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Targeting the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is promising in treating cancer in humans and offers potential for veterinary applications. However, no PD-L1 antibodies have been approved specifically for treating canine cancer. We aimed to develop PD-L1-specific antibodies using phage display technology for treating canine cancer. A synthetic antibody library was screened, and 18 high-affinity single-chain variable fragment clones were subsequently converted to the IgG format for enhancing binding affinity and functional stability. The clone #15 exhibited the highest binding affinity and most pronounced antitumor effects. The PD-1/PD-L1 interaction was inhibited by antibody #15. The binding and thermal stabilities of the antibodies were validated by flow cytometry and thermal stability assays, respectively. In NOG mice xenografted with canine osteosarcoma cells and treated with canine peripheral blood mononuclear cells and antibody #15, the tumor size and weight were reduced. Antibody #15 significantly increased apoptosis of tumor cells and lymphocyte populations. Therefore, anti-PD-L1 antibodies, particularly antibody #15, have substantial potential as novel immunotherapeutic agents against canine osteosarcoma. This study represents a significant advancement in veterinary oncology, with the potential of improving treatment outcomes for canine cancers and providing insights into similar strategies in human cancer therapy., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Research links gait impairment in Alzheimer's disease (AD) to cognitive abnormalities, brain atrophy, or amyloid-β (Aβ) deposition, with the exact cause unclear. This study investigated the relationship between gait, neuroimaging biomarkers, and cognition across the AD spectrum. We recruited 48 AD dementia patients, 27 with prodromal AD, and 41 cognitively unimpaired individuals, analyzing associations among gait parameters, cognitive scores, Aβ deposition, and cortical atrophy. Path and receiver operating characteristic (ROC) analyses evaluated gait impairment's interdependent interactions and diagnostic potential. Prodromal AD and AD dementia patients showed significantly slower gait pace than CU (p = 0.014 [velocity], p = 0.003 [step length]), linked to attention and executive functions, widespread Aβ deposition, and cortical atrophy, in the inferior parietal lobule, middle temporal gyrus, precuneus, and insula. Compared to CU, AD dementia patients exhibited greater gait variability and phase (p = 0.017 [step length standard deviation], p = 0.001 [double support percentage]), significantly correlated with cognition and Aβ deposition. Path analysis revealed a combined influence of Aβ deposition, cognitive impairment, and cortical atrophy on gait impairment, with > 80% observed gait impairments directly affected by Aβ deposition. ROC curves for diagnosing AD stages showed significant areas under the curve, suggesting gait characteristics as noninvasive biomarkers for early AD diagnosis and progression monitoring., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics statement: This study was approved by the institutional review board of Wonju Severance Christian Hospital (Ref# CR322029). The research protocol conformed with the principles of the Declaration of Helsinki and its subsequent revisions. Written informed consent was obtained from all participants and/or their legal guardians., (© 2025. The Author(s).)

To evaluate the effects of orthoptic training using a virtual reality (VR) head-mounted display game in patients with intermittent exotropia (IXT), a prospective, randomized, double-blind study was performed in 62 patients ≥ 13 years with IXT of ≥ 8 prism diopters (∆) and with a near ≥ distance angle, i.e., basic type and convergence insufficiency-type IXT. Patients were randomly assigned to a video-game group that induced convergence (exercise group) and a placebo-game group not inducing convergence (control group), and completed the program 15 min/day for 4 weeks. Subjective symptom scores, angle of exodeviation, near point of convergence, stereoacuity, fusional control scores using the Newcastle Control Score (NCS) and the Office Control Score (OCS) were noted. Outcome measures were assessed after 4 weeks, and re-evaluated after a washout period of 4 weeks. After using the VR game for 4 weeks, the near angle of exodeviation significantly decreased from 29.6 ± 9.5∆ to 25.3 ± 9.0∆ in the exercise group (p < 0.001), which was still maintained after 4 weeks of discontinuation (p = 0.008). There were no significant differences in the near angle of exodeviation in the control group at either the 4- or 8-week visits (p = 0.075, 0.093, respectively). The fusional control scores of the NCS and OCS significantly improved at the 4-week (p = 0.001, 0.003, respectively) and 8-week visits (p = 0.004, < 0.001, respectively) only in the exercise group. In conclusion, orthoptic training using a VR game improved the near angle of exodeviation and fusional control scores in IXT., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical standard: This study was approved by the Ethical Committee of Seoul National University Bundang Hospital., (© 2024. The Author(s).)

The purpose of this study was to compare preoperative anxiety and intraoperative pain between the first and second cataract surgeries in patients who underwent immediate sequential bilateral cataract surgery (ISBCS). This retrospective study was conducted between June 20, 2023, and September 20, 2023, at Korea University Guro Hospital. A total of 170 cataract surgeries was included, and 130 eyes underwent ISBCS. Clinical records, including patients' intraoperative pain score (visual analog scale [VAS] for pain, 1-10 points) and patients' preoperative anxiety score (VAS for anxiety (VASA), 1-10 points), were investigated. Also, correlations between clinical factors and pain scores were analyzed. The pain score did not significantly differ between the first and second surgeries in ISBCS patients (2.51 ± 1.16 vs. 2.43 ± 1.36 points) (P = 0.692). However, the anxiety score recorded before the second eye surgery was significantly lower compared to that recorded before the first eye surgery. (3.32 ± 1.68 vs. 2.31 ± 1.29 points) (P < 0.001). Among the clinical factors, only the anxiety score was significantly correlated with the pain score (P = 0.013). We suggest ISBCS may serve as a beneficial strategy for a better surgery experience, reducing patients' anxiety during surgery., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

There is limited data on the risk of second primary malignancies (SPMs) in Asian melanoma survivors. This study aimed to identify the risk of SPMs in Asian melanoma survivors. Standardized incidence ratios (SIRs) were calculated for overall and specific SPMs. The risk factor for overall SPM development was analyzed using a multivariable Cox regression model. A total of 10,070 patients with melanoma were included in the study. Melanoma survivors exhibited an increased risk of overall SPM (SIR, 1.51; 95% confidence interval [CI], 1.34-1.70). Additionally, specific SPMs were more common among melanoma survivors, including nonmelanoma skin cancer, oral cavity and pharyngeal cancer, renal cancer, female breast cancer, lung cancer, pancreatic cancer, and liver cancer. Independent risk factors for overall SPM development included a Charlson Comorbidity Index ≥ 1 (adjusted hazard ratio [aHR], 1.41; 95% CI, 1.07-1.87), and a body mass index ≥ 25 kg/m 2 (aHR, 1.47; 95% CI, 1.04-2.08). Inherent uncertainty related to diagnostic codes may exist. The risk of overall and specific SPMs was significantly elevated in Asian melanoma survivors, particularly among those with invasive melanoma. Among modifiable factors, a high body mass index (BMI) was associated with an increased risk of SPM., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Reviewed and approved by the Institutional Review Board of Asan Medical Center; approval no. 2021-0721. Informed consent: Informed consent was exempted from Institutional Review Board of Asan Medical Center due to the retrospective design., (© 2025. The Author(s).)

To understand the action mechanism of probiotics against postmenopausal symptoms, we examined the effects of Lactococcus lactis P32 (P L ) and Bifidobacterium bifidum P45 (P B ), which suppressed interleukin (IL)-6 and receptor activator of nuclear factor-κB (RANK) ligand (RNAKL) expression in Gardnerella vaginalis (Gv)-stimulated macrophages, on vaginitis, osteoporosis, and depression/cognitive impairment (DC) in mice with vaginally infected Gv, ovariectomy (Ov), or Ov/Gv (oG). Oral administration of P L or P B decreased Gv-induced DC-like behavior and tumor necrosis factor (TNF)-α, IL-6, RANK, and/or RANKL expression in the vagina, bone, hypothalamus, hippocampus, and colon, while Gv-suppressed bone osteoprotegerin and brain serotonin and brain-derived neurotrophic factor (BDNF) levels increased. They partially shifted vaginal and gut dysbiosis in Gv-infected mice to the gut microbiota composition in normal control mice. In mice with oG, oral administration of P L or P B decreased oG-induced DC-like behavior and TNF-α, IL-6, RANK, and/or RANKL expression in the vagina, bone, brain, and colon, while oG-suppressed bone osteoprotegerin and brain serotonin and BDNF levels increased. They also alleviated oG-induced vaginal and gut dysbiosis: they decreased Proteobacteria population. P L and P B (4:1) mix (P M ) suppressed DC-like behavior in mice with Gv, Ov, or oG. P M also suppressed TNF-α, IL-6, RANK, and/or RANKL expression in the vagina, bone, colon, and brain. P M alleviated Gv-induced vaginal and gut dysbiosis: it decreased Proteobacteria population. These findings suggest that P L and P B , singly or together, can alleviate postmenopausal symptoms including vaginitis, colitis, osteoporosis, and DC by suppressing RANK/RANKL-mediated NF-κB activation and alleviating vaginal/gut microbiota dysbiosis., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This study optimizes V T and ΔV T in amorphous indium-gallium-zinc-oxide (a-IGZO) field-effect transistors (FETs) by examining the influence of both channel length (L) and Ga composition. It was observed that as the ratio of In: Ga: Zn changed from 1:1:1 to 0.307:0.39:0.303 in the IGZO film, both V T and ΔV T decreased by 0.1 V at the shortest channel length (L = 0.5 μm). This reduction was attributed to the change in the oxygen concentration in IGZO due to the variation in Ga composition. In addition, as the channel length decreased from 10 μm to 0.5 μm, V T decreased by up to 0.7 V, and ΔV T decreased by up to 0.4 V. This observation was due to diffusion of oxygen vacancies (V O ) from the source and drain into the main channel. To provide a comprehensive understanding, we quantitatively modeled the doping concentration of IGZO and the trap density of gate insulator (GI) traps using TCAD simulation based on Ga composition and diffusion of V O . Using this approach, we propose a method to optimize the design of a-IGZO FETs with high V T and low ΔV T in short-channel devices by adjusting the Ga composition., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The unique saddle articulation of the trapeziometacarpal joint allows for a wide range of motion necessary for routine function of the thumb. Inherently unstable characteristics of the joint can lead painful instability. In this study, we modified a surgical dorsal ligament reconstruction technique for restoring trapeziometacarpal joint stability. We evaluated and compared the biomechanical efficacy of our reconstruction technique with that of dorsoradial capsulodesis by creating a cadaveric model of rotational instability. Twenty-four specimens were subjected to dorsoradial capsulodesis (n = 12) or dorsoradial ligament reconstruction using the abductor pollicis longus (APL) (n = 12). The modified dorsoradial ligament reconstruction entailed detaching one distally based slip of the APL. The harvested tendon's proximal end was passed through a bone tunnel created at the dorsoradial ridge of the trapezium. A suture anchor was inserted at the dorsal base of the metacarpal bone. The tendon stump was sutured to the metacarpal bone using fiber wire in figure-of-eight configuration. The load to failure of the trapeziometacarpal joint under compression was higher in the reconstruction group (p = 0.003). The improvement in the rotational arc (observed in all specimens) was significantly greater in the reconstruction group than the capsulodesis group (p = 0.003). Our technique reconstructs only the necessary ligament, requires a smaller incision and relatively simpler surgical procedure, and enables precise determination of the insertion and exit sites of the tendon, making it a promising treatment for trapeziometacarpal joint instability., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics statements: The study design was approved by the Institutional Review Board of Yonsei University Health System (approval number: 4-2024-0659). Informed consent was obtained for the use of cadavers legally donated to the Surgical Anatomy Education Centre at Yonsei University College of Medicine. The authors confirm that all applicable local and international ethical guidelines and laws for the use of human cadaveric donors in anatomical research were followed., (© 2024. The Author(s).)

Despite ultrasound guidance for central venous catheterization (CVC), the first-attempt success rate has remained around 52.6-62.1%. A significant reason is that the needle can sometimes be dislodged from the punctured vein during hand shifts. Here, a novel one-hand guidewire introducer (OGI) kit was developed to perform guidewire insertion in the central vein, eliminating hand shifts. To establish a protocol, the OGI kit was validated using a central line training phantom. A total of 48 randomized trials of guidewire insertion in the internal jugular vein in eight pigs were performed using either the conventional kit (group A) or the OGI kit (group B). All trials were technically successful with all eight pigs. First-attempt success rate (50% vs. 75%, p = 0.035) and global rating scale (12 (5-15) vs. 14 (8-15), p = 0.011) were significantly lower in group A than in group B. The number of needle redirections and guidewire insertions, time to guidewire insertion, and procedure-related complications were significantly higher in group A than in group B. Guidewire insertion using a novel OGI kit could be a promising approach for real-time ultrasound-guided CVC as it offers greater clinical usefulness., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This bicenter retrospective analysis included 162 patients who had undergone prostate biopsy following prebiopsy MRI, excluding those with PCa identified only in the peripheral zone (PZ). DLR T2WI achieved a 69% reduction in scan time relative to TSE T2WI. The intermethod agreement between the two T2WI sets in terms of the Prostate Imaging Reporting and Data System (PI-RADS) classification and extraprostatic extension (EPE) grade was measured using the intraclass correlation coefficient (ICC) and diagnostic performance was assessed with the area under the receiver operating characteristic curve (AUC). Clinically significant PCa (csPCa) was found in 74 (45.7%) patients. Both T2WI methods showed high intermethod agreement for the overall PI-RADS classification (ICC: 0.907-0.949), EPE assessment (ICC: 0.925-0.957) and lesion size measurement (ICC: 0.980-0.996). DLR T2WI and TSE T2WI showed similar AUCs (0.666-0.814 versus 0.684-0.832) for predicting EPE. The AUCs for detecting csPCa with DLR T2WI (0.834-0.935) and TSE T2WI (0.891-0.935) were comparable in 139 patients with TZ lesions with no significant differences (P > 0.05). The findings suggest that DLR T2WI is an efficient alternative for TZ lesion assessment, offering reduced scan times without compromising diagnostic accuracy., Competing Interests: Declarations. Competing interests: Marcel Dominik Nickel, Hyun-Soo Lee and Dongyeob Han are employees of Siemens Healthineers, but they did not influence the results of this study. Moon Hyung Choi is currently receiving a research grant from Company Siemens Healthineers and the research is not related to prostate MRI. Other 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. Ethical approval: This retrospective study involving human participants was performed in accordance with the ethical standards of the institutional and national research committees and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Institutional Review Board of the Catholic Medical Center approved this study (XC23WIDI0064). Informed consent: Informed consent was waived due to the retrospective design of the study., (© 2024. The Author(s).)

Malnutrition is a significant risk factor for postoperative outcomes in patients undergoing cardiac surgery. The Seoul National University Hospital-Nutrition Screening Index (SNUH-NSI) is an automated screening tool designed to comprehensively assess malnutrition risk. However, its predictive value in patients undergoing cardiac surgery remains unvalidated. This study included adult patients who underwent cardiac surgery at a tertiary teaching hospital between May 2008 and December 2019. Patients were classified as low-, intermediate-, or high-risk for malnutrition based on the SNUH-NSI. The association between malnutrition risk and postoperative cumulative all-cause mortality was evaluated using multivariable Cox regression analysis. The predictive ability of the SNUH-NSI was compared with conventional nutritional indices. Compared to the low-risk group, both the high-risk (adjusted hazard ratio [HR], 2.64; 95% confidence interval [CI], 2.19-3.19; P < 0.001) and intermediate-risk groups (adjusted HR, 1.54; 95% CI, 1.31-1.82; P < 0.001) demonstrated a significantly elevated risk of cumulative all-cause mortality. The multivariable model incorporating SNUH-NSI demonstrated moderate but superior predictive performance compared to that of other conventional nutritional indices. Preoperative malnutrition assessed by the SNUH-NSI was found to be a significant predictor of mortality following cardiac surgery. Implementing the SNUH-NSI for automated preoperative malnutrition screening could be an efficient and cost-effective approach., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The present study was designed to identify the preoperative clinical and imaging findings influencing adverse clinical outcomes in patients with chronic constrictive pericarditis after pericardiectomy. Patients with constrictive pericarditis who underwent pericardiectomy between January 2009 and September 2023 were retrospectively analyzed. Preoperative evaluations included assessments of clinical symptoms, comorbidities, laboratory tests, cardiac computed tomography (CT), and transthoracic echocardiography. The volume of pericardial calcifications was quantified on calcium scoring CT. Adverse clinical events were defined as cardiovascular death or hospitalization due to cardiac causes, and all-cause mortality was assessed. Univariable and multivariable Cox proportional hazard model analysis were performed to find factors associated with adverse clinical events. Among the 91 patients with available preoperative CT scans, 26 (28.6%) experienced adverse clinical events after pericardiectomy, with 19 (20.9%) experiencing cardiovascular deaths. On multivariable Cox analysis, larger pericardial calcium volume hazard ratio [HR], 1.004 (95% confidence interval [CI], 1.001-1.006) per 1cm 3 increase; p = 0.005), higher E/E' ratio (HR, 1.059, 95% CI, 1.015-1.105, p = 0.008), and lower albumin level (HR, 0.476, 95% CI, 0.229-0.986, p = 0.046) were significant factors associated with the adverse clinical events after pericardiectomy. The amount of pericardial calcification could be associated with the efficacy of pericardiectomy and potentially have implications for postoperative outcomes. Additionally, a high E/E ratio on echocardiography is indicative of unfavorable postoperative prognosis., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval and consent to participate This retrospective study was approved by the institutional review board of Asan Medical Center. Patients’ informed consent was waived due to retrospective nature of the study., (© 2024. The Author(s).)

Coronavirus disease-2019 (COVID-19), attributed to the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), has posed global health challenges since it first emerged in 2019, and its impact continues to persist. The neurotropic nature of SARS-CoV-2 remains undisclosed, though researchers are proposing hypotheses on how the virus is transmitted to the central nervous system. One of the prevailing hypotheses is that SARS-CoV-2 travels through the olfactory nerve system via the olfactory epithelium (OE). Using a K18-human angiotensin converting-enzyme 2 (hACE2) transgenic mouse model with impaired olfactory sensory neurons (OSNs) induced by zinc sulfate, we examined the role of the olfactory nerve in the brain invasion by SARS-CoV-2. Mice lacking OSNs exhibited reduced levels of viral transmission to the brain, leading to significantly improved outcomes following SARS-CoV-2 infection. Moreover, a positive correlation was observed between viral persistence in the OE and brain infection. These results indicate that early inhibition of the olfactory nerve pathway effectively prevents viral invasion of the brain in K18-hACE2 mice. Our study underscores the significance of the olfactory nerve pathway in the transmission of SARS-CoV-2 to the brain., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The Coronavirus disease 2019 (COVID-19) pandemic has led to a global health crisis, including ocular symptoms, primarily targeting the Angiotensin-Converting Enzyme 2 (ACE2) receptor. PM2.5 air pollution may increase infection risk by altering ACE2 expression. Silicon Dioxide (SiO 2 ) and carbon black (CB), major components of PM2.5 from sands and vehicle emissions, were studied for their effects on ACE2 and Transmembrane Protease Serine 2 (TMPRSS2) expression in corneal and conjunctival cells, and ocular tissues. Human corneal epithelial cells (HCECs) and conjunctival epithelial cells (HCjECs) were exposed to nanoparticles (NPs) for 24 hours, assessing viability via WST-8 assay. TNF-α, IL-6, and IL-1β levels in the medium were measured. An in vivo rat study administered NPs via eye drops, with Rose Bengal staining to evaluate damage. ACE2, TMPRSS2, and Angiotensin II (AngII) protein expressions were quantified by Western blot. ACE2 expression in HCjECs increased with NP exposure, while it decreased in HCECs. CB exposure increased TNF-α, IL-6, and IL-1β levels in HCECs. In vivo, corneal exposure to CB decreased ACE2 expression, whereas conjunctival exposure to SiO 2 increased ACE2 expression. These changes suggest that SiO2 exposure may increase the risk of COVID-19 through the ocular surface, while CB exposure may decrease it., (© 2024. The Author(s).)

This study aimed to investigate the short-term variability of ocular biometric measurements and to analyze the factors associated with high variability of biometric values in patients with cataract. This retrospective study included 60 eyes of 60 patients who underwent ocular biometry twice with the IOLMaster 700 (March to November 2023). Ocular surface parameters included tear film break-up time (TBUT), corneal and conjunctival staining scores (CSS/ConSS). Refractive surprise was defined as a mean absolute error exceeding 0.5 diopter (D). Participants included 22 men and 38 women with a mean age of 70.6 ± 8.4 years. The variability of mean keratometric (K) values and astigmatism showed notable variability compared to axial length (mean K: 0.18 ± 0.17D, astigmatism: 0.21 ± 0.26D, axial length: 0.01 ± 0.01 mm). A decreased TBUT and increased CSS were significantly associated with high variability (≥ 0.25D) of mean K (p = 0.040/0.008). The high K variability group (≥ 0.25D) revealed a significantly higher incidence of refractive surprise (> 0.5D) compared with the low K variability group (< 0.25D) (45.5%/17.9%, p = 0.037). Preoperative lower TBUT and higher CSS influenced the variability of K values in ocular biometry and may be related with postoperative refractive surprise due to erroneous K values., (© 2024. The Author(s).)

Dyskalemia is a common electrolyte abnormality. Since dyskalemia can cause fatal arrhythmias and cardiac arrest in severe cases, it is crucial to monitor serum potassium (K + ) levels on time. We developed deep learning models to detect hyperkalemia (K +  ≥ 5.5 mEq/L) and hypokalemia (K +  < 3.5 mEq/L) from electrocardiograms (ECGs), which are noninvasive and can be quickly measured. The retrospective cohort study was conducted at two hospitals from 2006 to 2020. The training set, validation set, internal testing cohort, and external validation cohort comprised 310,449, 15,828, 23,849, and 130,415 ECG-K + samples, respectively. Deep learning models demonstrated high diagnostic performance in detecting hyperkalemia (AUROC 0.929, 0.912, 0.887 with sensitivity 0.926, 0.924, 0.907 and specificity 0.706, 0.676, 0.635 for 12-lead, limb-lead, lead I ECGs) and hypokalemia (AUROC 0.925, 0.896, 0.885 with sensitivity 0.912, 0.896, 0.904 and specificity 0.790, 0.734, 0.694) in the internal testing cohort. The group predicted to be positive by the hyperkalemia model showed a lower 30-day survival rate compared to the negative group (p < 0.001), supporting the clinical efficacy of the model. We also compared the importance of ECG segments (P, QRS, and T) on dyskalemia prediction of the model for interpretability. By applying these models in clinical practice, it will be possible to diagnose dyskalemia simply and quickly, thereby contributing to the improvement of patient outcomes., (© 2024. The Author(s).)

This study aimed to investigate the association between non-traditional lipid profiles and the risk of 1-year vascular events in patients who were already using statins before stroke and had admission LDL-C < 100 mg/dL. This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with acute ischemic stroke patients who treated with statin before index stroke and LDL-C < 100 mg/dL on admission. Non-traditional lipid profiles including non-HDL, TC/HDL ratio, LDL/HDL ratio, and TG/HDL ratio were analyzed as a continuous or categorical variable. The primary vascular outcome within one year was a composite of recurrent stroke (either hemorrhagic or ischemic), myocardial infarction (MI) and all-cause mortality. Hazard ratios (95% Cis) for 1-year vascular outcomes were analyzed using the Cox PH model for each non-traditional lipid profiles groups. A total of 7028 patients (age 70.3 ± 10.8years, male 59.8%) were finally analyzed for the study. In unadjusted analysis, no significant associations were observed in the quartiles of LDL/HDL ratio and 1-year primary outcome. However, after adjustment of relevant variables, compared with Q1 of the LDL/HDL ratio, Q4 was significantly associated with increasing the risk of 1-year primary outcome (HR 1.48 [1.19-1.83]). For the LDL/HDL ratio, a linear relationship was observed (P for linearity < 0.001). Higher quartiles of the LDL/HDL ratio were significantly and linearly associated with increasing the risk of 1-year primary vascular outcomes. These findings suggest that even during statin therapy with LDL-C < 100 mg/dl on admission, there should be consideration for residual risk based on the LDL/HDL ratio, following stroke., (© 2024. The Author(s).)

It is uncertain whether the prognostic power of white matter hyperintensity (WMH) on post-stroke outcomes is modulated as a function of initial neurological severity, a critical determinant of outcome after stroke. This multi-center MRI study tested if higher WMH quintiles were associated with 3-month poor functional outcome (modified Rankin Scale ≥ 3) for mild versus moderate-to-severe ischemic stroke. Mild and moderate-to-severe stroke were defined as admission National Institute of Health Stroke Scale scores of 1-4 and ≥ 5, respectively. Mean age of the enrolled patients (n = 8918) was 67.2 ± 12.6 years and 60.1% male. The association between WMH quintiles and poor functional outcome was modified by stroke severity (p-for-interaction = 0.008). In mild stroke (n = 4994), WMH quintiles associated with the 3-month outcome in a dose-dependent manner for the 2nd to 5th quintile versus the 1st quintile, with adjusted-odds-ratios (aOR [95% confidence interval]) being 1.29 [0.96-1.73], 1.37 [1.02-1.82], 1.60 [1.19-2.13], and 1.89 [1.41-2.53], respectively. In moderate-to-severe stroke (n = 3924), however, there seemed to be a threshold effect: only the highest versus the lowest WMH quintile was significantly associated with poor functional outcome (aOR 1.69 [1.29-2.21]). WMH burden aggravates 3-month functional outcome after mild stroke, but has a lesser modulatory effect for moderate-to-severe stroke, likely due to saturation effects., (© 2024. The Author(s).)

The Internet of Things (IoT) generates substantial data through sensors for diverse applications, such as healthcare services. This article addresses the challenge of efficiently utilizing resources in resource-scarce IoT-enabled sensors to enhance data collection, transmission, and storage. Redundant data transmission from sensors covering overlapping areas incurs additional communication and storage costs. Existing schemes, namely Asymmetric Extremum (AE) and Rapid Asymmetric Maximum (RAM), employ fixed and variable-sized windows during chunking. However, these schemes face issues while selecting the index value to decide the variable window size, which may remain zero or very low, resulting in poor deduplication. This article resolves this issue in the proposed Controlled Cut-point Identification Algorithm (CCIA), designed to restrict the variable-sized window to a certain threshold. The index value for deciding the threshold will always be larger than the half size of the fixed window. It helps to find more duplicates, but the upper limit offset is also applied to avoid the unnecessarily large-sized window, which may cause extensive computation costs. The extensive simulations are performed by deploying Windows Communication Foundation services in the Azure cloud. The results demonstrate the superiority of CCIA in various metrics, including chunk number, average chunk size, minimum and maximum chunk number, variable chunking size, and probability of failure for cut point identification. In comparison to its competitors, RAM and AE, CCIA exhibits better performance across key parameters. Specifically, CCIA outperforms in total number of chunks (6.81%, 14.17%), average number of chunks (4.39%, 18.45%), and minimum chunk size (153%, 190%). These results highlight the effectiveness of CCIA in optimizing data transmission and storage within IoT systems, showcasing its potential for improved resource utilization and reduced operational costs., (© 2024. The Author(s).)

Cuticle quality can affect food safety by protecting poultry eggs from bacterial infection in the modern poultry industry. However, genetic factors related to cuticle nanostructure are not much reported due to limited bird models. In the current study, the genome-edited quail targeting myostatin (MSTN) gene was used to investigate the effect of MSTN mutation on the cuticle nanostructure and quality. To analyze nanostructure of the cuticle layer of the MSTN mutant and wild-type (WT) quail eggs, scanning electron microscope (SEM) images was taken. Thickness of the cuticle layer did not differ between the MSTN mutant and WT groups, but the size of the nanospheres in the surface of the cuticle layer was increased by MSTN mutation. In addition, increased size of the nanospheres in the MSTN mutant group was also shown in the upper region of the cross-sectional cuticle layer. Notably, both groups showed similar small-sized nanospheres in the lower region of the cuticle layer and the size was increased as they ascended to the upper region. The data suggested that MSTN mutation increased the size of the nanosphere in the upper region of the cuticle layer at a late phase rather than increasing the size of nanospheres in the lower region of the cuticle layer at an early phase of cuticle formation. However, the number of Escherichia coli attached to the surface did not differ between the two groups indicating no association between nanosphere size and bacterial attachment in quail eggs. The current study demonstrated a new function of the MSTN gene on regulation of cuticle nanostructure, for the first time. These results advanced our knowledge on the association between genetic factors and cuticle nanostructure and can be served as a reference to study the mechanism of cuticle formation in the future study., (© 2024. The Author(s).)

Although previous studies have suggested that meteorological factors and air pollutants can cause dry eye disease (DED), few clinical cohort studies have determined the individual and combined effects of these factors on DED. We investigated the effects of meteorological factors (humidity and temperature) and air pollutants [particles with a diameter ≤ 2.5 μ m (PM 2.5 ), ozone (O 3 ), nitrogen dioxide (NO 2 ), and carbon monoxide (CO)] on DED. A retrospective cohort study was conducted on 53 DED patients. DED was evaluated by Symptom Assessment in Dry Eye (SANDE), tear secretion, tear film break-up time (TBUT), ocular staining score (OSS), and tear osmolarity. To explore the individual, non-linear, and joint associations between meteorological factors, air pollutants, and DED parameters, we used generalized linear mixed model (GLMM) and Bayesian kernel machine regression (BKMR). After adjusting for all covariates, lower relative humidity or temperature was associated with a higher SANDE (p < 0.05). Higher PM 2.5 , O 3 , and NO 2 levels were associated with higher SANDE and tear osmolarity (p < 0.05). Higher O 3 levels were associated with lower tear secretion and TBUT, whereas higher NO 2 levels were associated with higher OSS (p < 0.05). BKMR analyses indicated that a mixture of meteorological factors and air pollutants was significantly associated with increased SANDE, OSS, tear osmolarity, and decreased tear secretion., (© 2024. The Author(s).)

Severe pneumonia results in high morbidity and mortality despite advanced treatments. This study investigates thoracic muscle mass from chest CT scans as a biomarker for predicting clinical outcomes in ICU patients with severe pneumonia. Analyzing electronic medical records and chest CT scans of 778 ICU patients with severe community-acquired pneumonia from January 2016 to December 2021, AI-enhanced 3D segmentation was used to assess thoracic muscle mass. Patients were categorized into clusters based on muscle mass profiles derived from CT scans, and their effects on clinical outcomes such as extubation success and in-hospital mortality were assessed. The study identified three clusters, showing that higher muscle mass (Cluster 1) correlated with lower in-hospital mortality (8% vs. 29% in Cluster 3) and improved clinical outcomes like extubation success. The model integrating muscle mass metrics outperformed conventional scores, with an AUC of 0.844 for predicting extubation success and 0.696 for predicting mortality. These findings highlight the strong predictive capacity of muscle mass evaluation over indices such as APACHE II and SOFA. Using AI to analyze thoracic muscle mass via chest CT provides a promising prognostic approach in severe pneumonia, advocating for its integration into clinical practice for better outcome predictions and personalized patient management., (© 2024. The Author(s).)

Mycobacterium avium complex pulmonary disease (MAC-PD) has a heterogeneous clinical course. However, immune profiles associated with MAC-PD clinical course are limited. We performed single-cell RNA sequencing of peripheral blood mononuclear cells from 21 MAC-PD patients divided into three clinical courses: group A, spontaneous culture conversion; group B, stable disease without antibiotic treatment; and group C, progressive disease with antibiotic treatment. A lower proportion of NK cells and higher proportion of monocytes were noted in group C compared to combined groups A and B. The proportion of classical monocytes was higher in group C compared to groups A and B, while the proportion of non-classical monocytes decreased. EGR1, HSPA1A, HSPA1B, and CD83 were up-regulated in spontaneous culture conversion group A compared to progressive disease group C. Up-regulation of MYOM2 and LILRA4 and down-regulation of MT-ATP8, CD83, and CCL3L1 was found in progressive disease group C. PCBP1, FOS, RGCC, S100B, G0S2, AREG, and LYN were highly expressed in favorable treatment response compared to unfavorable response. Our findings may offer a comprehensive understanding of the host immune profiles that influence a particular MAC-PD clinical course and could suggest an immunological mechanism associated with the disease progression of MAC-PD., (© 2024. The Author(s).)

Previously, we reported successful cellular expansion of a murine colorectal carcinoma cell line (CT-26) using a three-dimensional (3D) engineered extracellular matrix (EECM) fibrillar scaffold structure. CCL-247 were grown over a limited time period of 8 days on 3D EECM or tissue culture polystyrene (TCPS). Cells were then assayed for growth, electroporation efficiency and Vigil manufacturing release criteria. Using EECM scaffolds, we report an expansion of CCL-247 (HCT116), a colorectal carcinoma cell line, from a starting concentration of 2.45 × 10 5 cells to 1.9 × 10 6 cells per scaffold. Following expansion, 3D EECM-derived cells were assessed based on clinical release criteria of the Vigil manufacturing process utilized for Phase IIb trial operation with the FDA. 3D EECM-derived cells passed all Vigil manufacturing release criteria including cytokine expression. Here, we demonstrate successful Vigil product manufacture achieving the specifications necessary for the clinical trial product release of Vigil treatment. Our results confirm that 3D EECM can be utilized for the expansion of human cancer cell CCL-247, justifying further clinical development involving human tissue sample manufacturing including core needle biopsy and minimal ascites samples., (© 2024. The Author(s).)

Nontuberculous mycobacteria (NTM) infection diagnosis remains a challenge due to its overlapping clinical symptoms with tuberculosis (TB), leading to inappropriate treatment. Herein, we employed noninvasive metabolic phenotyping coupled with comprehensive statistical modeling to discover potential biomarkers for the differential diagnosis of NTM infection versus TB. Urine samples from 19 NTM and 35 TB patients were collected, and untargeted metabolomics was performed using rapid liquid chromatography-mass spectrometry. The urine metabolome was analyzed using a combination of univariate and multivariate statistical approaches, incorporating machine learning. Univariate analysis revealed significant alterations in amino acids, especially tryptophan metabolism, in NTM infection compared to TB. Specifically, NTM infection was associated with upregulated levels of methionine but downregulated levels of glutarate, valine, 3-hydroxyanthranilate, and tryptophan. Five machine learning models were used to classify NTM and TB. Notably, the random forest model demonstrated excellent performance [area under the receiver operating characteristic (ROC) curve greater than 0.8] in distinguishing NTM from TB. Six potential biomarkers for NTM infection diagnosis, including methionine, valine, glutarate, 3-hydroxyanthranilate, corticosterone, and indole-3-carboxyaldehyde, were revealed from univariate ROC analysis and machine learning models. Altogether, our study suggested new noninvasive biomarkers and laid a foundation for applying machine learning to NTM differential diagnosis., (© 2024. The Author(s).)

This study aimed to assess the efficacy of dual T-cell suppression using individually tailored doses of antithymocyte globulin (ATG) and attenuated dose of post-transplant cyclophosphamide (PTCy) in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We conducted a retrospective analysis of 78 adults with acute leukemia or myelodysplastic syndrome who underwent haplo-HSCT using intravenous busulfan and fludarabine conditioning. Thirty-two patients received attenuated ATG/PTCy, while 46 patients received ATG (7.5 mg/kg) as GVHD prophylaxis. The 100-day cumulative incidence of grade III-IV (9.7% vs. 32.4%, P = 0.018) acute GVHD, as well as 2-year moderate-severe chronic GVHD (13.9% vs. 43.9%, P = 0.018) in the ATG/PTCy group were significantly lower than those in the ATG group. The 2-year overall survival was comparable between the two groups. However, 2-year GVHD-free, relapse-free survival in the ATG/PTCy group was significantly higher compared to that in the ATG group (38.9% vs. 21.7%, P = 0.021). Moreover, during post-engraftment period, the ATG/PTCy group exhibited lower incidences of life-threatening bacterial (12.5% vs. 37%, P = 0.033) and viral infection (0% vs. 17.4%, P = 0.035) than the ATG group. In conclusion, the combination of individually tailored ATG and low-dose PTCy appears to be a promising strategy in haplo-HSCT., (© 2024. The Author(s).)

A positive resection margin after colorectal endoscopic submucosal dissection (ESD) is associated with an increased risk of recurrence. We aimed to identify the clinical significance of positive resection margins in colorectal neoplasms after ESD. We reviewed 632 patients who had en bloc colorectal ESD at two hospitals between 2015 and 2020. The recurrence rates and presence of residual tumor after surgery were evaluated. The rate of additional surgery after ESD and recurrence rate were significantly higher in patients with incomplete resection (n = 75) compared to patients with complete resection (n = 557). When focusing solely on non-invasive lesions, no significant differences in recurrence rates were observed between the groups with complete and incomplete resection (0.2% vs. 1.9%, p = 0.057). Among 84 patients with submucosal invasive carcinoma, 39 patients underwent additional surgery due to non-curative resection. Positive vertical margin and lymphovascular invasion were associated with residual tumor. Lymphovascular invasion was associated with lymph node metastasis. However, no residual tumor nor lymph node metastases were found in patients with only one unfavorable histological factor. In conclusion, a positive resection margin in non-invasive colorectal lesions, did not significantly impact the recurrence rate. Also, in T1 colorectal cancer with a positive vertical resection margin, salvage surgery can be considered in selected patients with additional risk factors., (© 2024. The Author(s).)

Endoscopic middle meatal antrostomy (MMA) is commonly used for maxillary sinus (MS) fungal ball removal. For challenging cases involving anterior or inferior recess, an additional inferior meatal approach (IMA) might be needed. We analyzed the differences in MS dimensions on CT scans according to the surgical approach to suggest preoperative variables that could facilitate an additional IMA. CT scans of 281 adult patients who underwent ESS for the MS fungal ball (139 MMA, 62 MMA & IMA) were evaluated for comparative analysis of 8 MS measurements based on the surgical approach. Complete removal was achieved in all cases. Age and sex didn't differ significantly (p > 0.05). The maximum distances between the anterior-posterior walls, the inferior ostium border to the lateral recess, and the ostium to the inferior wall of the MS were statistically greater in the MMA & IMA group compared to the MMA group (p = 0.003, p = 0.005, and p = 0.010, respectively), especially among females. This study underscores the clinical importance of specific measurements-anterior to posterior wall, medial wall to lateral recess, and ostium to inferior wall of the maxillary sinus-for guiding optimal surgical approaches in MS lesions., (© 2024. The Author(s).)

In this paper, the floating body effect (FBE) in indium-gallium-zinc-oxide (IGZO) thin-film transistor (TFT) and the mechanism of device failure caused by that are reported for the first time. If the toggle AC pulses are applied to the gate and drain simultaneously for the switching operation, the drain current of IGZO TFT increases dramatically and cannot show the on/off switching characteristics. This phenomenon was not reported before, and our study reveals that the main cause is the formation of a conductive path between the source and drain: short failure. It is attributed in part to the donor creation at the drain region during the high voltage (V high ) condition and in part to the donor creation at the source region during the falling edge and low voltage (V low ) conditions. Donor creation is attributed to the peroxide formation in the IGZO layer induced by the electrons under the high lateral field. Because the donor creation features positive charges, it lowers the threshold voltage of IGZO TFT. In detail, during the V high condition, the donor creation is generated by accumulated electrons with a high lateral field at the drain region. On the other hand, the floating electrons remaining at the short falling edge (i.e., FBE of the IGZO TFT) are affected by the high lateral field at the source region during the V low condition. As a result, the donor creation is generated at the source region. Therefore, the short failure occurs because the donor creations are generated and expanded to channel from the drain and source region as the AC stress accumulates. In summary, the FBE in IGZO TFT is reported, and its effect on the electrical characteristics of IGZO TFT (i.e., the short failure) is rigorously analyzed for the first time., (© 2024. The Author(s).)

Interfacial magnetic interactions between different elements are the origin of various spin-transport phenomena in multi-elemental magnetic systems. We investigate the coupling between the magnetic moments of the rare-earth, transition-metal, and heavy-metal elements across the interface in a GdFeCo/Pt thin film, an archetype system to investigate ferrimagnetic spintronics. The Pt magnetic moments induced by the antiferromagnetically aligned FeCo and Gd moments are measured using element-resolved x-ray measurements. It is revealed that the proximity-induced Pt magnetic moments are always aligned parallel to the FeCo magnetic moments, even below the ferrimagnetic compensation temperature where FeCo has a smaller moment than Gd. This is understood by a theoretical model showing distinct effects of the rare-earth Gd 4f and transition-metal FeCo 3d magnetic moments on the Pt electronic states. In particular, the Gd and FeCo work in-phase to align the Pt moment in the same direction, despite their antiferromagnetic configuration. The unexpected additive roles of the two antiferromagnetically coupled elements exemplify the importance of detailed interactions among the constituent elements in understanding magnetic and spintronic properties of thin film systems., (© 2024. The Author(s).)

Recently, resuscitative endovascular balloon occlusion of the aorta (REBOA) had been introduced as an innovative procedure for severe hemorrhage in the abdomen or pelvis. We aimed to investigate risk factors associated with mortality after REBOA and construct a model for predicting mortality. This multicenter retrospective study collected data from 251 patients admitted at five regional trauma centers across South Korea from 2015 to 2022. The indications for REBOA included patients experiencing hypovolemic shock due to hemorrhage in the abdomen, pelvis, or lower extremities, and those who were non-responders (systolic blood pressure (SBP) < 90 mmHg) to initial fluid treatment. The primary and secondary outcomes were mortality due to exsanguination and overall mortality, respectively. After feature selection using the least absolute shrinkage and selection operator (LASSO) logistic regression model to minimize overfitting, a multivariate logistic regression (MLR) model and nomogram were constructed. In the MLR model using risk factors selected in the LASSO, five risk factors, including initial heart rate (adjusted odds ratio [aOR], 0.99; 95% confidence interval [CI], 0.98-1.00; p = 0.030), initial Glasgow coma scale (aOR, 0.86; 95% CI 0.80-0.93; p < 0.001), RBC transfusion within 4 h (unit, aOR, 1.12; 95% CI 1.07-1.17; p < 0.001), balloon occlusion type (reference: partial occlusion; total occlusion, aOR, 2.53; 95% CI 1.27-5.02; p = 0.008; partial + total occlusion, aOR, 2.04; 95% CI 0.71-5.86; p = 0.187), and post-REBOA systolic blood pressure (SBP) (aOR, 0.98; 95% CI 0.97-0.99; p < 0.001) were significantly associated with mortality due to exsanguination. The prediction model showed an area under curve, sensitivity, and specificity of 0.855, 73.2%, and 83.6%, respectively. Decision curve analysis showed that the predictive model had increased net benefits across a wide range of threshold probabilities. This study developed a novel intuitive nomogram for predicting mortality in patients undergoing REBOA. Our proposed model exhibited excellent performance and revealed that total occlusion was associated with poor outcomes, with post-REBOA SBP potentially being an effective surrogate measure., (© 2024. The Author(s).)

Carbon nanotube networks (CNTs)-based devices are well suited for the physically unclonable function (PUF) due to the inherent randomness of the CNT network, but CNT networks can vary significantly during manufacturing due to various controllable process conditions, which have a significant impact on PUF performance. Therefore, optimization of process conditions is essential to have a PUF with excellent performance. However, because it is time-consuming and costly to fabricate directly under various conditions, we implement randomly formed CNT network using simulation and confirm the variable correlation of the CNT network optimized for PUF performance. At the same time, by implementing an analog PUF through simulation, we present a 2D patterned PUF that has excellent security and can compensate for error occurrence problems. To evaluate the performance of analog PUF, a new evaluation method different from the existing digital PUF is proposed, and the PUF performance is compared according to two process variables, CNT density and metallic CNT ratio, and the correlation with PUF performance is confirmed. This study can serve as a basis for research to produce optimized CNT PUF by applying simulation according to the needs of the process of forming a CNT network., (© 2024. The Author(s).)

This study aimed to compare the outcomes of flanged intraocular lens (IOL) fixation with new IOL exchange after dislocated IOL removal and repositioned dislocated IOL in patients with IOL dislocation. Eighty-nine eyes that underwent flanged IOL fixation were retrospectively included, with 51 eyes in the exchanged IOL group and 38 eyes in the repositioned IOL group. In both groups, best-corrected visual acuity (BCVA) improved at 1, 3, 6, and 12 months postoperatively and did not differ between the two groups at any of these time points. However, at 1 week postoperatively, BCVA in the repositioned IOL group improved compared with baseline, whereas that in the exchanged IOL group did not. Moreover, there were lesser changes in the corneal endothelial cell density (ECD) and corneal astigmatism in the repositioned IOL group than in the exchanged IOL group. The IOL positions, including IOL tilt and IOL decentration, were not different between the groups. Flanged IOL fixation with new IOL exchange and with repositioned dislocated IOL for patients with IOL dislocation had similar visual outcomes and IOL position. However, the latter had a smaller corneal ECD decrease and astigmatic change. This technique was effective in treating IOL dislocation while minimizing corneal injury., (© 2024. The Author(s).)

Autogenous iliac bone graft (AIBG) is the treatment of choice for managing bone defects, and favorable results have been reported for bone defects < 5 cm in length. In large bone defects ≥ 5 cm, it is difficult to obtain good results with simple bone grafting, and other management options have drawbacks, such as long immobilization periods and high complication rates. We hypothesized that AIBG in the strut form might show favorable results in large bone defects with minimal complications. This study aimed to investigate the outcomes of strut-type AIBG and evaluate its effectiveness compared to cancellous AIBG. This retrospective study included 50 patients who underwent AIBG for bone defects at a single institution between March 2011 and April 2020. We performed corticocancellous AIBG in a strut form to manage bone defects ≥ 5 cm in the lower extremities. The strut bone was harvested along the iliac crest and grafted slightly longer than the bone defect to apply a sufficient compressive force. Demographic information and radiographic and clinical results of patients who underwent strut AIBG (Group S) were analyzed. The outcomes of union, time to union, complications, and reoperation were compared with those of patients who underwent cancellous AIBG (Group C). The study population comprised 37 men (74%) and 13 women (26%), with a mean age of 50.0 (range: 19-78). The average follow-up period was 25.6 months (12-104 months). Group S included 16 patients with a mean bone defect length of 6.8 ± 1.2 cm. In Group S, union was achieved in all patients, with an average time to union of 6.7 months. Complications occurred in four cases, all related to wound problems. Group C comprised d 34 patients with a mean defect length of 2.8 ± 1.1 cm. Complications occurred in five patients in Group C, including four soft tissue problems and one implant failure. When comparing the outcomes of Groups S and C, no significant differences were observed. AIBG is an effective and safe technique for managing bone defects. Strut AIBG can be used effectively for bone defects ≥ 5 cm in the lower extremities., (© 2024. The Author(s).)

Hydrophobic surfaces have a wide range of applications, such as water harvesting, self-cleaning, and anti-biofouling. However, traditional methods of achieving hydrophobicity often involve the use of toxic materials such as fluoropolymers. This study aims to create controllable wettability surfaces with a three-dimensional geometry using a laser base powder bed fusion (PBF) process with commercially pure titanium (CP-Ti) and silicone oil as non-toxic materials. The optimal PBF process parameters for fabricating micropillar structures, which are critical for obtaining the surface roughness necessary for achieving hydrophobic properties, were investigated experimentally. After fabricating the micropillar structures using PBF, their surface energy was reduced by treatment with silicone oil. Silicone oil provides a low-surface-energy coating that contributes to the water-repellent nature of hydrophobic surfaces. The wettability of the treated CP-Ti surfaces was evaluated based on the diameter of the pillars and the space between them. The structure with the optimal diameter and spacing of micropillars exhibited a high contact angle (156.15°). A pronounced petal effect (sliding angle of 25.9°) was achieved because of the morphology of the pillars, indicating the controllability of wetting. The micropillar diameter, spacing, and silicone oil played crucial roles in determining the water contact and sliding angle, which are key metrics for surface wettability., (© 2024. The Author(s).)

Iontronic devices, recognized for user-friendly soft electronics, establish an electrical double layer (EDL) at the interface between ion gels and electrodes, significantly influencing device performance. Despite extensive research on ion gels and diverse electrode materials, achieving a stable interfacial formation remains a persistent challenge. In this work, we report a solution to address this challenge by employing CO 2 irradiation as a bottom-up methodology to directly fabricate highly conductive, conformable laser-induced graphene (LIG) electrodes on a polyimide (PI)-based ion gel. The PI ion gel exhibits exceptional EDL formation at the electrode interface, primarily attributable to efficient ion migration. Particularly, ionic laser-induced graphene (i-LIG) electrodes, derived from the PI ion gel as a precursor, yield high-quality graphene with enhanced crystallinity and an expanded porous structure in the upward direction. This outcome is achieved through a pronounced thermal transfer effect and intercalation phenomenon between graphene layers, facilitated by the presence of ionic liquids (ILs) within the PI ion gel. Ultimately, in comparison to alternative soft electrode-based vertical capacitors, the utilization of i-LIGs and PI ion gels in the vertical capacitor demonstrates reduced interfacial resistance and increased EDL capacitance, emphasizing the extensive potential of iontronic devices. These results not only highlight these features but also introduce a new perspective for advancing next-generation iontronic devices., (© 2024. The Author(s).)

This study evaluates the accuracy of a newly developed intraocular lens (IOL) power calculation method that applies four different IOL power calculation formulas according to 768 biometric subgroups based on keratometry, anterior chamber depth, and axial length. This retrospective cross-sectional study was conducted in at Korea University Ansan Hospital. A total of 1600 eyes from 1600 patients who underwent phacoemulsification and a ZCB00 IOL in-the-bag implantation were divided into two datasets: a reference dataset (1200 eyes) and a validation dataset (400 eyes). Using the reference dataset and the results of previous studies, the Eom IOL power calculator was developed using 768 biometric subgroups. The median absolute errors (MedAEs) and IOL Formula Performance Indexes (FPIs) of the Barrett Universal II, Haigis, Hoffer Q, Holladay 1, Ladas Super, SRK/T, and Eom formulas using the 400-eye validation dataset were compared. The MedAE of the Eom formula (0.22 D) was significantly smaller than that of the other four formulas, except for the Barrett Universal II and Ladas Super formulas (0.24 D and 0.23 D, respectively). The IOL FPI of the Eom formula was 0.553, which ranked first, followed by the Ladas Super (0.474), Barrett Universal II (0.470), Holladay 1 (0.444), Hoffer Q (0.396), Haigis (0.392), and SRK/T (0.361) formulas. In conclusion, the Eom IOL power calculator developed in this study demonstrated similar or slightly better accuracy than the Barrett Universal II and Ladas Super formulas and was superior to the four traditional IOL power calculation formulas., (© 2024. The Author(s).)

We conducted a prospective study to evaluate the efficacy of simulation-based education using a three-dimensional (3D)-printed schematic eye model in improving the retinoscopy refraction skills of medical students. A schematic eye model was printed using a fused deposition modeling-based 3D printer. Twenty medical students randomized into 3D (n = 10) and control (n = 10) groups received a 1-h lecture on the principles and methods of manifest refraction and were shown how to use the retinoscope and sciascope bars. The 3D group additionally attended a tutorial on the schematic eye. Both groups performed refractive examinations on four eyes of volunteer patients, and the results were recorded as a baseline. Instructor feedback and refraction practice was provided with the 3D group or with control group. To account for subject fatigue, patients spent no more than 8 min on the examination. After a 1-h break to allow for fatigue and familiarity, refraction tests were repeated on four randomly selected eyes of patients. Students' refraction readings were compared with the autorefractor values using a spherical equivalent value and blur strength. All participants measured the time required to complete the refraction test and reported their subjective confidence in the results of each refraction test. Refractive errors before and after training did not differ between the control and 3D groups, with a significant improvement in errors observed in both groups (p = 0.005 and 0.008, respectively). The time to complete refraction before and after training did not differ between the two groups, both of which showed a significant reduction in time (p = 0.005 and 0.028, respectively). Pre- and post-training confidence scores for the accuracy of each refraction on a 10-point Likert scale were not significantly different. However, when comparing score changes between pre- and post-training, only the control group showed a significant increase in confidence (p = 0.005). Tests for the non-inferiority of refractive errors after training indicated that the 3D group was non-inferior to the control group. In conclusion, training in retinoscopy refraction skills using a 3D-printed eye model resulted in significant improvement in accuracy and speed compared to practice with real patients. Except for better confidence in the control group, schematic eye model training was not inferior to practice with real patients., (© 2024. The Author(s).)

Skin electronics, facilitating a high-quality interface between external devices and human skin for recording physiological and/or electrophysiological signals as well as delivering external electrical and/or mechanical energy into the human body, has shown significant progress. However, achieving mechanically conformal contact and electrically low contact resistance at the device-skin interface remains challenging. Here, we propose a material strategy to potentially address such an issue by using phase separation of silver nanowires and silver nanoparticles (Ag NWs and Ag NPs) within a stretchable conductive nanocomposite (NC). This phase-separated NC ensures low contact resistance and high conductivity, which are key requirements in skin electronics, while maintaining excellent mechanical contact with the skin. To achieve phase separation, we hydrophobically treated the surfaces of Ag NWs and Ag NPs. Then, as the NC solidified, the solvent contained in the NC was slowly evaporated to sufficiently precipitate Ag NPs within the NC. As a result, the phase-separated NC exhibited high conductivity (~ 18,535 S cm -1 ), excellent stretchability (~ 80%), and low contact resistance on both the top and bottom NC surfaces (average ~ 0.132 Ω). The phase-separated NC has enabled implementation of high performance skin-mounted devices, including strain sensors, electrophysiological sensors, and a wearable heater., (© 2024. The Author(s).)

There has been significant research focused on the development of stretchable materials that can provide a large area with minimal material usage for use in solar cells and displays. However, most materials exhibit perpendicular shrinkage when stretched, which is particularly problematic for polymer-based substrates commonly used in stretchable devices. To address this issue, biaxial strain-controlled substrates have been proposed as a solution to increase device efficiency and conserve material resources. In this study, we present the design and fabrication of a biaxial strain-controlled substrate with a re-entrant honeycomb structure and a negative Poisson's ratio. Using a precisely machined mold with a shape error of less than 0.15%, we successfully fabricated polydimethylsiloxane substrates with a 500 μm thick re-entrant honeycomb structure, resulting in a 19.1% reduction in perpendicular shrinkage. This improvement translates to a potential increase in device efficiency by 9.44% and an 8.60% reduction in material usage for substrate fabrication. We demonstrate that this design and manufacturing method can be applied to the fabrication of efficient stretchable devices, such as solar cells and displays., (© 2023. The Author(s).)

Limited data exist on longitudinal changes in the sputum bacterial microbiome during treatment in nontuberculous mycobacterial pulmonary disease (NTM-PD) patients. We prospectively collected serial sputum samples from 14 NTM-PD patients during treatment, at the start (n = 14) and at 1 (n = 10), 3 (n = 10), 6 (n = 12), and 12 (n = 7) months. The bacterial microbiome changes were analyzed using 16S rRNA sequences (V3-V4 regions). Subgroup analysis included culture conversion (n = 9) and treatment refractory (n = 5) groups. In all patients, sputum alpha-diversity (ACE, Chao1, and Jackknife) significantly decreased during antibiotic treatment at 1, 3, 6, and 12 months compared to treatment initiation levels. Within the culture conversion group, genus/species-level beta-diversity showed differences at 1, 3, 6, and 12 months compared to treatment initiation (all p < 0.05). However, in the refractory group, there were no differences in beta-diversity at the genus/species levels in the sputum at any time point. In the linear discriminant analysis (LDA) effect sizes (LEfSe) analysis, the culture conversion group exhibited decreasing taxa at various levels (phylum/genus/species), but no significant increase in taxa was observed. LEfSe analysis of the refractory patient group revealed multiple taxa decreased during treatment. However, proportions of Veillonella dispar (LDA = 4.78), Fusobacterium periodonticum (LDA = 4.35), and Pseudomonas aeruginosa (LDA = 2.92) increased as the treatment period progressed in the refractory group. Sputum microbiota diversity decreases during NTM-PD treatment. In the culture conversion group, most taxa decrease, while some increase in the refractory group. These findings suggest that a distinct respiratory microbial community may exist in refractory NTM-PD patients compared to responsive antibiotic-treated patients., (© 2023. The Author(s).)

Routine laboratory tests are regularly performed in patients undergoing maintenance hemodialysis (HD) to detect anemia, chronic kidney disease-mineral bone disorders, and cardiovascular disease. More frequent laboratory tests may be associated with better outcomes. However, there is little evidence supporting a specific monitoring interval. This study evaluated the impact of regular laboratory testing on mortality in Korean patients undergoing maintenance HD. We used HD quality assessments, and National Health Insurance Service claims data from October to December 2015. In HD quality assessment, 22 tests are recommended every 1-6 months. A total of 34,950 patients were divided into two groups based on the regularity of laboratory testing. A Cox proportional hazards model was used to assess the effects of regular laboratory tests on patient mortality during a mean follow-up duration of 53.7 months. The proportion of patients with and without regular laboratory testing was 85.6% (n = 29,914) and 14.4% (n = 5036), respectively. Patients who underwent regular laboratory testing had a longer dialysis duration, lower serum phosphorus levels and diastolic blood pressure, and higher hemoglobin and single-pool Kt/V levels than those who did not. After adjusting for demographic and clinical parameters, regular laboratory testing independently reduced mortality risk (hazard ratio, 0.90; 95% confidence interval 0.85-0.95; P < 0.001). Regular laboratory testing was associated with a decreased mortality risk among patients undergoing HD. Management of end-stage kidney disease-related complications based on laboratory tests can improve survival., (© 2023. The Author(s).)

Oxide semiconductor thin-film transistors (TFTs) are used in the pixel array and gate driver circuits of organic light emitting diode (OLED) display panels. Long-term reliability characteristics of the TFTs are a barometer of the lifetime of OLED display panels. The long-term reliability of the driver TFTs is evaluated in a short time under high voltages and high temperature for an accelerated degradation test. If reliability parameters from the power law or stretched-exponential functions are the same for individual devices and devices in an operating panel, the lifetime of the panel can be accurately estimated. However, since compensation circuits are designed into operating panels, an environmental discrepancy exists between the accelerated test of single devices and the operation of devices in the panel. Herein, we propose a novel compensation stretched-exponential function (CSEF) model which captures the effect of the threshold voltage compensation circuit in the panel. The CSEF model not only bridges the discrepancy between individual devices and panel devices, but also provides a method to accurately and efficiently estimate the long-term lifetime of all display panels that utilize compensation circuits., (© 2023. Springer Nature Limited.)

Since SLCO1B1 encodes the uptake transporter OATP1B1, which can influence the pharmacokinetic and pharmacodynamic profiles of edoxaban, polymorphisms in SLCO1B1 may affect the edoxaban response. This study aimed to investigate the association between SLCO1B1 gene polymorphisms and the bleeding risk in patients receiving edoxaban. We genotyped 10 single-nucleotide polymorphisms (SNPs) from the SLCO1B1 gene in patients receiving edoxaban. We also analyzed rs3842 of ABCB1 as a confounder. The odds ratio (OR) and adjusted OR (AOR) were calculated from univariate and multivariable analysis, respectively. The area under the receiver operating characteristic curve (AUROC) was constructed for the discrimination of the model. A total of 159 patients receiving edoxaban were analyzed. Overdose and rs4149056 showed significant association with bleeding complications by around 11- and 5.5-fold, respectively. Additionally, patients with the rs4149057 variant allele (C) had a 3.9-fold increased bleeding risk compared with wild-type homozygote carriers (TT), whereas rs2306283 variant homozygote (GG) carriers had a 0.27-fold reduced bleeding risk compared with wild-type allele (A) carriers. Patients with the variant-type homozygote (CC) of ABCB1 rs3842 had a higher bleeding risk than T allele carriers (AOR = 5.3 and 5.9). The final models for multivariable analyses were acceptable based on the AUROC values (> 0.70). These findings may help predict bleeding risk in patients taking edoxaban and help personalize treatment., (© 2023. Springer Nature Limited.)

Antibiotics are increasingly recognized as causing neuropsychiatric side effects including depression and anxiety. Alterations in central serotonin and 5-HT receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with gastrointestinal disorders. Nevertheless, it is still unclear how antibiotics can cause anxiety and depression. In this study, oral administration of cefaclor, a second-generation cephalosporin antibiotic, induced anxiety- and depression-like behaviors and colitis with gut microbiota alteration in mice. Cefaclor reduced serotonin levels and fluctuated 5-HT receptor mRNA expressions such as Htr1a, Htr1b, and Htr6 in the hippocampus. Vagotomy attenuated the cefaclor-induced anxiety- and depression-like symptoms, while the cefaclor-induced changes in gut bacteria alteration and colitis were not affected. Fluoxetine attenuated cefaclor-induced anxiety- and depression-like behaviors. Furthermore, fluoxetine decreased cefaclor-resistant Enterobacteriaceae and Enterococcaceae. Taken together, our findings suggest that the use of antibiotics, particularly, cefaclor may cause gut dysbiosis-dependent anxiety and depression through the microbiota-gut-blood-brain and microbiota-gut-vagus nerve-brain pathway. Targeting antibiotics-resistant pathogenic bacteria may be a promising therapeutic strategy for the treatment of anxiety and depression., (© 2023. Springer Nature Limited.)

Despite challenges in severity scoring systems, artificial intelligence-enhanced electrocardiography (AI-ECG) could assist in early coronavirus disease 2019 (COVID-19) severity prediction. Between March 2020 and June 2022, we enrolled 1453 COVID-19 patients (mean age: 59.7 ± 20.1 years; 54.2% male) who underwent ECGs at our emergency department before severity classification. The AI-ECG algorithm was evaluated for severity assessment during admission, compared to the Early Warning Scores (EWSs) using the area under the curve (AUC) of the receiver operating characteristic curve, precision, recall, and F1 score. During the internal and external validation, the AI algorithm demonstrated reasonable outcomes in predicting COVID-19 severity with AUCs of 0.735 (95% CI: 0.662-0.807) and 0.734 (95% CI: 0.688-0.781). Combined with EWSs, it showed reliable performance with an AUC of 0.833 (95% CI: 0.830-0.835), precision of 0.764 (95% CI: 0.757-0.771), recall of 0.747 (95% CI: 0.741-0.753), and F1 score of 0.747 (95% CI: 0.741-0.753). In Cox proportional hazards models, the AI-ECG revealed a significantly higher hazard ratio (HR, 2.019; 95% CI: 1.156-3.525, p = 0.014) for mortality, even after adjusting for relevant parameters. Therefore, application of AI-ECG has the potential to assist in early COVID-19 severity prediction, leading to improved patient management., (© 2023. Springer Nature Limited.)

Conventional severity-of-illness scoring systems have shown suboptimal performance for predicting in-intensive care unit (ICU) mortality in patients with severe pneumonia. This study aimed to develop and validate machine learning (ML) models for mortality prediction in patients with severe pneumonia. This retrospective study evaluated patients admitted to the ICU for severe pneumonia between January 2016 and December 2021. The predictive performance was analyzed by comparing the area under the receiver operating characteristic curve (AU-ROC) of ML models to that of conventional severity-of-illness scoring systems. Three ML models were evaluated: (1) logistic regression with L2 regularization, (2) gradient-boosted decision tree (LightGBM), and (3) multilayer perceptron (MLP). Among the 816 pneumonia patients included, 223 (27.3%) patients died. All ML models significantly outperformed the Simplified Acute Physiology Score II (AU-ROC: 0.650 [0.584-0.716] vs 0.820 [0.771-0.869] for logistic regression vs 0.827 [0.777-0.876] for LightGBM 0.838 [0.791-0.884] for MLP; P < 0.001). In the analysis for NRI, the LightGBM and MLP models showed superior reclassification compared with the logistic regression model in predicting in-ICU mortality in all length of stay in the ICU subgroups; all age subgroups; all subgroups with any APACHE II score, PaO 2 /FiO 2 ratio < 200; all subgroups with or without history of respiratory disease; with or without history of CVA or dementia; treatment with mechanical ventilation, and use of inotropic agents. In conclusion, the ML models have excellent performance in predicting in-ICU mortality in patients with severe pneumonia. Moreover, this study highlights the potential advantages of selecting individual ML models for predicting in-ICU mortality in different subgroups., (© 2023. The Author(s).)

We investigated the correlation between standardized uptake value (SUV) of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and conductivity parameters in breast cancer and explored the feasibility of conductivity as an imaging biomarker. Both SUV and conductivity have the potential to reflect the tumors' heterogeneous characteristics, but their correlations have not been investigated until now. Forty four women diagnosed with breast cancer who underwent breast MRI and 18 F-FDG PET/CT at the time of diagnosis were included. Among them, 17 women received neoadjuvant chemotherapy followed by surgery and 27 women underwent upfront surgery. For conductivity parameters, maximum and mean values of the tumor region-of-interests were examined. For SUV parameters, SUVmax, SUVmean, and SUVpeak of the tumor region-of-interests were examined. Correlations between conductivity and SUV were evaluated, and among them, the highest correlation was observed between mean conductivity and SUVpeak (Spearman's correlation coefficient = 0.381). In a subgroup analysis for 27 women with upfront surgery, tumors with lymphovascular invasion (LVI) showed higher mean conductivity than those without LVI (median: 0.49 S/m vs 0.06 S/m, p < 0.001). In conclusion, our study shows a low positive correlation between SUVpeak and mean conductivity in breast cancer. Furthermore, conductivity showed a potential to noninvasively predict LVI status., (© 2023. The Author(s).)