, widely employed in dentistry to capture tooth morphology, has faced challenges, particularly due to potential discomfort and the risk of allergy reactions among specific patient groups. Consequently, 3D intraoral scanners (IOS), enabling contactless acquisition of dental shapes, have gained widespread adoption. However, for tooth segmentation in 3D dental images obtained through IOS, the majority of methods heavily rely on labor-intensive annotation of high-quality datasets. In this study, we introduce the Weighted Sparse Convolution and Transformer Feature Aggregation Network (WCTN) as a model designed for the segmentation of teeth within 3D dental datasets. The voxel-grid partitioning mechanism in this model efficiently clusters point clouds to extract features with minimal resource usage. Employing weighted sparse convolution operations, WCTN extracts local features from grouped points, followed by sequential capturing of global features through Transformer modules. An adaptive feature fusion strategy was devised, seamlessly combining local and global features to yield robust representations, particularly optimized for 3D dental datasets with uniform density. We evaluated three different versions of WCTN, distinguished by the number of features. Among them, the largest-scale model exhibited superior performance, compared to graph-based models and Transformer-based models with the overall accuracy improvements of 1.89% and 7.18%, respectively. This result highlights the outstanding performance achieved by aggregating diverse features. In conclusion, the proposed model possesses the potential to expedite and automate tooth segmentation tasks, promising to enhance current clinical practices.

Abstract Background Large-scale data on the photosynthetic characteristics of whole crop canopy is crucial for improving yield. However, current data collection methods remain challenging, and the time constraints associated with photosynthetic data collection further complicate matters. Developing a practical yet easy-to-use tool for collecting whole-canopy data is essential to address these challenges. Furthermore, it is necessary to obtain instantaneous measurements of photosynthetic rate over a wide range of CO2 concentrations under an unsteady state to enable faster data collection and obtain reliable biochemical limits of carbon assimilation. This study developed a semi-open chamber system with steady and unsteady state measurement techniques to collect biochemical photosynthetic data from an entire cucumber canopy, emphasizing the correction procedures for CO2 concentration of unsteady state measurements applicable regardless of chamber scale. Results After constructing a semi-open chamber system, we described how to correct measurement errors according to chamber volume. In order to assess the accuracy of the newly developed system, an analysis was conducted to determine the overall measurement error resulting from variations in the reference, sample CO2 concentration, and leakage flow rate. The total measurement error was accurate to no more than 10%. Furthermore, the difference between the photosynthetic rate of the single leaf and that of the whole-canopy was not significant in Rubisco activity-limited carboxylation range. In addition, the Farquhar–von Caemmerer–Berry (FvCB) model parameters and the photosynthetic rate estimation values were compared to evaluate the steady- and unsteady state measurement methods between the cucumber seedlings' single-leaf and whole-canopy. The average root mean square error of the FvCB model in the steady (standard A-Ci response) and unsteady states (800 to 400 ramp) of the chambers was 1.4 and 2.3, respectively. Results show that the developed system is suitable for measuring the gas exchange rate of the cucumber canopy. Conclusions We demonstrate the correction method for measurement errors to enable the gas exchange rate of the whole-canopy even in an unsteady state. The correction method of the measurement system of the gas exchange rate for the whole- canopy can be applied regardless of the volume of the chamber, and it can be applied simply to other chamber systems. In addition, an unsteady state measurement method for fast data collection was also applicable. However, it was deemed necessary to identify a more optimal measurement range by conducting measurements across a broader range of values.

Purpose The objective of this study was to assess the feasibility of incorporating virtual reality/augmented reality (VR/AR) programs into practical tests administered as part of the Korean Radiological Technologists Licensing Examination (KRTLE). This evaluation is grounded in a comprehensive survey that targeted enrolled students in departments of radiology across the nation. Methods In total, 682 students from radiology departments across the nation were participants in the survey. An online survey platform was used, and the questionnaire was structured into 5 distinct sections and 27 questions. A frequency analysis for each section of the survey was conducted using IBM SPSS ver. 27.0. Results Direct or indirect exposure to VR/AR content was reported by 67.7% of all respondents. Furthermore, 55.4% of the respondents expressed that VR/AR could be integrated into their classes, which signified a widespread acknowledgment of VR among the students. With regards to the integration of a VR/AR or mixed reality program into the practical tests for purposes of the KRTLE, a substantial amount of the respondents (57.3%) exhibited a positive inclination and recommended its introduction. Conclusion The application of VR/AR programs within practical tests of the KRTLE will be used as an alternative for evaluating clinical examination procedures and validating job skills.

We aimed to develop a more accurate transpiration model for cucumber (Cucumis sativus L.) plants to optimize irrigation and nutrient usage in soilless greenhouse cultivation. Accurate modeling of transpiration in greenhouse-grown cucumbers is crucial for effective cultivation practices. Existing models have limitations that hinder their applicability. Therefore, this research focused on refining the modeling approach to address these limitations. To achieve this, a comprehensive methodology was employed. The actual transpiration rates of three cucumber plants were measured using a load cell, enabling crop fresh weight changes to be calculated. The transpiration model was developed by making specific corrections to the formula derived from the Penman-Monteith equation. In addition, the study investigated the relationship between transpiration rate and solar radiation (Rad) and vapor pressure deficit (VPD), identifying a nonlinear association between these variables. The transpiration model was adjusted to account for these nonlinear relationships and compensate for Rad and VPD. Comparative analysis between the actual and estimated transpiration rates demonstrated that the developed cucumber transpiration model reduced overestimation by 23.69%. Furthermore, the model exhibited higher coefficients of determination and root mean square error (RMSE) values than existing models, suggesting its superior accuracy in predicting transpiration rates. Implementing the transpiration model-based irrigation method demonstrated the potential for ∼21% nutrient savings compared with conventional irrigation practices. This finding highlights the practical applications of the developed model—accounting for a nonlinearity of Rad and VPD—in optimizing irrigation practices for greenhouse cucumber cultivation.

Recently, reactive materials have been developed for penetrative projectiles to improve impact resistance and energy capacity. However, the design of a reactive material structure, involving shape and size, is challenging because of difficulties such as high non-linearity of impact resistance, manufacturing limitations of reactive materials and high expenses of penetration experiments. In this study, a design optimization methodology for the reactive material structure is developed based on the finite element analysis. A finite element model for penetration analysis is introduced to save the expenses of the experiments. Impact resistance is assessed through the analysis, and result is calibrated by comparing with experimental results. Based on the model, topology optimization is introduced to determine shape of the structure. The design variables and constraints of the optimization are proposed considering the manufacturing limitations, and the optimal shape that can be manufactured by cold spraying is determined. Based on the optimal shape, size optimization is introduced to determine the geometric dimensions of the structure. As a result, optimal design of the reactive material structure and steel case of the penetrative projectile, which maximizes the impact resistance, is determined. Using the design process proposed in this study, reactive material structures can be designed considering not only mechanical performances but also manufacturing limitations, with reasonable time and cost.

Advanced information and communication technologies (ICTs) have made data collection more efficient for agricultural studies. Using publicly available database in South Korea, we estimated the relationship between the management of air temperature and relative humidity and the strawberry yield during two harvest seasons. Longitudinal data of multiple greenhouses were merged and processed, and mixed-effects models were applied to account both observed and unobserved factors across the greenhouses. The averages of air temperature and relative humidity inside each greenhouse do not take volatility of the time-varying variables into consideration, so we assessed the management of each greenhouse by the percent of time that air temperature between 15 °C and 20 °C (denoted as T%) and the percent of time that relative humidity between 0% and 50% (denoted by H%). The statistical models estimated that the strawberry yield decreases with respect to the number of days since harvest began and the rate of decrease is slower when T% and H% are higher. This study used large-scale multilocation data to provide the practical suggestion that air temperature and relative humidity should be maintained within the optimal ranges to mitigate the loss of strawberry yield especially at the later phase of a harvest season.

The aim of this study is to provide basic information that contributes to vaccine inoculation policy after COVID-19. We used the secondary data of the influenza vaccine inoculation behavior survey for community-dwelling adults conducted in 2011, before the COVID-19 pandemic, but after the 2009 novel influenza A (H1N1) pdm 09 pandemic. All factors such as socio-demographic characteristics, health-related behaviors, family environment, physical and social environment, and area of residence were adjusted, and factors related to vaccine inoculation behavior were analyzed. Those living with pregnant women had a significantly higher odds ratio of inoculation; this was self-evident in that those people considered infection to their family. Regarding the social environment, those aged 20–64 years with a significantly higher adjusted odds ratio of inoculation were those with “at least five people with which they interacted in the neighborhood”. This result can be interpreted in two ways relating to altruism in Japan. Finally, we indicated the importance of learning from the past, including the case of 2009.

The receptacle of strawberry is a more direct part than the flower for predicting yield as they eventually become fruits. Thus, we tried to predict the yield by combining an AI technique for receptacle detection in images and statistical analysis on the relationship between the number of receptacles detected and the strawberry yield over a period of time. Five major cultivars were cultivated to consider the cultivar characteristics and environmental factors for two years were collected to consider the climate difference. Faster R–CNN based object detector was used to estimate the number of receptacles per strawberry plant in given two-dimensional images, which achieved a mAP of 0.6587 for our dataset. However, not all receptacles appear on the two-dimensional images, and Bayesian analysis was used to model the uncertainty associated with the number of receptacles missed by the AI. After estimating the probability of fruiting per receptacle, prediction models for the total strawberry yield at the end of harvest season were evaluated. Even though the detection accuracy was not perfect, the results indicated that counting the receptacles by object detection and estimating the probability of fruiting per receptacle by Bayesian modeling are more useful for predicting the total yield per plant than knowing its cumulative yield during the first month.

Abstract We aimed to compare the reliability of bone scintigraphy (BS) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)—derived parameters in the detection of active arthritis in 28-joint areas and evaluate the reliability of joint counts between BS and clinical assessment in patients with rheumatoid arthritis (RA). We enrolled 106 patients (67 in the development group and 39 in the validation groups) with active RA who underwent BS, 18F-FDG PET/computed tomography (CT), and clinical evaluation of disease activity. We compared the results of BS-derived joint assessment with those of PET-derived and clinical joint assessments. Subsequently we developed a disease activity score (DAS) using BS-positive joints and validated it in an independent group. The number of BS-positive joints in 28-joint areas significantly correlated with the swollen /tender joint counts (SJC/TJC) and PET-derived joint counts. A BS uptake score of 2 (strong positive) was significantly more sensitive compared with a BS uptake score of 1 (weak positive) in detecting a PET-positive joint among the 28-joints. After conducting multivariate analyses including erythrocyte sediment rate (ESR) and patient global assessment (PGA) in addition to BS-derived parameters, BS/DAS was obtained as follows: 0.056 × number of BS-positive joints in 28 joints + 0.012 × ESR + 0.030 × PGA. A significant correlation between BS/DAS and DAS28-ESR was confirmed in the validation group. Strong positive uptake of BS is sensitive and reproducible for the detection of active joints, and can complement the clinical assessment of disease activity in RA.

Abstract Introduction Retroperitoneal fibrosis (RPF) is characterized by a highly fibrotic retroperitoneal mass and encompasses the idiopathic form and secondary to malignancies. Because we have limited knowledge whether RPF is associated with malignancy, we aimed to investigate the relationship between RPF and malignancy and to compare the characteristics and prognosis of cancers among patients with RPF. Methods Medical records of 111 patients diagnosed as having RPF were reviewed and 38 cases of cancer, confirmed by biopsy, were identified. Standardized incidence ratios (SIRs) were calculated for cancers and stratified according to cancer type and RPF-cancer diagnosis interval. Cancer characteristics and outcomes were compared between RPF-cancer diagnosis intervals. Results The average age at RPF diagnosis was 59.2 ± 15.0 years, and 69.4% of the patients were male. The cancer SIRs in patients with RPF relative to age- and sex-matched individuals in the general population was 2.2 (1.6–3.1). SIRs of renal pelvis cancer and multiple myeloma were significantly higher than in the general population. When stratified by RPF-cancer intervals, the SIR for cancer was 9.9 within 1 year of RPF diagnosis, while no significant increase in the SIR was found after 1 year from RPF diagnosis. Cancer stage was more advanced at the time of diagnosis in patients within a 1-year interval for RPF than those with cancer within a >5-year interval, with a correspondingly increased mortality in the former patients. Conclusions RPF was significantly associated with malignancy, particularly those diagnosed within 1 year of RPF diagnosis. Cancer stages at diagnosis were more advanced and the mortality rate was higher in patients within a 1-year interval between RPF and cancer diagnosis than in those with a >5-year interval between diagnoses.

Human epidermal growth factor receptor isoform D (EGFR; isoform D) is a soluble protein from a 3 kb alternate mRNA transcript that arises from the human EGFR gene. Several studies have identified this circulating isoform of EGFR as a potential diagnostic biomarker for the detection of early stage of cancers. While the expression of the full-length EGFR (isoform A) is regulated by its cognate ligand, EGF, as well as by phorbol myristate acetate (PMA), no studies have examined the factors regulating the expression of EGFR isoform D. In this study, using breast cancer cell lines, we show that the HER receptor ligands, EGF and neuregulin (NRG-1β), as well as the phorbol ester, PMA, can increase the expression of EGFR isoform D, as well as isoform A. Our results, based on measurement of mRNA levels, suggest that EGF induced expression of both isoform A and isoform D occur through a mitogen activated protein kinase (MAPK)-dependent mechanism, and also suggest that protein kinase C is involved in PMA-induced regulation of both isoforms. We also demonstrate that NRG-1β increases isoform A and isoform D expression via the MAPK-dependent pathway, but this regulation occurs independently of phosphatidylinositol 3-kinase/Akt activation. These results suggest that regulation of EGFR isoform A and isoform D expression occur using similar mechanisms. Despite commonalities in the transcriptional regulation of these two EGFR isoforms, the half-lives of these two transcripts is quite different. Moreover, EGFR isoform D, unlike isoform A, is not post-transcriptionally modulated by EGFR activators in the breast cancer cell line MDA-MB-468.

Background/Aims The learning curve is essential in endoscopic submucosal dissection (ESD) training to improve outcomes and reduce the risk of procedure-related complications. We compared the outcomes of gastric ESD in live pigs performed by inexperienced endoscopists with or without ex vivo training. Materials and Methods At the Olympus Medical Training and Education Center, nine endoscopists inexperienced in ESD were randomly divided into two groups (group A: ex vivo training followed by in vivo training; group B: in vivo training only), and they performed gastric ESDs. Results A total of 18 ESDs were performed. The en bloc resection rate was 88.9% (16/18), and the complete resection rate was 94.4% (17/18). The median specimen size was 2.5 cm in group A and 2.1 cm in group B (P=0.227). There was no significant difference in the procedure time between the two groups, except for the marking time (0′58″ vs. 2′58″, P=0.027). However, group A took a shorter time in dissecting the same area than group B (109 vs. 246 sec/cm2, P=0.083). Complication rates were not significantly different between both groups. Conclusions The procedure time during in vivo ESD training in pigs may be shortened by prior ex vivo training. However, the ex vivo model presented poor air inflation, unstable fixation, and excessive mucosal hardness for cutting. An advanced simulator or sufficient ex vivo training may be effective in training for the ESD procedure.

Abstracts PURPOSE This study aimed to investigate the effect of turmeric intake alone or in combination with resistance training on liver enzymes in adult men who regularly consumed alcohol at least twice a week. METHODS Twelve men (age: 36.0±5.26 years, weight: 99.9±17.9 kg, and height: 184.0±6.5 cm) were randomly assigned to the turmeric intake (2-3 g/day) alone (TI, n=6) group or the TI plus resistance training (60 minutes of RT 3 times a week) (TI+RT, n=6) group for 8 weeks. Blood was collected before and after 8 weeks of treatment. The analyzed variables included glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), γ-glutamyl transferase (γ-GTP), and GOT/GPT ratio. RESULTS There was no significant interaction effect in all variables, but the main effect was found in all variables only in TI+RT group. The Cohen's d effect size on the main effects of the TI+RT group on GOT (d=0.548), GPT (d=0.835), γ-GTP (d=0.623), and GOT/ GPT ratio (d=0.800) ranged from 0.548-0.835, respectively. However, body composition such as percent body fat (%, p>.05) and muscle mass (kg, p>.05) did not show the main effect on time points as well as the interaction effect (p>.05). CONCLUSIONS Although the 8-week TI treatment did not show any statistically significant change, TI treatment showed a tendency to decrease in GOT, GPT, and γ-GTP, and the GOT/GPT ratio tends to increase. Therefore, there was a synergic effect of the TI plus RT treatment or the sum of the two treatments for 8 weeks.

Abstract The endoscopic features between herpes simplex virus (HSV) and cytomegalovirus (CMV) esophagitis overlap significantly, and hence the differential diagnosis between HSV and CMV esophagitis is sometimes difficult. Therefore, we developed a machine-learning-based classifier to discriminate between CMV and HSV esophagitis. We analyzed 87 patients with HSV esophagitis and 63 patients with CMV esophagitis and developed a machine-learning-based artificial intelligence (AI) system using a total of 666 endoscopic images with HSV esophagitis and 416 endoscopic images with CMV esophagitis. In the five repeated five-fold cross-validations based on the hue–saturation–brightness color model, logistic regression with a least absolute shrinkage and selection operation showed the best performance (sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the receiver operating characteristic curve: 100%, 100%, 100%, 100%, 100%, and 1.0, respectively). Previous history of transplantation was included in classifiers as a clinical factor; the lower the performance of these classifiers, the greater the effect of including this clinical factor. Our machine-learning-based AI system for differential diagnosis between HSV and CMV esophagitis showed high accuracy, which could help clinicians with diagnoses.

Far-red light was excluded in photosynthetic photon flux; however, recent studies have shown that it increases photosynthetic capacity. In addition, there were few studies on the whole canopy photosynthetic rate and continuous changes of morphology on cucumber seedlings affected by far-red light. This study evaluated the effect of conventional white LEDs adding far-red light on cucumber seedlings using a semi-open chamber system for the measurement of the whole canopy gas exchange rate, and the Raspberry Pi-based imaging system for the analysis of a continuous image. In the image, through the imaging system, it was confirmed that far-red light promoted the germination rate of cucumber seedlings and enhanced early growth. However, the dry weight of the shoot and root did not increase. The measured net apparent CO2 assimilation rate was improved by an increasing leaf area during the cultivation period. The conventional white LED light source with added far-red light increased the photosynthetic rate of cucumber seedlings’ whole canopy. However, at the early seedling stage, plant height and leaf area of the whole canopy was increased by far-red light, and it was revealed that the image data saturated faster. It was considered that the photosynthetic efficiency decreased due to a shading effect of the limited planting density of the cell tray. The results found that using appropriate far-red light, considering planting density, could increase the photosynthetic rate of the whole canopy of crops, thereby promoting crop growth, but it was judged that the use of far-red light in the early growth stage of cucumber seedlings should be considered carefully.

Esophageal cancer is one of the lethal malignant tumors because it is often diagnosed in the advanced stage with lymph node or distant metastasis. The recurrence rate of esophageal cancer is known to be about 40% to 50% even in the patients who underwent curative esophageal resection. Most frequent sites of metastases are known to be the liver. Furthermore, other distant metastases also could be developed in lung, bone, brain, kidney, adrenal, abdominal cavity, and skin. However, ampulla of Vater (AoV) metastasis rarely occurs from esophageal cancer. Therefore, we report herein a case of AoV metastasis from squamous cell carcinoma of the esophagus.

Abstract Background Various questionnaires have been developed to assess physical activity, but only a few simple questionnaires are suitable for self-administration in large groups of midlife working women. This study examined the usefulness of the Japan Nurses’ Health Study (JNHS) questionnaire for self-administered physical activity surveys. Methods The JNHS physical activity questionnaire consisted of items covering seven degrees of intensity. The metabolic equivalents (METs) for the physical activity intensity of the questionnaire were estimated from energy expenditure as measured by a uniaxial accelerometer with the Markov Chain Monte Carlo (MCMC) simulation. The estimated METs were then assigned to the JNHS baseline survey data, and the total energy expenditure (TEE) and the time spent performing ≥3 METs hour of physical activity, called moderate to vigorous intensity physical activity (MVPA), were calculated. Results For working situations, application of the MCMC simulation resulted in estimated reference values of 1.2 METs for “sitting work”, 1.6 METs for “standing work”, 1.8 METs for “walking work”, and 4.5 METs for “heavy work”. For non-working situations, the estimated values were 1.1 METs for sedentary time, 2.4 METs for “moderate physical activity”, 4.4 METs for “vigorous physical activity”, and 9.4 METs for “very vigorous physical activity”. When these estimated METs were used, the mean TEE/day was 1808 kcal. This corresponded to − 3.0% of the TEE/day generated by the accelerometer. These estimated MET values showed similar results as a previous study measuring activity using the doubly-labeled water method. The number of hours per week of MVPA significantly decreased with age, which is also consistent with previous findings. Conclusions Estimated reference MET values in this study were similar to those in previous studies of Japanese women. The JNHS questionnaire is therefore useful for epidemiological surveys of midlife working women because it assigns estimated MET values as physical activity intensities.

Abstract Aims/Introduction To examine the association between adult‐onset diabetes and life‐course bodyweight changes. Materials and Methods In a cross‐sectional study, 17,398 Japanese female nurses aged ≥30 years completed a self‐administered questionnaire in 2001–2007. Bodyweight indices were calculated for three life stages: birthweight (adjusted for gestational age), body mass index (BMI) at age 18 years and current BMI. Odds ratios for being diagnosed with adult‐onset diabetes were calculated according to the combined bodyweight categories of two life stages: at birth and age 18 years; and at age 18 years and the survey (current). Path analysis was carried out to decompose the effect of each bodyweight index into direct and mediating effects. Results After adjustment for age at survey and parental diabetes history, “low” birthweight (

STUDY QUESTION: What is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women? SUMMARY ANSWER: Higher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity. WHAT IS KNOWN ALREADY: Postmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI. STUDY DESIGN, SIZE, DURATION: This study is a secondary analysis of data collected from the baseline visit of the Womens Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: Women who reported early menarche (15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause 3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies. LIMITATIONS, REASONS FOR CAUTION: The WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention. STUDY FUNDING/COMPETING INTEREST(S): HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from ACSMS Body Composition Assessment Book and consulting fees from the WHI. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

The anticancer agent doxorubicin(dox) has been widely used in the treatment of a variety of hematological malignancies and solid tumors. Despite doxorubicin’s efficiency in killing tumor cells, severe damage to healthy tissues, along with cardiotoxicity, limits its clinical use. To overcome these adverse side effects, improve patient safety, and enhance therapeutic efficacy, we have designed a thermally responsive biopolymer doxorubicin carrier that can be specifically targeted to tumor tissue by locally applying mild hyperthermia (41 °C). The developed drug vehicle is composed of the following: a cell penetrating peptide (SynB1) to promote tumor and cellular uptake; thermally responsive Elastin-like polypeptide (ELP); and the (6-maleimidocaproyl) hydrazone derivative of doxorubicin (DOXO-EMCH) containing a pH-sensitive hydrazone linker that releases doxorubicin in the acidic tumor environment. We used the in vivo imaging system, IVIS, to determine biodistribution of doxorubicin-delivered ELP in MDA-MB-231 xenografts in nude mice. Tumor bearing mice were treated with a single IV injection of 10 mg/kg doxorubicin equivalent dose with free doxorubicin, thermally responsive SynB1 ELP 1-DOXO, and a thermally nonresponsive control biopolymer, SynB1 ELP 2-DOXO. Following a 2 h treatment with hyperthermia, tumors showed a 2-fold higher uptake when treated with SynB1 ELP 1-DOXO compared to free doxorubicin. Accumulation of the thermally non-responsive control SynB1 ELP2 –DOXO was comparable to free doxorubicin, indicating that an increase in dox accumulation with ELP is due to aggregation in response to thermal targeting. Higher levels of SynB1 ELP1–DOXO and SynB1 ELP2 –DOXO with respect to free doxorubicin were observed in kidneys. Fluorescence intensity from hearts of animals treated with SynB1 ELP1–DOXO show a 5-fold decrease in accumulation of doxorubicin than the same dose of free doxorubicin. SynB1-ELP1-DOXO biopolymers demonstrated a 6-fold increase in tumor/heart ratio in comparison to free doxorubicin, indicating preferential accumulation of the drug in tumors. These results demonstrate that thermally targeted polymers are a promising therapy to enhance tumor targeting and uptake of anticancer drugs and to minimize free drug toxicity in healthy tissues, representing a great potential for clinical application.

Carrot (Daucus carota), one of the most economically important root vegetables, shows a wide range of morphological and biochemical diversity. However, there is a lack of simultaneous systematic study regarding the biochemical composition and morphological characteristics in carrot genetic resources, which is crucial for crop improvement. For this reason, the morphological characteristics, carotenoids, and free sugar content of 180 carrot genetic resources grown in open field conditions from March to June 2020 were accessed to select the lines for a potential breeding program. Altogether, 15 qualitative and 4 quantitative agronomical characteristics were evaluated and grouped into four categories based on root color (orange, yellow, white, and purple). Three carotenoids (lutein, α-carotene, and β-carotene) and three free sugars (fructose, glucose, and sucrose) were also analyzed. The results revealed wide genetic variation in both qualitative and quantitative traits. Most of the genetic resources were orange (n = 142), followed by white (n = 16), yellow (n = 14), and purple (n = 8). Carotenoid profile and content were highly dependent on root color and showed wide genetic variability, while sugar content and profile were independent of the root color. Alpha- and β- carotene were the major carotenoids in orange carrots representing 43.3 and 41.0% of total carotenoids. In contrast, lutein was most dominant in other colored carrots (79.7–98.6% of total carotenoids). In most of the genetic resources, sucrose was the most dominant free sugar, followed by glucose and fructose. The results of this study showed that some genetic resources elevated carotenoid and sugar content. The morphological and biochemical diversity observed in this study might be useful for improving the agronomic traits and biochemical content of carrot lines for breeding programs.

Multistate molecular systems usually rely on external energy inputs to switch between states. Here, the authors show that a bispyridyl calixpyrrole system directed by only weak noncovalent interactions and metal coordination can access six discrete structural states, with directional and sequential control.

This study monitored changes in chlorophyll fluorescence (CF), growth parameters, soil moisture content, phytochemical content (proline, ascorbic acid, chlorophyll, total phenol content (TPC), and total flavonoid content (TFC)), and antioxidant activities in 12-day-old lettuce (Lactuca sativa L.) seedlings grown under drought stress (no irrigation) and control (well irrigated) treatments in controlled conditions for eight days. Measurements occurred at two-day intervals. Among ten CF parameters studied, effective quantum yield of photochemical energy conversion in PSII (Y(PSII)), coefficient of photochemical quenching (qP), and coefficient of photochemical quenching of variable fluorescence based on the lake model of PSII (qL) significantly decreased in drought-stressed seedlings from day 6 of treatment compared to control. In contrast, maximum quantum yield (Fv/Fm), ratio of fluorescence (Rfd), and quantum yield of non-regulated energy dissipation in PSII (Y(NO)) were significantly affected only at the end. All growth parameters decreased in drought-stressed seedlings compared to control. Proline started increasing from day 4 and showed ~660-fold elevation on day 8 compared to control. Chlorophyll, ascorbic acid, TPC, TFC, and antioxidant activities decreased in drought-stressed seedlings. Results showed major changes in all parameters in seedlings under prolonged drought stress. These findings clarify effects of drought stress in lettuce seedlings during progressive drought exposure and will be useful in the seedling industry.

Demilitarization requires the recovery and disposal of obsolete ammunition and explosives. Since open burning/detonation of hazardous waste has caused serious environmental and safety problems, thermal decomposition has emerged as one of the most feasible methods. RDX is widely used as a military explosive due to its high melting temperature and detonation power. In this work, the feasible conditions under which explosives can be safely incinerated have been investigated via a rotary kiln simulation. To solve this problem, phase change along with the reactions of RDX has been incisively analyzed. A global reaction mechanism consisting of condensed phase and gas phase reactions are used in Computational Fluid Dynamics simulation. User Defined Functions in FLUENT is utilized in this study to inculcate the reactions and phase change into the simulation. The results divulge the effect of temperature and the varying amounts of gas produced in the rotary kiln during the thermal decomposition of RDX. The result leads to the prospect of demilitarizing waste explosives to avoid the possibility of detonation.

Summary: Background: Early menopause is linked to an increased risk of cardiovascular disease mortality; however, the association between early menopause and incidence and timing of cardiovascular disease is unclear. We aimed to assess the associations between age at natural menopause and incidence and timing of cardiovascular disease. Methods: We harmonised and pooled individual-level data from 15 observational studies done across five countries and regions (Australia, Scandinavia, the USA, Japan, and the UK) between 1946 and 2013. Women who had reported their menopause status, age at natural menopause (if postmenopausal), and cardiovascular disease status (including coronary heart disease and stroke) were included. We excluded women who had hysterectomy or oophorectomy and women who did not report their age at menopause. The primary endpoint of this study was the occurrence of first non-fatal cardiovascular disease, defined as a composite outcome of incident coronary heart disease (including heart attack and angina) or stroke (including ischaemic stroke or haemorrhagic stroke). We used Cox proportional hazards models to estimate multivariate hazard ratios (HRs) and 95% CIs for the associations between age at menopause and incident cardiovascular disease event. We also adjusted the model to account for smoking status, menopausal hormone therapy status, body-mass index, and education levels. Age at natural menopause was categorised as premenopausal or perimenopausal, younger than 40 years (premature menopause), 40–44 years (early menopause), 45–49 years (relatively early), 50–51 years (reference category), 52–54 years (relatively late), and 55 years or older (late menopause). Findings: Overall, 301 438 women were included in our analysis. Of these 301 438 women, 12 962 (4·3%) had a first non-fatal cardiovascular disease event after menopause, of whom 9369 (3·1%) had coronary heart disease and 4338 (1·4%) had strokes. Compared with women who had menopause at age 50–51 years, the risk of cardiovascular disease was higher in women who had premature menopause (age

The Korean peninsula has diverse habitats and so would be expected to have a rich millipede fauna because of its location between the Paleoarctic and Oriental regions. To facilitate studies on millipedes, this work provides an updated list and discussion of Korean millipedes. A total of 69 species had been recorded up to 2010, but since then no new species have been reported. Among 69 species, 49 are endemic to the Korean peninsula. From 1950 to the present, an average of only seven new species from the Korean peninsula has been described per decade. This number does not reflect the biodiversity of millipedes in Korea, especially when compared to Taiwan, which has only one-third the area of the Korean peninsula, but from which a greater number of millipede species have been recorded (75 vs. 69 species). Japan has twofold the land area of the Korean peninsula, and an almost threefold higher number of millipede species. Further, more-intensive surveys will likely result in identification of more millipede species in the Korean peninsula.

People's year-round interpersonal step count variations according to meteorological conditions are not fully understood, because complete year-round data from a sufficient sample of the general population are difficult to acquire. This study examined the associations between meteorological conditions and objectively measured step counts using year-round data collected from a large cohort (N=24,625) in Yokohama, Japan from April 2015 to March 2016.Two-piece linear regression analysis was used to examine the associations between the monthly median daily step count and three meteorological indices (mean values of temperature, temperature-humidity index (THI), and net effective temperature (NET)).The number of steps per day peaked at temperatures between 19.4 and 20.7°C. At lower temperatures, the increase in steps per day was between 46.4 and 52.5 steps per 1°C increase. At temperatures higher than those at which step counts peaked, the decrease in steps per day was between 98.0 and 187.9 per 1°C increase. Furthermore, these effects were more obvious in elderly than non-elderly persons in both sexes. A similar tendency was seen when using THI and NET instead of temperature. Among the three meteorological indices, the highest R2 value with step counts was observed with THI in all four groups.Both high and low meteorological indices discourage people from walking and higher values of the indices adversely affect step count more than lower values, particularly among the elderly. Among the three indices assessed, THI best explains the seasonal fluctuations in step counts. Keywords: Elderly, Developed countries, Health policy, Humidity, Linear regression, Physical activity, Temperature

Chlorophyll fluorescence (CF), growth parameters, phytochemical contents [proline, chlorophyll, ascorbic acid, total phenol content (TPC), total flavonoid content (TFC)], and antioxidant activities were investigated in lettuce (Lactuca sativa L.) seedlings grown under different sodium chloride (NaCl) concentrations (0, 50, 100, 200, 300, and 400 mM) in a controlled environment for eight days. The parameters were evaluated at two days intervals. Almost of the CF and growth parameters as well as phytochemicals were significantly affected by both NaCl concentrations and progressive treatment schedule. The maximum quantum yield (Fv/Fm), effective quantum yield of photochemical energy conversion in PSII [Y(PSII)], coefficient of photochemical quenching (qP), coefficient of non-photochemical quenching (qN), and ratio of fluorescence decline (Rfd) showed decrements only at the highest saline concentration (400 mM), whereas the quantum yield of non-regulated energy dissipation in PSII [Y(NO)] exhibited a dissipation trend. All the growth parameters decreased with increasing NaCl concentrations, showing the highest decrease (~8 fold) in shoot fresh weight, compared to control seedlings. Proline significantly increased with increasing NaCl concentration and treatment time. Other phytochemicals decreased with the increase in NaCl concentration and reached their lowest at 400 mM. Overall, the results showed major changes in all parameters when the seedlings were grown at a NaCl concentration of 400 mM. The present findings will be useful for understanding the differential effect of NaCl concentrations in lettuce seedlings, and also might be useful to optimize the NaCl concentrations in other crops grown in controlled environmental conditions.

The aim of this study was to determine the conversion factors for the effective dose (ED) per dose length product (DLP) for various computed tomography (CT) protocols based on the 2007 recommendations of the International Commission on Radiological Protection (ICRP). CT dose data from 369 CT scanners and 13,625 patients were collected through a nationwide survey. Data from 3793 patients with a difference in height within 5% of computational human phantoms were selected to calculate ED and DLP. The anatomical CT scan ranges for 11 scan protocols (adult-10, pediatric-1) were determined by experts, and scan lengths were obtained by matching scan ranges to computational phantoms. ED and DLP were calculated using the NCICT program. For each CT protocol, ED/DLP conversion factors were calculated from ED and DLP. Estimated ED conversion factors were 0.00172, 0.00751, 0.00858, 0.01843, 0.01103, 0.02532, 0.01794, 0.02811, 0.02815, 0.02175, 0.00626, 0.00458, 0.00308, and 0.00233 mSv∙mGy−1∙cm−1 for the adult brain, intra-cranial angiography, C-spine, L-spine, neck, chest, abdomen and pelvis, coronary angiography, calcium scoring, aortography, and CT examinations of pediatric brain of

Individual glucosinolates (GSLs) were assessed to select cabbage genotypes for a potential breeding program. One hundred forty-six cabbage genotypes from different origins were grown in an open field from March to June 2019; the cabbage heads were used for GSL analyses. Seven aliphatics [glucoiberin (GIB), progoitrin (PRO), epi-progoitrin (EPI), sinigrin (SIN), glucoraphanin (GRA), glucoerucin (GER) and gluconapin (GNA)], one aromatic [gluconasturtiin (GNS)] and four indolyl GSLs [glucobrassicin (GBS), 4-hydroxyglucobrassicin (4HGBS), 4-methoxyglucobrassicin (4MGBS), neoglucobrassicin (NGBS)] were found this study. Significant variation was observed in the individual GSL content and in each class of GSLs among the cabbage genotypes. Aliphatic GSLs were predominant (58.5%) among the total GSLs, followed by indolyl GSL (40.7%) and aromatic GSLs (0.8%), showing 46.4, 51.2 and 137.8% coefficients of variation, respectively. GIB, GBS and NGBS were the most common GSLs found in all genotypes. GBS was the most dominant GSL, with an average value of 3.91 µmol g−1 (0.79 to 13.14 µmol g−1). SIN, GIB, PRO and GRA were the other major GSLs, showing average values of 3.45, 1.50, 0.77 and 0.62 µmol g−1, respectively. The genotypes with relatively high contents of GBS, SIN, GIB and GRA warrant detailed studies for future breeding programs since the hydrolysis products of these GSLs have several anti-cancer properties.

BackgroundCigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause.Methods and findingsA total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (ConclusionsThe probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause.

The majority of anticancer drugs have poor aqueous solubility, produce adverse effects in healthy tissue, and thus impose major limitations on both clinical efficacy and therapeutic safety of cancer chemotherapy. To help circumvent problems associated with solubility, most cancer drugs are now formulated with co-solubilizers. However, these agents often also introduce severe side effects, thereby restricting effective treatment and patient quality of life. A promising approach to addressing problems in anticancer drug solubility and selectivity is their conjugation with polymeric carriers to form polymer-based prodrugs. These polymer-based prodrugs are macromolecular carriers, designed to increase the aqueous solubility of antitumor drugs, can enhance bioavailability. Additionally, polymer-based prodrugs approach exploits unique features of tumor physiology to passively facilitate intratumoral accumulation, and so improve chemodrug pharmacokinetics and pharmacological properties. This review introduces basic concepts of polymer-based prodrugs, provides an overview of currently emerging synthetic, natural, and genetically engineered polymers that now deliver anticancer drugs in preclinical or clinical trials, and highlights their major anticipated applications in anticancer therapies.

Study DesignA retrospective observational and case control study.PurposeTo identify appropriate treatment options according to the types of surgical site infections (SSI) in instrumented posterior lumbar interbody fusion (PLIF).Overview of LiteratureThere has been no agreement or consensus with regard to this matter.MethodsThirty-two consecutive SSIs were included and followed for more than one year. The elapsed time to diagnosis (ETD) according to the type of SSI was analyzed. The treatment options for each type and consequent clinical results were reviewed. The risk factors of removing the implants were analyzed.ResultsThere were 6/32 (19%) superficial incisional, 6/32 (19%) deep incisional, and 20/32 (62%) organ/space infection cases (SII, DII, and O/SI, respectively) (p=0.002). ETD was 8.5±2.3 days in SII, 8.7±2.3 days in DII, and 164.5±131.1 days in O/SI (p=0.013). All cases of SII and DII retained implants and were treated by repeated irrigation and secondary closure. Among O/SIs, 10/20 were treated conservatively. Nine out of ten underwent posterior one stage simultaneous revision (POSSR) and in one case, the cage was removed anteriorly. Those who had ETDs longer than 3 months showed a significant risk of implant removal (p=0.008, odds ratio [OR]=40.3). The Oswestry disability index (ODI) improved from 47.3% to 33.8% in SII, from 55.0% to 32.3% in DII, and from 53.4% to 42.1% in O/SI (p=0.002). There was no difference among the three groups (p=0.106); however, there was a partial correlation between ETD and final ODI (r=0.382, p=0.034).ConclusionsLatent O/SI was the most common type of SSI in PLIF. In cases of SII and DII, early aggressive wound management and secondary closure was effective and implant removal was not necessary. In some cases of O/SI, implant removal was unavoidable. However, implant removal could be averted by an earlier diagnosis. POSSR was feasible and safe. Functional outcomes were improved; however, disability increased as ETD increased.

Glucosinolate (GSL) profiles and concentrations in various tissues (seeds, sprouts, mature root, and shoot) were determined and compared across nine Brassica species, including cauliflower, cabbage, broccoli, radish, baemuchae, pakchoi, Chinese cabbage, leaf mustard, and kale. The compositions and concentrations of individual GSLs varied among crops, tissues, and growth stages. Seeds had highest total GSL concentrations in most of crops, whereas shoots had the lowest GSL concentrations. Aliphatic GSL concentrations were the highest in seeds, followed by that in sprouts, shoots, and roots. Indole GSL concentration was the highest in the root or shoot tissues in most of the crops. In contrast, aromatic GSL concentrations were highest in roots. Of the nine crops examined, broccoli exhibited the highest total GSL concentration in seeds (110.76 µmol·g−1) and sprouts (162.19 µmol·g−1), whereas leaf mustard exhibited the highest total GSL concentration in shoots (61.76 µmol·g−1) and roots (73.61 µmol·g−1). The lowest GSL concentrations were observed in radish across all tissues examined.

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OBJECTIVE: The menopausal transition results in a progressive decrease in circulating estrogen levels. Experimental evidence in rodents has indicated that estrogen depletion leads to a reduction of energy expenditure and physical activity. It is unclear whether treatment with estrogen therapy increases physical activity level in postmenopausal women. METHODS: A total of 27,327 postmenopausal women aged 50-79 years enrolled in the Womens Health Initiative randomized double-blind trials of menopausal hormone therapy. Self-reported leisure-time physical activity at baseline, and years 1, 3, and 6 was quantified as metabolic equivalents (MET)-h/wk. In each trial, comparison between intervention and placebo groups of changes in physical activity levels from baseline to follow-up assessment was examined using linear regression models. RESULTS: In the CEE-alone trial, the increase in MET-h/wk was greater in the placebo group compared with the intervention group at years 3 ( P = 0.002) and 6 ( P < 0.001). Similar results were observed when analyses were restricted to women who maintained an adherence rate ≥80% during the trial or who were physically active at baseline. In the CEE + MPA trial, the primary analyses did not show significant differences between groups, but the increase of MET-h/wk was greater in the placebo group compared with the intervention group at year 3 ( P = 0.004) among women with an adherence rate ≥80%. CONCLUSIONS: The results from this clinical trial do not support the hypothesis that estrogen treatment increases physical activity among postmenopausal women.

BACKGROUND & AIMS: Systematic reviews, meta-analyses and Mendelian randomization studies suggest that cardiometabolic diseases may be associated with COVID-19 risk and prognosis, with evidence implicating insulin resistance (IR) as a common biological mechanism. As driving factors for IR, we examined body mass index (BMI) and waist circumference (WC) among postmenopausal women in association with COVID-19 outcomes (positivity and hospitalization), and the role of glucose homeostasis as a mediator of this relationship. METHODS: Associations of BMI and WC at baseline (1993-1998) with COVID-19 outcomes collected at Survey 1 (June-December, 2020) and/or Survey 2 (September-December, 2021) were evaluated among 42,770 Womens Health Initiative (WHI) participants (baseline age: 59.36 years) of whom 16,526 self-reported having taken ≥1 COVID-19 test, with 1242 reporting ≥1 positive COVID-19 test and 362 reporting ≥1 COVID-19 hospitalization. We applied logistic regression and causal mediation analyses to sub-samples with available fasting biomarkers of glucose homeostasis (glucose, insulin, Homeostatic Model Assessment for Insulin Resistance, Homeostasis Model Assessment for β-cell function, Quantitative Insulin-sensitivity Check Index, Triglyceride-Glucose index (TyG)) at baseline, whereby 57 of 759 reported COVID-19 test positivity and 23 of 1896 reported COVID-19 hospitalization. RESULTS: In fully adjusted models, higher BMI, WC and TyG were associated with COVID-19 test positivity and hospitalization. Glucose concentrations mediated associations of BMI and WC with COVID-19 positivity, whereas TyG mediated BMI and WCs associations with COVID-19 hospitalization. CONCLUSIONS: Obesity and central obesity markers collected an average of 24 years prior were associated with COVID-19 outcomes among postmenopausal women. Glucose concentration and TyG partly mediated these associations.

Background: Illicit drug use has become a global epidemic, yet it is unclear if drug smoking increases the risk of tobacco-related cancers.Objectives: We aimed to evaluate hypothesized associations between smoking three drugs - opium, phencyclidine (PCP) and crack cocaine and lung and upper aerodigestive tract (UADT) cancers.Methods: A population-based case-control study with 611 lung cancer cases (50% male), 601 UADT cancers cases (76% male), and 1,040 controls (60% male) was conducted in Los Angeles County (1999-2004). Epidemiologic data including drug smoking histories were collected in face-to-face interviews. Associations were estimated with logistic regressions.Results: Adjusting for potential confounders, ever vs. never crack smoking was positively associated with UADT cancers (aOR = 1.56, 95% CI: 1.05, 2.33), and a dose-response relationship was observed for lifetime smoking frequency (p for trend = .024). Heavy (> median) vs. never crack smoking was associated with UADT cancers (aOR = 1.81, 95% CI: 1.07, 3.08) and lung cancer (aOR = 1.58, 95% CI: 0.88, 2.83). A positive association was also observed between heavy PCP smoking and UADT cancers (aOR = 2.29, 95% CI: 0.91, 5.79). Little or no associations were found between opium smoking and lung cancer or UADT cancers.Conclusion: The positive associations between illicit drug use and lung and/or UADT cancers suggest that smoking these drugs may increase the risk of tobacco-related cancers. Despite the low frequency of drug smoking and possible residual confounding, our findings may provide additional insights on the development of lung and UADT cancers.

Adaptive thermogenesis by brown adipose tissue (BAT) dissipates calories as heat, making it an attractive anti-obesity target. Yet how BAT contributes to circulating metabolite exchange remains unclear. Here, we quantified metabolite exchange in BAT and skeletal muscle by arteriovenous metabolomics during cold exposure in fed male mice. This identified unexpected metabolites consumed, released and shared between organs. Quantitative analysis of tissue fluxes showed that glucose and lactate provide ~85% of carbon for adaptive thermogenesis and that cold and CL316,243 trigger markedly divergent fuel utilization profiles. In cold adaptation, BAT also dramatically increases nitrogen uptake by net consuming amino acids, except glutamine. Isotope tracing and functional studies suggest glutamine catabolism concurrent with synthesis via glutamine synthetase, which avoids ammonia buildup and boosts fuel oxidation. These data underscore the ability of BAT to function as a glucose and amino acid sink and provide a quantitative and comprehensive landscape of BAT fuel utilization to guide translational studies.