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Abstract Background A 21-day experiment was conducted to test the hypothesis that Ca requirements to maximize growth performance expressed as the standardized total tract digestible (STTD) Ca to STTD P ratio is less than 1.40:1. The second hypothesis was that increasing dietary Ca increases plasma Ca concentration and downregulates abundance of genes related to Ca absorption (TRPV6, S100G, and ATP2B1) in the duodenum, and tight junction proteins (OCLN, CLDN1, and ZO1) in the duodenum and ileum. Methods Twenty corn-soybean meal diets were formulated using a 4 × 5 factorial design with diets containing 0.16%, 0.33%, 0.42%, or 0.50% STTD P, and 0.14%, 0.29%, 0.44%, 0.59%, or 0.74% STTD Ca. Six hundred and forty pigs (initial weight: 11.1 ± 1.4 kg) were allotted to 20 diets and 5 blocks in a randomized complete block design. On day 21, weights of pigs and feed left in feeders were recorded and blood, duodenal tissue, ileal mucosa, and the right femur were collected from 1 pig per pen. Abundance of mRNA was determined in duodenal and ileal tissue via quantitative RT-PCR. Data were analyzed using a response surface model. Results The predicted maximum ADG (614 g), G:F (0.65), and bone ash (11.68 g) was obtained at STTD Ca:STTD P ratios of 1.39:1, 1.25:1, and 1.66:1, respectively, when STTD P was provided at the requirement (0.33%). If dietary STTD P was below the requirement, increasing dietary Ca resulted in reduced (P

A number of feed additives are marketed to assist in boosting the pigs' immune system, regulate gut microbiota, and reduce negative impacts of weaning and other environmental challenges. The most commonly used feed additives include acidifiers, zinc and copper, prebiotics, direct-fed microbials, yeast products, nucleotides, and plant extracts. Inclusion of pharmacological levels of zinc and copper, certain acidifiers, and several plant extracts have been reported to result in improved pig performance or improved immune function of pigs. It is also possible that use of prebiotics, direct-fed microbials, yeast, and nucleotides may have positive impacts on pig performance, but results have been less consistent and there is a need for more research in this area. Keywords: Acidifiers, Direct-fed microbials, Minerals, Plant extracts, Prebiotics, Pigs

Despite many recent studies on non-alcoholic fatty liver disease (NAFLD) therapeutics, the optimal treatment has yet to be determined. In this unfinished project, we combined secondary metabolites (SMs) from the gut microbiota (GM) and Hordeum vulgare (HV) to investigate their combinatorial effects via network pharmacology (NP). Additionally, we analyzed GM or barley – signalling pathways – targets – metabolites (GBSTMs) in combinatorial perspectives (HV, and GM). A total of 31 key targets were analysed via a protein-protein interaction (PPI) network, and JUN was identified as the uppermost target in NAFLD. On a bubble plot, we revealed that apelin signalling pathway, which had the lowest enrichment factor antagonize NAFLD. Holistically, we scrutinized GBSTM to identify key components (GM, signalling pathways, targets, and metabolites) associated with the Apelin signalling pathway. Consequently, we found that the primary GMs (Eubacterium limosum, Eggerthella sp. SDG-2, Alistipes indistinctus YIT 12060, Odoribacter laneus YIT 12061, Paraprevotella clara YIT 11840, Paraprevotella xylaniphila YIT 11841) to ameliorate NAFLD. The molecular docking test (MDT) suggested that tryptanthrin-JUN is an agonist, conversely, dihydroglycitein-HDAC5, 1,3-diphenylpropan-2-ol-NOS1, and (10[(Acetyloxy)methyl]-9-anthryl)methyl acetate-NOS2, which are antagonistic conformers in the apelin signalling pathway. Overall, these results suggest that combination therapy could be an effective strategy for treating NAFLD.

Osteocytes are located in the lacunae of fluid-filled bone and communicate with neighboring or distant cells by secreting small extracellular vesicles (sEVs) and growth factors as well as via dendrite–dendrite direct connections. However, the mechanism regulating sEV production in osteocytes is yet to be elucidated. In this study, we investigated sEV production and its underlying mechanism in osteocytes cultured on a three dimensional (3D) scaffold. We employed a perfusion system to apply shear stress stimulation to MLO-Y4 cells cultured on a 3D biphasic calcium phosphate (BCP) scaffold and analyzed sEV production and gene expression using RNA sequencing. We found that the expression of genes associated with sEV biogenesis and the secretory pathway were enhanced by fluid shear stress in MLO-Y4 cells cultured on a 3D BCP scaffold. In particular, fluid shear stress induced the expression of Ank, a pyrophosphate transporter, in 3D-cultured MLO-Y4 cells. The role of Ank in sEV production was further examined. Probenecid, an Ank inhibitor, significantly suppressed shear stress-induced sEV production, whereas Ank cDNA overexpression stimulated it. The inhibition of shear stress-induced sEV production by probenecid was recovered by the exogenous addition of pyrophosphate to MLO-Y4 cells. These findings suggest that shear stress-mediated sEV production in 3D-cultured osteocytes is regulated by extracellular pyrophosphate transported by Ank.

Abstract Guidelines encouraging social distancing, limited outings, and remote work due to COVID-19 have increased sedentary periods and reduced levels of physical activity. These habits increase the risk of metabolic diseases, obesity, cardiovascular disease, and diabetes mellitus. The World Health Organization recommends muscle-strengthening exercises as well as regular physical activity to promote overall health. This study investigates the effect of a wearable hip exoskeleton on muscle activity and heart rate during anaerobic exercise in 40 healthy adults (mean age of 40.00 ± 11.51 years; n = 20 females). Bot Fit, a wearable hip-type robotic exoskeleton, was developed by Samsung Electronics Co., Ltd. (Suwon, Republic of Korea) to enhance the effects of both aerobic and anaerobic exercise. All study participants performed a fitness exercise protocol, including knee-ups, good mornings, squats, mountain climbs, kick-backs, reverse lunges, and split jacks, with and without a Bot Fit. To evaluate the effect of anaerobic exercise with the Bot Fit, muscle activity and heart rate were measured during fitness exercises with and without a Bot Fit. Measured muscles were the rectus abdominis (RA), erector spinae (ES), rectus femoris (RF), vastus lateralis (VL), vastus medialis (VM), biceps femoris (BF), tibialis anterior (TA), gastrocnemius medialis (GCM), and gluteus maximus (GM). During anaerobic exercises with the Bot Fit, there was a significant increase in muscle activity compared to exercising without the Bot Fit. Muscle activity increased significantly in the RA, RF, VL, BF and TA muscles during knee-ups; in the ES, BF, and GM during good mornings; in the RF, VL, VM, BF, and GM during squats; in RA, RF, VL, VM, and GM during mountain climbs; in the RA and BF during kick-backs; in the RF, BF, and GCM during reverse lunges; and in the RF and VL during split jacks (p

Background/Aims: Ursodeoxycholic acid (UDCA) is the only well-established and widely used agent for dissolving gallstones. Epidemiological and animal studies have suggested potential therapeutic benefits of n-3 polyunsaturated fatty acids (PUFA) for dissolving cholesterol gallstones. We evaluated whether adding PUFA to UDCA improves gallstone dissolution in patients with cholesterol gallstones. Methods: This randomized, prospective, preliminary clinical trial compared the efficacy and safety of UDCA plus PUFA combination therapy (combination group) with those of UDCA monotherapy (monotherapy group). The inclusion criteria were a gallstone diameter ≤15 mm on ultrasonography, radiolucent stones on plain X-ray, and no to mild symptoms. Gallstone dissolution rates, response rates, and adverse events were evaluated. Results: Of the 59 screened patients, 45 patients completed treatment (24 and 21 in the monotherapy and combination groups, respectively). The gallstone dissolution rate tended to be higher in the combination group than in the monotherapy group (45.7% vs 9.9%, p=0.070). The radiological response rate was also significantly higher in the combination group (90.5% vs 41.7%, p=0.007). In both groups, dissolution and response rates were higher in patients with gallbladder sludge than in those with distinct stones. Four adverse events (two in each group) were observed, none of which were study drug-related or led to drug discontinuation. The incidence of these adverse events was similar in both groups (combination vs monotherapy: 9.5% vs 8.3%, p=0.890). Conclusions: UDCA plus PUFA therapy dissolves cholesterol gallstones more effectively than UDCA monotherapy, without significant complications. Further prospective, large-scale studies of this combination therapy are warranted.

Background/Aims With the global increase in patients with solid malignancies, it is helpful to understand the outcomes of intensive care unit (ICU) admission for these patients. This study evaluated the risk factors for ICU mortality and the short-and long-term outcomes in patients with solid malignancies who had unplanned ICU admission. Methods This retrospective cohort study included patients with solid malignancies treated at the medical ICU of a single tertiary center in South Korea between 2016 and 2022. Results Among the 955 patients, the ICU mortality rate was 23.5%. Lung cancer was the most common cancer type (34.2%) and was significantly associated with increased ICU mortality (odd ratio [OR] 1.58, p = 0.030). Higher Sequential Organ Failure Assessment scores at ICU admission (OR 1.11, p < 0.001), the need for mechanical ventilation (OR 6.74, p < 0.001), or renal replacement therapy during the ICU stay (OR 2.49, p < 0.001) were significantly associated with higher ICU mortality. The 1-year survival rate after ICU admission was 29.3%, with a median survival of 37 days for patients requiring mechanical ventilation, and 23 days for patients requiring renal replacement therapy. Conclusions This study showed that critically ill patients with solid malignancies had poor 1-year survival despite relatively low ICU mortality. These findings highlight the need for careful consideration of ICU admission in patients with solid malignancy, and decision-making should be based on an understanding of the expected short- and long-term prognosis of ICU admission after an informed discussion among patients, families, and physicians.

Abstract This study investigates the impact of environmental factors on the quality changes of mackerel (Scomber japonicus), a globally significant fish species valued for its high nutritional content, especially its unsaturated fatty acids and proteins. In South Korea, marine products like mackerel undergo auction, sorting, packaging, and transportation. Assessing the fish freshness and quality during these processes, before it reaches consumers, is crucial. This research aimed to track the changes in mackerel quality indicators after the auction and correlate them with the environmental factors affecting transportation. Using a transportation model established for both summer and winter, mackerel samples were categorized by their weight (200 and 300 g). Results show poorer quality indicators in summer compared to winter, particularly in the 200 g group. Microbiological indicators such as the total viable count (0.923) and total coliforms (0.958) were most strongly correlated with the season, whereas the lipid oxidation indicators acid value (0.627) and peroxide value (0.536) were moderately correlated with the season. Interestingly, the wider standard deviation distribution observed in summer suggests that individual mackerel characteristics may influence the degree of quality changes. These findings offer insights into mackerel quality fluctuations during auction and transportation, aiding in future efforts to maintain seafood quality amidst climate change.

Noise reduction in low-dose positron emission tomography (PET) is a well-researched topic aimed at reducing patient radiation doses and improving diagnosis. Software-based noise reduction mainly improves the contrast between regions by reducing the variation of the acquired image. However, it should be performed under appropriate parameters to reduce discrimination. We propose a method that derives optimal noise-reduction parameters using the multi-scale structural similarity index measure and visual information fidelity, which are metrics for image quality assessment. Simulation and experimental studies demonstrated the viability of the proposed algorithm. The contrast-to-noise ratio value of the denoised reconstruction slice, which was used as the optimal parameter, increased approximately three times compared to that of the low-dose slice while preserving the resolution. The results indicate that the proposed method successfully predicted the parameters according to the noise-reduction algorithm and PET system conditions in the sinogram domain. The proposed algorithm should help prevent misdiagnosis and provide standardized medical images for clinical application by performing appropriate noise reduction.

The prevalence of highly pathogenic avian influenza (HPAI) A(H5N1) viruses has increased in wild birds and poultry worldwide, and concomitant outbreaks in mammals have occurred. During 2023, outbreaks of HPAI H5N1 virus infections were reported in cats in South Korea. The H5N1 clade 2.3.4.4b viruses isolated from 2 cats harbored mutations in the polymerase basic protein 2 gene encoding single amino acid substitutions E627K or D701N, which are associated with virus adaptation in mammals. Hence, we analyzed the pathogenicity and transmission of the cat-derived H5N1 viruses in other mammals. Both isolates caused fatal infections in mice and ferrets. We observed contact infections between ferrets, confirming the viruses had high pathogenicity and transmission in mammals. Most HPAI H5N1 virus infections in humans have occurred through direct contact with poultry or a contaminated environment. Therefore, One Health surveillance of mammals, wild birds, and poultry is needed to prevent potential zoonotic threats.

Background Endothelial activation and stress index (EASIX) reflects endothelial dysfunction or damage. Because endothelial dysfunction is one of the key mechanisms, a few studies have shown the clinical usefulness of original and age-adjusted EASIX (age-EASIX) in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical utility of age-EASIX in predicting intensive care unit (ICU) mortality in critically ill patients with COVID-19 in South Korea. Methods Secondary analysis was performed using clinical data retrospectively collected from 22 nationwide hospitals in South Korea between January 1, 2020, and August 31, 2021. Patients were at least 19 years old and admitted to the ICU for severe COVID-19, demanding at least high-flow nasal cannula oxygen therapy. EASIX [lactate dehydrogenase (U/L)×creatinine (mg/dL)/platelet count (109 cells/L)] and age-EASIX (EASIX×age) were calculated and log2-transformed. Results The mean age of 908 critically ill patients with COVID-19 was 67.4 years with 59.7% male sex. The mean log2 age-EASIX was 7.38±1.45. Non-survivors (n=222, 24.4%) in the ICU had a significantly higher log2 age-EASIX than of survivors (8.2±1.52 vs. 7.1±1.32, p

Abstract Electrical cardioversion (ECV) a widely utilized intervention for persistent atrial fibrillation (AF) aimed at restoring sinus rhythm. However, ECV can be ineffective, raising questions about subsequent treatment options. This study aimed to compare the outcomes of non-ablation therapy versus ablation therapy following unsuccessful ECV. A total of 125 consecutive patients with persistent AF who underwent unsuccessful ECV between November 2017 and August 2023 was included in this retrospective analysis. Of these, 51.2% received only medical therapy (non-ablation therapy group, n = 64), while 48.8% underwent AF ablation (ablation therapy group, n = 61). Various ablation methods were employed, including catheter and thoracoscopic ablation. Ablation therapy was associated with significantly better AF-free survival compared to non-ablation therapy [hazard ratio (HR), 0.37; 95% confidence interval (CI) 0.22–0.61; p 5 year (HR 1.51; 95% CI 0.930–2.437; p = 0.10), BMI ≤ 25 kg/m2 (HR 1.61; 95% CI 1.004–2.581; p = 0.05) and diabetes (HR 2.38; 95% CI 0.902–6.266; p = 0.08) were considerable as predictor of AF recurrence. Ablation therapy following unsuccessful ECV was associated with maintaining sinus rhythm, regardless of the specific ablation method utilized.

Abstract Recently, an investigation into preventive measures for coronavirus disease 2019 (COVID-19) has garnered considerable attention. Consequently, strategies for the proactive prevention of viral pathogens have also attracted significant interest in the field of wearable devices and electronic textiles research, particularly due to their potential applications in personal protective equipment. In this study, we introduce smart textiles designed with optimized piezoelectric devices that exhibit antifouling performance against microorganisms and actively inactivate viruses. These active-type smart textiles, which incorporate advanced lead zirconate titanate (PZT) ceramics, a stretchable interconnector array, and polymeric fabric, demonstrate effective antifouling capabilities, detaching approximately 90% of Escherichia coli and 75% of SARS-CoV-2. Furthermore, they inactivate viruses, releasing ~26.8 ng of N protein from ruptured SARS-CoV-2, using ultrasonic waves within the wearable platform. Experimental results show that piezoelectric smart textiles significantly reduce the spread of COVID-19 by leveraging the electrical and acoustic properties of PZT ceramics.

Abstract Triple-negative breast cancer (TNBC), the most aggressive subtype, presents a critical challenge due to the absence of approved targeted therapies. Hence, there is an urgent need to identify effective therapeutic targets for this condition. While epidermal growth factor receptor (EGFR) is prominently expressed in TNBC and recognized as a therapeutic target, anti-EGFR therapies have yet to gain approval for breast cancer treatment due to their associated side effects and limited efficacy. Here, we discovered that intercellular adhesion molecule-1 (ICAM-1) exhibits elevated expression levels in metastatic breast cancer and serves as a pivotal binding adaptor for EGFR activation, playing a crucial role in malignant progression. The activation of EGFR by tumor-expressed ICAM-1 initiates biased signaling within the JAK1/STAT3 pathway, consequently driving epithelial-to-mesenchymal transition and facilitating heightened metastasis without influencing tumor growth. Remarkably, ICAM-1-neutralizing antibody treatment significantly suppressed cancer metastasis in a breast cancer orthotopic xenograft mouse model. In conclusion, our identification of ICAM-1 as a novel tumor intrinsic regulator of EGFR activation offers valuable insights for the development of TNBC-specific anti-EGFR therapies.

Abstract Background Schizophrenia is a complex neuropsychiatric disorder with various etiologic factors. Aberrant levels of neurotransmitters or growth factors such as dopamine, serotonin, and BDNF have been shown to cause cognitive impairment in schizophrenia. Recently, the gut microbiome has also been suggested as a factor in the development of the disorder. To explore this potential link, we conducted a pilot study to examine the relationship between the gut microbiome and plasma levels of neurotransmitters and growth factors in schizophrenia. Shotgun metagenome sequencing of total RNA from fecal samples were used to profile the gut microbiome of schizophrenia patients (SCZ) and healthy controls (HC). The MetaPhlAn2 and HUMaN2 pipelines were used for bioinformatic analyses. ELISA was used to measure the plasma levels of dopamine, serotonin, and BDNF. Spearman’s rank correlation coefficient was used for correlation analysis. Results We found that butyrate-producing bacteria were enriched in HC, whereas succinate-producing bacteria, namely Phascolarctobacterium succinatutens and Paraprevotella clara, were enriched in SCZ. The gut microbiota of SCZ was enriched in lipid biosynthesis pathways related to bile-resistant bacteria, whereas phospholipid pathways linked with butyrate-producing bacteria were enriched in HC. Alistipes indistinctus, Dorea longicatena, and Roseburia inulinivorans were negatively correlated with dopamine levels. Roseburia intestinalis and Parabacteroides goldsteini were negatively correlated with serotonin and BDNF levels, respectively. We found a significant correlation between dopamine and serotonin levels, and the super-pathway of purine deoxyribonucleoside degradation. Conclusions This study provides further support that gut microbiota could modulate neurotransmitter levels. The results suggest that gut microbiome-targeted therapies may help to rebalance neurotransmitter levels, offering new hope for the treatment of schizophrenia.

Abstract Introduction Physical inactivity and sedentary behavior both increase the risk of chronic disease and mortality. Regular participation in physical activity and reducing sedentary behavior play important roles in maintaining physical health and disease prevention. Objective The purpose of this study was to investigate the effect of programed walking exercise using a wearable hip exoskeleton, Bot Fit on muscle strength, muscle effort, and the kinematics of the pelvis in younger adults. Methods We designed three parallel experimental conditions and randomly assigned participants to one of three groups: those assigned to exercise using an interval program of Bot Fit (interval group), those who used a power program of Bot Fit (power group), and a control group who exercised without Bot Fit. A total of 45 young adults participated in 18 exercise-intervention sessions over six weeks, and all participants were assessed at two time points: before and after the 18 exercise sessions. Each assessment evaluated muscle strength, muscle effort, and the kinematics of the pelvis during walking. In addition, the number of steps, distance, energy expenditure, and heart rate for 30 min during the exercise sessions were recorded. Results A significant increase in the maximum voluntary contraction (MVC) of the left biceps femoris (BF) was evident in the interval group, while significant changes in the MVC of the bilateral BF were seen in the power group after Bot Fit exercise. A significant decrease of muscle effort in the right BF in the interval group and right lumbar erector spinae and bilateral BF in the power group were also observed. In addition, the symmetry index of pelvic tilt significantly improved in the interval group, and greater exercise volume and intensity in both the interval and power groups compared with the control group were confirmed as measured by the number of steps, distance, energy expenditure, and heart rate. Conclusions The results of this study confirmed the beneficial effect of programed walking exercise using the Bot Fit on muscle strength of trunk and lower extremities, muscle effort, and pelvic movement symmetry in younger adults. Personalized exercise programs can be provided for younger adults using various resistance or assistance modes of robotic device with the Bot Fit. Trial Registration ClinicalTrials.gov, NCT05862077. Registered 22 March 2022, https://register.clinicaltrials.gov/ .

Abstract Although the efficacy of trastuzumab deruxtecan (T-DXd) against HER2-positive gastric cancers (GCs) has driven its clinical application, the precise mechanisms governing its immunomodulatory role remain unclear. In this study, we examined the immune-related mechanisms of action of T-DXd in GC cells. T-DXd exhibited potent antitumor effects in GC cells across diverse HER2 expression levels by inducing DNA damage and apoptosis. Activation of the DNA damage response by T-DXd led to increased PD-L1 expression. RNA-Seq analysis revealed that T-DXd modulated immune-related pathways, resulting in the upregulation of genes associated with inflammation and IFN signaling. Importantly, T-DXd activated the cGAS-STING pathway, inducing an IFN-I response in HER2-positive GC cells. Furthermore, T-DXd activated dendritic cells via the cancer cell-intrinsic cGAS-STING-IFN axis and enhanced PBMC-mediated tumor cell killing by activating CD8+ T cells. These findings provide valuable insights into the role of the cytosolic DNA sensing pathway in the action of T-DXd and offer a compelling rationale for combining T-DXd with immune checkpoint blockade therapies in GC treatment.

Pseudoprogression of malignancy in patients treated with systemic immunotherapy is a well- recognised phenomenon and has also been seen in patients treated with combined chemoimmunotherapy. Neoadjuvant chemoimmunotherapy prior to surgery is a relatively new treatment strategy for the management of many malignancies. We report the case of a patient who was suspected to have primary lung squamous cell carcinoma progression following neoadjuvant chemoimmunotherapy. Tissue histopathology from biopsies demonstrated granulomatous sarcoid-like inflammation rather than progression or metastatic disease. The patient proceeded to have successful surgical clearance of residual tumour. Significantly, failure to suspect granulomatous reactions and pseudoprogression has profound influence on the trajectory of patient care, such as, the potential for patients to miss out on curative surgery. In this case report and review of the literature, we evaluate the role of pseudoprogression and the need for radiologists to be aware of this phenomenon so that they do not mistakenly report new metastases and derail the treatment paradigm for patients with curable malignant conditions.

Abstract Background Diets with high inclusion of corn co-products such as corn fermented protein (CFP) may contain excess Leu, which has a negative impact on feed intake and growth performance of pigs due to increased catabolism of Val and Ile and reduced availability of Trp in the brain for serotonin synthesis. However, we hypothesized that the negative effect of using CFP in diets for weanling pigs may be overcome if diets are fortified with crystalline sources of Val, Trp, and (or) Ile. Methods Three hundred and twenty weanling pigs were randomly allotted to one of 10 dietary treatments in a completely randomized design, with 4 pigs per pen and 8 replicate pens per treatment. A corn-soybean meal diet and 2 basal diets based on corn and 10% CFP or corn and 20% CFP were formulated. Seven additional diets were formulated by fortifying the basal diet with 20% CFP with Ile, Trp, Val, Ile and Val, Ile and Trp, Trp and Val, or Ile, Trp and Val. A two-phase feeding program was used, with d 1 to 14 being phase 1 and d 15 to 28 being phase 2. Fecal scores were recorded every other day. Blood samples were collected on d 14 and 28 from one pig per pen. On d 14, fecal samples were collected from one pig per pen in 3 of the 10 treatments to determine volatile fatty acids, ammonium concentration, and microbial protein. These pigs were also euthanized and ileal tissue was collected. Results There were no effects of dietary treatments on any of the parameters evaluated in phase 1. Inclusion of 10% or 20% CFP in diets reduced (P

Abstract Background Effective interventions for overall healthy subjects with mild cognitive impairment are currently limited. Choline alphoscerate (alpha glyceryl phosphorylcholine, αGPC) is a choline-containing phospholipid used to treat cognitive function impairments in specific neurological conditions. This study aimed to investigate the efficacy and safety of αGPC in individuals diagnosed with mild cognitive impairment. Methods In this multicenter, randomized, placebo-controlled trial, 100 study subjects with mild cognitive impairment underwent a double-blind SHCog™ soft capsule (600 mg αGPC) or placebo treatment for 12 weeks. The primary efficacy outcome included changes from baseline on the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog). Safety assessments included regular monitoring of adverse events, and clinical laboratory tests were conducted at baseline and the end of the trial. Results After 12 weeks of αGPC treatment, the ADAS-cog score decreased by 2.34 points, which was significantly greater than the change observed in the placebo group. No serious AEs were reported, and no study subjects discontinued the intervention because of AEs. There was no significant difference in incidence rate of AEs between the αGPC group and the placebo group. Conclusion This study suggests that αGPC is a safe and effective intervention for improving cognitive function in study subjects with mild cognitive impairment. Trial registration Clinical Research Information Service; Osong (Chungcheongbuk-do): Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); KCT0008797; A 12-week, multicenter, randomized, double-blind, placebo-controlled human application study to evaluate the efficacy and safety of SH_CAPK08 on cognitive function improvement in mild cognitive decline.

Abstract This study focused on identifying and characterizing 1,3-diphenylpropane derivatives from flavonoids that inhibit human indoleamine 2,3-dioxygenase 1 (hIDO1) enzymes, which play a role in immune regulation and are associated with various diseases. A series of isolated metabolites (1–7) demonstrated modest to high inhibition of hIDO1, with binding degree values ranging from 26.31 to 72.17%. In particular, during a target-based screening of natural products using hIDO1, kazinol J (6, a 1,3-diphenylpropane derivative) was found to potently inhibit hIDO1, with a binding degree of 72.17% at 1 ppm. Kazinol J (6) showed concentration-dependent and mixed inhibition kinetics and achieved slow and time-dependent inhibition of hIDO1. Additionally, docking simulations were performed to evaluate the inhibitory potential and binding interactions of the compounds with hIDO1. These findings suggest that these 1,3-diphenylpropane derivatives can serve as therapeutic agents for conditions involving hIDO1 dysregulation, such as cancer, autoimmune disorders, and infectious diseases.

Purpose This study aimed to investigate the difference in satisfaction and learning benefits between e-portfolios compared to paper portfolios during clinical practice in medical schools. Methods Utilization of and satisfaction with e-portfolios among 40 third-year medical students in the medicine department of Ajou University School of Medicine was collected using an online survey in December 2020. The collected data were analyzed using descriptive statistics and an analysis of variance. Results Students perceived that e-portfolios were highly beneficial for consistently documenting activities during clinical practice, when compared to paper-based portfolios (mean±standard deviation [SD]=2.60±1.22). However, the least rated aspect was that e-portfolios require less time than paper-based portfolios (mean±SD=1.80±1.14). Additionally, among the various clinical practice courses using e-portfolios, the highest satisfaction was observed with the fewest content items in the e-portfolio. Conclusion To maximize the potential benefits of e-portfolios, improvements in implementation and usability are essential. Additionally, for effective utilization of e-portfolios in clinical practice, it is necessary to clearly define students’ required competencies and ultimate goals, and structure content accordingly.

Xylanases require thermal stability to withstand the pelleting process, pH stability to function in the gastrointestinal tract, and resistance to xylanase inhibitors in raw materials to be effective in animal feed. A GH11 family xylanase originating from an anaerobic fungus, Orpinomyces sp. strain PC-2, has high specific activity and resistance to xylanase inhibitors intrinsically. It was engineered using rational protein design methods to obtain a thermal and pH stable enzyme, OXynA-M. OXynA-M showed resistance to three types of xylanase inhibitors, Triticum aestivum xylanase inhibitors TAXI-IB and TAXI-IIA and xylanase inhibitor protein XIP and showed melting temperature of 87.2°C when measured using differential scanning calorimetry. It was stable at all pH between 2.0–10.0 incubated up to 4 h. Xylo-oligosaccharides (XOS) production profile using a wheat arabinoxylan substrate revealed the production of xylobioses up to xylohexaoses, which are known to have prebiotic functionalities. An animal trial was conducted in broiler chickens to evaluate the in vivo efficacy of the xylanase. In total, 600 1-day-old chickens were divided into six dietary treatments, including a positive control (PC) (T1) without the addition of exogenous enzyme and the rest where exogenous xylanase was added at the rates of 1200, 2400, 4800, 9600, and 240000 U/kg of feed from T2–T6. An increase in OXynA-M xylanase improved the performance parameters in the enzyme-treated groups compared with the control. The viscosity of ileal digesta decreased with increasing enzyme dosage. A significantly lower viscosity of 6.54 cP was determined for the minimum dose in T2 (1200 U/kg), and the viscosity was further reduced in T6 (240000 U/kg) (P

Background The development of post-sepsis frailty is a common and significant problem, but it is a challenge to predict. Methods Data for deep learning were extracted from a national multicentre prospective observational cohort of patients with sepsis in Korea between September 2019 and December 2021. The primary outcome was frailty at survival discharge, defined as a clinical frailty score on the Clinical Frailty Scale ≥5. We developed a deep learning model for predicting frailty after sepsis by 10 variables routinely collected at the recognition of sepsis. With cross-validation, we trained and tuned six machine learning models, including four conventional and two neural network models. Moreover, we computed the importance of each predictor variable in the model. We measured the performance of these models using a temporal validation data set. Results A total of 8518 patients were included in the analysis; 5463 (64.1%) were frail, and 3055 (35.9%) were non-frail at discharge. The Extreme Gradient Boosting (XGB) achieved the highest area under the receiver operating characteristic curve (AUC) (0.8175) and accuracy (0.7414). To confirm the generalisation performance of artificial intelligence in predicting frailty at discharge, we conducted external validation with the COVID-19 data set. The XGB still showed a good performance with an AUC of 0.7668. The machine learning model could predict frailty despite the disparity in data distribution. Conclusion The machine learning-based model developed for predicting frailty after sepsis achieved high performance with limited baseline clinical parameters.

Abstract Background This study investigated the mediating effects of self-efficacy and social support on the relationship between stress and burnout among infection control nurses (ICNs) during an emerging infectious disease pandemic. Methods The study participants encompassed 210 ICNs with at least six months’ experience in an infection control unit at a general hospital in South Korea during the COVID-19 pandemic. Data were analyzed using independent t-tests or one-way analysis of variance (ANOVA), while descriptive statistics were performed using SPSS/WIN 26.0 software. Hayes’s PROCESS macro 4.2 software was used to verify the significance of the indirect effects of the mediators. Results Stress had a significant positive effect on burnout (β = 0.80, p

Abstract Objective To examine the association between patterns of alcohol consumption in the past and the risk of depression among medical aid beneficiaries and National Health Insurance beneficiaries in Korea. Methods We used data from the National Health Information Database (NHID) of 1,292,618 participants who underwent health checkups in 2015–16 and 2017–18. We categorized alcohol consumption into four groups: continuous high, increased, decreased, and non-consumers. We followed the participants from 2019 to 2021 and identified new episodes of depression. We calculated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for depression by alcohol consumption groups and socioeconomic status. Results Medical aid beneficiaries had higher risks of depression than National Health Insurance beneficiaries across all alcohol consumption groups. The highest risk was observed among continuous high consumers (aOR, 2.31; 95% CI, 1.36–3.93), followed by increased (aOR, 1.51; 95% CI, 1.17–1.94), decreased (aOR, 1.48; 95% CI, 1.18–1.84), and non-consumers (aOR, 1.37; 95% CI, 1.22–1.54). Conclusions Socioeconomic status and patterns of alcohol consumption in the past are associated with the risk of depression. Public health interventions should consider both factors to reduce alcohol-related depression and health inequalities.

Abstract Background Xerostomia is a pathological condition characterized by decreased salivation due to salivary gland dysfunction and is frequently attributed to irreversible damage as a side effect of radiation therapy. Stem cell–derived organoid therapy has garnered attention as a promising avenue for resolving this issue. However, Matrigel, a hydrogel commonly used in organoid culture, is considered inappropriate for clinical use due to its undefined composition and immunogenicity. In this study, we aimed to develop a method for culturing collagen-based human salivary gland organoids (hSGOs) suitable for clinical applications and evaluated their therapeutic effectiveness. Methods Human salivary gland stem cells were isolated from the salivary gland tissues and cultured in both Matrigel and collagen. We compared the gene and protein expression patterns of salivary gland–specific markers and measured amylase activity in the two types of hSGOs. To evaluate the therapeutic effects, we performed xenogeneic and allogeneic transplantation using human and mouse salivary gland organoids (hSGOs and mSGOs), respectively, in a mouse model of radiation-induced xerostomia. Results hSGOs cultured in Matrigel exhibited self-renewal capacity and differentiated into acinar and ductal cell lineages. In collagen, they maintained a comparable self-renewal ability and more closely replicated the characteristics of salivary gland tissue following differentiation. Upon xenotransplantation of collagen-based hSGOs, we observed engraftment, which was verified by detecting human-specific nucleoli and E-cadherin expression. The expression of mucins, especially MUC5B, within the transplanted hSGOs suggested a potential improvement in the salivary composition. Moreover, the allograft procedure using mSGOs led to increased salivation, validating the efficacy of our approach. Conclusions This study showed that collagen-based hSGOs can be used appropriately in clinical settings and demonstrated the effectiveness of an allograft procedure. Our research has laid the groundwork for the future application of collagen-based hSGOs in allogeneic clinical trials.

Abstract Branched-chain amino acids (BCAAs), particularly leucine, are indispensable AAs for immune regulation through metabolic rewiring. However, the molecular mechanism underlying this phenomenon remains unclear. Our investigation revealed that T-cell receptor (TCR)-activated human CD4+ T cells increase the expression of BCAT1, a cytosolic enzyme responsible for BCAA catabolism, and SLC7A5, a major BCAA transporter. This upregulation facilitates increased leucine influx and catabolism, which are particularly crucial for Th17 responses. Activated CD4+ T cells induce an alternative pathway of cytosolic leucine catabolism, generating a pivotal metabolite, β-hydroxy β-methylbutyric acid (HMB), by acting on BCAT1 and 4-hydroxyphenylpyruvate dioxygenase (HPD)/HPD-like protein (HPDL). Inhibition of BCAT1-mediated cytosolic leucine metabolism, either with BCAT1 inhibitor 2 (Bi2) or through BCAT1, HPD, or HPDL silencing using shRNA, attenuates IL-17 production, whereas HMB supplementation abrogates this effect. Mechanistically, HMB contributes to the regulation of the mTORC1-HIF1α pathway, a major signaling pathway for IL-17 production, by increasing the mRNA expression of HIF1α. This finding was corroborated by the observation that treatment with L-β-homoleucine (LβhL), a leucine analog and competitive inhibitor of BCAT1, decreased IL-17 production by TCR-activated CD4+ T cells. In an in vivo experimental autoimmune encephalomyelitis (EAE) model, blockade of BCAT1-mediated leucine catabolism, either through a BCAT1 inhibitor or LβhL treatment, mitigated EAE severity by decreasing HIF1α expression and IL-17 production in spinal cord mononuclear cells. Our findings elucidate the role of BCAT1-mediated cytoplasmic leucine catabolism in modulating IL-17 production via HMB-mediated regulation of mTORC1-HIF1α, providing insights into its relevance to inflammatory conditions.

The strategy of cultivating healthy fish by manipulating their gut microbiota composition using probiotics is crucial for establishing sustainable fish farms. Information on the gut microbiota composition of healthy fish is important for the efficient development of probiotics and the aquaculture strategies that would apply them. This study assessed the gut microbiota composition of farmed olive flounder according to the growth stage to provide useful information for the development of probiotics. The fish were classified according to their weight, and the intestines of five juveniles weighing less than 100 g and five subadults weighing between 400 and 800 g were used for analysis. The results of alpha diversity analysis confirmed higher richness and diversity in the subadult group than in the juvenile group. Beta diversity analysis revealed clear boundaries and distances between the groups; however, individuals within each group were similar. The two groups showed marked differences in their gut microbiota composition. Phylum-level analysis revealed that the most abundant phylum was Proteobacteria in the juvenile group and Firmicutes in the subadult group. Notably, genus-level analysis revealed that Vibrio accounted for more than 50% of the total composition in the juvenile group. Linear discriminant analysis effect size revealed that the genera Vibrio, Photobacterium, and Leuconostoc were representative of the juvenile group, whereas 19 genera, including Lactococcus and Vagococcus, were representative of the subadult group. Thus, information on the representative microorganisms abundantly present in the intestines of healthy olive flounder can be considered for the selection and development of a probiotic genus for olive flounder farming.

Habits formed during adolescence tend to persist into adulthood, and correcting poor habits or behaviors during this time is more effective than at other times. Particularly, parents and caregivers should encourage good hygiene habits in their adolescent children by setting a positive example themselves. Using logistic regression, we analyzed the association between brushing teeth after lunch and washing hands before lunch by family type among 54,848 adolescents from the 17th Youth Health Behavior Survey raw data in 2021. Four logistic regression models were used to adjust for confounders hierarchically. In all models, adolescents who practiced tooth brushing after lunch were 2.09 times more likely to practice hand washing before lunch than those who did not. With and without adjustment, we found that the association between adolescents’ tooth brushing and hand washing practices in two-parent households was stronger than the association between adolescents’ tooth brushing and hand washing practices in single-parent households. Associations were found between tooth brushing and hand washing practices, and these associations were higher among adolescents in two-parent households than among adolescents in single-parent households. The finding of a significant link between family type and personal hygiene habits indicates the need for interventions to enhance the oral health of children and adolescents. Such interventions should be customized to reflect the specific characteristics of the child’s household.

Purpose: The management of bowel bladder disorder (BBD) has only been indicated for subjective constipation without objective evidence. We attempted to highlight the radiological findings in patients with BBD and construct a scoring system to identify patients with BBD prior to treatment. Materials and Methods: Forty-five patients with lower urinary tract dysfunction (LUTD) received polyethylene glycol for 2 months before bladder medication for LUTD. Based on partial response to LUTD following treatment, we divided the patients into LUTD-fecal impaction (FI) and LUTD not attributed to FI (LUTD-NFI) groups. Pre/post-treatment kidney, ureter, and bladder (KUB) were compared with respect to several radiographic parameters. Items with significant changes after treatment were included in the scoring system. The accuracy and inter-rater agreement were also evaluated. Results: Cecal dilation, descending colon dilation, fecal quality, and overall haziness were found to undergo significant changes after laxative treatment. We assigned 0 to 2 points for each item, with a total score of 8. Receiver operating characteristic curve analysis revealed a cutoff value of 5 between LUTD-FI and LUTD-NFI, with 79% sensitivity and 88% specificity. The scoring system was instructed to six doctors who were unaware of it and was then tested on previous patients, which showed a substantial concordance rate (κ=0.79, p

Abstract Background Stroke causes long-term disabilities, highlighting the need for innovative rehabilitation strategies for reducing residual impairments. This study explored the potential of functional near-infrared spectroscopy (fNIRS) for monitoring cortical activation during rehabilitation using digital therapeutics. Methods This cross-sectional study included 18 patients with chronic stroke, of whom 13 were men. The mean age of the patients was 67.0 ± 7.1 years. Motor function was evaluated through various tests, including the Fugl–Meyer assessment for upper extremity (FMA-UE), grip and pinch strength test, and box and block test. All the patients completed the digital rehabilitation program (MotoCog®, Cybermedic Co., Ltd., Republic of Korea) while being monitored using fNIRS (NIRScout®, NIRx Inc., Germany). Statistical parametric mapping (SPM) was employed to analyze the cortical activation patterns from the fNIRS data. Furthermore, the K-nearest neighbor (K-NN) algorithm was used to analyze task performance and fNIRS data to classify the severity of motor impairment. Results The participants showed diverse task performances in the digital rehabilitation program, demonstrating distinct patterns of cortical activation that correlated with different motor function levels. Significant activation was observed in the ipsilesional primary motor area (M1), primary somatosensory area (S1), and contralateral prefrontal cortex. The activation patterns varied according to the FMA-UE scores. Positive correlations were observed between the FMA-UE scores and SPM t-values in the ipsilesional M1, whereas negative correlations were observed in the ipsilesional S1, frontal lobe, and parietal lobe. The incorporation of cortical hemodynamic responses with task scores in a digital rehabilitation program substantially improves the accuracy of the K-NN algorithm in classifying upper limb functional levels in patients with stroke. The accuracy for tasks, such as the gas stove-operation task, increased from 44.4% using only task scores to 83.3% when these scores were combined with oxy-Hb t-values from the ipsilesional M1. Conclusions The results advocated the development of tailored digital rehabilitation strategies by combining the behavioral and cerebral hemodynamic data of patients with stroke. This approach aligns with the evolving paradigm of personalized rehabilitation in stroke recovery, highlighting the need for further extensive research to optimize rehabilitation outcomes.

Abstract Various electrocardiographic changes occur during sepsis, but data on the clinical importance of a low QRS voltage in sepsis are still limited. We aimed to evaluate the association between low QRS voltage identified early in sepsis and mortality in patients with sepsis. Between September 2019 and December 2020, all consecutive adult patients diagnosed with sepsis in the emergency room or general ward at Samsung Medical Center were enrolled. Patients without a 12-lead electrocardiogram recorded within 48 h of recognition of sepsis were excluded. In 432 eligible patients, 12-lead electrocardiogram was recorded within the median of 24 min from the first recognition of sepsis, and low QRS voltage was identified in 115 (26.6%) patients. The low QRS group showed more severe organ dysfunction and had higher levels of N-terminal pro-brain natriuretic peptide. The hospital mortality was significantly higher in the low QRS voltage group than in the normal QRS voltage group (49.6% vs. 28.1%, p

Background/Aims Intensive care unit (ICU) quality is largely determined by the mortality rate. Therefore, we aimed to develop and validate a novel prognostic model for predicting mortality in Korean ICUs, using national insurance claims data. Methods Data were obtained from the health insurance claims database maintained by the Health Insurance Review and Assessment Service of South Korea. From patients who underwent the third ICU adequacy evaluation, 42,489 cases were enrolled and randomly divided into the derivation and validation cohorts. Using the models derived from the derivation cohort, we analyzed whether they accurately predicted death in the validation cohort. The models were verified using data from one general and two tertiary hospitals. Results Two severity correction models were created from the derivation cohort data, by applying variables selected through statistical analysis, through clinical consensus, and from performing multiple logistic regression analysis. Model 1 included six categorical variables (age, sex, Charlson comorbidity index, ventilator use, hemodialysis or continuous renal replacement therapy, and vasopressor use). Model 2 additionally included presence/absence of ICU specialists and nursing grades. In external validation, the performance of models 1 and 2 for predicting in-hospital and ICU mortality was not inferior to that of pre-existing scoring systems. Conclusions The novel and simple models could predict in-hospital and ICU mortality and were not inferior compared to the pre-existing scoring systems.

Background Statins reduce the risk of cardiovascular events in patients with chronic kidney disease (CKD). Although diabetes mellitus (DM) is a reported side effect of statin treatment, some studies have indicated that pitavastatin does not cause DM. The present study investigated the effect of pitavastatin on the fatty acid (FA) content of erythrocyte membranes, which affects the occurrence of DM and cardiovascular diseases. In addition, changes in adiponectin and glycated hemoglobin (HbA1c) levels were evaluated after pitavastatin treatment. Methods A total of 45 patients were enrolled, 28 of whom completed the study. Over 24 weeks, 16 patients received 2 mg pitavastatin and 12 patients received 10 mg atorvastatin. Dosages were adjusted after 12 weeks if additional lipid control was required. There were 10 and nine patients with DM in the pitavastatin and atorvastatin groups, respectively. Erythrocyte membrane FAs and adiponectin levels were measured using gas chromatography and enzyme-linked immunosorbent assay, respectively. Results In both groups, saturated FAs, palmitic acid, trans-oleic acid, total cholesterol, and low-density lipoprotein cholesterol levels were significantly lower than those at baseline. The arachidonic acid (AA) content in the erythrocyte membrane increased significantly in the pitavastatin group, but adiponectin levels were unaffected. HbA1c levels decreased in patients treated with pitavastatin. No adverse effects were associated with statin treatment. Conclusion Pitavastatin treatment in patients with CKD may improve glucose metabolism by altering erythrocyte membrane AA levels. In addition, pitavastatin did not adversely affect glucose control in patients with CKD and DM.

Objectives Sepsis is a leading global cause of mortality, and predicting its outcomes is vital for improving patient care. This study explored the capabilities of ChatGPT, a state-of-the-art natural language processing model, in predicting in-hospital mortality for sepsis patients. Methods This study utilized data from the Korean Sepsis Alliance (KSA) database, collected between 2019 and 2021, focusing on adult intensive care unit (ICU) patients and aiming to determine whether ChatGPT could predict all-cause mortality after ICU admission at 7 and 30 days. Structured prompts enabled ChatGPT to engage in in-context learning, with the number of patient examples varying from zero to six. The predictive capabilities of ChatGPT-3.5-turbo and ChatGPT-4 were then compared against a gradient boosting model (GBM) using various performance metrics. Results From the KSA database, 4,786 patients formed the 7-day mortality prediction dataset, of whom 718 died, and 4,025 patients formed the 30-day dataset, with 1,368 deaths. Age and clinical markers (e.g., Sequential Organ Failure Assessment score and lactic acid levels) showed significant differences between survivors and non-survivors in both datasets. For 7-day mortality predictions, the area under the receiver operating characteristic curve (AUROC) was 0.70–0.83 for GPT-4, 0.51–0.70 for GPT-3.5, and 0.79 for GBM. The AUROC for 30-day mortality was 0.51–0.59 for GPT-4, 0.47–0.57 for GPT-3.5, and 0.76 for GBM. Zero-shot predictions using GPT-4 for mortality from ICU admission to day 30 showed AUROCs from the mid-0.60s to 0.75 for GPT-4 and mainly from 0.47 to 0.63 for GPT-3.5. Conclusions GPT-4 demonstrated potential in predicting short-term in-hospital mortality, although its performance varied across different evaluation metrics.

Optimization of the extraction procedure was performed to enhance the antioxidant activity and whitening effect of Sasa quelpaertensis Nakai extract using response surface methodology (RSM). The central composite design, a component of RSM, was utilized to optimize and validate the ethanol extract for antioxidant activity and the hot water extract for the whitening effect, respectively. Activities of antioxidant and whitening were determined by DPPH and tyrosinase inhibition assays. The antioxidant activity was notably influenced by ethanol concentration (p = 0.0344) more than other factors. The optimal conditions for the antioxidant effect were 54% ethanol concentration, 52 °C, and 3 h extraction time, yielding an antioxidant activity of 83.65±1.56%. On the other hand, the whitening effect was significantly impacted by ultrasonic irradiation time (p = 0.0175) compared to other factors. The optimal conditions for whitening were 41 °C, 1:19 of sample-to-solvent ratio, and 8 min of ultrasonic irradiation, achieving a tyrosinase inhibition activity of 51.00±1.80%. High-performance liquid chromatography (HPLC) analysis was conducted to identify compounds such as tricin with antioxidant activity and p-coumaric acid, arbutin with whitening effect under the optimized conditions. The results suggest that the optimized extracts from S. quelpaertensis could be utilized as beneficial cosmeceutical materials.

Abstract Background Choosing a suitable job and leading a fulfilling professional life is vital for individuals, regardless of disability. Governments provide rehabilitation services to promote employment for individuals with disabilities, but research on their effects is limited. This study aimed to examine the impact of rehabilitation services on employment among people with physical disabilities in South Korea using propensity score matching. Methods This study utilized an observational research design. Data were obtained from the 2020 National Survey of Disabled Persons, including 1,757 individuals aged 20 or older with physical disabilities. Descriptive statistics, chi-square and independent t-tests, logistic regression, and propensity score matching were employed. Results The results for employment of individuals with physical disabilities showed no difference between the with rehabilitation services and the without rehabilitation services group. Based on subgroup analysis, when individuals with physical disabilities who rated their subjective health status low received rehabilitation services, it had a positive effect on employment. Conclusions The results of this study could serve as foundational data for future policies and educational directions concerning rehabilitation services for persons with disabilities.

Abstract There are numerous prognostic predictive models for evaluating mortality risk, but current scoring models might not fully cater to sepsis patients’ needs. This study developed and validated a new model for sepsis patients that is suitable for any care setting and accurately forecasts 28-day mortality. The derivation dataset, gathered from 20 hospitals between September 2019 and December 2021, contrasted with the validation dataset, collected from 15 hospitals from January 2022 to December 2022. In this study, 7436 patients were classified as members of the derivation dataset, and 2284 patients were classified as members of the validation dataset. The point system model emerged as the optimal model among the tested predictive models for foreseeing sepsis mortality. For community-acquired sepsis, the model’s performance was satisfactory (derivation dataset AUC: 0.779, 95% CI 0.765–0.792; validation dataset AUC: 0.787, 95% CI 0.765–0.810). Similarly, for hospital-acquired sepsis, it performed well (derivation dataset AUC: 0.768, 95% CI 0.748–0.788; validation dataset AUC: 0.729, 95% CI 0.687–0.770). The calculator, accessible at https://avonlea76.shinyapps.io/shiny_app_up/ , is user-friendly and compatible. The new predictive model of sepsis mortality is user-friendly and satisfactorily forecasts 28-day mortality. Its versatility lies in its applicability to all patients, encompassing both community-acquired and hospital-acquired sepsis.

Spinal cord injury (SCI) rehabilitation emphasizes locomotion. Robotic-assisted gait training (RAGT) is widely used in clinical settings because of its benefits; however, its efficacy remains controversial. We conducted a systematic review and meta-analysis to investigate the efficacy of RAGT in patients with SCI. We searched international and domestic databases for articles published until April 18, 2024. The meta-analysis employed a random effects model to determine the effect size as either mean difference (MD) or standardized MD (SMD). Evidence quality was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Twenty-three studies with a total of 690 participants were included in the final analysis. The overall pooled effect size for improvement in activities of daily living was 0.24, with SMD (95% confidence interval [95% CI], 0.04–0.43; GRADE: high) favoring RAGT over conventional rehabilitation. Muscular strength (MD, 0.23; 95% CI, 0.02–0.44; GRADE: high), walking index for SCI (MD, 0.31; 95% CI, 0.07–0.55; GRADE: moderate) and 6 min walk test distance (MD, 0.38; 95% CI, 0.14–0.63; GRADE: moderate) showed significant improvement in the robot group. Subgroup analysis revealed that subacute patients and intervention periods >2 months were more effective. This meta-analysis revealed that RAGT significantly improved activities of daily living, muscular strength, and walking abilities. Additional studies are needed to identify the optimal treatment protocol and specific patient groups for which the protocol is most effective.

Objective: Serological tests are widely used for scrub typhus diagnosis; however, their limitations are evident. This study aims to assess their practical value in clinical settings. Methods: We analyzed the data of adult patients with suspected scrub typhus who visited a tertiary care hospital in the Republic of Korea from September to December from 2019 to 2021. The included patients had an acute fever and at least one of the following ten secondary findings: myalgia, skin rash, eschar, headache, thrombocytopenia, increased liver enzyme levels, lymphadenopathy, hepatomegaly, splenomegaly, and pleural effusion. The diagnoses were grouped as scrub typhus or other diseases by two infectious disease physicians. Results: Among 136 patients who met the eligibility criteria, 109 had scrub typhus and 27 had different diseases. Single and paired total antibodies using immunofluorescence assay (IFA), and total antibodies using immunochromatography-based rapid diagnostic testing (ICT) were measured in 98%, 22%, and 75% of all patients, respectively. Confirmation using paired samples for scrub typhus was established at a median of 11 [interquartile range (IQR) 10-16] days following the first visit. Among the 82 admitted patients, the median admission time was 9 (IQR 7-13) days. According to IFA, 58 (55%) patients with scrub typhus had total immunoglobulin titers ≥1:320, while 23 (85%) patients with other disease had titers < 1:320. Positive ICT results were observed in 64 (74%) patients with scrub typhus and 10 (67%) patients with other diseases showed negative ICT results. Conclusions: Serological testing for scrub typhus is currently insufficient for decision-making in clinical practice.

Abstract Research on the microenvironment associated with gastric carcinogenesis has focused on cancers of the stomach and often underestimates premalignant stages such as metaplasia and dysplasia. Since epithelial interactions with T cells, macrophages, and type 2 innate lymphoid cells (ILC2s) are indispensable for the formation of precancerous lesions in the stomach, understanding the cellular interactions that promote gastric precancer warrants further investigation. Although various types of immune cells have been shown to play important roles in gastric carcinogenesis, it remains unclear how stromal cells such as fibroblasts influence epithelial transformation in the stomach, especially during precancerous stages. Fibroblasts exist as distinct populations across tissues and perform different functions depending on the expression patterns of cell surface markers and secreted factors. In this review, we provide an overview of known microenvironmental components in the stroma with an emphasis on fibroblast subpopulations and their roles during carcinogenesis in tissues including breast, pancreas, and stomach. Additionally, we offer insights into potential targets of tumor-promoting fibroblasts and identify open areas of research related to fibroblast plasticity and the modulation of gastric carcinogenesis.

Abstract N 6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.