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BackgroundHuman biomonitoring is crucial for regulatory toxicology, yet data on biomarker concentrations in the UAE are lacking. This study addresses this gap by analyzing urinary concentrations of 16 metals in UAE young adults, assessing correlations with personal characteristics, dietary patterns, and lifestyle habits.MethodsA cross-sectional pilot study was conducted among 144 randomly selected young adults (71 males and 73 females) from Sharjah, UAE, between January and March 2023. Participants provided urine samples, which were analyzed for 16 heavy metals using ICP-OES, and completed detailed questionnaires covering sociodemographic factors, lifestyle, and dietary habits. Descriptive statistics were used to summarize participant characteristics, and linear regression analysis was applied to explore associations between metal concentrations and factors such as gender, dietary habits, and exposure to environmental risks. Non-parametric tests, including the Mann-Whitney test, were used to assess differences by gender. Statistical significance was set at p < 0.05. Ethical approval was obtained, and informed consent was secured before participation.ResultsSignificant findings include dietary influences on metal exposure, with rice consumption linked to higher metal concentrations. Sex differences were significant, with females showing elevated levels of arsenic, lead, and cadmium. Lifestyle factors, such as smoking and incense use, were correlated with increased barium and boron levels.ConclusionThis study highlights the significant role of dietary habits, especially the consumption of rice, in metal exposure among young adults in Sharjah. The findings highlight the urgent need for comprehensive human biomonitoring to understand environmental exposures and reform public health policies. The gender-specific differences in metal distribution suggest the necessity for targeted public health strategies. The study, however, is limited by its cross-sectional nature and the focus on a specific geographic area, warranting further research for broader generalizability. Future investigations, particularly on the impact of incense exposure on metal levels, are essential for developing comprehensive health interventions and preventive strategies in the UAE.

Human Immunodeficiency Virus (HIV) is a significant threat to public health. HIV genotyping and antiretroviral resistance testing may have contributed to improved non-treated management. Immune markers might assist HIV-1 diagnosis and drug-resistant variant identification. HIV-1 immunogenicity and molecular characteristics of antiretroviral drug resistance are evaluated in 56 treatment-naive HIV patients. DNA sequencing and retroviral resistance testing identified HIV-1 genotypes. 55.4% of patients were susceptible to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) antiretroviral drugs, whereas 44.6% had drug-resistance mutations against at least one antiretroviral drug. 3.6% of cases had PI-resistant mutations, while 30.4% had NRTI-resistant mutations, and 30.4% had NNRTI-resistant mutations. In patients who are susceptible to PI, the mean value of human plasma sCD80 is 2.11 ± 0.65 ng/mL; in patients with mutations, it is 3.93 ± 2.91 ng/mL. Individuals who are susceptible to PI have plasma sCD27 levels of 78.7 ± 63.2 U/mL, whereas individuals who are mutant have levels of 56.5 ± 32.1 U/mL. IP-10's mean value was 363 ± 109.2 pg/mL for the susceptible patients and 429 ± 20.7 pg/mL for the mutated patients. In susceptible patients, the plasma sCD4 level is 0.163 ± 0.229 ng/mL; in mutant patients, it is 0.084 ± 0.012 ng/mL. The data showed a relative relation between immunological parameters such as sCD80, sCD27, sCD4, and IP-10 and mutation for drug resistance.

Background: Human biomonitoring is crucial for regulatory toxicology, yet data on biomarker concentrations in the UAE are lacking. This study addresses this gap by analyzing urinary concentrations of 16 metals in UAE young adults, assessing correlations with personal characteristics, dietary patterns, and lifestyle habits. Methods: A cross-sectional pilot study was conducted among 144 randomly selected young adults (71 males and 73 females) from Sharjah, UAE, between January and March 2023. Participants provided urine samples, which were analyzed for 16 heavy metals using ICP-OES, and completed detailed questionnaires covering sociodemographic factors, lifestyle, and dietary habits. Descriptive statistics were used to summarize participant characteristics, and linear regression analysis was applied to explore associations between metal concentrations and factors such as gender, dietary habits, and exposure to environmental risks. Non-parametric tests, including the Mann-Whitney test, were used to assess differences by gender. Statistical significance was set at p < 0.05. Ethical approval was obtained, and informed consent was secured before participation Results: Significant findings include dietary influences on metal exposure, with rice consumption linked to higher metal concentrations. Sex differences were significant, with females showing elevated levels of arsenic, lead, and cadmium. Lifestyle factors, such as smoking and incense use, were correlated with increased barium and boron levels. Conclusion: This study highlights the significant role of dietary habits, especially the consumption of rice, in metal exposure among young adults in Sharjah. The findings highlight the urgent need for comprehensive human biomonitoring to understand environmental exposures and reform public health policies. The gender-specific differences in metal distribution suggest the necessity for targeted public health strategies. The study, however, is limited by its cross-sectional nature and the focus on a specific geographic area, warranting further research for broader generalizability. Future investigations, particularly on the impact of incense exposure on metal levels, are essential for developing comprehensive health interventions and preventive strategies in the UAE. [ABSTRACT FROM AUTHOR]

Breastfeeding provides the optimal nutrition for an infant. However, breastfeeding practice is on decline globally. Attitude toward breastfeeding may determine the practice. This study aimed to examine postnatal mothers' attitude to breastfeeding and its determinants. A cross-sectional study was conducted, and data on attitude were collected using the Iowa Infant Feeding Attitude Scale (IIFAS). A convenience sample of 301 postnatal women were recruited from a major referral hospital in Jordan. Data on sociodemographic characteristics, pregnancy and delivery outcomes were collected. SPSS was used to analyze the data and identify the determinants of attitudes to breastfeeding. The mean total attitude score for participants was 65.0 ±7.15, which is close to the upper limit of the neutral attitude range. Factors associated with attitude that is positive to breastfeeding were high income (p = 0.048), pregnancy complications (p = 0.049), delivery complications (p = 0.008), prematurity (p = 0.042), intention to breastfeed (p = 0.002) and willingness to breastfeed (p = 0.005). With binary logistic regression modelling, determinants of attitude positive to breastfeeding were highest income level and willingness to breastfeed exclusively (OR = 14.77, 95%CI = 2.25-99.64 and OR = 3.41, 95%CI = 1.35-8.63 respectively). We conclude that mothers in Jordan have neutral attitude to breastfeeding. Breastfeeding promotion programs and initiatives should target low-income mothers and the general population. Policymakers and health care professionals can use the results of this study to encourage breastfeeding and improve breastfeeding rate in Jordan.

Human Immunodeficiency Virus (HIV) is a significant threat to public health. HIV genotyping and antiretroviral resistance testing may have contributed to improved non-treated management. Immune markers might assist HIV-1 diagnosis and drug-resistant variant identification. HIV-1 immunogenicity and molecular characteristics of antiretroviral drug resistance are evaluated in 56 treatment-naive HIV patients. DNA sequencing and retroviral resistance testing identified HIV-1 genotypes. 55.4% of patients were susceptible to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) antiretroviral drugs, whereas 44.6% had drug-resistance mutations against at least one antiretroviral drug. 3.6% of cases had PI-resistant mutations, while 30.4% had NRTI-resistant mutations, and 30.4% had NNRTI-resistant mutations. In patients who are susceptible to PI, the mean value of human plasma sCD80 is 2.11 ± 0.65 ng/mL; in patients with mutations, it is 3.93 ± 2.91 ng/mL. Individuals who are susceptible to PI have plasma sCD27 levels of 78.7 ± 63.2 U/mL, whereas individuals who are mutant have levels of 56.5 ± 32.1 U/mL. IP-10's mean value was 363 ± 109.2 pg/mL for the susceptible patients and 429 ± 20.7 pg/mL for the mutated patients. In susceptible patients, the plasma sCD4 level is 0.163 ± 0.229 ng/mL; in mutant patients, it is 0.084 ± 0.012 ng/mL. The data showed a relative relation between immunological parameters such as sCD80, sCD27, sCD4, and IP-10 and mutation for drug resistance. [ABSTRACT FROM AUTHOR]

BackgroundDevelopmental assessment is an important facility for early detection and intervention of developmental delay in children. Objective: to assess the performance of a sample of middle social class Egyptian infants and toddlers on Bayley Scales of Infant and Toddler Development-third edition (Bayley III), and to compare their cognitive, motor, and communication scores with that of the reference norms.MethodsIt was a cross-sectional pilot study, included 270 children aged 18-42 months. Mothers filled a questionnaire including questions about family socioeconomic background, perinatal history, and family history. Physical examination and growth assessment of children were performed. Developmental assessment of cognitive, language and motor skills was performed using the Bayley III scales and compared the American norm scores with the Egyptian mean scores.ResultsThe mean cognitive, language and motor composite scores were 92.5+18.5, 91.76+ 15.6, and 95.67+18.9 respectively. All were lower than the American mean (100+ 15) with highly significant differences. About one-fourth of the enrolled Egyptian children had below-average composite scores according to the US cutoff point. The ranks of Egyptian children on the American versus the Egyptian percentile curves were significantly different.ConclusionMean values of all assessed developmental domains of Egyptian children are within the norm-referenced average of Bayley III, but lower than the recorded American mean. Assessing Egyptian children according to the American norms may result in overestimating developmental delay. This pilot study raised the question about using different cutoff points suitable for the developmental trajectory of Egyptian children. Answering this question needs further studies on Bayley-III after cultural adaptation and standardization, using a larger, more diverse, and representative sample of the Egyptian population.

AIM:The study was designed to assess the possibility of using circulating miRNAs (serum miRNAs) as diagnostic biomarkers in colorectal cancer (CRC) and to identify their possibility as candidates for targeted therapy. METHODS:The study involved two sample sets: 1- a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD), 18 with colonic polyps (CP) and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group) and 2- a validation set which included 100 CRC patients. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR- 135b and miR- 92a) using the custom miScript miRNA PCR-based sybergreen array. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis. RESULTS:Data analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016), whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018). On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.017 and 0.016; respectively in CRC patients. However, the validation set showed that only miR-223 was significantly up-regulated in CRC patients (fold change = 4.06, p-value = 0.04). CONCLUSION:Aberrant miRNA expressions are highly involved in the cascade of colorectal carcinogenesis. We have found that (miR-17, miR-19a, miR-20a and miR-223) could be used as diagnostic biomarkers for CRC. On the other hand, miR-19b and miR-18a could be used as diagnostic biomarkers for CP and IBD respectively.

Nephrotoxicity is a major side effect for the antineoplastic drug cisplatin. Here, we employed pharmacological, biochemical, and molecular studies to investigate the role of peroxisome proliferator-activated receptors (PPARs) in cisplatin nephrotoxicity. Rats were treated with a single i.p. dose of cisplatin (5 mg/kg) alone or combined with pioglitazone (PPARγ agonist), fenofibrate (PPARα agonist), pioglitazone plus fenofibrate, or thalidomide (Tumor necrosis factor-α inhibitor; TNF-α). Cisplatin nephrotoxicity was evidenced by rises in renal indices of functional (blood urea nitrogen, BUN, and creatinine), inflammatory (TNF-α, interleukin 6, IL-6), oxidative (increased malondialdehyde, MDA, and decreased superoxide dismutase, SOD and nitric oxide metabolites, NOx), apoptotic (caspase 3), and histological (glomerular atrophy, acute tubular necrosis and vacuolation) profiles. Cisplatin effects were partly abolished upon concurrent exposure to pioglitazone, fenofibrate, or thalidomide; more renoprotection was observed in rats treated with pioglitazaone plus fenofibrate. Immunostaining showed that renal expressions of PPARα and PPARγ were reduced by cisplatin and restored to vehicle-treated values after simultaneous treatment with pioglitazone or fenofibrate. Fenofibrate or pioglitazone renoprotection remained unaltered after concurrent blockade of PPARα (GW6471) and PPARγ (GW9662), respectively. To complement the rat studies, we also report that in human embryonic kidney cells (HEK293 cells), increases caused by cisplatin in inflammatory, apoptotic, and oxidative biomarkers were (i) partly improved after exposure to pioglitazone, fenofibrate, or thalidomide, and (ii) completely disappeared in cells treated with a combination of all three drugs. These data establish that the combined use of pioglitazone and fenofibrate additively improved manifestations of cisplatin nephrotoxicity through perhaps GW6471/GW9662-insensitive mechanisms.

BACKGROUND: The importance of visual sense in Hymenopteran social behavior is suggested by the existence of a Hymenopteran insect-specific neural circuit related to visual processing and the fact that worker honeybee brain changes morphologically according to its foraging experience. To analyze molecular and neural bases that underlie the visual abilities of the honeybees, we used a cDNA microarray to search for gene(s) expressed in a neural cell-type preferential manner in a visual center of the honeybee brain, the optic lobes (OLs). METHODOLOGY/PRINCIPAL FINDINGS: Expression analysis of candidate genes using in situ hybridization revealed two genes expressed in a neural cell-type preferential manner in the OLs. One is a homologue of Drosophila futsch, which encodes a microtubule-associated protein and is preferentially expressed in the monopolar cells in the lamina of the OLs. The gene for another microtubule-associated protein, tau, which functionally overlaps with futsch, was also preferentially expressed in the monopolar cells, strongly suggesting the functional importance of these two microtubule-associated proteins in monopolar cells. The other gene encoded a homologue of Misexpression Suppressor of Dominant-negative Kinase Suppressor of Ras 2 (MESK2), which might activate Ras/MAPK-signaling in Drosophila. MESK2 was expressed preferentially in a subclass of neurons located in the ventral region between the lamina and medulla neuropil in the OLs, suggesting that this subclass is a novel OL neuron type characterized by MESK2-expression. These three genes exhibited similar expression patterns in the worker, drone, and queen brains, suggesting that they function similarly irrespective of the honeybee sex or caste. CONCLUSIONS: Here we identified genes that are expressed in a monopolar cell (Amfutsch and Amtau) or ventral medulla-preferential manner (AmMESK2) in insect OLs. These genes may aid in visualizing neurites of monopolar cells and ventral medulla cells, as well as in analyzing the function of these neurons.

Hikikomori, a form of severe social withdrawal has been found to be associated with behavioral addictions such as gaming addiction and problematic social media use (PSMU). Since literature related to hikikomori is lacking in the Middle East, this study aimed to determine whether there are significant differences in hikikomori-like traits between two different types of social media users and gamers and investigate loneliness as a potential mediator between hikikomori and the two types of problematic behaviors. A cross-sectional, correlational design was employed, collecting a final sample of 220 participants residing in Middle Eastern countries using a mixture of convenience and snowball sampling. Results showed that passive social media users demonstrated significantly greater hikikomori-like traits compared to active users. Furthermore, hikikomori-like traits exhibited significant positive associations with problematic gaming, PSMU, and loneliness. Two separate mediation analyses, the first with PSMU and a second with problematic gaming as predictors, revealed that loneliness acted as a significant mediator between both these problematic behaviors and hikikomori-like traits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Women with breast cancer (BC) are at high risk of developing cardiovascular disease (CVD). We examined adherence to CVD medications and their association with major CVD events over 14 years of follow-up in the Pathways Heart Study, a prospective study of 4,776 stage I-III BC patients diagnosed from 2005-2013., Methods: Eligibility included being alive 6 months post-BC diagnosis, with dyslipidemia, hypertension, or diabetes at diagnosis along with ≥1 prior outpatient order or dispensing for a statin, anti-hypertensive, or diabetes medication, respectively, in the 30 months prior. Medication adherence was measured from pharmacy data to calculate cumulative average adherence (CAA). Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via validated diagnosis and procedure codes. Working marginal structural models (MSM) fitted with inverse probability weighting evaluated the effect of adherence regimens on the hazards for each CVD event, while controlling for baseline and time-varying confounders. MSM parameterizations included: 1) CAA<100% versus CAA = 100% (ref), 2) CAA<80% versus CAA≥80% (ref) and 3) CAA<80% versus 80%≤CAA<100% versus CAA = 100%., Results: Poor statin adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.54; 95% CI: 1.09, 5.94) versus CAA≥80%. Poor statin adherence was also associated with a higher risk of stroke (HR = 8.13; 95% CI: 2.03, 32.51) but not risk of IHD and HF. Further, compared with perfect adherence (CAA = 100%), good adherence (80%≤CAA<100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.45; 95% CI: 1.05, 5.70). Levels of adherence to anti-hypertensives and diabetes medications had mixed or null associations with risk of CVD., Conclusions: Maintaining good adherence (≥80%) to statins after BC treatment is beneficial for cardiovascular health in patients with dyslipidemia. Future studies should determine factors associated with lower adherence to statins and ways to improve adherence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kwan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to develop and analyze the accuracy of predictive formulae for postoperative anterior chamber depth, tilt, and decentration of low-added-segment refractive intraocular lenses. This single-center, retrospective, observational study included the right eyes of 96 patients (mean age: 72.43 ± 6.58 years), who underwent a cataract surgery with implantation of a low-added segmented refractive intraocular lens at the Medical University Hospital between July 2019 and January 2021, and were followed up for more than 1 month postoperatively. The participants were divided into an estimation group to create a prediction formula and a validation group to verify the accuracy of the formula. Anterior segment optical coherence tomography (CASIA 2, Tomey Corporation, Japan) and swept-source optical coherence tomography biometry (IOL Master 700, Carl Zeiss Meditec AG) were used to measure the anterior ocular components. A predictive formula was devised for postoperative anterior chamber depth, intraocular lens tilt, and intraocular lens decentration (p <0.01) in the estimation group. A significant positive correlation was observed between the estimated values calculated using the prediction formula and the measured values for postoperative anterior chamber depth (r = 0.792), amount of intraocular lens tilt (r = 0.610), direction of intraocular lens tilt (r = 0.668), and amount of intraocular lens decentration (r = 0.431) (p < 0.01) in the validation group. In conclusion, our findings reveal that predicting the position of the low-added segmented refractive intraocular lens enables the prognosis of postoperative refractive values with a greater accuracy in determining the intraocular lens adaptation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Testicular dysfunction is a prevalent health problem frequently reported in individuals with diabetes mellitus (DM). Oxidative-inflammatory reactions, hormonal and spermatic abnormalities often accompany this illness. Herbal remedies "particularly wild plants" including chicory (Chicorium Intybus) and purslane (Portulaca Oleracea) are emerging as popular agents for people dealing with these issues due to their ability to act as antioxidants, reduce inflammation, and exhibit antidiabetic effects. According to the collected data, the daily administration of chicory (Ch) seed-extract (250 mg/kg) or purslane (Pu) seed-extract (200 mg/kg) to streptozotocin (STZ)-induced diabetic rats (50 mg/kg) for 30 days resulted in the normalization of fasting blood glucose (FBG), serum fructosamine, insulin levels, and insulin resistance (HOMA-IR), as well as reducing lipid peroxidation end-product malondialdehyde (MDA) level, aldehyde oxidase (AO) and xanthene oxidase (XO) activities. While caused a considerable improvement in glutathione (GSH) content, superoxide dismutase (SOD), catalase (CAT) activity, and total antioxidant capacity (TAC) when compared to diabetic rats. Ch and Pu extracts had a substantial impact on testicular parameters including sperm characterization, testosterone level, vimentin expression along with improvements in body and testis weight. They also mitigated hyperlipidemia by reducing total lipids (TL), total cholesterol (TC) levels, and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C). Furthermore, oral administration of either Ch or Pu notably attuned the elevated proinflammatory cytokines as tumor necrotic factor (TNF-α), C-reactive protein (CRP), and Interleukin-6 (IL-6) together with reducing apoptosis and DNA damage. This was achieved through the suppression of DNA-fragmentation marker 8OHdG, triggering of caspase-3 immuno-expression, and elevation of Bcl-2 protein. The histological studies provided evidence supporting the preventive effects of Ch and Pu against DM-induced testicular dysfunction. In conclusion, Ch and Pu seed-extracts mitigate testicular impairment during DM due to their antihyperglycemic, antilipidemic, antioxidant, anti-inflammatory, and antiapoptotic properties., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Saad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Purpose: Mean pulmonary artery pressure (mPAP) is a key index for chronic thromboembolic pulmonary hypertension (CTEPH). Using machine learning, we attempted to construct an accurate prediction model for mPAP in patients with CTEPH., Methods: A total of 136 patients diagnosed with CTEPH were included, for whom mPAP was measured. The following patient data were used as explanatory variables in the model: basic patient information (age and sex), blood tests (brain natriuretic peptide (BNP)), echocardiography (tricuspid valve pressure gradient (TRPG)), and chest radiography (cardiothoracic ratio (CTR), right second arc ratio, and presence of avascular area). Seven machine learning methods including linear regression were used for the multivariable prediction models. Additionally, prediction models were constructed using the AutoML software. Among the 136 patients, 2/3 and 1/3 were used as training and validation sets, respectively. The average of R squared was obtained from 10 different data splittings of the training and validation sets., Results: The optimal machine learning model was linear regression (averaged R squared, 0.360). The optimal combination of explanatory variables with linear regression was age, BNP level, TRPG level, and CTR (averaged R squared, 0.388). The R squared of the optimal multivariable linear regression model was higher than that of the univariable linear regression model with only TRPG., Conclusion: We constructed a more accurate prediction model for mPAP in patients with CTEPH than a model of TRPG only. The prediction performance of our model was improved by selecting the optimal machine learning method and combination of explanatory variables., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Matsunaga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Collection and cooking of wild vegetables have provided seasonal enjoyments for Japanese local people as provisioning and cultural ecosystem services. However, the Fukushima Daiichi Nuclear Power Plant accident in March 2011 caused extensive radiocesium contamination of wild vegetables. Restrictions on commercial shipments of wild vegetables have been in place for the last 10 years. Some species, including buds of Aralia elata, are currently showing radiocesium concentrations both above and below the Japanese reference level for food (100 Bq/kg), implying that there are factors decreasing and increasing the 137Cs concentration. Here, we evaluated easy-to-measure environmental variables (dose rate at the soil surface, organic soil layer thickness, slope steepness, and presence/absence of decontamination practices) and the 137Cs concentrations of 40 A. elata buds at 38 locations in Fukushima Prefecture to provide helpful information on avoiding collecting highly contaminated buds. The 137Cs concentrations in A. elata buds ranged from 1 to 6,280 Bq/kg fresh weight and increased significantly with increases in the dose rate at the soil surface (0.10-6.50 μSv/h). Meanwhile, the 137Cs concentration in A. elata buds were not reduced by decontamination practices. These findings suggest that measuring the latest dose rate at the soil surface at the base of A. elata plants is a helpful way to avoid collecting buds with higher 137Cs concentrations and aid in the management of species in polluted regions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sakai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to identify the trend of approximate participation rate in Japan's National Health and Nutrition Survey (NHNS&#95;J). The proportion of participants among all residents of surveyed districts (estimated participation rate: EPR) was calculated by 12 regional blocks, gender, and age group, and the trend and annual percent change (APC) were clarified. Based on the 1997-2019 NHNS&#95;J data, we created a database classified by prefecture, gender, and age group; in addition to these, the number of people per household by Population Census or population estimates were obtained from e-Stat and added to the database. All analyses were performed by regional block and gender and EPR for each year was calculated by the age group. Trends of EPR, overall and by the age group, were presented using graphs, illustrating the exponential regression curve. The graphs showed APC, standard error, and statistical significance by age group. The EPRs were declining in all the regional blocks. Additionally, the rates of decline in APC in young people under the age of 50 years were higher than those in the older age groups in 9 of 12 regional blocks. The nationwide APC in the age group <50 years was significantly larger than that in the age group ≥50 years. The declining EPR trend in NHNS&#95;J in all regional blocks (especially among younger people) suggests the need for a strategy to improve participation rates in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ishikawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In order to assess the electromagnetic exposure safety of passengers under the civil communication system of the subway, the radio-frequency (RF) electromagnetic environment of subway carriage is established by using COMSOL Multiphysics software, it includes a 1-1/4 " leaky coaxial cable (LCX1) and a 1-5/8" leaky coaxial cable (LCX2), which are designed to be the exposure sources, and twelve passengers at different position. The electromagnetic environment model has been verified through field measurement. The exposure dose distribution of twelve passengers is compared and analyzed, when LCX1 and LCX2 works respectively. The simulated results show that, to compare with LCX2, the electromagnetic dose absorbed by the passengers is reduced by 9.19% and 22.50% at 2100 MHz and 2600 MHz respectively. The specific absorption rate (SAR) of passengers obtains the maximum value of 1.91×10-4 W/Kg and the temperature rise to 0.214 K when the LCX1 works at 3400 MHz. By comparing with the public exposure limitation of the International Commission of Non-Ionizing Radiation Protection (ICNIRP), it demonstrates the electromagnetic exposure safety of the passengers under the civil communication system. More importantly, the proposed LCX1 not only could add the 5G signal cover but also lower the SAR absorbed by the passengers, which indicates that the public electromagnetic exposure dose could be reduced by adjusting the radiation performances of exposure source, which provide a new way for electromagnetic protecting., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study examines the effects of news events related to the European Union-Vietnam Free Trade Agreement (EVFTA) on the Vietnam stock market from 2010 to 2020. We calculate sectoral abnormal returns prior to, during, and after announcements and find that the Vietnamese stock market is susceptible to these events. We discovered that the announcement had a negative impact on the market, which might diminish the effectiveness of the Agreement. The findings show that more than half of Vietnam's sectors had an immediate reaction to EVFTA announcements, with fourteen reacting negatively and six responding positively. Two of the ten events did not have any immediate impact on these industries but all events resulted in either early or delayed reactions. We also find market scepticism and major changes in the deal led to the emergence of a diamond risk structure. We run multiple robustness tests to account for market integration and other factors that may affect stock returns. In addition, we explore potential sectoral systematic risk changes following these occurrences using different ARCH-type models. These additional tests confirm the robustness of our findings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Vaccine hesitancy is a major obstacle to the large efforts made by governments and health organizations toward achieving successful COVID-19 vaccination programs. Healthcare worker's (HCWs) acceptance or refusal of the vaccine is an influencing factor to the attitudes of their patients and general population. This study aimed to report the acceptance rates for COVID-19 vaccines among HCWs in Arab countries and identify key factors driving the attitudes of HCWs in the Arab world toward vaccines., Methods: This systematic review and meta-analysis followed the PRISMA guidelines. PubMed and Scopus databases were searched using pre-specified keywords. All cross-sectional studies that assessed COVID-19 vaccine hesitancy and/or acceptance among HCWs in Arab countries until July 2022, were included. The quality of the included studies and the risk of bias was assessed using the JBI critical appraisal tool. The pooled acceptance rate of the COVID-19 vaccine was assessed using a random-effects model with a 95% confidence interval., Results: A total of 861 articles were identified, of which, 43 were included in the study. All the studies were cross-sectional and survey-based. The total sample size was 57,250 HCWs and the acceptance rate of the COVID-19 vaccine was 60.4% (95% CI, 53.8% to 66.6%; I2, 41.9%). In addition, the COVID-19 vaccine acceptance rate among males was 65.4% (95% CI, 55.9% to 73.9%; I2, 0%) while among females was 48.2% (95% CI, 37.8% to 58.6%; I2, 0%). The most frequently reported factors associated with COVID-19 vaccine acceptance were being male, higher risk perception of contracting COVID-19, positive attitude toward the influenza vaccine, and higher educational level. Predictors of vaccine hesitancy most frequently included concerns about COVID-19 vaccine safety, living in rural areas, low monthly income, and fewer years of practice experience., Conclusion: A moderate acceptance rate of COVID-19 vaccines was reported among HCWs in the Arab World. Considering potential future pandemics, regulatory bodies should raise awareness regarding vaccine safety and efficacy and tailor their efforts to target HCWs who would consequently influence the public with their attitude towards vaccines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alalawi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The purpose is to clarify the relationship between patients with retinal vein occlusion (RVO), maximal intima-media complex thickness (Max IMT), and N-terminal pro-brain natriuretic peptide (NT-proBNP), which is useful in assessing atherosclerosis. This was a retrospective observation, single center study. The patients were 86 RVO patients (male: female = 43:43, mean age 63.3 years), 25 with central retinal vein occlusion (CRVO) and 61 with branch retinal vein occlusion (BRVO), classified as ≧50 years old and <50 years old, Max IMT≧1.1 and less, NT-pro BNP≧55 and less. Results showed that Max IMT ≧1.1 was significantly more common in both the CRVO and BRVO groups at ≧50 years, and NT-pro BNP ≧55 was significantly more common in the CRVO group. Max IMT≧1.1 was seen in 80% of the BRVO group and in 85% of patients aged ≧50 years. Sixty-eight percent of patients in the CRVO group had Max IMT≧1.1, but none of those < 50 years had Max IMT≧1.1. Forty-eight percent of RVO patients had NT-pro BNP≧55, and significantly more patients had Max IMT≧1.1 than those who did not have NT-pro BNP more than 55 (p = 0.02). Multiple regression analysis with Max IMT as the dependent variable showed that age and NT-pro BNP were significantly associated with RVO (p = 0.015, 0.022). RVO patients were more likely to have a Max IMT≧1.1, which was associated with atherosclerosis. Max IMT and NT-pro BNP were also associated with RVO patients, so NT-pro BNP may be a marker of RVO., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Onoe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The present study investigated lifestyle risk factors from metabolic syndrome-related lifestyles for a rapid decline in the estimated glomerular filtration rate (eGFR) among adults aged 40-74 years with treated and untreated type 2 diabetes., Methods and Results: This study analyzed data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, encompassing the period from fiscal year (FY) 2017 to FY2020. We established FY2018 as our baseline year. The subjects of this study were adults aged 40-74 in FY2018(baseline) who had type 2 diabetes and underwent specific health checkups in FY2020. We excluded adults with a medical record of kidney dialysis between FY2017 and FY2018, records of suspected type 1 diabetes between FY2017 and FY2020, or a baseline eGFR >85 mL/min/1.73 m2 or missing eGFR data as of FY2020. Eventually we analyzed 573,860 individuals. The outcome variable was a rapid decline in eGFR (≥30%) during the follow-up. Exposure lifestyle factors included skipping breakfast, late-night dinners, regular smoking, a high alcohol intake, non-refreshing sleep, and a lack of habitual exercise. Logistic regression models were stratified by age (40-59 and 60-74 years) and baseline eGFR levels (60-85, 30-59, and <30 mL/min/1.73 m2). Covariates included sex, a history of heart disease, a history of stroke, a history of renal failure, anemia, low-density lipoprotein, systolic blood pressure, hemoglobin A1C, body mass index, antidiabetic medications, antihypertension drugs, lipid-lowering drugs, the oral adsorbent Kremezin, non-steroidal anti-inflammatory drugs, and drugs for the treatment of renal anemia. A rapid decline in eGFR was detected in approximately 1.3% of participants (7,683 cases). In the baseline eGFR >30 subgroups (60-85 or 30-59 mL/min/1.73 m2), skipping breakfast and regular smoking were associated with a rapid decline in eGFR in both age groups, while a lack of habitual exercise and late-night dinners in the 60-74 age group and non-refreshing sleep in the 40-59 age group were identified as risk factors. Additionally, skipping breakfast was a risk factor for a rapid decline in eGFR in the 60-74 age group regardless of baseline eGFR levels. In the baseline eGFR <30 mL/min/1.73 m2 subgroup, skipping breakfast and non-refreshed sleep were risk factors for a rapid decline in eGFR., Conclusions: We found specific lifestyle risk factors were associated with a rapid eGFR decline among people with type 2 diabetes from a nationwide database in Japan. The associations varied by baseline eGFR level, age, and sex. Lifestyle modifications may effectively prevent the aggravation of diabetic kidney disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The purpose of this study was to investigate the effect of a 1% brinzolamide and 0.1% brimonidine fixed combination (BBFC) on ONH blood flow (BF) in rabbits., Methods: A crossover study was conducted on pigmented rabbits; a physiological saline solution, brinzolamide, or BBFC was administered for eight days. ONH BF, intraocular pressure (IOP) and systemic parameters were measured before the eighth day's first dose and at 6, 9, 12, and 14 hours after the dose. ONH BF was assessed using laser speckle flowgraphy, and mean blur rate (MBR) values were calculated. The percentage against baseline of each parameter was calculated, and intergroup comparisons were performed at each time point., Results: There were no significant differences in the percentage change in systemic parameters. At 6 hours after administration, the BBFC group showed a significantly higher percentage change in large vessel area-MBR (%MV) compared to the control group (98.6±16.8%MV vs. 81.3±7.9%MV, P = 0.03). On the other hand, the brinzolamide group did not show a significant difference. Both the brinzolamide and BBFC groups had significantly lower percentage change in IOP (%IOP) compared to the control group (90.6±5.0%IOP, 93.3±2.9%IOP, and 99.2±1.7%IOP, respectively, P < 0.01)., Conclusion: BBFC effectively reduces IOP and mitigates diurnal fluctuation-induced decreases in ONH BF., Competing Interests: Co-author EK is employed by Senju Pharmaceutical Co., Ltd., a commercial company. Additionally, corresponding author TN has received research funding from Senju Pharmaceutical Co., Ltd. The other authors have no potential conflicts of interest associated with this manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Takahashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

During the COVID-19 pandemic, face masks on patients and healthy people have been recommended to prevent airborne transmission of the virus. This increased the number of people who felt stressed while wearing masks. In this study, we investigated the stress-relieving effects of attaching aroma seals to masks. A double-blind, randomized controlled trial was conducted involving 62 university students. The participants were randomly assigned to two groups and instructed to apply a seal to their masks once a day throughout the study period. The primary measure used was the Depression, Anxiety, and Stress Scale-21 (DASS-21), while the secondary measures included the assessment of breathlessness associated with mask-wearing and the World Health Organization Five Well-Being Index (WHO-5). The intervention group, referred to as the aroma-seal use group, utilized aroma seals infused with orange-lime essential oil with the expectation of experiencing the healing effects of citrus. On the other hand, the non-intervention group, known as the placebo-seal use group, utilized identical seals without any aroma. Results indicated that the aroma-seal use group exhibited significant improvements in both the total DASS-21 scores and depression scores compared to their baseline values by the second week of the intervention. Furthermore, the aroma-seal use group demonstrated a reduced occurrence of breathlessness while wearing masks compared to the placebo-seal group. Additionally, when assessing the item "I have felt calm and relaxed" from the WHO-5 questionnaire, the aroma-seal use group displayed significantly higher scores than the placebo group. Therefore, using aroma seals containing orange-lime essential oil could be beneficial in relieving mental stress and reducing breathlessness while wearing a mask, thus improving mental health., Competing Interests: NO authors have competing interests Enter: The authors have declared that no competing interests exist., (Copyright: © 2023 Wakui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Type 1 diabetes (T1D) is a metabolic disease characterized by hyperglycemia and can affect multiple organs, leading to life-threatening complications. Increased prevalence of pulmonary disease is observed in T1D patients, and diabetes is a leading cause of comorbidity in several lung pathologies. A deficiency of alpha-1 antitrypsin (AAT) can lead to the development of emphysema. Decreased AAT plasma concentrations and anti-protease activity are documented in T1D patients. The objective of this study was to determine whether T1D exacerbates the progression of lung damage in AAT deficiency. First, pulmonary function testing (PFT) and histopathological changes in the lungs of C57BL/6J streptozotocin (STZ)-induced T1D mice were investigated 3 and 6 months after the onset of hyperglycemia. PFT demonstrated a restrictive pulmonary pattern in the lungs of STZ-injected mice, along with upregulation of mRNA expression of pro-fibrotic markers Acta2, Ccn2, and Fn1. Increased collagen deposition was observed 6 months after the onset of hyperglycemia. To study the effect of T1D on the progression of lung damage in AAT deficiency background, C57BL/6J AAT knockout (KO) mice were used. Control and STZ-challenged AAT KO mice did not show significant changes in lung function 3 months after the onset of hyperglycemia. However, histological examination of the lung demonstrated increased collagen accumulation and alveolar space enlargement in STZ-induced AAT KO mice. AAT pretreatment on TGF-β-stimulated primary lung fibroblasts reduced mRNA expression of pro-fibrotic markers ACTA2, CCN2, and FN1. Induction of T1D in AAT deficiency leads to a combined pulmonary fibrosis and emphysema (CPFE) phenotype in male mice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: COVID-19 precipitated a plethora of mental health difficulties, particularly for those with pre-existing mental health concerns such as depression or addictive tendencies. For some, the distress that emanated from the experience of the pandemic prompted excessive engagement in the safety of online interactions on social media. The present study examined whether variation in individuals' sense of control explained the association between depression and addictive social media use., Method: A sample of 1322 participants from two Middle Eastern nations provided data collected during the peak of the pandemic from February to May 2021. A combination of convenience and snowball sampling were used to recruit and collect data from college-aged students enrolled at two universities in Egypt and the United Arab Emirates, respectively. This study adopted a cross-sectional design in which participants completed a self-administered survey that consisted of measures that assessed depressive affect, sense of control, and addictive social media use., Results: Depression was significantly and positively associated with addictive SMU. Sense of control was negatively related to both depression and SMU and significantly mediated the association between these two variables (β = .62, SE = .03, 95%CI .56, .68)., Conclusion: This study identified a potential protective variable that could be targeted by psychological treatment to ameliorate the potential onset of addictive SMU in individuals with depressive symptoms under conditions of immense psychological distress such as a worldwide pandemic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Vally et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The impact of direct-acting antivirals (DAA) therapy on lipid and glucose metabolism and kidney function in patients with hepatitis C virus (HCV) infection, along with its side effects on blood cells, remains controversial. Therefore, we conducted a study that enrolled 280 patients with HCV infection who achieved sustained virologic response after treatment with DAA therapy without ribavirin to evaluate the metabolic changes, renal function, and anemia risk based on real-world data. This study was an observational prospective study with a follow-up period of 12 weeks after the initiation of DAA therapy. Data on biochemical tests, renal function, blood counts, viral load, and host genomics were recorded before treatment and after 12 weeks of treatment with DAAs. DAA therapy reduced fibrosis-4 scores and improved liver function, with significant reductions in aspartate transaminase, alanine aminotransferase, and total bilirubin levels. However, DAA therapy slightly increased uric acid, cholesterol, and low-density lipoprotein cholesterol levels. It significantly reduced fasting blood glucose levels and hemoglobin A1C index (HbA1C) in the study group, while hemoglobin (Hb) and hematocrit (HCT) concentrations decreased significantly (4.78 ± 21.79 g/L and 0.09% ± 0.11%, respectively). The estimated glomerular filtration rate (eGFR) decreased by 12.89 ± 39.04 mL/min/1.73m2. Most variations were not related to the genotype, except for Hb, HCT, and HbA1C. Anemia incidence increased from 23.58% before treatment to 30.72% after treatment. Patients with HCV-1 genotype had a higher rate of anemia than did patients with genotype 6 (36.23% vs. 24.62%). Multivariate analysis showed that the risk of anemia was related to female sex, cirrhosis status, fibrosis-4 score, pretreatment eGFR, and pretreatment Hb level. The results of our study can provide helpful information to clinicians for the prognosis and treatment of HCV infection., Competing Interests: NO authors have competing interests The authors have declared that no competing interests exist., (Copyright: © 2023 Thi Thu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Reticulocyte hemoglobin (CHr) is a measure of the amount of hemoglobin in reticulocytes and a marker of cell hemoglobinization. In this study, we aimed to find the optimal cut-off point for reticulocyte hemoglobin to diagnose iron deficiency anemia using multiple methods. A total of 309 patients were included. The median age at diagnosis was 54 years. Most were females (71.2%). 68% had iron deficiency anemia. Patients with IDA had significantly lower levels of CHr compared to those who had non-IDA (p < 0.0001). The optimal cut-off value of CHr for detecting IDA, determined using various methods, was 30.15 pg. This cut-off point had a sensitivity of 87.8% and a specificity of 77.7%. CHr showed a significant positive correlation with hemoglobin, mean corpuscular volume, serum iron, serum ferritin, and transferrin saturation and a significant negative correlation with total iron-binding capacity. CHr levels correlate with most established laboratory tests for IDA. It reliably detects IDA. Our results indicate the importance of CHr in diagnosing IDA, and that CHr should be used more widely in suspected cases of IDA since it is a cheap, fast, and reliable test., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alzu’bi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The novel coronavirus disease (COVID-19) pandemic has impacted pregnant women, increasing maternal and neonatal morbidity. The placenta is a potential target for the pathophysiological processes due to the increased thrombotic inflammatory activation and inadequate uteroplacental perfusion and oxygenation, potentially causing intrauterine growth restriction. This study investigates the impact of gestational age at diagnosis of COVID-19 and the presence of symptoms on intrauterine fetal growth in pregnant women., Methods: A retrospective review of COVID-19 positive pregnant women in Qatar from March 2020 to March 2021 was conducted. They were divided based on trimester of pregnancy in which they were infected. The outcomes included birthweight, customised fetal birthweight centiles, small for gestational age (SGA) baby and daily growth increments, compared between the trimesters and between symptomatic and asymptomatic women., Results: In our cohort, 218 women (20.5%) were infected in the first trimester, 399 (37.5%) in the second and 446 (42%) in the third. Women in the second trimester were significantly younger and symptomatic. Women infected in the first trimester were least likely to have diabetes. The mean birthweight, risk of SGA (11.5% vs 10% vs 14.6%, p = 0.302), and median customized growth centiles (47.6% vs 45.9% vs 46.1%)were similar between the groups. Symptomatic women had significantly lower mean birthweight (3147 gms vs 3222 gms) and median birthweight centiles (43.9% vs 54.0%)compared to the asymptomatic (p<0.05 for both). In women infected within 20 weeks of gestation, a delay in daily fetal growth increments was noted with symptomatic disease, although not statistically significant., Conclusion: This study shows that women with symptomatic disease had lower birth centiles and birth weights. This was regardless of the gestational age at which they were infected. Early symptomatic disease seems to have an impact on fetal growth velocity; however, larger studies are needed to corroborate these findings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Farrell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Myocardial infarction (MI) can result in fatal myocardial rupture or heart failure due to adverse remodeling and dysfunction of the left ventricle. Although recent studies have shown that exogenous interleukin (IL)-22 shows cardioprotective effect after MI, the pathophysiological significance of endogenous IL-22 is unknown. In this study, we investigated the role of endogenous IL-22 in a mouse model of MI. We produced MI model by permanent ligation of the left coronary artery in wild-type (WT) and IL-22 knock-out (KO) mice. The post-MI survival rate was significantly worse in IL-22KO mice than in WT mice due to a higher rate of cardiac rupture. Although IL-22KO mice exhibited a significantly greater infarct size than WT mice, there was no significant difference in left ventricular geometry or function between WT and IL-22KO mice. IL-22KO mice showed increase in infiltrating macrophages and myofibroblasts, and altered expression pattern of inflammation- and extracellular matrix (ECM)-related genes after MI. While IL-22KO mice showed no obvious changes in cardiac morphology or function before MI, expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were increased, whereas that of tissue inhibitor of MMPs (TIMP)-3 was decreased in cardiac tissue. Protein expression of IL-22 receptor complex, IL-22 receptor alpha 1 (IL-22R1) and IL-10 receptor beta (IL-10RB), were increased in cardiac tissue 3 days after MI, regardless of the genotype. We propose that endogenous IL-22 plays an important role in preventing cardiac rupture after MI, possibly by regulating inflammation and ECM metabolism., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yamamoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This retrospective study investigated the correlation between bone mineral density (BMD) and COVID-19 severity among COVID-19 patients who underwent chest computed tomography (CT) scans., Methods: This study was carried out at the King Abdullah Medical Complex in Jeddah, Saudi Arabia, one of the largest COVID-19 centers in the western province. All adult COVID-19 patients who had a chest CT between January 2020 and April 2022 were included in the study. The pulmonary severity scores (PSS) and vertebral BMD measurements were obtained from the patient's CT chest. Data from the patients' electronic records were collected., Results: The average patient age was 56.4 years, and most (73.5%) patients were men. Diabetes (n = 66, 48.5%), hypertension (n = 56, 41.2%), and coronary artery disease (n = 17, 12.5%) were the most prevalent comorbidities. Approximately two-thirds of hospitalized patients required ICU admission (64%), and one-third died (30%). The average length of stay in the hospital was 28.4 days. The mean CT pneumonia severity score (PSS) was 10.6 at the time of admission. Patients with lower vertebral BMD (< = 100) numbered 12 (8.8%), while those with higher vertebral BMD (>100) numbered 124 (91.2%). Only 46 out of the total survived patients (n = 95) were admitted to the ICU versus all deceased (P<0.01). The logistic regression analysis revealed that an elevated PSS upon admission resulted in a reduced chance of survival. Age, gender, and BMD did not predict survival chances., Conclusion: The BMD had no prognostic advantage, and the PSS was the significant factor that could have predicted the outcome., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bakhsh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chandelier (Ch) cells are cortical interneurons with axon terminal structures known as cartridges that synapse on the axon initial segment of excitatory pyramidal neurons. Previous studies indicate that the number of Ch cells is decreased in autism, and that GABA receptors are decreased in the Ch cell synaptic target in the prefrontal cortex. To further identify Ch cell alterations, we examined whether the length of cartridges, and the number, density, and size of Ch cell synaptic boutons, differed in the prefrontal cortex of cases with autism versus control cases. We collected samples of postmortem human prefrontal cortex (Brodmann Area (BA) 9, 46, and 47) from 20 cases with autism and 20 age- and sex-matched control cases. Ch cells were labeled using an antibody against parvalbumin, a marker that labeles soma, cartridges, and synaptic boutons. We found no significant difference in the average length of cartridges, or in the total number or density of boutons in control subjects vs. subjects with autism. However, we found a significant decrease in the size of Ch cell boutons in those with autism. The reduced size of Ch cell boutons may result in reduced inhibitory signal transmission and impact the balance of excitation to inhibition in the prefrontal cortex in autism., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Malignancy is often associated with therapeutic resistance and metastasis, usually arising after therapeutic treatment. These include radio- and chemo-therapies, which cause cancer cell death by inducing DNA double strand breaks (DSBs). However, it is still unclear how resistance to these DSBs is induced and whether it can be suppressed. Here, we show that DSBs induced by camptothecin (CPT) and radiation jeopardize genome stability in surviving cancer cells, ultimately leading to the development of resistance. Further, we show that cytosolic DNA, accumulating as a consequence of genomic destabilization, leads to increased cGAS/STING-pathway activation and, ultimately, increased cell migration, a precursor of metastasis. Interestingly, these genomic destabilization-associated phenotypes were suppressed by the PARP inhibitor Olaparib. Recognition of DSBs by Rad51 and genomic destabilization were largely reduced by Olaparib, while the DNA damage response and cancer cell death were effectively increased. Thus, Olaparib decreases the risk of therapeutic resistance and cell migration of cells that survive radio- and CPT-treatments., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: this work was supported by AstraZeneca K.K. and Merck Sharp & Dohme Corp.This does not alter our adherence to PLOS ONE policies on sharing data and materials. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright: © 2023 Suzuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to clarify the educational significance and issues associated with administering the objective structured clinical examination (OSCE) twice to midwifery students, i.e., before and after clinical training. In Sapporo City University in Japan, 37 assessment items of the OSCE were configured as "Overall," with 17 items as midwifery's normal delivery preparation (Part 1) and 20 items as midwifery's normal delivery assistance (Part 2). All students had attended lectures with textbooks. The first and second OSCEs were conducted before and after the clinical training, respectively. The scores of 54 students were retrospectively analyzed over 6 years (2014-2019). The results of the first and second OSCEs were compared. Statistical analysis was performed using Mann-Whitney U test, Wilcoxon signed rank-sum test, Fisher's exact test, and analysis of variance. The mean scores for "Overall" [0-37], "Part 1" [0-17], and "Part 2" [0-20] in the second OSCEs were significantly higher than those in the first OSCE (Overall: 22.7 vs 19.3, Part 1: 9.50 vs 7.71, Part 2: 13.2 vs 11.6, p<0.05, respectively). Regarding "Overall" and "Part 1," a positive correlation was observed between the first and second OSCEs, wherein the full scores of "Part 1," converted from 17 to 20 points to match the full scores of "Part 2," were significantly lower than those of Part 2 (p<0.05, respectively). There was a positive correlation between the scores of the first and second OSCEs in "Part 1" and "Part 2" (p<0.05). The scores increased between the two OSCEs, and participants could objectively grasp the knowledge and skills. The OSCEs conducted twice were useful in skilling-up the normal delivery preparation and assistance skills of midwifery students. However, developing an advanced educational method might be necessary for the midwifery students' preparation of normal delivery, because the scores in the OSCEs were lower., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Morikawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To investigate the cost-effectiveness of abatacept (ABA) as first-line (1L) therapy in Japanese rheumatoid arthritis (RA) patients using data from the Institute of Rheumatology, Rheumatoid Arthritis database., Methods: A decision-analytic model was used to estimate the cost per American College of Rheumatology response of at least 50% improvement (ACR50) responder and per patient in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) remission from a Japanese healthcare payers' perspective over a 2-year time horizon. Clinical characteristics of patients on ABA-1L were matched with those of patients on ABA second or later line (2L+) or tumour necrosis factor inhibitor (TNFi)-1L directly or using propensity scores. Resource utilisation and medical costs were calculated from the Japan Medical Data Center claims database. Parameter uncertainty was addressed by sensitivity and subgroup analyses (age, treatment duration, Japanese version of Health Assessment Questionnaire [J-HAQ] score)., Results: Incremental costs per member per month (ΔPMPM) for ABA-1L versus TNFi-1L and ABA-2L+ were -1,571 Japanese Yen (JPY) and 81 JPY, respectively. For ABA-1L versus TNFi-1L, ΔPMPM by ACR50 response was -11,715 JPY and by CDAI and SDAI remission 11,602 JPY and 47,003 JPY, respectively. Corresponding costs for ABA-1L were lower for all outcome parameters versus those for ABA-2L+. Scenario analyses showed that ABA-1L was cost-effective over TNFi-1L in patients <65 years for any outcome. Furthermore, ABA-1L was cost-effective over ABA-2L+ for all outcomes in patients with age <65 years, disease duration <5 years and J-HAQ ≥1.5., Conclusions: ABA-1L demonstrated a favourable cost-effectiveness profile in RA patients, accruing savings for the Japanese healthcare payers., Competing Interests: ET reports consulting fees from AbbVie Japan GK, Asahi Kasei Corp., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Pfizer Japan Inc. and Takeda Pharmaceutical Co., Ltd. and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie Japan GK, Astellas Pharma Inc., Asahi Kasei Corp., Ayumi Pharmaceutical Co., Bristol-Myers Squibb Co., Celltrion Healthcare Japan Co, Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kyowa Pharma Chemical Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Nippon Kayaku Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd. and UCB Japan Co., Ltd. EI reports consulting fees from Pfizer Japan Inc., Bristol-Myers Squibb Co., Ltd., Nippontect Systems Co., Ltd. and RCR Co., Ltd. AS is an employee of Medilead, Inc., which was commissioned to perform this study analysis by Tokyo Women’s Medical University. JN was employed by ICON plc. for this study. CP is an employee of ICON plc. and reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bristol-Myers Squibb Co., Ltd. DD is an employee of Bristol-Myers Squibb Co., Ltd. and reports stock or stock options from Bristol-Myers Squibb Co., Ltd. YY is an employee of Bristol-Myers Squibb Co., Ltd. MO reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chugai Pharmaceutical Co., Ltd., Sentan Igaku-Sha Ltd., Asahi Kasei Corp., Bunkodo Co., Ltd., Maruho Co., Ltd., Medical view Co., Ltd. and Kagakuhyoronsya Co., Ltd. KI reports consulting fees from Zimmer Biomet Holdings, Inc.; payment or honoraria for speakers bureaus from AbbVie, Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol-Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc., Janssen Pharmaceutical K.K., Eli Lilly Japan K.K, Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co. and UCB Japan Co. and for participation on a Data Safety Monitoring Board or Advisory Board from Gilead Sciences, Inc.; and unrestricted grant to Division of Multidisciplinary Management of Rheumatic Diseases from Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Ltd, Nippon Kayaku Co., Ltd. and Teijin Pharma Ltd. HY reports consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Teijin Pharma Ltd., Eisai Co., Ltd., YLBio, Pfizer Japan Inc., Astellas Pharma Inc., Mitsubishi Tanabe Pharma Co., Bristol-Myers Squibb Co., Ltd., AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer, Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc., Kaken, Nippon Kayaku Co., Ltd., Novartis, Ono, Taisyo-Toyama, Takeda, Torii Pharmaceutical Co., Ltd., UCB Japan Co., Ltd. and MSD. MH reports research grants from Bristol-Myers Squibb K.K.; grants or contracts from AbbVie Japan GK, Kaken Pharmaceutical Co. Ltd., Asahi Kasei Corp., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Nippon Kayaku Co., Ltd., Ayumi Pharmaceutical Co., Taisho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Takeda, Daiichi-Sankyo, Inc., Pfizer Japan Inc. and Eisai Co., Ltd.; consulting fees from AbbVie Japan GK and Bristol-Myers Squibb K.K. and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie GK, Nippon Kayaku Co., Ltd., Ayumi Pharmaceutical Co., Nippon Shinyaku Co., Ltd., Bristol-Myers Squibb K.K., Ltd., Pfizer Japan Inc., Chugai Pharmaceutical Co., Mitsubishi Tanabe Pharma Co., Eisai Co., Ltd., UCB Japan Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences Inc. and Janssen Pharmaceutical K.K. MA, KS, ES, NS and RY have no conflicts of interest to report., (Copyright: © 2022 Tanaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Automatic operations of multi-functional and time-lapse live-cell imaging are necessary for the biomedical science community to study active, multi-faceted, and long-term biological phenomena. To achieve automatic control, most existing solutions often require the purchase of extra software programs and hardware that rely on the manufacturers' own specifications. However, these software programs are usually non-user-programmable and unaffordable for many laboratories. To address this unmet need, we have developed a novel open-source software program, titled Automatic Multi-functional Integration Program (AMFIP), as a new Java-based and hardware-independent system that provides proven advantages over existing alternatives to the scientific community. Without extra hardware, AMFIP enables the functional synchronization of the μManager software platform, the Nikon NIS-Elements platform, and other 3rd party software to achieve automatic operations of most commercially available microscopy systems, including but not limited to those from Nikon. AMFIP provides a user-friendly and programmable graphical user interface (GUI), opening the door to expanding the customizability for myriad hardware and software systems according to user-specific experimental requirements and environments. To validate the intended purposes of developing AMFIP, we applied it to elucidate the question whether single cells, prior to their full spreading, can sense and respond to a soft solid substrate, and if so, how does the interaction depend on the cell spreading time and the stiffness of the substrate. Using a CRISPR/Cas9-engineered human epithelial Beas2B (B2B) cell line that expresses mNeonGreen2-tagged mechanosensitive Yes-associated protein (YAP), we show that single B2B cells develop distinct substrate-stiffness-dependent YAP expressions within 10 hours at most on the substrate, suggesting that cells are able to sense, distinguish, and respond to mechanical cues prior to the establishment of full cell spreading. In summary, AMFIP provides a reliable, open-source, and cost-free solution that has the validated long-term utility to satisfy the need of automatic imaging operations in the scientific community., Competing Interests: The authors have declared that no competing interests exist.

Brucellosis is an endemic zoonotic disease caused by Brucella species, which are intramacrophage pathogens that make treating this disease challenging. The negative effects of the treatment regime have prompted the development of new antimicrobials against brucellosis. A new treatment modality for antibiotic-resistant microorganisms is the use of nanoparticles (NPs). In this study, we examined the antibacterial activities of silver and gold NPs (SNPs and GNPs, respectively), the resistance developed by Brucella melitensis (B. melitensis) and Brucella abortus (B. abortus) strains and the toxicity of both of these NPs in experimental rats. To test the bactericidal effects of the SNPs and GNPs, we used 22 multidrug-resistant Brucella isolates (10 B. melitensis and 12 B. abortus). The minimal inhibitory concentrations (MICs) of both types of NPs were determined utilizing the microdilution technique. To test the stability of resistance, 7 B. melitensis and 6 B. abortus isolates were passaged ten times in culture with subinhibitory concentrations of NPs and another ten times without NPs. Histopathological analysis was completed after rats were given 0.25, 0.5, 1, and 2 mg/kg NPs orally for 28 consecutive days. The MIC values (μg/ml) of the 10-nm SNPs and 20-nm GNPs against B. melitensis were 22.43 ± 2.32 and 13.56 ± 1.22, while these values were 18.77 ± 1.33 and 12.45 ± 1.59 for B. abortus, respectively. After extensive in vitro exposure, most strains showed no resistance to the 10-nm SNPs or 20-nm GNPs. The NPs and antibiotics did not cross-react in any of the evolved Brucella strains. SNPs and GNPs at doses below 2 mg/kg were not harmful to rat tissue according to organ histopathological examinations. However, a greater dose of NPs (2 mg/kg) harmed all of the tissues studied. The bactericidal properties of NPs are demonstrated in this work. Brucella strains develop similar resistance to SNPs and GNPs, and at low dosages, neither SNPs nor GNPs were hazardous to rats., Competing Interests: The authors have declared that no competing interests exist.

Background: The relationship between bothersome symptoms and gastric pressure or CO2 injection volumes in drug-resistant functional dyspepsia (FD) patients remains unknown; therefore, this relationship was examined in drug-resistant FD and non-FD patients., Methods: Thirty drug-resistant FD patients and 30 non-FD patients were recruited. Gastric pressure was assessed using an external pressure transducer, and the CO2 injection volume was measured using an endoscopic CO2-supplied device and flow meter. The following variables were examined: gastric pressure at baseline and gastric pressure and the CO2 injection volume when patients initially felt abdominal tension and bothersome symptoms following the CO2 injection. The relationship between belching and bothersome symptoms was also investigated., Results: No significant differences were observed in basal gastric pressure between the groups. Initial and bothersome symptoms in the upper abdomen in drug-resistant FD patients developed at a significantly lower gastric pressure and significantly smaller CO2 injection volume than in non-FD patients. The frequency of belching was significantly lower in the drug-resistant FD group than in the non-FD group., Conclusion: Bothersome symptoms in drug-resistant FD patients develop at a lower gastric pressure and smaller CO2 injection volume than in non-FD patients. These patients also had difficulties with belching., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The COVID-19 pandemic has had a substantial impact on the normalcy of life. Similarly, social media use (SMU) has increased exponentially. This study examined the association between individuals' perception of the psychological burden related to the pandemic and addictive SMU., Method: A cross-sectional study was conducted between February and May 2021 in two national contexts, Egypt, and the United Arab Emirates. Data were gathered from a sample of 1322 participants drawn from a university population who completed measures of psychological burden related to COVID-19, anxious affect, and addictive SMU. Preliminary analyses of the potential association between the study variables were conducted using bivariate correlations followed by a pre-specified mediation model., Results: At a correlational level, all three study variables were positively associated with each other (r values ranged from .18 to .50 and all p values were < .05). A further mediation analysis confirmed that the total effect of psychological burden on addictive SMU was significant (β = .654, SE = .033, 95% CI .589-.720), and this relationship remained significant with inclusion of the mediator. Significant mediation was evident across the total sample as well as within each country-specific subsample., Conclusion: These results provide insight into the factors that contribute to the development of addictive SMU in relation to the COVID-19 pandemic. Findings are discussed in relation to the emotion regulation function that SMU might play for individuals in the midst of emotional distress., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Percutaneous patent ductus arteriosus (PDA) stenting is a therapeutic modality in patients with duct-dependent pulmonary circulation with reported success rates from 80-100%. The current study aims to assess the outcome and the indicators of success for PDA stenting in different ductal morphologies using various approaches., Methods: A prospective cohort study from a single tertiary center presented from January 2018 to December 2019 that included 96 consecutive infants with ductal-dependent pulmonary circulation and palliated with PDA stenting. Patients were divided according to PDA origin into 4 groups: Group 1: PDA from proximal descending aorta, Group 2: from undersurface of aortic arch, Group 3: opposite the subclavian artery, Group 4: opposite the innominate/brachiocephalic artery., Results: The median age of patients was 22 days and median weight was 3 kg. The procedure was successful in 78 patients (81.25%). PDA was tortuous in 70 out of 96 patients. Femoral artery was the preferred approach in Group 1 (63/67), while axillary artery access was preferred in the other groups (6/11 in Group 2, 11/17 in Group 3, 1/1 in Group 4, P <0.0001). The main cause of procedural failure was inadequate parked coronary wire inside one of the branch of pulmonary arteries (14 cases; 77.7%), while 2 cases (11.1%) were complicated by acute stent thrombosis, and another 2 cases with stent dislodgment. Other procedural complications comprised femoral artery thrombosis in 7 cases (7.2%). Patients with straight PDA, younger age at procedure and who had larger PDA at pulmonary end had higher odds for success (OR = 8.01, 2.94, 7.40, CI = 1.011-63.68, 0.960-0.99, 1.172-7.40,respectively, P = 0.048, 0.031,0.022 respectively)., Conclusions: The approach for PDA stenting and hence the outcome is markedly determined by the PDA origin and morphology. Patients with straight PDA, younger age at procedure and those who had relatively larger PDA at the pulmonary end had better opportunity for successful procedure., Competing Interests: The authors have declared that no competing interests exist.

Background: Multiple conditions are more prevalent in some minoritised ethnic groups and are associated with higher mortality rate but studies examining differential mortality once conditions are established is US-based. Our study tested whether the association between multiple conditions and mortality varies across ethnic groups in England., Methods and Findings: A random sample of primary care patients from Clinical Practice Research Datalink (CPRD) was followed from 1st January 2015 until 31st December 2019. Ethnicity, usually self-ascribed, was obtained from primary care records if present or from hospital records. Long-term conditions were counted from a list of 32 that have previously been associated with greater primary care, hospital admissions, or mortality risk. Cox regression models were used to estimate mortality by count of conditions, ethnicity and their interaction, with adjustment for age and sex for 532,059 patients with complete data. During five years of follow-up, 5.9% of patients died. Each additional condition at baseline was associated with increased mortality. The direction of the interaction of number of conditions with ethnicity showed a statistically higher mortality rate associated with long-term conditions in Pakistani, Black African, Black Caribbean and Other Black ethnic groups. In ethnicity-stratified models, the mortality rate per additional condition at age 50 was 1.33 (95% CI 1.31,1.35) for White ethnicity, 1.43 (95% CI 1.26,1.61) for Black Caribbean ethnicity and 1.78 (95% CI 1.41,2.24) for Other Black ethnicity., Conclusions: The higher mortality rate associated with having multiple conditions is greater in minoritised compared with White ethnic groups. Research is now needed to identify factors that contribute to these inequalities. Within the health care setting, there may be opportunities to target clinical and self-management support for people with multiple conditions from minoritised ethnic groups., Competing Interests: The authors have declared that no competing interests exist.

Purpose: We describe the temporal concordance of 3 hemodynamic monitors., Materials and Methods: Healthy volunteers performed preload changes while simultaneously wearing a non-invasive, pulse-contour stroke volume (SV) monitor, a bioreactance SV monitor and a wireless, wearable Doppler ultrasound patch over the common carotid artery. The sensitivity and specificity for detecting preload change over 3 temporal windows (early, middle and late) was assessed., Results: 40 preload changes were recorded in total (20 increase, 20 decrease). Immediately, the wearable Doppler had high sensitivity (100%) and specificity (100%) for detecting preload change with an area under the receiver operator curve (AUROC) of 0.98 for both velocity time integral (VTI, 10.5% threshold) and corrected flow time (FTc, 2.5% threshold). The sensitivity, specificity and AUROC for non-invasive pulse contour were equally good (9% SV threshold). For bioreactance, a 13% SV threshold immediately detected preload change with a sensitivity, specificity and AUROC of 60%, 95% and 0.75, respectively. After two SV outputs following preload change, the sensitivity, specificity and AUROC of bioreactance improved to 70%, 90% and 0.85, respectively., Conclusions: Carotid Doppler ultrasound and non-invasive pulse contour detected rapid hemodynamic change with equal accuracy; bioreactance improved over time. Algorithm-lag should be considered when interpreting clinical studies., Competing Interests: Igor Barjaktarevic M.D., Ph.D., Andrew M. Eibl B.Comm, Matthew Parrotta M.Sc., Bradley F. Long M.D., Mai Elfarnawany Ph.D., Joseph K. Eibl Ph.D. JSK, JE, AE, MP, ME are working with Flosonics, a start-up developing a commercial version of the Doppler patch. IB has received grants and consulting fees for GE Healthcare. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

5-Methylcytosine is one of the major epigenetic marks of DNA in living organisms. Some bacterial species possess DNA methyltransferases that modify cytosines on both strands to produce fully-methylated sites or on either strand to produce hemi-methylated sites. In this study, we characterized a DNA methyltransferase that produces two sequences with different methylation patterns: one methylated on both strands and another on one strand. M.BatI is the orphan DNA methyltransferase of Bacillus anthracis coded in one of the prophages on the chromosome. Analysis of M.BatI modified DNA by bisulfite sequencing revealed that the enzyme methylates the first cytosine in sequences of 5'-GCAGC-3', 5'-GCTGC-3', and 5'-GCGGC-3', but not of 5'-GCCGC-3'. This resulted in the production of fully-methylated 5'-GCWGC-3' and hemi-methylated 5'-GCSGC-3'. M.BatI also showed toxicity when expressed in E. coli, which was caused by a mechanism other than DNA modification activity. Homologs of M.BatI were found in other Bacillus species on different prophage like regions, suggesting the spread of the gene by several different phages. The discovery of the DNA methyltransferase with unique modification target specificity suggested unrevealed diversity of target sequences of bacterial cytosine DNA methyltransferase., Competing Interests: The authors have declared that no competing interests exist.