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Abstract Nicotinamide phosphoribosyltransferase (NAMPT) is a metabolic enzyme with key roles in inflammation. Previous studies have examined the consequences of its upregulated expression in cancer cells themselves, but studies are limited with respect to its role in the other cells within the tumor microenvironment (TME) during colorectal cancer (CRC) progression. Using single‐cell RNA sequencing (scRNA‐seq) data, it is founded that NAMPT is highly expressed in SPP1+ tumor‐associated macrophages (TAMs), a unique subset of TAMs associated with immunosuppressive activity. A NAMPThigh gene signature in SPP1+ TAMs correlated with worse prognostic outcomes in CRC patients. The effect of Nampt deletion in the myeloid compartment of mice during CRC development is explored. NAMPT deficiency in macrophages resulted in HIF‐1α destabilization, leading to reduction in M2‐like TAM polarization. NAMPT deficiency caused significant decreases in the efferocytosis activity of macrophages, which enhanced STING signaling and the induction of type I IFN‐response genes. Expression of these genes contributed to anti‐tumoral immunity via potentiation of cytotoxic T cell activity in the TME. Overall, these findings suggest that NAMPT‐initiated TAM‐specific genes can be useful in predicting poor CRC patient outcomes; strategies aimed at targeting NAMPT may provide a promising therapeutic approach for building an immunostimulatory TME in CRC progression.

Students vary in their perceptions of teachers' motivational supports, even within the same classroom, but it is unclear why this is the case. To enable the design of equitable environments and understand the theoretical nature of motivational climate, this study explored demographic differences in university students' perceptions of instruction across five large, introductory STEM (science, technology, engineering, and mathematics) courses (N = 2,486), along with end-of-semester outcomes. Results indicated that women and students from traditionally underrepresented racial or ethnic groups (Black, Hispanic/Latino/a, or Indigenous students) tended to perceive slightly higher motivational support in their courses compared to men and traditionally overrepresented (White or Asian) students, respectively. However, patterns were not uniform across all courses or variables. Men and women did not significantly differ on end-of-semester interest in any course, but women tended to have lower self-efficacy in some courses and significantly higher grades in programming compared to men. Implications include a caution for researchers against interpreting sample-specific or aggregated evidence of demographic differences as generalizing to broader populations or specific settings.

Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD+) salvage pathway and plays a crucial role in the maintenance of the NAD+ pool during inflammation. Considering that macrophages are essential for tissue homeostasis and inflammation, we sought to examine the functional impact of NAMPT in inflammatory macrophages, particularly in the context of inflammatory bowel disease (IBD). In this study, we show that mice with NAMPT deletion within the myeloid compartment (Namptf/fLysMCre+/-, Nampt mKO) have more pronounced colitis with lower survival rates, as well as numerous uncleared apoptotic corpses within the mucosal layer. Nampt-deficient macrophages exhibit reduced phagocytic activity due to insufficient NAD+ abundance, which is required to produce NADPH for the oxidative burst. Nicotinamide mononucleotide (NMN) treatment rescues NADPH levels in Nampt mKO macrophages and sustains superoxide generation via NADPH oxidase. Consequently, Nampt mKO mice fail to clear dead cells during tissue repair, leading to substantially prolonged chronic colitis. Moreover, systemic administration of NMN, to supply NAD+, effectively suppresses the disease severity of DSS-induced colitis. Collectively, our findings suggest that activation of the NAMPT-dependent NAD+ biosynthetic pathway, via NMN administration, is a potential therapeutic strategy for managing inflammatory diseases.

Although a diversity of religions exists in South Korea, with Buddhism and Christianity (Protestantism and Catholicism) being the two main faiths, Korean beliefs are deeply rooted in Confucianism. Despite the notion that the Confucian norm of filial piety discourages body donation to medical science, there has been a mindset shift in favor of body donation, driven by a heightened awareness of the body bequest programs and the care and dignity accorded to the altruistic body donors, together with the institution of commemorative services to honor them. As spirituality and religion are known to be factors that influence body donation, how religious- and non-religious-based memorial services are held to honor the donors as exemplified by two Korean medical schools--from a public university with no religious affiliation and from a Protestant-based university--are described here. The key concept of expressing gratitude and respect for the donors and their family members has positively impacted body bequest programs in this multi-religious society. Commemorative services held to pay tribute to the altruistic body donors may play an important role in inspiring a humanistic spirit in students, regardless of religious or non-religious beliefs, as exemplified by the two Korean medical schools. The takeaway here is that the elevation of spirituality in memorial services effectively resonates with society, thereby demonstrating the impact of spiritual principles independent of religious influence.

This study developed a brief training, the Integrative Writing Training (IWT), to introduce students to two types of rhetorical devices (i.e., direct and indirect integration) that can be used to communicate cross-textual connections through writing. The training did not significantly increase the volume of integration included in students' written responses, composed based on multiple texts, relative to a control group; although improvements were found when students were compared to others receiving a writing-organization focused training. Directions for future research and, particularly, the need to attend to students' use of rhetorical devices to communicate integration when writing based on multiple texts are discussed.

Research on classroom motivational climates and microclimates--students' shared and idiosyncratic perceptions of motivational classroom features--demonstrates their importance for fostering adaptive motivational and achievement-related outcomes. However, a lack of coherent theoretical guidance about the nature of students' classroom climate perceptions has yielded numerous conceptualizations and measurement approaches for these processes. Further, although existing theories and conceptualizations vary in the specific motivational climate features they propose, considerable conceptual overlap exists among them. Working toward conceptual clarity, theoretical integration, and guidance for measurement, we performed a systematic review to identify prominent measurement trends in motivational climate research. Results revealed teacher autonomy support and classroom goal structures as the most frequently measured classroom climate qualities. We observed a wide variety of validity evidence for the measures; in particular, a low incidence of studies assessed the factor structure and considered the multilevel nature of climate data, with most treating climate perceptions as student-level phenomena. In addition to providing a much-needed guide of existing measurement practices, this systematic review lays a foundation for the continued theoretical advancement of motivational climate. We call for more rigorous reporting of validity evidence, rationales for measure selection, and the underlying assumptions guiding measure selection when conducting classroom climate research, as well as focused development of instruments targeting less-frequently measured climate constructs.

Abstract Background Diabetes mellitus (DM) and proteinuria each independently raise the risk of atrial fibrillation (AF). We aimed to investigate the relationship between proteinuria and the risk of incident AF across glycemic stages. Methods A cohort of 4,044,524 individuals without prior AF and type 1 DM was selected from the 2009 Korean National Health Insurance Service health checkup data. The individuals were categorized into five glycemic stages: normal, prediabetes, new-onset DM, early DM (

Abstract The purpose of this study was to evaluate the difference in the incidence of the hypertensive phase (HP) between Ahmed glaucoma valve (AGV) patients who received intracameral air injection and those who did not. A total of 78 patients who underwent AGV surgery between January 1, 2016 and June 30, 2023 were included in this retrospective study. HP was defined as intraocular pressure (IOP) greater than 21 mmHg within the first 6 postoperative months. Among baseline characteristics, except for neovascular glaucoma and baseline IOP, there were no differences between the air injection and control groups. In the air injection group, the rate of HP was 19%, which was significantly lower than 49.1% in the control group (p = 0.017). In multivariate logistic regression analysis, baseline IOP had a significant positive correlation (OR: 1.120, p = 0.026), while age and intracameral air injection had a significant negative correlation with the incidence of HP (OR: 0.938, p = 0.028, OR: 0.142, p = 0.029). Postoperative IOP at 1 year and surgical success rates were not different between the two groups. Intracameral air injection during AGV surgery can significantly reduce the risk of HP. Intracameral air injection can be a simple procedure in AGV surgery for reducing HP.

Abstract Background Oral diseases with high prevalence worldwide are recognized as severe health problems. Probiotics are used to prevent oral diseases, including dental caries, oral malodor, periodontitis, and subgingival plaque. In this study, we aimed to confirm the antibacterial effect of probiotics on oral pathogens and to assess their characterization and safety as probiotics. Methods The antibacterial effects of Lacticaseibacillus rhamnosus MG4706, Lacticaseibacillus paracasei MG4715, and Limosilactobacillus reuteri MG4722 on the growth biofilm formation of Streptococcus mutans, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis were evaluated. We also investigated the production of antibacterial substances (H2O2 and reuterin) by these strains and their ability to adhere to oral epithelial cells. The safety of L. reuteri MG4722 was verified through whole-genome sequencing analysis and antibiotic susceptibility, lactate dehydrogenase activity, hemolytic activity, and bile acid hydrolase activity. The reuterin biosynthesis genes of L. reuteri MG4722 were identified using genomic analysis. Results L. reuteri MG4722 significantly inhibited the growth of S. mutans, A. actinomycetemcomitans, and P. gingivalis and suppressed the biofilm formation by A. actinomycetemcomitans. In addition, it showed considerable adhesion ability to oral epithelial cells. L. reuteri MG4722 produced H2O2 and reuterin as antibacterial substances, as confirmed by the presence of genes encoding the antibacterial compounds reuterin, reuteran, and reutericyclin. L. reuteri MG4722 showed no hemolysis, bile salt hydrolase activity, antibiotic resistance or toxicity to HT-29 cells, and no antibiotic-resistance genes were identified. Conclusion L. reuteri MG4722 demonstrated antibacterial effects on oral pathogens by producing antibacterial substances and adhering to oral epithelial cells. These results suggest that L. reuteri MG4722 could be an effective probiotic for oral health.

Abstract Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare white matter disease characterized by axonal and glial injury. Although its clinical characteristics have been described in case reports, the prevalence of CSF1R mutations in clinically suspected ALSP cases remains unclear. Herein, we analysed the frequency of CSF1R mutations in patients with probable or possible ALSP and describe the genetic, clinical, radiological, and pathological findings of ALSP cases in individuals of Korean ancestry. Twenty-eight patients with probable or possible ALSP diagnosed at Samsung Medical Center, Seoul, between January 2014 and August 2020, were retrospectively reviewed. All participants underwent brain magnetic resonance imaging (MRI) and CSF1R genetic testing. Overall, 9 of the 28 patients (32.1%) [5/6 (83.3%) of probable ALSP and 4/22 (18.2%) of possible ALSP] were confirmed to have pathogenic or likely pathogenic variants in CSF1R gene. Additionally, one patient without CSF1R mutation exhibited histopathological findings consistent with ALSP on brain biopsy. All patients with CSF1R mutation presented with cognitive impairment and/or psychiatric symptoms. Brain MRI revealed bilateral white matter hyperintensities in all patients, and 5/8 (62.5%) showed diffusion-restricted lesions. Notably, patients with CSF1R mutation had younger age at onset, rapidly progressive course, and diffuse hyperintensity in the splenium compared to patients without CSF1R mutation. Our findings suggest that for definite diagnosis, CSF1R genetic testing is recommended in patients who meet the diagnostic criteria for possible or probable ALSP. Our findings provide insights into the genetic, clinical, radiological, and pathological dimensions of ALSP in individuals of Korean ancestry.

Conventional personal health record (PHR) management systems are centralized, making them vulnerable to privacy breaches and single points of failure. Despite progress in standardizing healthcare data with the FHIR format, hospitals often lack efficient platforms for transferring PHRs, leading to redundant tests and delayed treatments. To address these challenges, we propose a decentralized PHR management system leveraging Personal Data Stores (PDS) and Decentralized Identifiers (DIDs) in line with the Web 3.0 model. Our system features secure interoperability and personal identification masking. Interoperability is achieved through DID digital certificates for verifying PDS addresses and a dynamic access key (AK) system to minimize credential exposure. Data de-identification, including anonymization and encryption, ensures privacy and prevents unauthorized access. We developed a prototype using the Solid open-source library and Hyperledger Aries protocol. Testing showed efficient performance, with DID validations and AK generation under one second, and data operations for 500 MB-sized PHRs completing in two seconds. De-identification processes were both effective and timely. The system demonstrated the ability to manage PHRs securely, empower users with control over their healthcare data, facilitate seamless and secure data transfer between patients and medical entities, and prevent exposure of sensitive information. This approach advances decentralized PHR management, supporting improved healthcare outcomes and patient experiences in the digital era.

Abstract Although chimeric antigen receptor (CAR) T cell therapy has shown remarkable efficacy against leukemic cells, it still has critical limitations. CAR macrophage has been regarded as a potential alternative to CAR T cells. However, due to the difficulties in gene transduction into macrophages, the production of primary human CAR macrophages from peripheral blood mononuclear cells (PBMC) using lentivirus is highly challenging. Here, we report on how to generate CAR macrophages from human PBMC with lentiviral particles. Using our lentiviral protocol, we produced functional CAR macrophages to lyse and phagocytose target cancer cells efficiently.

Abstract Background Given the crucial role of integrating acupuncture treatment into primary care for managing chronic diseases, this study endeavors to identify the utilization of acupuncture among chronic disease patients seeking primary care services in Korea. Additionally, it aims to evaluate their knowledge level and perceptions related to acupuncture use. Methods A descriptive cross-sectional study was conducted among chronic disease patients attending a primary care clinic in Korea. A self-reported questionnaire comprising 37 items was employed to evaluate the utilization of acupuncture treatment. These items covered socio-demographic information, respondents’ health status, levels of acupuncture knowledge, and patterns of acupuncture use. Using the SPSS Statistics 26.0 Network Version program, descriptive statistics, a chi-square test, and a logistic regression analysis were performed to identify factors associated with acupuncture treatment. Results Out of 370 respondents, 44.3% reported utilizing acupuncture treatment. The most popular reason for the utilization of acupuncture was to enhance the effectiveness of the current treatment. The patients with musculoskeletal disease had the highest utilization rate of 53.2%. The main source of information for acupuncture use was family and friends. The average score for the level of knowledge on acupuncture treatment among the respondents was 65.4%, and the knowledge level of the acupuncture group was high. Potential predictors of acupuncture use included musculoskeletal disease, and intention to recommend acupuncture. Conclusion This study highlights the widespread acceptance of acupuncture use among patients with chronic diseases in primary healthcare context. Integration of acupuncture into primary care emerges as a viable avenue for effective chronic disease management, and fostering a comprehensive and holistic approach to healthcare. Clinical trial number Not applicable.

A long short-term memory (LSTM) model is introduced to predict missing datapoints of dissolved oxygen (DO) in an eel (Anguilla japonica) recirculating aquaculture system. Field experiments allow to determine periodic patterns in DO data corresponding to day-night cycles and a DO decrease after feeding. To improve the accuracy of DO prediction by using a training-to-test data ratio of 5:1, training with data in sequential and reverse orders is performed and evaluated. The LSTM model used to predict DO levels in the fish tank has an error of approximately 3.25%. The proposed LSTM model trained on DO data has a high applicability and may support water quality control in aquaculture farms.

Abstract Metformin (MetF) is used worldwide as a first-line therapy for type 2 diabetes. Recently, interest in the pleiotropic effects of MetF, such as its anticancer and antiaging properties, has increased. However, the molecular target of MetF and the detailed mechanism underlying its ability to inhibit cell growth through autophagy induction remain incompletely understood. In this study, using an innovative label-free drug affinity responsive target stability (DARTS)-LC-MS/MS method, we discovered that mitochondrial voltage-dependent anion channel 1 (VDAC1) is a novel binding protein involved in the induction of autophagy-related cell death by high-dose MetF in hepatocellular carcinoma (HCC). Computational alanine scanning mutagenesis revealed that MetF and VDAC1 (D9, E203) interact electrostatically. MetF disrupts the IP3R-GRP75-VDAC1 complex, which plays a key role in stabilizing mitochondria-associated ER membranes (MAMs), by binding to VDAC1. This disruption leads to increased cytosolic calcium levels, thereby contributing to autophagy induction. MetF also decreased the AMP/ATP ratio and activated the AMPK pathway. Cells with genetic knockdown of VDAC1 mimicked the activity of MetF. In conclusion, this study provides new insights into the involvement of MetF in ionic interactions with VDAC1, contributing to its anticancer effects in HCC. These findings help elucidate the diverse biological and pharmacological effects of MetF, particularly its influence on autophagy, as well as the potential of MetF as a therapeutic agent for diseases characterized by VDAC1 overexpression.

Objective To identify the prevalence and factors associated with T-score discordance between the spine and hip, as well as between the paretic and non-paretic hips in hemiplegic stroke patients, this study investigated bone mineral density (BMD) patterns. Bone loss predominantly affects the paretic hip after a stroke, and typical clinical assessments using dual-energy X-ray absorptiometry (DXA) that scan the lumbar spine (LS) and a single hip may overlook an osteoporosis diagnosis. This oversight could potentially lead to suboptimal treatment for stroke patients. Methods This study was a multicenter retrospective analysis of 540 patients admitted for stroke rehabilitation between October 2014 and February 2022, who underwent DXA of LS and bilateral hips. Results The prevalence rates of concordance, low LS discordance, and low hip discordance between the LS and hips were 48.2%, 12.2%, and 39.6%, respectively. The discordance rate between bilateral hips was 17.0%. The paretic side had significantly lower total hip T-scores than the non-paretic side (p

Abstract Background Sepsis is a life-threatening condition that affects individuals of all ages; however, it presents unique challenges in very old patients due to their complex medical histories and potentially compromised immune systems. This study aimed to investigate the influence of underlying conditions and the performance of sepsis bundle protocols in very old patients with sepsis. Methods We conducted a nationwide cohort study of adult patients with sepsis prospectively collected from the Korean Sepsis Alliance Database. Underlying conditions, prognosis, and their association with sepsis bundle compliance in patients with sepsis aged ≥ 80 years were analyzed. Results Among the 11,981 patients with sepsis, 3,733 (31.2%) were very old patients aged ≥ 80 years. In-hospital survivors (69.8%) were younger, less likely male, with higher BMI, lower Charlson Comorbidity Index, lower Clinical Frailty Scale, and lower Sequential Organ Failure Assessment (SOFA) scores. The in-hospital survivor group had lower lactate measurement but higher fluid therapy and vasopressor usage within the 1-h bundle. Similar trends were seen in the 3-h and 6-h bundles. Furthermore, in-hospital survivors were more likely to receive appropriate empiric antibiotics within 24 h. In-hospital mortality was associated with age, Clinical Frailty Scale, SOFA score, comorbidities, Life sustaining treatment issue, interventions in the ICU and vasopressor use in the 1-h sepsis bundle. Conclusions Addressing underlying conditions and enhancing sepsis bundle adherence is crucial for better outcomes in very old patients with sepsis. Personalized approaches and increased awareness are essential. Further research should explore interventions to optimize sepsis care in this population.

This study investigates the chloride penetration resistance and electrochemical behavior of self-healing engineered cementitious composites (ECC). The experimental program involved exposing cracked ECC samples to NaCl solution, while monitoring chloride penetration and self-healing using water-permeability tests. Electrochemical measurements, including open circuit potential, linear polarization resistance, and electrochemical impedance spectroscopy, were used to evaluate reinforcement corrosion over a 91-day period. Results show that water-tightness does not guarantee protection against chloride ingress, as cracks with widths exceeding 0.15 mm allowed chloride penetration despite self-healing. Reinforcement depassivation occurred within 1–3 days of chloride exposure, but self-healing reduced the corrosion current back to pre-crack levels within 1–2 months, highlighting its role in delaying corrosion propagation. These findings emphasize the importance of crack width control in achieving effective self-healing and suggest that electrochemical impedance spectroscopy is a useful technique for monitoring the self-healing process in reinforced ECC structures.

Abstract Hormonal regulation during food ingestion and its association with pain prompted the investigation of the impact of glucagon-like peptide-1 (GLP-1) on transient receptor potential vanilloid 1 (TRPV1). Both endogenous and synthetic GLP-1, as well as a GLP-1R antagonist, exendin 9–39, reduced heat sensitivity in naïve mice. GLP-1-derived peptides (liraglutide, exendin-4, and exendin 9–39) effectively inhibited capsaicin (CAP)-induced currents and calcium responses in cultured sensory neurons and TRPV1-expressing cell lines. Notably, exendin 9–39 alleviated CAP-induced acute pain, as well as chronic pain induced by complete Freund’s adjuvant (CFA) and spared nerve injury (SNI), in mice without causing hyperthermia associated with other TRPV1 inhibitors. Electrophysiological analyses revealed that exendin 9–39 binds to the extracellular side of TRPV1, functioning as a noncompetitive inhibitor of CAP. Exendin 9–39 did not affect proton-induced TRPV1 activation, suggesting its selective antagonism. Among the exendin 9–39 fragments, exendin 20–29 specifically binds to TRPV1, alleviating pain in both acute and chronic pain models without interfering with GLP-1R function. Our study revealed a novel role for GLP-1 and its derivatives in pain relief, suggesting exendin 20–29 as a promising therapeutic candidate.

Abstract In clinical practice, the effect of a high vault on corneal endothelial cells after implantable collamer lens (ICL) implantation remains unclear. Many clinicians theoretically assume that a high postoperative vault leads to rapid endothelial damage, but no study has yet proven this hypothesis. We conducted a paired-eye study to compare changes in corneal endothelial cell density (ECD) between high and low postoperative vault groups. This retrospective study included 150 eyes of 75 patients with bilateral postoperative vault levels differing by more than 200 μm after ICL implantation. Patients were followed up for 7 years with ECD measurements, and changes in ECD were assessed between 6 months and 7 years post-surgery. Over the 7-year follow-up period, the percentage of ECD loss was 15.04% and 14.45% in the high- and low-vault groups, respectively. The bilateral paired-eye comparison revealed a significant reduction in ECD in the high-vault group at 3, 5, and 7 years postoperatively (P-value

Abstract This study examined the modifying effects of surgery status on the association between the Standard Deviation of NN Intervals (SDNN) of the heart rate variability and the post-traumatic stress disorder (PTSD) development. Participants with physical injury were recruited from a trauma center and followed for two years. Baseline assessment included SDNN and surgery status. Socio-demographic and clinical covariates were collected. PTSD was diagnosed at 3, 6, 12, and 24 months post-injury using the Clinician-Administered PTSD Scale for DSM-5. Logistic regression analyses were performed. Among 538 participants, 58 (10.8%) developed PTSD during the study, with prevalence rates of 8.4% at 3 months, 6.5% at 6 months, 4.7% at 12 months, and 2.5% at 24 months. A significant modifying effect was found that lower SDNN were significantly associated with PTSD in non-surgical patients but not in surgical patients, with significant interaction terms. This pattern was observed from 3 to 12 months but not at 24 months. Surgery-dependent associations between SDNN and PTSD development were observed, highlighting the need for tailored PTSD prevention strategies considering SDNN and surgery status.

Abstract In the context of acute brain injuries, where zinc neurotoxicity and oxidative stress are acknowledged contributors to neuronal damage, we investigated the pivotal role of lysosomes as a potential protective mechanism. Our research commenced with an exploration of epidermal growth factor (EGF) and its impact on lysosomal dynamics, particularly its neuroprotective potential against zinc-induced cytotoxicity. Using primary mouse cerebrocortical cultures, we observed the rapid induction of EGFR endocytosis triggered by EGF, resulting in a transient increase in lysosomal vesicles. Furthermore, EGF stimulated lysosomal biogenesis, evident through elevated expression of lysosomal-associated membrane protein 1 (LAMP-1) and the induction and activation of prominent lysosomal proteases, particularly cathepsin B (CTSB). This process of EGFR endocytosis was found to promote lysosomal augmentation, thus conferring protection against zinc-induced lysosomal membrane permeabilization (LMP) and subsequent neuronal death. Notably, the neuroprotective effects and lysosomal enhancement induced by EGF were almost completely reversed by the inhibition of clathrin-mediated and caveolin-mediated endocytosis pathways, along with the disruption of retrograde trafficking. Furthermore, tyrosine kinase inhibition of EGFR nullified EGFR endocytosis, resulting in the abrogation of EGF-induced lysosomal upregulation and neuroprotection. An intriguing aspect of our study is the successful replication of EGF’s neuroprotective effects through the overexpression of LAMP-1, which significantly reduced zinc-induced LMP and cell death, demonstrated in both primary mouse cerebrocortical neuronal cultures and human embryonic kidney (HEK) cells. Our research extended beyond zinc-induced neurotoxicity, as we observed EGF’s protective effects against other oxidative stressors linked to intracellular zinc release, including hydrogen peroxide (H2O2) and 1-methyl-4-phenylpyridinium ion (MPP+). Collectively, our findings unveil the intricate interplay between EGF-triggered EGFR endocytosis, lysosomal upregulation, an increase in the regulatory capacity for zinc homeostasis, and the subsequent alleviation of zinc-induced neurotoxicity. These results present promising avenues for therapeutic interventions to enhance neuroprotection by targeting lysosomal augmentation.

Abstract We present an architecture for encoding two qubits within the optical “clock” transition and nuclear spin-1/2 degree of freedom of neutral ytterbium-171 atoms. Inspired by recent high-fidelity control of all pairs of states within this four-dimensional “ququart” space, we present a toolbox for intra-ququart (single-atom) one- and two-qubit gates, inter-ququart (two-atom) Rydberg-based two- and four-qubit gates, and quantum nondemolition (QND) readout. We then use this toolbox to demonstrate the advantages of the ququart encoding for entanglement distillation and quantum error correction which exhibit superior hardware efficiency and better performance in some cases since fewer two-atom operations are required. Finally, leveraging single-state QND readout in our ququart encoding, we present a unique approach to studying interactive circuits and to realizing a symmetry protected topological phase of a spin-1 chain with a shallow, constant-depth circuit.

Psoriasis is a chronic inflammatory skin disorder characterized by the hyperproliferation of keratinocytes and immune system dysregulation, with significant needs due to the limitations and adverse effects of current treatments. In this study, we sought to discover novel herbal candidates and their active compounds for psoriasis by leveraging a multiscale network analysis. We conducted a comprehensive analysis of data from 348 medicinal herbs and their active compounds, identifying Piperis longi fructus, Pini koraiensis semen, Schisandrae fructus, and Cnidi fructus as top candidates without reported evidence. Key active compounds, such as piperine, piperlongumine, α-humulene, schizandrin A, schizandrin II, and torilin, were prioritized for their ability to target psoriasis-associated proteins, including STAT3, TNF, IL-6, and NF-κB. These compounds are involved in the modulation of critical inflammatory pathways, notably the MAPK signaling cascade, which plays a central role in psoriasis pathogenesis. Our findings suggest that these herbal compounds may not only mitigate inflammation but also regulate keratinocyte hyperproliferation, addressing fundamental mechanisms underlying the disease. This approach highlights the utility of multiscale network analysis in identifying promising natural therapies, offering new insights and potential avenues for safer and more effective psoriasis management.

In 2015, programmatic accreditation by the Commission on Accreditation of Allied Health Education Programs (CAAHEP) was initiated for art therapy education. The study examined art therapy faculty's perception of the CAAHEP accreditation process through a nation-wide online survey research. The mixed-method analysis supports the complexity of the current art therapy programmatic accreditation as perceived by faculty. Three main themes were identified: (1) accreditation as accountability, (2) additional burden and time-consuming, and (3) limited support and skill mismatch. The findings suggest that programmatic accreditation brings both benefits and challenges while also supporting the development of quality accreditation procedures for art therapy education.

Students want to learn computer science due to its usefulness for future careers, however they often meet challenges in introductory courses. In the increasingly digital world, it is important to understand some important psychological consequences of such challenges: perceived costs of pursuing computer science. This study thus investigated semester-long trajectories of four cost perceptions (effort, opportunity, psychological, and emotional) and their relations to achievement, major intentions, and career intentions (N = 831). All cost beliefs showed average increases, although with nuanced differences in levels and slopes, and the four costs differentially predicted student outcomes. Interestingly, the intercept of psychological cost negatively predicted final course grades while positively predicting major and career intentions. Women reported steeper increases in cost perceptions compared to men. The findings highlight the differential functioning of cost perceptions, with implications for the importance of targeting different aspects of cost perceptions to mitigate students' barriers to success in computer science.

Recognizing, building, describing, extending, and analyzing patterns are key components of algebraic reasoning. Oftentimes pattern-based instruction is used to support the understanding of functions and variables. In this study, elementary preservice teachers (n = 23) were asked to explore, extend, explain, create equations for, and analyze linear, geometric, and quadratic integer patterns using color tiles. Then they created, extended, described, and analyzed their own patterns while working in groups (n = 8). The research question was: What algebraic errors do PSTs demonstrate in the process of constructing, explaining, and analyzing their own linear, geometric, and quadratic patterns using color tiles? The analysis, which focused on errors and misunderstandings preservice teachers demonstrated in their final unit, revealed three specific areas of difficulties: figural errors, explanation challenges, and improper use of algebraic language. Participants failed to connect their algebraic images in a coherent manner, there was confusion in articulating their algebraic thought processes, and algebraic terminology was improperly used. Implications for teaching and further research are described.

We examine the role of culture in comprehension. Prominent theories of comprehension conceptualized the outcome of reading as learners' construction of a cognitive representation of texts. We emphasize that such representation reflects not only texts' content, but also individuals' understandings of the real world, as described in texts. We suggest that, thus, individuals should be supported to question and analyze the mental representations that they form; we use the term "culture" to capture such questioning and analysis. Rather than an individual difference factor, we argue for conceptualizing culture as a way of thinking, or as individuals' reasoning about the commonalities and differences in their and others' worldviews and the linking of these to underlying values. When such reasoning is engaged in reference to texts, we refer to this as culturalized comprehension; when such reasoning is further engaged to resist or recast the values introduced in texts to generate counternarratives, we refer to this as critical culturalized comprehension. In emphasizing the importance of culturalized and critical culturalized comprehension and describing the set of cognitive processes involved, we argue for research in educational psychology to examine how learners may be consciously, reflectively, and critically engaged in using texts to understand their world.

Police officers are vulnerable to psychological distress and trauma since they are constantly exposed to significant physical and mental violence. Poor mental health can lead to increased healthcare costs for individuals, organizations, and nations and negatively impacts public safety. Mental health interventions tailored to the nature of police work are needed; however, a research gap exists regarding understanding the mental health of police officers. This study aimed to explore the barriers, facilitators, and needs for mental health promotion among police officers. This study adopted a qualitative approach in South Korea. Twelve police officers working in a metropolitan city were recruited using purposive sampling methods. One-on-one interviews were conducted with open-ended questions regarding barriers, facilitators, and needs for improving mental health. Content analysis was used to derive relevant themes. The participants included 3 women and 9 men, with an average age of 37.8 years and working experience of 12.6 years. Three themes and 9 subcategories emerged. The theme related to barriers was “difficulty accessing resources”; the theme related to facilitators was “supportive environment for mental health prevention and management”; and the theme related to needs was “education and policies to promote mental health.” Considering the occupational and organizational characteristics of the police profession, individual and organizational interventions and policies are needed to adequately manage the mental health of police officers.

Category: Basic Sciences/Biologics Introduction/ Purpose: Combat boots are special shoes designed for soldiers to wear during activities in rough terrains, such as long marches or military training. Combat boots cause high plantar pressure and increase the injury rate of the lower extremities. Therefore, this study aimed to compare the difference of in-shoe plantar pressure between Korean combat boots and running shoes. We hypothesized that the newest Korean combat boots would have comparable plantar pressure distribution to running shoes. Methods: We prospectively recruited 30 asymptomatic male participants, who are considered as candidates for military services, from the local area. Two types of shoes (newly developed Korean combat boots and running shoes) were examined. Data of pedobarographic measurements were collected using the pedar ® -X in-shoe pressure measurement system. Peak pressure (PP), pressure time integral (PTI), contact area, and contact time were analyzed. Results: Both PP and PTI at the region of central and lateral forefoot (FF) were significantly higher in combat boots. The contact area of combat boots was significantly lower at the region of the hallux, 2-5 toes, medial FF, central FF, and midfoot. Contact time at the region of central FF and medial heel was significantly higher in combat boots. Conclusion: Understanding plantar pressure distribution of combat boots can be helpful in the development of combat boots and prevention of injury. Based on the results of our study, the next generation Korean combat boots should be developed to increase contact area and distribute impulse under the head of the metatarsal bone

Category: Ankle Arthritis; Hindfoot Introduction/Purpose: The clinical role of incongruent subtalar joints on ankle arthritis as well as that on the clinical outcome of surgical treatment such as total ankle arthroplasty (TAA) has not yet been fully understood. The mobile subtalar joint may compensate for malalignment of the arthritic ankle as well as counteract the effect of realigning surgeries. We aimed to determine the clinical effect of incongruent subtalar joint space on TAA. Methods: We retrospectively reviewed 34 patients who underwent TAA, which were grouped according to the status of subtalar joint incongruency. For clinical parameters, American Orthopaedic Foot & Ankle Society (AOFAS) score and pain visual analog scale (VAS) were collected. For radiographic parameters, preoperative talar tilt angle, medial distal tibial angle, and anterior distal tibial angle were measured. A comparison of clinical and radiographic parameters between groups as well as multiple regression analysis was performed to identify contributing factors to the final functional outcome. Results: Interobserver and intraobserver reliabilities of subtalar joint congruency demonstrated substantial agreement. At the final follow-up, the AOFAS score was significantly higher in the congruent group (n=13) compared to that of the incongruent group (n=21), (90.38 vs. 79.57, p=0.007). However, there was no significant difference in pain VAS between the groups at the final follow-up (p=0.181). For measured radiographic parameters, there were no significant differences between the two groups in talar tilt angle, medial distal tibial angle, and anterior distal tibial angle. In multiple regression analysis, the female sex (p=0.006) and incongruency of the subtalar joint (p=0.013) were found to be significant contributing factors to the final AOFAS score. Conclusion: Patients in which the preoperative subtalar joint is incongruent showed less favorable AOFAS scores after undergoing TAA. A thorough preoperative investigation should be taken into the state of the subtalar joint for TAA.

Category: Other; Basic Sciences/Biologics Introduction/Purpose: Plantar fasciitis is one of the most common causes of chronic heel pain. Typically, conservative treatment involves stretching exercises and the use of orthosis such as heel cups. To prescribe the appropriate orthosis, a fundamental understanding of plantar pressure distribution is essential. We evaluated the plantar pressure distribution of patients with unilateral plantar fasciitis by comparing it with contralateral unaffected sides. Methods: We prospectively recruited 20 participants who were diagnosed with unilateral plantar fasciitis and had been complaining of heel pain for at least 6 months. The emed ® system was used to measure the plantar pressure of both feet during gait. We measured the pedobarographic parameters, such as contact area, maximum force, peak pressure, force time integrals, and pressure time integrals. The analysis was performed using a 4-mask configuration (hindfoot, midfoot, forefoot, and toes). In addition, we measured radiographic parameters that could potentially affect plantar pressure in simple foot and ankle radiographs. Results: Both sides showed no significant difference in radiographic parameters. The affected side showed significantly higher contact area (28.9±10.3 vs. 26.3±8.2, p=0.007), maximum force (27.3±12.9 vs. 24.4±11.9, p=0.048), and force time integrals (0.6±0.3 vs. 0.5±0.2, p=0.044) in the midfoot. However, the unaffected side demonstrated significantly higher maximum force (67.5±11.4 vs. 60.1±8.4, p=0.030) and force time integrals (1.4±0.2 vs. 1.2±0.2, p=0.038) in the hindfoot. Conclusion: The increase in the contact area and maximum force in the midfoot on the side with plantar fasciitis can be interpreted as a result of weight transfer from the hindfoot to the midfoot due to heel pain. It can be suggested that Achilles tendon and plantar fascia stretching exercise is necessary to prevent weight transfer from the original hindfoot to the midfoot or forefoot. Moreover, the findings of this study could be helpful in prescribing appropriate orthosis for patients effectively.

IntroductionThis study examined the moderating effects of childhood abuse histories on the associations between low frequency (LF) and high frequency (HF) components of heart rate variability (HRV) and the development of post-traumatic stress disorder (PTSD).MethodsParticipants with physical injuries were recruited from a trauma center and followed for two years. Baseline assessments included LF, HF, and childhood abuse histories, assessed using the Nemesis Childhood Trauma Interview. Socio-demographic and clinical covariates were obtained. PTSD diagnoses were made at 3, 6, 12, and 24 months post-injury using the Clinician-Administered PTSD Scale for DSM-5. Logistic regression analyses assessed the associations.ResultsAmong 538 participants, 58 (10.8%) developed PTSD during the study period. A significant interaction was found: lower LF/HF were significantly associated with PTSD in patients with childhood abuse histories, but not in those without.ConclusionChildhood abuse history significantly moderates the relationship between LF-HF HRV components and PTSD development, suggesting that childhood adversities amplify the risk. These findings support the importance of screening for childhood abuse histories and monitoring HRV in physically injured patients as part of the assessment process.

BackgroundThere is no established second-line treatment for hepatocellular carcinoma (HCC) following atezolizumab-bevacizumab (ate-beva) failure. This study assessed the efficacy of hepatic arterial infusion chemotherapy (HAIC) as a salvage therapy by comparing survival outcomes and treatment responses between HAIC as a first-line treatment and as a second-line option after ate-beva failure.Materials and MethodsWe retrospectively analyzed 100 patients with advanced HCC treated with HAIC between March 2022 and July 2024. Patients were categorized into two groups: those who received HAIC as initial therapy (first-line HAIC group) and those who received HAIC following ate-beva failure (post-ate-beva group). Survival outcomes were assessed with Kaplan-Meier curves and log-rank tests, and factors associated with survival were identified through Cox regression analysis.ResultsThe post-ate-beva group exhibited longer overall survival (OS) (median OS 12.4 months) compared to the first-line HAIC group (median OS 6.8 months) (p = 0.073). Progression-free survival (PFS) was significantly superior in the post-ate-beva group (median PFS 8.2 months) compared to the first-line HAIC group (median PFS 3.1 months) (p = 0.018). The objective response rate was also notably higher in the post-ate-beva group than in the first-line HAIC group (35.3% vs. 18.1%, p = 0.031). In multivariate analysis, HAIC following ate-beva failure, compared to first-line HAIC, was significantly associated with favorable outcomes for both OS (p = 0.014) and PFS (p = 0.006).ConclusionThe superior survival outcomes and treatment responses observed in the post-ate-beva group suggest that HAIC may be an effective second-line treatment option for advanced HCC following ate-beva therapy failure. However, due to the retrospective nature and small sample size of the study, further prospective studies with larger patient populations are needed to strengthen the evidence.

IntroductionThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, notably delta and omicron, has significantly accelerated the global pandemic, worsening conditions worldwide. However, there is a lack of research concerning the molecular mechanisms related to immune responses and metabolism induced by these variants. MethodsHere, metabolomics combined with transcriptomics was performed to elucidate the immunometabolic changes in the lung of hamsters infected with delta and omicron variants.ResultsBoth variants caused acute inflammation and lung pathology in intranasally infected hamsters. Principal component analysis uncovered the delta variant significantly altered lung metabolite levels between the pre- and post-infection states. Additionally, metabolic pathways determined by assessment of metabolites and genes in lung revealed significant alterations in arginine biosynthesis, glutathione metabolism, and tryptophan metabolism upon infection with both variants and closely linked to inflammatory cytokines, indicating immune activation and oxidative stress in response to both variants. These metabolic changes were also evident in the serum, validating the presence of systemic alterations corresponding to those identified in lung. Notably, the delta variant induced a more robust metabolic regulation than the omicron variant. DiscussionThe study suggests that multi-omics is a valuable approach for understanding immunometabolic responses to infectious diseases, and providing insights for effective treatment strategies.

IntroductionThis qualitative study explored the socio-cultural adjustment and re-adjustment experiences of South Korean adolescents who studied in English-speaking countries and later returned to South Korea.MethodsThe study interviewed 12 adolescents (6 males, 6 females) aged 12–16 who studied in countries such as the U.S., Canada, England, New Zealand, and Australia.ResultsThe findings highlight the students’ adjustment processes abroad, including the initial “honeymoon” phase, followed by crises like language barriers, homesickness, and difficulties in relationships with peers and teachers. Upon returning to Korea, students faced challenges with academic performance, stricter school regulations, and social reintegration, often exacerbated by biases toward those who studied abroad.DiscussionThe study underscores the importance of support systems during both phases and highlights the need for educational interventions that can ease the transition both abroad and at home. This research contributes to understanding the complexities of cross-cultural adjustment and re-entry, especially in the context of adolescents’ identity and belonging, suggesting sustainable education system to support students’ both abroad and returning process.

Fractography of stress corrosion cracking (SCC) of 20% cold worked Type 304 H stainless steel containing δ-ferrite was studied using a compact tension (CT) specimen in oxidizing primary water with a scanning electron microscope (SEM) and electron back scattered diffraction (EBSD). The stress corrosion crack propagated mostly in transgranular stress corrosion cracking (TGSCC) mode and sometimes in intergranular stress corrosion cracking (IGSCC) mode. TGSCC paths were along the {111} plane with both high resolved shear stress and high resolved tensile stress. IGSCC preferentially propagated along the grain boundary perpendicular to the loading axis. The findings in this work suggest that TGSCC proceeds through formation of a weakening zone at the head of the crack tip by interaction of slip and corrosion and then cracking of the weakened zone by tensile stress.

Background/Objectives: Although preeclampsia (PE) and small for gestational age (SGA) are known to come from impaired placentation during the first trimester, prior studies have focused mostly on Doppler findings in the second trimester. Methods: In this retrospective pilot study, we enrolled 628 singleton pregnant women who underwent ultrasound in both the first and second trimesters and blood test. For SGA correlation, we further excluded 12 subjects with PE because PE may be the cause of SGA. We first presented the reference range of parameters of uterine artery Doppler in the first trimester and then grouped the subjects according to the presence of SGA (presence = 104, absence = 512) or PE (presence = 12, absence = 616) and investigated the association of uterine artery Doppler findings and serum markers in the first trimester with the occurrence of SGA or PE. Results: The uterine artery pulsatility index and the resistance index and the proportion of uterine artery notch decreased progressively in the first trimester. A lower serum beta-hCG level in the first trimester predicted the occurrence of SGA (adjusted odds ratio [AOR] = 0.53, p = 0.019), while the presence of the uterine artery notch in the first trimester predicted the development of PE (notch at least on one side: AOR = 8.65, p = 0.045 and notch on both sides: AOR = 8.91, p = 0.047). Regardless of whether a notch was present in the second trimester, a uterine artery notch in the first trimester was associated with an excellent negative predictive value (99.6%) for PE. Conclusions: This study suggests the clinical importance of assessing serum beta-hCG and the uterine artery notch in the first trimester to predict SGA and PE.

We investigate mixed states exhibiting nontrivial topological features, focusing on symmetry-protected topological (SPT) phases under various types of decoherence. Our findings demonstrate that these systems can retain topological information from the SPT ground state despite decoherence. In the ''doubled Hilbert space,'' we define symmetry-protected topological ensembles (SPT ensembles) and examine boundary anomalies in this space. We generalize the concept of the strange correlator, initially used to diagnose SPT ground states, to identify anomalies in mixed-state density matrices. Through exact calculations of stabilizer Hamiltonians and field theory evaluations, we show that nontrivial features of SPT states persist in two types of strange correlators: type-I and type-II. The type-I strange correlator reveals SPT information that can be efficiently detected and used experimentally, such as in preparing long-range entangled states. The type-II strange correlator encodes the full topological response of the decohered mixed state, reflecting the SPT state's pre-decoherence presence. Our work offers a unified framework for understanding decohered SPT phases from an information-theoretic perspective.

Lung cancer remains a major global health problem because of its high cancer-related mortality rate despite advances in therapeutic approaches. Non-small cell lung cancer (NSCLC), a major subtype of lung cancer, is more amenable to surgical intervention in its early stages. However, the prognosis for advanced NSCLC remains poor, owing to limited treatment options. This underscores the growing need for novel therapeutic strategies to complement existing treatments and improve patient outcomes. In recent years, pentacyclic triterpenoids, a group of natural compounds, have emerged as promising candidates for cancer therapy due to their anticancer properties. Pentacyclic triterpenoids, such as lupeol, betulinic acid, betulin, oleanolic acid, ursolic acid, glycyrrhetinic acid, glycyrrhizin, and asiatic acid, have demonstrated the ability to inhibit cell proliferation and angiogenesis, induce apoptosis, suppress metastasis, and modulate inflammatory and immune pathways in NSCLC cell line models. These compounds exert their effects by modulating important signaling pathways such as NF-κB, PI3K/Akt, and MAPK. Furthermore, advances in drug delivery technologies such as nanocarriers and targeted delivery systems have improved the bioavailability and therapeutic efficacy of triterpenoids. However, despite promising preclinical data, rigorous clinical trials are needed to verify their safety and efficacy. This review explores the role of triterpenoids in NSCLC and therapeutic potential in preclinical models, focusing on their molecular mechanisms of action.

This review aims to examine existing research on the development of ocular drug delivery devices utilizing hyaluronic acid (HA). Renowned for its exceptional biocompatibility, viscoelastic properties, and ability to enhance drug bioavailability, HA is a naturally occurring biopolymer. The review discussed specific mechanisms by which HA enhances drug delivery, including prolonging drug residence time on ocular surfaces, facilitating controlled drug release, and improving drug penetration through ocular tissues. By focusing on these unique functionalities, this review highlights the potential of HA-based systems to revolutionize ocular treatment. Various fabrication techniques for HA-based ocular drug delivery systems, including hydrogels, nanoparticles, and microneedles, are discussed, highlighting their respective advantages and limitations. Additionally, this review explores the clinical applications of HA-based devices in treating a range of ocular diseases, such as dry eye syndrome, glaucoma, retinal disorders, and ocular infections. By comparing the efficacy and safety profiles of these devices with traditional ocular drug delivery methods, this review aims to provide a comprehensive understanding of the potential benefits and challenges associated with HA-based systems. Moreover, this review discusses current limitations and future directions in the field, such as the need for standardized fabrication protocols, long-term biocompatibility studies, and large-scale clinical trials. The insights and advancements presented in this review aim to guide future research and development efforts, ultimately enhancing the effectiveness of ocular drug delivery and improving patient outcomes.