T cell immunotherapies engage neutrophils to eliminate tumor antigen escape variants.

Cancer immunotherapies, including adoptive T cell transfer, can be ineffective because tumors evolve to display antigen-loss-variant clones. Therapies that activate multiple branches of the immune system may eliminate escape variants. Here, we show that melanoma-specific CD4+ T cell therapy in combination with OX40 co-stimulation or CTLA-4 blockade can eradicate melanomas containing antigen escape variants. As expected, early on-target recognition of melanoma antigens by tumor-specific CD4+ T cells was required. Surprisingly, complete tumor eradication was dependent on neutrophils and partly dependent on inducible nitric oxide synthase. In support of these findings, extensive neutrophil activation was observed in mouse tumors and in biopsies of melanoma patients treated with immune checkpoint blockade. Transcriptomic and flow cytometry analyses revealed a distinct anti-tumorigenic neutrophil subset present in treated mice. Our findings uncover an interplay between T cells mediating the initial anti-tumor immune response and neutrophils mediating the destruction of tumor antigen loss variants.

The implication of holocytochrome c synthase mutation in Korean familial hypoplastic amelogenesis imperfecta.

OBJECTIVES: This study aimed to comprehensively characterise genetic variants of amelogenesis imperfecta in a single Korean family through whole-exome sequencing and bioinformatics analysis. MATERIAL AND METHODS: Thirty-one individuals of a Korean family, 9 of whom were affected and 22 unaffected by amelogenesis imperfecta, were enrolled. Whole-exome sequencing was performed on 12 saliva samples, including samples from 8 affected and 4 unaffected individuals. The possible candidate genes associated with the disease were screened by segregation analysis and variant filtering. In silico mutation impact analysis was then performed on the filtered variants based on sequence conservation and protein structure. RESULTS: Whole-exome sequencing data revealed an X-linked dominant, heterozygous genomic missense mutation in the mitochondrial gene holocytochrome c synthase (HCCS). We also found that HCCS is potentially related to the role of mitochondria in amelogenesis. The HCCS variant was expected to be deleterious in both evolution-based and large population-based analyses. Further, the variant was predicted to have a negative effect on catalytic function of HCCS by in silico analysis of protein structure. In addition, HCCS had significant association with amelogenesis in literature mining analysis. CONCLUSIONS: These findings suggest new evidence for the relationship between amelogenesis and mitochondria function, which could be implicated in the pathogenesis of amelogenesis imperfecta. CLINICAL RELEVANCE: The discovery of HCCS mutations and a deeper understanding of the pathogenesis of amelogenesis imperfecta could lead to finding solutions for the fundamental treatment of this disease. Furthermore, it enables dental practitioners to establish predictable prosthetic treatment plans at an early stage by early detection of amelogenesis imperfecta through personalised medicine.

Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance.

The role of epithelial-to-mesenchymal transition (EMT) in metastasis is a longstanding source of debate, largely owing to an inability to monitor transient and reversible EMT phenotypes in vivo. Here we establish an EMT lineage-tracing system to monitor this process in mice, using a mesenchymal-specific Cre-mediated fluorescent marker switch system in spontaneous breast-to-lung metastasis models. We show that within a predominantly epithelial primary tumour, a small proportion of tumour cells undergo EMT. Notably, lung metastases mainly consist of non-EMT tumour cells that maintain their epithelial phenotype. Inhibiting EMT by overexpressing the microRNA miR-200 does not affect lung metastasis development. However, EMT cells significantly contribute to recurrent lung metastasis formation after chemotherapy. These cells survived cyclophosphamide treatment owing to reduced proliferation, apoptotic tolerance and increased expression of chemoresistance-related genes. Overexpression of miR-200 abrogated this resistance. This study suggests the potential of an EMT-targeting strategy, in conjunction with conventional chemotherapies, for breast cancer treatment.

Bcl-2 Overexpression Induces Neurite Outgrowth via the Bmp4/Tbx3/NeuroD1 Cascade in H19-7 Cells.

Bcl-2 is overexpressed in the nervous system during neural development and plays an important role in modulating cell survival. In addition to its anti-apoptotic function, it has been suggested previously that Bcl-2 might act as a mediator of neuronal differentiation. However, the mechanism by which Bcl-2 might influence neurogenesis is not sufficiently understood. In this study, we aimed to determine the non-apoptotic functions of Bcl-2 during neuronal differentiation. First, we used microarrays to analyze the whole-genome expression patterns of rat neural stem cells overexpressing Bcl-2 and found that Bcl-2 overexpression induced the expression of various neurogenic genes. Moreover, Bcl-2 overexpression increased the neurite length as well as expression of Bmp4, Tbx3, and proneural basic helix-loop-helix genes, such as NeuroD1, NeuroD2, and Mash1, in H19-7 rat hippocampal precursor cells. To determine the hierarchy of these molecules, we selectively depleted Bmp4, Tbx3, and NeuroD1 in Bcl-2-overexpressing cells. Bmp4 depletion suppressed the upregulation of Tbx3 and NeuroD1 as well as neurite outgrowth, which was induced by Bcl-2 overexpression. Although Tbx3 knockdown repressed Bcl-2-mediated neurite elaboration and downregulated NeuroD1 expression, it did not affect Bcl-2-induced Bmp4 expression. While the depletion of NeuroD1 had no effect on the expression of Bcl-2, Bmp4, or Tbx3, Bcl-2-mediated neurite outgrowth was suppressed. Taken together, these results demonstrate that Bcl-2 regulates neurite outgrowth through the Bmp4/Tbx3/NeuroD1 cascade in H19-7 cells, indicating that Bcl-2 may have a direct role in neuronal development in addition to its well-known anti-apoptotic function in response to environmental insults.

Reversible Fermi Level Tuning of a Sb2Te3 Topological Insulator by Structural Deformation.

For three-dimensional (3D) topological insulators that have a layered structure, strain was used to control critical physical properties. Here, we show that tensile strain decreases bulk carrier density while accentuating transport of topological surface state using temperature-dependent resistance and magneto-resistance measurements, terahertz-time domain spectroscopy and density functional theory calculations. The induced strain was confirmed by transmittance X-ray scattering measurements. The results show the possibility of reversible topological surface state device control using structural deformation.

PLD1 activation mediates Amb a 1-induced Th2-associated cytokine expression via the JNK/ATF-2 pathway in BEAS-2B cells.

The purpose of this study was to identify the role of phospholipase D1 (PLD1) in Amb a 1-induced IL-5 and IL-13 expression. When BEAS-2B cells were stimulated with Amb a 1, PLD activity increased, and knockdown of PLD1 decreased Amb a 1-induced IL-5 and IL-13 expression. Amb a 1 also activated the PLCγ/p70S6K/JNK pathway. Furthermore, Amb a 1-induced PLD activation was also attenuated by PLCγ inhibition, and knockdown of PLD1 decreased Amb a 1-induced activation of P70S6K and JNK. When ATF-2 activity was blocked with ATF-2 siRNA, Amb a 1-induced IL-5 and IL-13 expression was completely abolished, indicating that ATF-2 is a transcriptional factor required for the expression of IL-5 and IL-13 in response to Amb a 1. Taken together, we suggest that PLD1 acts as an important regulator in Amb a 1-induced expression of IL-5 and IL-13 via a PLCγ/p70S6K/JNK/ATF-2 pathway in BEAS-2B cells.

Phosphorylation of IκBα at serine 32 by T-lymphokine-activated killer cell-originated protein kinase is essential for chemoresistance against doxorubicin in cervical cancer cells.

T-lymphokine-activated killer cell-originated protein kinase (TOPK) is known to be up-regulated in cancer cells and appears to contribute to cancer cell proliferation and survival. However, the molecular mechanism by which TOPK regulates cancer cell survival still remains elusive. Here we show that TOPK directly interacted with and phosphorylated IκBα at Ser-32, leading to p65 nuclear translocation and NF-κB activation. We also revealed that doxorubicin promoted the interaction between nonphosphorylated or phosphorylated TOPK and IκBα and that TOPK-mediated IκBα phosphorylation was enhanced in response to doxorubicin. Also, exogenously overexpressed TOPK augmented transcriptional activity driven by either NF-κB or inhibitor of apoptosis protein 2 (cIAP2) promoters. On the other hand, NF-κB activity including IκBα phosphorylation and p65 nuclear translocation, as well as cIAP2 gene expression, was markedly diminished in TOPK knockdown HeLa cervical cancer cells. Moreover, doxorubicin-mediated apoptosis was noticeably increased in TOPK knockdown HeLa cells, compared with control cells, which resulted from caspase-dependent signaling pathways. These results demonstrate that TOPK is a molecular target of doxorubicin and mediates doxorubicin chemoresistance of HeLa cells, suggesting a novel mechanism for TOPK barrier of doxorubicin-mediated cervical cancer cell apoptosis.

Machine learning approach to classifying declines of physical function and muscle strength associated with cognitive function in older women: gait characteristics based on three speeds.

Background: The aging process is associated with a cognitive and physical declines that affects neuromotor control, memory, executive functions, and motor abilities. Previous studies have made efforts to find biomarkers, utilizing complex factors such as gait as indicators of cognitive and physical health in older adults. However, while gait involves various complex factors, such as attention and the integration of sensory input, cognitive-related motor planning and execution, and the musculoskeletal system, research on biomarkers that simultaneously considers multiple factors is scarce. This study aimed to extract gait features through stepwise regression, based on three speeds, and evaluate the accuracy of machine-learning (ML) models based on the selected features to solve classification problems caused by declines in cognitive function (Cog) and physical function (PF), and in Cog and muscle strength (MS). Methods: Cognitive assessments, five times sit-to-stand, and handgrip strength were performed to evaluate the Cog, PF, and MS of 198 women aged 65 years or older. For gait assessment, all participants walked along a 19-meter straight path at three speeds [preferred walking speed (PWS), slower walking speed (SWS), and faster walking speed (FWS)]. The extracted gait features based on the three speeds were selected using stepwise regression. Results: The ML model accuracies were revealed as follows: 91.2% for the random forest model when using all gait features and 91.9% when using the three features (walking speed and coefficient of variation of the left double support phase at FWS and the right double support phase at SWS) selected for the Cog+PF+ and Cog-PF- classification. In addition, support vector machine showed a Cog+MS+ and Cog-MS- classification problem with 93.6% accuracy when using all gait features and two selected features (left step time at PWS and gait asymmetry at SWS). Conclusion: Our study provides insights into the gait characteristics of older women with decreased Cog, PF, and MS, based on the three walking speeds and ML analysis using selected gait features, and may help improve objective classification and evaluation according to declines in Cog, PF, and MS among older women.

Determinants of Dentist-Patient Relationships: A Scoping Review.

OBJECTIVES: The dentist-patient relationship (DPR) is considered to be a key element in dental clinical settings. This scoping review aimed to examine the extent of previous research on DPR, focussing on its determinants for the reification of the construct. METHODS: This research was directed by the guidance for systematic scoping reviews from the Joanna Briggs Institute. The inclusion/exclusion criteria were based on participants of general adults and dentists, the concept of determinants of DPR, and the context of dental health care encounters. A literature search was performed in 6 major electronic databases in July 2023. Key information from included articles was extracted to chart the results, mainly to identify the determinants of DPR. Each determinant of DPR was classified according to the conceptual model of DPR. RESULTS: A total of 1727 records were initially identified, and 16 articles were included in the review. Nine studies used a quantitative method and 7 were nonempirical articles. All but 2 articles were from the perspective of patients. Factors were grouped into 6 main domains: dentist, patient, society/environment, clinical structure, clinical process, and outcome. Amongst the 6 domains of DPR, most determining factors were related to the clinical process. "Communication" was most frequently counted, at 8 times, followed by "trust" (frequency, 6). At the patient level, "dental fear/anxiety" was frequently used to measure DPR. CONCLUSIONS: Previous literature about DPR indicated a few common and dentistry-specific determinants from the patient perspective. Further studies are encouraged to develop a more comprehensive framework and evaluation scale of DPR.

Molecular characterization and environmental impact of newly isolated lytic phage SLAM_phiST1N3 in the Cornellvirus genus for biocontrol of a multidrug-resistant Salmonella Typhimurium in the swine industry chain.

Salmonella Typhimurium is a highly lethal pathogenic bacterium in weaned piglets, causing significant treatment costs and economic losses in the swine industry. Additionally, due to its ability to induce zoonotic diseases, resulting in harm to humans through the transmission of the pathogen from pork, it presents a serious public health issue. Bacteriophages (phages), viruses that infect specific bacterial strains, have been proposed as an alternative to antibiotics for controlling pathogenic bacteria. In this study, we isolated SLAM_phiST1N3, a phage infecting a multidrug-resistant (MDR) S. Typhimurium wild-type strain isolated from diseased pigs. First, comparative genomics and phylogenetic analysis revealed that SLAM_phiST1N3 belongs to the Cornellvirus genus. Moreover, utilizing a novel classification approach introduced in this study, SLAM_phiST1N3 was classified at the species level. Host range experiments demonstrated that SLAM_phiST1N3 did not infect other pathogenic bacteria or probiotics derived from pigs or other livestock. While complete eradication of Salmonella was not achievable in the liquid inhibition assay, surprisingly, we succeeded in largely eliminating Salmonella in the FIMM analysis, a gut simulation system using weaned piglet feces. Furthermore, using the C. elegans model, we showcased the potential of SLAM_phiST1N3 to prevent S. Typhimurium infection in living organisms. In addition, it was confirmed that bacterial control could be achieved when phage was applied to Salmonella-contaminated pork. pH and temperature stability experiments demonstrated that SLAM_phiST1N3 can endure swine industry processes and digestive conditions. In conclusion, SLAM_phiST1N3 demonstrates potential environmental impact as a substance for Salmonella prevention across various aspects of the swine industry chain.

Intermittent MEK inhibition with GITR co-stimulation rescues T-cell function for increased efficacy with CTLA-4 blockade in solid tumor models.

MEK inhibitors (MEKis) have shown limited success as a treatment for MAPK/ERK pathway-dependent cancers due to various resistance mechanisms tumor cells can employ. CH5126766 (CKI27) is an inhibitor that binds to MEK and prevents release of RAF, reducing the relief of negative feedback commonly observed with other MEKis. We observed that CKI27 increased MHC expression on tumor cells and improved T cell-mediated killing. Yet, CKI27 also decreased T-cell proliferation, activation, and cytolytic activity by inhibiting the MAPK/ERK pathway that is activated downstream of T cell-receptor signaling. Therefore, we aimed to balance the positive and negative immunomodulatory effects of MEKis for optimal combination with immunotherapy. Intermittent administration of CKI27 allowed T cells to partially recover and co-stimulation via GITR and OX-40 agonist antibodies completely alleviated inhibition of function. In Kras mutant lung and colon tumor mouse models, intermittent CKI27 and anti-GITR significantly decreased tumor growth and prolonged survival when further combined with CTLA-4 immune checkpoint blockade. Moreover, this triple combination increased CD8+ and CD4+ T-cell proliferation, activation, and effector/memory subsets in the tumor draining lymph nodes and tumors and led to intratumoral regulatory T cell (Treg) destabilization. These data, collectively, will allow for more informed decisions when optimizing combination regimens by overcoming resistance, reducing toxicity, and generating long-term immune responses.

Metabolic Regulation of Longevity and Immune Response in Caenorhabditis elegans by Ingestion of Lacticaseibacillus rhamnosus IDCC 3201 Using Multi-Omics Analysis.

Probiotics, specifically Lacticaseibacillus rhamnosus, have garnered attention for their potential health benefits. This study focuses on evaluating the probiotic properties of candidate probiotics L. rhamnosus IDCC 3201 (3201) using the Caenorhabditis elegans surrogate animal model, a well-established in vivo system for studying host-bacteria interactions. The adhesive ability to the host's gastrointestinal tract is a crucial criterion for selecting potential probiotic bacteria. Our findings demonstrated that 3201 exhibits significantly higher adhesive capabilities compared with Escherichia coli OP50 (OP50), a standard laboratory food source for C. elegans and is comparable with the widely recognized probiotic L. rhamnosus GG (LGG). In lifespan assay, 3201 significantly increased the longevity of C. elegans compared with OP50. In addition, preconditioning with 3201 enhanced C. elegans immune response against four different foodborne pathogenic bacteria. To uncover the molecular basis of these effects, transcriptome analysis elucidated that 3201 modulates specific gene expression related to the innate immune response in C. elegans. C-type lectin-related genes and lysozyme-related genes, crucial components of the immune system, showed significant upregulation after feeding 3201 compared with OP50. These results suggested that preconditioning with 3201 may enhance the immune response against pathogens. Metabolome analysis revealed increased levels of fumaric acid and succinic acid, metabolites of the citric acid cycle, in C. elegans fed with 3201 compared with OP50. Furthermore, there was an increase in the levels of lactic acid, a well-known antimicrobial compound. This rise in lactic acid levels may have contributed to the robust defense mechanisms against pathogens. In conclusion, this study demonstrated the probiotic properties of the candidate probiotic L. rhamnosus IDCC 3201 by using multi-omics analysis.

Overexpression of phospholipase D enhances Bcl-2 expression by activating STAT3 through independent activation of ERK and p38MAPK in HeLa cells.

The purpose of this study was to identify the role of phospholipase D (PLD) isozymes in Bcl-2 expression. Overexpression of PLD1 or PLD2 increased Bcl-2 expression and phosphatidic acid (PA), the product of PLDs, also upregulated Bcl-2 expression. Treatment with PA activated the phospholipase A(2) (PLA(2))/G(i)/ERK1/2, RhoA/Rho-associated kinase (ROCK)/p38 MAPK, and Rac1/p38 MAPK pathways. PA-induced phosphorylation of ERK1/2 was attenuated by a PLA(2) inhibitor (mepacrine) and, a G(i) protein inhibitor (pertussis toxin, PTX). On the other hand, p38 MAPK phosphorylation was attenuated by a dominant negative Rac1 and a specific Rho-kinase inhibitor (Y-27632). These results suggest that PLA(2)/G(i) acts at the upstream of ERK1/2, while Rac1 and RhoA/ROCK act upstream of p38 MAPK. We next, tried to determine which transcription factor is involved in PLD-related Bcl-2 expression. When signal transducer and activator of transcription 3 (STAT3) activity was blocked by a STAT3 specific siRNA, PA-induced Bcl-2 expression was remarkably decreased, suggesting that STAT3 is an essential transcription factor linking PLD to Bcl-2 upregulation. Taken together, these findings indicate that PLD acts as an important regulator in Bcl-2 expression by activating STAT3 involving the phosphorylation of Ser727 through the PLA(2)/G(i)/ERK1/2, RhoA/ROCK/p38 MAPK, and Rac1/p38 MAPK pathways.

Phospholipase D1 mediates bFGF-induced Bcl-2 expression leading to neurite outgrowth in H19-7 cells.

The purpose of the present study was to investigate the role of PLD (phospholipase D) in bFGF (basic fibroblast growth factor)-induced Bcl-2 expression and to examine whether overexpressed Bcl-2 influences neurite outgrowth in immortalized hippocampal progenitor cells (H19-7 cells). We found that Bcl-2 expression was maximally induced by bFGF within 24 h, and that this effect was reduced by inhibiting PLD1 expression with PLD1 small interfering RNA or by overexpressing DN (dominant-negative)-PLD1, whereas PLD1 overexpression markedly induced Bcl-2 expression. bFGF treatment activated Ras, Src, PI3K (phosphoinositide 3-kinase), PLCγ (phospholipase Cγ) and PKCα (protein kinase Cα). Among these molecules, Src and PKCα were not required for Bcl-2 expression. PLD activity was decreased by Ras, PI3K or PLCγ inhibitor, suggesting that PLD1 activation occurred through Ras, PI3K or PLCγ. We found that Ras was the most upstream molecule among these proteins, followed by the PI3K/PLCγ pathway, indicating that bFGF-induced PLD activation took place through the Ras/PI3K/PLCγ pathway. Furthermore, PLD1 was required for activation of JNK (c-Jun N-terminal kinase), which led to activation of STAT3 (signal transducer and activator of transcription 3) and finally Bcl-2 expression. When Bcl-2 was overexpressed, neurite outgrowth was stimulated along with induction of neurotrophic factors such as brain-derived neurotrophic factor and neurotrophin 4/5. In conclusion, PLD1 acts as a downstream effector of bFGF/Ras/PI3K/PLCγ signalling and regulates Bcl-2 expression through JNK/STAT3, which leads to neurite outgrowth in H19-7 cells.

Molecular characterization and functionality of rumen-derived extracellular vesicles using a Caenorhabditis elegans animal model.

The rumen fluids contain a wide range of bacteria, protozoa, fungi, and viruses. The various ruminal microorganisms in the rumen provide nutrients by fermenting the forage they eat. During metabolic processes, microorganisms present in the rumen release diverse vesicles during the fermentation process. Therefore, in this study, we confirmed the function of rumen extracellular vesicles (EVs) and their interaction with the host. We confirmed the structure of the rumen EVs by transmission electron microscope (TEM) and the size of the particles using nanoparticle tracking analysis (NTA). Rumen EVs range in size from 100 nm to 400 nm and are composed of microvesicles, microparticles, and ectosomes. Using the Caenorhabditis elegans smart animal model, we verified the interaction between the host and rumen EVs. Exposure of C. elegans to rumen EVs did not significantly enhance longevity, whereas exposure to the pathogenic bacteria Escherichia coli O157:H7 and Staphylococcus aureus significantly increased lifespan. Furthermore, transcriptome analysis showed gene expression alterations in C. elegans exposed to rumen EVs, with significant changes in the metabolic pathway, fatty acid degradation, and biosynthesis of cofactors. Our study describes the effect of rumen EV interactions with the host and provides novel insights for discovering biotherapeutic agents in the animal industry.

Association of Muscle Mass, Muscle Strength, and Muscle Function with Gait Ability Assessed Using Inertial Measurement Unit Sensors in Older Women.

Aging-related muscle atrophy is associated with decreased muscle mass (MM), muscle strength (MS), and muscle function (MF) and may cause motor control, balance, and gait pattern impairments. This study determined associations of three speed-based gait variables with loss of MM, MS, and MF in older women. Overall, 432 older women aged ≥65 performed appendicular skeletal muscle, handgrip strength, and five times sit-to-stand test to evaluate MM, MS, and MF. A gait test was performed at three speeds by modifying the preferred walking speed (PWS; slower walking speed (SWS); faster-walking speed (FWS)) on a straight 19 m walkway. Stride length (SL) at PWS was significantly associated with MM. FWS and coefficient of variance (CV) of double support phase (DSP) and DSP at PWS showed significant associations with MS. CV of step time and stride time at SWS, FWS, and single support phase (SSP) at PWS showed significant associations with MF. SL at PWS, DSP at FWS, CV of DSP at PWS, stride time at SWS, and CV of SSP at PWS showed significant associations with composite MM, MS, and MF variables. Our study indicated that gait tasks under continuous and various speed conditions are useful for evaluating MM, MS, and MF.

Association between Severity of Freezing of Gait and Turning Characteristics in People with Parkinson's Disease.

For people with Parkinson's disease (PD) with freezing of gait (FOG) (freezers), symptoms mainly exhibit as unilateral motor impairments that may cause difficulty during postural transitions such as turning during daily activities. We investigated the turning characteristics that distinguished freezers among people with PD and analyzed the association between the New Freezing of Gait Questionnaire (NFOGQ) scores and the gait characteristics according to the turning direction for the affected limbs of freezers. The study recruited 57 people with PD (27 freezers, 30 non-freezers). All experiments measured the maximum 180° turning task with the "Off" medication state. Results revealed that the outer ankle range of motion in the direction of the inner step of the more affected limb (IMA) was identified to distinguish freezers and non-freezers (RN2 = 0.735). In addition, higher NFOGQ scores were associated with a more significant anteroposterior root mean square distance of the center of mass in the IMA direction and a greater inner stance phase in the outer step of the more affected limb (OMA) direction; explanatory power was 50.1%. Assessing the maximum speed and turning direction is useful for evaluating the differences in turning characteristics between freezers and non-freezers, which can help define freezers more accurately.

Prediction of Decline in Global Cognitive Function Using Machine Learning with Feature Ranking of Gait and Physical Fitness Outcomes in Older Adults.

Gait and physical fitness are related to cognitive function. A decrease in motor function and physical fitness can serve as an indicator of declining global cognitive function in older adults. This study aims to use machine learning (ML) to identify important features of gait and physical fitness to predict a decline in global cognitive function in older adults. A total of three hundred and six participants aged seventy-five years or older were included in the study, and their gait performance at various speeds and physical fitness were evaluated. Eight ML models were applied to data ranked by the p-value (LP) of linear regression and the importance gain (XI) of XGboost. Five optimal features were selected using elastic net on the LP data for men, and twenty optimal features were selected using support vector machine on the XI data for women. Thus, the important features for predicting a potential decline in global cognitive function in older adults were successfully identified herein. The proposed ML approach could inspire future studies on the early detection and prevention of cognitive function decline in older adults.

Estimating Health-Related Quality of Life Based on Demographic Characteristics, Questionnaires, Gait Ability, and Physical Fitness in Korean Elderly Adults.

The elderly population in South Korea accounted for 15.5% of the total population in 2019. Thus, it is important to study the various elements governing the process of healthy aging. Therefore, this study investigated multiple prediction models to determine the health-related quality of life (HRQoL) in elderly adults based on the demographics, questionnaires, gait ability, and physical fitness. We performed eight physical fitness tests on 775 participants wearing shoe-type inertial measurement units and completing walking tasks at slower, preferred, and faster speeds. The HRQoL for physical and mental components was evaluated using a 36-item, short-form health survey. The prediction models based on multiple linear regression with feature importance were analyzed considering the best physical and mental components. We used 11 variables and 5 variables to form the best subset of features underlying the physical and mental components, respectively. We laid particular emphasis on evaluating the functional endurance, muscle strength, stress level, and falling risk. Furthermore, stress, insomnia severity, number of diseases, lower body strength, and fear of falling were taken into consideration in addition to mental-health-related variables. Thus, the study findings provide reliable and objective results to improve the understanding of HRQoL in elderly adults.

Bacterial Quality, Prevalence of Pathogens, and Molecular Characterization of Biofilm-Producing Staphylococcus aureus from Korean Dairy Farm Environments.

Raw milk acts as a mediator of major foodborne pathogenic bacterial infections. However, the sources of pathogens that contaminate milk are often unclear. This study assessed the prevalence of sanitary quality-indicating bacteria (total aerobic bacteria, psychrotrophic bacteria, coliform, and yeast/molds), including seven foodborne pathogens, in a dairy farm environment and processing plant in Korea. The microbiological analysis showed that a few sites, such as vat bottoms, room floors, drain holes, and niches, showed high microbial loads in most dairy farms. Based on quantitative microbial tests, Bacillus cereus was detected in three farms and Staphylococcus aureus was detected in only one farm. Among them, S. aureus JDFM SA01 isolated from a milk filter showed strong biofilm formation and toxicity to the host Caenorhabditis elegans. Subsequently, RNA-seq was performed to characterize the biofilm formation ability of S. aureus JDFM SA01. In biofilms, the significant upregulation of genes encoding microbial surface components and recognizing adhesive matrix molecules promotes adhesion might explain the increased viability and biomass of biofilms. This study provided insight into the prevalence of pathogenic bacteria and microbial contamination levels across dairy farms.