Search

Candida albicans (C. albicans) is the primary etiologic agent of vaginal candidiasis. Lactobacillus species are predominant in the vaginal microbiome; they inhibit the development of vaginal candidiasis by producing antimicrobial agents, such as lactic acid and hydrogen peroxide. In this study, we investigated the effects of Limosilactobacillus fermentum (L. fermentum) KBL674 in a mouse model of vaginal candidiasis. L. fermentum KBL674 inhibited C. albicans hyphal growth. Moreover, oral administration of L. fermentum KBL674 significantly suppressed vaginal C. albicans infection and associated symptoms, including tissue thickness and immune cell infiltration. A substantial quantity of L. fermentum KBL674 was excreted by the mice within 6 h after oral administration, indicating that most L. fermentum KBL674 did not settle within the gastrointestinal tract. L. fermentum KBL674 modulated gut microbiome diversity, increasing abundances of the genera Akkermansia, Eubacterium, and Faecalibaculum and family Muribaculaceae. Abundances of these bacteria showed negative correlations with the vaginal C. albicans burden in the mouse model, suggesting links between the gut microbiome composition and the vaginal C. albicans burden. Therefore, L. fermentum KBL674 can reduce the vaginal C. albicans burden via direct or indirect inhibition and modulation of the gut microbiome composition preventively., Competing Interests: Declarations Ethics Approval and Consent to Participate The Institutional Animal Care and Use Committee at The Food Industry Promotional Agency of Korea approved all the procedures used in this study. The approval number was IACUC-22–017. The study methodologies were complied with the Guide for the Care and Use of Laboratory Animals. This study does not include any experiments involving human subjects. Competing Interests H.L. is the chief executive officer of weBiom Inc. S.J.J. and S.P. are employees of weBiom Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. The Author(s).)

Purpose: The COVID-19 pandemic significantly impacted breast cancer (BC) surgeries. Most studies showing reduced BC surgical volumes during the pandemic are from single institutions, few have described volume changes in different types of surgical procedures. This study aimed to assess the impact of the pandemic on BC surgery volumes and types at a population level., Methods: Patients diagnosed with BC between January 1, 2018, and June 25, 2022, in Ontario, Canada, were analysed from population-based datasets. Time periods were defined as pre-pandemic (Jan 2018-Mar 2020), immediate pandemic (Mar-Jun 2020), and peri-pandemic (Jun 2020-Jun 2022). Weekly BC surgery volume and type (lumpectomy, mastectomy, or mastectomy with immediate reconstruction) were evaluated using segmented negative binomial regression models., Results: Among 44 226 patients, 50 440 surgeries were performed. Weekly BC surgeries decreased by 16.9% during the immediate pandemic compared to pre-pandemic levels (180.5 vs. 217.1; p = 0.03). Surgical volumes recovered to pre-pandemic levels by June 2021. Mastectomies represented a higher proportion of BC surgeries during the pandemic (31.1% pre, 36.3% immediate, 32.4% peri-pandemic; p < 0.01). The proportion of mastectomies with immediate reconstruction remained stable during the immediate pandemic but increased in the peri-pandemic (20.1% vs. 17%; p < 0.01)., Conclusion: There was a significant reduction in all BC surgeries during the pandemic. Mastectomies accounted for a higher proportion of BC surgeries in the pandemic period however access to reconstruction was maintained. Surgical volumes recovered within a year despite ongoing pandemic hospitalizations. Future studies are needed to explore the pandemic's long-term impact on BC care., Competing Interests: Declarations Competing Interests The authors declare no competing interests. Ethical approval Ethical approval was obtained from the Research Ethics Board at the University Health Network, Toronto, Canada (22-5809). Consent to participate For this type of study, formal consent is not required., (© 2024. The Author(s).)

Purpose: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function., Methods: An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 10 9  CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-β and p-cresyl sulfate were administered with butyrate., Results: In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study., Conclusions: This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Influenza virus infection is an important public-health concern because of its high transmissibility and potential for severe complications. To mitigate the severity and complications of influenza, probiotics containing Lactobacillus are used and generally recognized as safe. We evaluated the anti-influenza effect of Limosilactobacillus reuteri (L. reuteri) KBL346, isolated from the fecel sample of healthy South Koreans, in mice. BALB/c mice were orally administered live and heat-inactivated L. reuteri KBL346. After infection with influenza virus (A/Puerto Rico/8/34) 0.5 times the 50% lethal dose (LD 50 ), body weight loss was improved and recovery was accelerated. Furthermore, L. reuteri KBL346 improved body weight loss and survival rate of mice infected with 4 times the LD 50 of influenza virus. Heat-inactivated L. reuteri KBL346 reduced the viral titer in the lung and the plasma immunoglobulin G level. Expression levels of genes encoding inflammatory cytokines, such as interferon-γ and toll-like receptor 2 (Tlr2), were decreased in the lung tissues of mice administered L. reuteri KBL346. Live and heat-inactivated L. reuteri KBL346 increased the expression level of Adamts4, which promotes recovery after infection, and decreased that of Tlr2. The α-diversity of the gut microbiome was modulated by the administration of L. reuteri KBL346. In addition, the structure of the gut microbial community differed according to the degree of weight loss. L. reuteri KBL346 has the potential to alleviate disease severity and improve histopathological changes in mice infected with influenza A/PR8, suggesting its efficacy as a probiotic against influenza infection., (© 2024. The Author(s).)

Background: The explosive growth of next-generation sequencing data has resulted in ultra-large-scale datasets and significant computational challenges. As the cost of next-generation sequencing (NGS) has decreased, the amount of genomic data has surged globally. However, the cost and complexity of the computational resources required continue to be substantial barriers to leveraging big data. A promising solution to these computational challenges is cloud computing, which provides researchers with the necessary CPUs, memory, storage, and software tools., Results: Here, we present Closha 2.0, a cloud computing service that offers a user-friendly platform for analyzing massive genomic datasets. Closha 2.0 is designed to provide a cloud-based environment that enables all genomic researchers, including those with limited or no programming experience, to easily analyze their genomic data. The new 2.0 version of Closha has more user-friendly features than the previous 1.0 version. Firstly, the workbench features a script editor that supports Python, R, and shell script programming, enabling users to write scripts and integrate them into their pipelines. This functionality is particularly useful for downstream analysis. Second, Closha 2.0 runs on containers, which execute each tool in an independent environment. This provides a stable environment and prevents dependency issues and version conflicts among tools. Additionally, users can execute each step of a pipeline individually, allowing them to test applications at each stage and adjust parameters to achieve the desired results. We also updated a high-speed data transmission tool called GBox that facilitates the rapid transfer of large datasets., Conclusions: The analysis pipelines on Closha 2.0 are reproducible, with all analysis parameters and inputs being permanently recorded. Closha 2.0 simplifies multi-step analysis with drag-and-drop functionality and provides a user-friendly interface for genomic scientists to obtain accurate results from NGS data. Closha 2.0 is freely available at https://www.kobic.re.kr/closha2 ., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The objectives of this study were to evaluate the potential of using thermophilic aerobic digestion (TAD) to hydrolyze aquaculture sludge, and to investigate the hydrolysis efficiency and changes in microbial community structure during TAD at 0, 15, and 30 practical salinity units (psu). As digestion progressed, soluble organic matter concentrations in all reactors increased to their maximum values at 6 h. The hydrolysis efficiency at 6 h decreased as salinity increased: 2.42% at 0 psu, 1.78% at 15 psu, and 1.04% at 30 psu. The microbial community compositions at the genus level prominently differed in the relative abundances of dominant bacteria between 0 psu and 30 psu. The relative abundance of genera Iodidimonas and Tepidiphilus increased significantly as salinity increased. Increase in the salinity at which thermophilic aerobic digestion of aquaculture sludge was conducted altered the microbial community structure, which in turn decreased the efficiency of organic matter hydrolysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chun, Kim, Ko, Shin, Kim and Cho.)

Aquaculture products, such as clams, scallops, and oysters, are major vectors of fecal-derived pathogens. Male-specific and somatic coliphages are strongly correlated with human noroviruses, the major enteric viruses worldwide. Geographic information system with local land-use patterns can also provide valuable information for tracking sources of fecal-derived pathogens. We examined distributions of four fecal indicator microorganisms, i.e., male-specific and somatic coliphage, total coliform, and Escherichia coli ( E. coli ) in three river and seawater sampling sites located on the coast of Gomso Bay in the Republic of Korea during the sampling period (from March 2015 to January 2016). Geospatial analyses of fecal indicators and correlation between environmental parameters and fecal indicators or among fecal indicators were also performed. Overall, river water samples showed highest concentrations of both types of coliphage in summer (July 2015). High concentrations of both total coliform and E. coli were detected in river water during the period from July to September 2015. High concentrations of all fecal indicators were found at site GL02, located in the innermost part of Gomso Bay, which has high-density agriculture and residential areas. Environmental factors related to precipitation-cumulative precipitation on and from 3 days before the sampling day (Prep-0 and Prep-3, respectively)-and salinity were strongly correlated with concentrations of all fecal indicators. The present results suggest that investigations of multiple fecal indicators with a systemic geospatial information are necessary for precisely tracking fecal contaminations of aquaculture products.

Visualization designers (e.g., journalists or data analysts) often rely on examples to explore the space of possible designs, yet we have little insight into how examples shape data visualization design outcomes. While the effects of examples have been studied in other disciplines, such as web design or engineering, the results are not readily applicable to visualization due to inconsistencies in findings and challenges unique to visualization design. Towards bridging this gap, we conduct an exploratory experiment involving 32 data visualization designers focusing on the influence of five factors (timing, quantity, diversity, data topic similarity, and data schema similarity) on objectively measurable design outcomes (e.g., numbers of designs and idea transfers). Our quantitative analysis shows that when examples are introduced after initial brainstorming, designers curate examples with topics less similar to the dataset they are working on and produce more designs with a high variation in visualization components. Also, designers copy more ideas from examples with higher data schema similarities. Our qualitative analysis of participants' thought processes provides insights into why designers incorporate examples into their designs, revealing potential factors that have not been previously investigated. Finally, we discuss how our results inform how designers may use examples during design ideation as well as future research on quantifying designs and supporting example-based visualization design. All supplemental materials are available in our OSF repo.

Dion Diep,1 Jasmine Ko,2 John Lan,3 Kinga T Koprowicz,3 Gordon Ko3,4 1MD Program, University of Toronto, Toronto, ON, Canada; 2Department of Kinesiology, McMaster University, Hamilton, ON, Canada; 3Canadian Centre of Integrative Medicine, Toronto, ON, Canada; 4Division of Physical Medicine & Rehabilitation, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaCorrespondence: Gordon KoClinical Adjunct Lecturer, Division of Physical Medicine & Rehabilitation, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON M4N 3M5, CanadaTel +1416-480-4342Fax +1416-480-6885Email drgordko@rogers.comIntroduction: There is a paucity of long-term treatment benefit and safety data of botulinum toxin A (BTX-A) for cervical dystonia (CD) and myofascial neck pain syndrome (MPS). Additionally, the prevalence of adjunct modality uses during this period is unknown despite evolving practices.Objective: To assess and compare treatment benefit, safety, and adjunct modality prevalences of long-term BTX-A injections between CD and MPS patients.Design: Retrospective cohort study.Setting: Private practice tertiary care clinics in Toronto.Patients: Convenience sample of 37 (52.9%) CD and 33 (47.1%) MPS patients treated for a mean±SD duration of 7.2± 4.3 and 8.3± 4.7 years, respectively.Interventions: BTX-A injections administered at least once yearly, for a duration longer than 1 year.Main Outcome Measures: Toronto Western Spasmodic Torticollis Rating Scales (TWSTRS) for disability and pain, Patient Global Impression of Change (PGIC) score, time to peak effect, duration of total response, adverse effects, and prevalence of adjunct modalities.Results: CD patients experienced improvements in TWSTRS disability (17.57± 6.79 to 9.81± 4.35, p< 0.001) and pain (14.61± 3.08 to 9.05± 3.49, p< 0.001) scores as well as PGIC score (52.00%± 23.60% to 64.80%± 23.60%, p=0.007). MPS patients experienced improvements in TWSTRS disability (15.86± 7.70 to 10.07± 7.01, p=0.01) and pain (15.25± 4.09 to 10.85± 4.49, p=0.01) scores. In both cohorts, there were no changes in time to peak effect and duration of total response. Adverse effects were minimal and self-limiting. Prevalences of adjunct modalities used by CD versus MPS patients were 28.13% versus 50.00% for anesthetic procedures, 23.08% versus 15.38% for image-guidance, 65.71% versus 56.25% for pectoralis minor injections, and 47.06% versus 53.13% for cannabis-use.Conclusion: There were demonstrated and comparable treatment benefit, safety, and adjunct modality prevalences. Our study is the first to demonstrate that long-term BTX-A injections for MPS, although commonly used off-label, can be effective and safe.Keywords: botulinum toxin, cervical dystonia, myofascial pain syndrome

Introduction: While studies have documented delays in breast cancer (BC) care during the COVID-19 pandemic due to healthcare restrictions, there have been no studies on the experiences, and, particularly, the challenges with providing care faced by breast surgeons during this unprecedented time. This paper aims to understand the perspectives of breast surgeons regarding the impact of the COVID-19 pandemic on BC care., Methods: We used purposeful and snowball sampling to identify breast surgeons in Ontario, Canada. One-on-one qualitative semi-structured interviews were conducted exploring the impact of the pandemic on BC treatment, psychosocial well-being of patients and providers, and the future state of BC care. Audio-recorded interviews were transcribed verbatim and analyzed using Thematic Analysis., Results: A total of 10 breast surgeons (5 community and 5 academic) were interviewed. Breast surgeons reported that the pandemic led to increased multidisciplinary collaboration and innovations in delivery of BC surgery (e.g., increased use of regional anesthesia). Multiple surgeons identified that the pandemic created disparities in BC care based geographic location and that existing disparities in care based on ethnicity or marginalization were exacerbated. Last, surgeons identified that virtual care improved, but also created some challenges to how BC care was delivered, with many hoping for this to be continued after the pandemic was over., Conclusions: In this study, breast surgeons identified unique challenges and solutions to BC care delivery during the pandemic. Concerns regarding disparities in care based on geographic location and marginalized patients require further study to improve future BC care., (Copyright © 2024. Published by Elsevier Inc.)

Background: Neurotrophic tyrosine receptor kinase ( NTRK ) gene fusions are rare oncogenic drivers prevalent in 0.3% of solid tumors. They are most common in salivary gland cancer (2.6%), thyroid cancer (1.6%), and soft-tissue sarcoma (1.5%). Currently, there are 2 US Food and Drug Administration-approved targeted therapies for NTRK gene fusions: larotrectinib, approved in 2018, and entrectinib, approved in 2019. To date, the real-world uptake of tyrosine receptor kinase inhibitor (TRKi) use for NTRK -positive solid tumors in academic cancer centers remains largely unknown., Objective: To describe the demographics, clinical and genomic characteristics, and testing and treatment patterns of patients with NTRK -positive solid tumors treated at US academic cancer centers., Methods: This was a retrospective chart review study conducted in academic cancer centers in the United States. All patients diagnosed with an NTRK fusion-positive ( NTRK 1, NTRK 2, NTRK 3) solid tumor (any stage) and who received cancer treatment at participating sites between January 1, 2012, and July 1, 2023, were included in this study. Patient demographics, clinical characteristics, genomic characteristics, NTRK testing data, and treatment patterns were collected from electronic medical records and analyzed using descriptive statistics as appropriate., Results: In total, 6 centers contributed data for 55 patients with NTRK -positive tumors. The mean age was 49.3 (SD = 20.5) years, 51% patients were female, and the majority were White (78%). The median duration of time from cancer diagnosis to NTRK testing was 85 days (IQR = 44-978). At the time of NTRK testing, 64% of patients had stage IV disease, compared with 33% at cancer diagnosis. Prevalent cancer types in the overall cohort included head and neck (15%), thyroid (15%), brain (13%), lung (13%), and colorectal (11%). NTRK 1 fusions were most common (45%), followed by NTRK 3 (40%) and NTRK 2 (15%). Across all lines of therapy, 51% of patients (n = 28) received a TRKi. Among TRKi-treated patients, 71% had stage IV disease at TRKi initiation. The median time from positive NTRK test to initiation of TRKi was 48 days (IQR = 9-207). TRKis were commonly given as first-line (30%) or second-line (48%) therapies. Median duration of therapy was 610 (IQR = 182-764) days for TRKi use and 207.5 (IQR = 42-539) days for all other first-line therapies., Conclusions: This study reports on contemporary real-world NTRK testing patterns and use of TRKis in solid tumors, including time between NTRK testing and initiation of TRKi therapy and duration of TRKi therapy.

Antibiotics are used to control infectious diseases. However, adverse effects of antibiotics, such as devastation of the gut microbiota and enhancement of the inflammatory response, have been reported. Health benefits of fermented milk are established and can be enhanced by the addition of probiotic strains. In this study, we evaluated effects of fermented milk containing Lacticaseibacillus rhamnosus ( L. rhamnosus ) SNUG50430 in a mouse model with antibiotic treatment. Fermented milk containing 2 × 10 5 colony-forming units of L. rhamnosus SNUG50430 was administered to six week-old female BALB/c mice for 1 week. Interleukin (IL)-10 levels in colon samples were significantly increased ( P < 0.05) compared to water-treated mice, whereas interferon-gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) were decreased, of mice treated with fermented milk containing L. rhamnosus SNUG50430-antibiotics-treated (FM+LR+Abx-treated) mice. Phylum Firmicutes composition in the gut was restored and the relative abundances of several bacteria, including the genera Coprococcus and Lactobacillus , were increased in FM+LR+Abx-treated mice compared to PBS+Abx-treated mice. Interestingly, abundances of genus Coprococcus and Lactobacillus were positively correlated with IL-5 and IL-10 levels ( P < 0.05) in colon samples and negative correlated with IFN-γ and TNF-α levels in serum samples ( P < 0.001). Acetate and butyrate were increased in mice with fermented milk and fecal microbiota of FM+LR+Abx-treated mice were highly enriched with butyrate metabolism pathway compared to water-treated mice ( P < 0.05). Thus, fermented milk containing L. rhamnosus SNUG50430 was shown to ameliorate adverse health effects caused by antibiotics through modulating immune responses and the gut microbiota.

Background: Larotrectinib is approved for patients with advanced NTRK gene fusion-positive solid tumors. Prior studies demonstrated promising results with larotrectinib compared with other systemic therapy. However, comparisons to checkpoint inhibitors, such as nivolumab or pembrolizumab, have not been done., Objective: To estimate and compare expected life-years (LYs) and quality-adjusted LYs (QALYs) for patients with nonsmall cell lung cancer (NSCLC) eligible for larotrectinib vs patients with unknown NTRK gene fusion status on nivolumab or pembrolizumab. We also assessed patients with metastatic differentiated thyroid cancer (DTC), as pembrolizumab may be considered in certain circumstances., Methods: We developed partitioned survival models to project long-term comparative effectiveness of larotrectinib vs nivolumab or pembrolizumab. Larotrectinib survival data were derived from an updated July 2021 analysis of 21 adult patients (≥18 years of age) with metastatic NTRK gene fusion-positive NSCLC and 21 with DTC. Survival inputs for nivolumab and pembrolizumab were obtained from published articles. Progression-free and overall survival were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Log-normal). Exponential fits were chosen based on goodness-of-fit and clinical plausibility., Results: In NSCLC, larotrectinib resulted in gains of 5.87 and 5.91 LYs compared to nivolumab and pembrolizumab, respectively, which translated to gains of 3.53 and 3.56 QALYs. In DTC, larotrectinib resulted in a gain of 5.23 LYs and 4.24 QALYs compared to pembrolizumab., Conclusions: In metastatic NSCLC and DTC, larotrectinib may produce substantial life expectancy and QALY gains compared to immune checkpoint inhibitors. Additional data with longer follow-up will further inform this comparison.

Ulcerative colitis, a major form of inflammatory bowel disease (IBD) associated with chronic colonic inflammation, may be induced via overreactive innate and adaptive immune responses. Restoration of gut microbiota abundance and diversity is important to control the pathogenesis. Lactobacillus spp., well-known probiotics, ameliorate IBD symptoms via various mechanisms, including modulation of cytokine production, restoration of gut tight junction activity and normal mucosal thickness, and alterations in the gut microbiota. Here, we studied the effects of oral administration of Lactobacillus rhamnosus (L. rhamnosus) KBL2290 from the feces of a healthy Korean individual to mice with DSS-induced colitis. Compared to the dextran sulfate sodium (DSS) + phosphate-buffered saline control group, the DSS + L. rhamnosus KBL2290 group evidenced significant improvements in colitis symptoms, including restoration of body weight and colon length, and decreases in the disease activity and histological scores, particularly reduced levels of pro-inflammatory cytokines and an elevated level of anti-inflammatory interleukin-10. Lactobacillus rhamnosus KBL2290 modulated the levels of mRNAs encoding chemokines and markers of inflammation; increased regulatory T cell numbers; and restored tight junction activity in the mouse colon. The relative abundances of genera Akkermansia, Lactococcus, Bilophila, and Prevotella increased significantly, as did the levels of butyrate and propionate (the major short-chain fatty acids). Therefore, oral L. rhamnosus KBL2290 may be a useful novel probiotic., (© 2023. The Author(s), under exclusive licence to Microbiological Society of Korea.)

Norovirus (NoV) is the most common viral cause of acute gastroenteritis worldwide. Vitamin A has demonstrated the potential to protect against gastrointestinal infections. However, the effects of vitamin A on human norovirus (HuNoV) infections remain poorly understood. This study aimed to investigate how vitamin A administration affects NoV replication. We demonstrated that treatment with retinol or retinoic acid (RA) inhibited NoV replication in vitro based on their effects on HuNoV replicon-bearing cells and murine norovirus-1 (MNV-1) replication in murine cells. MNV replication in vitro showed significant transcriptomic changes, which were partially reversed by retinol treatment. RNAi knockdown of CCL6, a chemokine gene that was downregulated by MNV infection but upregulated by retinol administration, resulted in increased MNV replication in vitro. This suggested a role of CCL6 in the host response to MNV infections. Similar gene expression patterns were observed in the murine intestine after oral administration of RA and/or MNV-1.CW1. CCL6 directly decreased HuNoV replication in HG23 cells, and might indirectly regulate the immune response against NoV infection. Finally, relative replication levels of MNV-1.CW1 and MNV-1.CR6 were significantly increased in CCL6 knockout RAW 264.7 cells. This study is the first to comprehensively profile transcriptomes in response to NoV infection and vitamin A treatment in vitro, and thus may provide new insights into dietary prophylaxis and NoV infections., (© 2023. The Author(s), under exclusive licence to Microbiological Society of Korea.)

Background: Supervised machine learning models have been widely used to predict and get insight into diseases by classifying patients based on personal health records. However, a class imbalance is an obstacle that disrupts the training of the models. In this study, we aimed to address class imbalance with a conditional normalizing flow model, one of the deep-learning-based semi-supervised models for anomaly detection. It is the first introduction of the normalizing flow algorithm for tabular biomedical data., Methods: We collected personal health records from South Korean citizens (n = 706), featuring genetic data obtained from direct-to-customer service (microarray chip), medical health check-ups, and lifestyle log data. Based on the health check-up data, six chronic diseases were labeled (obesity, diabetes, hypertriglyceridemia, dyslipidemia, liver dysfunction, and hypertension). After preprocessing, supervised classification models and semi-supervised anomaly detection models, including conditional normalizing flow, were evaluated for the classification of diabetes, which had extreme target imbalance (about 2%), based on AUROC and AUPRC. In addition, we evaluated their performance under the assumption of insufficient collection for patients with other chronic diseases by undersampling disease-affected samples., Results: While LightGBM (the best-performing model among supervised classification models) showed AUPRC 0.16 and AUROC 0.82, conditional normalizing flow achieved AUPRC 0.34 and AUROC 0.83 during fifty evaluations of the classification of diabetes, whose base rate was very low, at 0.02. Moreover, conditional normalizing flow performed better than the supervised model under a few disease-affected data numbers for the other five chronic diseases - obesity, hypertriglyceridemia, dyslipidemia, liver dysfunction, and hypertension. For example, while LightGBM performed AUPRC 0.20 and AUROC 0.75, conditional normalizing flow showed AUPRC 0.30 and AUROC 0.74 when predicting obesity, while undersampling disease-affected samples (positive undersampling) lowered the base rate to 0.02., Conclusions: Our research suggests the utility of conditional normalizing flow, particularly when the available cases are limited, for predicting chronic diseases using personal health records. This approach offers an effective solution to deal with sparse data and extreme class imbalances commonly encountered in the biomedical context., (© 2024. The Author(s).)

During the last decade, the generation and accumulation of petabase-scale high-throughput sequencing data have resulted in great challenges, including access to human data, as well as transfer, storage, and sharing of enormous amounts of data. To promote data-driven biological research, the Korean government announced that all biological data generated from government-funded research projects should be deposited at the Korea BioData Station (K-BDS), which consists of multiple databases for individual data types. Here, we introduce the Korean Nucleotide Archive (KoNA), a repository of nucleotide sequence data. As of July 2022, the Korean Read Archive in KoNA has collected over 477 TB of raw next-generation sequencing data from national genome projects. To ensure data quality and prepare for international alignment, a standard operating procedure was adopted, which is similar to that of the International Nucleotide Sequence Database Collaboration. The standard operating procedure includes quality control processes for submitted data and metadata using an automated pipeline, followed by manual examination. To ensure fast and stable data transfer, a high-speed transmission system called GBox is used in KoNA. Furthermore, the data uploaded to or downloaded from KoNA through GBox can be readily processed using a cloud computing service called Bio-Express. This seamless coupling of KoNA, GBox, and Bio-Express enhances the data experience, including submission, access, and analysis of raw nucleotide sequences. KoNA not only satisfies the unmet needs for a national sequence repository in Korea but also provides datasets to researchers globally and contributes to advances in genomics. The KoNA is available at https://www.kobic.re.kr/kona/., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)

Background: Nonmetastatic castration-resistant prostate cancer (nmCRPC) patients are often older and use concurrent medications that increase the potential for drug-drug interactions (pDDIs). This study assessed pDDI prevalence in real-world nmCRPC patients treated with apalutamide, darolutamide, or enzalutamide., Research Design and Methods: Castrated prostate cancer patients without metastases prior to androgen receptor inhibitor initiation were identified retrospectively via Optum Clinformatics Data Mart claims data (8/2019-3/2021). The top 100 concomitant medications were assessed for pDDIs., Results: Among 1,515 patients (mean age: 77 ± 8 years; mean Charlson Comorbidity Index: 3 ± 3), 340 initiated apalutamide, 112 darolutamide, and 1,063 enzalutamide. Common concomitant medication classes were cardiovascular (80%) and central nervous system (52%). Two-thirds of the patients received ≥5 concomitant medications; 30 (30/100 medications) pDDIs were identified for apalutamide and enzalutamide each and 2 (2/100 medications) for darolutamide. Most pDDIs had risk ratings of C or D, but four for apalutamide were rated X. Approximately 58% of the patients on apalutamide, 5% on darolutamide, and 54% on enzalutamide had ≥1 identified pDDI., Conclusions: Results showed a higher frequency of pDDIs in patients receiving apalutamide and enzalutamide vs darolutamide. The impact of these could not be determined retrospectively. DDI risk should be carefully evaluated when discussing optimal therapy for patients with nmCRPC.

There are limited data on the prevalence of next-generation sequencing (NGS) in the United States, especially in light of the increasing importance of identifying actionable oncogenic variants due to molecular biomarker-based therapy approvals. This retrospective study of adult patients with select metastatic solid tumors and central nervous system tumors from the Optum Clinformatics Data Mart US health care claims database (January 1, 2014, to June 30, 2021; N = 63,209) examined NGS use trends over time. A modest increase in NGS was observed across tumor types from 2015 (0.0% to 1.5%) to 2021 (2.1% to 17.4%). A similar increase in NGS rates was also observed across key periods; however, rates in the final key period remained <10% for patients with breast, colorectal, head and neck, soft tissue sarcoma, and thyroid cancers, as well as central nervous system tumors. The median time to NGS from diagnosis was shortest among patients with non-small-cell lung cancer and longest for patients with breast cancer. Predictors of NGS varied by tumor type; test rates for minorities in select tumor types appeared comparable to the White population. Despite improving payer policies to expand coverage of NGS and molecular biomarker-based therapy approvals, NGS rates remained low across tumor types. Given the potential for improved patient outcomes with molecular biomarker-based therapy, further efforts to improve NGS rates are warranted., Competing Interests: Disclosure Statement B.H., G.K., S.B., and S.A. are employees of Bayer HealthCare Pharmaceuticals, Inc. S.S. is a former employee of Bayer Healthcare Pharmaceuticals, Inc. A.F.-G. is a paid consultant of Bayer HealthCare Pharmaceuticals, Inc., and has received honoraria for presentations for Qiagen and Assuragen, Inc., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve replacement (TAVR) is a reasonable therapeutic approach among patients with symptomatic severe aortic stenosis irrespective of surgical risk. Data regarding sex-specific differences in the outcomes with newer generation valves are limited., Methods: Electronic databases were searched for studies assessing sex differences in the outcomes of patients undergoing TAVR with newer generation valves (SAPIEN 3 or Evolut). Random effects model was constructed for summary estimates., Results: Four observational studies with 4522 patients (44.8% women) were included in the meta-analysis. Women were older and had a lower prevalence of coronary artery disease and mean EuroScore. Women had a higher incidence of short-term mortality (up to 30 days) (risk ratio [RR]: 1.60, 95% confidence interval [CI]: 1.14-2.25), but no difference in 1-year mortality (RR: 0.92, 95% CI: 0.72-1.17). There was no significant difference in the incidence of major bleeding (RR: 1.16, 95% CI: 0.86-1.57), permanent pacemaker (PPM) (RR: 0.80, 95% CI: 0.62-1.04), or disabling stroke (RR: 1.16, 95% CI: 0.54-2.45)., Conclusion: In this meta-analysis, we found that women undergoing TAVR with newer-generation devices were older but had a lower prevalence of comorbidities. Women had a higher incidence of short-term mortality but no difference in the 1-year mortality, bleeding, PPM, or stroke compared with men. Future studies are required to confirm these findings., (© 2024 Wiley Periodicals LLC.)

Faecalibacterium prausnitzii is one of the most dominant commensal bacteria in the human gut, and certain anti-inflammatory functions have been attributed to a single microbial anti-inflammatory molecule (MAM). Simultaneously, substantial diversity among F. prausnitzii strains is acknowledged, emphasizing the need for strain-level functional studies aimed at developing innovative probiotics. Here, two distinct F. prausnitzii strains, KBL1026 and KBL1027, were isolated from Korean donors, exhibiting notable differences in the relative abundance of F. prausnitzii. Both strains were identified as the core Faecalibacterium amplicon sequence variant (ASV) within the healthy Korean cohort, and their MAM sequences showed a high similarity of 98.6%. However, when a single strain was introduced to mice with dextran sulfate sodium (DSS)-induced colitis, KBL1027 showed the most significant ameliorative effects, including alleviation of colonic inflammation and restoration of gut microbial dysbiosis. Moreover, the supernatant from KBL1027 elevated the secretion of IL-10 cytokine more than that of KBL1026 in mouse bone marrow-derived macrophage (BMDM) cells, suggesting that the strain-specific, anti-inflammatory efficacy of KBL1027 might involve effector compounds other than MAM. Through analysis of the Faecalibacterium pan-genome and comparative genomics, strain-specific functions related to extracellular polysaccharide biosynthesis were identified in KBL1027, which could contribute to the observed morphological disparities. Collectively, our findings highlight the strain-specific, anti-inflammatory functions of F. prausnitzii, even within the same core ASV, emphasizing the influence of their human origin., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Atopic dermatitis (AD) is a chronic inflammatory skin disease with repeated exacerbations of eczema and pruritus. Probiotics can prevent or treat AD appropriately via modulation of immune responses and gut microbiota. In this study, we evaluated effects of Lactobacillus acidophilus (L. acidophilus) KBL409 using a house dust mite (Dermatophagoides farinae)-induced in vivo AD model. Oral administration of L. acidophilus KBL409 significantly reduced dermatitis scores and decreased infiltration of immune cells in skin tissues. L. acidophilus KBL409 reduced in serum immunoglobulin E and mRNA levels of T helper (Th)1 (Interferon-γ), Th2 (Interleukin [IL]-4, IL-5, IL-13, and IL-31), and Th17 (IL-17A) cytokines in skin tissues. The anti-inflammatory cytokine IL-10 was increased and Foxp3 expression was up-regulated in AD-induced mice with L. acidophilus KBL409. Furthermore, L. acidophilus KBL409 significantly modulated gut microbiota and concentrations of short-chain fatty acids and amino acids, which could explain its effects on AD. Our results suggest that L. acidophilus KBL409 is the potential probiotic for AD treatment by modulating of immune responses and gut microbiota of host., (© 2024. The Author(s).)

Aim: Next-generation sequencing (NGS) of solid tumors can inform treatment decisions; however, uptake remains low. This objective of this systematic review was to identify barriers to and facilitators of NGS in US oncology settings. Materials & methods: Embase and MEDLINE were searched in March 2023 for articles published from 2012 to 2023 on barriers and facilitators of NGS adoption for solid tumors. Surveys, interviews and observational studies were eligible. Studies on genetic testing for hereditary cancers and non-US studies were excluded. The Motheral scale, Joanna Briggs Institute critical appraisal checklist and McGill Mixed Methods Appraisal Tool were used to assess study quality. Data were synthesized narratively. Results: Twenty-one studies were included. Study participants were clinicians, payers and administrators. Key barriers included complex reimbursement processes and uncertainties around clinical utility. Including recommendations for NGS in clinical practice guidelines was a key facilitator, although insurance policies were often more restrictive than guideline recommendations. Conclusion: Uptake of NGS is increasing but barriers remain. Changes to the current reimbursement frameworks are needed to increase access to NGS. The impact of implementing the 2018 National Coverage Determination, which allows access to NGS for all Medicare beneficiaries with advanced cancer, is not yet evident in the published literature.

Since the industrial revolution, which was accompanied with the use of fossil fuels as an energy source, the content of carbon dioxide (CO 2 ) in the atmosphere has increased. To mitigate global warming, industries that utilize fossil fuels have continuously explored new approaches to reduce CO 2 emissions and convert it to alternative fuels. The ocean is a vast source of absorbed CO 2 on Earth, and various studies have been conducted on the use of the ocean to reduce global CO 2 . This study focused on reducing CO 2 in the atmosphere by storing it as bicarbonate, a form of CO 2 that exists in the ocean. The optimum condition for the conversion of CO 2 into bicarbonate was investigated by considering the dissolved inorganic carbon (DIC; HCO 3 - , CO 3 2- , H 2 CO 3 ) concentration and pH. To confirm the biological impact of this conversion, biological impact experiments were conducted under various DIC concentrations using Skeletonema japonicum, a phytoplankton present in most areas of the sea. Based on the DIC concentration (2.09 mM) of the seawater, the DIC concentrations used in the Lab-scale experiment ranged from 2.5 mM to 18.75 mM, and the concentration with the highest conversion rate (< 6.38 mM) was applied in the pilot plant. Marine environmental impact modeling was performed to observe the effect of discharge to the ocean and its movement. The results revealed a slight growth inhibition of phytoplankton at DIC concentrations higher than the base concentration. Nevertheless, the change in the DIC concentration exerted no effect on the phytoplankton growth except at extremely high concentrations. Moreover, the high DIC concentration can be diluted by the ocean current flow rate, thus counterbalancing the growth inhibition effect. The results obtained in this study demonstrate the feasibility of CO 2 storage in the form of DIC, and will be helpful for further development of CO 2 mitigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Hybrid particles with immobilized silver nanoparticles (AgNPs) receive a lot of attention due to their excellent antibacterial activity with the prevention of inherent aggregation of AgNPs. In this study, serial sized silica substrate particles (231, 401, and 605 nm) and their corresponding hybrid particles with AgNPs (~ 30 nm) are prepared, with detailed bactericidal images of the corresponding particles at various times. Their bactericidal activity is elucidated for both Gram-positive Streptococcus agalactiae and Gram-negative Escherichia coli CN13, which show the size of 0.8 μm × 0.9 μm and 1.3 μm × 1.8 μm, respectively. There is a large difference in the bactericidal activity between the smallest (231 nm, 3-log 10 reduction) and larger (401 and 605 nm, 6-log 10 reduction) silica substrates, whereas there is hardly a difference between the latter. Their effective total surface area (ETSA) is considered important for their bactericidal activity, based on the nearly equal large ETSA of the well-dispersed two larger silica substrates and the much smaller ETSA of the agglomerated smallest substrates. Submicron-sized pits appear on the bacterial membrane by direct contact with the hybrid particles, implicating the importance of ETSA. Still, further research is needed with much different silica substrate sizes to fully elucidate the impact of the silica substrate on the bactericidal activity of immobilized AgNPs., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)