JAK2 is dispensable for maintenance of JAK2 mutant B-cell acute lymphoblastic leukemias.

Activating JAK2 point mutations are implicated in the pathogenesis of myeloid and lymphoid malignancies, including high-risk B-cell acute lymphoblastic leukemia (B-ALL). In preclinical studies, treatment of JAK2 mutant leukemias with type I JAK2 inhibitors (e.g., Food and Drug Administration [FDA]-approved ruxolitinib) provided limited single-agent responses, possibly due to paradoxical JAK2Y1007/1008 hyperphosphorylation induced by these agents. To determine the importance of mutant JAK2 in B-ALL initiation and maintenance, we developed unique genetically engineered mouse models of B-ALL driven by overexpressed Crlf2 and mutant Jak2, recapitulating the genetic aberrations found in human B-ALL. While expression of mutant Jak2 was necessary for leukemia induction, neither its continued expression nor enzymatic activity was required to maintain leukemia survival and rapid proliferation. CRLF2/JAK2 mutant B-ALLs with sustained depletion or pharmacological inhibition of JAK2 exhibited enhanced expression of c-Myc and prominent up-regulation of c-Myc target genes. Combined indirect targeting of c-Myc using the BET bromodomain inhibitor JQ1 and direct targeting of JAK2 with ruxolitinib potently killed JAK2 mutant B-ALLs.

Compressed Deep Learning to Classify Arrhythmia in an Embedded Wearable Device.

The importance of an embedded wearable device with automatic detection and alarming cannot be overstated, given that 15-30% of patients with atrial fibrillation are reported to be asymptomatic. These asymptomatic patients do not seek medical care, hence traditional diagnostic tools including Holter are not effective for the further prevention of associated stroke or heart failure. This is likely to be more so in the era of COVID-19, in which patients become more reluctant on hospitalization and checkups. However, little literature is available on this important topic. For this reason, this study developed efficient deep learning with model compression, which is designed to use ECG data and classify arrhythmia in an embedded wearable device. ECG-signal data came from Korea University Anam Hospital in Seoul, Korea, with 28,308 unique patients (15,412 normal and 12,896 arrhythmia). Resnets and Mobilenets with model compression (TensorFlow Lite) were applied and compared for the diagnosis of arrhythmia in an embedded wearable device. The weight size of the compressed model registered a remarkable decrease from 743 MB to 76 KB (1/10000), whereas its performance was almost the same as its original counterpart. Resnet and Mobilenet were similar in terms of accuracy, i.e., Resnet-50 Hz (97.3) vs. Mo-bilenet-50 Hz (97.2), Resnet-100 Hz (98.2) vs. Mobilenet-100 Hz (97.9). Here, 50 Hz/100 Hz denotes the down-sampling rate. However, Resnets took more flash memory and longer inference time than did Mobilenets. In conclusion, Mobilenet would be a more efficient model than Resnet to classify arrhythmia in an embedded wearable device.

The impact of overactive bladder on health-related quality of life in Korea: based on the results of a Korean Community Health Survey.

PURPOSE: This study aimed to assess the impact of overactive bladder on health-related quality of life (HRQoL) in a community-based sample of Korean population. METHODS: The data of adults aged 19 and over that who participated in the 2012 Korean Community Health Survey were analyzed. Overactive bladder severity was classified as normal, mild, moderate, or severe using the Overactive Bladder Symptom scores, and HRQoL was evaluated using EQ-5D-3L. Relations between HRQoL and the severities and symptoms of OAB were investigated. Sampling weighted adjusted multiple regression analysis was performed to determine the effect of OAB symptom severity on HRQoL. RESULTS: Of the 226,867 study subjects, 12,303 (5.4%) had OAB, and 552 (0.2%) had an OABSS of ≥ 12, indicating severe OAB. The problem -reporting rate significantly increased in all EQ-5D-3L dimensions as OAB severity increased. After adjusting for other variables, OAB severity had a significant effect on EQ-5D-3L index. Urge incontinence had greatest impact on quality of life. CONCLUSIONS: As the severity of OAB increased from mild to severe, quality of life decreased significantly. OAB was found to negatively affect HRQoL.

The frequency of impairments in everyday activities due to the overuse of the internet, gaming, or smartphone, and its relationship to health-related quality of life in Korea.

BACKGROUND: This study aimed to investigate the relationships between the frequency of impairments in daily activities due to the overuse of the Internet, gaming, or smartphones (IGS) and sociodemographic characteristics, social relationships (including family) & activities, psychosocial characteristics, health status, and health-related quality of life (HRQoL) of Korean adults. METHODS: Secondary data from the 2017 Community Health Survey, a large-scale sample survey conducted yearly in South Korea, were analyzed for 190,066 adults over 19 years of age. Three categories were created for impairment groups due to IGS overuse: No Impairment, Mild Impairment, and Moderate-to-Severe groups. And between-group differences were examined using a one-way ANOVA for health status measured with the EQ-5D-3 L and chi-square tests for all categorical dependent variables, which included sociodemographic characteristics, social relationships & activities, and psychosocial factors. The association between frequencies of daily activity impairments due to IGS overuse and the dependent variables were examined using a multivariate logistic regression analysis and a linear regression model. RESULTS: Approximately 21,345 (11.23%) of the 190,066 participants reported experiencing impairments in daily activities due to IGS overuse at least once in the previous year and the impairments were more severe in males than females. Participants experiencing impairments in daily activities contacted their friends a significantly higher number of times (4 times or more per month) and engaged in leisure activities more frequently (more than once per month) than those without impairments. There was also a significant positive relationship between IGS overuse and stress, depression, suicidal ideation, and suicide attempts. Among participants aged 19-64, impairments in daily activities due to IGS overuse were associated with a lower HRQoL. Conversely, for those aged 65 and over, mild and moderate-to-severe impairments due to IGS overuse were associated with a significantly higher HRQoL. CONCLUSIONS: Increased impairments in daily activities due to IGS overuse may negatively affect mental health. However, among older adults, the frequency of such impairments was positively associated with HRQoL. This finding could be considered to apply interventions with Internet usage or ICT devices for older adults to enhance their quality of life.

A cross sectional survey on health-related quality of life among parents of children with allergic symptoms using the EQ-5D-5L.

Object: This study aims to evaluate the HRQOL of parents of children with allergic diseases using the EQ-5D-5L. Methods: The subjects of the study were parents of children enrolled in primary schools and daycare centers. The EQ-5D-5L was self-administered in the sample population, and demographic and health information of their children were collected. We assessed the difference in EQ-5D-5L index and EQ-VAS of parents by the prevalence of allergic symptoms (wheezing, runny or blocked nose, and itchy rash) in their children in the past 12 months. In addition, we examined the difference in parents' EQ-5D-5L index and EQ-VAS score, based on the number of allergic symptoms of their children. Results: Of the 23,837 completed questionnaires, 22,904 were analyzed. There were significant differences in HRQOL between parents of children with and without allergic symptoms. There was a considerable difference in proportion of problem reporting in the "pain/discomfort" and "anxiety/depression" dimensions compared with the remaining dimensions of the EQ-5D-5L. Among three allergic symptoms, the HRQOL of parents of children with asthmatic symptoms was lowest at 0.936 on the EQ-5D-5L index and 79.3 on the EQ-VAS score. As the number of allergic symptoms of children increased, QOL of parents significantly decreased. Conclusions: Parents of children with allergic symptoms showed lower HRQOL than those parents whose children did not. The EQ-5D-5L instrument appeared to be useful to evaluate the HRQOL of parents of children with allergic diseases.

Health-related quality of life in adult males with lower urinary tract symptoms.

PURPOSE: To assess the status and impact of lower urinary tract symptoms (LUTS) on health-related quality of life (HRQoL) in a community-based sample of Korean adult males. METHODS: We analyzed the data of 101,606 adult males aged ≥ 19 years of age obtained during the 2011 Korean Community Health Survey. Subject data were assessed for LUTS and HRQoL using international prostate symptom scores, and EuroQol-five-dimensions three-level version (EQ-5D-3L) and EuroQol-visual analogue scale (EQ-VAS) scores. RESULTS: Of the 101,606 subjects, 53,323 (52.5%) reported having at least one LUTS and 3116 (3.1%) had an IPSS of ≥ 20, indicating severe LUTS. In those aged 19-39 years, 28.7% (8343/29,072) reported they had mild to severe LUTS. The prevalence of LUTS was high among those aged 40-59 years (47.7%), 60-79 years (80.5%), and ≥ 80 years (91.2%). In addition, EQ-5D-3L and EQ-VAS scores decreased as LUTS severity and frequency increased. CONCLUSIONS: Adult men of all ages with mild to severe LUTS have poorer health statuses and quality of life. Even among young males, LUTS severity and was found to negatively affect HRQoL.

Memory Self-Efficacy and Beliefs about Memory and Aging in Oldest-Old Adults in the Louisiana Healthy Aging Study (LHAS).

Background/Study Context. Adaptation to normative age-related declines in memory is an important but understudied aspect of successful aging. The purpose of the present study was to shed new light on memory self-efficacy and beliefs about memory and aging as two integral aspects of adult cognition with relevance to successful aging. METHODS: Young (19 to 27 years) and community-dwelling older adults (60 to 94 years) from the Louisiana Healthy Aging Study (LHAS) completed an adapted Memory Functioning Questionnaire (MFQ) which includes a memory self-efficacy subscale, the Memory Controllability Inventory (MCI), and the Aging Concerns Scale (ACS). RESULTS: Nonagenarians' self-reported memory and beliefs about memory and aging were of central interest. We compared their responses to three younger reference groups to examine hypothesized differences in self-reported memory and beliefs about memory and aging in very late life. Results yielded age effects for most of the MFQ and MCI subscales demonstrating more positive subjective views about memory functioning and control over memory for the young adults. Correlation and regression analyses were conducted to isolate factors that may be associated with memory self-efficacy. Age, symptoms of depression, and memory control beliefs accounted for approximately half of the variance in memory self-efficacy ratings. CONCLUSION: These data indicate that although memory self-efficacy may be age sensitive, we detected no differences in subjective views across the three older groups. Implications for cognitive adaptability and successful aging are considered.

Health-related quality of life by allergy symptoms in elementary school students.

BACKGROUND: Globally, allergic diseases are very common in childhood and may affect children's quality of life. This study aimed to explore health-related quality of life of elementary school students with allergy symptoms using the EQ-5D-Y and to examine the validity and feasibility of the EQ-5D-Y. METHODS: The study subjects were the students within 50 elementary schools which voluntarily participated in research project. In this sample population, the EQ-5D-Y questionnaire was self-administered by the students, and demographic and health information were collected from the student's parents. The parents' information was used to investigate the proportion of students with allergic symptoms (wheezing, runny or blocked nose, and itchy rash) in the past 12 months. In addition, we analyzed the correlation of symptom reporting and EQ-5D-Y including EQ-VAS. RESULTS: The overall return was 9117 responses, of which 198 (2.2%) lacked responses on the EQ-5D-Y dimension and 1258 (13.8%) on the VAS score. There were significant differences in symptom reporting in all EQ-5D-Y dimensions between groups with or without allergic symptoms. Particularly, there was a large difference in reporting rates in 'having pain or discomfort' and 'feeling worried, sad or unhappy' dimensions. As the number of allergic symptoms increased, in all dimensions also the problem reporting rate tended to increase. CONCLUSIONS: As expected, the presence of allergic symptoms is inversely correlated with the quality of life of children. The EQ-5D-Y instrument proved to be useful in terms of feasibility and construct validity in assessing the quality of life of Korean elementary school students.

The Gut Microbiota and Healthy Aging: A Mini-Review.

The gut microbiota shows a wide inter-individual variation, but its within-individual variation is relatively stable over time. A functional core microbiome, provided by abundant bacterial taxa, seems to be common to various human hosts regardless of their gender, geographic location, and age. With advancing chronological age, the gut microbiota becomes more diverse and variable. However, when measures of biological age are used with adjustment for chronological age, overall richness decreases, while a certain group of bacteria associated with frailty increases. This highlights the importance of considering biological or functional measures of aging. Studies using model organisms indicate that age-related gut dysbiosis may contribute to unhealthy aging and reduced longevity. The gut microbiome depends on the host nutrient signaling pathways for its beneficial effects on host health and lifespan, and gut dysbiosis disrupting the interdependence may diminish the beneficial effects or even have reverse effects. Gut dysbiosis can trigger the innate immune response and chronic low-grade inflammation, leading to many age-related degenerative pathologies and unhealthy aging. The gut microbiota communicates with the host through various biomolecules, nutrient signaling-independent pathways, and epigenetic mechanisms. Disturbance of these communications by age-related gut dysbiosis can affect the host health and lifespan. This may explain the impact of the gut microbiome on health and aging.

Molecular analysis of the hexon, penton base, and fiber-2 genes of Korean fowl adenovirus serotype 4 isolates from hydropericardium syndrome-affected chickens.

Fowl adenovirus serotype 4 (FAdV-4) is the causative agent of hydropericardium syndrome (HPS), a highly pathogenic disease in poultry. In the present study, hexon, penton base, and fiber-2 genes encoding major capsid proteins were analyzed in four FAdV-4 isolates from HPS-affected chickens in Korea. Nucleotide sequences of the entire hexon (2811 bases), penton base (1578 bases), and fiber-2 (1425 bases) genes from the Korean isolates were 97.5-99.3, 99.1-99.7, and 95.5-99.0 % identical, respectively, to those of foreign FAdV-4 isolates. In the N-terminal tail region of fiber-2, the KRP motif predicted to be the nuclear localization signal was identified in the Korean isolates, whereas KRP/A was detected in other isolates. The VYPF motif in fiber-2, which is known to interact with the penton base, was present in the same region of all FAdV-4 isolates that were compared. Amino acid variations in fiber-2 for HPS and non-HPS isolates revealed that D219 and T300 were conserved among ten HPS isolates from five countries, including Korea. T380 in fiber-2, previously found in HPS isolates, corresponded to A380 in the Korean isolates, indicating that T380 is not relevant for increased virulence. Phylogenetic analysis showed that the four Korean FAdV-4 isolates were more related to MX-SHP95, a Mexican FAdV-4 isolate of HPS origin, than to FAdV-4 isolates of Indian and Chinese origin, suggesting that the genetic relationship among FAdV-4 isolates is independent of geographic distribution. The molecular features of these genes will provide valuable information for vaccine development against HPS in the future.

Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians.

Energy expenditure decreases with age, but in the oldest-old, energy demand for maintenance of body functions increases with declining health. Uncoupling proteins have profound impact on mitochondrial metabolic processes; therefore, we focused attention on mitochondrial uncoupling protein genes. Alongside resting metabolic rate (RMR), two SNPs in the promoter region of UCP2 were associated with healthy aging. These SNPs mark potential binding sites for several transcription factors; thus, they may affect expression of the gene. A third SNP in the 3'-UTR of UCP3 interacted with RMR. This UCP3 SNP is known to impact UCP3 expression in tissue culture cells, and it has been associated with body weight and mitochondrial energy metabolism. The significant main effects of the UCP2 SNPs and the interaction effect of the UCP3 SNP were also observed after controlling for fat-free mass (FFM) and physical-activity related energy consumption. The association of UCP2/3 with healthy aging was not found in males. Thus, our study provides evidence that the genetic risk factors for healthy aging differ in males and females, as expected from the differences in the phenotypes associated with healthy aging between the two sexes. It also has implications for how mitochondrial function changes during aging.

Programmed Cell Death Genes Are Linked to Elevated Creatine Kinase Levels in Unhealthy Male Nonagenarians.

Declining health in the oldest-old takes an energy toll for the simple maintenance of body functions. The underlying mechanisms, however, differ in males and females. In females, the declines are explained by loss of muscle mass; but this is not the case in males, in whom they are associated with increased levels of circulating creatine kinase. This relationship raises the possibility that muscle damage rather than muscle loss is the cause of the increased energy demands of unhealthy aging in males. We have now examined factors that contribute to the increase in creatine kinase. Much of it (60%) can be explained by a history of cardiac problems and lower kidney function, while being mitigated by moderate physical activity, reinforcing the notion that tissue damage is a likely source. In a search for genetic risk factors associated with elevated creatine kinase, the Ku70 gene XRCC6 and the ceramide synthase gene LASS1 were investigated because of their roles in telomere length and longevity and healthy aging, respectively. Single nucleotide polymorphisms in these two genes were independently associated with creatine kinase levels. The XRCC6 variant was epistatic to one of the LASS1 variants but not to the other. These gene variants have potential regulatory activity. Ku70 is an inhibitor of the proapoptotic Bax, while the product of Lass1, ceramide, operates in both caspase-dependent and -independent pathways of programmed cell death, providing a potential cellular mechanism for the effects of these genes on tissue damage and circulating creatine kinase.

Estimation of minimally important differences in the EQ-5D and SF-6D indices and their utility in stroke.

BACKGROUND: The aim of the present study was to estimate minimally important differences (MIDs) in EQ-5D and SF-6D indices and to explore the responsiveness of EQ-5D and SF-6D indices in stroke. METHODS: We used observational longitudinal survey data of EQ-5D and SF-36 that were administered to stroke patients at baseline and at 10 months. A range of MIDs for both indexes was estimated using anchor-based approaches. The modified Rankin scale and the Barthel index were used as an anchor. RESULTS: The MID estimates for EQ-5D ranged from 0.08 to 0.12 and those for SF-6D ranged from 0.04 to 0.14 in stroke patients. The MID values for these two utility measures differed in absolute magnitude, as the SF-6D index has wider range that that of the EQ-5D index. CONCLUSIONS: The MID values for these two utility measures differed in absolute magnitude, as the SF-6D index has wider range that that of the EQ-5D index. These MID estimates may assist the interpretation of health related quality of life assessments related to health care intervention in stroke patients.

Dynamic nucleotide-dependent interactions of cysteine- and histidine-rich domain (CHORD)-containing Hsp90 cochaperones Chp-1 and melusin with cochaperones PP5 and Sgt1.

Mammals have two cysteine- and histidine-rich domain (CHORD)-containing Hsp90 cochaperones, Chp-1 and melusin, which are homologs of plant Rar1. It has been shown previously that Rar1 CHORD directly interacts with ADP bound to the nucleotide pocket of Hsp90. Here, we report that ADP and ATP can bind to Hsp90 cochaperones Chp-1 and PP5, inducing their conformational changes. Furthermore, we demonstrate that Chp-1 and melusin can interact with cochaperones PP5 and Sgt1 and with each other in an ATP-dependent manner. Based on the known structure of the Rar1-Hsp90 complex, His-186 has been identified as an important residue of Chp-1 for ADP/ATP binding. His-186 is necessary for the nucleotide-dependent interaction of Chp-1 not only with Hsp90 but also with Sgt1. In addition, Ca(2+), which is known to bind to melusin, enhances the interactions of melusin with Hsp90 and Sgt1. Furthermore, melusin acquires the ADP preference for Hsp90 binding in the presence of Ca(2+). Our newly discovered nucleotide-dependent interactions between cochaperones might provide additional complexity to the dynamics of the Hsp90 chaperone system, also suggesting potential Hsp90-independent roles for these cochaperones.

APOE ϵ4, rated life experiences, and affect among centenarians.

OBJECTIVES: The purpose of this study was to assess the relationship between apolipoprotein E (APOE), life events and engagement, and subjective well-being (as measured by positive and negative affect) among centenarians. Based on the life stress paradigm, we predicted that higher levels of stress would allow APOE to influence positive and negative affect. METHOD: 196 centenarians and near-centenarians (98 years and older) of the Georgia Centenarian Study participated in this research. The APOE, positive and negative affect, the number of recent (last 2 years) and lifelong (more than 20 years prior to testing) events, as well as a number of life engagement tasks were assessed. RESULTS: Results suggested that centenarians carrying the APOE ϵ4 allele rated lower in positive affect, the number of lifelong events, and in engaged lifestyle, when compared to centenarians without the APOE ϵ4 allele (t = 3.43, p < .01; t = 3.19, p < .01; and t = 2.33, p < .05, respectively). Blockwise multiple regressions indicated that the APOE ϵ4 predicted positive but not negative affect after controlling for demographics. Gene-environment interactions were obtained for the APOE ϵ4 and lifelong events, suggesting that carriers of the APOE ϵ4 allele had higher scores of negative affect after having experienced more events, whereas noncarriers had reduced negative affect levels after having experienced more events. CONCLUSION: APOE ϵ4 is directly related to positive affect and is related to negative affect in interaction with life events.

SeqAFNet: A Beat-Wise Sequential Neural Network for Atrial Fibrillation Classification in Adhesive Patch-Type Electrocardiographs.

Due to their convenience, adhesive patch-type electrocardiographs are commonly used for arrhythmia screening. This study aimed to develop a reliable method that can improve the classification performance of atrial fibrillation (AF) using these devices based on the 2020 European Society of Cardiology (ESC) guidelines for AF diagnosis in clinical practice. We developed a deep learning model that utilizes RR interval frames for precise, beat-wise classification of electrocardiogram (ECG) signals. This model is specifically designed to sequentially classify each R peak on the ECG, considering the rhythms surrounding each beat. It features a two-stage bidirectional Recurrent Neural Network (RNN) with a many-to-many architecture, which is particularly optimized for processing sequential and time-series data. The structure aims to extract local features and capture long-term dependencies associated with AF. After inference, outputs which indicating either AF or non-AF, derived from various temporal sequences are combined through an ensembling technique to enhance prediction accuracy. We collected AF data from a clinical trial that utilized the MEMO Patch, an adhesive patch-type electrocardiograph. When trained on public databases, the model demonstrated high accuracy on the patch dataset (accuracy: 0.986, precision: 0.981, sensitivity: 0.979, specificity: 0.992, and F1 score: 0.98), maintaining consistent performance across public datasets. SeqAFNet was robust for AF classification, making it a potential tool in real-world applications.

Large-Scale Field Trials of an Eimeria Vaccine Induce Positive Effects on the Production Index of Broilers.

Live coccidiosis vaccines have mainly been used to reduce Eimeria species infection, which is considered the most economically important disease in the poultry industry. Evaluation data on vaccine effectiveness through large-scale field experiments are lacking, especially in broilers. Thus, the effectiveness of a commercial coccidiosis vaccine was evaluated in approximately 900,000 chicks reared on three open-broiler farms where coccidiosis is prevalent. The vaccine's effectiveness after vaccination of 1-day-old chicks was monitored using three parameters (lesion score, fecal oocyst shedding, and production index, PI) in nine trials performed three times on each farm. Lesion scores were confirmed in three different areas of the intestine because the vaccine contained four Eimeria species. The average lesion scores were 0.36 to 0.64 in the duodenal region, 0.30 to 0.39 in the jejuno-ileal region, and 0.18 to 0.39 in the cecal region. The average fecal oocyst shedding rate ranged from 19,766 to 100,100 oocysts per gram, showing large variations depending on farms and buildings within the farm. Compared with the PI of the previous 9-10 trials on each farm, the PI increased by 2.45 to 23.55. Because of the potential for perturbation of the fecal microbiota by live coccidiosis vaccines, the fecal microbiota was investigated using 16S rRNA microbial profiling. Although the ß-diversity was significantly different in distribution and relative abundance among farms (PERMANOVA, pseudo-F = 4.863, p = 0.009), a Kyoto Encyclopedia of Genes and Genomes pathway analysis found no significant bacterial invasion of the epithelial cell pathway across farms. This large-scale field trial of a live Eimeria vaccine indicates that coccidiosis vaccines can have meaningful effects on the poultry industry and could be used as an alternative to the prophylactic use of anticoccidial drugs under field conditions.

SE-ResNet-ViT Hybrid Model for Noise Classification in Adhesive Patch-type Wearable Electrocardiographs.

In purpose of screening arrhythmia, wearable adhesive patch-type electrocardiographs that can measure electrocardiogram continuously for 14 days have been replacing the 24-hour Holter monitor. The reason for that is the patch-type electrocardiograph being smaller and lighter than the Holter monitor, making it more convenient for patients to coexist with in their daily lives. However, this type of electrocardiograph generates a lot of noise signals due to movements during various physical activities and extended wear time.While analyzing electrocardiograms automatically using software, noise signals make the analysis difficult and they may be misclassified as arrhythmia signals. These misclassified signals require a lot of effort and time from clinical technicians to reclassify them as noise. To resolve this problem, this study hypothesized that a deep learning algorithm could be used to screen noise signals. We used 7,467 noise signals and 15,638 ECG signals collected from arrhythmia patients and healthy people. The signals were divided into 10 seconds segments and labeled by cardiologists. We split the data into training and test datasets, ensuring no patient overlap.A hybrid noise classification model, Squeeze and Excitation - Residual Network - Vision Transformer (SE-ResNet-ViT) was developed using the training and validation datasets with an 8:2 ratio. We evaluated the performance of the model using a test dataset. The best F1 score was 0.964. The proposed model can effectively screen for noise signals and potentially reducing the time and effort required by clinical technicians.

Multilayer Coating with Red Ginseng Dietary Fiber Improves Intestinal Adhesion and Proliferation of Probiotics in Human Intestinal Epithelial Models.

To exert their beneficial effects, it is essential for the commensal bacteria of probiotic supplements to be sufficiently protected as they pass through the low pH environment of the stomach, and effectively colonize the intestinal epithelium downstream. Here, we investigated the effect of a multilayer coating containing red ginseng dietary fiber, on the acid tolerance, and the adhesion and proliferation capacities of three Lactobacillus strains (Limosilactobacillus reuteri KGC1901, Lacticaseibacillus casei KGC1201, Limosilactobacillus fermentum KGC1601) isolated from Panax ginseng, using HT-29 cells, mucin-coated plates, and human pluripotent stem cell-derived intestinal epithelial cells as in vitro models of human gut physiology. We observed that the multilayer-coated strains displayed improved survival rates after passage through gastric juice, as well as high adhesion and proliferation capacities within the various gut epithelial systems tested, compared to their uncoated counterparts. Our findings demonstrated that the multilayer coat effectively protected commensal microbiota and led to improved adhesion and colonization of intestinal epithelial cells, and consequently to higher probiotic efficacy.

Upregulation of extracellular proteins in a mouse model of Alzheimer's disease.

Various risk factors of Alzheimer's disease (AD) are known, such as advanced age, possession of certain genetic variants, accumulation of toxic amyloid-ß (Aß) peptides, and unhealthy lifestyle. An estimate of heritability of AD ranges from 0.13 to 0.25, indicating that its phenotypic variation is accounted for mostly by non-genetic factors. DNA methylation is regarded as an epigenetic mechanism that interfaces the genome with non-genetic factors. The Tg2576 mouse model has been insightful in AD research. These transgenic mice express a mutant form of human amyloid precursor protein linked to familial AD. At 9-13 months of age, these mice show elevated levels of Aß peptides and cognitive impairment. The current literature lacks integrative multiomics of the animal model. We applied transcriptomics and DNA methylomics to the same brain samples from ~ 11-month-old transgenic mice. We found that genes involved in extracellular matrix structures and functions are transcriptionally upregulated, and genes involved in extracellular protein secretion and localization are differentially methylated in the transgenic mice. Integrative analysis found enrichment of GO terms related to memory and synaptic functionability. Our results indicate a possibility of transcriptional modulation by DNA methylation underlying AD neuropathology.