Optimizing coagulant dosage using deep learning models with large-scale data.

Water treatment plants are facing challenges that necessitate transition to automated processes using advanced technologies. This study introduces a novel approach to optimize coagulant dosage in water treatment processes by employing a deep learning model. The study utilized minute-by-minute data monitored in real time over a span of five years, marking the first attempt in drinking water process modeling to leverage such a comprehensive dataset. The deep learning model integrates a one-dimensional convolutional neural network (Conv1D) and gated recurrent unit (GRU) to effectively extract features and model complex time-series data. Initially, the model predicted coagulant dosage and sedimentation basin turbidity, validated against a physicochemical model. Subsequently, the model optimized coagulant dosage in two ways: 1) maintaining sedimentation basin turbidity below the 1.0 NTU guideline, and 2) analyzing changes in sedimentation basin turbidity resulting from reduced coagulant dosage (5-20%). The findings of the study highlight the effectiveness of the deep learning model in optimizing coagulant dosage with substantial reductions in coagulant dosage (approximately 22% reduction and 21 million KRW/year). The results demonstrate the potential of deep learning models in enhancing the efficiency and cost-effectiveness of water treatment processes, ultimately facilitating process automation.

Frequency of actionable secondary findings in 7472 Korean genomes derived from the National Project of Bio Big Data pilot study.

Exome and genome sequencing (ES/GS) in genetic medicine and research leads to discovering genomic secondary findings (SFs) unrelated to the purpose of the primary test. There is a lack of agreement to return the SF results for individuals undergoing the test. The aim of this study is to investigate the frequency of actionable secondary findings using GS data obtained from the rare disease study and the Korean Genome and Epidemiology Study (KoGES) in the National Project of Bio Big Data pilot study. Pathogenic (P) or likely pathogenic (LP) variants of 78 SF genes recommended by the American College of Medical Genetics and Genomics (ACMG) were screened in the rare disease study and KoGES. The pathogenicity of SF gene variants was determined according to the ACMG interpretation. The overall SF rate was 3.75% for 280 individuals with 298 P/LP variants of 41 ACMG SF genes which were identified among 7472 study participants. The frequencies of genes associated with cardiovascular, cancer, and miscellaneous phenotypes were 2.17%, 1.22%, and 0.58%, respectively. The most frequent SF gene was TTN followed by BRCA2. The frequency of actionable SFs among participants with rare disease and general population participants in the Korean population presented here will assist in reporting results of medically actionable SFs in genomic medicine.

Coagulant dosage determination using deep learning-based graph attention multivariate time series forecasting model.

Determination of coagulant dosage in water treatment is a time-consuming process involving nonlinear data relationships and numerous factors. This study provides a deep learning approach to determine coagulant dosage and/or the settled water turbidity using long-term data between 2011 and 2021 to include the effect of various weather conditions. A graph attention multivariate time series forecasting (GAMTF) model was developed to determine coagulant dosage and was compared with conventional machine learning and deep learning models. The GAMTF model (R2 = 0.94, RMSE = 3.55) outperformed the other models (R2 = 0.63 - 0.89, RMSE = 4.80 - 38.98), and successfully predicted both coagulant dosage and settled water turbidity simultaneously. The GAMTF model improved the prediction accuracy by considering the hidden interrelationships between features and the past states of features. The results demonstrate the first successful application of multivariate time series deep learning model, especially, a state-of-the-art graph attention-based model, using long-term data for decision-support systems in water treatment processes.

Optimal allocation and operation of sewer monitoring sites for wastewater-based disease surveillance: A methodological proposal.

Wastewater-based epidemiology (WBE) is drawing increasing attention as a promising tool for an early warning of emerging infectious diseases such as COVID-19. This study demonstrated the utility of a spatial bisection method (SBM) and a global optimization algorithm (i.e., genetic algorithm, GA), to support better designing and operating a WBE program for disease surveillance and source identification. The performances of SBM and GA were compared in determining the optimal locations of sewer monitoring manholes to minimize the difference among the effective spatial monitoring scales of the selected manholes. While GA was more flexible in determining the spatial resolution of the monitoring areas, SBM allows stepwise selection of optimal sampling manholes with equiareal subcatchments and lowers computational cost. Upon detecting disease outbreaks at a regular sewer monitoring site, additional manholes within the catchment can be selected and monitored to identify source areas with a required spatial resolution. SBM offered an efficient method for rapidly searching for the optimal locations of additional sampling manholes to identify the source areas. This study provides strategic and technical elements of WBE including sampling site selection with required spatial resolution and a source identification method.

Clinical Characteristics and Outcomes of Neutropenic Sepsis: A Multicenter Cohort Study.

BACKGROUND: Sepsis is a leading cause of mortality in patients with neutropenia; however, data on whether neutropenic sepsis is associated with distinct clinical characteristics and outcomes are limited. Thus, this study was designed to clarify the clinical characteristics and outcomes of patients with neutropenic sepsis compared with those of patients without neutropenic sepsis diagnosed based on the Third International Consensus Definitions for Sepsis and Septic Shock criteria. METHODS: We analyzed data from the Korean Sepsis Alliance, a nationwide prospective multicenter cohort study evaluating the clinical characteristics, management, and outcomes of patients with sepsis from September 2019 to February 2020. Eligible patients were divided into the neutropenic (absolute neutrophil count of less than 1,500/mL) and non- neutropenic groups. The characteristics and outcomes were compared between the two groups. RESULTS: During the study period, 2,074 patients were enrolled from 16 tertiary referral or university-affiliated hospitals. Of them, 218 (10.5%) had neutropenia. The neutropenia group was younger and had a lower proportion of patients with chronic diseases compared with the non-neutropenia group. However, solid tumors (50.0% vs. 34.1%; P  > 0.001) and hematological malignancies (40.8% vs. 3.8%; P  < 0.001) were more common in the neutropenia group. The neutropenia group had a higher incidence of septic shock (43.6% vs. 22.9%; P  < 0.001) and higher Sequential Organ Failure Assessment score (7 vs. 5; P  < 0.001) than the nonneutropenia group. However, no significant differences in microbiologically confirmed infections and its pathogen distribution and the incidence of multidrug resistance were observed between the two groups. The neutropenic group had a higher hospital mortality than the non-neutropenic group (42.2% vs. 26.3%; P  < 0.001), and the Kaplan-Meier survival curve demonstrated a significant difference in survival within 1 week after diagnosing sepsis (log-rank test, P = 0.002). The incidence of adverse events during intensive care unit admission was not different between the two groups. Among hospital survivors, the neutropenic group was more frequently discharged to home (72.2% vs. 57.8%; P = 0.002). CONCLUSIONS: Neutropenic sepsis is associated with a higher-grade organ dysfunction during the diagnosis of sepsis and higher mortality without difference in the pathogen isolated.

Selection and Characterization of Probiotic Bacteria Exhibiting Antiadipogenic Potential in 3T3-L1 Preadipocytes.

Abnormal adipocyte growth, distinguished by an increase in cell numbers and cellular differentiation, is regarded as a major pathological characteristic of obesity. Thus, inhibition of adipogenic differentiation in adipocytes could prevent obesity. Recently, certain probiotic stains have been reported to regulate lipid metabolism in vitro and/or in vivo. In this backdrop, this study aimed to investigate basic probiotic properties and potential antiobesity characteristics of mouse 3T3-L1 preadipocytes. Six lactic acid bacteria (LAB) strains were prescreened for their cholesterol-lowering activity, antioxidant activity, and survival at low pH and in a solution containing bile salts. These six strains were investigated for antiadipogenic activity by employing 3T3-L1 mouse preadipocytes. 3T3-L1 cells were treated with selected strains during the differentiation process. Lactobacillus johnsonii 3121 and Lactobacillus rhamnosus 86 were found to be more capable of reducing triglyceride and lipid accumulation, as compared to control group, which are fully differentiated 3T3-L1 adipocytes. These strains also inhibited adipocyte differentiation by downregulating the adipogenic transcription factor in 3T3-L1 adipocytes. Taken together, these results indicate that L. johnsonni 3121 and L. rhamnosus 86 could potentially act as probiotic bacteria and prevent fat accumulation by regulating adipogenesis-related markers.

Antiobesity Effect of Novel Probiotic Strains in a Mouse Model of High-Fat Diet-Induced Obesity.

Obesity is one of the major causes of the development of metabolic diseases, particularly cardiovascular diseases and type-2 diabetes mellitus. Increased lipid accumulation and abnormal adipocyte growth, which is an increase in cell numbers and differentiation, have been documented as major pathological characteristics of obesity. Thus, the inhibition of adipogenic differentiation prevents and suppresses obesity. Recently, specific probiotic strains have been known to regulate lipid metabolism in vitro and/or in vivo. Previously, we demonstrated that Lactobacillus johnsonni 3121 and Lactobacillus rhamnosus 86 could act as novel probiotic strains and reduce cholesterol levels. Moreover, both strains significantly reduced lipid accumulation and inhibited adipocyte differentiation by downregulating the adipogenic transcription factor in 3T3-L1 adipocytes. Therefore, L. johnsonni 3121 and L. rhamnosus 86 were selected for in vivo evaluation of their anti-obesity effects using a high-fat diet-induced obese mouse model. Daily oral administration of L. johnsonni 3121 and L. rhamnosus 86 for 12 weeks significantly improved serum lipid profile and downregulated the expression of genes related to adipogenesis and lipogenesis in epididymal white adipose tissue of high-fat diet fed obese mice (p < 0.05). Fecal analysis also suggested that the two probiotic strains could normalize the altered obesity-related gut microbiota in high-fat diet-fed obese mice. These results collectively demonstrate that oral administration of L. johnsonni 3121 and L. rhamnosus 86 could prevent obesity, thereby improving metabolic health.

Anteholosticha foissneri n. sp., a marine hypotrich ciliate (Ciliophora: Spirotrichea) from Vietnam: Morphology, morphogenesis, and molecular phylogeny.

In a study of marine ciliate diversity, we collected an Anteholosticha monilata-like population from Vietnam. To identify this population, we analyzed its morphology, some morphogenetic stages, and molecular phylogeny. Based on these data, we conclude that the Vietnamese population is new to science. Anteholosticha foissneri n. sp. resembles Anteholosticha monilata-like species considering (1) the number and arrangement of macronuclear nodules and micronuclei; (2) the presence of cortical granules; and (3) the saline habitat. However, the new species can be easily distinguished from these species by the arrangement, color, and shape of the cortical granules. The divisional morphogenesis commences with the de novo proliferation of basal bodies as a single longitudinal patch left of the posteriormost midventral cirral pair. This character state has not been reported before in Anteholosticha (based on check of the available data) and probably reflects a distinct clade within the nuclear small subunit ribosomal RNA gene tree.

An empirical modeling approach to predicting pollutant loads and developing cost-effective stormwater treatment strategies for a large urban watershed.

Stormwater treatment strategies were evaluated for the upper Ballona Creek Watershed in Los Angeles, CA using an empirical model of stormwater runoff quantity and quality with zeroth-order regularization and a limited memory Broyden-Fletcher-Goldfarb-Shanno Bound constrained optimization routine. The model used landuse based estimation on the runoff volume, event mean concentration (EMC) and pollutant load employing ten different landuses, including highways and local roads. The model was validated by showing that its predictions were in reasonable agreement (r2 ~0.6 to 0.8) with total zinc (Zn), Total Kjeldahl Nitrogen (TKN), and Total Suspended Solids (TSS) loadings measured at the monitoring site at the bottom of the watershed. The developed model was used to demonstrate and quantify the benefits of the stormwater treatment practices (STPs) prioritized at specific landuses with high pollutant mass emission rates. For this demonstration, total Zn was selected as it is one of the most concerning pollutants in an extremely urbanized area such as the Ballona Creek Watershed. Transportation landuse including local roads and highways was found to be the best candidate for the STP applications due to their high percent load contribution per percent area. By focusing STPs for transportation landuse, the water quality goal of total Zn in the study watershed was expected be achieved at approximately 75% less cost.

Functional in vivo and in vitro effects of 20q11.21 genetic aberrations on hPSC differentiation.

Human pluripotent stem cells (hPSCs) have promising therapeutic applications due to their infinite capacity for self-renewal and pluripotency. Genomic stability is imperative for the clinical use of hPSCs; however, copy number variation (CNV), especially recurrent CNV at 20q11.21, may contribute genomic instability of hPSCs. Furthermore, the effects of CNVs in hPSCs at the whole-transcriptome scale are poorly understood. This study aimed to examine the functional in vivo and in vitro effects of frequently detected CNVs at 20q11.21 during early-stage differentiation of hPSCs. Comprehensive transcriptome profiling of abnormal hPSCs revealed that the differential gene expression patterns had a negative effect on differentiation potential. Transcriptional heterogeneity identified by single-cell RNA sequencing (scRNA-seq) of embryoid bodies from two different isogenic lines of hPSCs revealed alterations in differentiated cell distributions compared with that of normal cells. RNA-seq analysis of 22 teratomas identified several differentially expressed lineage-specific markers in hPSCs with CNVs, consistent with the histological results of the altered ecto/meso/endodermal ratio due to CNVs. Our results suggest that CNV amplification contributes to cell proliferation, apoptosis, and cell fate specification. This work shows the functional consequences of recurrent genetic abnormalities and thereby provides evidence to support the development of cell-based applications.

Generation of induced pluripotent stem cells (KSCBi009-A) from a patient with Prader-Willi syndrome (PWS) featuring deletion of the paternal chromosome region 15q11.2-q13.

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by the loss of paternally expressed genes in an imprinted region of chromosome 15q11.2-q13. We generated a human-induced pluripotent stem cell line, designated KSCBi009-A, from peripheral blood mononuclear cells of a 13-year-old male PWS patient exhibiting deletion of the paternal chromosome 15q11.2-q13 region. The deletion was confirmed via methylation-specific multiplex ligation probe amplification assay (MS-MLPA) of genomic DNA. The hiPSC line expressed pluripotency markers and differentiated into three germ layers. The cell line may serve as a valuable model of an imprinting PWS disorder useful in terms of drug discovery and development.

Embolization of pancreatic arteriovenous malformation: A case report.

BACKGROUND: Pancreatic arteriovenous malformation (AVM) is a rare disease with a number of different reported treatment methods, but there are as yet no established or definite treatments for the disease. CASE SUMMARY: A 43-year-old man visited the hospital due to periumbilical pain. The patient underwent imaging study and laboratory testing for evaluation of cause. Pancreatic AVM associated with pancreatitis was suspected on computed tomography and magnetic resonance imaging. The patient was diagnosed with pancreatic AVM with pancreatitis on imaging study and angiography. Transcatheter arterial embolization with various embolic materials was performed. Follow-up computed tomography scan revealed progressive regression of AVM and improvement of pancreatitis. At two-year follow-up, the patient showed no recurrence of symptom or pancreatitis. CONCLUSION: Transcatheter arterial embolization can be considered an effective treatment modality for selective cases of pancreatic AVM.

Development of genetic quality tests for good manufacturing practice-compliant induced pluripotent stem cells and their derivatives.

Although human induced pluripotent stem cell (hiPSC) lines are karyotypically normal, they retain the potential for mutation in the genome. Accordingly, intensive and relevant quality controls for clinical-grade hiPSCs remain imperative. As a conceptual approach, we performed RNA-seq-based broad-range genetic quality tests on GMP-compliant human leucocyte antigen (HLA)-homozygous hiPSCs and their derivatives under postdistribution conditions to investigate whether sequencing data could provide a basis for future quality control. We found differences in the degree of single-nucleotide polymorphism (SNP) occurring in cells cultured at three collaborating institutes. However, the cells cultured at each centre showed similar trends, in which more SNPs occurred in late-passage hiPSCs than in early-passage hiPSCs after differentiation. In eSNP karyotyping analysis, none of the predicted copy number variations (CNVs) were identified, which confirmed the results of SNP chip-based CNV analysis. HLA genotyping analysis revealed that each cell line was homozygous for HLA-A, HLA-B, and DRB1 and heterozygous for HLA-DPB type. Gene expression profiling showed a similar differentiation ability of early- and late-passage hiPSCs into cardiomyocyte-like, hepatic-like, and neuronal cell types. However, time-course analysis identified five clusters showing different patterns of gene expression, which were mainly related to the immune response. In conclusion, RNA-seq analysis appears to offer an informative genetic quality testing approach for such cell types and allows the early screening of candidate hiPSC seed stocks for clinical use by facilitating safety and potential risk evaluation.

Fresh Saengshik Showed a Positive Effect on Mitigating Dextran Sulfate Sodium-Induced Experimental Colitis in Mice.

This study was to compare the anticolitis activity of fresh Saengshik (FSS) with heated Saengshik (HSS) with dextran sulfate sodium (DSS)-induced experimental colitis mouse model. Both FSS- and HSS-fed colitis mice exhibited the effects of the increase in the body weight, the alleviation in the colon shortening, and the reduction of the ratio of colon weight to length. However, FSS-fed colitis mice showed a much more significant decrease in DSS-induced tissue damage by mucosal edema and crypt deficiency than did HSS-fed ones. Besides, FSS contributed to decreasing the serum levels of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and inhibiting the colonic mRNA expressions of these cytokines in colitis tissue of the mice. FSS also resulted in the lower colonic mRNA expression level of inflammation-related inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in colitis mice than did HSS. Overall results confirmed Saengshik, especially FSS, inhibits more effectively against DSS-induced inflammation reaction in colitis mice than HSS.

Simple differentiation method using FBS identifies DUSP6 as a marker for fine-tuning of FGF-ERK signaling activity in human pluripotent stem cells.

Assessment of differentiation potential is a basic requirement to obtain qualified human pluripotent stem cells (hPSCs). Here, we report a simple differentiation method using fetal bovine serum (FBS) to estimate differentiation potential and propensity of hPSCs. PluriTest using RNA-sequencing showed that cells differentiated after treatment with 5% FBS. Expression patterns of three germ layer markers revealed that cells cultured in Knockout Serum Replacement-containing medium (KSR) with mouse feeder cells had higher differentiation potential than cells cultured in a chemically defined medium (E8) with recombinant matrix proteins, especially into the mesoderm and endoderm lineages. Analysis of differentially expressed genes between KSR and E8 identified DUSP6 as a marker for where cells had been cultured. Expression of DUSP6 correlated with FGF-ERK signaling activity. Fine-tuning of FGF-ERK signaling activity to a range that can shut down DUSP6 transcription but sustain NANOG transcription partially increased the differentiation potential. Our data suggest that differentiation with 5% FBS is good to estimate differentiation potential and propensity at the early stage, and that DUSP6 is an excellent marker to monitor ERK signaling activity.

Drug Discovery Platform Targeting M. tuberculosis with Human Embryonic Stem Cell-Derived Macrophages.

A major limitation in anti-tuberculosis drug screening is the lack of reliable and scalable models for homogeneous human primary macrophage cells of non-cancer origin. Here we report a modified protocol for generating homogeneous populations of macrophage-like cells from human embryonic stem cells. The induced macrophages, referred to as iMACs, presented similar transcriptomic profiles and characteristic immunological features of classical macrophages and were permissive to viral and bacterial infection, in particular Mycobacterium tuberculosis (Mtb). More importantly, iMAC production was amenable to scale up. To evaluate iMAC efficiency in high-throughput anti-tuberculosis drug screening, we performed a phenotypic screening against intracellular Mtb, involving a library of 3,716 compounds that included FDA-approved drugs and other bioactive compounds. Our primary screen identified 120 hits, which were validated in a secondary screen by dose-intracellular and -extracellular Mtb assays. Our confirmatory studies identified a novel anti-Mtb compound, 10-DEBC, also showing activity against drug-resistant strains.

Generation of a PDX1-EGFP reporter human induced pluripotent stem cell line, KSCBi005-A-3, using the CRISPR/Cas9 system.

PDX1 plays a crucial role in the development and maintenance of ß-cells and directly regulates pancreatic ß-cell-specific transcription factors by binding to the insulin gene. Here, we introduced an EGFP reporter into the C-terminus of PDX1 in KSCBi005-A human induced pluripotent stem cells through homologous recombination using CRISPR/Cas9 nuclease. The cells had a normal karyotype, expressed several pluripotency markers, and maintained their differentiation potential. KSCBi005-A-3 cells can be used to monitor PDX1 expression in live cells during ß-cell differentiation; the cell line has been registered at the National Stem Cell Bank, Korea National Institute of Health.

Generation of patient-specific induced pluripotent stem cells (KSCBi007-A) derived from a patient with Prader-Willi syndrome retain maternal uniparental disomy (UPD).

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by loss of paternally expressed genes in an imprinted region of 15q11.2-q13. We established a human-induced pluripotent stem cell (hiPSC) line, KSCBi007-A, from the peripheral blood mononuclear cells of a 5-month-old girl with PWS that retained maternal uniparental disomy (UPD). Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) of genomic DNA revealed the maternal UPD in the hiPSCs. The generated hiPSC line expressed pluripotency markers and showed the ability to differentiate into three germ layers in vitro. This hiPSC line could be used as a cellular model of an imprinting disorder in humans.

Generation of a patient-specific induced pluripotent stem cell line, KSCBi006-A, for osteogenesis imperfecta type I with the COL1A1, c.3162delT mutation.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by brittle bones. OI type I is the most common and usually the mildest form. We generated human induced pluripotent stem cells (hiPSCs), KSCBi006-A, from the peripheral blood mononuclear cells of a patient with OI type I using the Sendai virus delivery method. The generated hiPSCs retained the disease-causing DNA mutation (COL1A1, c.3162delT) and showed a normal karyotype. KSCBi006-A also has pluripotency and the capacity for differentiation into the three germ layers. These patient-specific iPSCs provide a valuable cellular modeling platform for OI and a resource for drug screening.

Socio-economic factors of high trash generation in the city of Los Angeles.

Trash is one of major pollutants in urban runoff. Some studies have been conducted to verify the different impacts of land use on trash generation in a qualitative way and focused on the performance of trash control measures. Few studies have explored the human impacts on trash generation or developed a quantitative model to describe the phenomenon. This paper examined the impact of human activity on trash generation. Spatial regimes on high trash generation areas were identified using the selected variables from best subset model regression and validated with Moran's I scatter plot and spatial analysis of variance. Bidirectional spatial lag regression with regimes was performed to develop the final model to explain the spatial distribution of trash generation and identify its major causes. The result showed that economic status and occupation of the population were correlated with trash accumulation and the dominant land use type, and the distance to rivers most affected trash generation. The effects of these indicators were different within and outside the high trash generation areas.