Case-Case Genome-Wide Analyses Identify Subtype-Informative Variants that Confer Risk for Breast Cancer.

Breast cancer includes several subtypes with distinct characteristic biological, pathological, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate development of improved prevention and treatment approaches. Here, we conducted pairwise case-case comparisons among five breast cancer subtypes by applying a case-case GWAS (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium. The approach identified 13 statistically significant loci and eight suggestive loci, the majority of which were identified from comparisons between triple-negative breast cancer (TNBC) and luminal A breast cancer. Associations of lead variants in 12 loci remained statistically significant after accounting for previously reported breast cancer susceptibility variants, among which two were genome-wide significant. Fine mapping implicated putative functional/causal variants and risk genes at several loci, e.g., 3q26.31/TNFSF10, 8q22.3/NACAP1/GRHL2, and 8q23.3/LINC00536/TRPS1, for TNBC as compared to luminal cancer. Functional investigation further identified rs16867605 at 8q22.3 as a SNP that modulates enhancer activity of GRHL2. Subtype-informative polygenic risk scores (PRS) were derived, and patients with a high subtype-informative PRS had an up to 2-fold increased risk of being diagnosed with TNBC instead of luminal cancers. The CC-GWAS PRS remained statistically significant after adjusting for TNBC PRS derived from traditional case-control GWAS in The Cancer Genome Atlas and the African Ancestry Breast Cancer Genetic Consortium. The CC-GWAS PRS was also associated with overall survival and disease-specific survival among breast cancer patients. Overall, these findings have advanced our understanding of the genetic etiology of breast cancer subtypes, particularly for TNBC.

Functional use of carbon dioxide for the sustainable valorization of orange peel in the pyrolysis process.

Although biomass is carbon-neutral, its use as a primary feedstock faces challenges arising from inconsistent supply chains. Therefore, it becomes crucial to explore alternatives with reliable availability. This study proposes a strategic approach for the thermochemical valorization of food processing waste, which is abundantly generated at single sites within large-scale processing plants. As a model biomass waste from the food industry, orange peel waste was particularly chosen considering its substantial consumption. To impart sustainability to the pyrolysis system, CO2, a key greenhouse gas, was introduced. As such, this study highlights elucidating the functionality of CO2 as a reactive feedstock. Specifically, CO2 has the potential to react with volatile pyrolysates evolved from orange peel waste, leading to CO formation at ≥490 °C. The formation of chemical constituents, encompassing acids, ketones, furans, phenols, and aromatics, simultaneously decreased by 15.1 area% in the presence of CO2. To activate the efficacy of CO2 at the broader temperature spectrum, supplementary measures, such as an additional heating element (700 °C) and a nickel-based catalyst (Ni/Al2O3), were implemented. These configurations promote thermal cracking of the volatiles and their reaction kinetics with CO2, representing an opportunity for enhanced carbon utilization in the form of CO. Finally, the integrated process of CO2-assisted catalytic pyrolysis and water-gas shift reaction was proposed. A potential revenue when maximizing the productivity of H2 was estimated as 2.62 billion USD, equivalent to 1.11 times higher than the results from the inert (N2) environment. Therefore, utilizing CO2 in the pyrolysis system creates a promising approach for enhancing the sustainability of the thermochemical valorization platform while maximizing carbon utilization in the form of CO.

Reliability and Agreement Assessment of Sarcopenia Diagnosis through Comparison of Bioelectrical Impedance Analysis and Dual-Energy X-ray Absorptiometry.

A unified diagnostic criterion has yet to be established for sarcopenia. Therefore, we analyzed the reliability and validity of sarcopenia diagnosis using bioelectrical impedance analysis (BIA) compared with the gold standard, dual-energy X-ray absorptiometry (DEXA), and evaluated the predictive accuracy of BIA for diagnosis. The clinical trial, involving a total of 239 participants, was conducted between December 2018 and September 2019 on healthy volunteers without significant medical histories. The participants underwent health assessments, followed by sequential DEXA and BIA measurements. In both the low and normal appendicular skeletal muscle (ASM) groups, there were significant differences in the right arm, left arm, right leg, left leg, ASM, and ASM index (ASMI) between DEXA and BIA across all age groups (p < 0.05). BIA tended to overestimate compared to DEXA, but ASMI values for males and females were consistent with the criteria for sarcopenia. Bland-Altman analysis showed that each segment in both the low and normal ASM groups fell within the limits of agreement (LOA). The diagnosis of sarcopenia using BIA was significantly different from that using DEXA. However, it exhibited a significantly high correlation, fell within the LOA, and demonstrated high predictive accuracy. BIA can be considered an effective tool for diagnosing sarcopenia.

Novel Qnr Families as Conserved and Intrinsic Quinolone Resistance Determinants in Aeromonas spp.

The environment has been acknowledged as an origin, reservoir, and transmission route of antibiotic resistance genes (ARGs). Among diverse environments, freshwater environments have been recognized as pivotal in the transmission of ARGs between opportunistic pathogens and autochthonous bacteria such as Aeromonas spp. In this study, five environmental strains of Aeromonas spp. exhibiting multidrug resistance (MDR) were selected for whole-genome sequencing to ascertain their taxonomic assignment at the species-level and to delineate their ARG repertoires. Analyses of their genomes revealed the presence of one protein almost identical to AhQnr (A. hydrophila Qnr protein) and four novel proteins similar to AhQnr. To scrutinize the classification and taxonomic distribution of these proteins, all Aeromonas genomes deposited in the NCBI RefSeq genome database (1,222 genomes) were investigated. This revealed that these Aeromonas Qnr (AQnr) proteins are conserved intrinsic resistance determinants of the genus, exhibiting speciesspecific diversity. Additionally, structure prediction and analysis of contribution to quinolone resistance by AQnr proteins of the isolates, confirmed their functionality as quinolone resistance determinants. Given the origin of mobile qnr genes from aquatic bacteria and the crucial role of Aeromonas spp. in ARG dissemination in aquatic environments, a thorough understanding and strict surveillance of AQnr families prior to the clinical emergence are imperative. In this study, using comparative genome analyses and functional characterization of AQnr proteins in the genus Aeromonas, novel Aeromonas ARGs requiring surveillance has suggested.

Predictors of Choledocholithiasis in Cholecystectomy Patients and Their Cutoff Values and Prediction Model in Korea in Comparison with the 2019 ASGE Guidelines.

Background/Aims: : In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) established clinical predictors for choledocholithiasis. Our study was designed to evaluate these predictors within the Korean clinical context, establish cutoff values, and develop a predictive model. Methods: : This retrospective study analyzed patients who underwent laparoscopic cholecystectomy. The relationships between choledocholithiasis and predictors including age, blood tests, and imaging findings were assessed through univariate and multivariate logistic regression analyses. We established Korean cutoff values for these predictors and developed a scoring system for choledocholithiasis using a multivariate logistic regression. The performance of this scoring system was then compared with that of the 2019 ASGE guidelines through a receiver operating characteristic curve. Results: : We established Korean cutoff values for age (>70 years), alanine aminotransferase (>26.5 U/L), aspartate aminotransferase (>28.5 U/L), gamma-glutamyl transferase (GGT; >82.5 U/L), alkaline phosphatase (ALP; >77.5 U/L), and total bilirubin (>0.95 mg/dL). In the multivariate analysis, only age >70 years, GGT >77.5 U/L, ALP >77.5 U/L, and common bile duct dilatation remained significant. We then developed a new Korean risk stratification model from the multivariate analysis, with an area under the curve of 0.777 (95% confidence interval, 0.75 to 0.81). Our model was stratified into the low-risk, intermediate-risk, and high-risk groups with the scores being <1.0, 1.0-5.5, and >5.5, respectively. Conclusions: : Predictors of choledocholithiasis in cholecystectomy patients and their cutoff values in Korean should be adjusted and further studies are needed to develop appropriate guidelines.

Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia.

Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed an in vitro organotypic model capable of recapitulating key intrinsic and phenotypic properties of FD. Initially, transcriptomic profiling of individual cells isolated from patient lesional tissues unveiled intralesional molecular and cellular heterogeneity. Leveraging these insights, we established patient-derived organoids (PDOs) using primary cells obtained from patient FD lesions. Evaluation of PDOs demonstrated preservation of fibrosis-associated constituent cell types and transcriptional signatures observed in FD lesions. Additionally, PDOs retained distinct constellations of genomic and metabolic alterations characteristic of FD. Histological evaluation further corroborated the fidelity of PDOs in recapitulating important phenotypic features of FD that underscore their pathophysiological relevance. Our findings represent meaningful progress in the field, as they open up the possibility for in vitro modeling of rare bone lesions in a three-dimensional context and may signify the first step towards creating a personalized platform for research and therapeutic studies.

Associations of MRI-derived kidney volume, kidney function, body composition and physical performance in ≈38 000 UK Biobank participants: a population-based observational study.

Background: Kidney volume is used as a predictive and therapeutic marker for several clinical conditions. However, there is a lack of large-scale studies examining the relationship between kidney volume and various clinicodemographic factors, including kidney function, body composition and physical performance. Methods: In this observational study, MRI-derived kidney volume measurements from 38 526 UK Biobank participants were analysed. Major kidney volume-related measures included body surface area (BSA)-adjusted total kidney volume (TKV) and the difference in bilateral kidneys. Multivariable-adjusted linear regression and cubic spline analyses were used to explore the association between kidney volume-related measures and clinicodemographic factors. Cox or logistic regression was used to identify the risks of death, non-kidney cancer, myocardial infarction, ischaemic stroke and chronic kidney disease (CKD). Results: The median of BSA-adjusted TKV and the difference in kidney volume were 141.9 ml/m2 [interquartile range (IQR) 128.1-156.9] and 1.08-fold (IQR 1.04-1.15), respectively. Higher BSA-adjusted TKV was significantly associated with higher estimated glomerular filtration rate {eGFR; ß = 0.43 [95% confidence interval (CI) 0.42-0.44]; P < .001}, greater muscle volume [ß = 0.50 (95% CI 0.48-0.51); P < .001] and greater mean handgrip strength [ß = 0.15 (95% CI 0.13-0.16); P < .001] but lower visceral adipose tissue volume [VAT; ß = -0.09 (95% CI -0.11 to -0.07); P < .001] in adjusted models. A greater difference in bilateral kidney volumes was associated with lower eGFR, muscle volume and physical performance but with higher proteinuria and VAT. Higher BSA-adjusted TKV was significantly associated with a reduced risk of CKD [odds ratio (OR) 0.7 (95% CI 0.63-0.77); P < .001], while a greater difference in kidney volume was significantly associated with an increased risk of CKD [OR 1.13 (95% CI 1.07-1.20); P < .001]. Conclusion: Higher BSA-adjusted TKV and lower differences in bilateral kidney volumes are associated with higher kidney function, muscle volume and physical performance and a reduced risk of CKD.

Clinical implication of megestrol acetate in metastatic gastric cancer: a big data analysis from Health Insurance Review and Assessment (HIRA) database.

OBJECTIVE: Megestrol acetate (MA) is used to manage anorexia and cachexia in patients with advanced cancer. This study investigated the prescription patterns of MA in patients with metastatic gastric cancer, as well as evaluated its impact on survival outcomes and the incidence of venous thromboembolism (VTE). METHODS: A Health Insurance Review and Assessment (HIRA) service database was used to investigate differences in baseline characteristics, survival, and the incidence of VTE according to MA prescription patterns (i.e., prescription vs. no prescription) in patients diagnosed with metastatic gastric cancer from July 2014 to December 2015. RESULTS: A total of 1938 patients were included in this study. In total, 65% of the patients were prescribed MA. Older age, treatment in tertiary hospitals, and palliative chemotherapy were statistically significant predictive factors for MA prescription. Continuous prescription of MA was observed in 37% of patients. There was no statistically significant difference in survival between the MA and non-MA prescription groups on multivariate analysis. Among the 1427 patients included in the analysis for VTE incidence, 4.3% and 2.9% were diagnosed with VTE during the follow-up period in the MA and non-MA prescription groups, respectively. However, there was no statistically significant difference in VTE diagnosis between the groups on multivariate analysis. CONCLUSION: MA is commonly prescribed for metastatic gastric cancer, especially in elderly patients and those undergoing palliative chemotherapy, without significantly affecting survival or VTE risk.

Elucidation of critical chemical moieties of metallo-ß-lactamase inhibitors and prioritisation of target metallo-ß-lactamases.

The urgent demand for effective countermeasures against metallo-ß-lactamases (MBLs) necessitates development of novel metallo-ß-lactamase inhibitors (MBLIs). This study is dedicated to identifying critical chemical moieties within previously developed MBLIs, and critical MBLs should serve as the target in MBLI evaluations. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic literature analysis was conducted, and the NCBI RefSeq genome database was exploited to access the abundance profile and taxonomic distribution of MBLs and their variant types. Through the implementation of two distinct systematic approaches, we elucidated critical chemical moieties of MBLIs, providing pivotal information for rational drug design. We also prioritised MBLs and their variant types, highlighting the imperative need for comprehensive testing to ensure the potency and efficacy of the newly developed MBLIs. This approach contributes valuable information to advance the field of antimicrobial drug discovery.

Improvement of the anthropogenic emission rate estimate in Ulaanbaatar, Mongolia, for 2020-21 winter.

Ulaanbaatar (UB), the fast-growing capital of Mongolia, is known for its world's worst level of particulate matter (PM) concentrations in winter. However, current anthropogenic emission inventories over the UB are based on data from more than fifteen years ago, and satellite observations are scarce because UB is in high latitudes. During the winter of 2020-21, the first period of the Fine Particle Research Initiative in East Asia considering the National Differences (FRIEND), several times higher concentrations of PM in UB compared to other urban sites in East Asia were observed but not reproduced with a chemical transport model mainly due to the underestimated anthropogenic emissions. Therefore, we devised a method for sequentially adjusting emissions based on the reactivity of PM precursors using ground observations. We scaled emission rates for the inert species (CO, elemental carbon (EC), and organic carbon (OC)) to reproduce their observed ambient concentrations, followed by SO2 to reproduce the concentration of SO42-, which was examined to have the least uncertainty based on the abundance of observed NH3, and finally NO and NH3 for NO3-, and NH4+. This improved estimation is compared to regional inventories for Asia and suggests more than an order of magnitude increase in anthropogenic emissions in UB. Using the improved emission inventory, we were able to successfully reproduce independent observation data on PM2.5 concentrations in UB in December 2021 from the U.S. Embassy. During the campaign period, we found more than 50% of the SO42-, NO3-, and NH4+ increased in UB due to the improvement could travel to Beijing, China (BJ), and about 20% of the SO42- could travel to Noto, Japan (NT), more than 3000 km away. Also, the anthropogenic emissions in UB can effectively increase OC, NO3-, and NH4+ concentrations in BJ when Gobi dust storms occur.

Evaluation of risk stratification for acute kidney injury: a comparative analysis of EKFC, 2009 and 2021 CKD-EPI glomerular filtration estimating equations.

BACKGROUND: The adoption of the 2021 CKD-EPIcr equation for glomerular filtration rate (GFR) estimation provided a race-free eGFR calculation. However, the discriminative performance for AKI risk has been rarely validated. We aimed to evaluate the differences in acute kidney injury (AKI) prediction or reclassification power according to the three eGFR equations. METHODS: We performed a retrospective observational study within a tertiary hospital from 2011 to 2021. Acute kidney injury was defined according to KDIGO serum creatinine criteria. Glomerular filtration rate estimates were calculated by three GFR estimating equations: 2009 and 2021 CKD-EPIcr, and EKFC. In three equations, AKI prediction performance was evaluated with area under receiver operator curves (AUROC) and reclassification power was evaluated with net reclassification improvement analysis. RESULTS: A total of 187,139 individuals, including 27,447 (14.7%) AKI and 159,692 (85.3%) controls, were enrolled. In the multivariable regression prediction model, the 2009 CKD-EPIcr model (continuous eGFR model 2, 0.7583 [0.755-0.7617]) showed superior performance in AKI prediction to the 2021 CKD-EPIcr (0.7564 [0.7531-0.7597], < 0.001) or EKFC model in AUROC (0.7577 [0.7543-0.761], < 0.001). Moreover, in reclassification of AKI, the 2021 CKD-EPIcr and EKFC models showed a worse classification performance than the 2009 CKD-EPIcr model. (- 7.24 [- 8.21-- 6.21], - 2.38 [- 2.72-- 1.97]). CONCLUSION: Regarding AKI risk stratification, the 2009 CKD-EPIcr equation showed better discriminative performance compared to the 2021 CKD-EPIcr equation in the study population.

North Korean CO emissions reconstruction using DMZ ground observations, TROPOMI space-borne data, and the CMAQ air quality model.

Emission uncertainty in North Korea can act as an obstacle when developing air pollution management plans in the country and neighboring countries when the transboundary transport of air pollutants is considered. This study introduces a novel approach for adjusting and reallocating North Korean CO emissions, aiming to complement the limited observational and emissions data on the country's air pollutants. We utilized ground observations from demilitarized zone (DMZ) and vertical column density (VCD) data from a TROPOspheric Monitoring Instrument (TROPOMI), which were combined with the Community Multi-Scale Air Quality (CMAQ) chemistry transport model simulations. The Clean Air Support System (CAPSS) and Satellite Integrated Joint Monitoring of Air Quality (SIJAQ) emissions inventories served as the basis for our initial simulations. A two-step procedure was proposed to adjust both the emission intensity and the spatial distribution of emissions. First, air quality simulations were conducted to explore model sensitivity to changes in North Korean CO emissions with respect to ground concentrations. DMZ observations then constrained these simulations to estimate corresponding emission intensity. Second, the spatial structure of North Korean CO emission sources was reconstructed with the help of TROPOMI CO VCD distributions. Our two-step hybrid method outperformed individual emissions adjustment and spatial reallocation based solely on surface or satellite observations. Validation using ground observations from the Chinese Dandong site near the China-North Korea border revealed significantly improved model simulations when applying the updated CO emissions. The adjusted CO emissions were 10.9 times higher than those derived from the bottom-up emissions used in this study, highlighting the lack of information on North Korean pollutants and emission sources. This approach offers an efficient and practical solution for identifying potential missing emission sources when there is limited on-site information about air quality on emissions.

Sodium Intake Estimation in Hospital Patients Using AI-Based Imaging: Prospective Pilot Study.

BACKGROUND: Measurement of sodium intake in hospitalized patients is critical for their care. In this study, artificial intelligence (AI)-based imaging was performed to determine sodium intake in these patients. OBJECTIVE: The applicability of a diet management system was evaluated using AI-based imaging to assess the sodium content of diets prescribed for hospitalized patients. METHODS: Based on the information on the already investigated nutrients and quantity of food, consumed sodium was analyzed through photographs obtained before and after a meal. We used a hybrid model that first leveraged the capabilities of the You Only Look Once, version 4 (YOLOv4) architecture for the detection of food and dish areas in images. Following this initial detection, 2 distinct approaches were adopted for further classification: a custom ResNet-101 model and a hyperspectral imaging-based technique. These methodologies focused on accurate classification and estimation of the food quantity and sodium amount, respectively. The 24-hour urine sodium (UNa) value was measured as a reference for evaluating the sodium intake. RESULTS: Results were analyzed using complete data from 25 participants out of the total 54 enrolled individuals. The median sodium intake calculated by the AI algorithm (AI-Na) was determined to be 2022.7 mg per day/person (adjusted by administered fluids). A significant correlation was observed between AI-Na and 24-hour UNa, while there was a notable disparity between them. A regression analysis, considering patient characteristics (eg, gender, age, renal function, the use of diuretics, and administered fluids) yielded a formula accounting for the interaction between AI-Na and 24-hour UNa. Consequently, it was concluded that AI-Na holds clinical significance in estimating salt intake for hospitalized patients using images without the need for 24-hour UNa measurements. The degree of correlation between AI-Na and 24-hour UNa was found to vary depending on the use of diuretics. CONCLUSIONS: This study highlights the potential of AI-based imaging for determining sodium intake in hospitalized patients.

Dynamic suprahyoid muscle ultrasound in assessing oropharyngeal dysphagia in neurological disorders.

BACKGROUND: Appropriate evaluation and management of dysphagia are essential in neurological disorders. However, there is currently a lack of a simple yet reliable method for dysphagia evaluation. AIM: This study aimed to investigate the usefulness of new dynamic M-mode ultrasonography (US) parameters of suprahyoid muscle (SHM) to evaluate dysphagia. DESIGN: Prospective observational, cross-sectional study. SETTING: Inpatient setting at neurology department of tertiary medical center. POPULATION: A total of 89 patients with dysphagia and 175 healthy volunteers were enrolled in the study. Patients were subdivided into mild and severe dysphagia groups depending on the need for dietary changes and disease classification, which included amyotrophic lateral sclerosis, peripheral neuromuscular diseases, and stroke. METHODS: Dynamic M-mode US was performed during swallowing to obtain the SHM thickness (the baseline thickness of the SHM), SHM displacement (peak-to-peak amplitude of SHM movement), SHM difference (SHM displacement - SHM thickness), SHM ratio (SHM displacement/SHM thickness), peak-to-peak time, and total duration. A videofluoroscopic swallowing study (VFSS) was performed. RESULTS: Significant differences were found in SHM displacement and SHM difference according to dysphagia severity (P<0.001). The SHM ratio, total duration (P<0.001), and peak-to-peak time (P=0.001) differed significantly according to the patients' underlying diseases. The pharyngeal delay time and penetration-aspiration scale from the VFSS demonstrated significant negative correlations with SHM displacement and difference (P<0.001). By combining SHM difference and total duration, patients with dysphagia could be distinguished from healthy controls, with the highest negative predictive value of 95.6%. CONCLUSIONS: Dynamic M-mode US of the SHM provided added value in evaluating the severity of dysphagia and differentiating swallowing mechanics of dysphagia related to underlying neurological disorders. CLINICAL REHABILITATION IMPACT: Dynamic M-mode US of the SHM can serve as a supportive tool for rapid screening and repetitive follow-up of patients with dysphagia, which would contribute to dysphagia rehabilitation in patients with various neurological disorders.

Development of a greenhouse gas - air pollution interactions and synergies model for Korea (GAINS-Korea).

This study aimed to create Greenhouse Gas - Air Pollution Interactions and Synergies (GAINS)-Korea, an integrated model for evaluating climate and air quality policies in Korea, modeled after the international GAINS model. GAINS-Korea incorporates specific Korean data and enhances granularity for enabling local government-level analysis. The model includes source-receptor matrices used to simulate pollutant dispersion in Korea, generated through CAMx air quality modeling. GAINS-Korea's performance was evaluated by examining different scenarios for South Korea. The business as usual scenario projected emissions from 2010 to 2030, while the air quality scenario included policies to reduce air pollutants in line with air quality and greenhouse gas control plans. The maximum feasible reduction scenario incorporated more aggressive reduction technologies along with air quality measures. The developed model enabled the assessment of emission reduction effects by both greenhouse gas and air pollutant emission reduction policies across 17 local governments in Korea, including changes in PM2.5 (particulate matter less than 2.5 µm) concentration and associated benefits, such as reduced premature deaths. The model also provides a range of visualization tools for comparative analysis among different scenarios, making it a valuable resource for policy planning and evaluation, and supporting decision-making processes.

Solibacillus palustris sp. nov., isolated from wetland soil of ecology park.

A Gram-staining-positive, motile, aerobic and rod-shaped bacterium, designated strain MA9T was isolated from wetland soil of ecology park, in Seoul, Republic of Korea. This bacterium was characterized to determine its taxonomic position by using the polyphasic approach. Strain MA9T grew at 10-37 °C and at pH 6.0-9.5 on TSB. Menaquinone MK-7 was the predominant respiratory quinone and iso-C15 : 0, iso-C16 : 0 and C16 : 1 ω7c alcohol were the major fatty acids. The main polar lipids were phosphatidylethanolamine (PE), phosphatidylserine (PS), diphosphatidylglycerol (DPG) and phosphatidylglycerol (PG). The peptidoglycan type of the cell wall was A4α l-Lys-d-Glu. Based on 16S rRNA gene sequencing, strain MA9T clustered with species of the genus Solibacillus and appeared closely related to S. silvestris DSM 12223T (97.8 % sequence similarity), S. cecembensis DSM 21993T (97.6 %), S. isronensis DSM 21046T (97.6 %) and S. kalamii DSM 101595T (96.6 %). The G+C content of the genomic DNA was 37.0 mol%. Digital DNA-DNA hybridization between strain MA9T and type strains of S. silvestris, S. isronensis, S. cecembensis and S. kalamii resulted in values below 70 %. Strain MA9T could be differentiated genotypically and phenotypically from the recognized species of the genus Solibacillus. The isolate therefore represents a novel species, for which the name Solibacillus palustris sp. nov. is proposed, with the type strain MA9T (=KACC 22212T = LMG 32188T).

Investigating the applicability and assumptions of the regression relationship between flow discharge and nitrogen concentrations for load estimation.

The regression relationship between water discharge rates and nutrient concentrations can provide a quick and straightforward way to estimate nutrient loads. However, recent studies indicated that the relationship might produce large biases in load estimates and, therefore, may not be applicable in certain types of cases. The goal of this study is to explore the theoretical reasons behind the selective applicability of the regression relationship between flow rates and nitrate + nitrite concentrations. For this study, we examined daily flow and nitrate + nitrite concentration observations made at the outlets of 22 watersheds monitored by the Heidelberg Tributary Loading Program (HTLP). The statistical relationship between the flow rates and concentrations was explored using regression equations offered by the LOAD ESTimator (LOADEST). Results demonstrated that the use of the regression equations provided nitrate + nitrite load estimates at acceptable accuracy levels (NSE≥0.35 and |PBIAS|≤30.0%) in 14 watersheds (64 % of 22 study watersheds). The regression relationships provided highly biased results at eight watersheds (36 %), implying their limited applicability. The heteroscedasticity of the residuals led to the high bias and resulting inaccurate regression, which was commonly found in watersheds where low flow had high nitrate + nitrite concentration variations. Conversely, the regression relationships provided acceptable accuracy for watersheds that had a relatively constant variance of the nitrate + nitrite concentrations. The results indicate that the homoscedasticity of residuals is the key assumption to be satisfied to estimate nitrate + nitrite loads from a statistical regression between flow discharge and nitrate + nitrite concentrations. The transport capacity (capacity-limited) concept implicitly assumed in the regression relationship between flow discharge and nitrate + nitrite concentrations is not always applicable, especially to agricultural areas in which nitrate + nitrite loads are highly variable depending on management practices (supply-limited). The findings suggest that the regression relationship should be carefully applied to areas in which intensive agricultural activities, including crop management and conservation practices, are implemented. Thus, the transport capacity concept is reasonably regarded to contribute to the homoscedasticity of residuals.

A genome-wide association study of contralateral breast cancer in the Women's Environmental Cancer and Radiation Epidemiology Study.

BACKGROUND: Contralateral breast cancer (CBC) is the most common second primary cancer diagnosed in breast cancer survivors, yet the understanding of the genetic susceptibility of CBC, particularly with respect to common variants, remains incomplete. This study aimed to investigate the genetic basis of CBC to better understand this malignancy. FINDINGS: We performed a genome-wide association analysis in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study of women with first breast cancer diagnosed at age < 55 years including 1161 with CBC who served as cases and 1668 with unilateral breast cancer (UBC) who served as controls. We observed two loci (rs59657211, 9q32, SLC31A2/FAM225A and rs3815096, 6p22.1, TRIM31) with suggestive genome-wide significant associations (P < 1 × 10-6). We also found an increased risk of CBC associated with a breast cancer-specific polygenic risk score (PRS) comprised of 239 known breast cancer susceptibility single nucleotide polymorphisms (SNPs) (rate ratio per 1-SD change: 1.25; 95% confidence interval 1.14-1.36, P < 0.0001). The protective effect of chemotherapy on CBC risk was statistically significant only among patients with an elevated PRS (Pheterogeneity = 0.04). The AUC that included the PRS and known breast cancer risk factors was significantly elevated. CONCLUSIONS: The present GWAS identified two previously unreported loci with suggestive genome-wide significance. We also confirm that an elevated risk of CBC is associated with a comprehensive breast cancer susceptibility PRS that is independent of known breast cancer risk factors. These findings advance our understanding of genetic risk factors involved in CBC etiology.