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Introduction: The aim of this study was to investigate the predictive factors for persistent disease activity following anti-vascular endothelial growth factors (anti-VEGF) and their long-term effects in patients to be treated for neovascular age-related macular degeneration (nAMD) under real-world conditions., Methods: Retrospective data analysis of the PROOF study, a multi-center real-world retrospective chart review conducted across Korea in patients with nAMD included treatment-naive patients with nAMD who received first anti-VEGF (ranibizumab, bevacizumab, or aflibercept) between January 2017 and March 2019 was performed. All 600 patients (cohort 1) had a minimum follow-up of 12 months of which 453 patients (cohort 2) were followed-up for 24 months from baseline., Results: At month 12 after anti-VEGF therapy, 58.10% (95% confidence interval [CI]: 54.09, 62.12) of patients and at month 24, 66.02% of patients continued to have persistent retinal fluid. At both months 12 and 24, predictive factors for persistent disease activity were fibrovascular pigment epithelial detachments (PED) (P = 0.0494) and retinal fluid at month 3 after loading phase (P = 0.0082). The mean changes in visual acuity were + 6.2, + 10.1, and + 13.3 letters and in the central subfield thickness were - 79.1 µm, - 96.3 µm, and - 134.4 µm at 12 months from baseline, in the bevacizumab, aflibercept, and ranibizumab groups, respectively., Conclusions: The presence of retinal fluid after loading phase and fibrovascular PED were predictors of persistent disease activity after at least 1 year of anti-VEGF treatment., (© 2024. The Author(s).)

Objectives: The aim of this study was to evaluate the impact of wearing center-near (CN) and center-distance (CD) multifocal contact lenses (MFCLs) on spherical aberrations and visual acuity in patients with early presbyopia., Methods: Fifty participants with early presbyopia wore CN-MFCLs and CD-MFCLs for 1 week. The average corrected refractive power was -2.65±1.67 D. Spherical aberration was measured using an auto-refractor after 1 week of lens use., Results: No significant difference in overall visual acuity was observed when using either lens. Participants favored CD-MFCLs for distance vision and CN-MFCLs for near vision. This study highlighted variations in aberration and satisfaction based on age, refractive errors, and individual responses. Patients with positive spherical aberrations tended to benefit from CN-MFCLs, which improved both distance and near vision, although additional correction was required for clear distance vision. Patients with early presbyopia generally preferred CN-MFCLs when positive aberration was prevalent, whereas those with negative aberration reported greater satisfaction with distance vision when wearing CD-MFCLs., Conclusions: This study confirmed that wearing MFCLs leads to changes in spherical aberration and visual acuity in patients with early presbyopia, particularly when positive aberration prevails. Future research should investigate these effects across different stages of presbyopia., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

Purpose: To investigate whether standard keratometry (K) or total corneal power (TCP) leads to more accurate refractive outcomes for intraocular lens (IOL) power calculation., Setting: Public hospital., Design: Retrospective evaluation of a diagnostic test instrument., Methods: Preoperatively, all patients underwent optical biometry with Anterion, a swept-source optical coherence tomography device providing both K and TCP. The same IOL model was implanted in all cases. The whole sample was divided into a training dataset, used to optimize the formula constants, and a testing dataset, used to investigate the spherical equivalent prediction error (SEQ-PE) of 8 IOL power formulas. Trueness, precision, and accuracy were evaluated by means of the robust 2-sample t test. Cochran Q test was performed to assess whether the percentage of eyes with an SEQ-PE within each threshold was significantly different; in such an event, the McNemar test was then applied., Results: Both the training and testing datasets included 317 eyes. No significant differences were detected for trueness because of constant optimization. Precision and accuracy were better when K was entered, although a statistically significant difference was observed only with the EVO (precision: P = .02 and accuracy: P = .03) and Haigis ( P < .01 for both precision and accuracy) formulas. No significant differences were observed for the percentage of eyes with an absolute SEQ-PE within any threshold., Conclusions: With most formulas, IOL power calculation is not more accurate when TCP is used instead of K., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Level of Evidence: IV., Competing Interests: Declaration of conflicting interestsThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The purpose of this study was to present a new surgical technique to convert a single roll of Descemet membrane (DM) into a double roll using 2 cannulas in a balanced salt solution-filled Petri dish during DM endothelial keratoplasty., Methods: A single DM roll stained with trypan blue was placed in a balanced salt solution-filled Petri dish. Two cannulas (28G) were introduced from opposite ends of the single roll, inserted into the roll, and slowly spread apart to change the single roll into a double roll. The DM was aspirated into the modified Jones tube and loaded, maintaining a double-roll configuration with endothelium-down orientation in a bevel-up position. The modified Jones tube with the bevel down was inserted into the recipient anterior chamber through the main wound. The modified Jones tube was rotated to the bevel-up orientation. After checking the graft orientation, the DM was inserted into the recipient anterior chamber. The double-roll DM was easily unfolded by tapping the center of the cornea using a cannula. A 28G cannula was inserted under the DM, and the anterior chamber was filled with air., Results: Three months after surgery, the patient's corrected visual acuity in the right eye was 6/7.5 and the endothelial cell count was 1095/mm 2 . The corneal thickness was 533 μm, and the cornea was clear., Conclusions: The double-cannula maneuver mechanically changes the single roll of the donor DM to a double roll outside the recipient anterior chamber, making DM unfolding easier and minimizing the risk of upside-down apposition of the donor DM., Competing Interests: The authors have no funding or conflicts of interest to disclose.., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aims: Little is known about the practical clinical application of neuromodulators and psychiatric treatments in patients with functional gastrointestinal disorders (FGIDs). We investigate the knowledge, attitudes, and practices of Korean clinicians regarding the use of neuromodulators and psychiatric treatments for FGIDs., Methods: This prospective, online, cross-sectional study was conducted between May and August 2022. A questionnaire regarding the knowledge, attitude, and practice of neuromodulators and psychiatric treatments for FGIDs was developed and administered to primary care clinicians and gastroenterologists in university hospitals in Korea., Results: Overall, 451 clinicians from primary (n = 179, 39.7%), secondary (n = 113, 25.1%), and tertiary (n = 159, 35.3%) hospitals participated in the survey. Most of them considered that neuromodulators (98.7%) and psychiatric treatment (86.5%) were required for patients with FGIDs. However, approximately one-third of them did not prescribe neuromodulators, mainly due to unfamiliarity with the drugs, and only one-quarter considered psychiatric referral. Compared to gastroenterologists at university hospitals, primary care clinicians' prescriptions had a lower rate (87.2% vs 64.2%, P < 0.001) and shorter duration of neuromodulator. The psychiatric referral rate was lower for primary care clinicians than for gastroenterologists at university hospitals (19.0% vs 34.2%, P < 0.001)., Conclusions: Knowledge, attitude, and practice levels regarding neuromodulators and psychiatric treatment among clinicians are inhomogeneous, and a knowledge gap exists between primary care clinicians and gastroenterologists at university hospitals. Encouraging ongoing education for Korean clinicians regarding the appropriate use of neuromodulators and psychiatric treatments in patients with FGIDs is suggested.

4-tert-Octylphenol (OP), an endocrine disrupting chemical is widely used in the production of industrial products. Prenatal exposure to endocrine-disrupting chemicals negatively affects the brain. However, the influence of OP exposure during neurodevelopment in adult offspring remains unclear. Thus, in the present study, we investigated the effects of maternal OP exposure on brain development in adult offspring by analyzing primary glial cell cultures and mice. Our findings revealed that OP exposure led to a specific increase in the mRNA expression of the ionized calcium-binding adapter molecule 1 (Iba-1) and the proportion of amoeboid microglia in the primary glial cell culture and adult offspring mice. Exposure to OP increased the transcriptional activation of Iba-1 and estrogen response element, which were counteracted by estrogen receptor antagonists ICI 182,780. Moreover, OP exposure increased the nuclear localization of the estrogen receptor. Remarkably, OP exposure decreased the mRNA expression levels of proinflammatory cytokines and genes associated with immune response in the brains of the offspring. OP exposure upregulated actin filament-related genes and altered cytoskeletal gene expression, as demonstrated by microarray analysis. The morphological changes in microglia did not result in an inflammatory response following lipopolysaccharide treatment. Taken together, the effects of OP exposure during neurodevelopment persist into adulthood, resulting in microglial dysfunction mediated by estrogen receptor signaling pathways in the brains of adult offspring mice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eui-Man Jung reports financial support was provided by the National Research Foundation of Korea (NRF) funded by the Korean Government (MSIT) (grant number: 2021R1C1C100328611) and Global - Learning & Academic research institution for Master’s·PhD students, and Postdocs (LAMP) Program of the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education (No. RS-2023-00301938)., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Four soluble factors-putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102-were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45-55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.

Objective: Because of the possible therapeutic benefit of removing occult tumor cells, a source of recurrence and chemoresistance, total parietal peritonectomy (TPP) is an alternative treatment for advanced epithelial ovarian/fallopian tube/primary peritoneal cancer. Interventional studies comparing TPP with selective parietal peritonectomy (SPP) are in progress. Since surgeons skilled in TPP are essential for such trials to be conducted, this nationwide survey aimed to examine current peritonectomy practice among gynecologic oncologists in Korea., Methods: A 17-item questionnaire, developed by a surgery committee and reviewed by the scientific review board of the Korean Gynecology Oncology Group (KGOG), was distributed to 144 KGOG members. The questionnaire was divided into 3 categories: respondent demographics, peritonectomy practice during primary debulking surgery (PDS), and peritonectomy practice during interval debulking surgery (IDS)., Results: We received 88 (61.1%) valid responses. Of the valid respondents, 98.9% and 93.8% performed SPP during PDS and IDS, respectively. Only 4.9% of the respondents performed TPP during IDS. Most respondents performed peritonectomy in cases where optimal postoperative outcomes were expected. Approximately 50.6% of the respondents had performed peritonectomy independently, while the others did so in cooperation with non-gynecologic surgeons. The primary reasons for not performing TPP were concerns about morbidity and uncertainty about the clinical benefits of the procedure., Conclusion: SPP is the predominant technique used in both PDS and IDS in Korea. A small percentage (4.9%) of gynecologic oncologists have performed TPP during IDS. Accordingly, a study regarding the feasibility of TPP should be conducted before proceeding with a prospective clinical trial., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Aims: To assess the efficacy and safety of sarpogrelate (300 mg) for symptom improvement in patients having peripheral arterial disease (PAD) and/or being at risk of PAD in clinical practice using the Peripheral Artery Questionnaire (PAQ)., Background: Symptomatic changes with antiplatelets in patients with PAD are limited., Objective: To determine the effect and safety of sarpogrelate on the PAQ at 24 weeks from baseline., Method: A total of 1003 patients having PAD and/or being at risk of PAD from 17 tertiary hospitals in South Korea who were treated with sarpogrelate, were enrolled in this study. PAQs were collected at baseline and at 12 and 24 weeks, together with physical examination and vital signs measurements. Lifestyle pattern was also investigated., Results: The average PAQ Summary Score in the efficacy evaluation analysis group significantly improved from 62.9 ± 23.7 at baseline to 68.9 ± 21.7 at 24 weeks (P<0.0001). Physical limitation items significantly improved from 69.5 ± 30.0 at baseline to 72.9 ± 28.3 after 24 weeks (P=0.0011). Symptom stability also significantly improved from 52.1 ± 21.6 at baseline to 63.6 ± 22.9 after 24 weeks (P<0.0001). Symptoms, treatment satisfaction, quality of life, and social limitation domains all improved after treatment. A total of 201 patients reported adverse events (20.0%), not directly associated with treatment., Conclusion: Treatment with 300 mg (orally) of sarpogrelate demonstrated statistically significant improvements in all domains and for the summary score of the PAQ at 24 weeks, it gave good results in terms of safety. Sarpogrelate may be helpful in reducing symptoms related to PAD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: The current study developed and tested selected effects of the Together for Life (TFL) program for community-dwelling older adults using an embedded mixed methods design., Method: Nine community volunteers participated in the training program, and 14 people aged ≥65 years, living alone, enrolled in the study. Home visits were conducted by home health nurses every 2 weeks, supplemented by weekly home visits and phone counseling provided by volunteers, for a duration of 20 weeks. This mixed methods study used quantitative and qualitative approaches. Quantitative data were gathered through a questionnaire survey to assess the intervention's effects on health-related quality of life (HRQOL), loneliness, and depression. The qualitative component focused on participants' evaluation of the program., Results: Significant changes were noted in HRQOL scores with an effect size of 0.6 ( p = 0.01). Results indicated the positive impact of the TFL program on HRQOL among older adults as their health status was continuously monitored by volunteers who provided care and home health nurses who assisted with health management during the coronavirus disease 2019 (COVID-19) pandemic., Conclusion: In a pandemic, personalized health management, such as regular health check-ins provided by home health nurses and home or phone visits provided by volunteers, is crucial for isolated older adults. This pilot program enhanced participants' HRQOL through continuous health monitoring, volunteer care, and nurse support, even during the COVID-19 pandemic. [ Journal of Gerontological Nursing, xx (x), xx-xx.].

In Walker's nonmetric method, the nuchal crest serves as the representative region for indicating sexual dimorphism in cranial bones. However, the accuracy of sex estimation using the nuchal crest is lower than that using other anatomical regions. Furthermore, because of the protruding processes and structurally challenging features characterized by uneven and rough surfaces, there is a lack of metric methods for sex estimation, making quantification challenging. In this study, we aimed to validate a derived metric method for sex estimation by reconstructing the nuchal crest region in three-dimensional (3D) images obtained from computed tomography scans of cranial bones and compare its accuracy with that of the nonmetric method. A total of 648 images were collected, with 100 randomly selected for use in the nonmetric method. We applied our metric method to the remaining 548 images. Our findings showed that the surface area of the nuchal crests was greater in male individuals than in female individuals. The nuchal crest surface area quantified by the metric method increased the accuracy of sex estimation by 48% compared with that by the nonmetric method. Our metric method for sex estimation, which quantifies the nuchal crest surface area using 3D images of the skull, led to a high sex estimation accuracy of 93%. Future studies should focus on proposing and quantifying new measurement methods for areas showing sexual characteristics in the skull that are difficult to measure, thereby enhancing the accuracy and reliability of sex estimation in human skeletal identification across various fields.

Purpose: To investigate the risk factors for corneal endothelial cell density (ECD) loss of two types of iris-fixated phakic intraocular lenses (pIOL) and indicate the cutoff values for preventing irreversible ECD loss after explantation., Design: The retrospective, comparative, clinical cohort study METHODS: Total 114 eyes of 61 patients were included in this study. Fifty-five eyes with Artisan pIOL and 59 eyes with Artiflex pIOL had undergone explantation of pIOLs due to continuous ECD loss. Correlation analysis was performed to assess the ocular parameters associated with ECD loss. Receiver operating characteristic (ROC) curve was performed to set cutoff values of ocular parameters to prevent ECD loss after explantation., Result: The mean ECD before explantation was 1637 cells/mm 2 in Artisan group and 1769 cells/mm 2 in Artiflex group. The distance of cornea endothelium to IOL center and edges were all significantly higher in Artisan group (p <0.05). The risk factor of decreased ECD in Artisan group were small anterior chamber angle (ACA), and distance of nasal edge of IOL to endothelium and iris fixation to nasal limbus distance, and differences of fixation length. In Artiflex group, ACA, distance of nasal edge of IOL to endothelium, both limbus to IOL fixation length, fixation length, iris pigmentation grading were the risk factors. At 1 year after the pIOL removal, the population demonstrating ΔECD >10% were significantly higher in Artisan group than Artiflex group (p <0.05). In ROC curve analysis, the cutoff value of preoperative ECD to prevent significant post-explantation ECD loss was 1683.5 cells/mm 2 in Artisan group and 1648 cells/mm 2 in Artiflex group., Conclusion: This study examined the existing explantation guidelines for these lenses. In analyzing the longterm prognosis of cornea ECD with Iris-fixated phakic intraocular lens, it is important to identify the relevant anatomical factors. Small ACA, and short distances from IOL to endothelium and from limbus to iris fixation especially in the nasaSSSl region were significant risk factors to continuous ECD loss in both lenses. To minimize irreversible ECD loss after explantation, it is important to determine the optimal period of explantation by observing both ECD and structural changes., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Ferric ion (Fe3+) is a biologically abundant and important metal ion. We developed several cyclometalated iridium complex-based molecular sensors (1, ppy-1, 1-phen, 1a, and 1-OMe) for the detection of Fe3+ using an acetal moiety as the reaction site. The acetal moiety in iridium complexes undergoes Fe3+-catalyzed hydrolysis and subsequent formation of a formyl group, resulting in turn-off photoluminescent and electrochemiluminescent responses. Sensor 1 showed excellent selectivity toward Fe3+ over other biologically important metal ions. Furthermore, we compared the performance of the sensors based on the structural differences of the iridium complexes, and revealed a relationship between the structure and chemical properties through electrochemical experiments and computational calculations., (© 2024 Wiley‐VCH GmbH.)

Objective: We investigated genetic parameters of calving ease (CE) using several animal models in Korean Holstein and searched for suitable models for routine evaluation of CE., Methods: Two phenotypic datasets of CE on first-parity Korean Holstein calves were prepared. DS5 and DS10 included at least 5 and 10 CE records per herd-year level and comprised 117,921 and 80,389 observations, respectively. The CE phenotypes ranged from 1 to 4, from a normal to extreme difficulty calving scale. The CE was defined as a trait of the calf. The BLUPF90+ software was used for (co)variances estimation through four animal models with a maternal effect (M1 to M4), where all models included effects of a fixed calf-sex, a fixed dam calving age (covariate), and one or more fixed contemporary group (CG) terms. The CG effects were different across models- a herd-year-season (M1, HYS), a herd-year and year-season (M2, HY+YS), a herd-year and season (M3, HY+S), and a herd and year-season (M4, H+YS)., Results: Direct heritability (h2) estimates of CE ranged from 0.005 to 0.234 across models and datasets. Maternal h2 values were low (0.001 to 0.090). Genetic correlations between direct and maternal effects were strongly negative to lowly positive (-0.814 to 0.078), further emphasizing its importance in CE evaluation models. These genetic parameter estimates also indicate slower future selection progress of CE in Korean Holsteins. The M1 fitted many levels with fewer observations per level deriving unreliable parameters, and the M4 did not account for confounded herd and animal structures. The M2 and M3 were deemed more realistic for implementation, and they were better able to account for data structure issues (incompleteness and confounding) than other models., Conclusion: As the pioneering study to employ animal models in Korean Holstein CE evaluation, our findings hold significant potential for this breed's future and routine evaluation development.

During implant placement, dehiscence defects can result in complications like mucosal recession and peri-implantitis. While guided bone regeneration (GBR) is a common approach to managing these defects, it is often complex and time-intensive. This case series evaluates an alternative method using a collagen matrix (Collagen Graft2®) applied to peri-implant dehiscence defects without GBR. Through three case series, this approach effectively preserves buccal contour, enhances gingival thickness, and supports bone regeneration, leading to favorable peri-implant conditions. These findings suggest that collagen matrix application is a viable and less invasive option for treating peri-implant dehiscence defects; however, further studies are required to validate these results., Competing Interests: Conflicts of interest: none

Purpose: Trop family proteins, including epithelial cell adhesion molecule (EpCAM) and Trop-2, have garnered attention as potential therapeutic and diagnostic targets for various malignancies. This study aimed to elucidate the clinicopathological significance of these proteins in gastric carcinoma (GC) and to reinforce their potential as biomarkers for patient stratification in targeted therapies., Materials and Methods: Immunohistochemical (IHC) analyses of EpCAM and Trop-2 were performed on GC and precancerous lesions, following rigorous orthogonal validation of the antibodies to ensure specificity and sensitivity., Results: Strong membranous staining (3+) for Trop-2 was observed in 49.3% of the GC cases, whereas EpCAM was strongly expressed in almost all cases (93.2%), indicating its widespread expression in GC. A high Trop-2 expression level, characterized by an elevated H-score, was significantly associated with intestinal type by Lauren classification, gastric mucin type, presence of lymph node metastasis, human epidermal growth factor receptor 2-positivity, and Epstein-Barr virus (EBV)-positivity. Patients with a high Trop-2 expression level exhibited poorer survival outcomes on univariate and multivariate analyses. High EpCAM expression levels were prevalent in differentiated histologic type, microsatellite instability-high, and EBV-negative cancer, and were correlated with high densities of CD3 and CD8 T cells and elevated combined positive score for programmed death-ligand 1., Conclusions: These results highlight the differential expression of Trop-2 and EpCAM and their prognostic implications in GC. The use of meticulously validated antibodies ensured the reliability of our IHC data, thereby offering a robust foundation for future therapeutic strategies targeting Trop family members in GC., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2024. Korean Gastric Cancer Association.)

The fruit fly Drosophila melanogaster has emerged as a key model organism in neuroscience, in large part due to the concentration of collaboratively generated molecular, genetic and digital resources available for it. Here we complement the approximately 140,000 neuron FlyWire whole-brain connectome 1 with a systematic and hierarchical annotation of neuronal classes, cell types and developmental units (hemilineages). Of 8,453 annotated cell types, 3,643 were previously proposed in the partial hemibrain connectome 2 , and 4,581 are new types, mostly from brain regions outside the hemibrain subvolume. Although nearly all hemibrain neurons could be matched morphologically in FlyWire, about one-third of cell types proposed for the hemibrain could not be reliably reidentified. We therefore propose a new definition of cell type as groups of cells that are each quantitatively more similar to cells in a different brain than to any other cell in the same brain, and we validate this definition through joint analysis of FlyWire and hemibrain connectomes. Further analysis defined simple heuristics for the reliability of connections between brains, revealed broad stereotypy and occasional variability in neuron count and connectivity, and provided evidence for functional homeostasis in the mushroom body through adjustments of the absolute amount of excitatory input while maintaining the excitation/inhibition ratio. Our work defines a consensus cell type atlas for the fly brain and provides both an intellectual framework and open-source toolchain for brain-scale comparative connectomics., (© 2024. The Author(s).)

Connections between neurons can be mapped by acquiring and analysing electron microscopic brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative 1-6 , but nevertheless inadequate for understanding brain function more globally. Here we present a neuronal wiring diagram of a whole brain containing 5 × 10 7 chemical synapses 7 between 139,255 neurons reconstructed from an adult female Drosophila melanogaster 8,9 . The resource also incorporates annotations of cell classes and types, nerves, hemilineages and predictions of neurotransmitter identities 10-12 . Data products are available for download, programmatic access and interactive browsing and have been made interoperable with other fly data resources. We derive a projectome-a map of projections between regions-from the connectome and report on tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine and descending neurons) across both hemispheres and between the central brain and the optic lobes. Tracing from a subset of photoreceptors to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviours. The technologies and open ecosystem reported here set the stage for future large-scale connectome projects in other species., (© 2024. The Author(s).)

As connectomics advances, it will become commonplace to know far more about the structure of a nervous system than about its function. The starting point for many investigations will become neuronal wiring diagrams, which will be interpreted to make theoretical predictions about function. Here I demonstrate this emerging approach with the Drosophila optic lobe, analysing its structure to predict that three Dm3 (refs.  1-4 ) and three TmY (refs.  2,4 ) cell types are part of a circuit that serves the function of form vision. Receptive fields are predicted from connectivity, and suggest that the cell types encode the local orientation of a visual stimulus. Extraclassical 5,6 receptive fields are also predicted, with implications for robust orientation tuning 7 , position invariance 8,9 and completion of noisy or illusory contours 10,11 . The TmY types synapse onto neurons that project from the optic lobe to the central brain 12,13 , which are conjectured to compute conjunctions and disjunctions of oriented features. My predictions can be tested through neurophysiology, which would constrain the parameters and biophysical mechanisms in neural network models of fly vision 14 ., (© 2024. The Author(s).)

A catalogue of neuronal cell types has often been called a 'parts list' of the brain 1 , and regarded as a prerequisite for understanding brain function 2,3 . In the optic lobe of Drosophila, rules of connectivity between cell types have already proven to be essential for understanding fly vision 4,5 . Here we analyse the fly connectome to complete the list of cell types intrinsic to the optic lobe, as well as the rules governing their connectivity. Most new cell types contain 10 to 100 cells, and integrate information over medium distances in the visual field. Some existing type families (Tm, Li, and LPi) 6-10 at least double in number of types. A new serpentine medulla (Sm) interneuron family contains more types than any other. Three families of cross-neuropil types are revealed. The consistency of types is demonstrated by analysing the distances in high-dimensional feature space, and is further validated by algorithms that select small subsets of discriminative features. We use connectivity to hypothesize about the functional roles of cell types in motion, object and colour vision. Connectivity with 'boundary types' that straddle the optic lobe and central brain is also quantified. We showcase the advantages of connectomic cell typing: complete and unbiased sampling, a rich array of features based on connectivity and reduction of the connectome to a substantially simpler wiring diagram of cell types, with immediate relevance for brain function and development., (© 2024. The Author(s).)

Cancer immunotherapy aims to initiate or amplify immune responses that eliminate cancer cells and create immune memory to prevent relapse. Immune checkpoint inhibitors (ICIs), which target coinhibitory receptors on immune effector cells, such as CTLA-4 and PD-(L)1, have made significant strides in cancer treatment. However, they still face challenges in achieving widespread and durable responses. The effectiveness of anticancer immunity, which is determined by the interplay of coinhibitory and costimulatory signals in tumor-infiltrating immune cells, highlights the potential of costimulatory receptors as key targets for immunotherapy. This review explores our current understanding of the functions of CD2 and CD226, placing a special emphasis on their potential as novel agonist targets for cancer immunotherapy. CD2 and CD226, which are present mainly on T and NK cells, serve important functions in cell adhesion and recognition. These molecules are now recognized for their costimulatory benefits, particularly in the context of overcoming T-cell exhaustion and boosting antitumor responses. The importance of CD226, especially in anti-TIGIT therapy, along with the CD2‒CD58 axis in overcoming resistance to ICI or chimeric antigen receptor (CAR) T-cell therapies provides valuable insights into advancing beyond the current barriers of cancer immunotherapy, underscoring their promise as targets for novel agonist therapy., (© 2024. The Author(s).)

Objective: This study aimed to compare survival and complications between minimally invasive surgery and open surgery and evaluate related risk factors in patients with non-endometrioid endometrial cancer., Methods: Clinicopathologic characteristics; survival outcomes; complications; and prognostic factors associated with progression-free survival and overall survival were compared among patients with non-endometrioid endometrial cancer who underwent primary staging surgery using laparoscopic, robotic, or open abdominal surgery (2004-2017)., Results: In total, 91 patients were included: 41 and 50 underwent minimally invasive surgery and open surgery, respectively. The minimally invasive surgery and open surgery groups showed similar progression-free survival (5-year progression-free survival rate, 58.7 % vs. 58.5 %; P = .925) and overall survival (5-year overall survival rate, 73.6 % vs. 80.3 %; P = .834). Intraoperative (7.2 % vs. 6.0 %; P = .111) and postoperative surgical complications (14.6 % vs. 26.0 %; P = .165) were similar between the groups. However, blood loss was lower (mean, 305.1 vs. 561.2 ml, P < .001) and hospital stay was shorter (mean, 8.2 vs. 15.4 days, P < .001) in the minimally invasive surgery group. Using multivariate analysis, lymphovascular space invasion was identified as poor prognostic factor for progression-free survival (adjusted hazard ratio [HR], 3.054; 95 % confidence interval [CI], 1.521-6.132; P = .002) and overall survival (adjusted HR, 3.918; 95 % CI, 1.455-10.551; P = .007), whereas age ≥ 60 years was poor prognostic factor for only overall survival (adjusted HR, 5.0953; 95 % CI, 1.660-15.378; P = .004)., Conclusions: Surgical outcomes did not differ between the minimally invasive and open surgery group in patients with non-endometrioid endometrial cancer. Lymphovascular space invasion was a significant survival factor in this context., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: To evaluate whether treatment with erythropoiesis-stimulating agents (ESAs) for chemotherapy-induced anemia affects progression-free survival (PFS) in patients receiving front-line chemotherapy following surgery for ovarian cancer (OC)., Methods: We retrospectively reviewed all consecutive patients who received front-line chemotherapy after surgery between 2013 and 2019 at six institutions. The patients were divided according to the use of ESAs during front-line chemotherapy. The primary endpoint was PFS. The secondary endpoint was the occurrence of thromboembolism. Propensity score matching (PSM) analysis was used to compare survival between matched cohorts., Results: Overall, 2147 patients (433 receiving ESA and 1714 for no-ESA) were identified, with a median follow-up of 44.0 months. The ESA group showed a significantly higher proportion of stage III/IV disease (81.8% vs 61.1%; P < 0.001) and postoperative gross residual disease (32.3% vs 21.2%; P < 0.001) than the no-ESA group. In the multivariable Cox regression analysis, the use of ESAs did not affect PFS (adjusted hazard ratio, 1.03; 95% confidence interval [CI]: 0.89-1.20; P = 0.661). The incidence of thromboembolism was 10.2% in the ESA group and 4.6% in the no-ESA group (adjusted odds ratio, 6.58; 95% CI: 3.26-13.28; P < 0.001). When comparing the well-matched cohorts after PSM, PFS did not differ between the ESA (median PFS 23.5 months) and no-ESA groups (median PFS 22.2 months) (P = 0.540, log-rank test)., Conclusions: The use of ESAs during front-line chemotherapy did not negatively affect PFS in patients with OC after surgery but increased the risk of thromboembolism., (© 2024 International Federation of Gynecology and Obstetrics.)

Background and Purpose: Mitochondrial dysfunction contributes to the pathogenesis and maintenance of chemotherapy-induced peripheral neuropathy (CIPN), a significant limitation of cancer chemotherapy. Recently, the stimulation of mitophagy, a pivotal process for mitochondrial homeostasis, has emerged as a promising treatment strategy for neurodegenerative diseases, but its therapeutic effect on CIPN has not been explored. Here, we assessed the mitophagy-inducing activity of 3,5-dibromo-2-(2',4'-dibromophenoxy)-phenol (PDE701), a diphenyl ether derivative isolated from the marine sponge Dysidea sp., and investigated its therapeutic effect on a CIPN model., Experimental Approach: Mitophagy activity was determined by a previously established mitophagy assay using mitochondrial Keima (mt-Keima). Mitophagy induction was further verified by western blotting, immunofluorescence, and electron microscopy. Mitochondrial dysfunction was analysed by measuring mitochondrial superoxide levels in SH-SY5Y cells and Drosophila larvae. A thermal nociception assay was used to evaluate the therapeutic effect of PDE701 on the paclitaxel-induced thermal hyperalgesia phenotype in Drosophila larvae., Key Results: PDE701 specifically induced mitophagy but was not toxic to mitochondria. PDE701 ameliorated paclitaxel-induced mitochondrial dysfunction in both SH-SY5Y cells and Drosophila larvae. Importantly, PDE701 also significantly ameliorated paclitaxel-induced thermal hyperalgesia in Drosophila larvae. Knockdown of ATG5 or ATG7 abolished the effect of PDE701 on thermal hyperalgesia, suggesting that PDE701 exerts its therapeutic effect through mitophagy induction., Conclusion and Implications: This study identified PDE701 as a novel mitophagy inducer and a potential therapeutic compound for CIPN. Our results suggest that mitophagy stimulation is a promising strategy for the treatment of CIPN and that marine organisms are a potential source of mitophagy-inducing compounds., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Extended-spectrum β -lactamase (ESBL)-producing Salmonella is emerging as a worldwide public health concern. In this study, we aimed to investigate the antimicrobial resistance profiles and molecular characteristics of ESBL-producing Salmonella enterica serovar Typhimurium ( S. Typhimurium). We obtained a total of 995 S. Typhimurium isolates from the feces and carcasses of pigs ( n = 678), chickens ( n = 202), and cattle ( n = 115) during 2010-2021 in Korea. We found that 35 S. Typhimurium isolates (3.5%) showed resistance to ceftiofur: pigs (51.4%, 18/35) and cattle (42.9%, 15/35). All of the ceftiofur-resistant S. Typhimurium isolates demonstrated multidrug resistance. Moreover, ceftiofur-resistant S. Typhimurium isolates displayed significantly higher rates of resistance to chloramphenicol and trimethoprim/sulfamethoxazole than ceftiofur-susceptible S. Typhimurium isolates ( p < 0.05). The ceftiofur-resistant S. Typhimurium isolates produced four different CTX-M-type β -lactamase, comprising bla CTX-M-55 in the majority (51.4%, 18/35), followed by bla CTX-M-65 (28.6%, 10/35), bla CTX-M-14 (17.1%, 6/35), and bla CTX-M-1 (2.9%, 1/35). Among the 35 ceftiofur-resistant S. Typhimurium isolates, 16 bla CTX-M-55 -positive isolates and one bla CTX-M-1 -positive isolate were transferred to recipient Escherichia coli RG488 by conjugation. The predominantly found transposable units were bla CTX-M-55 - orf477 (45.7%, 16/35), followed by bla CTX-M-65 -IS 903 (28.6%, 10/35) and bla CTX-M-14 -IS 903 (17.1%, 6/35). Ceftiofur-resistant S. Typhimurium represented 19 types, with types P1-19 (22.9%, 8/35) and P12-34 (22.9%, 8/35) making up the majority and being found in most farms nationwide. Sequence types (STs) were different by animal species: ST19 (48.6%, 17/35) and ST34 (42.9%, 15/35) were mostly found STs in pigs and cattle, respectively. These findings showed that food animals, especially pigs and cattle, act as reservoirs of bla CTX-M -harboring S. Typhimurium that can potentially be spread to humans.

This study aimed to conduct an in-depth examination of gene expression and microenvironmental profiles of gastric neuroendocrine carcinoma (NEC) and mixed adeno-NEC (MANEC). Tissue microarrays from 55 patients with gastric MANEC (N = 32) or NEC (N = 23) were analyzed using digital spatial profiling (GeoMx DSP, NanoString Technologies). Representative regions of interest were selected from the adenocarcinoma (ADC) portion (ADC-MANEC) and the NEC portion (NEC-MANEC) of the MANEC cores, and pure NEC (pNEC) cores. All regions of interest were separated into epithelial components and stromal components using the masking procedure in the GeoMx platform, followed by transcriptome analysis. Comparison of gene expression between ADC-MANEC and NEC-MANEC/pNEC identified several differentially expressed genes in the epithelial (including PEG10, MAP1B, STMN3, and AKT3) and stromal (FN1, COL1A1, SPARC, and BGN) components. Gene set enrichment analysis revealed that pathways related to the E2F target and G2M checkpoint were more enriched in NEC-MANEC and pNEC than in ADC-MANEC. Deconvolution analysis showed that the microenvironmental profile varied according to histologic differentiation. In ADC-MANEC, intraepithelial infiltrating immune cells were relatively more numerous, whereas fibroblasts in the stroma were more abundant in NEC-MANEC and pNEC. This study confirmed the distinct expression profile of each histologic component of MANEC according to its tumor vs stromal compartment using the DSP platform. Although each component of MANEC shares the same genetic origin, distinctive phenotypes should not be overlooked when managing patients with MANEC. This study provides a useful validation data set for future studies., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose: Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability-high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors, presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential., Materials and Methods: We explored the molecular characteristics of CD8+ T-cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis., Results: In MSI-H gastric cancer, significantly higher proportions of effector memory T cell (Tem), exhausted T cell (Tex), proliferative exhausted T cell (pTex), and proliferative T cell were observed, while MSS gastric cancer exhibited significantly higher proportions of mucosal-associated invariant T cell and natural killer T cell. In MSI-H gastric cancer, Tex and pTex exhibited a significant upregulation of the exhaustion marker LAG3, as well as elevated expression of effector function markers such as IFNG, GZMB, GZMH, and GZMK, compared to those in MSS gastric cancer. The interferon γ (IFN-γ) signaling pathway of Tex and pTex was retained compared to those of MSS gastric cancer. The spatial transcriptome analysis demonstrates the IFN-γ signaling pathway between neighboring Tex and malignant cell, showcasing a significantly elevated interaction in MSI-H gastric cancer., Conclusion: Our study reveals novel finding indicating that IFN-γ signaling pathway is retained in Tex and pTex of MSI-H gastric cancer, offering a comprehensive perspective for future investigations into immunotherapy for gastric cancer.

Background: Uteroglobin is a multifunctional protein with anti-inflammatory properties. Studies have revealed the importance of inflammation in type 2 diabetes mellitus (T2D) pathogenesis. Here, we investigated the relationship between uteroglobin and T2D., Methods: We performed diagnostic tests for diabetes in subjects who had not been diagnosed with or treated for T2D. We established three groups, containing those with normal glucose tolerance (NGT), prediabetes and T2D, consisting of 80 people each, and compared their uteroglobin levels. In addition, 28 patients newly diagnosed with T2D were treated with metformin for 12 weeks, and 63 patients newly diagnosed with dyslipidaemia during the treatment for T2D were treated with statin for 12 weeks., Results: This study showed that uteroglobin levels were significantly lower in prediabetes and T2D groups than in the NGT group. Uteroglobin levels were not significantly correlated with other metabolic parameters, except BMI, HOMA-β and eGFR. In the group treated with metformin or statin, uteroglobin levels increased after treatment compared to before treatment., Conclusions: Uteroglobin is a sensitive factor that was decreased even in prediabetes and increased upon treatment with drugs with anti-inflammatory effects. Uteroglobin is a potential early biomarker that reflects a chronic inflammatory condition in T2D., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lim, Ju, Kim, Yi, Lee, Kim, Ku and Joung.)

Spatial representation of the self plays a vital role constructing our sense of bodily self-boundary that distinguishes the self from others. This perceptual border, known as the peripersonal space (PPS), has been suggested to be altered in individuals with schizophrenia (SZ). PPS represents a protective defensive zone that triggers alarm signals upon threat detection; thus disrupted PPS could lead to social interactional difficulties. However, very little is known about the impact of threat on PPS. To address this gap, a visual-tactile response-time (RT) experiment was conducted in immersive virtual reality (VR) for SZ and matched controls (CO). Participants were asked to detect a tactile vibration on their hand while an avatar (either threatening or neutral) approached them. Avatars were presented at different distance from the participants. PPS size and slope were estimated by identifying significant RT drop at the hypothesized self-other boundary. We also examined the relationship between PPS parameters, clinical symptoms and social disconnection. There was no overall group difference in PPS size. Perceived social threat posed in the avatars sharpened the self-boundary in CO but not in SZ. In SZ, shallower PPS slope was associated with delusion, persecution, negative symptoms and loneliness but not in CO. These results show that the regulation of self-other boundary in response to impending social threat may be maladaptive in SZ. Further research is needed on the causal mechanisms between self-disturbance and social impairments., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Approximately half of the patients with advanced pancreatic ductal adenocarcinoma (PDAC) receive subsequent lines of chemotherapy. Recently, the liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) regimen is recommended as subsequent lines of chemotherapy. However, little is known about the predictive factors for the nal-IRI + 5-FU/LV regimen, especially in patients with previous irinotecan (IRI) exposure., Objectives: We investigated the predictive factors associated with nal-IRI + 5-FU/LV treatment in patients with PDAC., Design: Multicenter, retrospective cohort study., Methods: This study included patients with advanced PDAC who received the nal-IRI + 5-FU/LV regimen for palliative purposes., Results: Overall, 268 patients were treated with nal-IRI + 5-FU/LV. The median overall survival (OS) was 7.9 months (95% confidence interval (CI): 7.0-8.8), while the median progression-free survival (PFS) was 2.6 months (95% CI: 1.9-3.2). An albumin level of<4.0 g/dL, neutrophil-to-lymphocyte ratio (NLR) of ⩾3.5, liver or peritoneal metastasis, and a history of >3 lines of palliative chemotherapy were associated with worse OS. An NLR of ⩾3.5 and liver metastasis were significant predictive factors for worse PFS. Previous exposure to IRI was not a significant predictor. Patients without prior IRI (no-IRI) treatment showed relatively longer OS and PFS compared to IRI responders and nonresponders, but these differences were not significant when compared specifically to the responders (OS: 8.8 vs 8.1 months, p = 0.388; PFS: 3.6 vs 2.6 months, p = 0.126)., Conclusion: An NLR of ⩾3.5 and liver metastasis were associated with worse PFS. Prior IRI exposure was not a significant predictive factor for OS and PFS, especially in IRI responders., Competing Interests: Seungmin Bang received funding from Servier., (© The Author(s), 2024.)

Prostate cancer (PCa) is the most prevalent cancer affecting American men. Castration-resistant prostate cancer (CRPC) can emerge during hormone therapy for PCa, manifesting with elevated serum prostate-specific antigen levels, continued disease progression, and/or metastasis to the new sites, resulting in a poor prognosis. A subset of CRPC patients shows a neuroendocrine (NE) phenotype, signifying reduced or no reliance on androgen receptor signaling and a particularly unfavorable prognosis. In this study, we incorporated computational approaches based on both gene expression profiles and protein-protein interaction networks. We identified 500 potential marker genes, which are significantly enriched in cell cycle and neuronal processes. The top 40 candidates, collectively named CDHu40, demonstrated superior performance in distinguishing NE PCa (NEPC) and non-NEPC samples based on gene expression profiles. CDHu40 outperformed most of the other published marker sets, excelling particularly at the prognostic level. Notably, some marker genes in CDHu40, absent in the other marker sets, have been reported to be associated with NEPC in the literature, such as DDC, FOLH1, BEX1, MAST1, and CACNA1A. Importantly, elevated CDHu40 scores derived from our predictive model showed a robust correlation with unfavorable survival outcomes in patients, indicating the potential of the CDHu40 score as a promising indicator for predicting the survival prognosis of those patients with the NE phenotype. Motif enrichment analysis on the top candidates suggests that REST and E2F6 may serve as key regulators in the NEPC progression., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA., Methods: In this prospective study, we enrolled 80 infants with MCAs who were admitted to a NICU at a single center and had received negative results from CMA and/or karyotyping. The phenotypic characteristics were classified according to the International Classification of Diseases and the Human Phenotype Ontology. We assessed the diagnostic yield of trio-WGS in infants with normal chromosomal result and explored the process of diagnosing by analyzing both phenotype and genotype. Also, we compared the phenotype and clinical outcomes between the groups diagnosed with WGS and the undiagnosed group., Results: The diagnostic yield of WGS was 26% (21/80), of which 76% were novel variants. There was a higher diagnostic yield in cases of craniofacial abnormalities, including those of the eye and ear, and a lower diagnostic yield in cases of gastrointestinal and genitourinary abnormalities. In addition, higher rates of rehabilitation therapy and gastrostomy were observed in WGS-diagnosed infants than in undiagnosed infants., Conclusion: This prospective cohort study assessed the usefulness of trio-WGS following chromosomal analysis for diagnosing MCAs in the NICU and revealed improvements in the diagnostic yield and clinical utility of WGS., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

We are now in the era of millimeter-scale electron microscopy (EM) volumes collected at nanometer resolution. Dense reconstruction of cellular compartments in these EM volumes has been enabled by recent advances in Machine Learning (ML). Automated segmentation methods produce exceptionally accurate reconstructions of cells, but post-hoc proofreading is still required to generate large connectomes free of merge and split errors. The elaborate 3-D meshes of neurons in these volumes contain detailed morphological information at multiple scales, from the diameter, shape, and branching patterns of axons and dendrites, down to the fine-scale structure of dendritic spines. However, extracting these features can require substantial effort to piece together existing tools into custom workflows. Building on existing open-source software for mesh manipulation, here we present "NEURD", a software package that decomposes meshed neurons into compact and extensively-annotated graph representations. With these feature-rich graphs, we automate a variety of tasks such as state of the art automated proofreading of merge errors, cell classification, spine detection, axon-dendritic proximities, and other annotations. These features enable many downstream analyses of neural morphology and connectivity, making these massive and complex datasets more accessible to neuroscience researchers focused on a variety of scientific questions.

Background: Non-allergic eosinophilic asthma (NAEA) is a distinct subtype of asthma. However, the immune mechanisms associated with NAEA are not yet clearly understood., Objective: To gain further insight into the pathogenesis of NAEA., Methods: The proportion of innate lymphoid cells (ILCs) in the blood of patients with allergic eosinophilic asthma (AEA) and NAEA was evaluated. Eosinophilic asthma was defined when fractional exhaled nitric oxide measured at diagnosis (before initiating anti-asthma medications) was greater than 50 ppb. We evaluated the genome-wide gene expression profiles in peripheral blood mononuclear cells obtained at enrollment (in a stable state)., Results: A total of 57 participants were enrolled (10 healthy controls, 23 patients with NAEA, and 24 patients with AEA). We found that the type 1 ILC (ILC1) proportion significantly decreased, but the type 2 ILC (ILC2) and type 3 ILC (ILC3) proportions significantly increased in the blood of both patients with NAEA and those with AEA compared with healthy controls. However, there were no significant differences in the ILC1~3 proportions between NAEA and AEA patients. We also identified distinct biological pathways in patients with NAEA (anti-viral pathway) or AEA (IL-4 and IL-13 signaling and neutrophil degranulation pathways) based on co-expressed gene modules showing significant correlations with the ILC proportions., Conclusion: ILC proportions in the blood did not differ between NAEA and AEA patients. However, different biological pathways were related to the ILC proportions in these patients. Our results provide further insight into eosinophilic airway inflammation in allergic and non-allergic patients.

Introduction: We aimed to describe patient awareness regarding fall prevention and education, perceived causes of falls, and changes in attitude after experiencing a fall through interviews with older Korean patients who experienced falls with resultant hip fractures., Materials and Methods: We conducted face-to-face semi-structured in-depth interviews with 11 patients who were admitted to Kangbuk Samsung Hospital for hip fractures caused by falls and were referred to the Department of Rehabilitation Medicine for postsurgical rehabilitation between June 2022 and June 2023. The data were analyzed using the phenomenological method developed by Colaizzi., Results: Before hip fracture, none of the patients had received fall prevention education or perceived its necessity; however, they recognized its necessity retrospectively. Participants described the causes of falls as carelessness, actions taken at the time of the fall, environmental factors, and decreased physical function. Most participants believed that falls could be prevented through personal caution and activity restrictions. Some mentioned fall prevention education, exercise, wearing appropriate shoes, environmental adjustments, and seeking assistance from others as methods of preventing future falls. Most patients reported adopting a safety-seeking attitude after experiencing hip fracture. Many patients had negative thoughts such as guilt or thoughts of death, whereas only a few reported increased interest in education and exercise., Conclusions: We observed a lack of fall prevention education, misunderstanding regarding the cause of falls, and negative psychological changes after experiencing hip fractures due to falls in older Korean individuals. Recognizing and managing patient perceptions is crucial for effective fall prevention, requiring both healthcare provider awareness and active participation from patients and caregivers., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Claudin 18.2 (CLDN18.2) is a promising target for targeted therapies in gastric cancer (GC). This study investigated the prevalence of CLDN18.2 expression in patients with stages II-IV GC or gastroesophageal junction (GEJ) adenocarcinoma and its correlation with clinicopathologic features and other crucial GC biomarkers., Methods: We enrolled 1000 patients diagnosed with stages II-IV GC after surgical treatment. Immunohistochemistry for CLDN18 (43-14A clone), PD-L1 (22C3 pharmDx), HER2, and FGFR2 was performed. CLDN18.2 positivity was defined as moderate-to-strong (2+/3+) membranous staining in ≥75% of tumor cells. CLDN18.2 expression was compared with biomarker expression, Epstein-Barr virus (EBV) association and microsatellite instability status, and clinicopathologic features., Result: CLDN18.2 was positive in 34.4% of the patients. CLDN18.2 positivity was significantly higher in the middle and upper thirds than in the lower third gastric location (P < .001), but there was no correlation with age, sex, or stage (P > .05). CLDN18.2 positivity was rare (2.8%) in mucinous adenocarcinoma but frequent (90.9%) in a majority of gastric carcinomas with lymphoid stroma. CLDN18.2 positivity was higher in EBV-associated (P < .001) and PD-L1-positive (PD-L1 CPS ≥ 5) GC (P = .014) but lower in HER2 positive GC (P = .005). CLDN18.2 positivity was not significantly associated with overall survival and disease-free survival., Conclusion: This study provides a comprehensive evaluation of CLDN18.2 status and its correlation with the clinicopathologic characteristics of patients with stages II-IV GC in Korea and with crucial biomarkers. It may be valuable for guiding future drug development, expanding treatment options, and ultimately improving patient outcomes in GC., (© The Author(s) 2024. Published by Oxford University Press.)

17 α -methyltestosterone (MT) is a synthetic steroid used to induce masculinization when administered during the larval stage of fish. However, the side effects of MT on eel are still poorly understood and, in this study, we examined the various effects of MT on juvenile eel A. japonica (100.63 ± 8.56 mm total length (TL)). To further investigate growth and sex differentiation, juvenile eels ( n = 1000) were exposed to 25 µg/g MT for 6 months. We analyzed growth-related factors, sex steroid hormones, skin pigmentation, and color-related gene expression. Through this study, we found a 90% sex conversion of juvenile eels to males using MT treatment. In the MT-treated eel group (285.97 ± 26.21 mm TL) where sexual maturity was induced, spermatogonia stages were observed in the gonads. In contrast, the control group (395.97 ± 27.72 mm TL) exhibited an 80% immaturity rate, with only 20% of the subjects that were rapidly developing displaying early oogonia. ELISA analysis results showed that the level of growth hormone, which is known to be secreted from spermatogonia, did not change as a result of MT treatment. We confirmed that MT delayed growth and caused morphological changes, particularly a shortened snout length and pigmentation of the fin. The total length, body weight, and snout length were considerably lower in the experimental group than in the control group. In addition, in histological analysis we also observed that some of the MT-treated group (5 out of 10 fish) showed liver atrophy and inflammation, and physiological analysis showed that the cortisol concentration increased in the MT-treated eels. Interestingly, we found that some pigment color-related genes, such as melanocortin 1 receptor (MC1R), tyrosinase (Tyr), and dopachrome tautomerase (DCT), were significantly overexpressed in the fins of MT-treated eels. These results suggest that the treatment of A. japonica larvae with MT induced masculinization but also causes growth side effects from the use of synthetic hormones.

Glial cells play a significant role in maintaining brain homeostasis and normal brain development, and their functions can be impaired by exposure to endocrine disruptors. 4-n-Nonylphenol (NP), a representative endocrine disruptor, is widely used in personal care products and industrial materials. NP accumulates in various organs, including the brain, of living organisms and adversely influences brain health. However, studies on the effects of NP on glial cells are limited. This study aims to investigate the effects of NP on glial cells using primary mixed glial cells and offspring mice exposed to NP during gestation and lactation. In vitro experiments revealed that NP exposure stimulated the astrocytes and microglia proliferation but not oligodendrocytes. NP exposure activated microglia and reduced myelin protein expression in oligodendrocytes. Moreover, maternal NP exposure increased the numbers of microglia and oligodendrocytes in the cerebral cortex of adult offspring. NP exposure caused anxiety- and depressive-like behaviors in adult mice. Collectively, these findings suggest that maternal NP exposure negatively affects the brain development in adult offspring mice., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Sialylation during N-glycosylation plays an important role in the half-life of therapeutic glycoproteins in vivo and has sparked interest in the production of therapeutic proteins using recombinant Chinese hamster ovary (rCHO) cells. To improve the sialylation of therapeutic proteins, we examined the effect of sialyllactose supplementation on sialylation of Fc-fusion glycoproteins produced in rCHO cells. Two enzymatically-synthesized sialyllactoses, 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL), were administered separately to two rCHO cell lines producing the same Fc-fusion glycoprotein derived from DUKX-B11 and DG44, respectively. Two sialyllactoses successfully increased sialylation of Fc-fusion glycoprotein in both cell lines, as evidenced by isoform distribution, sialylated N-glycan formation, and sialic acid content. Increased sialylation by adding sialyllactose was likely the result of increased amount of intracellular CMP-sialic acid (CMP-SA), the direct nucleotide sugar for sialylation. Furthermore, the degree of sialylation enhanced by sialyllactoses was slightly effective or nearly similar compared with the addition of N-acetylmannosamine (ManNAc), a representative nucleotide sugar precursor, to increase sialylation of glycoproteins. The effectiveness of sialyllactose was also confirmed using three commercially available CHO cell culture media. Taken together, these results suggest that enzymatically-synthesized sialyllactose represents a promising candidate for culture media supplementation to increase sialylation of glycoproteins in rCHO cell culture., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: India ink has been a popular choice for a tattooing agent in preoperative endoscopic localization but often results in unfavorable effects. Subsequently, autologous blood tattooing has arisen as an alternative option. Due to the limited availability of comparative studies on the matter, we conducted a study to compare the perioperative outcomes associated with India ink tattooing versus autologous blood tattooing., Methods: A total of 96 patients who underwent minimally invasive surgical procedures for left-sided colonic neoplasm following preoperative endoscopic localization were included in the study. These patients were categorized into two groups: 36 patients who received India ink tattooing and 60 patients who underwent autologous blood tattooing. The perioperative outcomes including procedure-related outcomes and postoperative outcomes were compared between the two groups., Results: There was no significant difference in visibility and spillage of tattooing agent between India ink group and autologous blood group. However, India ink group showed a higher incidence of post-tattooing fever, higher level of postoperative C-reactive protein level, longer time to first flatus, resumption of surgical soft diet, and duration of hospital stay, and a higher occurrence of postoperative complications including ileus and surgical site infection compared with the autologous blood group. In the multivariate analysis, India ink tattooing was significantly associated with the occurrence of postoperative complications. In the subgroup analysis involving patients with intraperitoneal spillage, the autologous blood group demonstrated significantly favorable perioperative outcomes compared with India ink group., Conclusions: Autologous blood tattooing demonstrated comparable visibility and enhanced safety, establishing it as a potential alternative to India ink for preoperative endoscopic localization., (© 2024. Springer Nature Switzerland AG.)

Combinatorial interactions between different regulators diversify and enrich the chance of transcriptional regulation in eukaryotic cells. However, a dose-dependent functional switch of homologous transcriptional repressors has rarely been reported. Here, we show that SHY2, an auxin/indole-3-acetic acid (Aux/IAA) repressor, exhibits a dose-dependent bimodal role in auxin-sensitive root-hair growth and gene transcription in Arabidopsis, whereas other Aux/IAA homologs consistently repress the auxin responses. The co-repressor (TOPLESS [TPL])-binding affinity of a bimodal Aux/IAA was lower than that of a consistently repressing Aux/IAA. The switch of a single amino acid residue in the TPL-binding motif between the bimodal form and the consistently repressing form switched their TPL-binding affinity and transcriptional and biological roles in auxin responses. Based on these data, we propose a model whereby competition between homologous repressors with different co-repressor-binding affinities could generate a bimodal output at the transcriptional and developmental levels., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Importance: Carbapenem-resistant Enterobacteriaceae are emerging as a global public health risk. Therefore, assessing the prevalence of carbapenem-resistant Escherichia coli (CRE) in both humans and animals is important., Objective: We aimed to ascertain the occurrence and characteristics of CRE isolated from companion animals, dogs and cats., Methods: E. coli strains were tested for antimicrobial susceptibility using the broth microdilution technique. Antimicrobial resistance genes were detected by polymerase chain reaction and sequencing analysis. The molecular characteristics of CRE were determined using multi-locus sequence typing, replicon typing, and pulsed-field gel electrophoresis (PFGE)., Results: In total, 13 CRE isolates (0.13%) were identified from dogs possessing bla NDM-5 along with β-lactamase genes, mostly bla CMY-2 (92.2%) and bla TEM-1 (53.8%). The commonly observed mutations were S83L and D87N in gyrA , S80I in parC , and S458A in parE . CRE carried non-beta-lactam resistance genes, with the majority being tet (B) (100%), sul (84.6%), and aac(3)-II (53.8%). Nine different PFGE patterns (P1-P9), IncX3-type plasmids (69.2%), and ST410 (84.6%) were predominantly detected., Conclusions and Relevance: This investigation provides significant insight into the prevalence and molecular characteristics of bla NDM-5 -carrying E. coli in dogs. The co-existence of bla NDM-5 and other antimicrobial resistance genes in E. coli potentially poses severe health hazards to humans., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

Purpose: To investigate the form and level of daily caffeine intake recommended above 400 mg in medical students expected to consume caffeinated beverages to enhance their performance., Methods: From May to June 2023, freshman through senior medical students at a medical school in Korea were administered a seven-item questionnaire designed to measure the amount of caffeine-containing foods consumed, the weekly interval between consumption, the reason for consumption, and the level of caffeine-induced symptoms experienced., Results: Out of 443 students, 361 responded (81.5%). The most commonly consumed caffeine beverages were coffee (79.2%), followed by soda (33.2%), tea (27.4%), chocolate (25.2%), and energy drinks (20.5%). The estimated (average±standard deviation) daily intake was estimated to 274.6±276.5 mg, and they consumed caffeine on an average of 4.25±2.26 days per week. Students who consumed 400 mg or more of caffeine daily consumed 19.9%. The primary motivation for caffeine intake was "to improve academic performance" (60.9%) and "preferred food" (51.8%). Among the responders, 98% of them replied they had symptoms that could be caused by caffeine, in order of palpitations (47.4%), frequent urination (42.9%), anxiety (27.1%), indigestion (17.5%), and excitement (17.5%). A total of 45.7% reported two symptoms, and 24.7% reported three or more., Conclusion: Caffeinated beverage consumption was routine among current medical students, with 20% consuming more than the recommended daily amount. Most students experienced at least one caffeine-induced symptom, with two symptoms in half, suggesting the need for policy measures and warnings about caffeine-containing foods.