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Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation in the synovial lining of the joints. Key inflammatory cytokines such as interleukin-6 (IL-6), TNF-α, and others play a critical role in the activation of local synovial leukocytes and the induction of chronic inflammation. Tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, has demonstrated significant clinical efficacy in treating RA patients. However, similar to other inflammatory cytokine blockers, such as TNF-alpha inhibitors, Interleukin-1 inhibitors, or CD20 inhibitors, some patients do not respond to treatment. To address this challenge, our study employed a high-precision proteomics approach to identify protein biomarkers capable of predicting clinical responses to Tocilizumab in RA patients. Through the use of data-independent acquisition (DIA) mass spectrometry, we analyzed serum samples from both TCZ responders and non-responders to discover potential biomarker candidates. These candidates were subsequently validated using individual serum samples from two independent cohorts: a training set (N = 70) and a test set (N = 18), allowing for the development of a robust multi-biomarker panel. The constructed multi-biomarker panel demonstrated an average discriminative power of 86 % between response and non-response groups, with a high area under the curve (AUC) value of 0.84. Additionally, the panel exhibited 100 % sensitivity and 60 % specificity. Collectively, our multi-biomarker panel holds promise as a diagnostic tool to predict non-responders to TCZ treatment in RA patients., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The most common mutation in southern Chinese individuals with late-onset multiple acyl-coenzyme A dehydrogenase deficiency (MADD; a fatty acid metabolism disorder) is c.250G > A (p.Ala84Thr) in the electron transfer flavoprotein dehydrogenase gene (ETFDH). Various phenotypes, including episodic weakness or rhabdomyolysis, exercise intolerance, and peripheral neuropathy, have been reported in both muscular and neuronal contexts. Our cellular models of MADD exhibit neurite growth defects and excessive apoptosis. Given that axonal degeneration and neuronal apoptosis may be regulated by B-cell lymphoma (BCL)-2 family proteins and mitochondrial outer membrane permeabilization through the activation of proapoptotic molecules, we measured the expression levels of proapoptotic BCL-2 family proteins (e.g., BCL-2-associated X protein and p53-upregulated modulator of apoptosis), cytochrome c, caspase-3, and caspase-9 in NSC-34 cells carrying the most common ETFDH mutation. The levels of these proteins were higher in the mutant cells than in the wide-type cells. Subsequent treatment of the mutant cells with coenzyme Q10 downregulated activated protein expression and mitigated neurite growth defects. These results suggest that the activation of the BCL-2/mitochondrial outer membrane permeabilization/apoptosis pathway promotes apoptosis in cellular models of MADD and that coenzyme Q10 can reverse this effect. Our findings aid the development of novel therapeutic strategies for reducing axonal degeneration and neuronal apoptosis in MADD., (© 2024. The Author(s).)

Objective: To elucidate the impact of poor prognostic factors (PPFs) in daily practice on achieving remission and the requirement for biologic or targeted synthetic DMARDs (b/tsDMARDs) in a large Korean cohort of patients with rheumatoid arthritis (RA)., Methods: Using the KORean Observational study Network for Arthritis (KORONA) database, patients with RA were categorized into three groups based on the number of PPFs (0-1, 2, or≥3): the presence of functional limitation, extra-articular disease, seropositivity, and bone erosions. Factors related to achieving remission and to initiating b/tsDMARDs were evaluated using Cox proportional hazard regression analyses after adjusting confounders., Results: Among 5076 patients with RA, group L (PPF≤1), group M (PPFs 2), and group H (PPFs≥3) were 1788 (35.2%), 2027 (39.9%), and 1261 (24.9%), respectively. Group H had higher disease activity and worse patient-reported outcomes than groups L and M. Among moderately-to-highly active patients at baseline, group H was significantly less likely to attain point (hazard ratio [HR]=0.55, 95% confidence interval [CI] 0.38-0.79) and sustained (HR=0.45, 95% CI 0.21-0.99) Boolean-based remission in 5-year. Groups M (HR=1.47, 95% CI 1.10-1.96) and H (HR=1.69, 95% CI 1.22-2.32) had an increased risk of escalation to b/tsDMARDs, compared to group L among b/tsDMARDs-naïve patients at baseline., Conclusion: Achieving remission was particularly challenging for group H, and more patients in groups M and H initiated b/tsDMARDS during the 5-year observation period. Therefore, the presence of PPFs≥3 significantly influences both patients' outcomes and clinician's treatment decisions regardless of disease activity., (Copyright © 2024 Sociýtý Franýaise de Rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Prime editing (PE) enables almost all types of precise genome editing in animals and plants. It has been successfully adapted to edit several plants with variable efficiency and versatility. However, this technique is inefficient for dicots for unknown reasons. Here, using new combinations of PE components, including an RNA chaperone and altered engineered prime editing guide RNAs driven by a PolII-PolIII composite promoter and a viral replicon system, we obtained up to 9.7% of the desired PE efficiency at the callus stage as assessed by targeted deep sequencing. Subsequently, we identified that up to 38.2% of transformants contained desired PE alleles in tomatoes and Arabidopsis, marking successful heritable PE transmission. Our PE tools also showed high accuracy, specificity and multiplexing capability, which unlocked the potential for practical PE applications in dicots, paving the way for transformative advancements in plant sciences., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In this study, the effects of Cl 2 radicals on dry development of spin-coated metal oxide resist (MOR) and changes in its surface binding states were investigated to verify the mechanism of dry development. Dry development characteristics of tin hydroxide (Tin OH), which is one of the MOR candidates for next generation lithography, were investigated as functions of process time and temperature using a Cl 2 radicals source. Non-UV-exposed Tin OH film showed a linear etch rate (1.77 nm/min) from the initial thickness of ∼50 nm, while the UV-exposed film showed slower etch behavior (1.46 nm/min) in addition to the increase of film thickness for up to 3 min during the Cl 2 radical dry development. UV-exposed photoresist (PR) contained more oxygen (Sn-O bonding) in the film due to the removal of butyl compounds from the clusters during the UV exposure process. Therefore, due to the lower reaction of chlorine radicals with Sn-O in the UV-exposed Tin OH than the other bindings, the non-UV-exposed PR was preferentially removed compared to the UV-exposed PR. As the temperature decreases, the overall etch rate decreases, but the difference in etch rate between exposed and unexposed Tin OH becomes larger. Finally, at a substrate temperature of -20 °C, the non-UV-exposed Tin OH with a thickness of 50 nm was completely removed, while ∼30 nm thick PR remained for UV-exposed Tin OH. Eventually, a negative tone development was possible with Cl 2 radical plasma due to the difference in activation energy between the UV-exposed and non-UV-exposed films. It is believed that dry development using Cl 2 radicals will be one of the most important process techniques for next-generation patterning to remove problems such as pattern leaning, line edge roughness, residue, etc., caused by wet development.

Absolute quantity imaging of biomolecules on a single cell level is critical for measurement assurance in biosciences and bioindustries. While infrared (IR) transmission microscopy is a powerful label-free imaging modality capable of chemical quantification, its applicability to hydrated biological samples remains challenging due to the strong IR absorption by water. Traditional IR imaging of hydrated cells relies on powerful light sources, such as synchrotrons, to mitigate the light absorption by water. However, we overcome this challenge by applying a solvent absorption compensation (SAC) technique to a home-built benchtop IR microscope based on an external-cavity quantum cascade laser. SAC-IR microscopy adjusts the incident light using a pair of polarizers to precompensate the IR absorption by water while retaining the full dynamic range. Integrating the IR absorbance over a cell yields the total mass of biomolecules per cell. We monitor the total mass of the biomolecules of live fibroblast cells over 12 h, demonstrating promise for advancing our understanding of the biomolecular processes occurring in live cells on the single-cell level.

Introduction: Colorectal cancer (CRC) represents a significant health burden worldwide, with a notable increase in early-onset colorectal cancer (EOCRC) cases, defined as those diagnosed before the age of 50 years., Materials and Methods: Using data from Taiwan's national cancer registry and a retrospective cohort from Chang Gung Memorial Hospital, this study analyzed CRC cases diagnosed between 2008 and 2019. The analysis compared the EOCRC and late-onset CRC (LOCRC) groups in terms of clinicopathological characteristics, pre-diagnostic symptoms, and survival outcomes., Results: The analysis revealed a continuous increase in the annual incidence of EOCRC, with colon cancer and rectal cancer rising by 3.2 % and 3.3 %, respectively. Patients with EOCRC presented with more aggressive disease characteristics, such as signet-ring cell adenocarcinoma, mucinous adenocarcinoma, and poorly differentiated grade. Advanced stages at diagnosis, stages III and IV, were more common with EOCRC (62.4 %) than with LOCRC (50.3 %). Patients with EOCRC reported rectal bleeding, changes in bowel habits, and abdominal pain more frequently than those in the LOCRC group. There is a strong association between stool-related symptoms and left-sided CRC. Despite similar surgical outcomes, the 5-year cancer-specific survival rate of patients with stage IV EOCRC was significantly lower than that of patients with LOCRC (32.8 % vs. 51.9 %, p = 0.012)., Conclusion: This study highlights a persistent rise in the incidence of EOCRC, with patients presenting with more aggressive disease and experiencing inferior survival. These findings underscore the importance of heightened awareness and early detection strategies for CRC, especially in younger populations, to improve the prognosis., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Conventional minimally invasive surgery requires mini-laparotomy to extract the pathological specimen. However, by using a natural orifice as the delivery route, natural orifice specimen extraction (NOSE) surgery avoids the need for a large incision. This study analyzed the short-term outcome of NOSE compared with conventional mini-laparotomy (CL) for colorectal cancer surgery., Methods: We conducted a retrospective analysis of 1,189 patients who underwent surgery for primary colorectal cancer between the cecum and upper rectum. Propensity score analyses were applied to the NOSE and CL groups in a 1:1 matched cohort., Results: After propensity score matching, each group included 201 patients. The NOSE group and CL group did not differ significantly in terms of baseline characteristics. Postoperative morbidity and mortality rates were comparable. Compared with the CL group, the NOSE group experienced a shorter time to first flatus (1.6 ± 0.8 vs. 2.0 ± 1.2 days, p < 0.001), first stool (2.7 ± 1.5 vs. 4.1 ± 1.9, p < 0.001), liquid diet (2.3 ± 1.3 vs. 3.6 ± 1.8 days, p < 0.001), soft diet (3.9 ± 2.0 vs. 5.2 ± 1.9 days, p < 0.001) and a shorter hospital stay (5.1 ± 3.5 vs. 7.4 ± 4.8 days, p < 0.001). The NOSE group exhibited lower mean pain intensity and lower highest pain intensity on postoperative days 1, 2, and 3., Conclusion: NOSE has several advantages over conventional mini-laparotomy following minimally invasive surgery for colon cancer. These advantages include reduced time to oral intake, shorter hospital stays, and less postoperative pain. NOSE can be adopted and applied to highly selective patients without additional risk of short-term complications., (© 2024. The Author(s).)

Objectives: To compare the risk of urolithiasis in gout patients initiating allopurinol, a xanthine oxidase inhibitor, vs benzbromarone, a uricosuric., Methods: Using the 2011-20 Korea National Health Insurance Service database, we conducted a cohort study on gout patients initiating allopurinol vs benzbromarone as the first-line urate-lowering treatment. The primary outcome was a new onset urinary stone. The secondary outcome was a stone requiring intervention. We estimated hazard ratios (HRs) and 95% CIs using Cox proportional hazard models with a 5:1 ratio propensity-score matching on >80 variables. Subgroup analyses were done by age, sex, thiazide use and cardiovascular risk., Results: 61 300 allopurinol initiators PS-matched on 12 260 benzbromarone initiators were included (mean age 59 years, 79% male). During a mean follow-up of 322 days, 619 urolithiasis cases occurred with an incidence rate of 0.87 per 100 person-years in allopurinol and 1.39 in benzbromarone initiators, showing a HR of 0.64 (95% CI, 0.51-0.80). Approximately 44% of urinary stones required intervention with a HR of 0.61 (95% CI, 0.43-0.88). The lower risk associated with allopurinol compared with benzbromarone persisted across subgroups but was greater in the high than non-high cardiovascular risk subgroup (P for interaction = 0.02)., Conclusion: This population-based cohort study found that allopurinol compared with benzbromarone was associated with a substantially lower risk of urolithiasis particularly in the presence of the high cardiovascular risk. This finding provides important safety information for clinicians' decision-making on urate-lowering treatments of different mechanisms of action., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Economic deprivation is expected to influence cancer mortality due to its impact on screening and treatment options, as well as healthy lifestyle. However, the relationship between insurance type, premiums, and mortality rates remains unclear. This study investigated the relationship between insurance type and mortality in patients with newly diagnosed cancer using data from the Korean National Health Insurance Database., Methods: this retrospective cohort study included 111,941 cancer patients diagnosed between 1 January 2007 and 31 December 2008, with a median follow-up period of 13.41 years. The insurance types were categorized as regional and workplace subscribers and income-based insurance premiums were divided into tertiles (T1, T2, and T3)., Results: Cox proportional hazards regression analysis adjusted for age, lifestyle factors, health metrics, and comorbidities showed workplace subscribers ( n = 76,944) had a lower all-cause mortality hazard ratio (HR) (95% confidence interval [CI]: 0.940 [0.919-0.961]) compared to regional subscribers ( n = 34,997). Higher income tertiles (T2, T3) were associated with lower mortality compared to the T1 group, notably in male regional and workplace subscribers, and female regional subscribers., Conclusion: The study identified that insurance types and premiums significantly influence mortality in cancer patients, highlighting the necessity for individualized insurance policies for cancer patients.

Glycans are oligosaccharides attached to proteins or lipids and affect their functions, such as drug efficacy, structural contribution, metabolism, immunogenicity, and molecular recognition. Conventional glycosylation analysis has relied on destructive, slow, system-sensitive methods, including enzymatic reactions, chromatography, fluorescence labeling, and mass spectrometry. Herein, we propose quantum cascade laser (QCL) infrared (IR) spectroscopy as a rapid, nondestructive method to quantify glycans and their monosaccharide composition. Previously, we demonstrated high-sensitivity IR spectroscopy of protein solution using solvent absorption compensation (SAC) and double-beam modulation (DBM) techniques. However, the SAC-DBM approach suffered a limited frequency scanning range (<400 cm -1 ) due to the light dispersion by acousto-optic modulators (AOMs). Here, we implemented a mirror-based double-pass AOM in the SAC-DBM scheme and successfully extended the frequency range to (970 to 1840 cm -1 ), which encompasses the vibrational fingerprint of biomolecules. The extended frequency range allowed the simultaneous observation of monosaccharide ring bands (1000 to 1200 cm -1 ) and protein amide bands (1500 to 1700 cm -1 ). We compared the IR spectra of six glycoproteins and two nonglycosylated proteins with the results from intact mass spectrometry. The IR absorbance ratios of the ring band to the amide band of glycoproteins in solutions showed a linear correlation with the ratios of glycan to protein backbone masses. Furthermore, a multivariate analysis produced monosaccharide compositions consistent with the reported database for the glycoproteins, and the monosaccharide compositions were used to improve the predictability of the glycan-protein mass ratio from the IR-absorbance ratio. This nondestructive, high-sensitivity QCL-IR spectroscopy could be used as a standard method to monitor batch-to-batch comparability during drug manufacturing and quantify the glycosylation and monosaccharide composition of new glycoproteins and other glycosylated biosystems.

Fungi have historically been the source of numerous important medicinal compounds, but full exploitation of their genetic potential for drug development has been hampered in traditional discovery paradigms. Here we describe a radically different approach, top-down drug discovery (TD 3 ), starting with a massive digital search through a database of over 100,000 fully genomicized fungi to identify loci encoding molecules with a predetermined human target. We exemplify TD 3 by the selection of cyclin-dependent kinases (CDKs) as targets and the discovery of two molecules, 1 and 2 , which inhibit therapeutically important human CDKs. 1 and 2 exhibit a remarkable mechanism, forming a site-selective covalent bond to the CDK active site Lys. We explored the structure-activity relationship via semi- and total synthesis, generating an analog, 43 , with improved kinase selectivity, bioavailability, and efficacy. This work highlights the power of TD 3 to identify mechanistically and structurally novel molecules for the development of new medicines.

Alveolar bone grafting (ABG) in bilateral cleft lip and palate (BCLP) patients provides a reconstructive challenge. We present a novel technique of combining autologous iliac crest bone graft (ICBG) with recombinant human bone morphogenic protein 2 (rhBMP-2) and cellular bone matrix (CBM) for ABG in BCLP patients. Complete bone fill occurred in 90% of patients, with 100% having bilateral canine eruption. No patients required repeat ABG, and no significant complications were reported. The alveolar cleft gap volume significantly decreased with an improvement of 75.87%. ABG with autologous ICBG with rhBMP-2 and CBM is an effective technique for patients with BCLP., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: This study aimed to investigate the risk of epilepsy after transient global amnesia (TGA)., Methods: Study population was recruited using the International Classification of Diseases codes from the Korean National Health Insurance Service database between 2002 and 2020. The incidence of epilepsy was compared between the TGA (n=12,390) and non-TGA (n=33,868) groups, determined using 1:3 propensity score matching. Using Cox proportional hazard regression model, we obtained adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident epilepsy in the TGA compared with non-TGA group. Logistic regression was performed to examine the independent variables determining incident epilepsy in the TGA group, and adjusted odds ratios (aORs) and 95% CIs were calculated., Results: The TGA group had a significantly higher cumulative incidence of epilepsy than controls (p <0.001, log-rank test). TGA was significantly associated with incident epilepsy in the Cox model (adjusted HR 1.46, 95% CI 1.36-1.56). The adjusted logistic regression showed that age (per 1 year, aOR 1.02, 95% CI 1.01-1.02), female sex (aOR 0.68, 95% CI 0.60-0.77), hypertension (aOR 1.14, 95% CI 1.00-1.30), diabetes (aOR 1.26, 95% CI 1.10-1.44), stroke (aOR 1.22, 95% CI 1.06-1.40), depression (aOR 1.44, 95% CI 1.22-1.69), anxiety (aOR 1.31, 95% CI 1.14-1.51), alcohol-related disease (aOR 1.96, 95% CI 1.38-2.78), low income (aOR 1.18, 95% CI 1.02-1.36) and rural residence (aOR 1.20, 95% CI 1.02-1.42) were associated with incident epilepsy., Conclusions: Our results suggest a longitudinal association of TGA with incident epilepsy., Competing Interests: Conflict of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Insufficient evidence exists to ascertain the long-term prognosis in patients with obesity undergoing laparoscopic surgery versus open surgery for colorectal cancer., Methods: Employing an institutional database from 2009 to 2019, we assessed individuals with a BMI of greater than or equal to 30 kg/m 2 who underwent surgery for primary stage I-III colorectal adenocarcinoma. The authors used propensity score-weighted analysis to compare short-term and oncologic outcomes between laparoscopic and open surgical approaches., Results: This study enrolled 473 patients (open vs. laparoscopic surgery: 220 vs. 253; median follow-up period, 60 months). The laparoscopy group showed a significantly longer operative time (252 vs. 212 min), a higher anastomotic-leakage rate (5.14% vs. 0.91%), and a greater proportion of Clavien-Dindo class greater than III complications (5.93% vs. 1.82%). The open group showed a higher wound infection rate (7.27% vs. 3.16%) and a higher readmission rate (6.36% vs. 2.37%). After propensity score weighting, laparoscopy was inferior to open surgery in terms of long-term overall survival (hazard ratio: 1.43), disease-free survival (1.39), and recurrence rate (21.1% vs. 14.5%). In the subgroup analysis, female patients, older individuals, stage III patients, patients with rectal cancer, and those who underwent surgery after 2014 showed inferior long-term outcomes after laparoscopy., Conclusions: Laparoscopic colorectal cancer surgery for patients with obesity requires significant caution. Despite good short-term outcomes, this procedure is associated with hidden risks and poor long-term prognoses. In female patients, older individuals, stage III patients, patients with rectal cancer, and those treated in the late surgery era subgroups, caution is advised when performing laparoscopic surgery., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Agrobacterium -mediated transformation remains a cornerstone of plant biology, fueling advancements in molecular genetics, new genomic techniques (NGTs), and the biotech industry. However, recalcitrant crops and technical hurdles persist as bottlenecks. The goal was to develop super-infective ternary vector systems that integrate a novel salicylic acid-degrading enzyme, GABA, and ethylene-degrading enzymes, targeting the transformation of crops by neutralizing plant defense system on Agrobacterium . Firstly, both the effect and activity of introducing enzymes were validated in EHA105, an important Agrobacterium strain. Our study demonstrates that all ternary vector (Tv) system variants significantly enhance reporter expression in transient assays with Nicotiana benthamiana and Cannabis sativa . Specifically, incorporating a constitutive virG mutation with novel enzyme combinations increased GFP and RUBY expression in C. sativa by >5-fold and 13-fold, respectively. The Tv system, combined with a geminivirus replicon, markedly boosted GUS gene expression in tomato, enhancing genome editing efficiency. Notably, compared to controls, Tv-VS demonstrated up to 18-fold and 4.5-fold increases in genome editing efficiency in C. sativa and tomato, respectively. Additionally, stable transformation rates in tomato and Arabidopsis improved significantly, with Tv-VS showing a remarkable 2.5-fold increase in transformation efficiency compared to control strains. The research marks notable progress in Agrobacterium -mediated plant transformation. The innovative ternary vectors overcome plant defense mechanisms, enabling genetic manipulation in previously challenging plant species. This development is anticipated to broaden the applications of plant genetic engineering, contributing to advancements in crop genome editing., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Background/aims: This cross-sectional study aimed to investigate biologics treatment disparities in rheumatoid arthritis (RA) patients based on socioeconomic status (SES)., Methods: Data from the KOrean Observational Study Network for Arthritis (KORONA) database were analyzed to assess various factors associated with SES, health behaviors, and biologics use. Logistic regression and structured equation modeling (SEM) were utilized for data analysis., Results: Among 5,077 RA patients included, 393 (7.7%) patients were identified as biologics users. Within the entire cohort, 31.8% of the participants were in the low-income and low-education groups, and 39.3% of the participants were in the high-income and high-education groups. Despite the patients with low income or low education experienced higher disease activity at diagnosis, had more comorbidities, exhibited higher medication compliance, underwent more check-ups, and had more hospital admissions than their counterparts, the odds of patients with low-income receiving biologics were 34% lower (adjusted odds ratio = 0.76, 95% confidence interval: 0.60-0.96, p = 0.021) after adjustment for demographics and comorbidities. SEM and pathway analyses confirmed the negative impact of low SES on biologics use., Conclusion: The findings suggest that SES plays a significant role in biologics use among RA patients, indicating potential healthcare inefficiencies for low SES patients. Moreover, adverse healthcare habits negatively affect biologics use in RA patients. The study highlights the importance of considering socioeconomic factors while discussing biologics use and promoting equitable access to biologics for optimal RA management.

Neuro-Behçet's disease (NBD) represents a significant complication of Behçet's syndrome, potentially leading to elevated mortality and disability rates. The standard treatment for parenchymal NBD typically entails administering high-dose corticosteroids to prompt rapid-onset effects, coupled with immunosuppressants to prevent subsequent relapses. A 48-year-old male with NBD presented with progressively worsening dysarthria over 9 months. This patient experienced increased intraocular pressure while using glucocorticoids, which worsened his pre-existing glaucoma. The patient had a prior diagnosis of NBD and presented with progressive dysarthria over a period of nine months, leading to a brain magnetic resonance imaging (MRI) scan. The brain MRI revealed multifocal punctate high signal intensities in the left frontoparietal area, insula, and basal ganglia. Instead of the standard steroid pulse therapy, the patient received adalimumab-cyclophosphamide combination as an alternative induction therapy. Subsequent serial brain MRI scans exhibited no emergence of new lesions, and the patient remained devoid of clinical relapses even after 17 months from the commencement of induction treatment. Adalimumab-cyclophosphamide combination could be used as a corticosteroid-free induction strategy for NBD. Further investigations are warranted to establish the most suitable combination regimen., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean College of Rheumatology. All rights reserved.)

Purpose: To date, there is no region-specific guideline for pediatric endoscopy training. This study aimed to illustrate the current status of pediatric endoscopy training in Asia-Pacific region and identify opportunities for improvement., Methods: A cross-sectional survey, using a standardized electronic questionnaire, was conducted among medical schools in the Asia-Pacific region in January 2024., Results: A total of 57 medical centers in 12 countries offering formal Pediatric Gastroenterology training programs participated in this regional survey. More than 75% of the centers had an average case load of <10 cases per week for both diagnostic and therapeutic endoscopies. Only 36% of the study programs employed competency-based outcomes for program development, whereas nearly half (48%) used volume-based curricula. Foreign body retrieval, polypectomy, percutaneous endoscopic gastrostomy, and esophageal variceal hemostasis, that is, sclerotherapy or band ligation (endoscopic variceal sclerotherapy and endoscopic variceal ligation), comprised the top four priorities that the trainees should acquire in the autonomous stage (unconscious) of competence. Regarding the learning environment, only 31.5% provided formal hands-on workshops/simulation training. The direct observation of procedural skills was the most commonly used assessment method. The application of a quality assurance (QA) system in both educational and patient care (Pediatric Endoscopy Quality Improvement Network) aspects was present in only 28% and 17% of the centers, respectively., Conclusion: Compared with Western academic societies, the limited availability of cases remains a major concern. To close this gap, simulation and adult endoscopy training are essential. The implementation of reliable and valid assessment tools and QA systems can lead to significant development in future programs., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2024 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

Objective: Giant cell arteritis (GCA) is a large-vessel vasculitis that primarily affects elderly individuals. However, data regarding Korean patients with GCA are scarce owing to its extremely low prevalence in East Asia. This study aimed to investigate the clinical characteristics of Korean patients with GCA and their outcomes, focusing on relapse., Methods: The medical records of 27 patients with GCA treated at three tertiary hospitals between 2007 and 2022 were retrospectively reviewed., Results: Seventeen (63.0%) patients were females, and the median age at diagnosis was 75 years. Large vessel involvement (LVI) was detected in 12 (44.4%) patients, and polymyalgia rheumatica (PMR) was present in 14 (51.9%) patients. Twelve (44.4%) patients had fever at onset. The presence of LVI or concurrent PMR at diagnosis was associated with a longer time to normalization of the C-reactive protein level (p=0.039) or erythrocyte sedimentation rate (p=0.034). During follow-up (median 33.8 months), four (14.8%) patients experienced relapse. Kaplan-Meier analyses showed that relapse was associated with visual loss (p=0.008) and the absence of fever (p=0.004) at onset, but not with LVI or concurrent PMR., Conclusion: Concurrent PMR and LVI were observed in approximately half of Korean patients with GCA, and the elapsed time to normalization of inflammatory markers in these patients was longer. The relapse rate in Korean GCA is lower than that in Western countries, and afebrile patients or patients with vision loss at onset have a higher risk of relapse, suggesting that physicians should carefully monitor patients with these characteristics., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean College of Rheumatology. All rights reserved.)

In this study, we introduce a novel method for stoma closure, aiming to reduce wound infection rates. This method involves creating the common channel of both limbs of a loop stoma extracorporeally, which is particularly beneficial during laparoscopic stoma closure surgery by potentially avoiding contamination of the wound. We applied this technique in 23 patients undergoing laparoscopic stoma reversal surgery, comprising both loop colostomy and ileostomy cases. Notably, postoperative outcomes were promising: only two patients experienced postoperative ileus, and importantly, there were no instances of wound infection. These findings suggest that our laparoscopic stoma reversal surgery approach is not only safe and feasible but also offers a significant advantage in reducing wound infection rates., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Marine dinoflagellate species in the genus Alexandrium are well known to produce paralytic shellfish poison as well as common coastal species with cosmopolitan distribution. However, few studies on the feeding of copepods on Alexandrium species have been conducted. The toxic dinoflagellate Alexandrium pseudogonyaulax contains goniodomin A and causes red tides in many countries. To investigate the relationship between the toxic dinoflagellate A. pseudogonyaulax and the calanoid copepods Acartia spp., we quantified the ingestion rates of Acartia spp. feeding on A. pseudogonyaulax as a function of prey concentration. Additionally, we estimated grazing coefficients by integrating data from field observations of Acartia spp. and coexisting A. pseudogonyaulax with laboratory measurements of ingestion rates obtained during this investigation. Furthermore, we compared the ingestion rates of Acartia spp. and other predators feeding on Alexandrium species as previously reported. The ingestion rates of Acartia spp. on A. pseudogonyaulax increased continuously with increasing mean prey concentration. The highest values among the ingestion rate of Acartia spp. feeding on A . pseudogonyaulax was 3,407 cells predator -1 d -1 (4,872 ng C predator -1 d -1 ) at the given prey concentration. The calculated grazing coefficients for Acartia spp. on A. pseudogonyaulax in Shiwha Bay, Korea, were up to 0.073 d -1 . The results of this study suggest that A. pseudogonyaulax may decrease or maintain the population of Acartia spp. in marine food webs., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Lee, Hwang, Choi and Yoo.)

The abnormal innate immune response is a prominent feature underlying autoimmune diseases. One emerging factor that can trigger dysregulated immune activation is cytosolic mitochondrial double-stranded RNAs (mt-dsRNAs). However, the mechanism by which mt-dsRNAs stimulate immune responses remains poorly understood. Here, we discover SRA stem-loop interacting RNA binding protein (SLIRP) as a key amplifier of mt-dsRNA-triggered antiviral signals. In autoimmune diseases, SLIRP is commonly upregulated, and targeted knockdown of SLIRP dampens the interferon response. We find that the activation of melanoma differentiation-associated gene 5 (MDA5) by exogenous dsRNAs upregulates SLIRP, which then stabilizes mt-dsRNAs and promotes their cytosolic release to activate MDA5 further, augmenting the interferon response. Furthermore, the downregulation of SLIRP partially rescues the abnormal interferon-stimulated gene expression in autoimmune patients' primary cells and makes cells vulnerable to certain viral infections. Our study unveils SLIRP as a pivotal mediator of interferon response through positive feedback amplification of antiviral signaling., Competing Interests: DECLARATION OF INTERESTS Jaeseon Lee, Soojin Jang, and Kyung Jin Lee are employees of ORGANOIDSCIENCES Ltd. Other authors have no conflict of interest to declare.

Pituitary adenoma-induced excess endocrine growth hormone (GH) secretion can lead to breast cancer development and metastasis. Herein, we used an acromegaly mouse model to investigate the role of excess endocrine GH on triple-negative breast cancer (TNBC) growth and metastasis. Additionally, we aimed to elucidate the molecular mechanism of transcription factor 20 (TCF20)/nuclear factor erythroid 2-related factor 2 (NRF2) signaling-mediated aggressiveness and metastasis of TNBC. Excess endocrine GH induced TCF20 activates the transcription of NRF2 and NRF2-target genes to facilitate TNBC metastasis. Inhibition of GH receptor (GHR) and TCF20 activity using the GHR antagonist or small-interfering RNA-induced gene knockdown resulted in reduced tumor volume and metastasis, suggesting that excess endocrine GH stimulates TCF20/NRF2 pathways in TNBC and promotes metastasis to the lung. GHR inhibitors present an effective therapeutic strategy to prevent TNBC cell growth and metastasis. Our findings revealed functional and mechanistic roles of the GH-TCF20-NRF2 signaling axis in TBNC progression., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify L-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest L-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy., (© 2024. The Author(s).)

Background: The comparative risk of cause-specific mortality in patients with Behçet disease (BD) vs. the general population is not known., Objectives: To compare the risk of all-cause and cause-specific mortality in patients with BD vs. the general population., Methods: Using data from the Korea National Health Insurance Service database for the period 2002-20, we conducted a cohort study comparing patients with BD with the general population, matched according to age and sex (1 : 4 ratio). We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality. Subgroup analyses by age and sex were done., Results: We included 24 669 patients with BD and 98 676 age- and sex-matched controls [mean (SD) age 40.5 (12.9) years; 34% male]. During a mean follow-up of 11.9 years, the incidence rate (IR) of death per 100 person-years was 0.36 in patients with BD and 0.29 in controls [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.20-1.38]. The risk of mortality was highest in the first year after BD diagnosis (HR 2.66, 95% CI 2.09-3.40). Patients with BD died more often in this period as a result of malignancy (HR 1.96, 95% CI 1.30-2.98); cardiovascular (HR 2.68, 95% CI 1.45-4.97), gastrointestinal (HR 3.50, 95% CI 1.35-9.07) and respiratory disease (HR 5.00, 95% CI 1.34-18.62); and infection (HR 3.33, 95% CI 1.02-10.92). Mortality as a result of neurological (HR 1.58, 95% CI 1.06-2.35) or genitourinary disease (HR 2.20, 95% CI 1.43-3.37) was also more common in patients with BD during the overall follow-up. Subgroup analyses showed consistent results. The risk of cardiovascular mortality vs. the general population was higher in younger patients (P = 0.006) and the risk of gastrointestinal mortality was increased in women vs. men (P = 0.04)., Conclusions: This population-based cohort study revealed that the first year after diagnosis is the highest risk period for excess mortality in people with BD. The mortality burden in BD derives from a wide spectrum of organ involvement and should serve as a warning to clinicians about the systemic nature of the disease., Competing Interests: Conflicts of interest This work was designed and conducted independently of the sponsor, and the authors attained the full right for the final wording., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Context: The association between colorectal cancer (CRC) and new-onset diabetes mellitus remains unclear., Objective: To examine the association between CRC and the risk of subsequent diabetes mellitus and to further investigate the impact of chemotherapy on diabetes mellitus risk in CRC., Design: A nationwide cohort study., Methods: Using the Taiwan Cancer Registry Database (2007-2018) linked with health databases, 86,268 patients with CRC and an equal propensity score-matched cohort from the general population were enrolled. Among them, 37,277 CRC patients from the Taiwan Cancer Registry (2007-2016) were analyzed for diabetes mellitus risk associated with chemotherapy. Chemotherapy exposure within 3 years of diagnosis was categorized as no chemotherapy, <90 days, 90-180 days, and >180 days. Differences in diabetes mellitus risk were assessed across these categories., Results: Each group involved 86,268 participants after propensity score matching. The patients with CRC had a 14% higher risk of developing diabetes mellitus than the matched general population (hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.09-1.20). The highest risk was observed within the first year after diagnosis followed by a sustained elevated risk. Long-term chemotherapy (>180 days within 3 years) was associated with a 60-70% increased risk of subsequent diabetes mellitus (HR: 1.64, 95% CI: 1.07-2.49)., Conclusion: Patients with CRC are associated with an elevated risk of diabetes mellitus, and long-term chemotherapy, particularly involving capecitabine, increases diabetes mellitus risk. Thus, monitoring blood glucose levels is crucial for patients with CRC, especially during extended chemotherapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: To investigate the long-term effects of taking 5-alpha reductase inhibitors (5ARIs) on the development of bladder cancer (BC) and the implementation of radical cystectomy (RC), a standard procedure for advanced BC., Materials and Methods: From the National Health Insurance Sharing Service database, males aged over 40 years who underwent serum prostate-specific antigen testing from 2006 through 2017 were identified, which is required for the prescription of 5ARIs. The association between the administration duration of 5ARIs and the practice for BC was analyzed., Results: Of the 3,843,968 subjects, 1,514,713 (39.4%) took 5ARIs for an average of 1.53 years, remaining 2,329,255 (60.6%) as non-5ARI counterparts. The incidence of BC was higher in the non-5ARI than in the 5ARI group (1.25% vs. 0.87%, p<0.001), as was the implementation rate of RC (11.1% vs. 10.4%, p=0.037). In a multivariate analysis, the non-5ARI group had a significant risk of BC (hazard ratio [HR]=2.289, 95% confidence interval [CI]=2.241-2.338) and RC (HR=2.199, 95% CI=2.061-2.348) than the 5ARI group. Among the 5ARIs group, though the incidence of BC was maintained (slope=-0.002 per year, p=0.79) after an initial increase for two years, the rate of RC decreased (slope=-1.1, p<0.001) consistently for ten years during the administration., Conclusions: Compared to the untreated group, 5ARIs use was associated with lower rates of BC and RC. In contrast to the increase in BC seen with short-term use of less than two years, long-term use of 5ARIs decreased the rate of RC in a duration-dependent manner for ten years, suggesting a strategy to prevent disease progression., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Background: Studies on prognostic factors for patients undergoing surgery to treat solitary liver metastases originating from colorectal cancer (CRC) are limited. This study aimed to analyze significant prognostic factors associated with tumor recurrence and long-term survival after liver resection for solitary colorectal liver metastasis., Methods: Data from 230 patients with solitary liver metastases from CRC who received liver resection between 2010 and 2019 were retrospectively analyzed. Recurrence-free survival (RFS) and overall survival (OS) were accessed with the Kaplan-Meier method and log-rank test. Cox regression multivariate analysis identified independent variables associated with RFS and OS. Nomograms were developed to predict patient outcomes after surgery., Results: The 3- and 5-year OS rates were 72.3% and 59.8%, respectively. The 3- and 5-year RFS rates were 40.0% and 27.1%, respectively. Multivariate analysis revealed age ≥ 70 years, resection margin width < 10 mm, initial N2 stage, hypoalbuminemia before surgery, and neutrophil-to-lymphocyte ratio (NLR) ≥ 3 after surgery as independent prognostic factors for OS. For RFS, initial N2 stage, hypoalbuminemia before surgery, NLR ≥ 3 after surgery, elevated carcinoembryonic antigen (CEA) levels after surgery, and CEA ratio (after/before liver resection) < 0.3 were identified as independent prognostic factors., Conclusion: This study demonstrated that initial N2 stage, hypoalbuminemia before liver resection, and NLR ≥ 3 after liver resection exert a significant association on the RFS and OS of patients undergoing surgery for solitary liver metastases from CRC. Thus, upfront chemotherapy, prompt postoperative chemotherapy, and intensive postoperative surveillance are mandatory for patients having these adverse factors., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Improving adherence to antihypertensive medication (AHM) is a key challenge in hypertension management. This study aimed to assess the impact of ambulatory blood pressure monitoring (ABPM) on AHM adherence., Methods: We utilized the Korean National Health Insurance Service database. Among patients newly diagnosed with hypertension who started AHM between July 2010 and December 2013, we compared clinical characteristics and adherence between 28,116 patients who underwent ABPM prior to starting AHM and 118,594 patients who did not undergo ABPM. Good adherence was defined as a proportion of days covered (PDC) of 0.8 or higher., Results: The total study population was 146,710, with a mean age of 50.5 ± 6.4 years; 44.3% were female. Co-morbidities were noted in 4.2%. About a third of patients (33.1%) showed good adherence. The ABPM group had a notably higher PDC (total PDC: 0.64 ± 0.35 vs. 0.45 ± 0.39; P < 0.001), irrespective of the number of medications, dosing frequency, or prescription duration. After adjusting for significant clinical variables, ABPM was still closely linked with good adherence (odds ratio, 2.35; 95% confidence interval, 2.28-2.41; P < 0.001)., Conclusions: In newly diagnosed hypertension, undergoing ABPM prior to AHM prescription appears to enhance adherence to AHM. The exact mechanisms driving this association warrant further exploration., (© 2024. The Author(s).)

Purpose: Low anterior resection syndrome (LARS) has had many impacts on the lives of patients and substantial differences in emotional and social functions. The aim of this study was to investigate the correlation analysis of different personality traits in rectal cancer patients with LARS after undergoing curative surgery., Methods: This study was designed as a prospective cohort study. The inclusion criteria included (1) participants diagnosed with rectal cancer who underwent surgical resection of malignant tumors and (2) ECOG 0-1. The primary outcome was the correlation between different personality traits and low anterior resection syndrome in rectal cancer patients after radical surgery. Low anterior resection syndrome incidence rates were estimated by questionnaires and personality groups by the Type A and Type D Scale-14 Personality Inventory., Results: For all 161 participants in this study, the presence of a tumor at the lower anal verge and the receipt of neoadjuvant CCRT had a statistically significant positive correlation with the LARS score at 1 month, 6 months, and 1 year (Pearson correlation coefficient = -0.283, -0.374, and - 0.205, respectively), with a p value of less than 0.05. Personalities with Type A, Type D, and Type D-SI scores had a statistically significant positive correlation with LARS score at 1 month (Pearson correlation coefficient = 0.172, 0.162, and 0,164, p value = 0.03, 0.04, and 0.04)., Conclusion: Type A and Type D personalities are highly linked to LARS. Personalized support approaches can ultimately assist rectal cancer patients in overcoming difficulties after surgery and recovery and enhance their functional outcomes., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Transition metal dichalcogenides (TMDs) are actively studied in various fields of optics and optoelectronics, including nonlinear optics of second-harmonic generation (SHG). By stacking two different TMD materials to form a heterobilyaer, unique optical properties emerge, with stronger SHG at a twist angle of 0° between TMDs and weaker SHG at a twist angle of 60°. In this work, we demonstrate the enhancement of SHG in a heterobilayer consisting of WSe 2 and WS 2 monolayers stacked at a twist angle of 64.1°, using a nanoparticle to induce local strain. The interatomic spacing of the heterobilayer is deformed by the nanoparticle, breaking the inversion symmetry, resulting in a substantial increase in the SHG of the heterobilayer at room temperature. The SHG increases depending on the polarization of the pump laser: 15-fold for linear polarization, 9-fold for right-circular polarization, and up to 100-fold for left-circular polarization. In addition, the SHG enhanced in the heterobilayer with local strain satisfies the same chiral selection rule as in the unstrained TMD region, demonstrating that the chiral selection rule of SHG is insensitive to local strain. Our findings will increase the applicability of TMD heterobilayers in nonlinear optoelectronics and valleytronics., (© 2024 IOP Publishing Ltd.)

Introduction: The long-term cognitive outcomes after transient global amnesia (TGA) have been contradictory in the literature. Our study aimed to longitudinally investigate the association between TGA and incident dementia using long-term data from a nationwide population-based cohort in South Korea., Methods: The study population was recruited between 2002 and 2020 using the International Classification of Diseases (Tenth Revision; ICD-10) codes from the Korean National Health Insurance Service database. The cumulative incidence curve was plotted to compare the incidence of dementia between the TGA (ICD-10 code G45.4; n = 10,276) and non-TGA (n = 27,389) groups, determined using 1:3 propensity score matching. Using Cox proportional hazard regression models, we obtained crude and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the incident dementia in patients with TGA compared to non-TGA controls. To examine independent variables determining dementia in the TGA group, logistic regression analysis was performed, and adjusted odds ratios (aORs) and 95% CIs were calculated., Results: The TGA group had a significantly higher cumulative incidence of dementia than the non-TGA group (p &lt; 0.001, log-rank test). TGA was significantly associated with incident dementia in the univariate and multivariate Cox models (HR 1.34, 95% CI 1.28-1.39 and aHR 1.40, 95% CI 1.34-1.46, respectively). The adjusted logistic regression for incident dementia in the TGA group showed that age (per 1 year, aOR 1.09, 95% CI 1.09-1.10), female sex (aOR 1.31, 95% CI 1.18-1.45), diabetes (aOR 1.21, 95% CI 1.08-1.35), stroke (aOR 1.30, 95% CI 1.16-1.46), depression (aOR 1.53, 95% CI 1.33-1.76), anxiety (aOR 1.24, 95% CI 1.01-1.39), and rural residence (aOR 1.24, 95% CI 1.10-1.41) were independently associated with incident dementia., Conclusion: Our results suggest a longitudinal association of TGA with incident dementia., (© 2024 S. Karger AG, Basel.)

Purpose: Pollen forecasting systems can provide information for coping with respiratory allergies. They estimate daily pollen production, dispersal, deposition, and removal based on daily weather conditions to predict daily pollen concentrations and provide allergy warnings. As of 2023, the Korea Meteorological Administration (KMA) provides 2-day forecast of allergenic pollens. However, unlike these models, long-term analysis of annual observations of tree pollen reveal annual variations. Therefore, in this study, we aimed to develop annual prediction models for allergenic tree pollens based on long-term multi-site pollen and meteorological data., Methods: Daily pollen concentrations were observed using Hirst-type volumetric spore traps at nine sites in Korea from 1998 to 2021, and daily weather data from the closest KMA stations were utilized. Models were developed to predict the seasonal pollen integral of seven tree species based on monthly mean temperature, wind speed, and total precipitation using three variable selection methods: 1) the t -test based key variable screening followed by linear regression with stepwise procedure (TM), 2) direct linear regression with stepwise procedure from the full variable model (FM), and 3) LASSO regression from the full variable model (LM)., Results: Data obtained during 1998-2017 and 2018=2021 were utilized for model development and validation, respectively. The root mean squared error, mean absolute error, mean error, and coefficient of determination (R²) revealed that the TM models were best suited for actual forecasting, even though R² in the TM model was lower than those of the FM and LM models., Conclusions: The annual variation model in this study can be integrated with the daily pollen forecast model by controlling the annual pollen potential, and the accuracy of the daily forecast can be improved accordingly., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: Columnar cell carcinoma is a rare subtype of papillary thyroid carcinoma (CCV-PTC) that accounts for only 0.15% to 0.2% of all Papillary Thyroid Carcinomas (PTCs). It has aggressive behavior but a better prognosis than anaplastic thyroid carcinoma., Case Presentation: A 64-year-old female presented with a huge thyroid mass resulting in compressive myelopathy and was diagnosed as CCV-PTC, not anaplastic carcinoma. After multidisciplinary discussions, we decided to proceed with otolaryngological, thoracic, and orthopaedic surgery. All tumours were unresectable, and we planned to proceed with R2 resection to resolve the gait disturbance and anterior fusion to resolve spinal instability., Conclusion: Advanced-stage thyroid cancer is relatively uncommon, but desirable treatment effects can be expected through accurate pathological diagnosis. Immunohistochemical staining and tissue-specific markers can be helpful., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: To assess the feasibility of deep learning (DL)-based k-space-to-image reconstruction and super resolution for whole-spine diffusion-weighted imaging (DWI)., Method: This retrospective study included 97 consecutive patients with hematologic and/or oncologic diseases who underwent DL-processed whole-spine MRI from July 2022 to March 2023. For each patient, conventional (CONV) axial single-shot echo-planar DWI (b = 50, 800 s/mm 2 ) was performed, followed by DL reconstruction and super resolution processing. The presence of malignant lesions and qualitative (overall image quality and diagnostic confidence) and quantitative (nonuniformity [NU], lesion contrast, signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], and ADC values) parameters were assessed for DL and CONV DWI., Results: Ultimately, 67 patients (mean age, 63.0 years; 35 females) were analyzed. The proportions of vertebrae with malignant lesions for both protocols were not significantly different (P: [0.55-0.99]). The overall image quality and diagnostic confidence scores were higher for DL DWI (all P ≤ 0.002) than CONV DWI. The NU, lesion contrast, SNR, and CNR of each vertebral segment (P ≤ 0.04) but not the NU of the sacral segment (P = 0.51) showed significant differences between protocols. For DL DWI, the NU was lower, and lesion contrast, SNR, and CNR were higher than those of CONV DWI (median values of all segments; 19.8 vs. 22.2, 5.4 vs. 4.3, 7.3 vs. 5.5, and 0.8 vs. 0.7). Mean ADC values of the lesions did not significantly differ between the protocols (P: [0.16-0.89])., Conclusions: DL reconstruction can improve the image quality of whole-spine diffusion imaging., Competing Interests: Declaration of Competing Interest This study was performed using a Siemens Healthcare magnetic resonance imaging scanner with a DWI research application sequence. T.B., an employee of Siemens Healthcare GmbH, Erlangen, Germany, implemented the DWI sequence. H.S.L., an employee of Siemens Healthineers Ltd., Seoul, Republic of Korea, supported the optimization of the protocol. T.B. and H.S.L. did not have access to any of the real data used in this study. The other authors (D.K.K., S.Y.L., Y.J.H., J.Y.L., S.W.L., S.E.L., J.Y.J., S.H.P.) declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Helicobacter pylori infection is primarily acquired in childhood and can lead to peptic ulcer diseases and gastric cancer. The prevalence of H. pylori infection varies widely in different countries. The aim of this study was to explore the change of pediatric H. pylori seroprevalence in the past two decades and to investigate the risk factors for pediatric H. pylori seropositivity in southern Taiwan., Materials and Methods: This study enrolled children aged 7-12 years in Tainan City in 2018 and compared the result with our previous data in 1998, 2005, and 2010. Parents of the participants were invited to fill out questionnaires, including information of personal history, family history of peptic ulcer diseases, annual household income, and source of drinking water. Blood samples were analyzed for anti-H. pylori IgG by enzyme-linked immunosorbent assay., Results: A total of 391, 629, 618, and 488 elementary school students in Tainan City were enrolled in 1998, 2005, 2010, and 2018, respectively. There was a significant decline in H. pylori seroprevalence from 9.2% in 1998, 7.8% in 2005, 6.2% in 2010 to 4.7% in 2018 (p < 0.001). Neither gender difference nor age difference was found in H. pylori seropositivity in each year of enrollment. Low household income was significantly associated with pediatric H. pylori seropositivity., Conclusions: The seroprevalence of H. pylori infection among elementary schoolchildren has remarkably declined in southern Taiwan in the past two decades. Low household income was a risk factor for pediatric H. pylori seropositivity., (© 2024 John Wiley & Sons Ltd.)

The binding between receptor‑activated nuclear factor‑κB (RANK) and the RANK ligand (RANKL) during osteoclast development is an important target for drugs that treat osteoporosis. The leucine‑rich repeat‑containing G‑protein‑coupled receptor 4 (LGR4) acts as a negative regulator of RANK‑RANKL that suppresses canonical RANK signaling during osteoclast differentiation. Therefore, LGR4 agonists may be useful in inhibiting osteoclastogenesis and effectively treating osteoporosis. In the present study, bone marrow‑derived macrophages and a mouse model of RANKL‑induced bone loss were used to investigate the effect of mutant RANKL (MT RANKL), which was previously developed based on the crystal structure of the RANKL complex. In the present study, the binding affinity of wild‑type (WT) RANKL and MT RANKL to RANK and LGR4 was determined using microscale thermophoresis analysis, and the effect of the ligands on the AKT‑glycogen synthase kinase‑3β (GSK‑3β)‑nuclear factor of activated T cells, cytoplasmic, calcineurin‑dependent 1 (NFATc1) signaling cascade was investigated using western blotting and confocal microscopy. In addition, the expression of LGR4 and the colocalization of LGR4 with MT RANKL were analyzed in a mouse model of RANKL‑induced bone loss. The results showed that in osteoclast precursor cells, MT RANKL bound with high affinity to LGR4 and increased GSK‑3β phosphorylation independently of AKT, resulting in the inhibition of NFATc1 nuclear translocation. In the mouse model, MT RANKL colocalized with LGR4 and inhibited bone resorption. These results indicated that MT RANKL may inhibit RANKL‑induced osteoclastogenesis through an LGR4‑dependent pathway and this could be exploited to develop new therapies for osteoporosis.