Search

Ethnopharmacological Relevance: Wumei Wan (WMW), a traditional Chinese medicine prescription, has been proved to be effective in treating Colitis-associated colorectal cancer (CAC), but it has not been proven to be effective in different stages of CAC., Aim of the Study: The purpose of our study is to investigate the therapeutic effect and mechanism of WMW on the progression of CAC., Materials and Methods: Azioximethane (AOM) and dextran sulfate sodium (DSS) were used to treat mice for the purpose of establishing CAC models. WMW was administered in different stages of CAC. The presentative chemical components in WMW were confirmed by LC-MS/MS under the optimized conditions. The detection of inflammatory cytokines in the serum and colon of mice were estimated by qRT-PCR and ELISA. The changes of T cells and myeloid-derived suppressor cells (MDSCs) in each group were detected by flow cytometry. The metabolic components in serum of mice were detected by UPLC-MS/MS. Expression of genes and proteins were detected by eukaryotic transcriptomics and Western blot to explore the key pathway of WMW in preventing CAC., Results: WMW had significant effect on inhibiting inflammatory responses and tumors during the early development stage of CAC when compared to other times. WMW increased the length of mice's colons, reduced the level of IL-1β, IL-6, TNF-α in colon tissues, and effectively alleviated colonic inflammation, and improved the pathological damage of colon tissues. WMW could significantly reduce the infiltration of MDSCs in the spleen, increase CD4 + T cells and CD8 + T cells in the spleen of CAC mice, and effectively reform the immune microenvironment in CAC mice. Transcriptomics analysis revealed that 2204 genes had different patterns of overlap in the colon tissues of mice between control group, AOM + DSS group, and early administration of WMW group. And KEGG enrichment analysis showed that PI3K/Akt signaling pathway, ECM-receptor interaction, IL-17 signaling pathway, MAPK signaling pathway, pancreatic secretion, thermogenesis, and Rap1 signaling pathway were all involved. The serum metabolomics results of WMW showed that the metabolic compositions of the control group, AOM + DSS group and the early stage of WMW were different, and 42 differential metabolites with the opposite trends of changes were screened. The metabolic pathways mainly included pyrimidine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, and purine metabolism. And amino acids and related metabolites may play an important role in WMW prevention of CAC., Conclusion: WMW can effectively prevent the occurrence and development of CAC, especially in the initial stage. WMW can reduce the immune infiltration of MDSCs in the early stage. Early intervention of WMW can improve the metabolic disorder caused by AOM + DSS, especially correct the amino acid metabolism. PI3K/Akt signaling pathway was inhabited in early administration of WMW, which can regulate the amplification and function of MDSCs., Competing Interests: Declaration of competing interest All authors disclosed no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Functional hydrogels have emerged as foundational materials in diagnostics, therapy, and wearable devices, owing to their high stretchability, flexibility, sensing, and outstanding biocompatibility. Their significance stems from their resemblance to biological tissue and their exceptional versatility in electrical, mechanical, and biofunctional engineering, positioning themselves as a bridge between living organisms and electronic systems, paving the way for the development of highly compatible, efficient, and stable interfaces. These multifaceted capability revolutionizes the essence of hydrogel-based wearable devices, distinguishing them from conventional biomedical devices in real-world practical applications. In this comprehensive review, we first discuss the fundamental chemistry of hydrogels, elucidating their distinct properties and functionalities. Subsequently, we examine the applications of these bioelectronics within the human body, unveiling their transformative potential in diagnostics, therapy, and human-machine interfaces (HMI) in real wearable bioelectronics. This exploration serves as a scientific compass for researchers navigating the interdisciplinary landscape of chemistry, materials science, and bioelectronics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Although diabetes is one of the leading causes of death among Korean Americans, the levels and predictors of diabetes knowledge in this group have not been sufficiently reported. This study aimed to (1) describe the level of diabetes knowledge of Korean immigrant women in the U.S. and (2) examine whether there is an interaction effect between social support and education on diabetes knowledge., Design: This study conducted a cross-sectional survey design. The sample included 227 Korean immigrant women living in the southeast region of the U.S. The fourteen items of the Diabetes Knowledge Test were used to assess the diabetes knowledge level of Korean American women. A multiple linear regression analysis was conducted to examine the interaction effect between social support and education on diabetes knowledge., Results: Only 6% of the participants presented a good diabetes knowledge level, 12.5% had a poor level, and the majority (81.5%) had a moderate level. We found a significant interaction effect between social support and education on diabetes knowledge. The highest diabetes knowledge was observed when individuals with a lower education level had higher social support., Conclusion: Future health practices and policies may focus on increasing knowledge among Korean American women with lower education levels and lower social support. Implementing peer-led initiatives can enhance diabetes knowledge and encourage better self-care practices within the community.

Background: Thyroid storm is a rare but potentially lethal manifestation of thyrotoxicosis. Guidelines recommend nonoperative management of thyroid storm, but thyroidectomy can be performed if patients fail medical therapy or need immediate resolution of the storm. Outcomes of thyroidectomy for management of thyroid storm remain ill-defined., Methods: Using the National Inpatient Sample from 2016 to 2020, a retrospective analysis was conducted of patients admitted with thyroid storm. Outcomes of interest included operative complications and mortality. Multivariable logistic regression was performed to assess factors associated with receiving thyroidectomy and mortality., Results: An estimated 16,175 admissions had a diagnosis of thyroid storm. The incidence of thyroid storm increased from .91 per 100,000 people in 2016 to 1.03 per 100,000 people in 2020, with a concomitant increase in mortality from 2.9% to 5.3% ( P < .001). Operative intervention was pursued in 635 (3.9%) cases with a perioperative complication rate of 30%. On multivariable regression, development of acute decompensated heart failure (adjusted odds ratio [AOR] 1.66, 95% Confidence Interval [CI] 1.03-2.68, P = .037) and acute renal failure (AOR 2.10, 95% CI 1.17-3.75, P = .013) increased odds of receiving surgery. The same multivariable model did not show a significant association between thyroidectomy and mortality., Discussion: The incidence of thyroid storm and associated mortality increased during the study period. Thyroidectomy is rarely performed during the same admission, with an overall perioperative complication rate of 30% and no effect on mortality. Patients with acute decompensated heart failure and renal failure were more likely to receive an operative intervention., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Dopamine-modified hyaluronic acid (DA-HA) has been initially developed as an efficient coating and adhesion material for industrial uses. However, the biological activity and safety of DA-HA in the brain have not been explored yet. Here, we report a series of evidence that DA-HA exhibits similar functionality as dopamine (DA), but with much lower toxicity arising from autoxidation. DA-HA shows very little autoxidation even after 48-h incubation. This is profoundly different from DA and its derivatives including l-DOPA, which all induce severe neuronal death after pre-autoxidation, indicating that autoxidation is the cause of neuronal death. Furthermore, in vivo injection of DA-HA induces significantly lower toxicity compared to 6-OHDA, a well-known oxidized and toxic form of DA, and alleviates the apomorphine-induced rotational behavior in the 6-OHDA animal model of Parkinson's disease. Our study proposes that DA-HA with DA-like functionalities and minimal toxicity has a great potential to treat DA-related disease., Competing Interests: Declaration of competing interest A patent was filed (KR 10-2022-0058461/2023.05.11) by the Institute for Basic Science (IBS) and Korea Institute of Toxicology (KIT)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to investigate the clinical efficacy of MiSight 1 day soft contact lenses (MiSight CL) in Korean children with mild-to-moderate myopia. In addition, the study compared the effects of MiSight CL in children who had or had not previously used orthokeratology contact lenses (Ortho-K)., Methods: A total of 66 children aged 5 to 16 years, who were prescribed MiSight CL, were included in the study. Based on a myopia degree of -4 diopters (D), children were divided into mild and severe myopia groups to compare the effectiveness of myopia suppression. In addition, 55 eyes previously using Ortho-K were compared with 76 eyes using MiSight CL for the first time., Results: The average follow-up period was 6.58±3.74 months. The average refractive value before using MiSight CL was 3.64±1.56 D, and there was no significant change in the final visit. Comparing myopia suppression between different degrees of myopia and previous use of Ortho-K lenses, there was no significant change in refractive error before and after using MiSight CL (unpaired t test, P >0.05). The main reason for Ortho-K failure was low visual acuity after correction. Regardless of Ortho-K history, children showed good visual acuity after wearing MiSight CL, and no other side effects were observed., Conclusions: MiSight CL effectively inhibited the progression of myopia in Korean children with mild-to-moderate myopia. MiSight CL offer the advantage of easy application, making them a viable alternative when Ortho-K are not suitable., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

Background: Cervical and upper thoracic esophageal cancer (ESCA) presents treatment challenges due to limited clinical evidence. This multi-center study (ChC&UES) explores radical radio(chemo)therapy efficacy and safety, especially focusing on radiation dose., Method: We retrospectively analyzed clinical data from 1,422 cases across 8 medical centers. According to the radiation dose for primary gross tumor, patients were divided into standard dose radiotherapy (SD, 50-55 Gy) or high dose (HD, > 55 Gy) radiotherapy. HD was further subdivided into conventional- high-dose group (HD-conventional, 55-63 Gy) and ultra-high-dose group (HD-ultra, ≥ 63 Gy). Primary outcome was Overall Survival (OS)., Results: The median OS was 33.0 months (95% CI: 29.401-36.521) in the whole cohort. Compared with SD, HD shown significant improved survival in cervical ESCA in Kaplan-Meier (P = 0.029) and cox multivariate regression analysis (P = 0.024) while shown comparable survival in upper thoracic ESCA (P = 0.735). No significant difference existed between HD-conventional and HD-ultra in cervical (P = 0.976) and upper thoracic (P = 0.610) ESCA. Incidences of radiation esophagitis and pneumonia from HD were comparable to SD (P = 0.097, 0.240), while myosuppression risk was higher(P = 0.039). The Bonferroni method revealed that, for both cervical and upper thoracic ESCA, HD-ultra enhance the objective response rate (ORR) compared to SD (P < 0.05)., Conclusion: HD radiotherapy benefits cervical but not upper thoracic ESCA, while increasing bone marrow suppression risk. Further dose escalating (≥ 63 Gy) doesn't improve survival but enhances ORR., (© 2024. The Author(s).)

Experiments are increasingly performed in vitro; therefore, cell culture technology is essential for scientific progress. Fetal bovine serum (FBS) is a key cell culture supplement providing growth factors, amino acids, and hormones. However, FBS is not readily available on the market, has contamination risks, and has ethical concerns. This study aimed to investigate Haematococcus pluvialis extracts (HE) as a potential substitute for FBS. Therefore, we assessed the effects of HE on cell maintenance, growth, and cycle progression in human lung fibroblasts (MRC-5). Cell progression and monosaccharide, fatty acid, and free amino acid compositions were analyzed using cell cycle analysis, bio-liquid chromatography, gas chromatography, and high-performance liquid chromatography, respectively. The results of nutritional profiles showed that the extracts contained essential amino acids required for synthesizing non-essential amino acids and other metabolic intermediates. Furthermore, most of the components present in HE were consistent with those found in FBS. HE enhanced cell viability and regulated cell cycle phases. Additionally, the interaction between growth factor cocktails and HE significantly improved cell viability, promoted cell cycle progression, and activated key cell cycle regulators, such as cyclin A and cyclin-dependent kinases 1 (CDK1). Our findings suggest that HE have considerable potential to substitute FBS in MRC-5 cell cultures and have functional and ethical advantages.

MicroRNAs (miRNAs) are endogenous, non-coding RNAs, which are functional in a variety of biological processes through post-transcriptional regulation of gene expression. However, the role of miRNAs in the interaction between Bacillus thuringiensis and insects remains unclear. In this study, small RNA libraries were constructed for B. thuringiensis -infected (Bt) and uninfected (CK) Spodoptera exigua larvae (treated with double-distilled water) using Illumina sequencing. Utilising the miRDeep2 and Randfold, a total of 233 known and 726 novel miRNAs were identified, among which 16 up-regulated and 34 down-regulated differentially expressed (DE) miRNAs were identified compared to the CK. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that potential target genes of DE miRNAs were associated with ABC transporters, fatty acid metabolism and MAPK signalling pathway which are related to the development, reproduction and immunity. Moreover, two miRNA core genes, SeDicer1 and SeAgo1 were identified. The phylogenetic tree showed that lepidopteran Dicer1 clustered into one branch, with SeDicer1 in the position closest to Spodoptera litura Dicer1. A similar phylogenetic relationship was observed in the Ago1 protein. Expression of SeDicer1 increased at 72 h post infection (hpi) with B. thuringiensis ; however, expression of SeDicer1 and SeAgo1 decreased at 96 hpi. The RNAi results showed that the knockdown of SeDicer1 directly caused the down-regulation of miRNAs and promoted the mortality of S. exigua infected by B. thuringiensis GS57. In conclusion, our study is crucial to understand the relationship between miRNAs and various biological processes caused by B. thuringiensis infection, and develop an integrated pest management strategy for S. exigua via miRNAs.

This study aimed to investigate the correlation between the composition of volatile compounds, consumer acceptance, and drivers of (dis)liking of Protaetia brevitarsis larvae fermented using lactic acid bacteria and yeast. Volatile compounds were analyzed using HS-SPME-Arrow-GC-MS, and a sensory evaluation was conducted with 72 consumers. A total of 113 volatile compounds were detected, and principal component analysis indicated that the samples could be divided into three groups. The calculated relative odor activity values (ROAV) revealed the presence of 27 compounds (ROAV >1). Volatile compounds with high ROAV were predominantly found during yeast fermentation. The sensory evaluation results indicated a strong correlation between low levels of off-odor intensity and high odor liking, emphasizing that odor profile had a more direct association with consumer acceptance than odor intensity. These findings suggest that yeast fermentation using volatile compounds, which positively influences consumer acceptance, is appropriate for Protaetia brevitarsis larvae., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Lung-recruitment maneuvers (LRM) have been shown to reduce postoperative pain after laparoscopic surgery. This study aimed to investigate the association of LRM with the incidence of shoulder pain after laparoscopic cholecystectomy., Methods: A randomized controlled study was conducted with 110 patients undergoing elective laparoscopic cholecystectomy from July 2022 to March 2023. Participants were randomized to receive either routine exsufflation or LRM at pneumoperitoneum release. The postoperative shoulder pain and abdominal pain were assessed at 1, 4, 6, 12, and 24 h after surgery using a numeric rating scale. Analgesic consumption and postoperative nausea or vomiting (PONV) were evaluated during the first 24 h after surgery., Results: The incidence of shoulder pain during the first 24 h after surgery was significantly lower in the LRM group compared to the control group (26.9 vs. 59.3%; P = 0.001). The median [interquartile range] score of worst shoulder pain was significantly lower compared to the control group (3 [2-3] vs 4 [3-5.5]; P = 0.003). Participants in the LRM group showed reduced abdominal pain at rest at 4 and 24 h after surgery, and experienced significantly lower intensities of abdominal pain during mobilization at all time points over 24 h after surgery. There were no significant differences in opioid consumption or the incidence of PONV between the groups., Conclusions: LRM reduces both the incidence and intensity of shoulder pain during 24 h after laparoscopic cholecystectomy. Additionally, LRM was associated with reduced intensity of abdominal pain during mobilization over the study period., (© 2024. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

The development of serum-free media (SFM) is critical to advance cell culture techniques used in viral vaccine production and address the ethical concerns and contamination risks associated with fetal bovine serum (FBS). This study evaluated the effects of marine microalgal extracts and growth factor cocktails on the activity of Madin-Darby canine kidney (MDCK) and Vero cells. Five marine microalgal species were used: Spirulina platensis (SP), Dunaliella salina (DS), Haematococcus pluvialis (HP), Nannochloropsis salina (NS), and Tetraselmis sp. (TS). DS and SP extracts significantly increased the proliferation rate of both MDCK and Vero cells. DS had a proliferation rate of 149.56% and 195.50% in MDCK and Vero cells, respectively, compared with that in serum-free medium (SFM). Notably, DS and SP extracts significantly increased superoxide dismutase (SOD) activity, which was 118.61% in MDCK cells and 130.08% in Vero cells for DS, and 108.72% in MDCK cells and 125.63% in Vero cells for SP, indicating a reduction in intracellular oxidative stress. Marine microalgal extracts, especially DS and SP, are feasible alternatives to FBS in cell culture as they promote cell proliferation, ensure safety, and supply essential nutrients while reducing oxidative stress.

This study aimed to investigate whether metabolic dysfunction-associated fatty liver disease (MAFLD) defined by the fatty liver index (FLI) affects the decline in kidney function and whether this relationship is still observed in MAFLD defined by ultrasonography (USG). A retrospective cohort study was conducted using de-identified data from participants who received health checkups at Samsung Changwon Hospital between 2002 and 2018. The primary and secondary exposures were the presence of FLI- and USG-defined MAFLD, respectively. The primary outcome was 5-years slope of eGFR. The secondary outcome was a rapid decline in kidney function, defined as a 5-years slope of estimated glomerular filtration rate (eGFR) of less than - 3 mL/min/1.73 m 2 per year. A total of 37,500 participants were included in the analysis. Participants with FLI-defined MAFLD had a larger decline in 5-year eGFR slope than those without FLI-defined MAFLD (beta coefficients - 0.11; 95% CI - 0.14 to - 0.08). Participants with FLI-defined MAFLD had a higher risk of rapid kidney function decline than those without FLI-defined MAFLD (odds ratio 1.33; 95% confidence intervals (CIs) 1.05-1.69). However, USG-defined MAFLD was less related to kidney function decline. In conclusion, the presence of FLI-defined MAFLD was associated with larger and faster kidney function decline., (© 2024. The Author(s).)

To determine the optimal film management technique for garlic planting, this study aimed to investigate the effects of various film cover methods on soil quality and garlic yield in garlic cropping systems. To achieve these goals, trials with different film cover methods were conducted at the Jiangsu Academy of Agricultural Sciences in Nanjing. To investigate the impact of changes in soil quality and garlic yield, we set up four treatments： no film treatment （CK）, black polyethylene film treatment （HPE）, black poly（butylene- adipate-co-terephthalate） （PBAT） with straw composite film treatment （HSJ）, and white PBAT film treatment （BJ） in a garlic cropping system. Our results indicated that specific mulch coverings had a positive effect on both soil quality and garlic yield. The film cover treatments resulted in significant changes in soil physicochemical properties and bacterial and fungal biomasses and indirectly improved soil quality. Compared to that under the no film treatment, the BJ treatment boosted soil quality by 70%, with the most significant impact, followed by that under the HPE and HSJ treatments, with improvements of 52% and 36%. Random forest modeling indicated that soil organic matter and total nitrogen were the most important factors influencing soil quality. The different film covers significantly increased the diameter of garlic bulbs and single quality. The HSJ treatment exhibited the most significant increase in garlic yield, with 46%, 19%, and 6% improvement compared to that in the CK, HPE, and BJ treatments, respectively. Correlation analysis showed that soil quality under film cover was significantly correlated with the starch content of garlic bulbs, garlic diameter, and single quality. This study highlights that selecting the appropriate mulch film aids in the production of garlic and helps to develop farmland that produces both high-quality and high-yield crops.

Absent in melanoma 2(AIM2) exacerbates atherosclerosis by inflammasome assembly. However, AIM2-mediated inflammation in diabetic cardiomyopathy remains incompletely understood. Here we investigate the role of AIM2 in high glucose (HG)- and diabetes-induced inflammatory cardiomyopathy. By RNA-seq, we found that AIM2 were significantly upregulated in HG-induced macrophages, upregulation of AIM2 in cardiac infiltrating macrophages was confirmed in a high-fat diet (HFD)/streptozotocin (STZ)-induceddiabetic mouse model . Therefore, AIM2 knockout mice were constructed. Compared to WT mice, HFD/STZ-induced cardiac hypertrophy and dysfunction were significantly improved in AIM2 -/- mice, despite no changes in blood glucose and body weight. Further, AIM2 deficiency inhibited cardiac recruitment of M1-macrophages and cytokine production. Mechanistically, AIM2-deficient macrophgaes reduced IL-1β and TNF-α secretion, which impaired the NLRC4/IRF1 signaling in cardiomyocytes, and reduced further recruitment of macrophages, attenuated cardiac inflammation and hypertrophy, these effects were confirmed by silencing IRF1 in WT mice, and significantly reversed by overexpression of IRF1 in AIM2 -/- mice. Taken together, our findings suggest that AIM2 serves as a novel target for the treatment of diabetic cardiomyopathy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Plant-based meat analogs require improvements in taste and texture to better replicate traditional meat. L-theanine and tannin, abundant in green tea, influence food taste and physicochemical properties. This study evaluated the quality characteristics of green tea extract (GE)-supplemented plant-based patties (PP) and the mechanisms affecting taste and texture. Green tea was extracted with water (GWE) or 70 % ethanol (GEE). GEE contained higher tannin and lower L-theanine levels than GWE. Both GWE and GEE reduced protein deterioration and lipid oxidation in PP throughout the 28-day storage period. PP with 1.0 % GEE (PP-GEE1.0) showed improved emulsion stability and texture due to non-covalent interactions including hydrophobic interaction and hydrogen bonds, and increased β-sheet structures between tannin and pea protein. PP-GEE1.0 also had superior sensory characteristics due to an optimal balance of L-theanine and tannin. Overall, the incorporation of GE, particularly GEE significantly improved physicochemical properties, sensory quality, and storage stability of PP., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Medical students perceive the transition to clerkship education as stressful and challenging and view themselves as novices during their rotation in clerkship education. The developmental perspective is thus important because the transition to clerkship supports rather than hinders growth. Accordingly, this study examines medical students' transition to clerkship and their developmental features., Methods: In-depth interviews were conducted with 18 medical students or graduates who had completed clerkships as medical students. Based on Straussian grounded theory, the collected data were analyzed in terms of the differences between pre- and post-clerkship education., Results: Our data analysis revealed five stages of the transition process: "anticipation and anxiety," "reality check," "seeking solutions," "practical application," and "transition and stability." The core category, that is, "growing up from being students to being student doctors," was driven by patients who perceived the participants as student doctors. Meanwhile, the participants recognized that having a solution that is agreed upon by colleagues was more important than knowing the correct answer. The participants undergoing the transition to clerkship showed developmental features divided into three categories: personal, social, and professional. Specifically, they attempted to balance clerkship and life through personal development, learned to navigate around the hospital and reduced tension through social development, and developed clinical competencies focused on efficiency through professional development., Conclusions: This study explores the process of students' transition to clerkship education and the developmental features that emerge during this period. The students were motivated by patients who perceived them as student doctors. Through the transition, they maintained a work-life balance and adapted to hospitals but developed an overly doctor-centered attitude by cultivating clinical competencies with a focus on efficiency. To develop them into medical professionals, it is essential to assist their transition and cultivate a patient-centered attitude., (© 2024. The Author(s).)

Competing Interests: The authors have no conflicts of interest to declare.

Alternative protein sources with greater nutritional value and a lower environmental footprint have recently attracted interest in the production of meat substitutes. However, it is required that these alternatives mimic the texture and structure of meat. This study investigated varying ratios of textured vegetable proteins (TVP) to Tenebrio molitor larvae (brown mealworm; TM) with the addition of transglutaminase (TG) to determine the quality characteristics of these emulsions. The results demonstrated low protein solubility of the emulsions as TVP content increased. Furthermore, when the proportion of TM was high, the TG-treated emulsion had a low pH. Additionally, when there was a high TM ratio to TVP in the TG treatment, the emulsions demonstrated better thermal stability and water holding capacity. Regarding the rheological properties of the emulsion, both the frequency-dependent storage modulus (G') and loss modulus (G'') increased as the proportion of TVP in the emulsion increased with and without the addition of TG. Differential scanning calorimetry analyses demonstrated two protein denaturation peaks in all treatments, with high peak temperatures for both treatments with a high proportion of TM. The hardness and chewiness of the emulsion were highest in the treatment (T6 and T8) with TG, and the gumminess of the emulsion was greatest when TM only or when equal ratios of TVP and TM were treated with TG, respectively. In conclusion, the addition of TM to TVP with TG improves the overall texture of the protein mixture, making it a suitable meat alternative., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Purpose: This study aimed to investigate the overall operational status of medical school admission interview evaluations in South Korea and explore the operational experience of universities conducting interview evaluations., Methods: This study used a mixed-methods approach, combining quantitative and qualitative methods. Through a nationwide survey and data collection from 39 medical schools, the quantitative analysis explored interview evaluations procedures, the purpose of the interview evaluations, and the competencies expected of medical school freshmen. Concurrently, qualitative data were obtained through focus group discussions with 12 professors from 10 medical schools, providing in-depth insights into the operational experiences and challenges faced during interview evaluations., Results: In the quantitative data, interview evaluations were most prevalent in the "comprehensive school records screening" for rolling admissions (85.5%), but less common in regular admissions (18.6%). Private schools (64.2%) showed a statistically significant higher proportion of interview admissions than public schools (11.1%) in the "high school grades focused admission" (p&lt;0.01). Metropolitan areas (50.0%) conducted interview evaluations more frequently than non-metropolitan areas (11.1%) in the "College Scholastic Ability Test-focused admissions" (p&lt;0.05). In the qualitative data, professors recognize the dominant role of "negative selection" in filtering out unsuitable candidates. Challenges in maintaining a consistent evaluator pool and team-based question development were acknowledged. Strategies, such as seeking student feedback for question improvement and conducting study meetings for interviewer preparation are essential., Conclusion: This study illuminates the operation of admissions interview evaluations in South Korea, revealing variations across regions and admissions types. These findings offer insights for enhancing medical school admission processes, guiding future research and policy.

PARP inhibitors (PARPi) show selective efficacy in tumors with homologous recombination repair (HRR)-defects but the activation mechanism of HRR pathway in PARPi-treated cells remains enigmatic. To unveil it, we searched for the mediator bridging PARP1 to ATM pathways by screening 211 human ubiquitin-related proteins. We discovered TRIM44 as a crucial mediator that recruits the MRN complex to damaged chromatin, independent of PARP1 activity. TRIM44 binds PARP1 and regulates the ubiquitination-PARylation balance of PARP1, which facilitates timely recruitment of the MRN complex for DSB repair. Upon exposure to PARPi, TRIM44 shifts its binding from PARP1 to the MRN complex via its ZnF UBP domain. Knockdown of TRIM44 in cells significantly enhances the sensitivity to olaparib and overcomes the resistance to olaparib induced by 53BP1 deficiency. These observations emphasize the central role of TRIM44 in tethering PARP1 to the ATM-mediated repair pathway. Suppression of TRIM44 may enhance PARPi effectiveness and broaden their use even to HR-proficient tumors., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background & Aims: Precise assessment of postoperative volume status is important to administrate optimal fluid management. Bioelectrical impedance analysis (BIA) which measures the body composition using electric character. Extracellular water (ECW) ratio by BIA represented as the ratio of ECW to total body water (TBW) and is known to reflect the hydration status. Based on this, we aimed to determine whether aggressive fluid control using ECW ratio could improve clinical outcomes through a single blind, randomized controlled trial., Methods: From November 2021 to December 2022, intensive care unit (ICU) patients admitted after surgery were randomly assigned to an intervention group or a control group whether postoperative fluid management was controlled via BIA. Among patients in the intervention group, dehydrated patients received a bolus infusion with crystalloid fluid whereas diuretics were administrated to overhydrated patients until the value of ECW ratio fell within its normal setting range (0.390-0.406). Contrarily, BIA was performed once a day for the control group. Patients in the control group received traditional fluid treatment regardless of BIA results. Primary outcome was in-hospital mortality in two groups. The secondary outcomes were postoperative morbidities, 28-day mortality., Results: 77 patients of the intervention group and 90 patients of the control group were finally analyzed. The in-hospital mortality (0 in intervention, 4.4% in control, p = 0.125) and 28-day mortality (1.3% in intervention, 14.4% in control, p = 0.002) showed lower incidence in the intervention group than in the control group. In multivariate analysis, the overhydrated status whose ECW ratio exceeding 0.406 [odds ratio (OR): 2.731, 95% confidence interval (CI): 1.001-7.663, p = 0.049] and high capillary leak index (CLI) value at ICU admission (OR: 1.024, 95% CI: 1.008-1.039, p = 0.002) were risk factors of postoperative morbidities. Regarding the 28-day mortality, high CLI value (OR: 1.025, 95% CI: 1.002-1.050, p = 0.037) and traditional strategy without BIA monitoring (OR: 9.903, 95% CI: 1.095-89.566, p = 0.041) were the significant predisposing factors., Conclusion: Our results revealed the rigorous fluid treatment with volume control based on ECW ratio by BIA failed to achieve significant improvement in in-hospital mortality, but it could reduce 28-day mortality of ICU patients. Monitoring of ECW ratio may help establish optimal fluid treatment strategies for postoperative ICU patients who are susceptible to fluid imbalances with fluid overload., Trial Registration: ClinicalTrials.gov, NCT06097923, retrospectively registered on October 16, 2023, https://clinicaltrials.gov/study/NCT06097923?term=NCT06097923&rank=1., Competing Interests: Conflict of interest The authors declare that there are no potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Anaerobic methanotrophic archaea (ANME) play key roles in buffering the methane budget in the deep-sea environment. This study aimed to explore the optimal environmental conditions for ANME enrichment. The result showed that the sample at 10.5 MPa contained the largest copy numbers of methyl-coenzyme M reductase alpha subunit (mcrA) gene (1.1 × 10 6 copies/g) compared to any other pressures and the sample at 4 °C contained higher mcrA gene (1.6 × 10 6 copies/g) than other temperatures. The optimal enrichment pressure for ANME-2c is 10.5 MPa at 4 °C, with an optimal subsequent incubation for ANME-2c less than 211days. Moreover, the beta nearest taxon index was significantly correlated with the incubation time (P<0.05). Total inorganic carbon and sulfate ion were key environmental factors driving community construction. This study offers insights into how ANME-2c was enriched and how species coexist in shared habitats during enrichment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Aim of the Study: We evaluated whether an artificial intelligence (AI)-driven robot cardiopulmonary resuscitation (CPR) could improve hemodynamic parameters and clinical outcomes., Methods: We developed an AI-driven CPR robot which utilizes an integrated feedback system with an AI model predicting carotid blood flow (CBF). Twelve pigs were assigned to the AI robot group (n = 6) and the LUCAS 3 group (n = 6). They underwent 6 min of CPR after 7 min of ventricular fibrillation. In the AI robot group, the robot explored for the optimal compression position, depth and rate during the first 270-second period, and continued CPR with the optimal setup during the next 90-second period and beyond. The primary outcome was CBF during the last 90-second period. The secondary outcomes were coronary perfusion pressure (CPP), end-tidal carbon dioxide level (ETCO 2 ) and return of spontaneous circulation (ROSC)., Results: The AI model's prediction performance was excellent (Pearson correlation coefficient = 0.98). CBF did not differ between the two groups [estimate and standard error (SE), -23.210 ± 20.193, P = 0.250]. CPP, ETCO 2 level and rate of ROSC also did not show difference [estimate and SE, -0.214 ± 7.245, P = 0.976 for CPP; estimate and SE, 1.745 ± 3.199, P = 0.585 for ETCO 2 ; 5/6 (83.3%) vs. 4/6 (66.7%), P = 1.000 for ROSC)., Conclusion: This study provides proof of concept that an AI-driven CPR robot in porcine cardiac arrest is feasible. Compared to a LUCAS 3, an AI-driven CPR robot produced comparable hemodynamic and clinical outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “Gil Joon Suh reports financial support was provided by National Research Foundation of Korea. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper”., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This analysis aimed to examine the factors predictive of service utilization among patients with anxiety and/or depression. Quick and appropriate treatment for anxiety and depression can reduce disease burden and improve social functioning. Currently, less than half of the population with comorbid anxiety and depression receives the recommended treatment., Aims: This analysis aims to identify factors predictive of utilizing mental health treatment for those with anxiety and/or depression by analyzing intrinsic, patient-centered factors., Methods: This study is a cross-sectional cohort analysis using National Health Interview Survey (NHIS) 2019 data. The sample size is 7,156 adults aged 18 to 64 with family incomes ≤100% of the federal poverty level. We used multivariate logistic regression analysis to identify factors predictive of care utilization in this population. Variables of interest include scores on Patient Health Questionnaire-8 (PHQ-8) and Generalized Anxiety Disorder-7 (GAD-7), service utilization, level of social functioning, having a usual source for care, and previous mental health care utilization. Additional covariates were age, gender, race, country of origin, education, marital status, and insurance coverage., Results: Twenty-one percent of respondents reported using mental health services. Factors predictive of care utilization were older age, female gender, limited social functioning, having a usual source of care, and insurance coverage., Conclusion: There are significant barriers to receiving quick and appropriate care for anxiety and/or depression. Strategies should focus on reducing barriers for young adults, men, and the uninsured/underinsured. Strategies for integrating mental health services into primary care could increase the percentage of people with anxiety and/or depression who receive services., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rationale & Objective: In this pilot study, we hypothesized that autosomal dominant polycystic kidney disease (ADPKD) is characterized by impaired kidney oxidative metabolism that associates with kidney size and cyst burden., Study Design: Cross-sectional study., Setting & Participants: Twenty adults with ADPKD (age, 31±6 years; 65% women; body mass index [BMI], 26.8 [22.7-30.4] kg/m 2 ; estimated glomerular filtration rate [eGFR, 2021 CKD-EPI creatinine], 103±18mL/min/1.73m 2 ; height-adjusted total kidney volume [HTKV], 731±370mL/m; Mayo classifications 1B [5%], 1C [42%], 1D [21%], and 1E [32%]) and 11 controls in normal weight category (NWC) (age, 25±3 years; 45% women; BMI, 22.5 [21.7-24.2] kg/m2; eGFR, 113±15mL/min/1.73m 2 ; HTKV, 159±31mL/m) at the University of Colorado Anschutz Medical Campus., Predictors: ADPKD status (yes/no) and severity (Mayo classifications)., Outcome: HTKV and cyst burden by magnetic resonance imaging, kidney oxidative metabolism, and perfusion by 11 C-acetate positron emission tomography/computed tomography, insulin sensitivity by hyperinsulinemic-euglycemic clamps (presented as ratio of M-value of steady state insulin concentration [M/I])., Analytical Approach: For categorical variables, χ 2 /Fisher's exact tests, and for continuous variables t tests/Mann-Whitney U tests. Pearson correlation was used to estimate the relationships between variables., Results: Compared with NWC individuals, the participants with ADPKD exhibited lower mean±SD M/I ratio (0.586±0.205 vs 0.424±0.171 [mg/kg lean/min]/(μIU/mL), P=0.04), lower median cortical perfusion (1.93 [IQR, 1.80-2.09] vs 0.68 [IQR, 0.47-1.04] mL/min/g, P<0.001) and lower median total kidney oxidative metabolism (0.17 [IQR, 0.16-0.19] vs. 0.14 [IQR, 0.12-0.15] min -1 , P=0.001) in voxel-wise models excluding cysts. HTKV correlated inversely with cortical perfusion (r: -0.83, P < 0.001), total kidney oxidative metabolism (r: -0.61, P<0.001) and M/I (r: -0.41, P = 0.03)., Limitations: Small sample size and cross-sectional design., Conclusions: Adults with ADPKD and preserved kidney function exhibited impaired renal perfusion and kidney oxidative metabolism across a wide range of cysts and kidney enlargements., Funding: Grants from government (National Institutes of Health, Centers for Disease Control and Prevention) and not-for-profit (JDRF) entities., Trial Registration: Registered at ClinicalTrials.gov with study numbers NCT04407481 and NCT04074668., Plain-Language Summary: In our study, we explored how a common genetic kidney condition, autosomal dominant polycystic kidney disease (ADPKD), relates to kidney metabolism. ADPKD leads to the growth of numerous cysts in the kidneys, which can impact their ability to work properly. We wanted to understand the kidneys' ability to process oxygen and blood flow in ADPKD. Our approach involved using advanced imaging techniques to observe kidney metabolism and blood flow in people with ADPKD compared with healthy individuals. We discovered that those with ADPKD had significant changes in kidney oxygen metabolism even when their kidney function was still normal. These findings are crucial as they provide deeper insights into ADPKD, potentially guiding future treatments to target these changes., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

A resurgence of Mycoplasma pneumoniae (MP)-the leading cause of community-acquired bacterial pneumonia, particularly in children-occurred following the COVID-19 pandemic. We aimed to investigate the clinical manifestations, macrolide resistance patterns, and therapeutic approaches related to the MP pneumonia epidemic. Children and adolescents diagnosed with MP pneumonia in September-December 2023 were screened. Clinical data were retrospectively collected from 13 major hospitals using concordant microbiological criteria, including either a positive PCR result or four-fold increase in serological markers. Demographic characteristics, treatment modalities, and clinical outcomes were analyzed. Of the 474 screened patients, 374 (median age: 7.7 [IQR, 5.4-9.6] years; hospitalization rate: 88.6%) met the microbiological confirmation criteria. Most patients experienced fever (98.9%), and lobular/lobar consolidation (59.1%) was the dominant radiological finding. The macrolide resistance rate remained high at 87.0%; corticosteroids were widely used (55.6%) alongside macrolides, despite resistance. Patients with consolidation had prolonged fever (median 8 vs. 7 days, p = 0.020) and higher hospitalization rates (92.3% vs. 83.0%, p = 0.008). Macrolide resistance did not significantly influence radiological outcomes. This study highlights the ongoing challenge of macrolide resistance in MP pneumonia and need for tailored therapeutic approaches. Despite high resistance, macrolides remain commonly prescribed, often concurrently with corticosteroids.

The association of overweight/obesity and metabolically unhealthy (MU) with the risk of developing Barrett's esophagus (BE) remains uncertain. We evaluated whether MU and overweight/obesity are associated with increased BE incidence and whether they have a synergistic impact on BE development. We analyzed the body mass index (BMI) and metabolic indicators at baseline of 402,510 individuals from the UK Biobank with no history of BE. Overweight/obesity and MU were defined as BMI ≥ 25.0 kg/m 2 and presence of ≥ 1 MU indicators, respectively. Accordingly, the participants were categorized into four groups: (1) metabolically healthy non-overweight/obesity (MHNO), (2) metabolically unhealthy non-overweight/obesity (MUNO), (3) metabolically healthy overweight/obesity (MHO), and (4) metabolically unhealthy overweight/obesity (MUO). During a median follow-up of 13.5 years, 6195 (1.5%) individuals were newly diagnosed with BE. Among them, 39,281 (9.8%), 92,000 (22.9%), 25,297 (6.3%), and 245,932 (61.1%) individuals were classified as MHNO, MUNO, MHO, and MUO, respectively. In Cox regression analyses, both MU and overweight/obesity were independently associated with BE incidence. Moreover, BE incidence was significantly higher in the MUNO, MHO, and MUO groups, compared to the MHNO group. MU and overweight/obesity are independent risk factors for BE and have a synergistic effect on BE development., (© 2024. The Author(s).)

Objectives: This study aimed to identify the specific vaccine strain associated with herpes zoster (HZ) in children following a series of diagnosed cases and to explore whether differences in single nucleotide polymorphisms (SNPs) among various vaccine strains are linked to an increased incidence of herpes zoster after vaccination., Methods: From February 2021 to March 2024, children <12 years old suspected of vaccine-related varicella-like rash or HZ were included. Varicella zoster virus DNA isolated from the patients were sequenced to differentiate vaccine type versus wild-type. 3D protein structures of pORF62 were simulated using open reading frame 62 sequences extracted from whole genome sequencing of vOka, MAV/06, Oka/SK vaccines, and pOka reference., Results: A total of 27 children with a median age of 2.1 (interquartile range, 1.5-3.4) years old presented with vaccine-related varicella-like rash (n = 4/27, 14.8%) or HZ (n = 23/27, 85.2%). One patient with varicella-like rash and 34.8% (n = 8/23) with HZ had disseminated skin involvement. All were immunized with the Oka/SK strain varicella vaccine. Genotyping showed 88.2% (n = 15/17) had SNPs specific to the Oka/SK strain, and two had SNPs considered pOka type contained within the Oka/SK vaccine. Despite accumulations of SNPs in ORF 62 of Oka/SK, the translated amino acid sequence and 3D protein structure were identical to wild-type pOka's pORF62. In vOKA and MAV/06, changes in amino acids occurred at two positions, S628G and R958G, within pORF62. The predicted 3D protein structure of vOka and MAV/06's pORF62 showed that the α helical structure within region I undergoes conformational change, potentially increasing difficulties in interactions with infection-related proteins and thereby decreasing virulence. pORF62 in pOka and Oka/SK exhibited more stable structure complex of the α helical structure., Discussion: Lack of structural alternations in region I of pORF62 due to the absence of critical genetic polymorphisms in open reading frame 62 could be associated with the heightened incidence of adverse events., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study was to 1) describe oncology caregivers' pre-treatment preparation experiences, 2) elicit their feedback about approaches to improve the pre-treatment preparation experience, and 3) explore the potential use of visual aids into the pre-treatment education experience that will inform future clinician-led VR experiences., Methods: Using a qualitative descriptive design and convenience sampling technique, adult oncology caregivers were recruited to complete anonymous demographic and qualitative surveys posted on social media sites (i.e. American Cancer Society, Facebook, and LinkedIn) and a university supported community research registry (i.e. Pitt + Me). Demographic data were calculated using descriptive analyses (frequency and percentage) and qualitative data were analyzed using an inductive coding approach., Results: Participants (N=18) were mostly female (n=13, 72%), white (n=14, 78%), married (n=14, 78%), and had a college degree or higher (n=16, 89%). They categorically ranged in age from 26 years to above 65 years, with the majority (n=11, 61%) between 36-55 years of age. Caregivers described the cancer information as overwhelming and in need of additional side effect information and emotional support. To meet their unmet needs, participants suggested providing additional resources, different approaches to learning, better explanation of processes and procedures, diverse emotional support, and more interactions with the oncology team., Conclusion: Clinician created VR experiences designed for and informed by oncology caregivers do not exist yet. VR could provide an alternative pediogogical approach to complement standard oncology treatment preparation. These study findings begin the exploration into innovative preparation approaches that could meet oncology caregivers' unmet emotional and educational needs during a stressful period., Key Highlights: There is a dearth of clinicians creating and testing VR experiences for patients, let alone caregivers. Oncology caregivers are the unseen 'backbone' supporting their loved one and providing an innovative modality to support them could improve outcomes. VR has the potential improve outcomes for caregivers, which may improve outcomes for patients., (2024 The journal and its content is copyrighted by the Delaware Academy of Medicine / Delaware Public Health Association (Academy/DPHA).)

Background: The aim of this study was to elucidate individual difference factors that modulate the attentional processing of game stimuli to explain the heterogeneity of extant findings. The current study examined whether individual differences in components of attentional control (AC-shifting and AC-focusing) moderated the link between internet gaming addiction symptom and attentional engagement to and disengagement biases from game-relevant cues., Methods: A total of 75 male undergraduate students who have played League of Legend (LOL) for more than 2 years completed well-established self-report questionnaires of internet gaming disorder symptoms and attentional control. The attentional bias toward game stimuli was measured for attentional engagement and disengagement using the attentional response to the distal vs. proximal emotional information (ARDPEI) task., Results: The results revealed that attentional control was a significant moderator of the relationship between internet game addiction symptoms and attentional disengagement bias. Further analyses revealed a positive relationship between internet game addiction symptoms and attentional disengagement bias only among those with low levels of AC-shifting ability. Contrary to our expectations, AC-shifting also moderated the relationship between internet gaming disorder and attentional engagement bias. The positive relationship between internet game addiction symptoms and attentional engagement bias only appeared among those with low levels of AC-shifting ability. Individual differences in AC-focusing did not moderate the relationship between internet gaming disorder and any attentional bias., Conclusion: This study confirmed that the greater the symptoms of game addiction, the stronger the attentional bias, especially in individuals with low AC-shifting ability. Therefore, it is necessary to examine sub-factors of AC in understanding the nature of attentional bias mechanisms in the development of internet game addiction and consider it as a psychological intervention to improve attentional bias., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Heo, Lee and Lee.)

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and multiple vital organs, but the immunological pathogenesis of SSc remains unclear. We show here that miR-19b promotes Th9 cells that exacerbate SSc. Specifically, miR-19b and interleukin (IL)-9 increase in CD4 + T cells in experimental SSc in mice induced with bleomycin. Inhibiting miR-19b reduces Th9 cells and ameliorates the disease. Mechanistically, transforming growth factor beta (TGF-β) plus IL-4 activates pSmad3-Ser 213 and TRAF6-K63 ubiquitination by suppressing NLRC3. Activated TRAF6 sequentially promotes TGF-β-activated kinase 1 (TAK1) and nuclear factor κB (NF-κB) p65 phosphorylation, leading to the upregulation of miR-19b. Notably, miR-19b activated Il9 gene expression by directly suppressing atypical E2F family member E2f8. In patients with SSc, higher levels of IL9 and MIR-19B correlate with worse disease progression. Our findings reveal miR-19b as a key factor in Th9 cell-mediated SSc pathogenesis and should have clinical implications for patients with SSc., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The surgical treatment of optic pathway gliomas (OPG) remains controversial, with visual outcomes often unpredictable. The present study explored surgical and clinical factors influencing visual acuity (VA) after OPG treatment and developed anatomical subtypes correlated with clinical symptoms., Methods: Children with OPG who underwent initial partial tumor resection at Beijing Tiantan Hospital from January 2011 to December 2022 were retrospectively analyzed. Multivariate logistic regression and random forest analyses were performed to identify risk factors for post-treatment VA deterioration and a decision tree model was created based on significant factors., Results: A total of 140 patients were enrolled. Multivariate logistic regression analysis identified surgical approach and initial VA as independent predictors of post-treatment VA deterioration (P < 0.05). Surgical approach, initial VA, and extent of tumor resection were the most significant factors for risk assessment and were included in the decision tree model, with surgical approach as the most important "root" node. The model demonstrated good predictive performance, with area under the curve values of 0.75 and 0.66 for the training and test datasets, respectively. A simple anatomical classification was developed, which revealed clinical characteristic differences among OPG types. Meanwhile, a correlation analysis of post-treatment visual deterioration was performed for each of the three anatomical types., Conclusion: This study offers a predictive model for visual outcomes following initial tumor-reduction surgery in OPG patients, which may help in visual outcomes risk stratification. Additionally, the anatomical classification effectively indicates OPG growth direction, offering potential insights into clinical symptoms., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Family caregivers (CGs) of individuals with cancer are increasingly relied upon to provide long-term, sometimes intense care, although their integration into clinical cancer care remains minimal. The Caregiver Advocacy, Research, and Education (CARE) Center is a novel nurse-led academic-clinical partnership to support family CGs of individuals with gynecologic cancer. This study aims to describe the implementation of the Center protocols and report metrics of CG needs and Center support., Materials and Methods: The Center's goals are to identify, assess, and provide tailored support to CGs. Initially, Center protocols included assessment of CGs' self-identified distress (distress thermometer, 0 = no distress to 10 = extreme distress) and needs (yes or no). Tailored support on the basis of CG distress was provided by in-person and remote staff who provided complementary, concurrent support based on CG need: evidence-based self-management guides, self-management support, referral to specialty services. Center documentation was analyzed to describe Center reach and CG distress., Results: From November 2019 to June 2023, CGs (N = 1,250) were identified through referrals, new patient outreach, and inpatient visits. Seven hundred and six CGs (56.5%) were assessed through a needs-based assessment, and 515 (41.2%) CGs received tailored support. CGs were mostly men (53.0%) and the mean distress was 4.4/10 (standard deviation, 3.1). CG distress was moderately associated with CG needs including maintaining emotional (ρ = 0.40; P < .001) and physical (ρ = 0.31; P < .001) health and managing patient symptoms (ρ = 0.33; P < .001)., Conclusion: Center protocols facilitate identification of high-need CGs within a cancer clinic. Future research will longitudinally evaluate the impact of Center protocols on CG and patient outcomes, incorporating updated assessment tools.

A series of successes in RNA interference (RNAi) therapies for liver diseases using lipid nanoparticles and N -acetylgalactosamine have heralded a current era of RNA therapeutics. However, alternative delivery strategies are required to take RNAi out of the comfort zone of hepatocytes. Here we report SIRPα IgV/anti-CD47 siRNA (vS-siCD47) conjugates that selectively and persistently disrupt the antiphagocytic CD47/SIRPα axis in solid tumors. Conjugation of the SIRPα IgV domain protein to siRNAs enables tumor dash through CD47-mediated erythrocyte piggyback, primarily blocking the physical interaction between CD47 on cancer cells and SIRPα on phagocytes. After internalization of the vS-siCD47 conjugates within cancer cells, the detached free-standing anti-CD47 siRNAs subsequently attack CD47 through the RNAi mechanism. The dual-action approach of the vS-siCD47 conjugate effectively overcomes the "don't eat me" barrier and stimulates phagocyte-mediated tumor destruction, demonstrating a highly selective and potent CD47-blocking immunotherapy. This delivery strategy, employing IgV domain protein-siRNA conjugates with a dual mode of target suppression, holds promise for expanding RNAi applications beyond hepatocytes and advancing RNAi-based cancer immunotherapies for solid tumors.

Phosphogypsum is a solid waste with great environmental stockpile pressure produced by the wet production of phosphoric acid. Although there are various methods to purify and utilize phosphogypsum, the means for environmentally friendly, low energy consumption, and high value-added utilization still need to be further explored. Here, CaSO 4 ·2H 2 O crystal was directly purified and regulated from phosphogypsum by using the anti-solvent method. The antisolvent can be adsorbed in the c -axis direction of the crystal and further inhibit the growth rate in this direction, resulting in a change in the morphology of the crystal. By adjusting the polarity and chain length of the anti-solvent, the morphology of CaSO 4 ·2H 2 O crystal can change from butterfly-like flake crystals to hexagonal prism-like crystals. When n-propanol with long chain was used as the anti-solvent, the morphology of the CaSO 4 ·2H 2 O crystal showed a hexagonal prism with a specific surface area of 19.98 m 2 /g and a Cu 2+ loading efficiency of 52.67%. The encouraging results open up new possibilities for the application of phosphogypsum.

Proper nutrition during childhood is crucial for preventing chronic diseases and ensuring optimal growth. This study aimed to develop and validate the Korean version of the KIDMED (K-KIDMED) questionnaire to accurately measure Mediterranean diet (MD) adherence among Korean children and adolescents. A total of 226 parents, representing their children and adolescents, completed the K-KIDMED, a 112-item food frequency questionnaire (FFQ), and a 24-h dietary recall method through an anonymous online survey. The K-KIDMED comprised 11 questions, with five excluded from the original scoring as they did not apply to the FFQ. Scores were categorized into three levels of adherence to the MD: low (1 or less), average (2-4), and good (5 or more). The agreement between total MD scores from the Korean version of the Mediterranean diet adherence screener and the FFQ was moderate (intraclass correlation coefficient = 0.455, 95% confidence interval: 0.346, 0.553). Among the 226 children and adolescents, 36.7% had low adherence to the KIDMED, 43.3% had intermediate adherence, and 19.9% had good adherence. Higher K-KIDMED scores were correlated with greater intakes of fiber, vitamin K, vitamin B6, and potassium (all p < 0.05). We developed the K-KIDMED as a valid tool to assess MD adherence in Korean children and adolescents.

Objectives: This systematic review aims to explore virtual reality (VR) applications for rehabilitation purposes among people with intellectual and developmental disabilities (IDD), identify their effects on rehabilitation outcomes, explore themes to consider in VR intervention design, and provide guidance for designers and researchers in creating therapeutic environments using VR technology., Background: VR has gained increasing attention in healthcare settings to assist in achieving rehabilitation goals for people with IDD. VR is particularly advantageous since it simulates the real world while providing controllable, safe, and versatile environments. It is necessary to expand the current body of knowledge on VR intervention's outcomes by synthesizing further information on VR application characteristics as well as identifying design considerations regarding feasibility, usability, safety, and other aspects that will benefit future VR intervention design and research., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framed the current review. Multiple databases were searched to identify studies published between 2001 and 2023. The review qualitatively organized VR environment design considerations according to three themes: feasibility, usability, and safety., Results: This review included 27 articles and included 868 participants. The overall findings indicated that VR interventions are promising in enhancing rehabilitation outcomes among people with IDD, such as physical, cognitive, emotional, and functional independence domains., Conclusion: This review provides design recommendations to create effective, usable, and safe VR interventions for individuals with IDD. The suggested design implications should be applied with the awareness that VR is a relatively emerging technology with rapidly evolving features., Competing Interests: Declaration of Conflicting InterestsThe authors declare that there is no conflict of interest.

Cardiovascular disease is a major global health concern, with early detection being critical. This study assesses the effectiveness of a portable ECG device, based on Internet of Medical Things (IoMT) technology, for remote cardiovascular monitoring during daily activities. We conducted a clinical trial involving 2000 participants who wore the HiCardi device while engaging in hiking activities. The device monitored their ECG, heart rate, respiration, and body temperature in real-time. If an abnormal signal was detected while a physician was remotely monitoring the ECG at the IoMT monitoring center, he notified the clinical research coordinator (CRC) at the empirical research site, and the CRC advised the participant to visit a hospital. Follow-up calls were made to determine compliance and outcomes. Of the 2000 participants, 318 showed abnormal signals, and 182 were advised to visit a hospital. The follow-up revealed that 139 (76.37%) responded, and 30 (21.58% of those who responded) sought further medical examination. Most visits (80.00%) occurred within one month. Diagnostic approaches included ECG (56.67%), ECG and ultrasound (20.00%), ultrasound alone (16.67%), ECG and X-ray (3.33%), and general treatment (3.33%). Seven participants (23.33% of those who visited) were diagnosed with cardiovascular disease, including conditions such as arrhythmia, atrial fibrillation, and stent requirements. The portable ECG device using the patch-type electrocardiograph detected abnormal cardiovascular signals, leading to timely diagnoses and interventions, demonstrating its potential for broad applications in preventative healthcare., Competing Interests: The authors declare no conflicts of interest.

Gizzerosine is a biogenic amine produced in fish meal drying process and posted higher mortality due to gizzard erosion in poultry than histamine. However, it is difficult to obtain gizzerosine and achieve sensitive practical detection due to its simple structure. Herein, a monoclonal antibody (mAb) specific to gizzerosine was generated based on the new structural design and a fluorescence immunosensor for sensitive and on-site detection of gizzerosine in feed was first established. Molecular modeling of the three-dimensional (3D) structure and surface electrostatic potential of gizzerosine indicated that the carbonyl group of gizzerosine hapten might affect the important sites of antigen-antibody interactions. The proposed structure was used to obtain the sensitive and specific mAb with IC 50 of 3.88 ng/mL in indirect competitive ELISA which was approximately 100-fold lower than that of direct competitive ELISA. Considering the practical application scenarios, a fluorescence immunosensor based on microporous dry method integrated with independent quality control line was established to improve detection stability. Under the optimum conditions, the proposed immunosensor showed a good linear relationship from 1.10 to 19.78 ng/mL and provided a low detection limit of 50 ng/g which was approximately 80-fold lower than the maximum recommended amount (0.4 mg/kg) of gizzerosine in feed. The recoveries of 6 kinds of feed ranged from 83.1 % to 114.3 %, which was in good consistence with that of UHPLC-MS/MS. Overall, this work provides a fast, cost-effective and reliable on-site tool for rapid screening of gizzerosine residues in feed samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Importance: EGFR-variant non-small cell lung cancer (NSCLC) is associated with a high rate of central nervous system (CNS) metastases, even with treatment with first-generation or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)., Objective: To investigate CNS activity with lazertinib, a third-generation EGFR TKI., Design, Setting, and Participants: This multicenter single-arm, phase 2 nonrandomized controlled trial was conducted in South Korea and included patients with EGFR-variant NSCLC who had asymptomatic or mildly symptomatic brain metastases after unsuccessful treatment with first-generation or second-generation EGFR TKIs. Data were collected from June 2021 to April 2022, with a data cutoff date of December 15, 2022., Exposure: Lazertinib, 240 mg, once daily., Main Outcomes and Measures: The primary end point was intracranial objective response rate (iORR) in the evaluable population according to the Response Evaluation Criteria in Solid Tumours version 1.1 assessed by the investigators. Secondary end points included intracranial progression-free survival (iPFS) and iORR in patients with T790M-negative disease and isolated CNS progression as well as overall ORR, duration of response, intracranial duration of response, disease control rate, overall survival, cerebrospinal fluid penetration of lazertinib, and safety., Results: Among 40 included patients, 25 (63%) were women, and the median (range) age was 63 (29-85) years. A total of 38 patients were evaluable for tumor response, including 12 patients with leptomeningeal metastases. At data cutoff, the median (range) follow-up was 13.6 (2.9-17.7) months. The iORR for the evaluable population was 55% (21 of 38; 95% CI, 38.3-71.4); for patients with T790M-positive disease, 80% (4 of 5; 95% CI, 28.4-99.5); for patients with T790M-negative disease, 43% (9 of 21; 95% CI, 21.8-66.0); and for patients with T790M-unknown disease, 67% (8 of 12; 95% CI, 34.9-90.1). The median iPFS was 15.8 months (95% CI, 15.2-not reached) for the evaluable population, 15.2 months (95% CI, 4.2-not reached) for the T790M-positive subgroup, 15.4 months (95% CI, 7.9-not reached) for the T790M-negative subgroup, and 18.0 months (95% CI, 3.9-not reached) for the T790M-unknown subgroup. The cerebrospinal fluid penetration rate of lazertinib was 46.2% (95% CI, 10.0-49.6), providing further support for its mechanism of intracranial response. Most adverse events were grade 1 or 2., Conclusions and Relevance: In this study, lazertinib had substantial CNS activity, regardless of T790M status, against the progression of intracranial metastases with or without leptomeningeal metastases after unsuccessful treatment with first-generation or second-generation EGFR TKIs in patients with metastatic EGFR-variant NSCLC. These results suggest that using lazertinib instead of brain local treatment could be a potential strategy in patients with EGFR-variant NSCLC whose CNS metastases progressed after prior EGFR TKI treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT05326425.

Background: Atopic dermatitis (AD) is a chronic inflammatory cutaneous disorder, that emerges from intricate interplays among genetic predisposition, immune dysregulation, environmental factors, and compromised skin barrier. Understanding the inflammatory pathway in AD is important due to its fundamental role in the pathogenesis of AD. This study aimed to explore the diverse spectrum of proteins linked to the inflammation of AD and the relationship between systemic biomarkers and clinical severity in AD., Methods: We examined the blood samples from 48 patients with AD and 48 healthy controls (HCs) using the Proximity Extension Assay (Olink). Differentially expressed proteins (DEPs) were identified and Pearson correlation analysis was conducted to determine systemic proteomic biomarkers associated with severity of AD., Results: A total of 29 DEPs were significantly up-regulated and 2 DEPs were significantly down-regulated in AD compared with the HC. The MCP-4, IL-18, MCP-3, TNFRSF9, and IL-17C were the top 5 highest DEPs associated with the severity of AD., Conclusion: Our study sheds light on the intricate network of inflammatory proteins in AD and their potential implications for disease severity. Our results indicate that these systemic inflammatory proteins could be valuable for assessing AD severity and enhancing our understanding of the disease's complexity and its potential management strategies., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Cardiovascular diseases (CVDs) have been associated with atopic dermatitis (AD), including in Korean patients. Previous studies on AD have primarily focused on patients of European ancestry, while the Asian endotype exhibits distinct characteristics. This study aimed to characterize the blood proteomic signature of Korean patients with moderate-to-severe AD, with an emphasis on proteins related to CVDs., Methods: A total of 78 participants, including 39 patients with moderate-to-severe AD and 39 age- and sex-matched healthy controls, were enrolled. Blood proteomics analysis was performed using the Olink CVD II panel, which measures the expression levels of 92 proteins associated with CVDs., Results: Unsupervised hierarchical clustering revealed 44 upregulated and 5 downregulated proteins in AD patients compared to healthy controls. Principal component analysis (PCA) effectively distinguished AD patients from healthy subjects based on the complete set of proteins or the subset of upregulated proteins. A multiple linear regression model comprising CCL17 and FGF21 showed a strong correlation with disease severity (R = 0.619). Correlation analysis identified 25 highly correlated proteins, including STK4, ITGB1BP2, and DECR1, which were newly found to be upregulated in Korean AD patients. Pathway analysis highlighted the involvement of these proteins in vascular system, inflammation, and lipid metabolism pathways., Conclusion: The blood proteomic profile of moderate-to-severe AD patients in Korea differed from healthy controls using the CVD II panel. This study provides potential biomarkers for the AD-CVD association and insights into the pathways contributing to this relationship in the Korean population., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Authors.)

Insomnia is a common sleep disorder with significant societal and economic impacts. Current pharmacotherapies for insomnia are often accompanied by side effects, necessitating the development of new therapeutic drugs. In this study, the hypnotic effects and mechanisms of Sedum kamtschaticum 30% ethanol extract (ESK) and one of its active compounds, myricitrin, were investigated using pentobarbital-induced sleep experiments, immunohistochemistry (IHC), receptor binding assays, and enzyme-linked immunosorbent assay (ELISA). The pentobarbital-induced sleep experiments revealed that ESK and myricitrin reduced sleep latency and prolonged total sleep time in a dose-dependent manner. Based on c-Fos immunostaining, ESK, and myricitrin enhanced the GABAergic neural activity in sleep-promoting ventrolateral preoptic nucleus (VLPO) GABAergic. By measuring the level of GABA released from VLPO GABAergic neurons, ESK and myricitrin were found to increase GABA release in the hypothalamus. These effects were significantly inhibited by SCH. Moreover, ESK exhibited a concentration-dependent binding affinity for the adenosine A 2A receptors (A 2A R). In conclusion, ESK and myricitrin have hypnotic effects, and their underlying mechanisms may be related to the activation of A 2A R.

Microorganisms produce extracellular enzymes to meet elemental requirements and cope with stoichiometric imbalances of resources. To gain insights into the cycling of C, N, and P, the activities of the C∶N∶P acquisition enzymes have been extensively investigated. To detect the effects of long-term fertilization practices on soil nutrient balance and characteristics of soil enzymatic stoichiometry in black soil, four different fertilization treatments were selected： no fertilization （CK）, nitrogen fertilizer （N）, phosphorus fertilizer （P）, and combination of nitrogen and phosphorus fertilizers （NP）. Soil samples were collected in both April 2021 and April 2022 to determine soil enzyme activities and their stoichiometric characteristics. The results showed that soil acid phosphatase and β -D-glucosidase activities were significantly higher in the N and NP treatments than in CK by 68%-158% and 26%-222%, respectively. Soil β -N-acetylaminoglucosidase activities were significantly higher in the P and NP treatments, with the highest around 75.48 nmol·（g·h） -1 and 106.81 nmol·（g·h） -1 , respectively. Two-way ANOVA analysis showed that N and P inputs had a great impact on soil enzyme activities. Redundancy analysis showed that the main factors controlling enzyme activities were soil pH, microbial biomass phosphorus, and soil available P content. It was found that N inputs significantly increased enzyme vector length, which was ranged from 1.32 to 1.52, and the enzyme vector angles were all larger than 45°, suggesting C and P co-limited in the black soils. These findings suggest that 40 years of fertilization have had a great impact on soil enzymes and the related resource use strategy, which provides great implications for assessing soil nutrients balance and soil sustainability.

Background/objectives: Platycodon grandiflorum (PG) is used in traditional oriental medicine to treat several ailments., Methods: The study investigated the anti-inflammatory and neuroprotective effects of PGW ( P. grandiflorum ) extract in Aβ25-35-induced inflammation in BV2 microglia cells., Result: PGW demonstrated significant inhibition of nitric oxide (NO) production, with reductions of 30.4, 36.7, and 61.2% at concentrations of 50, 100, and 200 μg/mL, respectively. Moreover, PGW effectively suppressed the production of pro-inflammatory cytokines IL-1β and IL-6 and exhibited significant inhibitory activity against TNF-α at 200 μg/mL. Furthermore, PGW treatment mitigated apoptosis in Aβ-induced BV2 cells by modulating the mitochondrial apoptosis pathway, regulating Bcl-2 family protein synthesis, and inhibiting caspase activation. Mechanistically, PGW attenuated the activation of the MAPK (JNK, ERK, p38) pathway induced by Aβ, showing a concentration-dependent decrease in phosphorylation levels of these proteins. Additionally, PGW inhibited the NF-κB pathway activation by reducing the phosphorylation levels of p65 and IκBα in a concentration-dependent manner., Conclusion: PGW demonstrated anti-inflammatory and neuroprotective effects in Aβ-induced neuronal cells, suggesting its potential as a therapeutic agent for neuroinflammatory associated with neurodegenerative diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ji, Kang, Kim, Kim and Jang.)

High-aspect-ratio patterns are required for next-generation three-dimensional (3D) semiconductor devices. However, it is challenging to eliminate voids and seams during gap-filling of these high-aspect-ratio patterns, such as deep trenches, especially for nanoscale high-aspect-ratio patterns. In this study, a SiO 2 plasma-enhanced atomic layer deposition process incorporated with ion collision using bias power to the substrate was used for bottom-up trench gap-filling. The effect of bias power frequency on SiO 2 trench gap-filling was then investigated. Results showed that changes in bias power frequency did not significantly change the process rate, such as SiO 2 growth per cycle. At relatively low bias power frequencies, high-energy ions formed an overhang at the entrance of the high-aspect-ratio trench pattern through sputter etching and redeposition, blocking the pattern entrance. However, at relatively high-frequency bias power, overhang formation due to sputtering did not occur. In the trench interior, due to a scattering effect of ions, deposition was thicker at the bottom of the trench than that at the top, achieving bottom-up gap-filling and void-free gap-filling.

Background/aims: Potassium channel tetramerization domain containing 17 (KCTD17) protein, an adaptor for the cullin3 (Cul3) ubiquitin ligase complex, has been implicated in various human diseases; however, its role in hepatocellular carcinoma (HCC) remains elusive. Here, we aimed to elucidate the clinical features of KCTD17, and investigate the mechanisms by which KCTD17 affects HCC progression., Methods: We analyzed transcriptomic data from patients with HCC. Hepatocyte-specific KCTD17 deficient mice were treated with diethylnitrosamine (DEN) to assess its effect on HCC progression. Additionally, we tested KCTD17-directed antisense oligonucleotides for their therapeutic potential in vivo., Results: Our investigation revealed the upregulation of KCTD17 expression in both tumors from patients with HCC and mouse models of HCC, in comparison to non-tumor controls. We identified the leucine zipper-like transcriptional regulator 1 (Lztr1) protein, a previously identified Ras destabilizer, as a substrate for KCTD17-Cul3 complex. KCTD17-mediated Lztr1 degradation led to Ras stabilization, resulting in increased proliferation, migration, and wound healing in liver cancer cells. Hepatocyte-specific KCTD17 deficient mice or liver cancer xenograft models were less susceptible to carcinogenesis or tumor growth. Similarly, treatment with KCTD17-directed antisense oligonucleotides (ASO) in a mouse model of HCC markedly lowered tumor volume as well as Ras protein levels, compared to those in control ASO-treated mice., Conclusions: KCTD17 induces the stabilization of Ras and downstream signaling pathways and HCC progression and may represent a novel therapeutic target for HCC.

Rationale: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by an antibody that inhibits coagulation factor VIII activity. More than half of patients with AHA cannot identify underlying disorders. The remaining patients are associated with malignancies, autoimmune diseases, skin diseases, infections, and medications. Here, we present a case of 56-year-old Korean man with underlying hypertension, dyslipidemia, and diabetes mellitus who developed AHA following the second dose of BNT162b2 COVID-19 vaccination., Patient Concerns: He presented with a large 20 × 30 cm-sized hematoma along the psoas muscle and intracranial hemorrhage, necessitating intensive care with mechanical ventilation and continuous renal replacement therapy. Laboratory testing demonstrated that activated partial thromboplastin time and prothrombin times were 74.7 seconds (normal range 29-43 seconds) and 17.2 seconds (normal range 12.5-14.7 seconds), respectively., Diagnoses: Laboratory tests confirmed AHA with undetectable factor VIII activity (<1.5%) and a positive factor VIII antibody with a titer of 8.49 Bethesda units/mL., Interventions: Recombinant factor VIIa (NovoSeven®) was administered every 2 hours to control the bleeding, alongside immunosuppression with methylprednisolone 1 mg/kg daily and cyclophosphamide 2 mg/kg daily to eliminate the autoantibody., Outcomes: Despite the treatments, the patient developed sepsis and succumbed 14 weeks after admission., Lessons: This rare case underscores the importance of monitoring for AHA following COVID-19 vaccination. Although the benefits outweigh the risks of vaccination, AHA should be considered in the differential diagnosis of unusual bleeding following the vaccinations. Early diagnosis and management before severe bleeding are critical for successfully controlling life-threatening bleeding., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)