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A total of 280 pigs (DNA 241 × 600, initially 10.4 ± 0.24 kg BW) were used in a 21-day growth study to determine the available P (aP) release curve for Sunphase HT phytase (Wuhan Sunhy Biology Co., Ltd., Wuhan, P.R., China). At approximately 19 d of age, pigs were weaned, randomly allotted to pens, and fed common starter diets. On d 21 post-weaning, considered d 0 of the study, pigs were blocked by average pen body weight (BW) and randomly allotted to 1 of 7 dietary treatments with 5 pigs per pen and 8 pens per treatment. Dietary treatments were derived from a single basal diet and ingredients including phytase, monocalcium P, limestone, and sand were added to create the treatment diets. Treatments included 3 diets containing increasing (0.11, 0.19, and 0.27% aP) inorganic P from monocalcium P, or 4 diets with increasing phytase (250, 500, 1,000, or 2,000 FTU/kg) added to the diet formulated to 0.11% aP. All diets were cornsoybean meal-canola meal-based and were formulated to contain 1.24% SID Lys and an analyzed Ca:P ratio of 1.10:1. Before the beginning of the study, all pigs were fed a diet containing 0.11% aP for a 3-d period (d 18 to 21 post-weaning). At the conclusion of the study, 1 pig, closest to the mean weight of each pen, was euthanized and the right fibula, rib, and metacarpal were collected to determine bone ash and density. After cleaning, bones were submerged in ultra-purified water under vacuum for 4 h. Weights were then collected, and bone density was calculated. For bone ash, bones were placed in a drying oven at 105oC for 7 d and then ashed in a muffle furnace at 600oC for 24 h (Table 1). For the overall experimental period, feeding increasing levels of aP from inorganic P improved (linear, P = 0.014) ADG, G:F, and final BW. Similarly, feeding increasing phytase increased (linear, P = 0.011) ADG and final BW as well as improved (quadratic, P = 0.023) G:F. For fibula bone ash weight and percentage bone ash, rib bone ash weight and bone density, and all metacarpal bone properties, pigs fed increasing levels of aP from inorganic P exhibited a linear improvement (P = 0.019), with a quadratic response (P = 0.030) for fibula bone density and rib percentage ash. Additionally, pigs fed increasing phytase had increased (P < 0.05) bone ash weight, percentage bone ash, and bone density in either a linear or quadratic fashion depending on the bone analyzed. The available P release curve generated for Sunphase HT phytase for percentage bone ash combining values from right fibula, rib, and metacarpal is: aP = (0.360 × FTU) ÷ (2,330.250 + FTU). [ABSTRACT FROM AUTHOR]

Objectives: To compare microvascular flow imaging (MVFI) and power Doppler ultrasonography imaging (PDUS) for detecting intratumoral vascularity in recurrent thyroid cancer both before and after radiofrequency ablation (RFA)., Methods: This retrospective study included 80 patients (age, 57 ± 12 years; 54 women) with 110 recurrent tumors who underwent RFA between January 2021 and June 2023. A total of 151 PDUS and MVFI image sets were analyzed (85 pre-RFA, 66 post-RFA). Two readers assessed vascularity on the images using a four-point scale with a 2-week interval between PDUS and MVFI to estimate inter-reader agreement. Intra-reader agreement was determined by reinterpreting images in reverse order (MVFI-PDUS) after a 1-month gap. Additionally, diagnostic performance for identifying viable tumors after RFA was assessed in 44 lesions using thyroid-protocol CT as a reference standard., Results: MVFI demonstrated higher vascular grades than PDUS, both before (reader 1: 3.04 ± 1.15 vs. 1.93 ± 1.07, p < 0.001; reader 2: 3.20 ± 0.96 vs. 2.12 ± 1.07, p < 0.001) and after RFA (reader 1: 2.44 ± 1.28 vs. 1.67 ± 1.06, p < 0.001; reader 2: 2.62 ± 1.23 vs. 1.83 ± 0.99, p < 0.001). Inter-reader agreement was substantial (κ = 0.743) and intra-reader agreement was almost perfect (κ = 0.840). MVFI showed higher sensitivity (81.5%-88.9%) and accuracy (84.1%-86.4%) than PDUS (sensitivity: 51.9%, p < 0.01; accuracy: 63.6-70.5%, p < 0.04), without sacrificing specificity., Conclusion: MVFI was superior to PDUS for assessing intratumoral vascularity and showed good inter- and intra-reader agreement, highlighting its clinical value for assessing pre-RFA vascularity and accurately identifying post-RFA viable tumors in recurrent thyroid cancer., Clinical Relevance Statement: Microvascular flow imaging (MVFI) is superior to power-Doppler US for assessing intratumoral vascularity; therefore, MVFI can be a valuable tool for assessing vascularity before radiofrequency ablation (RFA) and for identifying viable tumors after RFA in patients with recurrent thyroid cancer., Key Points: The value of microvascular flow imaging (MVFI) for evaluating intratumoral vascularity is unexplored. MVFI demonstrated higher vascular grades than power Doppler US before and after ablation. Microvascular flow imaging showed higher sensitivity and accuracy than power Doppler US without sacrificing specificity., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Jung Hwan Baek, MD, PhD. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: No complex statistical methods were necessary for this paper. Informed consent: Written informed consent was obtained from all subjects (patients) in this study. Ethical approval: Institutional Review Board approval was obtained. Study subjects or cohorts overlap: No study subjects or cohorts have been previously reported. Methodology: Retrospective Observational Performed at one institution, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Objectives: The purposes of this study were to investigate the frequency of screwdriver stripping in the head of the locking screw that attaches to the side plate to the femur shaft among the patients who underwent implant removal after femoral neck system (FNS) for femoral neck fracture, to determine the risk factors for locking head screw stripping in FNS treatment of femoral neck fracture, and to suggest a surgical tip that removes FNS, which is difficult to remove due to screw stripping., Design: Retrospective cohort study., Setting: Eight Urban tertiary referral academic hospitals., Patient Selection Criteria: Included were patients with Orthopedic Trauma Association/Arbeitsgemeinschaft für Osteosynthesefragen 31-B1, 31-B2, and 31-B3 femoral neck fractures who underwent surgical fixation with FNS from November 2019 to February 2023., Outcome Measures and Comparisons: The frequency of locking head screw stripping of FNS during the implant removal was evaluated., Results: Among the 47 patients (18 (38%) men and 29 (62%) women) who met the inclusion criteria with an average age of 59.2 years (range, 28-94 years), 13 (27.7%) experienced screwdriver stripping in the head of the distal locking screw during FNS removal surgery. A higher body mass index showed a borderline significant association with the stripping in the adjusted model (odds ratio = 1.233; 95% confidence interval: 0.988-1.539; P = 0.064). No other variables showed significant association with the stripped locking head screw ( P > 0.05)., Conclusions: Stripping of the screwdriver within the head of the distal locking screw occurred in over one-quarter of cases. While a higher body mass index demonstrated a borderline significant association, none of the other variables examined showed a statistically significant relationship with the stripped locking head screw., Levels of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

For successful infection, the life-threatening pathogen Vibrio vulnificus elaborately regulates the expression of survival and virulence genes using various transcription factors (TFs). In this study, a library of the V. vulnificus mutants carrying specific signature tags in 285 TF genes was constructed and subjected to 16 phenotypic analyses. Consequently, 89 TFs affecting more than one phenotype of V. vulnificus were identified. Of these, 59 TFs affected the in vitro survival including growth, stress resistance, biofilm formation and motility, and 64 TFs affected the virulence of V. vulnificus. Particularly, 27 of the 64 TFs enhanced the in vitro hemolytic or cytotoxic activities, and 8 of the 27 TFs also increased the in vivo brine shrimp or murine infectivities of V. vulnificus. Among the eight TFs, HlyU, IscR, NagC, MetJ and Tet2 did not affect the growth of V. vulnificus but still regulated the expression of major exotoxin genes, including rtxA, vvhA and plpA, thereby emerging as potential drug targets for anti-virulence therapies with low selective pressure for developing resistance. Altogether, this study characterized the functions of TFs at a genome-wide scale and identified novel targets to control the virulence of V. vulnificus., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

A cell fate change such as tumorigenesis incurs critical transition. It remains a longstanding challenge whether the underlying mechanism can be unraveled and a molecular switch that can reverse such transition is found. Here a systems framework, REVERT, is presented with which can reconstruct the core molecular regulatory network model and a reversion switch based on single-cell transcriptome data over the transition process is identified. The usefulness of REVERT is demonstrated by applying it to single-cell transcriptome of patient-derived matched organoids of colon cancer and normal colon. REVERT is a generic framework that can be applied to investigate various cell fate transition phenomena., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: To evaluate the effectiveness and safety of radiofrequency ablation (RFA) for the treatment of symptomatic distant metastasis of differentiated thyroid carcinoma., Materials and Methods: The medical records of 12 patients who underwent RFA for the palliative treatment of 18 symptomatic distant metastases from thyroid cancer between January 2008 and December 2020 were analyzed. All patients were assessed for their degree of discomfort and underwent periodical evaluations as outpatients, including clinical examination, imaging, and serologic markers., Results: Among the 18 tumors treated, nine were soft tissue, and nine were bone metastases. The mean size of the treated tumors was 5.3 cm (range, 1.7-10.7 cm). All patients complained of pain, discomfort and/or bulging of the metastatic mass before RFA. After RFA, 11 out of the 18 patients with metastatic tumors (61.1%) reported a subjective improvement in symptoms. Nine out of 18 tumors decreased in size, with a mean size reduction ratio of 43% ± 22%. Although symptom improvement was achieved in 61.1% of the tumors, after a mean follow-up duration of 37.4 months, five patients experienced progression of the tumor, four patients had a stable tumor status, and three patients died from pneumonia. There were no major adverse events related to RFA during the treatment or follow-up period., Conclusion: RFA can be used as palliative therapy to relieve the symptoms caused by metastatic tumors; however, it has a limited role in improving the overall prognosis in patients with distant metastasis from thyroid cancer., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no relevant conflicts of interest to disclose., (© 2025. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Objectives : In this single-center retrospective study, we aimed to verify the extent of duodenal follicular lymphoma (DFL) and investigate the role and clinical significance of video capsule endoscopy (VCE) in the treatment process. Methods : We analyzed the clinical and imaging data of 40 patients diagnosed with DFL. Results : Imaging workup and bone marrow biopsies revealed DFL only in the gastrointestinal tract (stage I) in 22 patients and in local lymph nodes (stage II 1 ), distant lymph nodes (stage II 2 ), pancreas (stage II 2 E pancreas ), and extranodal regions (stage IV) in 1, 3, 1, and 13 patients, respectively. Fifteen of the 23 patients with localized (stages I and II 1 ) DFL underwent VCE for comprehensive small bowel evaluation, which revealed lesion extension beyond the duodenum in 10 patients (66.7%). A watch-and-wait strategy was implemented for one patient and systemic chemotherapy was administered to the remaining nine. Of the eight patients without VCE, seven and one received radiotherapy and observation, respectively. Nine of the 23 patients (39.1%) received systemic treatment based on positive VCE results. Only one of the 17 patients with advanced-stage DFL (stages II 2 and IV) accepted radiotherapy; 16 underwent systemic chemotherapy. During follow-up (median, 48.4 months), two relapse events occurred in the advanced stage, with no lymphoma-associated deaths. DFL tends to be indolent and has favorable outcomes. Conclusions : Proactive VCE for diagnosing DFL is recommended to determine small bowel involvement, which may influence subsequent treatment decisions.

Background/Objectives : Anti-CD20 monoclonal antibodies combined with alkylator-based chemotherapy enhance survival in chronic lymphocytic leukemia (CLL). However, the risks of infection and bone marrow suppression may mean that new, targeted therapies are more appropriate for some patients than fludarabine-cyclophosphamide-rituximab (FCR). In the Republic of Korea, where insurance limits coverage to novel agents, FCR therapy should be carefully considered for patients with CLL. Methods : Using clinical data from 144 FCR-treated patients with CLL, we retrospectively analyzed clinical characteristics impacting survival outcomes, the impact of cytopenia after FCR, and the durable remission status in terms of measurable residual disease (MRD). We compared the impact of bicytopenia with those of other hematologic conditions. Results : The 5-year overall survival (OS) and 5-year progression-free survival (PFS) for all patients were 84.4% and 68.3%, respectively. FCR-treated patients in the bicytopenia and TP53 -positive groups exhibited poor OS and PFS; in particular, the bicytopenia group often experienced prolonged anemia and thrombocytopenia (6-12 months). The responder group achieved sustained remission for a median of 5 years for MRD negativity. Conclusions : In bicytopenia, FCR can induce prolonged cytopenia, making it difficult to switch to second-line therapy or complete cycles of chemoimmunotherapy, directly affecting poor survival outcomes. The cautious application of FCR therapy in CLL without bicytopenia or TP53 positivity can achieve long-term remission.

Purpose: Bypass surgery is regarded as the standard treatment option for symptomatic and hemodynamically unstable moyamoya disease (MMD). However, there is ongoing debate about the most effective type of bypass surgery. We aimed to analyze the long-term outcomes of combined and indirect bypasses for MMD patients through intra-individual comparisons., Methods: Of the 896 patients who underwent 1084 bypass surgeries between 2007 and 2021, 24 patients with MMD who underwent combined bypass on one side and indirect bypass on the other side were ultimately enrolled in this study. Clinical, angiographic and hemodynamic outcomes were retrospectively evaluated., Results: Three asymptomatic strokes (12.5%) occurred within 30 postoperative days in each group. Postoperative strokes after 30 days occurred in 3 patients (12.5%) with 3 hemorrhagic events and 1 cerebral infarction, only in indirect bypass, while no stroke occurred in hemispheres treated with combined bypass. The revascularization area relative to supratentorial area was significantly greater in combined bypass than in indirect bypass, both in short-term and long-term periods (64.9% versus 43.9% in short-term and 75.7% versus 54.9% in long-term; P < .001, respectively). Hemodynamic outcomes showed significantly greater increases in acetazolamide-challenged cerebral blood flow (CBF acz ) during short-term follow-up (P = .04) and in both basal CBF (CBF bas ) and CBF acz during long-term follow-up (P = .014 and P = .009, respectively) in combined bypass than in indirect bypass., Conclusion: Combined bypass may be a more effective treatment option for MMD based on its higher revascularization area and favorable hemodynamic results compared to indirect bypass in the same patient., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Hairy cell leukemia (HCL) has a favorable clinical outcome with appropriate treatment; however, further research is needed on managing patients with relapsed or refractory disease and the risk of infection during prolonged periods. This study examined the long-term effects of 2-chlorodeoxyadenosine (2-CdA), particularly using a weekly infusion protocol, in treatment-naïve patients with HCL. This retrospective study evaluated the long-term follow-up data from 21 South Korean patients diagnosed with HCL. Among them, 20 patients were treated with a weekly infusion protocol (0.14 mg/kg/day over 5-6 weeks), whereas one received daily continuous intravenous infusion (0.1 mg/kg/day over 7 days). The median age and follow-up period of the patients were 50 (range, 32-77) years and 39.0 (range, 7.3-223.3) months, respectively. None of the patients with HCL died from 2-CdA-related toxicity. One patient preferred a daily treatment schedule for shorter durations, and this patient required prolonged hospital stay due to an anal abscess. The overall survival (OS) was 85.7% (95% confidence interval [CI], 33.4-97.9), without reaching the median OS. The progression-free survival (PFS) was 31.3% (95% CI, 5.6-62.3), with a median PFS of 66.5 months. Among the 19 patients who achieved remission, 5 relapsed (26.3%), with a median cumulative incidence of relapse of 116.7 months. The non-relapsed mortality rate was 13.6% (95% CI, 0.4-49.1). Weekly 2-CdA provides enhanced flexibility in clinical practice, with excellent long-term OS and PFS rates, making it a valuable treatment option for patients with HCL in an outpatient setting., Competing Interests: Declarations. Institutional review board statement: This study was approved by the Institutional Review Board (IRB) and Ethics Committee of the Catholic Medical Center, South Korea (KC24RASI0524) and was conducted according to the Declaration of Helsinki guidelines. Informed consent: Because this research involved minimal risk and could be conducted with a waiver of informed consent, the requirement for obtaining consent from participants did not apply to this study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The prognostic significance of extranodal sites in stage IV diffuse large B-cell lymphoma (DLBCL) remains uncertain, making it challenging to select appropriate treatment strategies for individual patients. In this study, we aimed to evaluate the influence of different extranodal sites on prognosis in young patients with stage IV DLBCL who achieved complete remission (CR) following initial chemo-immunotherapy and to explore the potential of autologous hematopoietic stem cell transplantation (ASCT) as a consolidation treatment for specific patient subgroups., Methods: We retrospectively reviewed data from 119 patients with DLBCL aged < 60 years who achieved CR after chemo-immunotherapy between 2008 and 2020. Patient survival rates were analyzed in correlation with different extranodal sites using univariate and multivariate models. Additionally, we assessed the effect of ASCT on 5-year progression-free survival (PFS) and overall survival (OS) in patients with different extranodal sites involved., Study Design: A retrospective bicenter study., Results: Univariate analysis revealed a significant decrease in survival rates in patients with a Deauville score of 3 and those with extranodal DLBCL affecting the spleen, bone marrow, nasosinus, and liver. In multivariate analysis, only nasosinusal involvement remained a significant predictor of reduced OS. Patients with spleen involvement benefited significantly from ASCT in terms of 5-year PFS and OS, whereas those with nasosinusal involvement did not demonstrate any survival advantage with ASCT., Conclusion: Our findings highlight the influence of specific extranodal sites on the prognosis of patients with stage IV DLBCL. The data indicate a clear need for precise patient stratification based on extranodal involvement for more effective treatment planning. Notably, patients with spleen involvement appear to benefit from ASCT, suggesting that this strategy could be useful in this subgroup. Further prospective studies are needed to confirm and incorporate these findings into clinical practice., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To investigate the diagnostic performance and interobserver agreement of quantitative CT parameters indicating strong lymph node (LN) enhancement in differentiated thyroid cancer (DTC), comparing them with qualitative analysis by radiologists of varying experience., Materials and Methods: This study included 463 LNs from 399 patients with DTC. Three radiologists independently analyzed strong LN enhancement on CT. Qualitative analysis of strong enhancement was defined as LN cortex showing greater enhancement than adjacent muscles on the arterial phase. Quantitative analysis included the mean attenuation value (MAV) of LN on arterial phase (LN A ) and venous phase (LN V ), LN A normalized to the common carotid artery (NAV CCA ), internal jugular vein (NAV IJV ), and sternocleidomastoid muscle (NAV SCM ), attenuation difference [AD; (LN A  - MAV SCM )], and relative washout ratio [((LN A  - LN V )/LN A ) × 100]. The interobserver agreement and diagnostic performance of the quantitative and qualitative analyses were evaluated., Results: Interobserver agreement was excellent for all quantitative CT parameters (ICC, 0.83-0.94) and substantial for qualitative assessment (κ = 0.61). All CT parameters except for LN V showed good diagnostic performance for metastatic LNs (AUC, 0.81-0.85). NAV CCA (0.85, 95% CI: 0.8-0.9) and AD (0.85, 95% CI: 0.81-0.89) had the highest AUCs. All quantitative parameters except for NAV IJV had significantly higher AUCs than qualitative assessments by inexperienced radiologists, with no significant difference from assessments by an experienced radiologist., Conclusion: Quantitative assessment of LN enhancement on arterial phase CT showed higher interobserver agreement and AUC values than qualitative analysis by inexperienced radiologists, supporting the need for a standardized quantitative CT parameter-based model for determining strong LN enhancement., Clinical Relevance Statement: When assessing strong LN enhancement in DTC, quantitative CT parameters indicating strong enhancement can improve interobserver agreement, regardless of experience level. Therefore, the development of a standardized diagnostic model based on quantitative CT parameters might be necessary., Key Points: Accurate preoperative assessment of LN metastasis in thyroid cancer is crucial. Quantitative CT parameters indicating strong LN enhancement demonstrated excellent interobserver agreement and good diagnostic performance. Quantitative assessment of contrast enhancement offers a more objective model for the identification of metastatic LNs., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is the corresponding author Sae Rom Chung. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: No complex statistical methods were necessary for this paper. Informed consent: Written informed consent was waived by the Institutional Review Board. Ethical approval: Institutional Review Board approval was obtained. Study subjects or cohorts overlap: All of the patients were reported in a previous retrospective study that investigated the ultrasonography (US) features for diagnosing cervical LN metastasis in patients with thyroid cancer and compared the US-based risk stratification system between the European and Korean guidelines [41]. While the previous study focused on the US features of LN metastasis, our study addressed the diagnostic performance and interobserver agreement of quantitative CT parameters indicating strong enhancement of the metastatic LN. Methodology: Retrospective Diagnostic or prognostic study Performed at one institution, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Double-lumen endotracheal tubes (DLT) are essential for one-lung ventilation during thoracic surgery. Bronchoscopy is crucial for correct placement of a DLT to avoid complications such as hypoxemia. This study evaluated the effectiveness of the triple-cuffed DLT (tcDLT) in the supine and lateral positions for correct placement without bronchoscopic guidance., Methods: This prospective observational study included 167 patients scheduled for elective thoracic surgery requiring one-lung ventilation. The incidence of successful placement of left-sided tcDLTs was compared between the supine and lateral decubitus positions under bronchoscopic surveillance. Successful tcDLT placement was defined as the placement of the proximal end of the bronchial cuff within 5 mm of the carina., Results: Among 153 patients who completed the study, the successful tcDLT placement rate in the lateral position (70.6%) was significantly higher than that in the supine position (50.3%). The rate of difference was 20.3% (95% confidence interval [CI], 10.6-29.9%). The extended successful placement rate, including slightly deeper placements, showed no significant differences between the positions (88.9%; 95% CI, 83.9-93.9% in supine, 86.3%; 95% CI, 80.8-91.7% in lateral)., Conclusions: tcDLT facilitates correct tube placement in both the supine and lateral positions, with a higher lateral success rate. This finding supports the idea that tcDLTs offer a reliable alternative for lung separation when bronchoscopy is not feasible.

In this paper, a concept of integrated CO 2 capture and reverse water-gas shift (ICCrWGS) process was proposed using NH 3 as the H 2 carrier. The CO 2 efficiency and total thermal energy consumption for the conventional rWGS, ICCrWGS using H 2 (H 2 -ICCrWGS) and NH 3 (NH 3 -ICCrWGS), were calculated. ICCrWGS using H 2 and NH 3 was conducted over the thermally stable Ni/CaZr dual-function materials (DFMs). NH 3 decomposition, CO 2 capture capacity, CO 2 conversion, and CO selectivity were addressed at different reaction temperatures, and the optimal temperature was determined to be 650 °C. The Ni/CaZr DFMs exhibited stable CO 2 capture capacity and CO productivity during ICCrWGS using the NH 3 carrier. A carbonate spillover mechanism for CO production over the Ni/CaZr DFMs in NH 3 -ICCrWGS was proposed using in situ diffuse reflectance infrared Fourier transform spectroscopy. It was found that CO is produced from the bridged bidentate carbonate route in the Ni-CaO interface.

Pulmonary fibrosis is a severe and progressive lung disease characterized by lung tissue scarring. Transforming growth factor beta 1 (TGFβ1) is crucial in causing pulmonary fibrosis by promoting the activation of fibroblasts and their differentiation into myofibroblasts, which are responsible for excessive extracellular matrix deposition. This study aimed to identify genes activated by TGFβ1 that promote fibrosis and to understand the regulatory pathway controlling myofibroblast. Endothelin-1 (ET-1) was identified as the top-ranking gene in the fibrosis-related gene set using quantitative PCR array analysis. TGFβ1 upregulated EGR1 expression through the ERK1/2 and JNK1/2 MAPK pathways. EGR1 and p-SMAD2 proteins interacted with the ET-1 gene promoter region to regulate TGFβ1-induced ET-1 expression in IMR-90 pulmonary fibroblasts. Mice lacking the Egr1 gene showed reduced ET-1 levels in a model of pulmonary fibrosis induced by intratracheal administration of bleomycin. These findings suggest that targeting EGR1 is a promising approach for treating pulmonary fibrosis, especially idiopathic pulmonary fibrosis, by affecting ET-1 expression and profibrotic reactions., 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 Inc. All rights reserved.)

Background: This study assessed the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for treatment of skin-involving recurrent thyroid cancer. Methods: In this retrospective case series study, 43 patients (mean age: 67.9 ± 14.4 years; 31 females) with skin-involving recurrent thyroid cancer were treated with RFA for a total of 50 tumors between May 2008 and March 2023. The location of the tumor was classified into epidermis, dermis, or hypodermis on the basis of the involved skin layer. After RFA, the technique efficacy (absence of detectable vasculature and volume reduction at 12 months), clinical success (resolution of symptoms or cosmetic problems), volume reduction ratio (VRR), complete disappearance of tumor, and complications were assessed. Results: Of the 50 recurrent tumors, 9 involved the epidermis, 10 involved the dermis, and 31 involved the hypodermis. A total of 88 RFA sessions (mean, 1.8; range: 1-6) were performed. The technique efficacy at 1 year was 72% (36/50 [confidence interval or CI: 59.6-84.4%]). At the last follow-up (median [interquartile range]: 2.7 [1.1-4.5] years), the clinical success rate was 86% (44/50), the complete disappearance rate 54% (27/50), and the mean VRR 77.3% ± 44.2%. In a subgroup analysis comparing epidermis/dermis vs. hypodermis, there was no statistical difference in technique efficacy (57.9% [11/19] vs. 80.6% [25/31], p = 0.085), clinical success rate (78.9% [15/19] vs. 90.3% [28/31], p = 0.265), complete disappearance rate (42.1% [8/19] vs. 51.6% [16/31], p = 0.541), or mean VRR (65.5% vs. 84.6%, p = 0.141). Skin burns were observed in 4.9% per treatment session (2/41 [CI: 0-11.3%]) of epidermis/dermis-involving tumor procedures and none of the hypodermal tumor procedures. No patients experienced life-threatening or major complications. Conclusions: RFA might serve as a promising approach for managing skin-involving recurrent thyroid cancer, with no major complications reported in this preliminary study. Recurrent tumors involving the epidermis/dermis may pose a higher risk of skin burns than tumors involving the hypodermis. Early intervention with RFA before the tumor extends to the epidermis/dermis may thus be preferable.

This study introduces a novel method for the fabrication of concave microwells involving water vapor permeation through polydimethylsiloxane (PDMS). This method leverages the exceptional water vapor permeability of PDMS to enable a scalable and cost-effective fabrication process, addressing the limitations of existing techniques such as photolithography that are resource-intensive and complex. PDMS is more permeable to water vapor than to other gas molecules, resulting in the formation of microwells. Smooth-sloped concave microwells are formed by depositing droplets of 10% ethylene glycol on a PDMS substrate followed by curing at 70 °C and evaporation of water vapor. These microwells exhibit a unique structural gradient that is highly conducive for biological applications. Concave microwells were further used as a platform to generate animal cell spheroids, demonstrating their potential for three-dimensional cell culture. Unlike conventional methods, this approach allows precise control over microwell morphology by simply adjusting droplet size and curing conditions, offering enhanced tunability and reproducibility. The formation yield of these microwells is dependent on the volume of the water droplets, demonstrating the importance of droplet size in controlling microwell morphology. This approach provides a simple and effective method for creating microwells without complex lithographic processes, making it a highly promising tool for a range of biomedical applications, including tissue engineering, cancer research, and high-throughput drug screening.

Objectives: The objective of this study was to compare clinical outcomes between in situ fixation and fixation after closed reduction (CR) in patients aged 50 and above with valgus impacted femoral neck fractures using data from multiple centers., Methods: Design: Retrospective multicenter cohort study., Setting: Five tertiary-care university hospitals., Patient Selection Criteria: Patients aged 50 and above, treated with operative fixation of valgus impacted femoral neck fractures using multiple cannulated screws from 2003 to 2019., Outcome Measures and Comparisons: Complications such as fixation failure, osteonecrosis of femoral head (ONFH), and reoperation were compared between the groups (in situ fixation group and fixation after CR group). Postoperative EuroQol-5 Dimension (EQ-5D), Harris Hip Score (HHS), and Koval's grade were compared., Results: The mean age of the 206 patients (161 in situ fixation group, 45 in fixation after CR group) who met the inclusion criteria was 68.9 ± 10.9 years (range, 50 to 95 years). There were 39 men and 167 women. Fixation failure occurred in 11.2% (6.8% of in situ fixation group vs 26.7% of fixation after CR group, p = 0.002). Reoperation was required for 10.2% (7.5% of in situ fixation group vs 20% of fixation after CR group, p = 0.023). Fixation failure and reoperation rates were significantly higher in the fixation after CR group than in the in-situ fixation group (odds ratio = 4.757, p = 0.002 and odds ratio = 3.104, p = 0.023, respectively). At the two-year follow-up, ONFH occurred in 5.8% (9 out of 161, in situ fixation group vs 3 out of 45, fixation after CR group). There was no significant difference in the occurrence of ONFH between the two groups (p = 0.727). The Koval's grade at 6 and 12 months demonstrated better results in the in-situ group (p = 0.027, 0.044, respectively). Postoperative EQ-5D and HHS scores showed no statistically significant differences between the two groups., Conclusion: In patients aged 50 years or older with valgus impacted femoral neck fractures, when fixation was done after reduction, the reoperation rate was higher due to fixation failure compared to in-situ fixation. There was no significant difference in the incidence of ONFH in valgus impacted femoral neck fractures regardless of whether reduction was performed., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/Objectives : Myeloid neoplasms encompass a diverse group of disorders. In this study, we aimed to analyze the clinical and genomic data of patients with myeloproliferative neoplasm (MPN), myelodysplastic neoplasm (MDS), and their overlapping conditions, such as MDS/MPN and aplastic anemia (AA), to help redefine the disease classification. Methods : Clinico-genomic data of 1585 patients diagnosed with MPN ( n = 715), MDS ( n = 698), MDS/MPN ( n = 78), and AA ( n = 94) were collected. Patterns of 53 recurrent genomic abnormalities were compartmentalized into 10 groups using a Dirichlet process (DP). Results: These genomic groups were correlated with specific genomic features, survival outcomes, and disease subtypes. Groups DP1 and DP5, characterized by JAK2 and CALR mutations, respectively, showed very favorable prognoses among the patients with MPN. Groups DP2, DP7, and DP9 demonstrated very adverse prognoses across the disease subtypes. DP2 included patients with MDS harboring TP53 mutations and complex karyotypes; DP9 comprised patients with acute myeloid leukemia-related mutations, including NPM1 ; and DP7 included patients with SETBP1 mutations. Groups DP10 and DP8, linked to SF3B1 and DDX41 mutations or chromosome 1q derivatives, presented a favorable risk profile. Improved survival was observed with transplantation in groups DP2, DP7, and DP9. Conclusions : These findings highlight the role of genomic classifications in guiding personalized treatment strategies, ultimately enhancing the understanding and management of myeloid neoplasms.

Introduction: Peripheral T-cell lymphomas (PTCLs) have poor outcomes in the relapsed/refractory (R/R) setting. In this study, we evaluated the efficacy of dexamethasone, L-asparaginase, ifosfamide, carboplatin, and etoposide (DL-ICE) chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with R/R PTCLs., Methods: We retrospectively analyzed 80 adult patients with R/R PTCLs treated with DL-ICE chemotherapy between September 2009 and March 2023. Patients achieving complete or partial remission were eligible for consolidative allo-HSCT. Overall survival (OS) and progression-free survival (PFS) were evaluated., Results: The overall response rate to DL-ICE was 37.5%, with 30% achieving complete remission (CR). With a median follow-up of 96.4 months, the median OS and PFS were 8.9 and 3.8 months, respectively. Seventeen patients (21%) underwent allo-HSCT, including 11 with non-CR status. The 5-year OS was significantly higher in the allo-HSCT group compared to that in the group with chemotherapy alone (64.7% vs 18.3%, p <0.001). Multivariate analysis identified advanced stage, EBV viremia, and non-CR status as poor prognostic factors., Discussion: DL-ICE chemotherapy demonstrated modest activity in R/R PTCLs. Consolidation with allo-HSCT, even in patients who do not achieve CR, resulted in long-term survival in a subset of patients. Early consideration of allo-HSCT may improve outcomes for patients with R/R PTCLs., 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 Kim, Kim, Han, Min, Cho and Jeon.)

Pulmonary fibrosis is a progressive lung condition characterized by the excessive activation of myofibroblasts. Transforming growth factor beta 1 (TGFβ1) plays a crucial role in the differentiation of fibroblasts into myofibroblasts. In addition, toll-like receptor 2 (TLR2), known for its role in immune responses, contributes to pulmonary fibrosis by promoting myofibroblast differentiation. However, the interplay between TGFβ1 and TLR2 signaling pathways in myofibroblast differentiation has remained elusive. In the present study, we investigated the involvement of TLR2 in TGFβ1-induced fibroblast differentiation into myofibroblasts using IMR-90 human pulmonary fibroblasts as a model cell line. We found that TLR2 activation induced myofibroblast differentiation by enhancing the expression of early growth response 1 (EGR1) via the mitogen-activated protein kinase (MAPK) signaling pathway. Elevated EGR1 levels were detected in the lung tissues of a bleomycin (BLM)-induced mouse model of pulmonary fibrosis. Moreover, the administration of tomaralimab, an antagonistic anti-TLR2 antibody, reduced the EGR1 expression and collagen deposition. Altogether, targeting the TLR2-EGR1 pathway could be a promising therapeutic approach for pulmonary fibrosis by blocking TGFβ1-induced myofibroblast differentiation., 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 Inc. All rights reserved.)

The nervous and immune systems are closely interconnected, and influence the onset and progress of various diseases. Accordingly, understanding the interaction of the neural system and the immune system becomes very important for the treatment of intractable diseases with the analysis of therapeutic mechanisms, such as autoimmune diseases, neurodegenerative diseases, cancers, and so on. The conventional immunomodulation treatments have been mainly carried out by drug administration, but they have suffered from systemic negative side-effects with only limited effects on the specific disease. In this Perspective, photonic nanomaterials and devices are reviewed and discussed for digitally controlled neurostimulating photomedicine via photobiomodulation and optogenetics from the unique viewpoint of neuro-immune cross-talks. The prospects and perspectives to integrate photonic nanomaterials with advanced wearable and implantable healthcare devices are also provided and highlighted to revolutionize the therapeutic strategies by the interaction of neural and immune systems, and optimize the treatment protocols for futuristic digital photomedicine. This approach will revolutionize the fields of neurostimulation and immune regulation for further clinical applications., (© 2024 Wiley‐VCH GmbH.)

The genus Enterococcus is increasingly recognized for its involvement in various human infections, with several species known to be pathogenic. This study characterized Enterococcus sp. SMC-9, isolated from bile of a patient with cholangitis, and compared its characteristics with those of Enterococcus montenegrensis CoE-012-22T, recently isolated from dried beef sausage. A comprehensive analysis, encompassing phylogenetic, genomic, and phenotypic studies, confirmed that strain SMC-9 belongs to the same species as E. montenegrensis CoE-012-22T. However, comparative genomic analysis revealed key differences in virulence and antibiotic resistance gene profiles between the two strains. Notably, genes related to exopolysaccharide biosynthesis and the L-rhamnose biosynthesis pathway were found exclusively in strain SMC-9, suggesting their role in the strain's colonization of the biliary tract and its involvement in cholangitis. Additionally, the tetracycline resistance gene tet(M), which was absent in E. montenegrensis CoE-012-22T, was identified in strain SMC-9, explaining its high tetracycline minimum inhibitory concentration (>16 μg/mL). These findings highlight the unique pathogenic traits of strain SMC-9 compared to E. montenegrensis CoE-012-22T. Our study underscores the significant genetic and phenotypic variations that can exist among strains within the same species, highlighting the critical need for strain typing to assess their potential impact on patient outcomes and public health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: This study aimed to investigate the prevalence of claudin 18.2 (CLDN18.2) positivity, with a particular focus on intratumoral heterogeneity, and its association with clinicopathological features in metastatic or unresectable gastric cancer (GC)., Patients and Methods: We investigated 400 patients who received systemic chemotherapy for unresectable, metastatic, or recurrent GC. Immunohistochemistry for CLDN18 (43-14A), human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and fibroblast growth factor receptor 2, as well as HER2 silver in situ hybridization (ISH), Epstein-Barr virus (EBV) ISH, and microsatellite instability testing were carried out. CD3+, CD8+, CD4+, and Foxp3-positive immune cell densities were calculated using digital image analysis., Results: In GC cases with any CLDN18.2 expression, more than half of the cases (61.3%) showed different expression results between four different tissue microarray (TMA) cores. When comparing CLDN18.2 status between whole tissue sections and the combined results from the four TMA cores, discrepancies were observed in only 2 out of 85 GC cases (2.4%), with 1 false positive and 1 false negative. After considering intratumoral heterogeneity, a CLDN18.2 positivity rate of 31.3% was observed among the 400 GC patients. CLDN18.2 positivity was rare in GCs located in the antrum (or lower third) and in HER2-positive cases but was common in EBV-positive GCs (P < 0.05). No differences in overall survival (OS) were observed according to CLDN18.2 positivity (P = 0.116). Additionally, there was no association between OS and CLDN18.2 positivity in patients treated with fluoropyrimidine plus platinum, chemotherapy plus trastuzumab, paclitaxel with or without ramucirumab, and immuno-oncologic agents. CLDN18.2-positive/PD-L1-high GCs showed statistically significantly longer OS than others (P = 0.025) and higher CD8+ T-cell densities in both the tumor center and periphery (P < 0.001)., Conclusions: Characterizing unresectable, metastatic, or recurrent GC with positive CLDN18.2 expression and evaluating intratumoral heterogeneity and prognostic implications of various therapeutics help advance treatment strategies and develop new therapies for patients with GC., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL23/ IL17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigen-B27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.

Introduction: There is a strong rationale for targeting HER3, as HER3 contributes to tumorigenesis and treatment resistance. However, the prognostic role of HER3 and their association with immunoregulatory protein expression has not been established., Methods: The main objective of this study was to investigate the prognostic role of HER3 expression and identify immunoregulatory marker expression according to HER3 status. HER3 expression and 10 immunoregulatory protein (PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4) expression was identified in 320 stage I-III breast cancer patients who received curative surgery at Seoul National University Hospital in 2008. The median follow-up duration was 88.8 months. Criteria for HER3 IHC was adopted from HER2 IHC score and only those with 3 + was considered positive., Results: Among 320 patients, 213 (67.2 %) had luminal A disease, 30 (9.5 %) had luminal B disease, 28 (8.8 %) had HER2-positive disease, and 46 (14.5 %) had triple negative disease. HER3 expression was shown in 153 patients (47.8 %). Tumors with HER3-expression had more immunogenic tumor microenvironment compared to HER3-negative tumor. In addition, patients with HER3 expression had favorable 5-year relapse free survival compared to HER3-negative patients (5-year RFS 92.5 % vs. 85.2 %, p = 0.038). However, in the multivariate analysis, HER3 expression was not a prognostic factor, but expression of immunoregulatory protein was a prognostic factor., Conclusions: This study identified immunoregulatory protein expression according to HER3 status in breast cancer patients. As tumor with HER3 expression have more immunogenic microenvironment, investigating combination treatment of HER3 targeting agent and immunotherapy in HER3 expressing breast cancer may be promising., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Williams syndrome (WS) is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23, characterized by intellectual disability, distinctive craniofacial and dental features, and cardiovascular problems. Previous studies have explored the roles of individual genes within these microdeletions in contributing to WS phenotypes. Here, we report five patients with WS with 1.4 Mb-1.5 Mb microdeletions that include RFC2, as well as one patient with a 167-kb microdeletion involving RFC2 and six patients with intragenic variants within RFC2. To investigate the potential involvement of RFC2 in WS pathogenicity, we generate a rfc2 knockout (KO) zebrafish using CRISPR-Cas9 technology. Additionally, we generate a KO zebrafish of its paralog gene, rfc5, to better understand the functions of these RFC genes in development and disease. Both rfc2 and rfc5 KO zebrafish exhibit similar phenotypes reminiscent of WS, including small head and brain, jaw and dental defects, and vascular problems. RNA-seq analysis reveals that genes associated with neural cell survival and differentiation are specifically affected in rfc2 KO zebrafish. In addition, heterozygous rfc2 KO adult zebrafish demonstrate an anxiety-like behavior with increased social cohesion. These results suggest that RFC2 may contribute to the pathogenicity of WS, as evidenced by the zebrafish model., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Current guidelines recommend a two-step algorithm rather than relying solely on a single test for diagnosing Clostridioides difficile infection. This algorithm starts with enzyme immunoassay (EIA) for detecting glutamate dehydrogenase (GDH) and toxins A/B, followed by nucleic acid amplification test (NAAT) for GDH-positive but toxin-negative cases. This study compared the performance of three commercial NAATs: the STANDARD M10 C. difficile , Xpert C. difficile , and BD MAX Cdiff assays, utilized as confirmatory testing of the two-step algorithm. Two hundred archived stool specimens, previously tested GDH-positive but toxin-negative by EIA, were analyzed in parallel with these NAATs and toxigenic culture, which served as the reference standard. Sensitivity, specificity, positive predictive value, and negative predictive value were 89.1%, 92.6%, 94.6%, and 85.2%, respectively, for the M10 assay; 95.8%, 86.4%, 91.2%, and 93.3%, respectively, for the Xpert assay; and 89.8%, 91.4%, 93.8%, and 86.0%, respectively, for the BD MAX assay. The rates of invalid results were 1.0%, 0.5%, and 1.0% for the M10, Xpert, and BD MAX assays, respectively. In conclusion, the M10 assay is a reliable diagnostic tool, performing comparably to the Xpert and BD MAX assays when used as confirmatory testing in the two-step algorithm.IMPORTANCEWhile numerous studies have assessed nucleic acid amplification tests (NAATs) as stand-alone tests for diagnosing Clostridioides difficile infection, limited research has compared their performance as confirmatory tests in a two-step algorithm. This study evaluated the performance of three commercial NAATs (M10, Xpert, and BD MAX assays) using 200 archived stool specimens initially tested as glutamate dehydrogenase (GDH)-positive but toxin-negative by GDH/toxin A/B enzyme immunoassay, the first step in the two-step algorithm. All three assays demonstrated high sensitivity (89.1% to 95.8%) and specificity (86.4% to 92.6%), with low rates of invalid results (≤1%). Our findings suggest that the M10 assay performs comparably to the Xpert and BD MAX assays when used as confirmatory testing in the two-step algorithm. Offering similar performance and turnaround time to these widely used assays at a slightly lower cost, the M10 assay serves as a practical alternative in this setting.

Context: Roux-en-Y gastric bypass (RYGB) has deleterious effects on bone mass, microarchitecture, and strength. The skeletal effects of sleeve gastrectomy (SG), now the most commonly performed bariatric surgical procedure, are incompletely understood., Objective: We examined changes in bone turnover, areal and volumetric bone mineral density (aBMD, vBMD), and appendicular bone microarchitecture and estimated strength after SG. We compared the results to those previously reported after RYGB, hypothesizing lesser effects after SG than RYGB., Design, Setting, Participants: Prospective observational cohort study of 54 adults with obesity undergoing SG at an academic center., Main Outcome Measure(s): Skeletal characterization with biochemical markers of bone turnover, dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) was performed preoperatively and 6- and 12-months postoperatively., Results: Over 12 months, mean percentage weight loss was 28.8%. Bone turnover marker levels increased, and total hip aBMD decreased -8.0% (95% CI -9.1%, -6.7%, p<0.01). Spinal aBMD and vBMD declines were larger in postmenopausal women than men. Tibial and radial trabecular and cortical microstructure worsened, as did tibial estimated strength, particularly in postmenopausal women. When compared to data from a RYGB cohort with identical design and measurements, some SG biochemical, vBMD, and radial microstructural changes were smaller, while other changes were not., Conclusions: Bone mass, microstructure, and strength decrease after SG. Some skeletal parameters change less after SG than after RYGB, while for others, we find no evidence for smaller effects after SG. Postmenopausal women may be at highest risk of skeletal consequences after SG., (Published by Oxford University Press on behalf of the Endocrine Society 2024.)

Brachiocephalic artery aneurysm is uncommon but may require surgery because it tends to enlarge, rupture, or cause symptoms related to thrombosis or compression. This case report describes a brachiocephalic artery aneurysm in a 72-year-old man who presented at the hospital with dyspnea and hemoptysis resulting from impending rupture and tracheal communication., Competing Interests: Conflict of Interest Disclosure: The authors report no conflicts of interest., (© 2024 The Authors. Published by The Texas Heart Institute®.)

Objectives: This study investigated the characteristics of adolescent-onset epilepsy (AOE) and conducted genetic tests on a cohort of 76 Korean patients to identify variants and expand the spectrum of mutations associated with AOE., Methods: Clinical exome sequencing after routine karyotyping and chromosomal microarray was performed to identify causative variants and expand the spectrum of mutations associated with AOE., Results: In cases of AOE without neurodevelopmental delay (NDD), this study identified four likely pathogenic variants (LPVs) or variants of uncertain significance (VUS) and two copy number variations (CNVs). To explore the unique features of AOE; clinical manifestations were compared between patients with and without NDD. The analysis revealed statistically significant differences in the prevalence of males and the yield of genetic testing results. AOE without NDD had a lower prevalence in males (49%) compared to AOE with NDD (60%) ( p = 0.007). Genetic alterations: AOE with NDD exhibited a higher frequency of genetic alterations (35%) compared to AOE without NDD (12%) ( p = 0.011). Thorough evaluation of AOE can be particularly challenging in adolescent patients. Some individuals may display genetic variations due to a phenomenon known as locus heterogeneity, where different genetic causes lead to similar clinical presentations., Conclusions: Implementing a robust genetic workflow is crucial for accurately diagnosing AOE, even in cases with complex genetic underpinnings. This study underscores the importance of genetic testing as an essential diagnostic tool for AOE. Identifying genetic variants and understanding their clinical correlations can aid in improving diagnostic accuracy and optimizing treatment approaches for adolescent patients with epilepsy.

This study evaluated the effects of Parachlorella sp. KSN1 (PA) supplementation on the gut microbiota and intestinal immunity of broilers of different ages. A total of 180 Ross 308 broiler chicks were weighed and divided into early (1 to 10 days post hatch) and late (11 to 28 days post hatch) periods, with six replicates of 10 chicks per cage assigned to two dietary groups. The experimental diets included a corn-soybean meal-based control diet and a treatment diet supplemented with 0.5% PA, replacing corn or corn starch, and fed ad libitum for the assigned experimental period. On days 10 and 28, two broilers from each of the six replicate cages, with 7 broilers per cage in each group, were selected and euthanized, and cecal feces and intestinal tissue samples were collected. PA supplementation did not significantly affect broilers growth performance during both the early and the late periods. However, PA supplementation altered the cecal microbiome, with Clostridiaceae and Clostridium exhibiting prominent and consistent changes. In terms of intestinal immunity, PA supplementation significantly increased the number of CD3+ and CD4+ T cells when administered only during the early period. Cecal IgA levels were significantly increased by PA supplementation during both the early and late periods. A significant positive correlation was observed between IgA, Clostridiaceae and Clostridium during the early and late periods. Gene expression analysis identified 40 upregulated genes, including polymeric immunoglobulin receptor (pIgR), and 142 downregulated genes, including marginal zone B and B1 cell specific protein and immunoglobulin lambda-like polypeptide 1 that were associated with the IgA response in PA-treated broilers during the early period. This study demonstrated that PA supplementation promotes gut microbial colonization and intestinal immunity development during the early age of broilers. These findings suggest that the early growth period of broilers is the optimal time for dietary immunomodulation to promote gut health in broilers., 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. Published by Elsevier Inc.)

Introduction: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare, aggressive subtype of primary gastrointestinal T-cell lymphoma. Owing to the absence of symptoms characteristic of MEITL, diagnosis can be challenging, and the low response rate to conventional chemotherapy leads to an abysmal prognosis. This study aimed to define the clinicopathologic characteristics of MEITL in Korea, evaluate the clinical outcomes of intensive chemotherapy with and without hematopoietic stem cell transplantation (HSCT), and explore prognostic factors., Methods: This single-center retrospective study examined the clinical data of 35 patients diagnosed with MEITL at Seoul St. Mary's Hospital from May 2012 to May 2023., Results: We included 22 men and 13 women (median age: 59 years; range: 37-79 years). Many patients exhibited acute abdominal pain (n=23, 65.7%) related to bowel perforation (n=21, 60.0%). Most patients (30/35, 85.7%) underwent surgical intervention to diagnose MEITL, whereas only five were diagnosed via endoscopic evaluation. Of the 32 patients receiving first-line therapy, 4 died before assessment, 10 achieved a complete response (CR), 6 had a relapse, and 18 exhibited progressive disease (PD). Seven of 10 patients received upfront HSCT, either autologous (auto-HSCT, n=4) or allogeneic (allo-HSCT, n=3). All four patients on auto-HSCT died after relapse. All three patients who received allo-HSCT maintained a CR by the final follow-up. Three of 6 patients who relapsed and 13 of 18 exhibiting PD received salvage therapy; one patient on salvage auto-HSCT with cytokine-induced killer cell infusion has survived progression free. Salvage allo-HSCT was performed on 6 of 16 patients; among them, 2 achieved a CR, 2 died after relapse, and 2 died owing to septic shock while maintaining a CR. The remaining patients, who received salvage therapy without HSCT, mostly died owing to PD. The median overall survival was 12.1 months, and the median follow-up was 33.2 months. The 1- and 5-year overall survival was 50.9% and 13.3%, respectively., Discussion: MEITL is an aggressive disease resistant to conventional therapy. Therefore, intensive chemotherapy followed by upfront allo-HSCT should be considered upon diagnosis. These findings underscore the need for novel therapeutic strategies and further investigation into optimizing treatment protocols for MEITL., 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 Min, Oh, Jeon, Kim, Kim, Kwag, Park, Park, Yoon, Lee, Cho, Eom, Kim, Lee, Kim, Min, Lee and Cho.)

Proline is a major substrate in collagen biosynthesis and is required for collagen molecule formations. However, detailed explanations of the molecular basis through which proline functions in collagen biosynthesis have yet to be provided. Thus, genome-wide screening was employed to elucidate these in the pre-osteoblastic MC3T3-E1 and human periodontal ligament fibroblast (hPDLF) cell lines. Indeed, both cell lines represent important sources for collagen biosynthesis and tissue regeneration in the dental region, specifically treating extracellular proline during cultivations. The altered gene expression patterns were identified, and the precise expression patterns were confirmed by microarray. Cell viability and osteogenic differentiation patterns were examined using a range of experimental methods, such as the MTS assay, ALP staining, ARS staining, and collagen (COL)-type1A ELISA. Overall, we revealed a cell line-specific function of exogenous proline in collagen biosynthesis during osteogenic differentiation conditions with the candidate signaling pathways. These putative signaling networks could represent plausible answers to understanding collagen biosynthesis for regenerating connective tissues such as skin, muscle, and bone., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: Not applicable. Informed consent: Not applicable., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Most non-muscle invasive bladder cancers have been treated by transurethral resection and following intravesical injection of immunotherapeutic agents. However, the delivery efficiency of therapeutic agents into bladder wall is low due to frequent urination, which leads to the failure of treatment with side effects. Here, we report a urease-powered nanomotor containing the agonist of stimulator of interferon genes (STING) for the efficient activation of immune cells in the bladder wall. After characterization, we perform in vitro motion analysis and assess in vivo swarming behaviors of nanomotors. The intravesical instillation results in the effective penetration and retention of nanomotors in the bladder. In addition, we confirm the anti-tumor effect of nanomotor containing the STING agonist (94.2% of inhibition), with recruitment of CD8 + T cells (11.2-fold compared with PBS) and enhanced anti-tumor immune responses in bladder cancer model in female mice. Furthermore, we demonstrate the better anti-tumor effect of nanomotor containing the STING agonist than those of the gold standard Bacille Calmette-Guerin therapy and the anti-PD-1 inhibitor pembrolizumab in bladder cancer model. Taken together, the urease-powered nanomotor would provide a paradigm as a next-generation platform for bladder cancer immunotherapy., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Myelofibrosis, which includes primary myelofibrosis (PMF) and secondary myelofibrosis (SMF), can exhibit cytopenic features associated with poor outcomes; however, the underlying mechanisms are unclear. Moreover, characterized by its aggressive nature and limited therapeutic options, myelofibrosis poses a major clinical challenge in hematology. Therefore, in this study, we aimed to identify genetic and immunologic features associated with thrombocytopenia progression and poor prognosis., Methods: The study involved 226 patients with PMF or SMF, who were categorized into three groups: platelet count ≥ 100 × 10 9 /L (PLT ≥ 100 group; n = 131), progression to thrombocytopenia (PROG group; n = 64), and platelet count < 100 × 10 9 /L (PLT < 100 group; n = 31)., Results: Survival analysis revealed 4-year overall survival rate of 57.7%, 89.4%, and 93.9% for the PLT < 100, PROG, and PLT ≥ 100 groups, respectively. Time-dependent covariate analysis of the PLT ≥ 100 and PROG groups revealed inferior overall survival rate of the PROG group. Multivariate analysis indicated that progression to thrombocytopenia and ASXL1 and IDH1 mutations were associated with poor overall survival. Flow cytometry revealed fewer CD45RA + CD4 + T cells in the PROG group than in the PLT ≥ 100 group. ASXL1 mutations were more prevalent in the PROG group than in the other groups, correlating with a reduced number of CD45RA + CD4 + T cells., Discussion: ASXL1 mutation and low CD45RA + CD4 + T-cell counts correlated with progression to thrombocytopenia. Our findings underscore the clinical significance of thrombocytopenia dynamics in MF progression and prognosis, with implications for patient management and therapeutic interventions., 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 Kim, Eom, Lee, Lee, Kim and Lee.)

Objective: Intellectual disability is often the outcome of neurodevelopmental disorders and is characterized by significant impairments in intellectual and adaptive functioning. X-linked intellectual disability (XLID) is a subset of these disorders caused by genetic defects on the X chromosome, affecting about 2 out of 1,000 males. In syndromic form, it leads to a broad range of cognitive, behavioral, ocular, and physical disabilities., Methods: Employing exome or genome sequencing, here we identified 4 missense variants (c.475C > G; p.H159D, c.1373C > A; p.T458N, and c.1585G > A; p.E529K, c.953C > T; p.S318L) and a putative truncating variant (c.1413&#95;1414del; p.Y471*) in the SRPK3 gene in 9 XLID patients from 5 unrelated families. To validate SRPK3 as a novel XLID gene, we established a knockout (KO) model of the SRPK3 orthologue in zebrafish., Results: The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Together, these data indicate a pathological role of SRPK3 in neurodevelopmental disorders. In post-fertilization day 5 larvae (free swimming stage), KO zebrafish exhibited severe deficits in eye movement and swim bladder inflation, mimicking uncontrolled ocular movement and physical clumsiness observed in human patients. In adult KO zebrafish, cerebellar agenesis and behavioral abnormalities were observed, recapitulating human phenotypes of cerebellar atrophy and intellectual disability., Interpretation: Overall, these results suggest a crucial role of SRPK3 in the pathogenesis of syndromic X-linked intellectual disability and provide new insights into brain development, cognitive and ocular dysfunction in both humans and zebrafish. ANN NEUROL 2024;96:914-931., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: The arterial to end-tidal carbon dioxide gradient (P [a-Et] CO 2 ) reveals the ventilation-perfusion (V/Q) status of critically ill patients. V/Q mismatch has several causes and affects the clinical outcomes of critically ill patients. We investigated the relationship between P (a-Et) CO 2 and the clinical outcomes in critically ill patients., Methods: Critically ill patients (n = 1,978) on mechanical ventilation and capnography in the intensive care units of two institutions were enrolled and categorized into three groups: P (a-Et) CO 2 ≤10 mmHg (low group), 10 mmHg < P (a-Et) CO 2 ≤ 20 mmHg (medium group), and 20 mmHg < P (a-Et) CO 2 (high group)., Results: The Acute Physiology and Chronic Health Evaluation II score was 29.5 ± 8.1, 31.3 ± 8.2, and 33.3 ± 8.7 in the low, medium, and high groups, respectively (p < 0.001). Overall mortality rates were 25.5 %, 35.6 %, and 52.8 % in the low, medium, and high groups, respectively (p < 0.001). The odds ratio was 1.456 (95 % confidence interval [CI]: 1.117-1.897, p = 0.002) and 2.320 (95 % CI: 1.635-3.293, p < 0.001) for the medium and high groups, respectively, with the low group as a reference. The area under the receiver operating characteristic curve of P (a-Et) CO 2 for overall mortality was 0.604 (p < 0.001)., Conclusions: P (a-Et) CO 2 is a simple, easily accessible indicator that potentially impacts patient care and outcomes as an independent marker for assessing disease severity and predicting mortality, especially in non-respiratory critical care scenarios., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Ethnopharmacological Relevance: The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD)., Aim of the Study: The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA)., Materials and Methods: An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured., Results: In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited β-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-β-apiofuranosyl (1 → 6)-β-glucopyranoside., Conclusions: WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD., 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.)

Although the efficacy of trastuzumab deruxtecan (T-DXd) against HER2-positive gastric cancers (GCs) has driven its clinical application, the precise mechanisms governing its immunomodulatory role remain unclear. In this study, we examined the immune-related mechanisms of action of T-DXd in GC cells. T-DXd exhibited potent antitumor effects in GC cells across diverse HER2 expression levels by inducing DNA damage and apoptosis. Activation of the DNA damage response by T-DXd led to increased PD-L1 expression. RNA-Seq analysis revealed that T-DXd modulated immune-related pathways, resulting in the upregulation of genes associated with inflammation and IFN signaling. Importantly, T-DXd activated the cGAS-STING pathway, inducing an IFN-I response in HER2-positive GC cells. Furthermore, T-DXd activated dendritic cells via the cancer cell-intrinsic cGAS-STING-IFN axis and enhanced PBMC-mediated tumor cell killing by activating CD8 + T cells. These findings provide valuable insights into the role of the cytosolic DNA sensing pathway in the action of T-DXd and offer a compelling rationale for combining T-DXd with immune checkpoint blockade therapies in GC treatment., (© 2024. The Author(s).)

Background: Cardiovascular diseases are a leading cause of mortality and a significant contributor to temporary and permanent disabilities worldwide. This study aimed to investigate the burden of primary and residual cardiometabolic risk factors in a sample of young adults in the Russian city of Kazan., Methods: This case-control study used the Cardiometabolic Disease Staging (CMDS) classification system, which has been validated in several countries. The study included 191 individuals aged 25-44 years who met the inclusion criteria but did not meet any exclusion criteria. Data collection involved a patient card with questions from the World Health Organization's STEPS instrument, face-to-face patient interviews, and a physical examination. Anthropometric assessments included height, weight, and waist circumference measurements. Body composition was evaluated using bioelectrical impedance measurements. Patients also underwent in-depth laboratory biochemical analyses., Results: The study cohort was comprised of 97 females (50.8%) and 94 males (49.2%). The median age of participants was 35.00 years [IQR: 30.00-39.00]. The study cohort showed an increase in all anthropometric parameters, with abdominal obesity and overweight reaching 100% in the CMDS 3. Apart from atherogenic lipids and raised blood pressure, other risk factors that precipitate residual risk and were not part of CMDS, such as insulin levels, insulin resistance, leptin values, and hyperuricemia, increased as CMDS levels increased., Conclusions: The prevalence of cardiometabolic risk factors was high in young adults in Kazan. This study highlights the need for the early identification and management of cardiometabolic risk factors in young adults to prevent the development of cardiovascular diseases later in life., (© 2024. The Author(s).)

In this study, silver nanoparticles (AgNPs) were synthesized using a green method from an extract of the edible insect Oxya chinensis sinuosa (O&#95;extract). The formation of AgNPs (O&#95;AgNPs) was confirmed via UV-vis spectroscopy, and their stability was assessed using Turbiscan analysis. The size and morphology of the synthesized particles were characterized using transmission electron microscopy and field-emission scanning electron microscopy. Dynamic light scattering and zeta potential analyses further confirmed the size distribution and dispersion stability of the particles. The average particle size was 111.8 ± 1.5 nm, indicating relatively high stability. The synthesized O&#95;AgNPs were further characterized using X-ray photoelectron spectroscopy (XPS), high-resolution X-ray diffraction (HR-XRD), and Fourier transform infrared (FTIR) spectroscopy. XPS analysis confirmed the chemical composition of the O&#95;AgNP surface, whereas HR-XRD confirmed its crystallinity. FTIR analysis suggested that the O&#95;extract plays a crucial role in the synthesis process. The antibacterial activity of the O&#95;AgNPs was demonstrated using a disk diffusion assay, which revealed effective activity against common foodborne pathogens, including Salmonella Typhimurium, Escherichia coli , Staphylococcus aureus , and Bacillus cereus . O&#95;AgNPs exhibited clear antibacterial activity, with inhibition zones of 15.08 ± 0.45 mm for S . Typhimurium, 15.03 ± 0.15 mm for E. coli , 15.24 ± 0.66 mm for S. aureus , and 13.30 ± 0.16 mm for B. cereus . These findings suggest that the O&#95;AgNPs synthesized from the O&#95;extract have potential for use as antibacterial agents against foodborne bacteria.

The human gut microbiota significantly influences various physiological systems, including immune, nervous, and metabolic systems. Recent studies suggest that gut microbiota may affect sleep quality with certain bacteria and metabolites being linked to sleep patterns. However, the underlying chemical signaling pathway remains unclear. In this study, we investigated the effect of four gut bacteria-derived metabolites, tryptamine ( 1 ), indolokine A5 ( 2 ), 2-(1' H -indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE, 3 ), and phenethylamine (PEA, 4 ), on sleep characteristics in mice and melatonin biosynthesis pathways in zebrafish. Their sleep-promoting effects were evaluated in a pentobarbital-induced sleep mouse model, revealing significant increases in sleep duration and blood melatonin levels, particularly with ITE ( 3 ) and PEA ( 4 ). Further tests in zebrafish embryos showed that ITE ( 3 ) and PEA ( 4 ) increased the expression of genes for melatonin biosynthesis ( Aanat1 , Aanat2 , Tph1a , and Hiomt ) in a concentration-dependent manner, indicating their potential as therapeutic agents for sleep disorders., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Growing evidence supports that early- or middle-life traumatic brain injury (TBI) is a risk factor for developing Alzheimer's disease (AD) and AD-related dementia (ADRD). Nevertheless, the molecular mechanisms underlying TBI-induced AD-like pathology and cognitive deficits remain unclear. In this study, we found that a single TBI (induced by controlled cortical impact) reduced the expression of BCL2-associated athanogene 3 (BAG3) in neurons and oligodendrocytes, which is associated with decreased proteins related to the autophagy-lysosome pathway (ALP) and increased hyperphosphorylated tau (ptau) accumulation in excitatory neurons and oligodendrocytes, gliosis, synaptic dysfunction, and cognitive deficits in wild-type (WT) and human tau knock-in (hTKI) mice. These pathological changes were also found in human cases with a TBI history and exaggerated in human AD cases with TBI. The knockdown of BAG3 significantly inhibited autophagic flux, while overexpression of BAG3 significantly increased it in vitro. Specific overexpression of neuronal BAG3 in the hippocampus attenuated AD-like pathology and cognitive deficits induced by TBI in hTKI mice, which is associated with increased ALP-related proteins. Our data suggest that targeting neuronal BAG3 may be a therapeutic strategy for preventing or reducing AD-like pathology and cognitive deficits induced by TBI., (© 2024. The Author(s).)

Thyroid immune-related adverse events (irAEs) are associated with programmed cell death protein 1 (PD-1) blockade efficacy in non-small cell lung cancer (NSCLC). However, their independence from PD-L1 expression and quantitative impact on predicting PD-1 blockade efficacy remain unexplored. This multicenter, retrospective, longitudinal study from Korea included 71 metastatic NSCLC patients who underwent PD-L1 expression and thyroid function testing during PD-1 blockade. Disease progression by the Response Evaluation Criteria for Solid Tumors was the main outcome. Three-stage analyses were performed: (1) multivariate Cox regression models adjusted for PD-L1 expression according to thyroid irAEs; (2) subgroup analyses; (3) regrouping and comparing predictivity of current and alternative staging. Patients with thyroid irAE + exhibited a longer progression-free survival [7/20 vs. 34/51, adjusted HR 0.19 (0.07-0.47); P < 0.001] than those with thyroid irAE-, independent of PD-L1 expression; the results remained across most subgroups without interaction. The three groups showed different adjusted HR for disease progression (Group 1: PD L1 + and thyroid irAE + ; Group 2: PD-L1 + or thyroid irAE + : 5.08 [1.48-17.34]; Group 3: PD-L1- and thyroid irAE- : 30.49 [6.60-140.78]). Alternative staging (Group 1 in stage IVB → stage IVA; Group 3 in stage IVA → stage IVB) improved the prognostic value (PVE: 21.7% vs. 6.44%; C-index: 0.706 vs. 0.617) compared with the 8th Tumor-Node-Metastasis staging. Our study suggests thyroid irAEs and PD-L1 expression are independent biomarkers that improve predicting PD-1 blockade efficacy in NSCLC. Thyroid irAEs would be helpful to identify NSCLC patients who benefit from PD-1 blockade in early course of treatment., (© 2024. The Author(s).)