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Background: Asian Americans (AA) face cultural and linguistic barriers to health care access, resulting in poor health outcomes. This study investigates the experiences of AAs using language interpretation services (LIS) in health care settings., Methods: Using a mixed-methods approach, we conducted a community survey (N=401) and seven focus groups between April and September 2023. We use the Andersen model to understand the experience around LIS for AAs and calculated descriptive statistics for predisposing (i.e., sociodemographic factors and attitudes toward LIS), enabling (i.e., perceived barriers), and need factors (i.e., perceived need for LIS). Focus groups were analyzed using a modified template approach to text analysis., Results: Quantitative and qualitative analyses found that although AAs recognize the benefits and need for LIS, various barriers (e.g., lack of interpreters when booking an appointment) preclude these communities from accessing these services., Conclusions: Results from this study will help inform interventions that seek to improve LIS within health care systems.

Background: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to approximately 500 million cases and 6 million deaths worldwide. Previous investigations into the pathophysiology of SARS-CoV-2 primarily focused on peripheral blood mononuclear cells from patients, lacking detailed mechanistic insights into the virus's impact on inflamed tissue. Existing animal models, such as hamster and ferret, do not faithfully replicate the severe SARS-CoV-2 infection seen in patients, underscoring the need for more relevant animal system-based research., Methods: In this study, we employed single-cell RNA sequencing (scRNA-seq) with lung tissues from K18-hACE2 transgenic (TG) mice during SARS-CoV-2 infection. This approach allowed for a comprehensive examination of the molecular and cellular responses to the virus in lung tissue., Findings: Upon SARS-CoV-2 infection, K18-hACE2 TG mice exhibited severe lung pathologies, including acute pneumonia, alveolar collapse, and immune cell infiltration. Through scRNA-seq, we identified 36 different types of cells dynamically orchestrating SARS-CoV-2-induced pathologies. Notably, SPP1 + macrophages in the myeloid compartment emerged as key drivers of severe lung inflammation and fibrosis in K18-hACE2 TG mice. Dynamic receptor-ligand interactions, involving various cell types such as immunological and bronchial cells, defined an enhanced TGFβ signaling pathway linked to delayed tissue regeneration, severe lung injury, and fibrotic processes., Interpretation: Our study provides a comprehensive understanding of SARS-CoV-2 pathogenesis in lung tissue, surpassing previous limitations in investigating inflamed tissues. The identified SPP1+ macrophages and the dysregulated TGFβ signaling pathway offer potential targets for therapeutic intervention. Insights from this research may contribute to the development of innovative diagnostics and therapies for COVID-19., Funding: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020M3A9I2109027, 2021R1A2C2004501)., Competing Interests: Declaration of interests The authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate the association between the longitudinal changes in both macular vessel density (mVD) and macular ganglion cell-inner plexiform layer thickness (mGCIPLT) and visual field (VF) progression (including central VF progression) in open-angle glaucoma (OAG) patients with central visual field (CVF) damage at different glaucoma stages., Design: Retrospective longitudinal study., Participants: This study enrolled 223 OAG eyes with CVF loss at baseline classified as early-to-moderate (133 eyes) or advanced (90 eyes) stage based on the VF mean deviation (MD) (-10 dB)., Methods: Serial mVDs at parafoveal and perifoveal sectors and mGCIPLT measurements were obtained using OCT angiography and OCT during a mean follow-up of 3.5 years. Visual field progression was determined using both the event- and trend-based analyses during follow-up., Main Outcome Measures: Linear mixed-effects models were used to compare the rates of change in each parameter between VF progressors and nonprogressors. Logistic regression analyses were performed to determine the risk factors for VF progression., Results: In early-to-moderate stage, progressors showed significantly faster rates of change in the mGCIPLT (-1.02 vs. -0.47 μm/year), parafoveal (-1.12 vs. -0.40%/year), and perifoveal mVDs (-0.83 vs. -0.44%/year) than nonprogressors (all P < 0.05). In advanced stage cases, only the rates of change in mVDs (parafoveal: -1.47 vs. -0.44%/year; perifoveal: -1.04 vs. -0.27%/year; all P < 0.05) showed significant differences between the groups. By multivariable logistic regression analyses, the faster rate of mVD loss was a predictor of VF progression regardless of glaucoma stage, while the rate of mGCIPLT loss was significantly associated with VF progression only in early-to-moderate stage cases., Conclusions: Progressive mVD loss is significantly associated with VF progression (including central VF progression) in the OAG eyes with CVF loss regardless of the glaucoma stage., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The identification of genetic factors that regulate the cancer immune microenvironment is important for understanding the mechanism of tumor progression and establishing an effective treatment strategy. Polycystic kidney and hepatic disease 1-like protein 1 (PKHD1L1) is a large transmembrane protein that is highly expressed in immune cells; however, its association with tumor progression remains unclear. Here, we systematically analyzed the clinical relevance of PKHD1L1 in the tumor microenvironment in multiple cancer types using various bioinformatic tools. We found that the PKHD1L1 mRNA expression levels were significantly lower in skin cutaneous melanoma (SKCM) and lung adenocarcinoma (LUAD) than in normal tissues. The decreased expression of PKHD1L1 was significantly associated with unfavorable overall survival (OS) in SKCM and LUAD. Additionally, PKHD1L1 expression was positively correlated with the levels of infiltrating B cells, cluster of differentiation (CD)-8 + T cells, and natural killer (NK) cells, suggesting that the infiltration of immune cells could be associated with a good prognosis due to increased PKHD1L1 expression. Gene ontology (GO) analysis also revealed the relationship between PKHD1L1 -co-altered genes and the activation of lymphocytes, including B and T cells. Collectively, this study shows that PKHD1L1 expression is positively correlated with a good prognosis via the induction of immune infiltration, suggesting that PKHD1L1 has potential prognostic value in SKCM and LUAD.

We investigated the difference in optical coherence tomography angiography characteristics between the patients with compressive optic neuropathy (CON, n = 26) and glaucomatous optic neuropathy (GON, n = 26), who were matched for the severity of visual field defect. The peripapillary retinal nerve fiber layer (pRNFL) thickness in the nasal and temporal sectors was thinner in the CON group, whereas the inferior pRNFL thickness was thinner in the GON group. Accordingly, the CON group had lower peripapillary vessel density (pVD) in the nasal and temporal sectors, and the GON group in the inferior sector. In the macular area, the CON group had a thinner macular ganglion cell-inner plexiform layer in the superior and nasal sectors, whereas the GON group in the inferior sector. However, the CON group did not have a lower macular VD than the GON group in any sector, whereas the GON group exhibited lower superficial capillary plexus VD in the superior, inferior, and temporal sectors. Comparison of the structure-vasculature correlation revealed a significant difference in the nasal and temporal peripapillary areas and superior and nasal macular sectors; a decrease in VD was greater in the GON group than in the CON group when the comparable structural change occurred., (© 2023. The Author(s).)

Purpose: The Armed Forces Trauma Center of Korea was established in April 2022. This study was conducted to report our 1-year experience of treating soldiers with open fractures of the lower extremity., Methods: In this case series, we reviewed the medical records of 51 Korean soldiers with open fractures of the lower extremity between April 2022 and March 2023 at a trauma center. We analyzed patients with Gustilo-Anderson type II and III fractures and reported the duration of transportation, injury mechanisms, injured sites, and associated injuries. We also presented laboratory findings, surgery types, intensive care unit stays, hospital stays, rehabilitation results, and reasons for psychiatric consultation. Additionally, we described patients' mode of transport., Results: This study enrolled nine male patients who were between 21 and 26 years old. Six patients had type II and three had type III fractures. Transport from the accident scene to the emergency room ranged from 75 to 455 minutes, and from the emergency room to the operating room ranged from 35 to 200 minutes. Injury mechanisms included gunshot wounds, landmine explosions, grenade explosions, and entrapment by ship mooring ropes. One case had serious associated injuries (inhalation burn, open facial bone fractures, and hemopneumothorax). No cases with serious blood loss or coagulopathies were found, but most cases had a significant elevation of creatinine kinase. Two patients underwent vascular reconstruction, whereas four patients received flap surgery. After rehabilitation, six patients could walk, one patient could move their joints actively, and two patients performed active assistive movement. Eight patients were referred to the psychiatry department due to suicidal attempts and posttraumatic stress disorder., Conclusions: This study provides insights into how to improve treatment for patients with military trauma, as well as medical services such as the transport system, by revising treatment protocols and systematizing treatment., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (© 2023 The Korean Society of Traumatology.)

Background: Limited data are available regarding the association between psoriasis and common dental conditions., Objectives: To investigate the risk of potential dental comorbidities in patients with psoriasis., Methods: We conducted a nationwide population-based cohort study to analyse the claims data of patients with psoriasis (n = 15 165) and age- and sex-matched controls (n = 75 825). The incidence risk of the following potential dental conditions was analysed: dental caries, pulp and periapical disease, periodontal disease, gingival changes and tooth loss., Results: After adjusting for potential cofactors, the adjusted hazard ratios (aHRs) of dental caries [1.105; 95% confidence interval (CI) 1.078-1.132], pulp and periapical disease (1.07; 95% CI 1.044-1.096) and periodontal disease (1.108; 95% CI 1.088-1.129) were significantly higher than those in the control cohort (P < 0.001). However, among the subset of patients with psoriasis who received systemic antipsoriatic treatment (n = 4275), the aHR risk of all potential dental comorbidities was not significantly higher from that of the control cohort., Conclusions: Patients with psoriasis have an increased risk of dental comorbidities, and systemic antipsoriatic treatment may help mitigate this increased risk., Competing Interests: Conflicts of interest The authors have no conflict of interests to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Elevated intraocular pressure (IOP) in glaucoma causes retinal ganglion cell (RGC) loss and damage to the optic nerve. Although IOP is controlled pharmacologically, no treatment is available to restore retinal and optic nerve function. In this paper, we aimed to develop a novel gene therapy for glaucoma using an AAV2-based thioredoxin 2 (Trx2)-exoenzyme C3 transferase (C3) fusion protein expression vector (scAAV2-Trx2-C3). We evaluated the therapeutic effects of this vector in vitro and in vivo using dexamethasone (DEX)-induced glaucoma models. We found that scAAV2-Trx2-C3-treated HeLa cells had significantly reduced GTP-bound active RhoA and increased phosphor-cofilin Ser3 protein expression levels. scAAV2-Trx2-C3 was also shown to inhibit oxidative stress, fibronectin expression, and alpha-SMA expression in DEX-treated HeLa cells. NeuN immunostaining and TUNEL assay in mouse retinal tissues was performed to evaluate its neuroprotective effect upon RGCs, whereas changes in mouse IOP were monitored via rebound tonometer. The present study showed that scAAV2-Trx2-C3 can protect RGCs from degeneration and reduce IOP in a DEX-induced mouse model of glaucoma, while immunohistochemistry revealed that the expression of fibronectin and alpha-SMA was decreased after the transduction of scAAV2-Trx2-C3 in murine eye tissues. Our results suggest that AAV2-Trx2-C3 modulates the outflow resistance of the trabecular meshwork, protects retinal and other ocular tissues from oxidative damage, and may lead to the development of a gene therapeutic for glaucoma.

Age-related microglial activation is associated with cognitive impairment. Tonicity-responsive enhancer-binding protein (TonEBP) is a critical mediator of microglial activation in response to neuroinflammation. However, the precise role of TonEBP in the middle-aged brain is not yet known. We used TonEBP haploinsufficient mice to investigate the role of TonEBP in middle-aged or amyloid β oligomer (AβO)-injected brains and examined the effect of TonEBP knockdown on AβO-treated BV2 microglial cells. Consistent with an increase in microglial activation with aging, hippocampal TonEBP expression levels were increased in middle-aged (12-month-old) and old (24-month-old) mice compared with young (6-month-old) mice. Middle-aged TonEBP haploinsufficient mice showed reduced microglial activation and fewer memory deficits than wild-type mice. Electron microscopy revealed that synaptic pruning by microglial processes was reduced by TonEBP haploinsufficiency. TonEBP haploinsufficiency also reduced dendritic spine loss and improved memory deficits in AβO-treated mice. Furthermore, TonEBP knockdown attenuated migration and phagocytosis in AβO-treated BV2 cells. These findings suggest that TonEBP plays important roles in age-related microglial activation and memory deficits.

Many patients demand minimally invasive treatments for skin rejuvenation, such as nonablative laser and superficial chemical peels. Combination therapy yet has not been studied histopathologically. The purpose of this study is to assess the histopathological efficacy of a 1927-nm thulium laser-assisted salicylic acid (SA) peel in skin rejuvenation. A six-segment table was drawn on the shaved back of C57BL/6 mouse. All segments were irradiated with the thulium laser-different tips and passes were used for specific segments. A 30% SA peel was then applied to the right-hand segments. After treatment, the skin samples were collected from each segment and examined for dermal thickness, collagen density, and melanin content. Greater thickness was seen in the combination therapy group compared with the laser alone group and in those segments receiving more passes with larger beam-sized tip. Collagen density increased in all treated skin segments, irrespective of the group. No adverse events were noted in the treated areas. The sample size was small and mouse skin has histological differences with human skin. The combination of a thulium laser and 30% SA peel has a synergistic effect on dermal thickness, so that can be suggested as a novel skin rejuvenation technique., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background and Purpose: All young males in South Korea must undergo a physical examination for their participation in military service. We aimed to determine the prevalence rate (PR) of various neuromuscular diseases in young South Korean males using the data of exempted patients and soldiers., Methods: The number of males exempted based on specific items of physical examination corresponding to neuromuscular disease during 2011-2020 were obtained from the records of the Military Manpower Administration. The list of enlisted soldier patients who were discharged from military service due to neuromuscular diseases during 2011-2020 was obtained from the Armed Forces Medical Command, and their medical records were reviewed., Results: The PR of neuromuscular diseases was calculated among 948 identified males: 713 exempted males and 235 soldiers. The PRs of overall hereditary neuropathies, Hirayama disease (HD), myasthenia gravis (MG), and inherited muscle diseases in South Korean males in their early 20s were 8.34 (95% confidence interval [CI], 7.39-9.30), 5.54 (95% CI, 4.76-6.32), 2.97 (95% CI, 2.40-3.55), and 10.38 (95% CI, 9.31-11.46) per 100,000 persons, respectively. Among the enlisted soldiers, hereditary neuropathy with liability to pressure palsy was the most common neuromuscular disease, with a prevalence among the enlisted soldiers of 3.11 (95% CI, 2.42-3.80) per 100,000 persons. Myotonic dystrophy was the most prevalent myopathy, followed by facioscapulohumeral muscular dystrophy., Conclusions: The 10-year PRs of hereditary polyneuropathies, HD, MG, and inherited muscle diseases in young South Korean males have been reported. These data could be valuable to understanding each neuromuscular disease in the young male population of South Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 Korean Neurological Association.)

An intermittent fasting (IF) regimen has been shown to protect against metabolic dysfunction-associated steatohepatitis (MASH). However, the precise mechanism remains unclear. Here, we explored how IF reduced hepatic lipid accumulation, inflammation, and fibrosis in mice with MASH. The mice were fed a high-fat diet (HFD) for 30 weeks and either continued on the HFD or were subjected to IF for the final 22 weeks. IF reduced body weight, insulin resistance, and hepatic lipid accumulation in HFD-fed mice. Lipidome analysis revealed that IF modified HFD-induced hepatic lipid composition. In particular, HFD-induced impaired autophagic flux was reversed by IF. The decreased hepatic lysosome-associated membrane protein 1 level in HFD-fed mice was upregulated in HFD+IF-fed mice. However, increased hepatic lysosomal acid lipase protein levels in HFD-fed mice were reduced by IF. IF attenuated HFD-induced hepatic inflammation and galectin-3-positive Kupffer cells. In addition to the increases in hepatic hydroxyproline and lumican levels, lipocalin-2-mediated signaling was reversed in HFD-fed mice by IF. Taken together, our findings indicate that the enhancement of the autophagy-lysosomal pathway may be a critical mechanism of MASH reduction by IF.

We investigated the relationship between foveal avascular zone (FAZ)-related parameters, assessed by optical coherence tomography angiography (OCT-A), and visual field (VF) progression in early-stage open-angle glaucoma (OAG) eyes with central visual field (CVF) defects. Early-stage glaucoma eyes [VF mean deviation (MD) ≥ - 6 dB] with CVF defects were included. The rates of longitudinal change in FAZ-related parameters and structural parameters were evaluated and compared between VF progressors and non-progressors, using linear mixed effects models. Cox proportional hazards model and linear regression models were used to identify factors associated with VF progression, the VF MD reduction rate and the change rate of mean total deviation in central 12 VF points (MTD 10 ). A total of 131 eyes were included and VF progression was detected in 32 eyes (24.4%) during 3.45 years of follow-up. The rates of reduction in vessel density in the 300 µm width annular region surrounding the FAZ (FD300) and macular ganglion cell-inner plexiform layer thickness (mGCIPLT) were significantly faster in progressors than in non-progressors. The faster VF MD or MTD 10 reduction rates were associated with faster rates of FD300 loss and mGCIPLT reduction. The FD300 reduction rate is significantly associated with VF progression in early-stage OAG eyes with CVF defects. FD300 may be an adjunctive biomarker of VF progression in glaucomatous eyes with CVF defects., (© 2023. Springer Nature Limited.)

Purpose: To investigate the impact of a morning blood pressure surge (MBPS) at baseline on subsequent visual field (VF) progression in hypertensive, normal-tension glaucoma (NTG) patients receiving oral anti-hypertensive treatment., Design: Retrospective cohort study., Methods: A total of 127 eyes from 127 newly diagnosed NTG patients treated for systemic hypertension and followed up for at least 2 years were analyzed. All patients underwent baseline 24-hour ambulatory blood pressure monitoring (ABPM) and at least 5 serial VF examinations during the follow-up period. VF progression was defined according to the Early Manifest Glaucoma Trial criteria. The associations of VF progression with 24-hour ABPM-based blood pressure (BP) parameters (including MBPS) and other clinical variables were analyzed using Cox regression analyses. Kaplan-Meier survival analysis was used to compare VF survival estimates in patients with and without MBPS., Results: VF progression was detected in 38 eyes (29.9%) over a 5.2-year mean follow-up. In the multivariate Cox regression model, a greater MBPS (hazard ratio [HR] = 1.033; P = .024) and lower nighttime mean arterial pressure (MAP) trough (HR = 0.965; P = .031) at baseline were significant independent predictors of subsequent VF progression. The likelihood of VF progression was significantly greater in patients with higher MBPS (P = .021) at baseline according to Kaplan-Meier survival analysis., Conclusions: An increased MBPS at baseline is a significant independent predictor of subsequent VF progression in NTG patients with systemic hypertension. This may be another relevant BP parameter associated with VF progression in hypertensive NTG patients receiving oral anti-hypertensive treatment., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Prcis: Reduced optic disc vessel density determined by swept-source optical coherence tomography angiography (SS-OCTA) was associated with visual field (VF) deterioration in glaucomatous eyes, which suggested that this parameter can be a potential biomarker that correlates well with functional deterioration., Purpose: The purpose of this study was to identify the association between optic disc perfusion evaluated by SS-OCTA and VF progression in primary open angle glaucoma (POAG) eyes., Methods: A total of 266 POAG eyes of 266 patients (5.4 y of mean follow-up) were included. Optic nerve head SS-OCTA was performed to evaluate the optic disc vessel density (dVD), parapapillary choroidal vessel density (pcVD), choroidal microvascular dropout (cMvD), and optic disc microvascular dropout (dMvD). VF progression was defined using Early Manifest Glaucoma Trial criteria. Factors associated with VF worsening were assessed by Cox proportional hazard analysis., Results: Eighty (30.1%) out of the 266 POAG eyes showed VF progression. The progression group showed a significantly higher proportion of disc hemorrhage, cMvD, and dMvD but lower dVD and pcVD than the stable group (all P <0.05). Considering the strong association between the parameters [dMvD vs. dVD ( r = -0.757, P =0.010], cMvD vs. pcVD ( r = -0.745, P =0.012), dMvD vs. cMvD ( r = 0.802, P <0.001], dVD vs. pcVD ( r = 0.862, P <0.001), CMvD vs. dVD ( r = -0.698, P =0.031), and dMvD vs. pcVD ( r = -0.688, P =0.034)], 6 models with different combinations of covariates compensating for multicollinearity were developed. Younger age, presence of disc hemorrhage, and lower dVD were consistently associated with progression in all models that included these parameters., Conclusions: Optic disc perfusion, represented as dVD, may be a useful biomarker that correlates well with functional deterioration in POAG eyes., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The periorbital area plays an important role cosmetically. Periorbital wrinkles are attributed to long-term, repeated use of orbicularis oris muscles and UV-induced dermal collagen degeneration. Fractional microneedle radiofrequency (RF) treats scars and laxity by creating vertical channels of injury in the dermis, triggering a scarless healing cascade and neocollagenesis., Objective: To evaluate the effect and safety of a novel fractional microneedle RF device on periorbital wrinkles based on several objective indicators., Methods: Eleven healthy Korean patients aged 30 to 75 years with periorbital wrinkles were included in this study. Wrinkle grades were evaluated using the Fitzpatrick wrinkle assessment scale (WAS). The melanin and erythema index, transepidermal water loss (TEWL), and three parameters for elasticity were recorded. Skin biopsies were obtained in patients who consented., Results: All patients exhibited wrinkle improvement in the lateral periorbital area, and two patients also showed efficacy in the lower eyelid area. There was a statistically significant decrease in WAS and a significant improvement in the melanin index of V4 and V5. TEWL also showed a considerable decline on V4 and V5, suggesting that the water content of the skin increased with repeated laser sessions. A peak increase in viscoelasticity and a decrease in retraction time following the first laser application were observed. In the histopathologic examination, the dermis had a denser collagen and elastin content., Conclusion: Microneedle fractional RF resulted in statistically significant long-term clinical improvement of periorbital wrinkles and enhanced pigmentation and skin hydration., Competing Interests: The authors have nothing to disclose., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Background: In cases with advanced glaucomatous disc changes, further changes associated with other optic neuropathies cannot be easily identified. We present a case of preexisting open-angle glaucoma and concurrent involvement of sarcoidosis-associated optic neuropathy., Case Presentation: A 53-year-old man presented with gradual visual loss in his left eye, which began 1 year ago and accelerated 3 months ago. The best-corrected visual acuity in the right eye was 20/20 and counting fingers in the left. Intraocular pressures (IOP) were 12 mmHg in the right eye and 34 mmHg in the left. We diagnosed him with advanced open-angle glaucoma in the left eye based on the advanced glaucomatous cupping of the left optic disc. The IOP in the left eye dropped to 10 mmHg and was well controlled with antiglaucomatous medication; however, his left optic disc developed pallor 3 months after the treatment. The patient was revealed to be diagnosed with sarcoidosis a month ago and had been treated with systemic corticosteroids thereafter by a pulmonologist. Orbital magnetic resonance imaging revealed sarcoidosis-associated optic neuropathy in the left eye. Subsequently, optic neuropathy occurred in his right eye., Conclusions: In eyes with advanced glaucomatous disc change, detecting the coexistence of other optic neuropathies can be difficult. This report highlights the importance of careful ophthalmic examinations and investigation for etiologies of other optic neuropathies if non-glaucomatous changes are suspected even in eyes with advanced glaucoma., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Understanding marine bacterioplankton composition and distribution is necessary for improving predictions of ecosystem responses to environmental change. Here, we used 16S rRNA metabarcoding to investigate marine bacterioplankton diversity and identify potential pathogenic bacteria in seawater samples collected in March, May, September, and December 2013 from two sites near Jeju Island, South Korea. We identified 1343 operational taxonomic units (OTUs) and observed that community diversity varied between months. Alpha- and Gamma-proteobacteria were the most abundant classes, and in all months, the predominant genera were Candidatus Pelagibacter , Leisingera , and Citromicrobium . The highest number of OTUs was observed in September, and Vibrio (7.80%), Pseudoalteromonas (6.53%), and Citromicrobium (6.16%) showed higher relative abundances or were detected only in this month. Water temperature and salinity significantly affected bacterial distribution, and these conditions, characteristic of September, were adverse for Aestuariibacter but favored Citromicrobium . Potentially pathogenic bacteria, among which Vibrio (28 OTUs) and Pseudoalteromonas (six OTUs) were the most abundant in September, were detected in 49 OTUs, and their abundances were significantly correlated with water temperature, increasing rapidly in September, the warmest month. These findings suggest that monthly temperature and salinity variations affect marine bacterioplankton diversity and potential pathogen abundance.

The expression profiles of conventional reference genes (RGs), including ACTB and GAPDH, used in quantitative real-time PCR (qPCR), vary depending on tissue types and environmental conditions. We searched for suitable RGs for qPCR to determine the response to radiotherapy in colorectal cancer (CRC) cell lines, organoids, and patient-derived tissues. Ten CRC cell lines (Caco-2, COLO 205, DLD-1, HCT116, HCT-15, HT-29, RKO, SW1116, SW480, and SW620) and organoids were selected and irradiated with 2, 10 or 21 grays (Gy) based on the previous related studies conducted over the last decade. The expression stability of 14 housekeeping genes (HKGs; ACTB, B2M, G6PD, GAPDH, GUSB, HMBS, HPRT1, IPO8, PGK1, PPIA, TBP, TFRC, UBC, and YWHAZ) after irradiation was evaluated using RefFinder using raw quantification cycle (Cq) values obtained from samples before and after irradiation. The expression stability of HKGs were also evaluated for paired fresh frozen tissues or formalin-fixed, paraffin-embedded samples obtained from CRC patients before and after chemoradiotherapy. The expression of YWHAZ and TBP encoding 14-3-3-zeta protein and TATA-binding protein were more stable than the other 12 HKGs in CRC cell lines, organoids, and patient-derived tissues after irradiation. The findings suggest that YWHAZ and TBP are potential RG candidates for normalizing qPCR results in CRC radiotherapy experiments., (© 2023. Springer Nature Limited.)

This study employed 16S rRNA metabarcoding to establish the diversity of prokaryotic communities and specific characteristics of potentially pathogenic prokaryotic primary colonizers of four plastic materials (EPS, expanded polystyrene; PE, polyethylene; PP, polypropylene; and PET, polyethylene terephthalate). Bacteria inhabiting plastic and seawater differ; thus, distinct changes in the attached prokaryotic community were observed over an exposure time of 21 days, specifically on Days 3, 6, 9, and 12-21. Frist colonizers were Gammaproteobacteria and Alphaproteobacteria; Bacilli and Clostridia represented secondary colonizers. On Day 3, Pseudoalteromonas had a relative abundance >80 %; whereas, the prevalence of Vibrio spp. (potentially pathogenic prokaryotes) increased rapidly on Days 6 and 9. However, after Day 12, the prevalence of other potential pathogens, namely, Clostridium spp., steadily increased. Despite the diversity of the plastic surfaces, attached prokaryotes changed over time instead of showing similar adherent diversity in all plastic materials., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Prcis: Reduction in the angular circumference of choroidal microvascular dropout (CMvD AC) was found in POAG patients after trabeculectomy. Greater percentage of IOP reduction was significantly associated with decreased CMvD AC., Purpose: The purpose of this study was to investigate the change of choroidal microvasculature dropout (CMvD) after trabeculectomy and its associated factors in primary open angle glaucoma (POAG) eyes using optical coherence tomography angiography., Methods: Fifty eyes of 50 POAG participants who had preoperative CMvD and underwent trabeculectomy were prospectively enrolled. Angular circumference (AC) of CMvD was determined from choroidal layer images by optical coherence tomography angiography preoperatively and at postoperative 1 year. The cutoff for significant AC of CMvD decrease was determined by the Bland-Altman method, and accordingly, patients were divided into 2, decreased and stable/increased CMvD AC groups. Changes in intraocular pressure (IOP) and CMvD AC were compared between the groups preoperatively and at postoperative 1 year. Factors associated with CMvD AC decrease were assessed by linear regression analysis., Results: The cutoff for significant CMvD AC decrease was 3.58 degrees; accordingly, 26 eyes (52.0%) were categorized as decreased CMvD AC group. No significant intergroup differences in baseline characteristics were found. However, the decreased CMvD AC group presented significantly lower IOP (10.7±3.7 vs. 12.9±2.6 mm Hg, P =0.022), lower CMvD AC (32.03±33.95% vs. 53.44±39.33%, P =0.044), and higher parapapillary choroidal vessel density ( P =0.014) compared with the increased/stable CMvD AC group at postoperative 1 year. The greater percentage of IOP reduction was significantly associated with decreased CMvD AC ( P =0.046)., Conclusions: CMvD AC reduction associated with IOP lowering was found after trabeculectomy. The long-term clinical relevance of postoperative CMvD reduction should be further investigated., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Type 2 diabetes is associated with a risk factor for Alzheimer's disease (AD). Activation of glial cells, such as microglia and astrocytes, is crucial for the development of neuroinflammation in both diabetes and AD. The role of amyloid-beta oligomer (AβO) in the hippocampus of diabetic mice has been investigated; however, the effect of galectin-3 and lipocalin-2 (LCN2) on amyloid toxicity-related glial activation in diabetic mice is not known. To fill this knowledge gap, we fed mice a high-fat diet (HFD) for 20 weeks to induce a diabetic state and then injected the hippocampus with AβO. Sholl analysis of iba-1-positive microglia showed retraction of microglial ramifications in the hippocampus of HFD-fed diabetic mice. AβO treatment caused more retraction of microglial process in HFD-fed mice. In particular, microglial galectin-3 levels and astrocytic LCN2 levels were increased in the hippocampus of HFD-fed mice with AβO treatment. These findings suggest that galectin-3 and LCN2 are involved in amyloid toxicity mechanisms, especially glial activation under diabetic conditions., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A hyperspectral scanning system was developed for three-dimensional (3D) surface mapping in underground spaces, such as mine shafts and tunnels. A hyperspectral line-scanning camera was mounted on the rotating driver unit coaxial with the tunnel to image both the mine wall and the ceiling. Uniform light was illuminated on the target surface to be imaged using a halogen lamp rotating together with the hyperspectral imaging sensor. Inertial Measuring Unit (IMU) was also attached to the sensor unit together with the hyperspectral camera so that sensor's geometric information could be acquired simultaneously during imaging. All sensor and controller units were mounted on a cart-type platform for easy movement in the tunnel, and a battery mounted on the platform supplied power for system operation and the halogen light source. The developed scanning system was tested in an actual mine, and 3D hyperspectral images of the internal surface of the mine shaft were successfully obtained., (© 2023. The Author(s).)

Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Mitochondrial uncoupling protein 1 (UCP1) is activated in BAT during cold stress and dissipates mitochondrial proton motive force generated by the electron transport chain to generate heat. However, other mitochondrial factors required for brown adipocyte respiration and thermogenesis under cold stress are largely unknown. Here, we show LETM1 domain-containing protein 1 (LETMD1) is a BAT-enriched and cold-induced protein required for cold-stimulated respiration and thermogenesis of BAT. Proximity labeling studies reveal that LETMD1 is a mitochondrial matrix protein. Letmd1 knockout male mice display aberrant BAT mitochondria and fail to carry out adaptive thermogenesis under cold stress. Letmd1 knockout BAT is deficient in oxidative phosphorylation (OXPHOS) complex proteins and has impaired mitochondrial respiration. In addition, BAT-specific Letmd1 deficient mice exhibit phenotypes identical to those observed in Letmd1 knockout mice. Collectively, we demonstrate that the BAT-enriched mitochondrial matrix protein LETMD1 plays a tissue-autonomous role that is essential for BAT mitochondrial function and thermogenesis., (© 2023. The Author(s).)

Purpose: This study aimed to compare the postoperative outcomes and patient-surveyed scar assessments of single-port laparoscopic appendectomy (SPLA) with the outcomes of multiport laparoscopic appendectomy (MPLA)., Methods: Between August 2014 and November 2017, the prospective randomized study comprised 98 patients diagnosed with acute appendicitis and indicated for surgery. Fifty-one patients had MPLA and 47 patients received SPLA. The primary endpoint was the total score of Patient Scar Assessment Questionnaire (PSAQ) administered to patients 6 weeks after surgery., Results: SPLA involved a shorter median operative time than MPLA (47.5 minutes vs. 60.0 minutes, p = 0.02). There were no apparent differences in the time before diet tolerance, length of hospital stay, and postoperative complication. SPLA patients had shorter total incision length (2.0 cm vs. 2.5 cm, p < 0.01) and required fewer analgesics on the day of surgery than MPLA patients ( p = 0.011). The PSAQ favored the SPLA approach, revealing significant differences in total score (48 vs. 55, p = 0.026), appearance (15 vs. 18, p = 0.002), and consciousness (8 vs. 10, p = 0.005), while satisfaction with appearance and symptoms scale did not ( p = 0.162 and p = 0.690, respectively)., Conclusion: The postoperative scar evaluated by the patient was better with SPLA than with MPLA, and patient satisfaction with the scar was comparable between the two techniques., Competing Interests: Conflict of interest All authors have no conflicts of interest to declare., (© 2023 The Korean Society of Endo-Laparoscopic & Robotic Surgery.)

Background: Although patient navigation has shown promise for increasing participation in colorectal cancer screening and follow-up, little evidence is available to guide implementation of patient navigation in clinical practice. We characterize 8 patient navigation programs being implemented as part of multi-component interventions of the National Cancer Institute's Cancer Moonshot Accelerating Colorectal Cancer Screening and Follow-Up Through Implementation Science (ACCSIS) initiative., Methods: We developed a data collection template organized by ACCSIS framework domains. The template was populated by a representative from each of the 8 ACCSIS research projects. We report standardized descriptions of 1) the socio-ecological context in which the navigation program was being conducted, 2) navigation program characteristics, 3) activities undertaken to facilitate program implementation (eg, training), and 4) outcomes used in program evaluation., Results: ACCSIS patient navigation programs varied broadly in their socio-ecological context and settings, the populations they served, and how they were implemented in practice. Six research projects adapted and implemented evidence-based patient navigation programs; the remaining projects developed new programs. Five projects began navigation when patients were due for initial colorectal cancer screening; 3 projects began navigation later in the screening process, when patients were due for follow-up colonoscopy after an abnormal stool-test result. Seven projects relied on existing clinical staff to deliver the navigation; 1 hired a centralized research navigator. All project researchers plan to evaluate the effectiveness and implementation of their programs., Conclusions: Our detailed program descriptions may facilitate cross-project comparisons and guide future implementation and evaluation of patient navigation programs in clinical practice., (© The Author(s) 2023. Published by Oxford University Press.)

Objectives: This study investigated Korean dental hygiene students' perceptions and attitudes toward artificial intelligence (AI) and aimed to identify needs for education to strengthen professional competencies., Methods: A 24-question online survey was conducted to the dental hygiene students from four Korean schools in 2021. The questionnaire included seven questions on basic characteristics and 17 AI-related questions on the student's attitudes toward AI, the confidence in AI, predictions about AI, and its future prospects. Responses were analyzed according to the frequencies and correlations between the participants' subjective level of knowledge about AI and questions using chi-square test., Results: Invitations were sent out to 1310 students and 800 (61.1%) participated. Note that 44.2% of participants were interested in AI, and 93.1% accessed AI-related information through the internet. Participants expressed lower confidence in AI's diagnosis (14.8%) and judgment (8.1%) than in those of humans, and 21.9% believed AI would replace their job. The proportions of participants with positive perceptions of the usefulness and the potential for improvement of AI in dentistry were 65.5% and 55.4%, respectively. Participants from schools who had existing AI knowledge expressed higher demands for AI-related content as compared to those who did not (p < 0.05)., Conclusion: Although dental hygiene students expressed low level of confidence in AI, they were interested in AI and had positive views of its application and potential for improvement. However, the fact they had little AI-related information from dental hygiene curriculum strongly suggests the need for AI-related lectures in schools to prepare for the future., (© 2023 American Dental Education Association.)

Despite their abundance and ecological importance, little is known about the diversity of marine viruses, in part because most cannot be cultured in the laboratory. Here, we used high-throughput viral metagenomics of uncultivated viruses to investigate the dynamics of DNA viruses in tropical seawater sampled from Chuuk State, Federated States of Micronesia, in March, June, and December 2014. Among the identified viruses, 71-79% were bacteriophages belonging to the families Myoviridae , Siphoviridae , and Podoviridae ( Caudoviriales ), listed in order of abundance at all sampling times. Although the measured environmental factors (temperature, salinity, and pH) remained unchanged in the seawater over time, viral dynamics changed. The proportion of cyanophages (34.7%) was highest in June, whereas the proportion of mimiviruses, phycodnaviruses, and other nucleo-cytoplasmic large DNA viruses (NCLDVs) was higher in March and December. Although host species were not analysed, the dramatic viral community change observed in June was likely due to changes in the abundance of cyanophage-infected cyanobacteria, whereas that in NCLDVs was likely due to the abundance of potential eukaryote-infected hosts. These results serve as a basis for comparative analyses of other marine viral communities, and guide policy-making when considering marine life care in Chuuk State.

Historically, colorectal cancer (CRC) screening rates have been lower among African Americans. Previous studies that have examined the relationship between community characteristics and adherence to CRC screening have generally focused on a single community parameter, making it challenging to evaluate the overall impact of the social and built environment. In this study, we will estimate the overall effect of social and built environment and identify the most important community factors relevant to CRC screening. Data are from the Multiethnic Prevention and Surveillance Study (COMPASS), a longitudinal study among adults in Chicago, collected between May 2013 to March 2020. A total 2,836 African Americans completed the survey. Participants' addresses were geocoded and linked to seven community characteristics (i.e., community safety, community crime, household poverty, community unemployment, housing cost burden, housing vacancies, low food access). A structured questionnaire measured adherence to CRC screening. Weighted quantile sum (WQS) regression was used to evaluate the impact of community disadvantages on CRC screening. When analyzing all community characteristics as a mixture, overall community disadvantage was associated with less adherence to CRC screening even after controlling for individual-level factors. In the adjusted WQS model, unemployment was the most important community characteristic (37.6%), followed by community insecurity (26.1%) and severe housing cost burden (16.3%). Results from this study indicate that successful efforts to improve adherence to CRC screening rates should prioritize individuals living in communities with high rates of insecurity and low socioeconomic status., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Identifying the clinical relevance of superficial versus deep layer macular vessel density (mVD) in glaucoma is important for monitoring glaucoma patients. Our current retrospective longitudinal study investigated the association of superficial and deep layer mVD parameters with glaucomatous visual field (VF) progression in mild to moderate open-angle glaucoma (OAG) eyes with central visual field (CVF) damage. Serial optical coherence tomography (OCT) angiography-derived mVD measurements were obtained in 182 mild to moderate OAG eyes (mean deviation ≥ -10 decibels). Forty-eight eyes (26.4%) showed VF progression during a mean follow-up of 3.5 years. The parafoveal and perifoveal mVDs of both superficial and deep layers showed significantly faster reduction rates in the VF progressors than in the non-progressors according to linear mixed effects models (P < 0.05). Cox and linear regression analyses showed that greater reduction rates of both the superficial layer parafoveal and perifoveal mVDs, but not their deep layer counterparts, were significant predictors of VF progression and faster VF loss (P < 0.05). In conclusion, faster rates of change in superficial but not deep layer mVD parameters are significantly associated with subsequent VF progression and faster VF deterioration in mild to moderate OAG eyes with CVF damage., (© 2023. The Author(s).)

Importance: Practice patterns of hydroxychloroquine retinopathy screening have not yet been reported at a national level in South Korea., Objective: To investigate the practice patterns of timing and modality for hydroxychloroquine retinopathy screening in South Korea., Design, Setting, and Participants: This nationwide population-based cohort study of patients in South Korea used data from the national Health Insurance Review and Assessment database. Patients at risk were identified as those who had initiated hydroxychloroquine therapy between January 1, 2009, and December 31, 2020, and used it for 6 months or more. Patients were excluded if they underwent any of the 4 screening modalities recommended by the American Academy of Ophthalmology (AAO) for other ophthalmic diseases prior to hydroxychloroquine use. The timing and modalities of screening used in baseline and monitoring examinations were assessed between January 1, 2015, and December 31, 2021, among patients at risk and long-term (≥5 years) users., Exposure: Adherence of baseline screening practices to the 2016 AAO recommendations (fundus examination within 1 year of drug use) was evaluated; adherence of monitoring examinations in year 5 was classified as appropriate (≥2 tests recommended by the AAO), unscreened (no test performed), and underscreened (insufficient number of tests)., Main Outcomes and Measures: Timing of screening and modalities used at baseline and monitoring examinations., Results: A total of 65 406 patients at risk (mean [SD] age, 53.0 [15.5] years; 50 622 women [77.4%]) were included; 29 776 patients were long-term users (mean [SD] age, 50.1 [14.7] years; 24 898 women [83.6%]). Baseline screening was performed for 20.8% of the patients within 1 year, with a gradual increase from 16.6% in 2015 to 25.6% in 2021. Monitoring examinations, mostly using optical coherence tomography and/or visual field tests, were performed for only 13.5% of the long-term users in year 5 and for 31.6% of the long-term users after 5 years. Appropriate monitoring was performed for less than 10% of long-term users each year from 2015 to 2021; however, the percentage gradually increased over time. The percentage of patients undergoing any monitoring examination in year 5 was 2.3 times greater for those who had received baseline screening than for those who did not (27.4% vs 11.9%; P < .001)., Conclusions and Relevance: This study suggests there is an improving trend in retinopathy screening among hydroxychloroquine users in South Korea; however, most long-term users remained unscreened after 5 years of use. Baseline screening may be useful in reducing the number of unscreened long-term users.

Objective: Various and accurate psychiatric assessments in patients with breast cancer who frequently suffer from psychological problems due to long-term survivors are warranted. This systematic review aimed to investigate the current evidence on psychometric properties of psychiatric assessment for evaluating psychological problems in breast cancer patients., Methods: This systematic review progressed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Four electronic databases such as Web of Science, PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature were searched. This study protocol was registered on Open Science Framework., Results: Of the 2,040 articles, 21 papers were finally included. Among them, only five studies showed the performance of psychiatric assessment tools. Among 13 assessment tools used in the selected articles, the Hospital Anxiety and Depression Scale (HADS), Distress Thermometer (DT), or Mini-Mental Adjustment to Cancer Scale was frequently used for the evaluation of psychological problems. The DT and Psychosocial Distress Questionnaire-Breast Cancer showed acceptable performances for the prediction of depression and anxiety assessed by the HADS., Conclusion: This systematic review found psychiatric assessment tools with acceptable reliability and validity for breast cancer patients. However, comparative studies on reliability and validity of various scales are required to provide useful information for the selection of appropriate assessment tools based on the clinical settings and treatment stages of breast cancer. Joint research among the fields of psychiatry and breast surgery is needed for research to establish the convergent, concurrent, and predictive validity of psychiatric assessment tools in breast cancer patients.

Purpose: To investigate the association between the quantitative assessment of iridotrabecular contact (ITC), measured by swept-source anterior segment optical coherence tomography (SS AS-OCT), and intraocular pressure (IOP) control after phacoemulsification in patients with primary angle closure disease (PACD)., Design: Retrospective, clinical cohort study., Methods: Preoperative and postoperative anterior chamber angle parameters were measured using SS AS-OCT. IOP was measured preoperatively and until 6 months postoperatively. Percent IOP reduction and fluctuation after surgery were calculated, and their relationships with SS AS-OCT parameters were assessed by correlation analyses and locally weighted scatterplot smoothing (LOWESS) regression with change-point analysis., Results: A total of 51 eyes of 51 PACD patients were included. Preoperative ITC index and area (r = 0.626, r = 0.551), as well as changes in ITC index and area (r = 0.632, r = 0.543) after surgery, were significantly correlated with postoperative IOP reduction, after adjusting for age and gender (all P <.001). Higher postoperative ITC index (r = 0.405, P = .005) and ITC area (r = 0.460, P = 0.001) were associated with greater postoperative IOP fluctuations. Change points on LOWESS curves were observed for preoperative ITC index (33.0%) and change in ITC index (27.0%) and percent IOP reductions were significantly correlated with them above (β = 0.386, β = 0.664, all P < .001) but not below the change points., Conclusions: Quantitative assessment of circumferential ITC can predict postoperative IOP control after phacoemulsification, and thus it may be used as a reference for determining lens extraction in PACD eyes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Lipocalin-2 (LCN2) is an acute phase protein used as a biomarker for acute lung injury (ALI). Although the innate immune functions of LCN2 have been studied, how LCN2 contributes to ALI induced by lipopolysaccharide (LPS) remains unknown. In this study, we investigated the effect of LCN2 deletion on LPS-induced ALI using RNA-sequencing. LPS-treated LCN2 knockout (KO) mice had a decreased histopathological score and reduced neutrophil and macrophage infiltration in lung tissue compared with LPS-treated WT mice. RNA-sequencing analysis identified 38 differentially expressed genes (DEGs), including Cxcl5, Cxcl13, Xcl1, Saa1, and Cd14. In particular, Gene Ontology analysis of DEGs revealed a significant reduction in the inflammatory response, neutrophil chemotaxis, and chemokine-mediated signaling in LPS-treated LCN2KO mice compared with LPS-treated WT mice. Thus, these results suggest that LCN2 deletion alleviates LPS-induced ALI and that LCN2 may be involved in chemotaxis-related gene expression., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Previous studies suggested that chronic periodontitis may be a risk factor for psoriasis. However, no study has confirmed this relationship for all stages of periodontal disease (gingivitis and periodontitis). This nationwide population-based retrospective cohort study aimed to investigate whether periodontal disease is an independent risk factor for the development of subsequent psoriasis. Patients aged ≥ 20 years who underwent both medical and oral checkups from the National Health Screening Program between 2002 and 2007 were selected from a customized database provided by the National Health Insurance Service (NHIS). Then, patients with periodontal disease (n = 3,682,468) and without periodontal disease (control, n = 3,637,128) according to oral examination results were identified. We tracked each patient for subsequent psoriasis diagnosis until the end of 2018 using NHIS database. The incidence rates of psoriasis per 1000 person-years were 0.36 and 0.34 in the periodontal disease group and control groups, respectively. After adjusting for potential cofactors, no significant increase in risk (adjusted hazard ratio, 0.994; 95% confidence interval, 0.974-1.015) was observed. Similar results were observed when analyzing the risk of psoriasis in patients who required scaling or periodontal surgery. In conclusion, periodontal disease is not an independent risk factor of psoriasis., (© 2023. The Author(s).)

This multicenter (four institutions), randomized, investigator-masked, parallel-group clinical trial evaluated and compared the efficacy and safety of preservative-free and preserved brimonidine tartrate 0.15% in open-angle glaucoma and ocular hypertension. Sixty eyes of 60 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomized to preserved (n = 31) and preservative-free (n = 29) brimonidine groups. The enrolled eyes received brimonidine monotherapy three times daily. Main outcome measures were corneal/conjunctival staining score, ocular surface disease index, patient satisfaction score, drug tolerance, and drug adherence rate 12 weeks post first administration. Secondary outcome measurements included visual acuity, IOP, drug tolerance, tear-film break-up time, hemodynamic changes including blood pressure and heart rates, and ocular adverse events. After 12 weeks, both preserved and preservative-free groups showed similar IOP reduction, corneal and conjunctival staining scores, drug tolerance, and adherence rates. The preservative-free group showed significantly better tear-film break-up time and higher patient satisfaction regarding drug use and management. Systolic and diastolic blood pressure reductions during the 12 weeks were significantly lower in the preserved group than in the preservative-free group. Preservative-free brimonidine tartrate showed comparable efficacy and safety, better corneal tear film stability, and patient satisfaction than preserved brimonidine., (© 2023. The Author(s).)

Background: Various clinical applications have been attempted using artificial intelligence (AI) clinical decision support system (CDSS), and it has become a starting point for personalized cancer treatment. We aimed to identify the degree of agreement between the AI-CDSS, Watson for Oncology (WFO), and the clinician in treatment recommendations for Korean breast cancer patients and to provide guidelines for future improvement., Methods: One hundred and eighty-three breast cancer patients who underwent treatment at the Pusan National University Hospital between January 1, 2016 and May 31, 2017 were enrolled in this study. The concordance between WFO's and clinicians' treatment recommendations were examined according to various factors., Results: WFO gave the same treatment option recommendations as clinicians in 74 (40.4%) of the cases. According to the logistic regression, the difference in recommendation concordance between stage I and stage III was statistically significant (P = 0.004), and there was no difference among other factors., Conclusion: The concordance of treatment recommendations was low overall. However, this is largely attributable to the differences of medical insurance system and healthcare environment between the United States and Korea. In the future, region-specific features should be considered or reflected during the development of AI-CDSS.

Purpose: This study compared the malignancy risk of intermediate suspicion thyroid nodules according to the presence of suspicious ultrasonographic (US) findings., Methods: From January 2014 to December 2014, 299 consecutive intermediate suspicion thyroid nodules in 281 patients (mean age, 50.6±12.5 years) with final diagnoses were included in this study. Two radiologists retrospectively reviewed the US findings and subcategorized the intermediate suspicion category into nodules without suspicious findings and nodules with suspicious findings, including punctate echogenic foci, nonparallel orientation, or irregular margins. The malignancy rates were compared between the two subcategory groups., Results: Of the 299 intermediate suspicion thyroid nodules, 230 (76.9%) were subcategorized as nodules without suspicious findings and 69 (23.1%) as nodules with suspicious findings. The total malignancy rate was 33.4% (100/299) and the malignancy rate of nodules with suspicious findings was significantly higher than that of nodules without suspicious findings (47.8% vs. 29.1%, P=0.004). In nodules with suspicious findings, the most common suspicious finding was punctate echogenic foci (48/82, 58.5%) followed by nonparallel orientation (22/82, 26.8%) and irregular margins (12/82, 14.6%). Thirteen nodules had two suspicious findings simultaneously. A linearly increasing trend in the malignancy rate was observed according to the number of suspicious US findings (P for trend=0.001)., Conclusion: Intermediate suspicion thyroid nodules with suspicious findings showed a higher malignancy rate than those without suspicious findings. Further management guidelines for nodules with suspicious findings should differ from guidelines for nodules without suspicious findings, even in the same US category.

The COVID-19 pandemic has created significant challenges but also unprecedented opportunities for transportation researchers and practitioners. In this article, the major lessons and gaps in knowledge for those working in the transportation sector are identified, including the following: (1) integration between public health and transportation; (2) technology to support contact tracing and tracking of travelers; (3) focus on vulnerable, at-risk operators, patrons, and underserved members of society; (4) re-engineering of travel demand models to support social distancing, quarantine, and public health interventions; (5) challenges with Big Data and information technologies; (6) trust relationships between the general public, government, private sector, and others in disaster management; (7) conflict management during disasters; (8) complexities of transdisciplinary knowledge and engagement; (9) demands for training and education; and (10) transformative change to support community resilience. With a focus on transportation planning and community resilience, the lessons from the pandemic need to be shared and customized for different systems, services, modalities, and users. While many of the interventions during the pandemic have been based on public health, the management, response, recovery, adaptation, and transformation of transportation systems resulting from the crisis require multi-disciplinary, multi-jurisdictional communications and coordination, and resource sharing. Further research to support knowledge to action is needed., Competing Interests: The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© National Academy of Sciences: Transportation Research Board 2022.)

Maca is a well-known biennial herb with various physiological properties, such as antioxidant activity and immune response regulation. In this study, the antioxidant, anti-inflammatory, and anti-melanogenic effects of fermented maca root extracts were investigated. The fermentation was carried out using Lactobacillus strains, such as Lactiplantibacillus plantarum subsp. plantarum , Lacticaseibacillus rhamnosus , Lacticaseibacillus casei , and Lactobacillus gasseri . In RAW 264.7 cells, the non-fermented maca root extracts increased the secretion of nitric oxide (NO), an inflammatory mediator, in a dose-dependent manner. In contrast, the fermented extracts showed considerably lower NO secretion than the non-fermented extracts at concentrations of 5% and 10%. This indicates the effective anti-inflammatory effects of fermented maca. The fermented maca root extracts also inhibited tyrosinase activity, melanin synthesis, and melanogenesis by suppressing MITF-related mechanisms. These results show that fermented maca root extracts exhibit higher anti-inflammatory and anti-melanogenesis effects than non-fermented maca root extracts. Thus, maca root extracts fermented using Lactobacillus strains have the potential to be used as an effective cosmeceutical raw material.

Background and Aims: In obesity and type 2 diabetes mellitus, leptin promotes insulin resistance and contributes to the progression of NASH via activation of hepatic stellate cells (HSCs). However, the pathogenic mechanisms that trigger HSC activation in leptin-deficient obesity are still unknown. This study aimed to determine how HSC-targeting lipocalin-2 (LCN2) mediates the transition from simple steatosis to NASH., Approach and Results: Male wild-type (WT) and ob/ob mice were fed a high-fat diet (HFD) for 20 weeks to establish an animal model of NASH with fibrosis. Ob/ob mice were subject to caloric restriction or recombinant leptin treatment. Double knockout (DKO) mice lacking both leptin and lcn2 were also fed an HFD for 20 weeks. In addition, HFD-fed ob/ob mice were treated with gadolinium trichloride to deplete Kupffer cells. The LX-2 human HSCs and primary HSCs from ob/ob mice were used to investigate the effects of LCN2 on HSC activation. Serum and hepatic LCN2 expression levels were prominently increased in HFD-fed ob/ob mice compared with normal diet-fed ob/ob mice or HFD-fed WT mice, and these changes were closely linked to liver fibrosis and increased hepatic α-SMA/matrix metalloproteinase 9 (MMP9)/signal transducer and activator of transcription 3 (STAT3) protein levels. HFD-fed DKO mice showed a marked reduction of α-SMA protein compared with HFD-fed ob/ob mice. In particular, the colocalization of LCN2 and α-SMA was increased in HSCs from HFD-fed ob/ob mice. In primary HSCs from ob/ob mice, exogenous LCN2 treatment induced HSC activation and MMP9 secretion. By contrast, LCN2 receptor 24p3R deficiency or a STAT3 inhibitor reduced the activation and migration of primary HSCs., Conclusions: LCN2 acts as a key mediator of HSC activation in leptin-deficient obesity via α-SMA/MMP9/STAT3 signaling, thereby exacerbating NASH., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of American Association for the Study of Liver Diseases.)

Recently, roadway releases of N , N '-substituted p -phenylenediamine (PPD) antioxidants and their transformation products (TPs) received significant attention due to the highly toxic 6PPD-quinone. However, the occurrence of PPDs and TPs in recycled tire rubber products remains uncharacterized. Here, we analyzed tire wear particles (TWPs), recycled rubber doormats, and turf-field crumb rubbers for seven PPD antioxidants, five PPD-quinones (PPDQs), and five other 6PPD TPs using liquid chromatography-tandem mass spectrometry. PPD antioxidants, PPDQs, and other TPs were present in all samples with chemical profiles dominated by 6PPD, DTPD, DPPD, and their corresponding PPDQs. Interestingly, the individual [PPDQ]/[PPD] and [TP]/[PPD] ratios significantly increased as total concentrations of the PPD-derived chemical decreased, indicating that TPs (including PPDQs) dominated the PPD-derived compounds with increased environmental weathering. Furthermore, we quantified 15 other industrial rubber additives (including bonding agents, vulcanization accelerators, benzotriazole and benzothiazole derivatives, and diphenylamine antioxidants), observing that PPD-derived chemical concentrations were 0.5-6 times higher than these often-studied additives. We also screened various other elastomeric consumer products, consistently detecting PPD-derived compounds in lab stoppers, sneaker soles, and rubber garden hose samples. These data emphasize that PPD antioxidants, PPDQs, and related TPs are important, previously overlooked contaminant classes in tire rubbers and elastomeric consumer products.

Lipocalin-2 (LCN2) is an acute-phase protein that regulates inflammatory responses to bacteria or lipopolysaccharide (LPS). Although the bacteriostatic role of LCN2 is well studied, the function of LCN2 in acute lung damage remains unclear. Here, LCN2 knockout (KO) mice were used to investigate the role of LCN2 in LPS-treated mice with or without recombinant LCN2 (rLCN2). In addition, we employed patients with pneumonia. RAW264.7 cells were given LCN2 inhibition or rLCN2 with or without iron chelator deferiprone. LCN2 KO mice had a higher survival rate than wild-type (WT) mice after LPS treatment. In addition to elevated LCN2 levels in serum and bronchoalveolar lavage fluid (BALF), LPS treatment also increased LCN2 protein in alveolar macrophage lysates of BALF. LCN2 deletion attenuated neutrophil and macrophage infiltration in the lungs of LPS-treated mice as well as serum and BALF interleukin-6 (IL-6). Circulating proinflammatory cytokines and LCN2-positive macrophages were prominently increased in the BALF of pneumonia patients. In addition to increase of iron-stained macrophages in pneumonia patients, increased iron-stained macrophages and oxidative stress in LPS-treated mice were inhibited by LCN2 deletion. In contrast, rLCN2 pretreatment aggravated lung inflammation and oxidative stress in LPS-treated WT mice and then resulted in higher mortality. In RAW264.7 cells, exogenous LCN2 treatment also increased inflammation and oxidative stress, whereas LCN2 knockdown markedly diminished these effects. Furthermore, deferiprone inhibited inflammation, oxidative stress, and phagocytosis in RAW264.7 cells with high LCN2 levels, as well as LPS-induced acute lung injury in WT and LCN2 KO mice. Thus, these findings suggest that LCN2 plays a key role in inflammation and oxidative stress following acute lung injury and that LCN2 is a potential therapeutic target for pneumonia or acute lung injury., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Amyloid-β (Aβ) in the form of neurotoxic aggregates is regarded as the main pathological initiator and key therapeutic target of Alzheimer's disease. However, anti-Aβ drug development has been impeded by the lack of a target needed for structure-based drug design and low permeability of the blood-brain barrier (BBB). An attractive therapeutic strategy is the development of amyloid-based anti-Aβ peptidomimetics that exploit the self-assembling nature of Aβ and penetrate the BBB. Herein, we designed a dimeric peptide drug candidate based on the N-terminal fragment of Aβ, DAB, found to cross the BBB and solubilize Aβ oligomers and fibrils. Administration of DAB reduced amyloid burden in 5XFAD mice, and downregulated neuroinflammation and prevented memory impairment in the Y-maze test. Peptide mapping assays and molecular docking studies were utilized to elucidate DAB-Aβ interaction. To further understand the active regions of DAB, we assessed the dissociative activity of DAB with sequence modifications., (© 2022 Wiley-VCH GmbH.)

To understand the co-variance between common free-living bacteria and Cochlodinium polykrikoides harmful algal blooms (HABs) and their metabolic functions, we investigated 110 sampling sites in the Southern Sea of South Korea. These sampling sites were divided into three groups based on environmental factors and phytoplankton data with a similarity of 85% using non-metric multidimensional scaling. One group represented high-severity C. polykrikoides blooms, while the other two represented low-severity or no blooms. In high-severity HABs, inorganic phosphorous and dissolved organic carbon concentrations were strongly correlated with C. polykrikoides density (p < 0.01). This may reflect the changes in biochemical cycling due to inorganic and organic substrates released by HAB cells (or by cell destruction). Furthermore, 88 common bacterial operational taxonomic units (OTUs, with mean relative abundance > 1%) were identified. These included Gammaproteobacteria (36 OTUs), Flavobacteriia (24), Alphaproteobacteria (18), and other taxa (11). When C. polykrikoides blooms intensified, the relative abundances of Gammaproteobacteria also increased. OTU #030 (Flavicella sp., Flavobacteria, 96%) was positively correlated with C. polykrikoides abundance (r = 0.77, p < 0.001). Functional analysis based on the dominant bacterial OTUs revealed that chemoheterotrophy-related functions were more common in high-severity sites of HABs than in other groups. Therefore, the occurrence of HABs highlighted their interactions with bacteria and affected the bacterial community structure and metabolic functions., Competing Interests: Declaration of Competing Interest There are no conflicts of interests to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We sought to investigate the association between optic nerve head (ONH)/choroidal microvasculature perfusion and optic disc hemorrhage (ODH) in eyes with primary open-angle glaucoma (POAG) using swept-source optical coherence tomography angiography (SS-OCTA). A total of 266 POAG eyes (59 with a single instance of ODH, 40 with a history of recurrent ODH, and 167 eyes without ODH) with a mean follow-up of 5.4 years were included. Intradisc vessel density (VD), parapapillary choroidal VD, optic disc microvascular dropout (MvD), and choroidal microvascular dropout (CMvD), were evaluated on a 3 × 3 mm SS-OCTA image of ONH and compared between eyes with and without ODH. Recurrent ODH was defined as occurrence 1 year after first ODH detection during the total follow-up period. Logistic regression analyses were performed to investigate factors associated with ODH. The prevalence of CMvD, optic disc MvD, and β-parapapillary atrophy were not different among the no ODH, single ODH, and recurrent ODH groups. Eyes with ODH had lower intradisc VDs than those without ODH (P = 0.021), but no difference was found in intradisc VDs between the single and recurrent ODH groups (P = 0.977). Better VF MD at baseline (odds ratio [OR], 1.150; 95% confidence interval [CI], 1.055-1.254; P = 0.002) and lower intradisc VD (OR, 0.863; 95% CI, 0.812-0.918; P < 0.001) were associated with ODH occurrence. Among POAG eyes, those with ODH had lower intradisc VDs than those without ODH. POAG eyes in an earlier disease stage or those with lower intradisc VDs should be monitored for the possibility of ODH occurrence., (© 2023. The Author(s).)